Podcasts about natural medicine journal

Jen Green speaks at the 2025 Public Forum on Healing with Integrative Cancer Care in February. The gathering was designed to bridges wisdom traditions with emerging frontiers in healing. This year's forum explores transformation through the intersections of integrative cancer care with consciousness and healing arts, featuring distinguished speakers and practitioners from diverse backgrounds. The day included engaging presentations on patient advocacy, expressive arts, and innovative approaches to cancer care. Jen Green, ND, FABNO Jen Green is a Naturopathic Doctor (ND) who is board certified in Naturopathic Oncology (FABNO). She received her Arts & Science degree from McMaster University, and graduated from the Canadian College of Naturopathic Medicine in 2000. Dr Green founded the Naturopathic Department at Beaumont Hospitals, Michigan in 2008 and served as the department head for five years. Jen wrote the cardio-oncology chapter in the Textbook for Naturopathic Oncology and has published papers in BMC Complementary Medicine and Therapies, American Urology Association Update Series, Journal of Alternative & Complementary Medicine, and the Natural Medicine Journal. Jen Green lectures in both the US and Canada: https://drjengreen.com/conference___lecture Dr Green currently serves as a Research Director for KNOW, the Knowledge in Integrative Oncology Website (www.knowoncology.org). KNOW is an educational platform that supports decision making in cancer care. The KNOW database is updated quarterly with human studies on natural agents or nutrition and cancer care. Dr Green has served on the board of the Oncology Association Naturopathic Physicians and Michigan Association of Naturopathic Physicians. She currently sits on the advisory board of Cancer Choices. After practicing integrative oncology for 24 years, Jen underwent chemoradiation for head and neck cancer in 2024, which deepened her understanding of what it is to be a cancer patient. She is dedicated to teaching a heart-centered, evidence-based and individualized approach to integrative supportive cancer care. The New School at Commonweal is a collaborative learning community offering conversations about nature, culture, and inner life---so that we can all find meaning, meet inspiring people, and explore the beauty and grief of our changing world. Please like/follow our YouTube channel for more great podcasts. Find out more about The New School at Commonweal on our website: tns.commonweal.org. And like/follow our Soundcloud channel for more great podcasts.

Nutritionist Leyla Muedin discusses intermittent fasting, specifically addressing whether skipping morning coffee affects metabolism. She explains different approaches to intermittent fasting, including Bulletproof Coffee and time-restricted eating (TRE). Leyla also delves into a study on the effectiveness of TRE in weight loss and cardiometabolic health, highlighting that eating within a specific time window (7am-3pm) led to greater weight loss and improved mood compared to a broader eating period. She emphasizes the importance of a minimum nightly fast of 12 hours for autophagy and overall health benefits.

The field of naturopathic oncology has grown dramatically over the past decade. But how much do you know about this naturopathic sub-specialty and what does the future hold for the profession and the patients it treats? Host and Natural Medicine Journal founder Karolyn A. Gazella talks with naturopathic oncologist Payam Kiani, ND, FABNO, who is also the President of the Oncology Association of Naturopathic Physicians (OncANP). Dr Kiani provides an overview of integrative oncology, describes some of the challenges the profession has faced, and previews the organization's upcoming conference. About the Expert Payam Kiani, ND, FABNO, is a naturopathic doctor with a focus on integrative cancer care. As the president of the Oncology Association of Naturopathic Physicians (OncANP), Dr Kiani is committed to supporting patients and practitioners in the journey toward improved health outcomes. Since 2005, he has been in private practice, bringing over 2 decades of clinical expertise to his patients. Dr Kiani earned his bachelor of science in life sciences from McMaster University before completing his naturopathic doctor training at the Canadian College of Naturopathic Medicine (CCNM). For nearly 10 years, he served as a faculty member and clinical supervisor at CCNM, an experience that solidified his passion for education, mentorship, and shaping the future of naturopathic medicine. As a father of 2, he's dedicated to setting an example of service to his community and contributing as a global citizen. On weekends, he embraces his love for the ocean, spending as much time as possible swimming and recharging in nature.

Dr. Hoffman continues his conversation with Karolyn A. Gazella, founder of the Natural Medicine Journal and the host of the Natural Medicine Journal Podcast series.

Karolyn Gazella, the founder of the Natural Medicine Journal, discusses the growing field of integrative medicine, focusing on a fascinating study that demonstrates how fish oil can slow progression of Alzheimer's. She also highlights how diet and lifestyle can overcome “bad” genes, the microbiome's influence on resilience and eye health, and how physician empathy can improve patient outcomes. Karolyn also shares her extensive experience in publishing and podcasting about holistic health since 1992, and highlights the evolving respect for naturopathic practices within the medical community.

Summary Dr. Mark Davis discusses the difference between irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), specifically ulcerative colitis and Crohn's disease. He explains that IBS is a functional disease with no detectable organic changes, while IBD is an autoimmune disease with detectable changes in the tissues. Dr. Davis also explores the impact of the gut on the rest of the body, particularly the brain, through the nervous system and the blood. He highlights the role of the vagus nerve in gut-brain communication and the influence of the gut microbiome on cognitive function. Additionally, he discusses fecal microbiota transplantation (FMT) as a treatment for C. diff colitis and its potential benefits for IBD and neurodegenerative conditions. In this conversation, Dr. Mark Davis discusses the screening process for stool donors and the importance of selecting healthy individuals. He also addresses the connection between gut health and mental health, specifically in patients with inflammatory bowel disease (IBD). Dr. Davis shares various treatment approaches for anxiety and depression, including herbal medicine and therapeutic massage. The conversation also explores the potential link between IBD and Alzheimer's disease, as well as the role of diet in reducing inflammation and increasing microbial diversity in the gut. Dr. Davis concludes by discussing the potential benefits of combining helminthic therapy and fecal microbiota transplantation (FMT) for patients with multiple sclerosis (MS). 01:30 Introduction and Background 13:06 Exploring the Gut-Brain Connection 17:17 The Potential of FMT 33:54 Gut-Brain Connection in IBD 40:09 IBD and Alzheimer's Disease 44:53 Diet and Gut Health 48:56 Combining Helminthic Therapy and FMT for MS Dr. Mark Davis Dr. Davis received his doctorate of naturopathic medicine with honors in research from National University of Natural Medicine, and he is a fellow of the American Board of Naturopathic Gastroenterology. He is faculty at Sonoran University of Health Sciences (where he teaches the naturopathic gastroenterology course), and former ranked faculty at Maryland University of Integrative Health, a founder and board member of the Gastroenterology Association of Naturopathic Physicians, and on the editorial board of the Natural Medicine Journal. Dr. Davis is licensed in California, Maryland, Oregon, and the District of Columbia. You can find him at https://www.markdavisnd.net/ Click any link below to connect with Laurel Brennan, MOTR/L, RYT, CHC, ReCODE 2.0  Brain Health Quiz: What is Your Risk for Cognitive Decline? ⁠⁠https://www.rootcauseology.com/⁠⁠ for information on Brain Health Services, Yoga, and⁠ ⁠Brain Health Retreats⁠ Instagram @rootcauseology⁠⁠ ⁠⁠ TikTok @rootcauseology⁠⁠ ⁠⁠Facebook @rootcauseology⁠⁠  YouTube RootCauseologywithLaurelBrennan LinkedIn https://www.linkedin.com/in/laurel-brennan-38931945/ Private⁠ ⁠Facebook Group, Brain Wellness & Dementia Prevention Schedule a Free Consultation

On this podcast episode, you will get a “state-of-the-union” of naturopathic medicine. Karolyn is joined by 3 naturopathic medicine experts: Natural Medicine Journal Editor-in-Chief, Tina Kaczor, ND, FABNO; Executive Director of the American Association of Naturopathic Physicians (AANP), Laura Farr; and the President and CEO of the Institute for Natural Medicine (INM), Michelle Simon, PhD, ND. All 3 experts provide different perspectives on naturopathic medicine, specifically regarding consumer education, research, legislation, and future goals. About the Experts Laura Culberson Farr has served as Executive Director of the American Association of Naturopathic Physicians since 2017 and has worked with the naturopathic profession since 2005. A political organizer by training, her advocacy work as a grassroots organizer and consultant spans over 28 years. She has a deep knowledge of the complexities of healthcare reform, and has become an expert on how naturopathic doctors, conventional clinics and insurers can work together to improve patient care and reduce healthcare costs. She is married to a naturopathic physician and is passionately committed to integrating naturopathic medicine into primary care systems across the country. Michelle Simon, PhD, ND, is President and CEO of the Institute for Natural Medicine (INM), a 501(c)3 organization dedicated to educating consumers about natural medicine.  INM focuses on increasing awareness of natural medicine, demonstrating its efficacy in helping to transform healthcare systems, and connecting patients to naturopathic doctors. She earned her naturopathic doctorate from Bastyr University and her PhD in Biomedical Engineering is from the University of North Carolina at Chapel Hill. She has been awarded Physician of the Year by the American Association of Naturopathic Physicians and Champion of Naturopathic Medicine by the Washington Association of Naturopathic Physicians. Tina Kaczor, ND, FABNO, is editor in-chief of Natural Medicine Journal and the creator of Round Table Cancer Care. Kaczor is a naturopathic physician board certified in naturopathic oncology. She received her naturopathic doctorate from the National University of Natural Medicine and completed her residency at Cancer Treatment Centers of America. She is also the editor of the Textbook of Naturopathic Oncology and cofounder of The Cancer Pod, a podcast for cancer patients, survivors, caregivers, and everyone in between.

Episode 224 of my Curate Your Health Podcast is out! Link below.   Dr. John Neustadt is here today to talk about bone health and osteoporosis. He explains how bone density tests are inadequate. He wants to educate people on how to improve your bone health and protect yourselves. Medications, such as antacids, are damaging bones and increasing the risk of fractures. Patients should discuss switching to safer medications with their provider. Also, reducing spicy foods, eating earlier in the evening, and shifting your position in bed, can help with acid reflux. To help strengthen your bones, he suggests exercise, resistance training and eating a healthy diet with high protein, whole grains, fruits and vegetables.    He can be found at: https://www.nbihealth.com/, https://www.facebook.com/nbihealth/, https://www.youtube.com/user/NBIHealth, https://www.linkedin.com/in/john-neustadt-nd-1553576/, and https://twitter.com/JohnNeustadt   Dr. John Neustadt has an international reputation as a doctor, researcher, and integrative medical expert. He became renowned in this field through his nutritional medicine research, clinical work, books he wrote, work with the FDA on evaluating the use of natural products for the potential treatment of rare diseases, developing million-dollar businesses, educating physicians on improving patient outcomes and the general public on how to make sure they're getting the care they need and the results they want, and as a medical expert advising businesses on product development and how to create superfans.   Dr. Neustadt has published more than 100 medical articles, written four health and wellness books and is now a #1 Amazon Best Selling Author in the field of Osteoporosis. His most recent book is, Fracture-Proof Your Bones: A Comprehensive Guide to Osteoporosis. Dr. Neustadt was also an editor of the textbook, Laboratory Evaluations for Integrative and Functional Medicine, which was used across the United States to train and educate physicians on using functional medicine with their patients.    Dr. Neustadt is a highly sought out speaker at medical conferences, he was recognized as one of the Top Ten Cited Authors in the world for his work. His research on integrative and functional medicine has been featured in the Natural Medicine Journal, Integrative Medicine: A Clinician's Journal, Holistic Primary Care, Molecular Nutrition & Food Research, and Experimental and Molecular Pathology.    Dr. Neustadt earned his naturopathic medical degree from Bastyr University where he was awarded the Founder's Award for academic and clinical excellence. He opened his clinic, Montana Integrative Medicine (MIM), in 2005 in Bozeman, Montana. He specialized in hard-to-treat, chronic degenerative diseases through an integrative approach that emphasized identifying and correcting the underlying causes of disease. For his clinical work, Dr. Neustadt was the first naturopathic doctor to be voted Best Doctor among all physicians in his area. When the award was announced, this is what the local newspaper had to say:  “It is noteworthy that Dr. Neustadt did not win ‘best naturopathic doctor;' he won best doctor.   Dr. Hammerstedt and her lifestyle coaching team can be found at www.wholisthealth.com and @wholisthealth on Facebook and Instagram as well as the Facebook group Curate Your Health. Wholist helps high performing women and men lose weight for the last time, with an innovative food and mindset coaching program to blueprint YOUR optimal body and mind, with real food, real work, real results...and no products or BS. Come curate YOUR sustainable health future, and personal and professional dynasty.   And remember, Who you choose to be Matters. You are valuable, You are worth this, You are your WholeYou.  

The Oncology Association of Naturopathic Physicians (OncANP) is on a mission to advance the philosophy, science, and practice of naturopathic oncology. In this interview, Erica Joseph, ND, FABNO, discusses important issues associated with naturopathic oncology, including collaborating with conventional oncology, past research, and future objectives.   About the Expert Erica Joseph, ND, FABNO, is a board-certified naturopathic oncologist and acupuncturist practicing at Seattle Integrative Oncology (SIO), where she completed a 2-year oncology-based naturopathic residency. She received her doctorate in naturopathic medicine, as well as a master's degree in acupuncture, and a bachelor's degree in psychology and biology from Bastyr University. Joseph currently sees patients in both private practice and at the Providence Regional Cancer Partnership in Everett, WA, where she helps lead the integrative cancer care program. The private practice of Joseph and her colleagues at Seattle Integrative Oncology proudly provides one of the few naturopathic residencies in the Pacific Northwest. Outside her practice, Joseph has served as president of the Oncology Association of Naturopathic Physicians (OncANP) since 2021. She is also a peer reviewer for the Journal of Integrative and Complimentary Medicine (JICM) and a contributor to the Natural Medicine Journal.

Dr. Nirala Jacobi interviews Dr. Mark Davis about helminth therapy and fecal microbiota transplantation (FMT) in the treatment of various conditions. Helminth therapy involves using tiny worm-like organisms called helminths as medicine for humans. Dr. Davis explains that there are four helminths that have been found to be safe and beneficial for humans. These helminths can be used to treat conditions such as multiple sclerosis, ulcerative colitis, Crohn's disease, and autism spectrum disorder. FMT, on the other hand, involves transplanting fecal microbiota from a healthy donor into the gut of a patient. FMT has been found to be effective in treating conditions such as Clostridium difficile (C. diff) colitis and hepatic encephalopathy. Dr. Davis also discusses his new ventures in Panama, where he plans to offer helminth therapy and FMT in a hospital setting. He also mentions his work on vaginal microbiota transplantation for women's health conditions. Dr Mark Davis, ND is a 2011 graduate of NUNM, and a fellow of the American College of Naturopathic Gastroenterology. He's on the board of directors of the Gastroenterology Association of Naturopathic Physicians, and the editorial board of the Natural Medicine Journal. Dr. Davis teaches the naturopathic gastroenterology course at Southwest College of Naturopathic Medicine, and he has focused on patients with IBD since 2016.

Two amazing natural remedies! First Jared and Cheryl discuss the history and uses of OPC's from grape seed extract. You will learn about oxidative stress, polyphenols and how to use this powerful antioxidant in the most effective way possible. Next you will learn all about boswellia, which comes from the same tree as frankincense oil. They discuss the truly unique ability of boswellia extract to reduce 5-LOX in ways that drugs and other herbs simply cannot. 5-LOX is the pathway of inflammation in the gut and respiratory system. This centuries old Ayervedic remedy has modern human research proving its efficacy in balancing inflammation in these areas and more.Cheryl Myers, Chief of Scientific Affairs for EuroPharma, Inc., is a healthcare professional withcertifications in cancer, pain control, and issues of aging. She is an expert in dietary supplements and natural medicines who has been a featured guest on hundreds of radio and television shows. Cheryl is a member of the editorial board of the Natural Medicine Journal, and her own published research has included topics such as menopause, diabetes, sleep disorders, and gastrointestinal function.Products:BosmedClinical OPC French Grape Seed ExtractCuramedVisit the podcast website here: VitalityRadio.comYou can follow @vitalityradio and @vitalitynutritionbountiful on Instagram, or Vitality Radio and Vitality Nutrition on Facebook. Join us also in the Vitality Radio Podcast Listener Community on Facebook. Shop the products that Jared mentions at vitalitynutrition.com. Let us know your thoughts about this episode using the hashtag #vitalityradio and please rate and review us on Apple Podcasts. Thank you!Just a reminder that this podcast is for educational purposes only. The FDA has not evaluated the podcast. The information is not intended to diagnose, treat, cure, or prevent any disease. The advice given is not intended to replace the advice of your medical professional.

Dr. Shani Fox has stepped up over and over again to help cancer survivors through their greatest challenges, including taming the fear of recurrence, repairing devastated relationships, and making the most of the life they survived for. Bringing her unique expertise as both a holistic physician and certified life mastery coach, she has impacted countless cancer survivors with her life-changing workshops and warm personal presence.  Dr. Shani is the author of The Cancer Survivor's Fear First Aid Kit and is a popular speaker and podcast guest for survivor communities. Her posts and articles have been published in the Huffington Post, Breast Cancer Wellness magazine, and the peer-reviewed Natural Medicine Journal. ✨A few highlights from the show:   1. Listen to your inner voice and get good at listening to what you know is true. 2. People often do not feel heard in the medical system. 3. Fear of recurrence is the most common side effect of cancer. 4. Many people finish treatment feeling disempowered because the system has been making decisions for them. 5. Cancer is complex! You can't simply draw a straight line from a certain cause to the reason why a person got cancer.

Environmental medicine has become an important sub-specialty within integrative and functional medicine. Here, Natural Medicine Journal founder Karolyn A. Gazella interviews 2 leading environmental medicine specialists to learn more about the field and how clinicians can incorporate it into their clinical practice. She talks with Lyn Patrick, ND, and Anne Marie Fine,NMD, FAAEM, who are both naturopathic physicians with advanced training in environmental medicine. About the Experts Lyn Patrick, ND, graduated from Bastyr University in 1984 with a doctorate in naturopathic medicine and has been in private practice in Arizona and Colorado for 35 years. She is a published author of numerous articles in peer-reviewed medical journals, a past contributing editor for Alternative Medicine Review, and recently authored a chapter in the textbook Clinical Environmental Medicine (Elsevier 2019). She speaks internationally on environmental medicine, nonalcoholic fatty liver disease, endocrine disruption, metal toxicology, and other topics. She is currently faculty for the Metabolic Medicine Institute Fellowship in collaboration with George Washington School of Medicine and Health Sciences. She is also a founding partner and presenter at the Environmental Health Symposium, an annual international environmental medicine conference based in the United States.   After the passing of her longtime colleague Dr. Walter Crinnion, Patrick is continuing to educate primary care providers in the area of environmental medicine through the EMEI Global platform and the EMEI Review podcast. In her spare time, she enjoys biking, hiking, and kayaking the mountains, lakes, and rivers of southwestern Colorado.   Anne Marie Fine, NMD, FAAEM, is one of the world's leading authorities in environmental medicine. She is the medical director of Environmental Medicine Education International, LLC, a one-year, post-graduate course for physicians in this emerging specialty. Fine is a licensed and board-certified naturopathic physician and has held licenses to practice medicine in Arizona and California for over 20 years. Fine is a fellow of the American Academy of Environmental Medicine and past vice president of the National Association of Environmental Medicine. She currently serves on the board of the Integrative Health Policy Consortium and as a science advisor to Made Safe. She is also the Founder of Fine Natural Products, LLC, a best-selling author, consultant to the personal care product industry, published author of numerous articles in international peer-reviewed journals, and internationally recognized speaker. Fine is a former CPA and financial executive who graduated from the Mendoza School of Business at the University of Notre Dame.

Join us for a great conversation with our guest Dr. Heather Zwickey, PhD.  We talk about the early days of EBM in Integrative Medicine. From, "Why are you trying to destroy our medicine?!" to EBM champions and the thorough integration of the EBM 'way of thinking' into training institutions. Check out more on www.DrJournalClub.com and become a member. Learn more about Dr. Zwickey here: www.heatherzwickey.comSome of Dr. Zwickey's papers on the topics we discussed. Allen, E S., Connelly, E.N., Morris, C.D., Elmer, P.J., and H. Zwickey.  A Train the Trainer Model for Integrating Evidence-Based Medicine into a Complementary and Alternative Medicine Training Program. Explore (NY). 2011 Mar-Apr;7(2):88-93.Connelly, E. N., Elmer, P. J., Morris, C. D., and H. Zwickey.  The Vanguard Faculty Program: Research Training for Complementary and Alternative Medicine Faculty.  Journal of Alternative and Complementary Medicine.  2010 Oct;16(10):1117-23.Senders, A., Erlandsen, E. and H. Zwickey. The Importance of Research Literacy. The Natural Medicine Journal. 2014 Aug: 6(8):Zwickey, H., Schiffke, H., Fleishman, S., Haas, M., Cruser, D., LeFebvre, R., Sullivan, B., Taylor, B. and B. Gaster. Teaching Evidence-Based Medicine at Complementary and Alternative Medicine Institutions. Strategies, Competencies and Evaluation. Journal of Alternative and Complementary Medicine. 2014 Dec;20(12):925-31. PMID: 25380144 Learn more and become a member at www.DrJournalClub.comCheck out our complete offerings of NANCEAC-approved Continuing Education Courses.

Dr. John Neustadt has an international reputation as a researcher and integrative medical expert. Dr. John became renowned in this field through his nutritional medicine research, clinical work, books, and work with the FDA on evaluating the use of natural products for the potential treatment of rare diseases, developing million-dollar businesses educating physicians on improving patient outcomes, and the general public on how to make sure they're getting the care they need and the results they want! In this episode, Tee and Dr. John discuss the importance of achieving sleep naturally and cover some of the simple techniques that John uses with his patients to achieve this process. Dr. John also unpacks some of the biological processes of sleep and why it is so vital for healing, wellness, focus, and mental health. Dr. Neustadt is a highly sought-after speaker at medical conferences, he was recognized as one of the Top Ten Cited Authors in the world for his work. Dr. John's research on integrative and functional medicine has been featured in the Natural Medicine Journal, Integrative Medicine: A Clinician's Journal, Holistic Primary Care, Molecular Nutrition & Food Research, and Experimental and Molecular Pathology.  Dr. Neustadt earned his naturopathic medical degree from Bastyr University where he was awarded the Founder's Award for academic and clinical excellence. He opened his clinic, Montana Integrative Medicine (MIM), in 2005 in Bozeman, Montana. He specialized in hard-to-treat, chronic degenerative diseases through an integrative approach that emphasized identifying and correcting the underlying causes of disease. For his clinical work, Dr. Neustadt was the first naturopathic doctor to be voted Best Doctor among all physicians in his area. When the award was announced, this is what the local newspaper had to say: “It is noteworthy that Dr. Neustadt did not win ‘best naturopathic doctor;' he won the best doctor.  Discount for Listeners: 30% discount on all NBI products to listeners. Simply use the NBI30 coupon code during checkout in the NBI store. The discount will combine with the quantity discounts, allowing people to save even more money!   Connect With Dr. John Email: DrNeustadt@NBIHealth.com  Phone: (858) 527-5459  Website: NBIHealth.com  Twitter: https://twitter.com/JohnNeustadt Facebook: https://www.facebook.com/nbihealth/ Youtube: https://www.youtube.com/@NBIHealth _______________________________________________ Follow Therese "Tee" Forton-Barnes and The Green Living Gurus: Tee's Organics - Therese's Healthy Products for You and Your Home: https://thegreenlivinggurus.com/shop-tees-organics/ The Green Living Gurus Website: https://thegreenlivinggurus.com/ Instagram: https://www.instagram.com/greenlivinggurus/ Youtube: https://www.youtube.com/channel/UCW7_phs1GZUPzG21Zgjnqtw Facebook: https://www.facebook.com/GreenLivingGurus Healthy Living Group on Facebook Tip the podcaster! Support Tee and the endless information that she provides: Patreon: https://www.patreon.com/TheGreenLivingGurus Venmo: @Therese-Forton-Barnes last four digits of her cell are 8868 For further info contact Tee: Email: Tee@TheGreenLivingGurus.com Cell: 716-868-8868

Sponsored by DaVinci Laboratories Millennials are now the nation's largest living adult generation, surpassing Baby Boomers in 2019. In the world of integrative medicine, this presents a significant opportunity to help a lot of patients achieve better health and protect themselves from common chronic illnesses. In this interview, Tina Kaczor, ND, FABNO, talks about practical, effective integrative health strategies that can reduce disease risk in millennials. In addition to being NMJ's editor-in-chief, Kaczor is the editor of the Textbook of Naturopathic Oncology and host of the popular podcast The Cancer Pod (https://podcasts.apple.com/us/podcast/the-cancer-pod-a-resource-for-cancer-patients/id1584013388). ----- "Simple and Relaxing Minimal Ambient" by Coma-Media and “Inspirational Background” by AudioCoffee via pixabay.com. About the Expert Tina Kaczor, ND, FABNO, is editor in-chief of Natural Medicine Journal and the creator of Round Table Cancer Care. She is a naturopathic physician board certified in naturopathic oncology. Kaczor received her naturopathic doctorate from the National University of Natural Medicine and completed her residency at Cancer Treatment Centers of America. She is also the editor of the Textbook of Naturopathic Oncology and cofounder of The Cancer Pod, a podcast for cancer patients, survivors, caregivers, and everyone in between. About the Sponsor NEARLY 50 YEARS OF KNOWLEDGE We are a family-owned and managed company and are always willing to assist you in any way possible on matters relating to nutrition. Every day, we work hard to set new standards for quality and product innovation so we can keep you as healthy and informed as possible. Meet Our Family.

Karolyn A. Gazella, founder of the Natural Medicine Journal and host of the NMJ Podcast, joins Lise Alschuler, ND, FABNO, editor, Abstracts & Commentary, of the Natural Medicine Journal, for a discussion about the journal's mission, vision, and commitment to supporting the naturopathic and integrative healthcare communities. About the Experts Lise Alschuler, ND, FABNO, is a professor of clinical medicine at the University of Arizona where she is the associate director of the Fellowship in Integrative Medicine at the Andrew Weil Center for Integrative Medicine. Alschuler obtained her naturopathic medical degree from Bastyr University where she completed her residency in general naturopathic medicine. She received her bachelor of science degree from Brown University. She is board-certified in naturopathic oncology. Alschuler is past-president of the American Association of Naturopathic Physicians and a founding board member, immediate past-president and current board member of the Oncology Association of Naturopathic Physicians. She is coauthor of Definitive Guide to Cancer, now in its 3rd edition, and Definitive Guide to Thriving After Cancer. Karolyn A. Gazella is the founder of the Natural Medicine Journal and the host of the Natural Medicine Journal Podcast series. She also co-hosts the Five to Thrive Live weekly radio show on the Cancer Support Network, which is also widely available as a podcast. She has been writing and publishing integrative health information since 1992 and is the author or co-author of several books and booklets on a variety of holistic health topics. ------ "Simple and Relaxing Minimal Ambient" by Coma-Media and “Inspirational Background” by AudioCoffee via pixabay.com.

Chronic fatigue syndrome (CFS) is a poorly understood condition that affects up to 2.5 million Americans. Since the Covid-19 pandemic has left untold numbers of people with postviral symptoms that resemble CFS, interest in understanding the condition has been renewed. In a recent NMJ Podcast interview Natural Medicine Journal editor-in-chief Tina Kaczor, ND, FABNO, spoke with Jacob Teitelbaum, MD, who has studied postviral CFS for decades.  About the Expert Jacob Teitelbaum, MD, is one of the most frequently quoted integrative pain and fibromyalgia medical authorities in the world. He is the author of the best-selling From Fatigued to Fantastic!, Pain Free, 1,2,3!, the Complete Guide to Beating Sugar Addiction, Real Cause Real Cure, the Fatigue and Fibromyalgia Solution, Diabetes Is Optional, and the popular free smartphone app Cures A-Z. He is the lead author of 5 studies and 3 textbook chapters on fibromyalgia and chronic fatigue syndrome treatments, and a study on treatment of autism using Nambudripad's Allergy Elimination Techniques (NAET). The views expressed in this interview are those of the guest and do not represent the views of Natural Medicine Journal, its staff, or its publishers. ------ "Simple and Relaxing Minimal Ambient" by Coma-Media and “Inspirational Background” by AudioCoffee via pixabay.com.

A conversation with naturopathic oncologist and colon cancer expert Tina Kaczor, ND, FABNO On October 9, 2022, the New England Journal of Medicine published a study that questioned the benefits of colonoscopy, which was then picked up by many national media outlets. In this interview, Natural Medicine Journal Editor-in-Chief Tina Kaczor, ND, FABNO, discusses the study and talks about utilizing an integrative approach to reduce colon cancer risk. She also provides guidance on how to discuss this topic with patients.    About the Expert Tina Kaczor, ND, FABNO, is editor-in-chief of Natural Medicine Journal and the creator of Round Table Cancer Care. Kaczor is a naturopathic physician board certified in naturopathic oncology. She received her naturopathic doctorate from the National University of Natural Medicine and completed her residency at Cancer Treatment Centers of America. She is also the editor of the Textbook of Naturopathic Oncology and cofounder of The Cancer Pod, a podcast for cancer patients, survivors, caregivers, and everyone in between.

On this show Karolyn talks with Dr. Tina Kaczor who is a naturopathic oncologist in Oregon. Dr. Kaczor will compare and contrast chemo brain and covid brain and provide practical advice on how to strengthen brain function with diet, lifestyle, and dietary supplements. Dr. Kaczor is also the co-host of the popular podcast, The Cancer Pod, and the Editor-in-Chief of the Natural Medicine Journal.Five To Thrive Live is broadcast live Tuesdays at 7PM ET.Five To Thrive Live Radio Show is broadcast on W4CS Radio – The Cancer Support Network (www.w4cs.com) part of Talk 4 Radio (www.talk4radio.com) on the Talk 4 Media Network (www.talk4media.com).Five To Thrive Live Podcast is also available on Talk 4 Podcasting (www.talk4podcasting.com), iHeartRadio, Amazon Music, Pandora, Spotify, Audible, and over 100 other podcast outlets.

Sponsored by DaVinci Laboratories   The health and appearance of a patient's skin can be a direct reflection of their health status. In addition, many patients are very interested in maintaining or regaining youthful, healthy-looking skin. Collagen peptides and other natural ingredients can help enhance a patient's skin health routine. In this interview, Natural Medicine Journal Editor-in-Chief and naturopathic oncologist Tina Kaczor, ND, FABNO, discusses how collagen can help enhance skin health and how to choose the most effective form of collagen. She also talks about potential complementary ingredients.   About the Expert Tina Kaczor, ND, FABNO, is editor in-chief of Natural Medicine Journal and the creator of Round Table Cancer Care. Kaczor is a naturopathic physician board certified in naturopathic oncology. She received her naturopathic doctorate from the National University of Natural Medicine and completed her residency at Cancer Treatment Centers of America. She is also the editor of the Textbook of Naturopathic Oncology and cofounder of The Cancer Pod, a podcast for cancer patients, survivors, caregivers, and everyone in between. About the Sponsor DaVinci Labs believes that better health starts with better information. We have compiled an array of educational media aimed at providing the most cutting-edge education and practice support for today's integrative practitioner, as well as providing everything an inquisitive consumer needs to know to take control of their own health: Blogs Learning Center Empowering Patients & Practitioners for a Naturally Healthy World

Today, I am joined by one of my good friends, Dr. Meighan Valero! Dr. Valero is one of the preeminent naturopathic doctors in Canada with a focus on cancer. She believes in an integrative and evidence-based approach to supporting patients with cancer throughout conventional therapy. She utilizes a combination of techniques such as intravenous therapy, supplementation, dietary and lifestyle counseling, acupuncture, and botanical medicine. She is incredibly credentialed and experienced at what she does.   Unfortunately, it is no exaggeration to say that we all will have cancer touch our lives at some point. One in two of us will be diagnosed with cancer in our lifetimes. Understanding what is possible from an integrative approach is something that we all deserve to know and I cannot think of anyone better to drive this conversation than Dr. Meighan Valero!   In this episode, she is sharing her own personal story that has driven her to passionately explore and provide incredible integrative cancer care, as well as how she works with her current patients when it comes to addressing cancer.   Key Takeaways: [1:04] About today's episode with my good friend, Dr. Meighan Valero. [2:37] Welcoming Dr. Valero to the podcast! [3:16] Meighan shares her story and why this particular avenue of naturopathic medicine is something she is incredibly passionate about. [6:02] What integrative oncology is and what it has the potential to be for patients with cancer. [9:47] What health consumers should know about FABNO credentialing. [13:08] Red flags to be on the lookout for when exploring integrative options with respect to cancer management. [15:22] Meighan shares what the experience is like to work with her as a patient, and gives advice to patients looking to approach their oncologist in asking them to work with a naturopathic doctor. [22:13] How patients can approach this conversation with both of their medical teams and what they can do to be proactive in their care. [25:51] One of the problems with only engaging with the traditional approach to cancer and why blending both camps is the most effective. [27:33] What treatment looks like after cancer. [30:11] Meighan's key-performance indicators! [24:36] Where to learn more about what Meighan is doing in this world. [35:36] Reflections from today's episode. [37:26] About next week's episode!   Mentioned in This Episode:Dr. Meighan Valero The Entrepology Podcast Ep. 243: “Body: You Can Live and Thrive with Cancer — This is How with Dr. Lori Bouchard, ND” Integrative Oncology | Dr. Meighan Valero ND | TEDxWindsor (Video) FABNO Certification The Metabolic Approach to Cancer: Integrating Deep Nutrition, the Ketogenic Diet, and Nontoxic Bio-Individualized Therapies, by Dr. Nasha Winters, ND and Jess Higgins Kelley, MNT Peloton   More About Dr. Meighan Valero Dr. Valero's practice focus is on adjunctive cancer care and chronic illness. Born and raised in Windsor, ON, she completed a Bachelor of Arts and Science degree with a major in Biochemistry and a minor in Psychology. She worked as a cancer research assistant for Dr. Siyaram Pandey at the University of Windsor for five years and later graduated from the Canadian College of Naturopathic Medicine where she received special training in naturopathic oncology as an intern in Toronto and became the first Oncology Research Resident in Ottawa. Her passion lies in developing individualized treatment protocols for those who wish to prevent cancer, those living with cancer, and those with a desire to learn the tools and necessary lifestyle changes to prevent a recurrence of a previously treated cancer.   She believes in an integrative and evidence-based approach to supporting patients with cancer throughout conventional therapy. She utilizes a combination of techniques such as intravenous therapy, supplementation, dietary and lifestyle counseling, acupuncture, and botanical medicine. Dr. Valero is very open to establishing professional relationships with local oncologists in order to work together for the overall well-being and improved quality of life of the patient.   She has authored several research publications including: “Complementary Strategies for the Management of Radiation Therapy Side Effects,” published in the Journal of the Advanced Practitioner in Oncology, “Identifying and Treating Magnesium Deficiency in Cancer Patients Receiving Platinum-Based Chemotherapy,” published in Natural Medicine Journal, “Chemotherapy-Related Cognitive Impairment”; “Chemotherapy and Radiation-Induced Oral Mucositis,” published in The Journal of IHP.   Connect with my Guest: Websites: ValeroWellness.com and V-Apothecary.com Social Media: Instagram @DoctorValero, Instagram @ValeroWellness, Facebook @ValeroWellness, Instagram @V.Apothecary & Facebook V.Apothecary   If you enjoyed our conversation and would like to hear more: Please subscribe to The Entrepology Podcast on Stitcher or iTunes. We would also appreciate a review!   Come Join Your Community on The Entrepology Collective Facebook Page! They say that you're the product of the five people with whom you spend the most time. Imagine you could spend time with hundreds of fellow entrepreneurs and go-getters looking to up-level their business, body, and mindset! Come hang out with us on Facebook and let us collectively inspire and support you towards your vision of contribution, your commitment towards better health, and your journey of mindset mastery. We're in this together! Come join us today!   CALL TO ACTION If you haven't already, be sure to listen to episode 243 of The Entrepology Podcast with Dr. Lori Bouchard, where we spoke about living and thriving with cancer. And, if you loved this week's episode, be sure to leave a review anywhere you listen to podcasts!  

Preventing and reversing age-related brain dysfunction has become a key clinical goal for many practitioners and their patients. In this interview, integrative health expert Tina Kaczor, ND, FABNO, explains some of the key mechanisms associated with the development of age-related brain dysfunction and dementia. She also describes specific nutrients and herbs that can help protect and enhance brain function along with diet and lifestyle advice. About the Expert Tina Kaczor, ND, FABNO, is editor in-chief of Natural Medicine Journal and the creator of Round Table Cancer Care. She is a naturopathic physician board certified in naturopathic oncology. Kaczor received her naturopathic doctorate from the National University of Natural Medicine and completed her residency at Cancer Treatment Centers of America. She is also the editor of the Textbook of Naturopathic Oncology and cofounder of The Cancer Pod, a podcast for cancer patients, survivors, caregivers, and everyone in between. About the Sponsor NEARLY 50 YEARS OF KNOWLEDGE We are a family-owned and managed company and are always willing to assist you in any way possible on matters relating to nutrition. Every day, we work hard to set new standards for quality and product innovation so we can keep you as healthy and informed as possible. Meet Our Family.

“None of us is less worthy than the other. We are life-celebrating itself” In this episode, Dr Shani Fox talks about her motivation for leaving her corporate job for a PhD program at the age of 40. She shares the Cancer Survivor's Fear First Aid Kit, which is useful for cancer survivors and the people around them. She talks about how we can deal with fear, vulnerability and guilt. Connect with Dr Shani Fox Website: https://drshanifox.com/ Facebook Group for Women: https://www.facebook.com/groups/risingbeyondcancer/ “If it is to be, it is up to me.” Thank you for joining me on this MIRROR TALK podcast journey. Kindly stay connected by subscribing or following on any platform. Please do not forget to leave a review and rating. Let us connect on Instagram: https://www.instagram.com/mirrortalk.podcast/ More inspiring episodes and show notes here: https://mirrortalkpodcast.com/ I love you, I see you, I appreciate you. SPONSORED BY KITCASTER: Dear friend, you can grow your personal and business brand by creating a strong network through podcasting. Create real human connections, have the ability to share your story and interesting point of view. To get started, you can make use of the special offer for friends of this podcast on https://kitcaster.com/mirror ABOUT DR. SHANI FOX Dr Shani Fox has stepped up over and over again to help cancer survivors through their greatest challenges, including taming fear of recurrence, repairing devastated relationships and making the most of the life they survived for. Bringing her unique expertise as both holistic physician and certified life mastery coach, she has impacted countless cancer survivors with her life-changing workshops and warm personal presence. Dr Shani is the author of The Cancer Survivor's Fear First Aid Kit and is a popular speaker and podcast guest for survivor communities. Her posts and articles have been published in the Huffington Post, Breast Cancer Wellness magazine and the peer-reviewed Natural Medicine Journal.

In this episode, we're joined by Dr. Shani Fox. One out of two men and one out of three women will encounter cancer firsthand in their lifetime, and all of us know someone who's had to meet the challenge of cancer. Dr. Shani Fox has stepped up over and over again to help cancer patients and survivors through their greatest challenges, including taming fear of recurrence, repairing devastated relationships and making the most of the life they survived for. Bringing her unique expertise as both holistic physician and certified life mastery coach, Dr. Shani has impacted thousands of survivors with her life-changing messages and warm personal presence. Dr. Shani is also the author of The Cancer Survivor's Fear First Aid Kit and a popular radio and podcast guest for survivor communities. Her posts and articles have been published in the Huffington Post, Breast Cancer Wellness magazine and the peer-reviewed Natural Medicine Journal. In this episode, we explore: the body and mind link lifestyles that support wellness functioning in a world where fear is present all the time meeting people where they are disempowerment make or break factors that help survivors thrive resisting kindness Mentioned in this episode TED Talk - Susan Cain: The Power of Introverts TED Talk - Brene Brown: The Power of Vulnerability Brene Brown: The Call to Courage You can connect with Dr. Shani via Facebook, Linkedin or via her website Follow our host Hannah @hannah.stainer on Instagram or on twitter. Follow our podcast @psykhecoaching on Instagram, Twitter, Facebook or connect with us via our website where you can download your gratitude journal by signing up to our mailing list. Support the podcast by sending us a coffee via Ko-Fi We're now on Clubhouse, connect with Hannah @hstainer and join us to chat about mental health and wellbeing. If you've loved this episode as much as we have please do share it on social media and tag us in your post. And we always love to hear what you think so please rate and review on itunes or wherever you listen to your podcasts. Thanks for listening! Hannah & the Psykhe Podcast team x --- Send in a voice message: https://anchor.fm/psykhe/message

There is a lot going on with vaccines right now and it can sometimes be difficult to stay abreast of the most current information. In this interview, immunologist and Natural Medicine Journal covid-19 resource Heather Zwickey, PhD, answers questions about antibody dependence enhancement, vaccines and mammograms, how the Johnson & Jonson vaccine is different, herd immunity, and more.Natural Medicine Journal Podcast is brought to you by Talk 4 Podcasting (www.talk4podcasting.com/) on the Talk 4 Media Network (www.talk4media.com).

Enhancing immunity in some patients may require a comprehensive approach to stress management. In this interview, integrative health expert and Natural Medicine Journal editorial board member Ramneek Bhogal, DC, DABCI, provides clinical insights on how best to help patients deal with stress while enhancing immunity. Bhogal provides clinical rationale for the use of targeted dietary supplements to help with stress management and immune enhancement.  About the Expert Ramneek Bhogal, DC, DABCI, enjoys private practice at Wolfe Family Chiropractic in Metamora, MI. A graduate of Palmer College of Chiropractic, he is also a diplomate of the American Board of Chiropractic Internists and has trained with the Institute of Functional Medicine. Bhogal has been published in peer-reviewed journals and recently coauthored a chapter in a pediatric chiropractic textbook with his wife, Stephanie O’Neill Bhogal, DC, DICCP. Together, they also established Peak Potential Outreach, a nonprofit organization committed to bringing healthcare to the globally underprivileged. About the Sponsor NEARLY 50 YEARS OF KNOWLEDGE We are a family-owned and managed company and are always willing to assist you in any way possible on matters relating to nutrition. Every day, we work hard to set new standards for quality and product innovation so we can keep you as healthy and informed as possible. Meet Our Family.

Are you tired of hearing conflicting opinions about which types of diets are good and bad for you? It seems like everyone has something to say.    Dr. Daniel Chong is here to straighten out some of our misconceptions especially when it comes to cholesterol and plant-based diets.    Dr. Daniel Chong is a cardiovascular expert and graduate from the National University of Natural Medicine in Portland. He's been a practicing naturopathic physician since 2000, and his work primarily focuses on helping people optimize cardiovascular and metabolic health. He's also a contributing editor in the cardiology section for the Natural Medicine Journal and has worked for four years as a clinical consultant for Boston Heart Diagnostics Laboratory.   We're talking all about lowering cholesterol, reducing inflammation and using food as a tool for improving our health.   If you want to learn more about the many benefits of a plant-based diet, be sure to tune in!    I would love to connect on Facebook or Instagram!   Show notes available at www.drerinkinney.com/7

Dr. Shani Fox has stepped up over and over again to help cancer patients and survivors through their greatest challenges, including taming fear of recurrence, repairing devastated relationships and making the most of the life they survived for.  Bringing her unique expertise as both holistic physician and certified life mastery coach, she's impacted thousands of survivors with her life-changing messages and warm personal presence. Dr. Shani is also the author of The Cancer Survivor's Fear First Aid Kit and a popular radio and podcast guest for survivor communities.  Her posts and articles have been published in the Huffington Post, Breast Cancer Wellness magazine and the peer-reviewed Natural Medicine Journal.You create your life. We are teaching you to create your life on purpose. Happiness and Freedom are your birthright!  We have curated an AMAZING Happiness and Health Package with 9 amazing teachers and a TON of free gifts: guides, video series, e-courses, meditations and more! Go grab that here! https://www.behappyfirst.org/JulyHere's your direct link to some free guided meditations! Check out the General Meditation or the Connect with Your Body Meditation to get back in touch with your sacred physical form. Love, respect, communication… the basics for any great relationship. When you have a great relationship with Your Body, Your Body will give you everything you want!  https://www.behappyfirst.org/meditateWatch or listen to past episodes of The How To Choose Happiness and Freedom Show on the Be Happy First Website. https://www.behappyfirst.org/showLearn the 5 Secrets to Being Happy and Free here! https://www.behappyfirst.org/journalplaybookI love you and I'm so glad you're here!  Be sure to subscribe to this channel, "like and follow" the Be Happy First Facebook Page  https://www.facebook.com/behappyfirst/Join our PRIVATE Facebook Group Be Happy First Together for deeper conversations and support. https://www.facebook.com/groups/1252277614898225/Welcome to the Be Happy First Tribe! Remember, Happiness is a Choice! You can always choose to Be Happy First!  

Enhancing immunity in some patients may require a comprehensive approach to stress management. In this interview, integrative health expert and Natural Medicine Journal editorial board member Ramneek Bhogal, DC, DABCI, provides clinical insights on how best to help patients deal with stress while enhancing immunity. Dr. Bhogal provides clinical rationale for the use of targeted dietary supplements to help with stress management and immune enhancement.Natural Medicine Journal Podcast is brought to you by Talk 4 Podcasting (www.talk4podcasting.com/) on the Talk 4 Media Network (www.talk4media.com).

This episode features Natural Medicine Journal covid-19 expert, Dr. Heather Zwickey who answers questions about mRNA technology, long-term immunity, and how to help enhance a patient's response to the vaccine. She also talks about Moderna's request to cut the dose in half and describes which patients may need to be careful regarding vaccine efficacy. Dr. Zwickey is an immunologist and professor at National University of Natural Medicine in Portland, OR.Natural Medicine Journal Podcast is brought to you by Talk 4 Podcasting (www.talk4podcasting.com/) on the Talk 4 Media Network (www.talk4media.com).

Creating Abundance In Spite of Cancer   In this episode, Dr. Shani talks about healing and hope for Cancer Survivors in their recovery process.   Take away: Cancer is something that happens to you, it is not who you are. Action step: Remember that there's part of you that was and always healthy. Your job is to get back to who you really are. Money Learnings: Dr. Shani learned nothing about money from her parents not until she took Accounting.  Bio: Dr. Shani is the author of The Cancer Survivor’s Fear First Aid Kit and is a popular speaker, podcast guest and workshop leader for survivor communities. She has been published in the Huffington Post, Breast Cancer Wellness magazine and the peer-reviewed Natural Medicine Journal. Dr. Shani invites you to view her free training “Your Path to Freedom: Releasing Fear About Cancer” at her website, drshanifox.com.   Highlights from this episode: Link to episode page Milestone Birthday long walks How abundance get generated Health & spirituality - how it intersects and go together The first step to take to get out of fear The Compost Theory Signs that somebody is struggling How much mindset play in survival Burning questions from her patients Sharing vulnerability helps Cancer prevention drshani@drshanifox.com   Richer Soul Life Beyond Money. You got rich, now what? Let’s talk about your journey to more a purposeful, intentional, amazing life. Where are you going to go and how are you going to get there? Let’s figure that out together. At the core is the financial well being to be able to do what you want, when you want, how you want. It’s about personal freedom!   Thanks for listening!   Show Sponsor: http://profitcomesfirst.com/   Schedule your free no obligation call: https://bookme.name/rockyl/lite/intro-appointment-15-minutes   If you like the show please leave a review on iTunes: http://bit.do/richersoul   https://www.facebook.com/richersoul   http://richersoul.com/   rocky@richersoul.com   Some music provided by Junan from Junan Podcast   Any financial advice is for educational purposes only and you should consult with an expert for your specific needs.  

Please, help me to welcome Dr. Shani Fox, a Holistic Medicine Physician, an Author, and Mastery Coach to be on My Best Healer podcast. Dr. Shani Fox has stepped up over and over again to help cancer patients and survivors through their greatest challenges, including taming fear of recurrence, repairing devastated relationships, and making the most of the life they survived for. Bringing her unique expertise as both holistic physician and certified life mastery coach, Dr. Shani has impacted thousands of survivors with her life-changing messages and warm personal presence.Dr. Shani is the author of The Cancer Survivor's Fear First Aid Kit and a popular radio and podcast guest for cancer survivor communities. Her posts and articles have been published in the Huffington Post, Breast Cancer Wellness magazine, and the peer-reviewed Natural Medicine Journal. Thank you for listening, feel free to share this episode of My Best Healer with the world. Because when you share it, it shows you care.Always Stay Awesome and Amazing.Yours,Dr. Ezzat Moghazywww.mybetshealer.comSupport the show (https://www.mybesthealer.com/)

African Americans and other people of color throughout the United States are suffering disproportionately from Covid-19. In this interview, Udaya Thomas, MSN, MPH, APRN, CYT, talks about how integrative practitioners can better serve the health needs of underserved populations during this pandemic. Thomas is an integrative primary care nurse practitioner and the board president of Integrative Medicine for the Underserved, a nonprofit organization of multidisciplinary practitioners committed to affordable, accessible integrative healthcare for all. About the Expert A. Udaya Thomas, MSN, MPH, APRN, CYT, is a board-certified nurse practitioner in primary care and practices integrative medicine in a Safety-Net hospital system for the underserved in Southeast Florida at Memorial Primary Care. She is also pursuing her PhD in nursing at Walden University’s interdisciplinary health track, focusing on the integration of behavioral health in primary care. Udaya is also the board president of the non-profit organization Integrative Medicine for the Underserved (IM4US). Disclosure: Thomas is partially funded by Grant #5T06SM060559-07 of Substance Abuse Mental Health Service Association (SAMHSA) American Nursing Association (ANA) Minority Fellowship Program (MFP). SAMHSA is a government resource for practitioners and the ANA MFP is currently accepting applications for more minority fellows. Transcript Karolyn Gazella: Today, our topic is serving the healthcare needs of underserved populations. We'll also discuss the fact that African Americans and other people of color are suffering disproportionately from Covid-19. Hello, I'm Karolyn Gazella, your host and the publisher of the Natural Medicine Journal. My guest is integrative primary care nurse practitioner Udaya Thomas. Udaya presently works in a safety net hospital system for the underserved in Southeast Florida at Memorial Primary Care and she is also pursuing her PhD in nursing. Udaya, thank you so much for joining me. Udaya Thomas: Thanks for having me Karolyn. It's great to be with you and thanks also to my colleague Priscilla Abercrombie, Past President of IM4US for connecting us. Gazella: Yes, that's great. Yeah. Now before we jump into our topic, tell us a little bit about your present clinical work at Memorial Primary Care. Thomas: Well, I work as a primary care nurse practitioner in a patient-centered medical home, and actually for the past 5 weeks instead of person care, we've had to go virtual with Covid-19 pandemic, but our administration led us into a quick change and we're doing 100 percent telehealth encounters. Patients can also message me directly to give them access to me whenever they need it. Gazella: That's great. Now, where does your interest in healthcare disparity spring from? Thomas: I would say from growing up as a first-generation Indian immigrant in a low-resource rural community, I've always actually been interested in integrative approaches. So I chose nursing and public health as my path to work for the underserved in this country. Gazella: That's great. So you're the president of Integrative Medicine for the Underserved, also known as IM4US. Tell us a little bit about that organization. Thomas: IM4US is a nonprofit organization of multidisciplinary practitioners who are committed to affordable, accessible, integrative health for the underserved. IM4US is the only integrative health organization focused solely on the underserved, which makes us fairly unique. We support practitioners that serve underserved populations to outreach, education, research, and advocacy. We also have equity, diversity, and inclusion principles for all the work that we do. And while we typically have an in-person annual conference, due to the coronavirus precautions, we've moved our 10th annual conference to a virtual conference. Our underserved communities have been specifically affected by the crisis, not only because they're more likely to be susceptible to getting ill, but being out of work for this long really puts them at risk by not having an income, leading to less resources and poor health outcomes. Gazella: Yeah, and I want to talk about that in a little bit more detail because right now, given the data that we've received presently more African Americans and other people of color throughout the United States are dying of Covid-19 compared to Whites. Now this crisis is really shining a bright light on existing healthcare disparity. So from your perspective, what is the present Covid-19 crisis telling us about this huge healthcare gap that exists in this country? Thomas: There's so many factors. As Dr. Zwickey mentioned and at the end of your last podcast with her, the coronavirus pandemic has really turned on a loudspeaker to how many disparities there really are. Studies have shown that social determinants of health are responsible for on average 50% of people's health outcomes. For example, The Hill published last week that African Americans are 6 times more likely to die than their white counterparts in Chicago. Yesterday morning, Governor Cuomo commented on CNN, the new rise in Latino cases and deaths in New York. Suffice it to say that comparative to their percentage in the population, minorities are greatly affected and dying at a much higher rate. Current estimates as you might know, are up to 70% areas with concentrated low-income minorities. So is it their racial background or ethnicity that puts them at risk? Well, in the case of coronavirus and most illnesses, actually no. Rather, it's poor social determinants of health, the lack of employment, safe and stable housing, literacy level, and access to healthy food options that determine health outcomes. These determinants are responsible for most health inequities, as well as lack of access to equitable care. For example, Karolyn, a New York hospital was recently highlighted in the lower-income part of town that is struggling with fewer resources compared to wealthier areas. It's a systemic issue. Because of all the challenges and sometimes trust issues, minorities may delay seeking care too. At IM4US we help practitioners attempt to level the playing field by offering low-cost solutions and increase access to integrative modalities and care and to increase trust. We also provide members opportunities to get involved with educational and policy initiatives to support the underserved. Gazella: Yeah, I love that about your organization and it's going to be especially interesting for our listeners and readers because they already practice integrative medicine. So the fact that they can take their medicine and now serve the underserved, I think it's really a cool thing. And you know, you mentioned that 70% of deaths that studies showed that even though 70% of the deaths were in African Americans, African Americans only represented 32% of the population. So that is a really big healthcare disparity issue that we have. Now, as you mentioned, it is a systemic issue and it's clear that it needs to be addressed systemically. But what can integrative practitioners do to help ensure that they're not contributing to the problem or perpetuating healthcare disparity issues in their clinical practice? Thomas: Mm-hmm (affirmative) Great question, Karolyn. While there are many things that practitioners and specifically integrative practitioners can do, but just to mention a few really important things that could make a great impact. One, they can do implicit bias training. This is a free training and it's online and it allows practitioners to find out their own biases as we all have them, whether we work for the underserved or not. Secondly, practices if they don't already have one, can try to secure a legal aid attorney to offer low-income patients legal advice and representation when facing issues like discrimination or eviction for example, and third, they can join our movement. IM4US promotes groups as a way to build trust and increase access to integrative care. In light of the current crisis, we're recommending telehealth groups whether in the time of Covid-19 or not, we can also offer medical group visits via telehealth. It's a great way to connect patients, HIPAA-compliant consent of course together with care team members to increase social connection, reduce loneliness, anxiety and fear that the public is currently living with. Gazella: Yeah, that's true. What about people who may not have internet access? Does the telehealth visits still work? Thomas: Great question. Actually we are putting together some continuing education for our upcoming conference and on that specific topic because we want to address access to everybody. I know actually that even when I do telehealth visits just with family members together, hearing multiple voices together and knowing that they're connected to their practitioner and their care team, whether through telephone or through video really makes their spirits lift and a sense of relief that they had contact with you. And you're right, many don't have high internet speed or access to join by video, but making group chats available is also helpful and just knowing someone is on the other line can save a life. Gazella: Yeah. Like when you mentioned in the very beginning that your patients actually have access to you and they can message you. That's huge. And I would think that that would be a big part of their healing and a part of their care. Now, where can people find more information about IAM4US? Thomas: Well, we have a website and I'll give you the address. It's www.im4us.org. Gazella: Perfect. We'll also put a link to that website on our Natural Medicine Journal site so people can just click over and find access. It's a great organization, lots of resources, and really doing some good work to help underserved populations. So Udaya, thank you so much for joining me today. Thomas: You're welcome, Karolyn. We've been around for about 12 years, so we're still considered somewhat young, but like I said, we're having our 10th anniversary this year and we're really excited to have more of the community join us. Gazella: Yeah, absolutely. Well, happy anniversary- Thomas: Thank you. Gazella: … and this is a conversation that we're going to keep going. I think it's such an important one. You know we provided some good information, but let's just keep talking about it. I think this is very, very important. I also want to remind listeners that you can find all of our past podcasts at naturalmedicinejournal.com. Today I mentioned the ones that I've done with Dr. Zwickey on Covid-19. But we have lots of information at naturalmedicinejournal.com and our podcasts are also available on Pandora, Spotify, iHeartRadio, iTunes, and many other podcast outlets. So thanks for listening everyone and stay safe.

This podcast with Dr. Tina Kaczor addresses new information regarding the loss of smell and taste as a symptoms, as well as airborne spread of the virus. In addition, Karolyn talks about her niece who is a nurse with symptoms who recently tested positive for Covid-19. In addition to being Editor-in-Chief of the Natural Medicine Journal, Tina Kaczor, ND, FABNO, has been seeing patients since earning her doctorate from National University of Natural Medicine in 2000.

This interview was recorded on April 4, 2020. This podcast addresses new information regarding the loss of smell and taste as symptoms, as well as airborne spread of the virus. In addition to being editor-in-chief of the Natural Medicine Journal, Tina Kaczor, ND, FABNO, has been seeing patients since earning her doctorate from the National University of Natural Medicine in 2000. About the Expert Tina Kaczor, ND, FABNO, is editor-in-chief of Natural Medicine Journal and a naturopathic physician, board certified in naturopathic oncology. She received her naturopathic doctorate from National University of Natural Medicine, and completed her residency in naturopathic oncology at Cancer Treatment Centers of America, Tulsa, Oklahoma. Kaczor received undergraduate degrees from the State University of New York at Buffalo. She is the past president and treasurer of the Oncology Association of Naturopathic Physicians and secretary of the American Board of Naturopathic Oncology. She has been published in several peer-reviewed journals. Kaczor is based in Portland, Oregon.

According to the National Osteoporosis Foundation, about 10 million Americans have osteoporosis and another 44 million have low bone density which places them at risk of developing osteoporosis. As Baby Boomers age, that number is expected to climb as 10,000 people turning 65 every day. In this interview, bone health expert John Neustadt, ND, explains why bone density scan is not the most clinically important endpoint and how to identify fracture risk in clinical practice. Neustadt details his whole-person approach to reducing fracture risk that includes medications, diet, lifestyle, environmental, and dietary supplements. About the Author John Neustadt, ND, received his naturopathic doctorate from Bastyr University. He was founder and medical director of Montana Integrative Medicine and founder and president of Nutritional Biochemistry, Inc. (NBI) and NBI Pharmaceuticals. Neustadt is a medical expert for TAP Integrative, a nonprofit organization educating doctors about integrative medicine. He has published more than 100 research reviews and was recognized by Elsevier as a Top Ten Cited Author for his work. Neustadt’s continuing-education podcast on Insomnia: An Integrative Approach is available for free through the Natural Medicine Journal. About the Sponsor   NBI was started by John Neustadt, ND, in 2006 when he couldn’t find formulas he needed for his patients. NBI’s clinically validated products unlock people’s full health potential. NBI products solve 2 problems he was having. Existing products didn’t contain the dose or combination of nutrients used in clinical trials and shown to work. Equally frustrating, other companies would cite studies on their websites, but then use lower amounts of nutrients than what was used in the study or use entirely different nutrients that weren’t supported by the research. Neustadt’s approach to formulating product is based on more than 2 decades of clinical research, clinical work with patients and has published more than 100 research reviews and 3 books and was recognized by Elsevier as a Top Ten Cited Author in the world for his work. NBI’s Osteo-K and Osteo-K Minis deliver the clinical dose of nutrients shown in more than 25 clinical trials to grow stronger bones and reduce fractures more than 80 percent. NBI is and always has been a family-owned company. We don’t manufacture anything we wouldn’t take ourselves or give to our own family. No matter what we do, our promise to physicians using our products is to help their patients, and to customers purchasing directly from NBI, is uncompromising quality. NBI is a name you can trust. But don’t take our word for it. Spend some time on our website, learn about our products, and educate yourself on the hundreds of research citations and studies that they’re based on. Use coupon NMJOSTEOK and save 10% off your next purchase of Osteo-K or Osteo-K Minis. Coupon code is valid through December 31, 2020 for one use per customer. Coupon code has no cash value and may not be combined with any other discount code.

In this interview Heather Zwickey, PhD, provides an important update about Covid-19 for healthcare professionals. She discusses the concerning fact that people can be asymptomatic for a longer period of time than previously expected and that the viral shedding may take longer as well. She also discusses the connection between pollen allergies and Covid-19, as well as GI symptoms, conjunctivitis, and supporting the gut microbiome. Zwickey is executive program chair and a professor at National University of Natural Medicine in Portland, OR, and also has previous training and experience with infectious diseases. About the Expert Heather Zwickey, PhD, earned a PhD in Immunology and Microbiology from the University of Colorado Health Sciences Center with a focus on infectious disease. Zwickey went on to complete a postdoctoral fellowship and teach medical school at Yale University. At the National University of Natural Medicine in Portland, OR, Zwickey launched the Helfgott Research Institute and established the School of Graduate Studies, developing programs in research, nutrition, and global health, among others. She currently leads an NIH funded clinical research training program. She teaches at many universities and speaks at conferences worldwide. At Helfgott Research Institute, Zwickey applies her immunology expertise to natural medicine, with specific interest in the gut-brain axis in neuroinflammation.   Transcript Karolyn Gazella: There is no question that the Covid-19 crisis continues to be a rapidly moving target. Hello, I'm Karolyn Gazella, your host and the publisher of the Natural Medicine Journal, an online peer-reviewed journal for integrative healthcare professionals. Yes, things are moving fast when it comes to Covid-19, but we at the Natural Medicine Journal remain committed to keeping abreast as best we can. Today we're going to be tackling the ever-changing picture of Covid-19 symptoms, as well as new research on pollen counts and Covid-19 and protecting the gut microbiome. My go to expert on this topic continues to be highly respected integrative health researcher and immunologist, Dr Heather Zwickey. If this is your first time listening to Dr Zwickey, she is executive program chair and a professor at National University of Natural Medicine in Portland, Oregon. Dr Zwickey also has previous training and experience with infectious diseases. Dr Zwickey, thank you once again for joining me to talk about this very complex topic. Heather Zwickey, PhD: Thanks for having me. Gazella: So let's start by having you give us an update since we last spoke 2 weeks ago. Anything new from your perspective? Zwickey: Yes, there's a couple of things that are coming out I think that are worth noting for physicians. First, as we're finally hearing, young people also get this virus. They may not die, but many are being hospitalized. And I think as we talked about last time we chatted, the average age was 44 in China, it was not in the 80s. So keep in mind that younger people are still susceptible. And I think one of the biggest updates is the time of exposure to symptoms. We originally thought it was 2 to 3 days, but now we're seeing that it can be anywhere from 2 to 11 days. That's a huge time span. And we don't know why. It could be the number of viral particles that people are exposed to, or it could be various health factors related to the health of the patient. We just don't know. But during that entire time span, people could be asymptomatic and yet be shedding virus. Gazella: Yeah. That is really important. And it's a good reminder as to why we're focusing on social distancing so aggressively right now. So that's great. And I do want to talk about the symptom profile, but first I want to discuss a brand new study that just came out in the journal Allergy that looked at pollen counts and Covid-19. Now obviously this can affect a lot of patients this time of year who are dealing with allergies. So what's the connection and what should practitioners consider telling their allergy patients about this new information? Zwickey: So few things to think about with respect to this. The first thing is that people start worrying when they start having symptoms of allergies because many of the symptoms are shared with upper respiratory viral infections. So the stress isn't good. Secondly, we already know that there's a shortage of tests, and if people start worrying that their allergies are Covid-19 they're going to start using tests that we actually need for people who have Covid-19. So that's not good. But from an immunological perspective, the way that we think about this is allergies are a TH2 response. So when you start mounting an allergy response to birch, or ragweed, or any sort of pollen, you need a TH2 response for the allergy response. But what you need to fight the infection is a TH1 response, not TH2. In some respiratory infections we're seeing that allergies are reducing the proinflammatory response, including the type 1 and type 3 interferons, and that's usually what we see starting to launch the anti-infection response. So if you have allergies, specifically allergies to birch pollen is what was reported in the journal Allergy, you may have less type 1 and type 3 interferons and mount less of an immune response to any upper respiratory infection. So the data that they used actually came from rhinovirus. We don't know exactly what allergies are going to do to a SARS-CoV-2 infection. In young people it could actually minimize their symptoms even more, even though they're infectious. And in older people and higher-risk populations, people who have comorbidities, it could reduce their ability to fight an infection. Gazella: That's fascinating. Is there any advice that we should be giving patients who have allergies during this crisis? Zwickey: Yeah, it's interesting. If you just get online and you Google allergies versus Covid-19, one of the things you'll find are symptom comparisons. So if you have allergies, you're probably not going to have a fever. That's the biggest thing. And if you don't have a fever, it's more likely the allergy and not the Covid-19. If you have a fever, then I would start thinking, well, this could be something different. And then if you get the cough that goes with the fever, now is when you start thinking, well, this could be Covid-19. So just get online and look at those symptom pictures and see where you're at. A headache is not a sign of Covid-19, a headache alone. But a headache, a sinus headache especially, may come with your allergies. Gazella: That's great advice. Should people with allergies stay indoors more on windy days, or is there any lifestyle-based advice? Zwickey: It's all the same things we've been telling people with allergies for a long time. Yes, you should stay indoor on windy days, you shouldn't open your car windows. Or if you're driving, put the air on recirculate instead of fresh air so that you're not exposed to more and more of that pollen. The other thing you may consider is using a local honey, which usually contains pollen. And we know if you eat the allergen you are less likely to have that TH2 response to it. So, all of those things are true in these cases. Gazella: Great. Great advice. So let's dig a little bit more deeply into the topic of symptoms. Now, I have to say, I've been fascinated by the fact that Covid-19 has a growing list of really diverse symptoms, in addition to the typical fever and dry cough that you mentioned. For example, I've been reading articles that GI issues can be a symptom. Now, while it's not a primary symptom, patients with a fever and GI issues may have Covid-19. What's this connection all about? Zwickey: So the same ACE-2 receptors that we've already talked about that are in the lungs and the kidneys are also in the gut. So if you happen to swallow the virus instead of breathe it, it'll infect the gut instead of the lungs. And when you mount an immune response, one of the cytokines that's made in the gut is TNF alpha, and we know that TNF alpha alone can cause diarrhea. Importantly, many people who have GI symptoms can also be shedding virus in stool. And that brings up something else I wanted to mention, the data from the Chinese that are coming out right now are showing that viral shedding is 20 days. It's not 2 weeks, it's 3 weeks. So think about the fact that we've had people in quarantine for 2 weeks and then we let them go, and they can actually be shedding for another full week. In fact, Chinese scientists said that some patients actually shed up to 37 days. So that's why there's a continued focus on physical distancing. And I'm trying to change the vernacular from social distancing to physical distancing because people need to be social. It's such a good coping skill and I really hope people are communicating with their friends and family. Gazella: That is a great point. Physical distancing. I'm going to make sure to use that in the future as well. Now, another symptom that's been discussed in mainstream media is pink eye or red eyes. Now this totally makes sense because people touch their eyes pretty frequently, and if they have the virus on their hands, they can infect the eyes. What do we need to know about this symptom when it comes to Covid-19? Zwickey: So first of all, it's true. There is a conjunctivitis that can be associated with Covid-19, although it's relatively rare. Data coming out of China and Italy suggest it's about 1 in 1,000 will develop conjunctivitis. So the first thing remember as a doc is to treat these patients as Covid-19 patients. They are infectious, they're shedding virus. And a lot of times when we see the red eye we think that it's limited to the eye. It's not. Also remember that this isn't bacterial, so the antibacterial drops that you drop in people's eyes aren't going to work. You're to treat this like you would treat any other Covid-19 infection, and it can be severe. People can develop a lot of inflammation in their eye from this particular virus. So treating inflammation the way you would as a physician is the way to go. Gazella: Okay, great advice. Now, is it common for a virus to expand its symptom profile like this? Does this tell us anything about the severity or the uniqueness of this particular virus? Zwickey: Well, it's not so much an expansion of symptoms. These symptoms have been happening all along, they were just happening in much lower numbers, which meant that doctors didn't know if they were unique to individuals or part of the SARS-CoV-2 infection. So until the numbers became really high we weren't seeing them in high enough numbers to report them. So this is kind of a lesson in epidemiology. If there's low numbers, they could be random. When the numbers get higher, now we can form correlations. Now there's another piece of this. Viruses can infect any tissue for which there is a receptor, and for SARS-CoV-2 the receptor, ACE-2, is distributed among many different tissues. And because the receptor's widespread, there's widespread symptoms. We call this tissue tropism, that the virus is attracted to the tissues that express the receptor. Another virus that does stuff like this is measles. Measles binds to 3 different receptors in 3 different tissues, and as a result you see measles in the lungs and the gut, and in immune cells as well. So, it's true for other viruses, it's just that until you get the law of large numbers, we don't see the symptoms appear in high enough quantity to associate it with this particular infection. Gazella: Okay, great. That was a great explanation. So I want to end our conversation with the gut microbiome, kind of going back to our conversation about GI symptoms. Now, there's a significant connection between the gut, the immune system, and our ability to fight viruses. What steps can we take to help protect and enhance the gut microbiome? Zwickey: Yeah, this is so true. We know that if you disrupt the gut microbiome, you make anyone, animal, human or insect susceptible to infections. So the A number 1 thing you can do for the microbiome, of course, is eat vegetables, especially vegetables with good prebiotic fibers. I'm thinking onions, Jerusalem artichoke, sunchokes, leeks, garlic. Potatoes are a vegetable, but they're not the best for feeding the microbiome. Although I'd much rather have you eat a potato than a cookie, but I'd rather have you eat asparagus or greens than a potato. The other thing that most of us forget get is spices are prebiotic. So cooking with spices, rosemary, thyme, basil, oregano, cinnamon, all of those things are going to help feed the bacteria in your gut, your gut microbiome. The next thing that many people would think of is probiotics, and I go probiotic first with food. So thinking about keifer, kombucha, sauerkraut, and yogurt. And usually people are going to gravitate towards the yogurt because they like the sweet taste, but remember the sugar isn't good. So if you're going to go for yogurt, you're going to go for the low-sugar versions. And then probiotic supplements, of course, could be helping the gut for some people. And while it's true that we have shown that probiotics can improve gut health, we don't actually know which probiotics work best with each individual. And remember, each person's microbiome is different, we all have our own ecosystem. So it'll be great when we can individualize them, but in the meantime, I would consider it self-experimentation, that if you're going to try a probiotic and you haven't ever tried one before, if it doesn't make you feel good, stop. That's not your combo and try something different. What you're doing with your gut is you're regulating both your immune system and your nervous system. So 80% of your immune system is in your gut and more than that for your nervous system. In fact, the microbes in your gut are responsible for making much of the serotonin in your body, and serotonin is contributing to your immune response. So, keep in mind that if your gut's not healthy, then even if every aspect of you feels healthy, you're not healthy. Gazella: Great, great points. Well, once again, Dr Zwickey, this has been very informational. Thank you so much for joining me and keeping us abreast of the various complexities associated with Covid-19. Thank you so much. Zwickey: You're welcome. Gazella: So this podcast is brought to you by Natural Medicine Journal. You can find more information at naturalmedicinejournal.com. Thank you for listening. And if you found this information interesting, please share it with your colleagues. Stay safe, everyone.

Natural Medicine Journal editorial board member and frequent contributor Kurt Beil, ND, LAc, MPH, specializes in the use of natural environments and urban green space as a key bridge to healing. In this podcast, he discusses how he utilizes the healing power of nature with his patients. Beil describes the most recent green space research and gives healthcare professionals advice on how they can incorporate this healing tool into clinical practice. About the Expert Kurt Beil, ND, LAc, MPH, is a naturopathic and Chinese medicine practitioner in Sandy, Oregon with an ongoing commuter practice to his native Hudson Valley in New York state. He is a Research Investigator at NUNM’s Helfgott Research Institute, where he completed his post-doctoral research project on biomarker and psychometric assessment of the restorative and therapeutic effect of natural vs. built urban environments. Beil holds a Master’s degree in public health focused on the benefits of green space as a sustainable public health promotion tool, and speaks and writes regularly about these topics. He has taught courses on these topics at NUNM and the Academy of Integrative Health & Medicine, has been an advisor to the Children & Nature Network’s “Nature Research Database” and was the founding co-chair of the Nature & Health subcommittee of the Intertwine Alliance in Portland. He is currently an editor and regular contributor to the Natural Medicine Journal, and writes a weekly blog on the topics of Nature & Health. Beil also maintains a Facebook group (“Naturopaths for Nature”) for the naturopathic medicine community on the clinical health benefits of contact with nature. He can be reached at drkurt@earthlink.net or www.drkurtbeil.com.

Michael Lewis, MD, FACPM, FACN, is the president of the Brain Health Education and Research Institute, which he founded in 2011 upon retiring as a Colonel after a distinguished 31-year career in the US Army. In this interview, Lewis provides listeners with an overview and update on the clinical applications of cannabidiol (CBD). In addition to discussing recent research, Lewis describes mechanisms of action, safety, and dosage of CBD in clinical practice. About the Expert Michael D. Lewis, MD, FACPM, FACN, is an expert on nutritional interventions for brain health, particularly the prevention and rehabilitation of brain injury. In 2012 upon retiring as a Colonel after 31 years in the US Army, he founded the nonprofit Brain Health Education and Research Institute. He is a graduate of the US Military Academy at West Point and Tulane University School of Medicine. Lewis is board-certified and a Fellow of the American College of Preventive Medicine and American College of Nutrition. He completed postgraduate training at Walter Reed Army Medical Center, Johns Hopkins University, and Walter Reed Army Institute of Research. He is in private practice in Potomac, MD, and is a consultant to the US Army and Navy as well as several nutrition companies around the world. A highly sought-after speaker, Lewis has done hundreds of radio shows, podcasts, medical conferences, and television appearances and is the author of the Amazon best-selling book, When Brains Collide: What Every Athlete and Parent Should Know About the Prevention and Treatment of Concussions and Head Injuries. About the Sponsor CV Sciences is on a mission to improve the well‐being of people and planet. We believe that the future of hemp is unlimited. Through innovative and responsible application of science, we strive to enhance the prosperity and health of our employees, customers, and communities. We are committed to pioneering the CBD evolution as the leading producer of quality hemp CBD products under the PlusCBD™ Oil brand. For more information please visit www.PlusCBDoil.com. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, publisher of the Natural Medicine Journal. Today I'll be talking with Dr Michael Lewis about the clinical applications of cannabidiol, or CBD. Before we begin, I'd like to thank the sponsor of this topic, who is CV Sciences Incorporated. Dr Michael Lewis is the president of the Brain Health Education and Research Institute, which he founded after retiring as a colonel in the US army. Dr Lewis, thank you so much for joining me. Michael Lewis, MD, FACPM, FACN: Oh, it's a great pleasure to be with you today. Gazella: So before we begin, I'm always curious about why physicians are interested in what they're interested in. So, as a physician, what draws you to the use of CBD in clinical practice? Lewis: Well, the easy answer is because it's effective, but of course there's always a longer story. How did I fall into this? I mean, I spent 31 and a half years, my entire adult life in the army. And cannabis is not something that's a particularly ... It's rather frowned upon as, as you might guess. And so I really had no experience with cannabis or cannabidiol at all, but I've always been open to nutrition, and in the last 10, 15 years more much more open towards is there ways we can use targeted nutrition or nutritional therapy to ... I was in the army, so I was looking at it for helping people, helping soldiers recover from traumatic brain injury or concussions. So it really started out of fish oil and omega 3s, because the brain's made of fat. And then it kind of ... As I started to learn more and more, there started to be this interaction with the CBD industry. I finally, after I retired from the army, took a good look at it, and, more importantly, started to get great experiences with my patients using the combination of fish oil and CBD. Gazella: Yeah. And you focus a lot on brain health, so that makes sense, the connection between a traumatic brain injury. So what conditions ... In addition to, I'm assuming traumatic brain injury, what conditions do you feel that CBD works well for either as a primary or adjuvant treatment or even as proactive prevention? Lewis: Well, the biggest thing is as far as any specific one thing I would have to say anxiety, for sure. So 100% of my patients have issues with anxiety, and pretty much there's lots of anxiety just in today's society, with a 24-hour news cycle and all the craziness that's going on in the world. So it's about balance, and CBD, it interacts with our cannabinoid receptors and it's really about kind of achieving that balance. Not so much like that pharmaceutical model where you kind of hit something and you shut off a process and relieve the symptoms. The use of CBD is really much more about achieving a better balance, and nowhere has that been more important for my patients than in the world of anxiety. Helping calm that voice down in the back of your head. But I also find that it helps with chronic pain, particularly headaches. Can help decrease it. It doesn't always eliminate them, but I can tell you without a doubt, anxiety is my number one reason, whether you have a head injury or just dealing with anxiety. Gazella: Yeah. That makes a lot of sense. Now you're talking about balance and that speaks to potential mechanisms of action, how CBD actually works in the body. Can you expand on that a little bit more? How much do we really know about how CBD works in the human body? Lewis: Well, the interesting thing is we've known about CBD and its uses medicinally for thousands of years. Every major culture in the history of the world has used cannabis for medicinal purposes. So we know a lot, but yet we don't. Because of the issues with prohibition and then the war on drugs … we really kind of missed this golden era of clinical research, scientific research where we're really able to understand the mechanisms. Whereas in for thousands of years it was used because we just knew it was effective. Now we have a much better way of understanding why, and the why is really ... The why and the how is really it turned out that we have these indigenous cannabinoid receptors throughout our body and principally in our brains, CB1, or cannabinoid type one receptors, CB1 receptors in our brain associated with neurons and, and neuronal function and CB2 type receptors more closely associated with our immune system. So when you're out of bounds and you think about you're out of balance on your immune system, you're more susceptible to colds and viruses and infections and stuff like that. So it's about this homeostasis, this balance, not just with your immune system but with our brains, with how we're thinking. And the really neat and interesting thing is ... One way to try to describe it is the CB1 receptors in particular, we have these chemicals that are in our bodies. I mean, we know about serotonin and therefore you have serotonin reuptake inhibitors, for example, SSRIs for antidepressant medicines. Well, we also have these internal cannabinoids that we now know about. One in particular, anandamide ananda meaning bliss, or an anandamide bliss molecule, and it's an on-demand thing. So we used to call them endorphins. That runner's high, we would say that's an endorphin rush. We now know that that's our own body making on demand this stuff called anandamide that interacts with these receptors that keeps us happy, keeps us calm, keeps us thinking more clearly. And you can imagine, as somebody that's struggling with brain health issues maybe from concussion or from chemotherapy or just chronic stress in life, that can really make a difference. Whether or not somebody's happy and functioning in life is whether their cannabinoid system is working internally, but nature also gives us a way to interact with that through the cannabis plant, and as well as diet and exercise. Gazella: Yeah, it does seem like we're learning more and more about the endocannabinoid system and the fact that that system in the body has such wide-reaching health effects, and I'd like to talk a little bit about the research. I understand what you're saying that we lost some opportunities in researching this plant because it was, frankly, hard to get and illegal and researchers had difficulty in doing really highly organized research. However, it does seem like the research is increasing. Now recently I read a study that was presented at the International Society of Sports Nutrition conference specifically on CBD. Can you tell us a little bit about that study? Lewis: Well, I wasn't involved in the study. I'm only somewhat familiar with it, but it was a placebo-controlled randomized clinical trial and it was really looking at healthy people and to see if CBD versus a placebo would make a difference in everyday life events, such as quality of sleep and perception of how clear am I thinking, how am I doing throughout the day, energy levels and so on. And there was a ... It hasn't been published yet, but there was a, I'll say, statistically significant difference, particularly, my understanding is with the quality of sleep that those people that were put on the active CBD versus the placebo had a much greater reported quality of sleep, using very standardized sleep quality indexes that are used in research every day. Gazella: Yeah. That's what drew me to this study is the fact that it was done on healthy people and it did in fact impact sleep quality, because that's a huge issue. And somebody can be deemed as being healthy and yet still struggle with sleep. So I really liked that about that study. Now, what else does the previous published research tell us about the efficacy of CBD? Have there been a lot of studies on efficacy and CBD? Lewis: There's not been ... Relative to a lot of other things, whether you're talking omega 3s, fish oil or pharmaceuticals, there's not been a lot of research, published research. So it's really just because we're kind of coming out of this prohibition era, there's lots of research starting to get done, and there's some issues on how to actually go about doing some of the research, because your cannabis plant and my cannabis plant may not be the same. Gazella: So Dr Lewis, you were just talking about the variance between the plants, the cannabis plant, like one plant can be different from another plant. So when we're dealing with any botanical, the way that we extract the active compounds is so important. Tell us about the extraction process that's used for CBD oil. Lewis: Well, so the extraction is really important, but it actually starts way before that. If you want a consistent product at the end, you've got to have consistency all the way through. And one of the things about Plus CBD Oil that I really like is ever since they even began, when they started to import ... And they're the largest importer of European hemp. It's grown in the Netherlands, it's processed in Germany. But ever since the very beginning, they've only used 2 strains of the cannabis plant. And so the seeds are highly controlled, always using these 2 strains, and so you get consistency all the way from the seed through the entire process. If you're buying hemp left and right from Colorado and from California and from Europe and from Kentucky, you're not going to get that kind of consistency. And I would hope that that's what people want in a product. Certainly one of the things that I think sets Plus CBD Oil apart is that consistency. And then when it's extracted from the plant, it's not using solvents and alcohol or other things that can adulterate the plant. And we certainly see that with some of the cheap brands that are out on the market. But what we use is a CO2 extraction. So you're not getting that issue with solvents and other things that can adulterate it. And so consistency is really, really important. Not just to me, but to the product and hopefully to the consumer, all the way from the seed to the end product that sits on the shelf. Gazella: Yeah, that makes a lot of sense. Consistency from seed to extraction. Now, is there anything else that you look for when choosing an effective CBD product? Lewis: Well, one of the things of course is good documented third party testing. So as an example, there's a barcode or what's the ... QRS code? I always forget the name of those little square codes, but they're on the label of every product and you can scan that and actually pull down that third party certificate of analysis of what's in that particular lot of that particular bottle of that product. And so you're able to look at that and that's really, I think, very important to know what it is that you're taking. One of the concerns is the cannabis plant is widely varied. Everything from how much THC content to CBD content to the turpines to the flavonoids, to the minerals and so on, and different strains, different products are going to be widely varied and so you really want to know what you're going to consume. It's helpful to have that kind of a third party analysis that's right there available to anybody that wants it. Gazella: Oh, I agree. And the convenience factor alone is great for our healthcare professionals who want to look at that third party testing. That's great. Let's talk a little bit about dosage. So what dosage do you recommend for CBD, and more importantly, does the dosage vary based on if you're using it for proactive prevention or if you're using it for treatment, and if you're using it for treatment for anxiety versus dramatic brain injury? Talk a little bit about dosage and how it's used in clinical practice. Lewis: Well, it's one of the greatest challenges, I think, that we face as practitioners is knowing what dosage to use because everybody's different. And here's the problem is that your dose and my dose may be very different. And so we've got to start somewhere. And I've got a pretty typical way that I like to start with patients, but I'm always ... It's all about educating the patient and to emphasize that you've got to find your individual dose. So if we look at the Plus CBD Oil products, I think the thing that's made the biggest difference for me and my patients was about 3 or so ... 3 or 4 years ago, they came out with little soft gels, tiny little pearl-sized soft gels. That to me may make all the difference in the world. I mean, tinctures and drops under the tongue and lysosomal and all these different ways to do and deliver CBD are great, but patient compliance is so much better when it's just a tiny little pill, and you know, for example, the gold soft gel, you're getting 15 milligrams of CBD as part of the whole plant, broad-spectrum hemp complex. But you know every soft gel you're getting 15 milligrams, and you can look at the certificate of analysis and third party studies by consumer labs and so on to know that they're always dead on, and there that's not necessarily the case with a lot of other products. They're widely varied. So I think that that is really important. I like 2 different products and the 3 main lines, they have soft gels, they have a red label, which is for their raw product and that's actually mostly CBDA, the acidic form of the cannabinoid, of CBD and the other cannabinoids. And then it's gently heated because you have to decarboxylase the CBDA and the other cannabinoids to make them active, which is why in terms of marijuana you have to smoke marijuana or bake it because you have to activate it for it to be active for it to cross the blood-brain barrier and do the job on the brain that you want to use THC for. But with hemp of course we're only dealing with trace amounts of THC, virtually none, but still trace amounts. So I actually ... The function of CBDA in their raw product is very different than the CBD. It's great for inflammation, great for the body. And then I like to combine that with one that's really good for the brain, and that's their more concentrated product, their gold product. So I actually start patients on a gold and a red soft gel, and I start them twice a day, one of both morning and bedtime, and then have to educate. Some people, they don't like how the gold makes them feel during the day and they like to only take it at night. I have patients that take 3 at night and none during the day. I have people that take 2 every couple of hours during the day. So it just really depends on the person. But the easiest thing is start twice a day and adjust from there, either more frequently, or to a higher amount. Gazella: Yeah, that makes a lot of sense. Because we are very individualized, especially when it comes to a substance like this. So let's talk a little bit about the future. As a clinician, I'm curious as to what you would like to see happen with CBD in the future? What more needs to be done from a research or clinical perspective when it comes to the use of CBD? Lewis: Well, I think the obvious thing is that it's not widely accepted, and this holds true for a lot of botanicals, but the stigma that cannabis has had for the last 70, 80 years, it's going to take a little bit of time to overcome that. And one of the ways we can overcome that is with good science to prove that it works, but we'd certainly have challenges because the variability in a plant and the variability in products. We always try to boil it down to what's that one thing? And that one thing we always [inaudible 00:19:04] nomenclature we say at CBD ... Well, when we talk about CBD oil, almost always we're talking about not really CBD oil. We're talking about industrial hemp oil that happens to have CBD and has a lack of THC. But that strain and this strain can be very different. So that consistency among products is really difficult. How do you do research around something that varies so widely? And that's one of the bigger challenges. Well, again, we will always want to boil it down to that one thing and that's why the FDA approved Epidiolex, because it's 99.9% pure CBD, but it misses out on all of those other important things in the hemp plant that make that entourage effect, that synergistic effect between all the different things. And so the safety profile is actually very different compared to something like Plus CBD Oil that has a tremendous safety profile. Gazella: Yeah, I was actually going to ask you about safety. So are there any patients who should not use CBD? Lewis: Every once in a while you run into a patient that just is exquisitely sensitive to pretty much anything. And so whether it's Tylenol or Benadryl or other things. Most patients, if you give them Benadryl, it makes them sleepy. That's why I send Tylenol PM or Advil PM, so on. But every once in a while you run into that patient that is a hyper metabolizer, and Benadryl makes them wired. It keeps them awake. Well, you can have a similar thing with CBD, it's processed through the P450 system in the liver. So genetically some people are just prone to have different effects in medications that are metabolized by the liver. So those are the ones that you have to watch out for. So what I typically do is I drop them way back and start them really, really low dose, like get a dropper, and we just do one drop or one spray once a day and see how they do, and then go to 2 and then 3 and then 4 and build them up so that their body gets used to it. It doesn't mean that they don't need CBD or else I wouldn't be doing this with a patient, but their bodies just need a much slower ramp up to be able to adjust to it. Gazella: You know, that makes a lot of sense. Because I've heard about the reverse effect with other substances like melatonin, you mentioned Benadryl. It's good to know that if there is that reverse effect that you don't have to just stop completely. You can just do this titration where you start really small and just ramp up slowly, so that's good to know. And you've had good luck with that in clinical practice? Lewis: Very much so. And those are the patients that ... I'm dealing, again, with head injury patients or concussion patients that have been struggling for months or even years with the symptoms following a concussion and they're the ones that really need it. They really need the CBD. And so I'm not so quick to just say, "Stop taking it." But where I've found the success is, all right, we're going to start back over at ground zero and we're going to step up really cautiously, really slowly. And once you work through that process over a month or so, it is absolutely life-changing for those patients. Gazella: That's great. That's good to know. And I would agree with you. I think in the future it would be good to see the stigma ... To overcome that stigma, to get some more consistency with the plant and some more human trials associated with the efficacy of CBD. I think those are all really great future goals for this particular substance. Well, Dr Lewis, once again, thank you for joining me today, and I'd also like to thank the sponsor of this topic, and that is CV Sciences Incorporated. Thanks again, Dr Lewis. Lewis: Oh, my pleasure. Hopefully we can do it again sometime soon. Gazella: Absolutely. Let's stay in touch. Well, have a great day everyone.

In this interview, leading botanical researcher Ajay Goel, PhD, AGAF, describes 3 herbs that he has studied which show great promise in cancer care: curcumin, boswellia, and French grape seed extract. Goel discusses the research associated with these botanicals, as well as any contraindications or safety issues.   About the Expert Ajay Goel, PhD, AGAF, is a professor and chair of the Department of Translational Genomics and Oncology at the Beckman Research Institute City of Hope Comprehensive Cancer Center in Duarte, CA, as well as director of biotech innovations at the City of Hope Medical Center. He has been recognized as an American Gastrointestinal Association Fellow (AGAF) for his research on colorectal cancer. Goel has spent more than 20 years researching cancer. He has been the lead author or contributor to more than 300 scientific articles published in peer-reviewed international journals and has also authored several book chapters. Goel is currently researching the prevention of gastrointestinal cancers using integrative and alternative approaches, including botanical products. Three of the primary botanicals he is investigating are curcumin (from turmeric), boswellia, and French grape seed.  About the Sponsor EuroMedica® specializes in bringing proven natural medicines to the United States and in developing unique formulas containing clinically tested, safe, and effective ingredients. EuroMedica’s founder and president, Terry Lemerond, has more than 45 years' experience in the nutritional supplement industry, beginning with the founding of his first companies, Enzymatic Therapy and PhytoPharmica, and culminating in his current company, EuroMedica. Terry Lemerond is credited as the first to introduce standardized ginkgo, glucosamine sulfate, and IP-6 to the United States. Several of EuroMedica’s products have been featured in published scientific papers. New clinical trials, some including the well known BCM-95®/Curcugreen™ Curcumin, are now underway at prestigious research centers. EuroMedica is perhaps best known for Curaphen® Professional Pain Formula and CuraPro® products, both containing BCM-95®/Curcugreen™ Curcumin. Additonally, EuroMedica provides unique and proprietary products including EurOmega-3®, Traumaplant® Comfrey Cream from Germany, Bladder Manager® featuring the clinically studied SagaPro®, ProHydra-7™ with SB-150™ Seabuckthorn Oil, and Clinical Glutathione™ with Sublinthion®. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we'll be talking about three key botanicals for cancer care, but first I'd like to thank the sponsor of this topic who is EuroMedica. My guest today is Dr Ajay Goel, who is a professor and chair of the molecular diagnostic department with the Beckman Research Institute at the City of Hope Comprehensive Cancer Center. Dr Goel, thank you so much for joining me. Dr Ajay Goel: Good morning. Thanks for having me on the show. It's a pleasure. Gazella: So before we dig into our topic, I'm always curious as to what motivates researchers. And in your case, why were you drawn to the study of botanicals? Goel: Thanks for asking this very relevant question. So I think my answer would be twofold. One, I've always been a firm believer, and there's a lot of data gathered over the last decades or even centuries, that natural medicines are a lot more potent, lot more valuable, a lot more effective then we have given them credit for. If you look at some of the oldest systems of medicines like Chinese traditional system medicine or Indian system of Ayurvedic medicine, they've been there for centuries. They've been there for a long time and we knew that some of the botanicals which were used in these traditional medicinal approaches, they work beautifully. What we didn't have was, we didn't have all the science behind it, but we can negate the fact that these botanicals did not work. So that's one. Second, I work in oncology and I work very closely with my oncology colleagues and what bothered me all this time is that first, we don't have good modern drugs for treating patients with cancer. So that's one, but whatever drugs we have, the problem is they don't work on most patients. But even in the patients, very small number of patients where they work, they have huge toxicity profile. They have adverse effects associated with them, which makes them almost, I've seen patients who would say that I would rather give up my care rather than accepting any of these modern drugs. So I think that's a twofold answer. One, the natural medicines are lot more powerful. And second, they don't have all the baggage, they don't have all the side effects and toxicity, which most of the modern drugs give us. So I think those were the two motivational reasons for me to continue to research the field of botanical medicine. Gazella: Yeah, that makes a lot of sense to me. Now today we're going to be focusing on three botanicals in particular. I'd like to start with curcumin, and I have to say, we here at the Natural Medicine Journal really enjoy talking about curcumin because the science is so fascinating and interesting. And there's just a lot of it frankly. So specific to cancer, what are the key mechanisms of action when it comes to curcumin? Goel: So again, very wonderful question, and just like you said, curcumin is probably, and I check this on a daily basis or a weekly basis, the body of scientific evidence behind curcumin and especially in the context of cancer grows on a daily basis. You know? So to the best of my knowledge, this is the only botanical for which we have the most amount of scientific evidence. And by that I mean, scientifically peer reviewed publications showing the efficacy of curcumin in virtually every kind of cancer, and all kinds of other diseases as well. Now, what is the mechanism of action? How does it work in patients who have cancer? Actually, we can talk about it all day long because there's not one singular mechanism which stands out. But if have to pick one or two, I think it boils down to curcumin's ability to fight inflammation. So I think it's probably one of the most potent anti-inflammatory agent. And as we recognize all the molecular underpinnings are the basis of most disease, including cancer. We recognize that although once a patient has cancer, we know that many of the genes are not behaving the way they're supposed to. But what is the process which starts this misbehavior of genes? It's always inflammation. And when we talk about inflammation, we're not talking about acute inflammation, something which we all can easily recognize if you fall or get hurt, we have a bruise or a localized pain somewhere. Now what we're talking about is chronic inflammation, which is completely asymptomatic, there are no symptoms for that. But that is very intimately linked with our foods and diets and lifestyles, and as you would know our lifestyles have changed a lot in the last few years and few couple of decades. And that is the reason why we have such a huge epidemic of cancer because chronic inflammation stays there, and if it continues to persist, it leads to many diseases including cancer. And so if I have to pick one mechanism, it'll be anti-inflammatory activities of curcumin. Gazella: And you said that there might be another second mechanism that you're drawn to as well. Goel: Yeah, so the second mechanism would be it's antioxidant potential. What that essentially means is, its ability to capture and get rid of all the free articles floating around in ourselves. Because if we let these free radicals, which are very reactive, hang around in the cells, they begin to oxidize lipids and fats and proteins, basically rupturing all the cells. So if you can capture and scavenge, or just absorb all of these free radicals, get rid of this and increase this amount of antioxidative stress that is the second properties. It's a very, very potent antioxidant along with its anti-inflammatory potential. Gazella: Great. Now I know that you have done some work with curcumin and cancer. Can you describe some of your research? I realized that there's a lot of research in this area, so maybe choose some of the more recent published trials on curcumin. Goel: Yes, absolutely. So curcumin is one of my most favorite botanicals. As you can tell I've worked on it for a long time, and we have published quite a bit on curcumin. So if I have to highlight some of the trials which we are very proud of would be fairly simple in a way. So one of the things we recognize, how do cancer cells grow? So cancer cells love to grow because that's in their benefit, that's to their advantage. And one of the ways cancer cells continue to grow without dying is they basically shuttle away all the nutrition from the surrounding healthy cells around them. So they are very slick. They are clever. So for their own survival they need nutrition. And the way they get this nutrition is by fooling the healthy cells around them by telling them this is to their advantage. Please allow me to continue to derive all the nutrition from you, away from you. And what we showed in one of the beautiful studies, which has been cited a lot, is that cancers don't grow in a silo, they grow in communication. We call it tumor microenvironment, which basically means tumor cells are growing, your healthy cells are growing, your stromal cells are growing. And if some strategies, some drug, some botanical, can basically block that sense of communication between cancer cells and healthy cells, what would happen? Healthy cells would not give the nutrition to the cancer cells. And when that happens, the cancer cells will die. And that's exactly what we showed in a very elegant study a few years back. There had been cancer cells are treated with curcumin, within a matter of hours or days, these cells begin to wither away. And what we showed was this is exactly curcumin does. It basically stops a communication of cancer cells with the healthy cells. And once that happens and the healthy cells stop giving the nutrition to the cancer cells and eventually the cancer cells die away. So that's one mechanism which is very, very important. Second, which is very relevant to a lot of the patients who get cancer actually, they typically would meet their physician saying, I already have a cancer and you're prescribing me the chemotherapy or radiation therapy. Can I take curcumin along with, maybe it'll enhance the benefits of my treatment? And most of the times if the physicians are not aware of the beneficial effects of curcumin, they will tend to suggest, no, please don't interfere with my care and don't take anything, any supplement, especially along with my care. And that is not true because we showed, and there are many other studies done on this aspect too where we very clearly showed that patients who have, especially colon cancer or even pancreatic cancer, because those are the areas of my research, that in these cells, in these patients, if these patients are given curcumin along with their standard of care chemotherapy, actually the efficacy of the chemotherapy multiplies many, many fold. And the quality of life of these patients while they're already on chemotherapy when they take curcumin along with improves significantly. Which is a good thing because now the patient don't have to experience all the toxicity from the chemotherapy, but continue to improve the quality of life. On the same lines, we published another study where we showed actually the combination of chemotherapy along with curcumin, actually, if you use it, you can reduce the dose of chemotherapy by tenfold, or 10 times, and still have the same level of benefit which you would have with chemotherapy alone. So this is amazing because what that means is you could reduce not only the dose of the chemotherapy by 10 times, you're reducing that expense by 10 times. And you also, more importantly, reducing the toxicity by tenfold, but still having the same level of benefit. So these are some of those studies which are very, very important. And more recently, which we'll probably cover in the conversation later, we have begun to see that when we combine curcumin with other drugs or other botanicals there's a lot of synergy between these. Which is, again, something which we are very excited about. Gazella: Yeah, I mean this is some amazing research, and we could probably talk about curcumin all day long, just focusing on the research. But I would like to talk about the form of curcumin, because there is a lot of debate, some controversy surrounding the form of curcumin that can be used or should be used for efficacy. Now this is due in part because of absorption issues. I'm curious as to what form you prefer to use in your research, and why do you prefer that form over the several other forms of curcumin that are presently on the market? Goel: Thank you for asking this question, I think this is very, very relevant to anybody who would consider taking curcumin because the form of curcumin I've used in my research for the last 10 plus years is called BCM 95 curcumin. And the reason I chose this curcumin for all my research for over the years is simply threefold. One, this is a high absorption curcumin. So what that means is, curcumin by itself, if you take a generic curcumin, one of the challenges or limitations of curcumin is that it is poorly absorbed by our human bodies. If you take some amount of it, most of it will come out of your body within a matter of hours. So if that's the case, your body is not going to be healed. Your body is not going to derive all the benefits of curcumin if much of it comes out so fast. So it is very, very important that anybody considering taking curcumin, they should take a curcumin which is high absorption curcumin. So that is the reason I use BCM 95 curcumin because there's been studies done that it is somewhere between 10 to 12 times better absorbed compared to generic acumen. That's one. Second, not only is it absorbed in the body 10 to 12 fold better, but it stays in the body longer too, which is almost a no brainer that if you are taking something for therapeutic purposes you would want that thing to stay in the body longer, because longer it stays there it'll continue to fight inflammation like we talked. It'll continue to fight oxidative stress. So the second thing is it stays in the body longer. Third, which is equally important is that this is, I call it a clean curcumin, because it's all natural. So one of the limitations of many forms of curcumin is that people, many of the manufacturers or vendors will try to increase their yield of curcumin from turmeric. And in the process they will use strong synthetic chemicals to get as much curcumin they can get out of turmeric. And in the process what happens is you have curcumin, but as a consumer, as a patient, or as a physician when you're giving this curcumin to your patients, you're basically ingesting small amounts of chemicals which are not good for your body. So that's the third reason I used BCM 95 because it does not use any strong chemicals. It is all natural and one of the mechanisms, the way it is better absorbed in the bodies is that the curcumin is actually mixed together with the natural essential oils which are present in the root of turmeric, and that is a way to enhance its absorption. So it's all natural, better absorbed, stays in the body longer. Gazella: That makes a lot of sense. Now are there any contra indications or safety issues with curcumin specific to oncology? Goel: To the best of my knowledge, no. There have been studies done, we call these dose escalation studies where people will take highest possible dose of curcumin until they see some toxicity. And these studies have been done in human trials and people have used up to 12 grams of curcumin a day for, I think, I believe it was six months, and virtually no toxicity or adverse effects at all. Some people do sometimes feel for a very short term, some sort of upset stomach, but that only lasts for a day or two. But typically in terms of toxicity or serious adverse effects or any concerns, absolutely zero. Gazella: Okay, good. Now before we move on to our next botanical, what is the therapeutic dosage that you recommend of the BCM 95 in oncology? I imagine it varies based on the individual and their circumstances, but is there a general dosage range? Goel: Absolutely. So again, we can't, because curcumin and other botanicals they're not drugs, so there's a fair degree of range of forgiveness if you take a little bit more, or a little bit less, because they are very safe. So we don't have to worry that much. So based on my experience, especially if you're working with a high quality curcumin extract such as BCM 95 I think for the oncology patient a general range should is somewhere around two grams to three grams a day. Which should be split equally in three or four doses over their entire days. You don't want to take your all two or three grams in one dose. So it should be split in, you know, morning, afternoon, evening, or maybe four doses if somebody can manage. So somewhere in the range of two to three grams a day. And then depending upon their disease severity stage of the cancer and so forth I've seen patients even using up to five grams, but I think that would be extreme situation. But about three grams I would say is the average dose over entire day. Gazella: Okay, perfect. So let's talk about boswellia. Now when we think of boswellia, I personally think about joint pain and osteoarthritis. How does boswellia work when it comes to cancer care? And just describe for us the oncology mechanisms of the actions for this particular botanical. Goel: Absolutely. Again, so boswellia, just like you said, most people when they think about boswellia they think about joint pains and osteoarthritis and so forth because that's where it's been used for longest times. And one of the traditional uses for boswellia has been in arthritis, and even in patients who have actually another condition would be asthma. People have used boswellia quite a bit there. But in terms of cancer, I mean evidence is not there that much, but we have done quite a bit of studies. And I would say in the last three to five years there's a lot more studies around cancer. And one of the ways it helps in patients who have cancer is, again, it's ability to fight inflammation. So when we talk about inflammation, we just covered earlier we were talking about again, chronic inflammation. And when we talk about chronic inflammation, inflammation in our body is not controlled by one pathway. There are multiple pathways of controlling inflammation. We just talked about curcumin. And one of the preferred ways curcumin functions there is by inhibiting an enzyme called cyclooxygenase two or COX-2. So that's a very, very key pathway which basically triggers inflammation, and curcumin works beautifully there. But there's another pathway which is equally important when it comes to inflammation we call it five lipoxygenase pathway, or 5-LOX pathway, and if that pathway is active, that will mean there'll be increased inflammation in our body which we don't want. And what we have shown is that in cancer patients, if they take boswellia, what happens is this 5-LOX activity goes down. And when that goes down there is a reduced inflammation and these patients tend to do so much better in terms of the response to cancer. So I think one of the preferred mechanism for boswellia, especially in the context of cancer, will be anti-inflammatory activity, and that activity mediated through 5-LOX pathway. Gazella: And now you mentioned that these are human clinical trials involving boswellia and oncology, is that the case? Goel: Not really. Some of these things are preclinical studies, but my understanding is there a couple of trials currently being planned. But for curcumin there are many human trials. And of course [crosstalk 00:18:40]. But for boswellia, most of the evidence so far has been preclinical evidence, which means before human trials. Gazella: Got it. Okay. So now I understand when it comes to boswellia that boswellic acids are important. So what should practitioners look for when deciding on which a boswellia product to use, or what form of this botanical would be the most effective? Goel: Again, thanks for asking such an important question. So just like we covered curcumin, and again, I think that's a normal notion that when we take any botanicals we have to be sure that we're taking the best product out there for which we have the best science. So when it comes to boswellia, I think one must consider taking... So when we look at boswellic acids, which are extracted from boswellia serrata tree, it's actually a combination of multiple boswellic acids present in there. And some of them are actually anti-inflammatory, while other actually ingredients or the actives in total boswellic extract could be pro-inflammatory, which is something you don't want. So if you have something pro-inflammatory is going to increase more inflammation, which is not desired. So one of the most important active anti-inflammatory boswellic acid is called AKBA, or one keto alpha boswellic acid. So as a consumer who is desiring to take boswellic acid for cancer or for other indications to fight inflammation, you have to look for a boswellia extract which is highly enriched for AKBA. So you need to look for a product which is pure and has highest amount of AKBA content, because that is the one which has most anti-inflammatory activities. If you take a total extract with other boswellic acid in there, there may be some component of pro-inflammatory boswellic acid. So one has to pay attention to the extract which is rich and AKBA. Gazella: Can you spell that for me Dr Goel? Goel: Yes. So the acronym is A-K-B-A. So it stands for one alpha keto boswellic acid. Gazella: Perfect. Yeah. A lot of our healthcare professionals who are listening will want to know that, so thank you for that. Now are there any safety concerns with boswellia? Goel: Again, to the best of my knowledge, no. But again, compared to curcumin, we don't have too many safety studies. But based on my experience, based on our studies we have done, I think one of the things when we talk about safety we have to keep in mind the amount of, or the dose of, any product we are using, whether it's curcumin or boswellia or anything else for that matter, anything in life. So I think if you're going to cover this, so boswellia, again, in the context of cancer patients, I think those are for about two to three gram also has shown a lot of anti-inflammatory and anti-cancer activity. So I think to the best of my knowledge, if somebody is using these range or even twice as much, I don't think there's any concern for toxicity of any sort. Gazella: Okay, that's good to know. So now I want to talk about the third and final botanical, which is French grape seed extract. And again, we don't often think about cancer when it comes to this particular botanical. So how does the preliminary research show us that French grape seed extract works when it comes to oncology? Goel: Yeah, so I'm very excited, and when we begin to work quite a bit on a French grape seed extract, just like you said, when people think about grape seed extract, or grapes in general, I think most people think about resveratrol and so forth. Which is used in many different contexts and especially anti-aging products and so forth. But if you know, resveratrol typically comes from the skin of grapes and from the flesh of the grapes. But grape seed extract, just like the name says, comes from the seeds of the grapes. And it's unfortunate that being in US, we tend to go to stores and many times we ended up finding grapes which are very proudly sold as seedless grapes. So I think it's not necessarily a good thing. But when we look at grapes with seeds, they have these very, very active molecules. We call them OPCs, oligomeric polys anthocyanidins. So OPCs, and they are present in grape seed extract, which are again very, very important anti-inflammatories, antioxidants. And we are particularly excited about this particular VX1 French grape seed extract, because if you take a genetic grape seed extract, it'll have lot of tannins and a very small amount of OPCs. So if you ground up all the grape seed extract it'll have probably majority of it will be large molecular weight tannins. So as a consumer, if you take the generic grape seed extract, what happens is you're thinking you're taking 300 or 500 milligram of grape seed extract. But most of it, more than 90% of it will never enter our cells. That's what we want because if it goes into the cells it produces anti-inflammatory or antioxidant activity. But most of the generic grape seed extracts are so enriched in high molecular tannins, which are unable to enter our cells. But this particular grape seed extract, French grape seed extract is unique because it gets rid of all these large molecular tannins, and it is enriched for these very, very small OPCs which can easily enter the cells, cause this anti-inflammatory activity, antioxidant activity, and give health to patients who have cancer. So we have done several studies in the last two, three years, and we are seeing phenomenal results as an anti-cancer agent. Gazella: Well that's great. And here again, we have another example where the form is important. And it's my understanding that with this particular extract you should look for it to be standardized to contain that appropriate concentration of polyphenols. So to get the most therapeutic effect, what specific form of this extract do you recommend? What should practitioners look for on the label? Goel: So I think what they should be looking for a grape seed extract which is highly enriched or standardize for highest amount of OPCs, which is again oligomeric proanthocyanidins. So you have to look for a extract which is enriched for these because these are the small polyphenols which can enter our cells and show the activity what we're looking for. Because if you're just using a generic extract, which is not standardized for OPCs, you will not get the benefits what you seek. Gazella: Right, exactly. And it won't match what's happening in the research literature. Goel: Absolutely. Gazella: Again, any safety issues with this one? Goel: Nope, not at all. But these are very, very safe compounds for the most part. And we have done quite a few studies where we use very large doses of these compounds and we have not seen any sort of adverse effect or toxicities. Gazella: Okay, perfect. Now in the beginning of our interview you mentioned the synergies, specifically with curcumin, that when you combine curcumin with other botanicals. So regarding these three herbs that we just discussed, do you see any synergy between the three? Would there be any advantages to using these three in particular together? Goel: Absolutely. Although we have not done studies on all three together, but we have done studies where we've combined curcumin with boswellia. Again, the curcumin extract being BCM 95 curcumin, and boswellia being extract which is named as BosPure, which is highly enriched for AKBA. So we have done studies where we have combined curcumin and boswellia together and we have seen amazing synergistic activity. And the reason I say it is amazing is because we have compared the efficacy of this combination of curcumin with boswellia, and we have compared it to the efficacy to standard of care chemotherapies. And it was amazing to see that just the combination of these two compounds was much more potent than chemotherapy alone. That's beautiful because now you don't need to worry about taking a chemotherapy because if you can take these two natural, safe, inexpensive compounds and have the same level of benefit for chemotherapy or even better, then this is a win/win. More recently we have done a study where we have combined curcumin with this French grape seed extract, same kind of activity. That the combination was so potent, a lot more efficacious compared to standard of chemotherapy. And another thing in this particular study we noticed where we combine curcumin with French grape seed extract, that this combination was very, very important in killing cancer stem cells. Which is very important because patients who have cancer, we can get rid of the cancer cells, but most times we leave behind something we know, cancer stem cells, which are basically super powered version of the cancer cells, which those who don't respond to any kind of treatment. And if you leave them behind, these patients will experience, you know, cancer coming back in six months or one year because these cells are left behind. But what in this study where we have used combination of curcumin and French grape seed extract we have shown actually this combination is not only very, very promising in killing cancer cells, but it gets sort of most of the cancer stem cells, which is wonderful news for the cancer patients. What that means is if they use this combination, there's a very less or likelihood that their cancer will ever come back. So we are very excited. We are planning on studies, we will try to combine all three compounds together. But so far we have looked at individual combination of these two. Gazella: Yeah, that is exciting, especially about the stem cell. Now I'm assuming that so far these have been all in vitro studies. Goel: Actually no. So this reasons study that we did, we call it a ex vivo study, which what that means is we actually using human cancer sample from a patient itself. So in this combination study, we actually took the colon cancer tissue from the patient who had colon cancer, and we have developed a unique way to grow this tumor outside of the human body. But the good news is we are looking at actual cancer sample from an actual patient who have colon cancer. So these are not real human trials, but they are not neither in vitro studies. So we call them ex vivo studies where we can continue to see the effect of these compounds, these botanicals and drugs, on the actual human tumor. Gazella: That's great. Yeah. And you know, it makes sense, and the curcumin and boswellia in particular makes sense because you were talking about the two different inflammatory pathways that they impact. One, you know COX-2, and then the one is the 5-LOX pathway. So that would make sense that combining the two you're going to have even a heightened anti-inflammatory effect. Goel: Absolutely. And similarly when we combine curcumin with this French grape seed extract, because this French grape seed extract works on absolutely very different anti-inflammatory pathways too. And I think although we are still working on the mechanistic aspects of this, but what we are seeing is that when you combine curcumin with this French grape seed extract, I think in a matter of few days we can see the effect, which is very, very, very pronounced and very important in killing cancer cells. Gazella: Well that's great. Well, you know Dr Goel, you have been a true leader when it comes to researching botanicals in oncology care. So I'm curious about, you know, what your thoughts are on what the future holds when it comes to the utilization of botanicals and cancer care? What can we expect to see in this area of integrative oncology? Goel: I think that's a very important question. And I think, I've been working in those fields for 20 plus years, and I can already tell you I've seen a change already. And I think we will continue to see this change. And by change I mean as that patients have become a lot more smarter because they have access to all the scientific studies and literature, which is online and so forth. So they become more curious. They ask the right questions, they desire to use some of these integrative approaches in their cancer care and so forth. And I can tell you that every single day, you know, I hear from a lot more patients who are beginning to adopt some of these integrative approaches on their own, sometimes with the consent of their physician, sometimes on their own. But since you asked me what are the future, I think the future is that we are going to see continued awareness and continued educational effort of recognizing the benefits. And at the same time, that's where we started, the benefits of these botanicals as well as the safety of these compounds in helping patients who have cancer and other diseases. And I have no doubt about it, we are already seeing a huge growth and awareness about the potential of these natural medicines. And I can only imagine that it'll continue to grow. And I think at some point the mainstream modern medicine will begin to use these things. Maybe not stand alone, but possibly as adjunct or in combination with the standard modern drugs they're using. So the future is bright. Gazella: I would agree, and I hope that certainly does happen. It's exciting to watch, honestly. Well, this has been very informational. Once again, I would like to thank our sponsor who is EuroMedica. And Dr Goel, I'd like to thank you for joining me today. Let's stay connected so we can stay on top of the research, the exciting research that you're doing. Goel: Absolutely. Thank you so much for having me on the show, and I really enjoyed it. Gazella: Great. Have a great day. Goel: You too. Bye-bye.

This article is part of the 2019 Oncology Special Issue of Natural Medicine Journal. Read the full issue here.    Tina Kaczor, ND, FABNO, interviews Shauna Birdsall, ND, FABNO, on what clinicians need to know about skin cancers. From preventing squamous cell carcinomas to recognizing melanoma, Birdsall details the essentials of cancer-related dermatology. This interview includes a broad review of what you can do to help patients prevent skin cancer. Do you remember the ABCDE’s of recognizing melanoma? Where do squamous and basal cell carcinomas usually occur? What is the ideal range for serum vitamin D? What other supplements have evidence for reducing the risk of squamous cell cancers? We cover all this and more in this in-depth discussion between integrative oncology experts. About the Expert Shauna M. Birdsall, ND, FABNO, is a naturopathic physician and fellow of the American Board of Naturopathic Oncology. Birdsall graduated from National University of Natural Medicine in 2000. After completing a residency at Cancer Treatment Centers of America (CTCA) at Midwestern Regional Medical Center in 2002, she provided patient care and supervised naturopathic medical students there until 2008. She took on a leadership role at Western Regional Medical Center at CTCA in Goodyear, AZ, in 2008 and was later elected vice chief of the medical staff there. She also chaired the Medical Executive Committee, Credentials Committee, Peer Review Committee, and served as the Medical Director of Integrative Oncology until 2018. Birdsall recently joined Avante Medical Center in Anchorage, AK. One of Phoenix Magazine’s Top Doctors 2014-2018, Birdsall is strongly committed to providing individualized, compassionate, evidence-based care to empower and provide hope to cancer patients. Transcript Tina Kaczor, ND, FABNO: Hello. I'm Tina Kaczor, editor-in-chief here at the Natural Medicine Journal. I'm talking today with Dr. Shauna Birdsall about skin cancers, and Dr. Shauna Birdsall has graduated from the National College of Natural Medicine in the year 2000. After that, she went to Cancer Treatment Centers of America, and she has been a specialist in integrative oncology since graduation. She's most recently taken a position at Avante Medical Center in Anchorage, Alaska, where she'll be providing patient care in a hospital-based setting. Shauna, thanks so much for joining me. Shauna Birdsall, ND, FABNO: Oh, thank you for having me. Kaczor: Dr. Birdsall, you've recently worked closely with a lot of dermatologists in a dermatologist setting, and you and I got talking about that. I was intrigued by a lot of the things that you learned, and I would like you to elaborate a little bit on how working closely alongside these dermatologists maybe changed your perspective of oncology and skin cancer specifically. Birdsall: I have to say I was blown away, and this is a bit embarrassing. Working with patients undergoing chemotherapy and radiation for cancers like breast cancer and pancreatic cancer, I had always seen dermatology as more on the periphery. Working with dermatologists showed me how often dermatologists are diagnosing things like melanoma and really saving people's lives. It completely changed my perception around the integral nature of the specialty. Kaczor: Yeah. I think that's what struck me, because you and I have parallel universes in the idea of our professions. We both graduated in the same year, and we've both been doing integrative oncology. I have to say I haven't worked closely with dermatologists. I share your inclination to say, "Ah, yeah, skin, we can catch that. No problem. We always catch skin cancer," and, I mean, that's despite the fact that of course we've both worked with people with metastatic melanoma. We'll get to that and the importance of prevention, especially to prevent such tragedies as metastatic disease. I'd like you to give us a primer, and just give us a really basic overview for the clinicians out there on the types of skin cancers that there are, and who they most likely effect as well. Birdsall: Sure. First of all, skin cancer is the most common type of cancer, and in the United States this year, more than 5 million people will be diagnosed with skin cancers. First and foremost, we like to talk about actinic keratoses. These are also known as AKs, and they are really precancerous lesions. You'll hear, the resounding themes of those that have sun exposure as being at risk for these cancers as I go on, but essentially actinic keratoses are often flaky or scaly patches of skin, and it's important that those are identified and treated, as sometimes they can lead to squamous cell carcinoma. The most common type of skin cancer is basal cell carcinoma or BCC. This accounts for about 80% of skin cancers, and BCCs usually look like a flesh-colored pearl or bump, or a pinkish patch of skin. All of these skin cancers are going to be more prevalent in patients with fair skin, although patients with skin of all colors can develop these skin cancers. Then, as I mentioned we're going to repeatedly talk about risk with sun exposure, and that means that the areas of the body that are most frequently exposed to sun such as the face, head, chest, arms and legs are going to be the most prevalent areas that you can see these cancers. Squamous cell carcinoma is the most second type of skin cancer, and you're going to also see squamous cell cancers on areas like the rim of the ear. You really need to be able to make sure that those are identified, as those cancers can spread more deeply into tissues and cause additional damage, as well as metastasize elsewhere. Melanoma, as we talked about earlier, is the deadliest form of skin cancer. It's actually been on the rise for the last 50 years. Melanoma in situ annual incidents in the United States is 9.5%, and in the United States melanoma has become the fifth-most common cancer in men and women. Melanoma increases with age, and you do see again the sun exposure and fair skin as common risk factors. I think later on, we'll talk about more risk factors for melanoma. Kaczor: Yeah. That's an incredible statistic. Nearly 10% incidence for in situ melanoma. Wow. Birdsall: Yes. Which is why I really started waking up to the issues with skin cancer detection and prevention, working with dermatologists, because I just was blown away, as I mentioned, with how often they were diagnosing either melanoma in situ or melanomas. Kaczor: That's just checking. I mean, that's just skin checks, not coming in with that complaint. Birdsall: Yes. Kaczor: Most of our listeners are practitioners that are primary practitioners. Very few are going to be specialists in skincare, of course. I'd like us to maybe, if you could, go through how to recognize melanoma, and maybe making sure that when we are seeing our patients ... and this could be in a specific skin exam, or it could also just be an incidental finding on their arm or their face or whatever. What are we looking for with melanoma? Birdsall: Melanomas frequently develop in a mole or suddenly appears as a new dark spot on the skin. If you'll recall, we have the ABCDE warning signs, and I'm just going to go through those just for all of our review. A stands for asymmetry. B stands for border, either irregular, scalloped or poorly defined. C stands for color, varied really from one area to another in the same mole, and you can see shades of tan and brown, black, white, pink, red or blue. I think one of the most shocking melanomas that I saw was a melanoma inside the web of the toes in a patient that just looked like a little pink spot. D stands for diameter. While melanomas are usually greater than 6 millimeters in size, which is the size of a pencil eraser, when initially diagnosed they can be smaller. E stands for evolving, a mole or a skin lesion that looks different from the rest or is changing in size, shape or color. What is important to know as well is that melanomas don't necessarily read the textbooks. As I mentioned, they can look like something that, for those of us who are not dermatologists, may not look like something of concern, which is why I became aware of the need for annual skin exams. Kaczor: Yeah. Yeah. It is remarkable that some of them don't look like much, and I think that erring on the side of caution, especially as our patients get older and older, because aging is a risk factor for all cancers, and I'm assuming skin cancer is included in there. Okay. Is there anything else? Last notes besides ABCD and E, and anything else that people should be looking for clinically before we close that discussion? Birdsall: An area that's itching, bleeding. An area that opens up and appears to heal over, and then opens up again. Anything like that also needs to be evaluated. Kaczor: Okay. Yeah. Referral to a dermatologist is simple enough that I think it's ... again, erring on the side of caution seems like a smart thing to do. We talked about melanoma, and experience shows us that of course it's the most likely to go somewhere. It's most likely to spread and become fatal for some patients, but I'm curious. Basal cell and squamous cell carcinoma, what is the risk of any local or metastatic disease with those? Birdsall: In the majority of patients with cutaneous squamous cell carcinoma or basal cell carcinoma, the disease remains limited to the skin and with appropriate treatment is considered, "cured," which you and I both know we don't get to use that word very often in oncology. It's exciting that something can be cured with appropriate treatment. However, in 3 to 7% of patients with cutaneous squamous cell carcinoma, and rarely in individuals with basal cell carcinoma, local, regional or distant metastases can occur, which increases the risk for mortality or death. Kaczor: Do you happen to know, is this analogous to melanoma in that the depth of the lesion has anything to do with it? Do you know? Birdsall: Yes. For both basal cell and squamous cell carcinomas, both the depth and the size can contribute to risk, which is why even though a patient might only have a small spot, why it's important that it be caught early and treated, because left to its own devices, the larger it gets, the more at risk a patient is. Kaczor: Okay. Well, that makes logical sense. As far as melanomas go, you mentioned in situ is nearly 10%. Are most of them still caught in the early stages, before they go anywhere? Birdsall: Yes. Yeah. About 85% of melanomas are caught when there's only localized disease, so Stage I or Stage II at presentation, which as you and I both know, that's when you see the best survival rates. At diagnosis, about 15% have regional nodal disease, and only about 2% have distant metastases at the time of diagnosis. We're getting better at diagnosing skin cancers and melanoma, and it's theorized that dermatologists are more likely to biopsy these days because of seeing a higher prevalence. Kaczor: I see. Okay. Can I ask one question? That is, in some states, including where I am in Oregon, naturopathic physicians can do minor surgery. The question I have ... I know my opinion on this, but I want to hear your opinion on this. It's not uncommon for shave biopsies to happen in-office. This is true of primary care physicians across the board, not just naturopaths. If someone suspects a melanoma, yea or nay on something like a biopsy of that, whether it's a punch biopsy or a shave biopsy? Birdsall: Nay, and the reason is that there is research that the sooner after initial diagnosis ... so the sooner after initial biopsy ... that patient is able to get definitive treatment for their melanoma, the better. One of the risks, if someone other than a dermatologist or another health professional biopsies melanoma, is that there's then a delay potentially in getting the patient in to the provider that's going to be able to provide definitive treatment for that melanoma. That's one of the risks. Really, you want to see the highest level of specialty if you suspect a melanoma. Kaczor: Okay. I think that needs to be reiterated time and again, because every once in a while you come across those patients, and your hair stands up when they tell you what first happened to their lesion, and you just hope that it didn't go anywhere. Okay. Let's talk about, again, we're talking to our audience is generally practitioners that are frontline folks, and which patient populations, which types of people, should there be particular vigilance for skin cancers, like higher levels of suspicion, and who exactly? Birdsall: Okay. I warned you that we'd keep going back to a couple of things. Fair-skinned individuals, particularly those with blonde hair, red hair, lighter-colored eyes, blue eyes, although again, the warning that skin cancers can occur in patients of any skin color, and then that hallmark UV, exposure to UV radiation. More sun exposure, more risk. Also, however, living in sunny climates or higher altitudes, again because you're getting more direct exposure to UV radiation, as well as lower latitudes. Moles, patients that have more than 50 moles are at higher risk, and patients that have had a history of dysplastic nevi nearby or abnormal moles. Patients with actinic keratoses are at higher risk. Patients with either a family history of skin cancer or a personal history of skin cancer, and immune suppression. I want to just take a moment to talk about immune suppression, because that can include a variety of different patient populations. That can include patients living with HIV or AIDS, or oncology patients that maybe are receiving chemotherapy or maybe their immune system hasn't recovered from prior chemotherapy, and it does include patients on immunosuppressive drugs such as for organ transplants. Patients who've had an organ transplant are at high risk for skin cancers because they're likely to have a lifetime of immune suppression because of those immunosuppressive drugs. Lastly, exposure to radiation. You and I think of patients that have been exposed to radiation like breast cancer patients, lung cancer patients, et cetera. However, sometimes patients are exposed to radiation for skin conditions like basal cell carcinoma or eczema or acne, just different types of radiation. Then, exposure to chemical substances like arsenic can also increase risk, and then age increases risk. We're just at higher risk, the longer that we're living a lifetime out, being exposed to the sun. Kaczor: Is it true that childhood exposures can have an effect decades later? Like someone who grew up down in San Diego, for example, but they live in Minnesota? Birdsall: Yes, especially to melanoma. I am a-fair skinned person and I had an unfortunate history of a couple of different blistering sunburns, and that history of childhood sunburns and history of blistering sunburns can increase risk, especially for melanoma. Kaczor: Okay. Yeah. That's good to have validated, because I've always heard that. Maybe in our patient intakes, it's something we should put on our intake forms. Not only where did you grow up, but did you get burned, sunburned? Birdsall: Yes. Kaczor: Back in the day, of course, there was a time when people intentionally went out there and called a burn halfway to a tan. Birdsall: That actually reminds me. I don't think of indoor tanning frequently these days, but exposure to indoor tanning and tanning beds. Maybe your patient is very responsible now as an adult, but maybe in their teenage years had a long history of exposure to tanning beds. Kaczor: Yeah, yeah. It's something that's easily overlooked in an intake. Maybe we should make sure that that's top of mind. Let's talk a little bit about screening and prevention, and how can we make sure that we do catch things early, especially melanoma. What are the current recommendations, even, for skin cancer prevention? Birdsall: It's interesting. As far as screening, it remains somewhat of a controversy, which surprised me. US Preventive Task Force is considered one of the authorities on screenings, and to date, the US Preventive Task Force hasn't found sufficient evidence either for or against skin screenings. What's interesting is there is a lot of debate amongst other experts in the field. The American Cancer Society actually recommends a cancer-related checkup every three years for patients between age 28 to 40, and then also encompassed in that cancer-related checkup is other kinds of screenings in addition to skin cancer screenings, and then every year for anyone over 40. Interestingly, the American Medical Association really sees it as individualized, and recommends that a patient should talk to their physician about frequency for skin cancer screenings, and those at moderate risk even should see their PCP or dermatologist annually. The American Academy of Dermatology issued a statement regarding their disappointment over the recommendation by the US Preventive Task Force, and felt that the public should know that that recommendation that was neither for nor against annual skin cancer screening did not apply to individuals with suspicious skin lesions or those with increased skin cancer risk, and does not apply to the practice of skin self-exams. The American Academy of Dermatology recommends that patients really function as their own health advocate by regularly conducting skin self-exams and that if the patients see anything unusual, that they should see a dermatologist. Unfortunately, we all know that there's not always consistency with patients regarding advising for self-exam, and a patient can't necessarily see the back of their neck or their back, that may have had a lot of sun exposure. A number of dermatology providers still recommend annual skin exams, which after working with dermatologists, I'm definitely an advocate for as well. Kaczor: Yeah. Yeah, that makes sense. All it takes is a few cases. We're all a product of our experience, right? You see a few cases where it could have been prevented, and it seems and it is tragic. What can we do? I guess once we identify patients who are at higher risk, due to either childhood or exposure or fair skin or immune suppression, like what can we do to prevent skin cancers? Birdsall: Again, not to sound like a broken record, but decreasing sun exposure is the first thing. Interestingly enough, while I was just reviewing the research when I was preparing for our interview, I was looking at the Environmental Working Group and sunscreens, because there are definitely sunscreen ingredients these days that people have concerns about. For a patient that might be more holistically inclined, they might feel somewhat reluctant to put some of the ingredients that are in sunscreens on their skin, and so there's still a number of things that we can recommend. One is the physical sunscreens that are more of a barrier, and zinc oxide and titanium dioxide were considered generally safe and effective by the Environmental Working Group, and those are sunscreens with definitely friendlier ingredients that people may feel a lot more comfortable using and recommending. Secondly, wearing clothing shields our skin from sun exposure. There's some really interesting sun-protective clothing that is coming out as well if people are in the sun more frequently. Just trying to stay out of the sun during the peak periods or during high heat indexes is also something that patients can do as well. Then, doing annual skin exams. Because as you and I talked about, we may not feel concerned about a lesion that a dermatologist may instantly pick up on as something that may need to be further evaluated. Kaczor: Yeah. On that note, I don't remember when I read this, but years ago I remember reading they did surveys of lesions, and they had primary care physicians and dermatologists assess them and see who was most accurate. Nobody bats a thousand, but it was remarkable how much better the dermatologists were at visually assessing lesions correctly. Birdsall: Well, what was interesting working with dermatologists is I'd ask them why they were attracted to their field, why they went into dermatology, and they said because it's actually a field of medicine that you visually diagnose. You can visually see what's going on. Internal medicine, you might look at the results of a patient's lab work or a chest X-ray, but dermatology, you can actually see pathology and treat it. Kaczor: Yeah. How interesting. Yeah, so I guess you're good at that. Some people are better than others, I think. We are naturopaths, and so let's talk a little bit about diet and supplements and other things that we can do. What can we do from a supplement standpoint? Is there anything we can add or anything we should avoid, for that matter, that could lower the risk of developing cancer, skin cancer specifically? Birdsall: There was a really interesting Phase 3 randomized trial of nicotinamide for skin cancer prevention published in the New England Journal of Medicine in October of 2015, and in the study, 386 participants who had a history of at least 2 non-melanoma skin cancers ... again, that's basal cell carcinoma or squamous cell carcinoma ... in the past 5 years were randomized to receive 500 milligrams of nicotinamide twice daily or placebo for 12 months. They were seen by dermatologists every 3 months. At the end of the study, the rate of new non-melanoma skin cancers was lowered by 23% in the nicotinamide group, and noteworthy was the fact that there was no benefit after the nicotinamide was discontinued. I would say about 70% of the dermatologists that I was working with recommended nicotinamide to their patients. That's actually compelling data from my perspective in regards to a supplement. There's another supplement that has less research but is something interesting to watch called polypodium leucotomos, which is a fern from Central and South America. It was actually shown in studies to prevent both UVA- and UVB-induced toxicity and DNA damage. There was a study showing that 240 milligrams of a supplement containing that ingredient twice daily suppressed sunburn, and was found to extend the time outdoors before skin started to tan, so that's another possibility. I think we know as naturopathic doctors that vitamin C, E, zinc, beta carotene, omega-3 fatty acids, lycopene and polyphenols, especially in things like green tea, do also help to prevent free radical damage, which is what the exposure to UV radiation causes as well. Kaczor: Okay. Yeah. Is there a specific role ... I don't I honestly don't remember where I have this idea from, so you can validate or invalidate my presumption ... about using vitamin A specifically for actinic keratosis? Birdsall: Sure. There was a study on high-dose vitamin A reducing the incidence of actinic keratosis converting to squamous cell carcinoma, and the study looked at doses ranging from 25,000 IU a day, 50,000 IU a day and 75,000 IU a day. They did indeed find that that did prevent those AKs from turning into SCCs pretty significantly. However, from my perspective, there'd need to be a risk/benefit weighing of that for any particular patient. Kaczor: Yeah. Because 25,000 to 75,000 IU daily for an extended period is ... Birdsall: Correct. I had some concern after looking at that. Kaczor: Yeah. Yeah. Recently, I mean, I generally wasn't too concerned with vitamin A levels as we gave them until ... because we would often use this dose for antiviral effects. Recently I came across a study that did suggest that high doses for prolonged periods actually can lead to or at least are correlated with fatty liver. I was a little surprised by that. I came upon it, of course, by way of patient care and doing a little due diligence. Anyways, that's just a little caveat Birdsall: Right. I just am looking at that study and thinking about the fact that you would need to be on that long-term. I just had some concerns about using that particular amount of time. Kaczor: Yeah, yeah. Not just the known, but the unknowns. Okay. Let's turn to vitamin D, because that whole "Do I'd get enough sun for vitamin D, am I getting so much sun that I'm increasing my risk of skin cancer," it seems to be a bit of a conundrum. On the same note and maybe in the context of this, is there a difference between sunburns and suntans and their link to skin cancer? Birdsall: Okay. I think that there's definitely good evidence to suggest that vitamin D production from sun exposure poses too much of a risk for skin cancer. That's probably not the way that we want to be getting enough vitamin D, and there is more risk with a sunburn. However, suntans, our concept of tanning as being something that adds to our attractiveness, which I think in this day and age has faded with all the concern and the risk. Tanning does pose a risk too. That is still damage to your skin. Actually, as I was reviewing the research and thinking about this interview ... I'm just going to throw this in now, even though it's a little tangential and random ... if you have patients that are worried about the anti-aging, about the appearance of their skin, really the very best thing that they could do is to avoid sun exposure, to apply sunscreen, et cetera, because even that tanning still actually represents damage. Kaczor: Okay. The vitamin D, what I hear you saying is it's best taken supplementally. Birdsall: Yes. Kaczor: Because we have access of doing labs for our patients and such, is there an ideal dose to give, or do we base it on laboratory values? What is your opinion on that? Birdsall: My opinion is that we need to base it on laboratory values, because there's so much individual variation on intake of vitamin D and the impact of that intake. One patient may consume a lot of dietary sources of vitamin D and actually be at perhaps not an optimal, optimal level, but not be deficient in vitamin D. Another patient may take some vitamin D supplements and actually get to pretty high levels of vitamin D pretty quickly. I think the only thing that we can do for our patients right now is to do lab testing. Having said that, there is a lot of controversy over what the right values are, what the right range is. Again, when I was doing research just to make sure that I was totally up to date before we talked, it looks like people are in agreement over the fact that a 25-hydroxy vitamin D level below 20 nanograms per milliliter is considered deficient and does need repletion. We have more concurrence over that value. What's still controversial is what is that optimal range? Is it between 30 and 40? Is it 50? What we do know is that vitamin D can reach toxic levels, and that that's not good either, and that there is more and more data on too high of a level of vitamin D posing risk. I think that that again argues for making sure that we're adequately testing our patients, because say they're deficient, we decide that they need repletion. It's still hard to monitor, without doing that testing, where they're at from a vitamin D level as you're doing repletion. Kaczor: Sure. Sure. Yeah, I totally agree. I think that laboratory values should be just part of a routine lab for most people, given the many ways that vitamin D adequacy protects us from so many diseases. My last question is having to do with those who know they have a family history of skin cancers, maybe even particularly melanoma, but skin cancers in general. Is it appropriate, I suppose, for certain patients with a strong family history to look at genetic predispositions and hereditary syndromes that include skin cancer? Birdsall: That's interesting, again still a little bit of a controversy. We can test for a couple of genetic mutations related to melanoma. People who have a mutation on a gene known as CDKN2A have a higher risk of developing melanoma, pancreatic cancer, or a tumor of the central nervous system. A mutation on the gene called BAP1 means a higher risk of getting melanoma, melanoma of the eye or mesothelioma, and kidney cancer. However, the challenge is that if a patient carries a mutation on one of those genes, their lifetime risk of getting melanoma ranges from 60% to 90%. However, only about 10% of the people who develop melanoma have one of these genes. What we do know is that we're still evolving our scientific knowledge of genetic mutations, and it's highly likely that there are additional genetic mutations that we just haven't found yet for melanoma. This is a really important conversation for a patient to have with their healthcare provider, or even ideally with a genetic counselor, who can counsel them on the risks and benefits of genetic testing overall. Kaczor: Yeah. Yeah. Genetic counselors are a great referral for us to have, because we don't need to figure everything out and they have it all either at their fingertips or in their minds, so they're they're great professionals to ally with. All right. Well, I think that that's a really good survey and a nice review of reminders of things we may know, and maybe some things that are definitely new to our listeners. I can't thank you enough for taking some time and sharing your expertise with us today. Thanks, Shauna. Birdsall: Thanks. Thanks for having me. Kaczor: Take care.

The mission of the Climate Collaborative is to leverage the power of the natural product industry to positively impact climate change. Their goal is to bring the industry together in an effort to reverse climate change. In this interview, the organization's director, Erin Callahan, describes how they intend to achieve this lofty goal. Here's more NMJ coverage on how climate change will impact our food supply: Climate Change and Food Quality More Anticipated Damage to Food Quality from Global Warming About the Expert Erin Callahan is the director of the Climate Collaborative, responsible for management and execution of the Collaborative’s work, including all programming, communications, and outreach. Erin has a range of corporate campaigning and sustainability experience. She previously worked for CDP, managing corporate engagement for the We Mean Business coalition’s commitments campaign. In that role, Erin worked with hundreds of the world’s largest companies, industry groups, and investors, supporting them in making leadership commitments on climate change. She has also worked in public relations and international development and earned a master’s degree in international relations and economics from Johns Hopkins University School of Advanced International Studies. She is based in Oakland, CA. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we are tackling the big topic of reversing climate change. My guest is Erin Callahan, who is the director of Climate Collaborative. Erin, thanks so much for joining me. Erin Callahan: Thanks for having me. Gazella: Well, first let's have you tell us a little bit about the history of the Climate Collaborative. Callahan: Yeah. I'd love to. Well, thank you again for having me, I'm really excited to talk about some of our work. So the first thing to note is that we're a relatively new organization. We launched about 2 and a half years ago, just over that, at Natural Products Expo West, which is the largest food show in the US. And we launched because it did become really clear that within the natural product space, which is the fastest growing part of the food and ag sector and full of innovative companies, who are really helping define their mission and work via social impact and issues related to it, there wasn't yet a convening space for companies to come together on climate change. And we in fact did this study that showed that around 97% of the companies we surveyed really understood the urgency to be doing something on climate change, but almost 80% of them didn't know how to translate that understanding into action. There was a big gap between knowing that they wanted to do something and having the capacity to tackle it within their businesses. And so we launched to kind of address that gap. We really wanted to create a community of companies within the industry who could learn from each other, move forward together and get the rest of the industry really excited about climate change. And so that's what we've been trying to do for the past 2 and a half years. And I can certainly talk about the ways in which we do that, if that would be useful. Gazella: Yeah. Let's start with what you've been focusing on since 2017 when you started. So what's been the focus over the last couple of years? Callahan: Yeah. Well, you know, when Jessica Roth, the founder of Happy Family Organics the baby food company, and Lara Dickinson, the founder of OSC2, they were the cofounders of the Climate Collaborative and they really wanted to launch it as an industry collaboration. So we're a project of 2 organizations, SFTA and OSC2, and have collaboration deeply built into our model. And so over the past year we've really been working to try and extend that, kind of, baseline of collaboration and understanding that to tackle a problem as big as climate change, we can't act alone. No one in the industry can think that they're going to solve it on their own in a silo, so we've really been trying to build robust industry collaboration. And we've done that by creating this roadmap of nine commitment areas that represent the key emissions drivers for most companies in the sector. So it's packaging, food waste, agricultural practices, transportation, policy engagement, and we ask companies to make commitments, public commitments, in one or all of those areas. And that sends a message out to the industry that, "Hey. We are taking this seriously, we're setting public goals, and we are working as part of a bigger movement within the industry to do this." And so we asked companies to make commitments and then we help them on the implementation side. So we host webinars, we connect companies to partners and solutions providers, we try to connect companies to case studies and representations of what best practice looks like within the industry and work really closely with a really wide range of partners. And, crucially, we do this all for free. We're a nonprofit, so it's really important to us to not have cost, or any other issue, be a barrier to entry for companies. We work mostly with small and medium-sized companies who otherwise might not have the resources to start tackling this stuff. And so we really want to enable companies, regardless of where they're getting started, to be able to get on a pathway to action. And to do so as part of a really whole of industry movement. So we have everything from farmers and producers, to distributors and food retailers and brands, all working together collectively across the supply chain. Recognizing you need every link to really make change. And so that's been the baseline for the past 2 and a half years has really been building a strong base of companies who are committed to action. Kind of building this movement within the industry, and then starting to go down the road of providing really robust programming that can help them on the implementation side. You know, our theory of change is commit, act, impact, and we're kind of trying, you know, over the course of years of being around, to move companies from making these public commitments toward acting on them and then ultimately seeing real impact in the industry. And that's been the journey so far. Gazella: Yeah. I think it's brilliant. I mean, that's really why I was drawn to your organization, because you have this holistic collaborative from start to finish and you're getting commitments from organizations. So how many organizations have made this commitment that you're talking about? You know, you have 9 commitment areas, and they need to commit to 1 or all, how many organizations have done so? Callahan: Yeah. It's really incredible. We've got over 400. We've got nearly 450 companies signed up. We're at about 440 companies who've made over 1,600 commitments. And that's, I think, over 2 a day. I did the math recently, since we launched, commitments coming in. And, in fact, our busiest single month ever was this past August 2 and a half years in. And so I think what that shows is that the energy and momentum and sense of importance and value of what we're doing is only picking up as companies see climate change impacting their supply chains more and more and hear their customers talking about it and inherit it becoming a policy issue ahead of the 2020 elections. It's only becoming more important and central to what companies are doing, and that is incredibly heartening to see. We are so happy to see that progress. And so, yeah, we've got about 440 companies committed. They've made... You know, those represent General Mills and Dannon, really large food companies that everyone here has heard of and probably have their products in the pantry, but also really small startups and everything in between. So we're really happy to work with kind of a really wide range of companies who are at every stage of the sustainability journey and kind of going really deeply on things. Like packaging, in some cases, and, in some cases, trying to tackle everything. And, you know, so we really do have the full spread represented. Gazella: That's great. Well, congratulations on that progress so far. Now, obviously, your organization feels climate change is a big problem and we here at The Natural Medicine Journal are trying to cover this as well, so how concerned should we be about climate change? You know, what damage can and will occur with climate change if we don't act together, as you're talking about? Callahan: Yeah. Well, a lot is the short answer. And I think... I feel like everyone, this year especially, something's changed and we're all kind of scared of looking around and seeing... You know, this August, for example, all of us were watching sort of helplessly as the Amazon burned, and Hurricane Dorian just hovered as this slow-moving, giant storm over The Bahamas, and just these great tragedies affecting millions of lives and livelihoods and communities and just not being able to do anything. And, you know, that's a trend that's only worsening. I'm from the Mississippi/Gulf Coast and grew up watching hurricanes get worse throughout my childhood. And Katrina destroyed my hometown. And so these are very visceral things that I think we're starting to see and not be able to not connect... We can no longer avoid connecting it to climate change, and so I think everyone's sort of feeling it very viscerally. And then, you know, on the data side, we've got a huge amount of evidence to back up the fact that climate change is happening. It's getting worse. We're already seeing the impacts, and if we don't act quickly and at scale, the problems are going to be tremendous. You know, when we look at UNFCCC Reports, and even an EPA report that came out in November 2018, that showed that absent action, this could slash 1/10 of the US economy by 2100. You know, the UN has showed us that we have about 10 years to act to avoid catastrophic damage. We're on a road to exceed 1.5 degree increase in global temperatures, and we have to stop that. We have to take action to reverse it. And, you know, I moved to California year ago and within a couple of months was wearing a mask to avoid the smoke and fires, and saw my friends have to pull their kids out of school, and so I... It's a very emotional thing and it's a very practical thing that we have a lot of evidence backing up the risk of inaction. And getting into the health a little bit, it's very clear that climate change is absolutely a public health issue, in addition to an environmental issue and so many other types of issues. And so I think part of the conversation is how do we break this scary complex issue out of a silo of just being isolated to kind of environmentalism? And really focus on how is this having an impact on generations? How is it impacting the lives and livelihoods of the poorest people who are the most vulnerable to climate impacts? The youngest people who are going to bear the brunt of the problems that we see now? So, you know, I think that that's all becoming increasingly clear and hard to ignore, which is, you know, both heartening and terrifying. It's been really great to see the type of action that happened last week at the climate strikes in New York, right? I think they had to shut down Battery Park because there were so many people gathered. And this is all because of 16-year-old climate activists, Greta Thundberg, who, I think, is just been one person who has created this giant, global movement that gives me real hope. But it also just shows the energy and strength behind how many young people are recognizing the threat to their future that they see. Gazella: Yeah. I would agree. Well said. And before we get into the practical information, you know in the description of this an interview, I called your goal to reverse climate change lofty. I was actually surprised when I read on your website that the goal was to reverse climate change. What do you think? Is this a pretty lofty goal? And, even more important, is that a realistic goal? Callahan: Well, yes, it is a very lofty goal. And I think we absolutely can't do it single-handedly, so I don't have any illusions. As much as it would be wonderful if I could work with these 450 companies to single-handedly reverse climate change, I don't think that's possible. I think what we're trying to do at the Climate Collaborative is highly ambitious, and, essentially, what we're trying to do is create a new model of doing business within the natural product space that is replicable and scalable. And that shows that there is a way that companies can take advantage of the tremendous opportunity that responding to climate change represents. Be first movers on creating new systems and ways of doing business that are an inevitability, I really believe. In terms of new ways of doing agriculture that helps restore carbon in the soil, new types of packaging, reductions in food waste. The shift toward these types of practices is inevitable, and why not have this innovative industry be at the helm of creating those shifts? And so, you know, that is really... We want to create a model that then cascades across the food sector. And I think... So when you ask, are we looking to really reverse climate change? I think that when you look at the fact that the food and agricultural system accounts for about 23% of global emissions, it's going to be absolutely key to solving climate change and have this huge kind of double-edged sword of being a huge potential opportunity as a solution, through carbon soil sequestration and other mechanisms, but also is a tremendous risk factor if we don't take action. And so I really look towards the types and group of companies that we work with as leaders in creating those new systems. And so maybe not reversing all of the climate change, but maybe reversing how the food sector responds to climate change. And any company with an agricultural supply chain, how they can shift their practices to really create a new model for the food system. And so I hope we can do at least that much. I still believe that is an incredibly lofty goal, in that there are a lot of structural barriers to getting there. When you look at certain policies that disincentivize the types of practices that our companies are looking to start making or already making, and then the absence of things like a price on carbon and absence of policy and incentives rather than disincentives for farmers to be changing their practices to help restore carbon in the soil and all of that. So that's why policy is such a crucial piece of what we do as one of our 9 commitment areas. And it's potentially the most important, because every company in our network could get to net zero emissions and it would be the drop in the bucket, when you look at global emissions. So policy has to go alongside whatever action that companies take, and my hope is you can then create a virtuous circle where you have companies acting and proving policy mechanisms can support these actions at scale, and then wider set of businesses taking up these policies and then you kind of create that virtuous circle. So, that's my hope. But I completely agree, it is still really lofty. But I think we don't have really any other choice but to be ambitious and lofty in our goal setting these days. So, I am hopeful. Gazella: Well, I agree. And I was going to ask you, "Why the natural health industry?" But you bring up such a good point, if you can create this new model that can then be replicated, you could have that ripple effect and have that, as you mentioned, cascade into the food sector. So to me that makes sense, so now I'm feeling better about my term lofty. Because I think- Callahan: Oh. Good. Gazella: Yeah. That makes total sense to me now. So let's get to the heart of the matter. So exactly how is your organization going to reverse climate change? Or, you know, if we put this into more digestible pieces, how is your organization going to create this new model of doing business that can then be replicated? Callahan: Yeah. Well, the first thing is getting companies to make public events. And I think that... You know, I mentioned before, and kind of getting to your point around why the natural health and products industry, and I think that is because it's almost a quarter of global emissions when you look at the food and land system. There was just a Land Use Report that the Intergovernmental Panel on Climate Change put out that just showed how critical the sector is in responding to climate change, and that kind of double-edged sword of it being a solution and a problem. So that's why these companies. And, you know, I think that within the food sector, our companies already have a status of first movers. When you look at issues like organic and non-GMO, fair trade, the natural products space, they've been first movers on those. And then have then become standards that we all know, we all shop and look for those labels, and we're all kind of very aware and it's cascaded across the food sectors. So we have model of what it could be and how that scale could work and look, and now we need to make climate that issue. And that's part of the type of model we've tried to adopt here at the Climate Collaborative. In terms of how we do that on climate, it is predominantly through our commitment areas. So we have these 9 commitment areas. They're focused around carbon farming and regenerative agricultural practices. So it's changing on-farm practices so that you're pulling carbon into the soil and keeping it there, and that things like compost applications and cover crops. Intensive rotational grazing, when you're looking at pastures with animals. So changing your on-farm practices to really help draw down carbon, and that's a huge opportunity. If, you know, you're familiar with Paul Hawken's Project Drawdown, which is this giant list of climate solutions, that's number 11 on the list. Another one that we work on, number 3 of his solutions, is food waste. And that is, you know, about a third of food is wasted and so we're trying to help at least the corporate part of that, so companies and their supply chains, to reduce food waste. And at source. So not just looking at waste diversion and donations, but really looking at how can we reduce the waste that's produced in the first place and make a more efficient supply chain from producers to grocers selling it to consumers? So we had a big project this year where we did intensive consultations with retailers in the US on reducing their food waste in store. Packaging is another really big issue that we look at. It's the single biggest challenge for companies, you know? Everyone, I think, has paid attention to the plastic straw bans, and plastic in the oceans, and been very aware... It's a very visceral thing because you hold it in your hands and you see it, and then you throw it in the trash or the recycling and... It was just a very visceral way to be aware of your footprint, I think. And so that has been the single biggest issue and challenge area for the companies we work with and we do a lot to try and help them reduce their packaging impact. And, you know, there's policy, energy efficiency, switching to renewable energy, so we're looking at very concrete practical solutions that are very action-focused. You know, I would say that for companies it's also really important to take a look at your footprint and say, you know, "Where are my emissions concentrated?" Start measuring and setting goals, and so we do encourage that. And, above all, we want companies to just say, "Okay. Let's start taking action. Let's start doing something and be part of, kind of, a larger community of companies within the industry doing that." So we do that through working groups. We have one on regenerative ag, we have on consumer engagement, one just for retailers and we really try to just kind of get companies able to talk to each other a little bit more about their efforts. So that's a little bit. I'm happy to go into more detail, but those are a few of our projects. Gazella: No. I think that's great because what we're going to do is we're going to put a link to the Climate Collaborative website, and I know that you list these 9 commitments. And you have a ton of information on your website, videos and such, so I highly recommend that any manufacturers who are listening, you know, or anybody really, click over to the Climate Collaborative to learn more. Now, technically our journal is a part of the integrative health community and not necessarily the natural health community, per se, with a lot of retailers and manufacturers and such, but I'm wondering how our readers, are individual doctors, can help with this effort. So what advice do you have for the individual? And, in particular, I mean, our doctors are seeing patients and they're influential, you know? So what advice do you have for them to make an impact in this area of climate change? Callahan: Yeah. Well, a couple of things come to mind there. Firstly, we host one day of the year called Climate Day, which is my favorite day of the year. It's where we bring the whole industry together and get a set of thought leadership speakers, and everyone in the room just talking about the biggest issues that we need to tackle on climate change over the next year. And last year one of our keynotes with Yvon Chouinard, the founder of Patagonia, which, I think, if there's a company who's doing just fantastic work on climate change and making their whole mission focused around reversing, it's Patagonia. They've just been real leaders. And he was interviewed by Dr. Zach Bush who some of your listeners might be familiar with. I actually wasn't too familiar with him, but it might be an interesting conversation to reference in this because his whole talk was really around the relationship between the microbiome in all of us and climate, our biome. And what are those connecting, and how does one impact the other, and how does how we manage the climate then filter down to the nutrition and the food that we eat? And, overall, the microbiome and health of our bodies? And so I just want to reference that, because I think that there's a lot of interesting stuff happening. A lot of interesting research happening there right now that I'm fascinated by and there's a lot to mine there. So, that is one thing. The other thing is, I think when it comes to doctors, or really anyone as an educated, active citizen, 1) voting and advocacy matters. And then, 2) being a really conscious consumer. And asking the businesses that you're purchasing from and working with what their practices are, and asking them questions about their packaging, asking them questions about their footprint. And business is new because of stakeholder action and requests and consumers are such a crucial stakeholder. It's why we're launching this consumer aspect of the product this year. But I think creating an aware base of people who are talking to these companies, and working with them, in some cases, and shopping for... You know, with their products. Make smart choices but with your dollars. We have a group of fantastic companies that are really piloting new work and it's really important that we acknowledge that through engagement with those companies, through dialoguing. By pushing them farther and getting engaged in their mission, but also just generally when shopping by making really informed choices about the company that you're looking at. And that's a very hard thing to do. I mean, I'm a consumer and it's really hard to hold the fact that I need something in a certain price point, I need it to be really good, I need it to be exactly for what I'm doing, I need to get it pretty conveniently. And then also, on top of that, I need to care about what's its footprint? Where did they source the ingredients? You know? And then also is it fair trade? Is it... You know, are they using renewable energy? What's the packaging? It's a lot to hold, but I think the more you can be okay and accept that complexity and really try to make informed purchasing decisions, the farther where we're going to go. And, luckily, we're already seeing real movement. You know, I think 70% of Americans are looking to see more from the companies they're doing from a study that came out last year. I mean, you look at the younger demographics, those numbers get even higher and they really are making their purchasing decisions based on the footprint and choices of the companies they purchase from. So I think the more we can all lean into that, the better. Gazella: Yeah. I would agree. And I think that's great advice. So, in closing, why don't you go ahead and describe some of your short-term goals moving forward. Say, within the next year or 2, what is your organization want to accomplish in the near term? Callahan: Yeah. Well, firstly, on the outreach side, we've got an incredible base of companies committed. We're at about 440, like I mentioned, I want us to get to 500 by March of 2020. That is my goal. It really matters to keep that energy and momentum up, and so I'm looking to bring on new companies. We're really looking to actually move in to a lot of health and nutrition companies and we're going to be at a conference in a couple of weeks talking to them. And, you know, that's kind of a subsector of the industry that we really want more actively engaged, so that's the one thing. And then on the programming side and the work of it side, we're just over a year away from the 2020 elections. Giving our companies pathways toward active engagement on policy issues ahead of that election and getting them informed on what they can be seeking out on and supporting, is a real, real priority of mine. We're working with a great set of policy partners on that front to do that and that's something that we're going to really try to be doing a lot of over the next year. Outside of that, I mentioned consumer engagement. We are launching a consumer engagement part of the project over the next year, where we're trying to actually create a common set of messages that companies are using to engage in dialogues with consumers. And also to raise awareness on specific issues. Like soil health, like food waste, packaging, and really try to create dynamic, fun, engaging conversations with consumers that are action-focused as well. So we're hoping to really get that off the ground in the next year as well. And then our rooted community, the regenerative agriculture community that we have, we meet 4 to 6 times a year right now and going to be doing our first on-farm site visit over the next year as well. And I really hope we can be doing more of that, and constantly just trying to roadmap the business case for action. I think a lot of companies understand the altruistic and moral reasons to act, but when you back that up with saying that there are real business cases to be doing certain things like this, especially when you're working upstream in your supply chain with farmers who have very small margins and also really know... They know how best to manage their farms, and so when you have these conversations, what are the incentives we can provide and what data do we have to back that up? So we're constantly looking to increase the amount of data that we have on that and to connect your companies to it to really help promote these practices within the industry. So, those are a few key priorities. I think, overall, we're also just trying to keep the energy and momentum up in the industry. Climate is a really complex issue with a lot of nuances and not a lot of clear black and white solutions that we can just easily adopt, and so the more we can get companies excited and motivated and willing to work together, which I think they increasingly are, the more opportunity we have to really see transformative change in how the industry at scale is really attacking some of these issues. So that's my biggest hope. Is that we just keep the energy up, from as wide a group of stakeholders as possible, around focusing on climate and moving forward with real action. Gazella: Well, those sound like some great goals and it sounds like you're going to be very busy in the coming couple of years. Callahan: I think so. Yeah. Gazella: Yeah. Well, I just want to congratulate you on creating the... Well, your founders creating he Climate Collaborative and your work as the director. I really applaud you. I think it's great work. It is lofty and it's huge, but it's so important. So thank you so much for joining me today and telling us about your work. And I encourage our listeners to go and check out the Climate Collaborative, and thank you, Erin, for joining me today. Callahan: Thank you so much. Gazella: Have a great day. Callahan: You too.

In this interview, Benton Bramwell, ND, discusses the unique Mediterranean herb Arum palaestinum. Listeners will learn about the traditional use of this herb, as well as current research that helps illuminate its modern-day clinical applications including oncology specifically. Synergy, safety, and dosage will also be discussed. About the Expert Benton Bramwell, ND, graduated from the National University of Naturopathic Medicine in 2002. He manages a private practice and also provides consulting services to food and dietary supplement industries in matters of scientific and regulatory affairs. He enjoys the wonderful outdoors, especially working the vegetable gardens with his family and going on bicycle rides that allow him to think and exercise at the same time. About the Sponsor Hyatt Life Sciences is Putting Science Behind the Tradition™ Headquartered in America’s heartland, Sterling, Kansas, Hyatt Life Sciences continually searches for unique botanical entities and combinations that have been used traditionally in their countries of origin for hundreds of years. Rather than depending only on tradition and legend as many nutraceutical companies do, scientists at Hyatt Life Sciences research, test, and evaluate each herb, root, and component to discover the scientific reason for the ingredient’s benefit. We offer products only after each ingredient has been thoroughly researched for benefit, safety, and purity. At Hyatt, we are committed to Putting Science Behind the Tradition™. Read more. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we're going to have an interesting discussion about the Mediterranean herb Arum palaestinum. My expert guest is Dr. Benton Bramwell. Before we begin, I'd like to thank the sponsor of this topic, Hyatt Life Sciences. Dr Bramwell, thank you for joining me. Benton Bramwell, ND: Pleasure to be here, Karolyn. Gazella: Well, let's start with the basics. Where does Arum palaestinum grow? Bramwell: Great question. Arum palaestinum grows in the Mediterranean region and is particularly known and used in the Middle Eastern portion of the Mediterranean. Gazella: Okay. Perfect. Bramwell: Quite a history to it actually, Karolyn. It's been known in the region for actually, literally, thousands of years. In fact, it shows up on some drawings in ancient Egyptian temples. We believe it was probably brought to Egypt from Canaan in about 1440 BC. It's been there for a while. Gazella: Yes. Yes. Also from a historical perspective, what conditions was it used traditionally for? Bramwell: It appears from the historical literature that it's been used for many different kinds of conditions. Primarily for a treatment for cancer, historically, but also as a treatment for infections and open wounds, as a treatment for kidney stones, and even for a worm treatment in animals and humans. Also, it's a way to strengthen bones. This is one herb that has been used in a very diverse applications, perhaps not the least of which because it happens to also be a wonderful food. It made its way from food into medicine. Really that distinction as, of course, you know in a lot of places in the world, there really is no distinction, right? A lot of times the best medicines come from our feed. This is certainly a prime example of that. Gazella: Yes, exactly. Let's fast forward to today. What are the main clinical applications of this botanical today? Bramwell: Yes, we're still learning about that in terms of modern application, where it's going to be the best fit. We certainly continue to see it used clinically in the ways that has been used traditionally previously. That's in the Middle East. It's still used as a complimentary supportive adjunctive support for patients with cancer. It's also finding its way into skincare, and I think we're catching up, frankly, in the modern scientific age as to where it should be best used. I think we still have a lot to learn there, but we're learning as we go. Gazella: That's a pretty diverse list of conditions that this herb can help with, which is kind of common with some botanicals. I'm assuming that's because there's a variety of mechanisms of action. Is that a correct assumption? Can you tell us exactly how this botanical works in the body? Bramwell: Right. I can tell you what we're starting to see there and understand. There are a variety of mechanisms. Just for a minute, let's focus on where it might fit in terms of something that makes supportive sense for the patient with cancer. What we're seeing is that it may very well, at least in the in vitro models that we're seeing, it may very well help with the cellular process of apoptosis. That's the process by which a cell decides that it's time to basically do itself in. It's programmed cell death, right? There are some interesting mechanisms through proteins that are caspases. I think that we're going to continue to see the literature develop there quite a bit, but I think that's one important mechanism. It's also important in terms of cell signaling by means of phosphorylation. There are many pathways in the cell which run off messenger systems based on phosphorylation. It seems that Arum palaestinum probably inhibits some of those pathways as well, or at least the compounds from. Those are several of the mechanisms that we see in play. Gazella: Okay, good. I understand that there's a topical application of this plant. Can you tell us a little bit about the topical application and what that formulation actually looks like? Bramwell: Yes, I can tell you a little bit about that. I'm glad to see that one coming forward. It's certainly in line with the traditional use. That product, Arumacil, it contains the Arum palaestinum extract, as well as dimethicone and petrolatum. The object there is to help protect the skin, give it a chance to heal, basically. I wouldn't be surprised, and I don't think the literature has necessarily caught up to us here, but one of the main categories of plant chemicals that we're talking about here are flavonoids. Flavonoids are known in the literature to have antiviral effects. Again, a little bit more to learn there, but I wouldn't be surprised at all to find this topical application of good use, clinically for people with cold sores and other minor skin irritations, frankly. You're going to get a lot of antioxidant action from these compounds, as well as potentially some antiviral, although I think we need to learn more about them. Gazella: Okay. That makes a lot of sense. From what I've read, this is a pretty complex botanical. It has a lot of different constituents. From the therapeutic perspective, what are some of the key active compounds in the plant? Bramwell: Well, there are many actually. In the literature where I've spent some time, and from what we can find, there's about 180 phytochemicals that we can at least tentatively be identified at this point in time. Most of those, as I mentioned, are flavonoids of one kind or another. As I look at the list of what's been identified, some of those I would pull out would luteolin, which I think is going to prove to be very important from an anti-inflammatory point of view. That's certainly an active bioflavonoid, in particular, a class of flavonoids called flat bones. I think that's going to, doing the [inaudible 00:07:52] one of the important ones. But there are others as well. There are derivatives of rutin in there, and epicatechin. So I think those are all going to be important. In addition to the flavonoids, there are also phenolic acids and derivatives of phenolic acids in here as well. Rosmarinic acid is one that pops out, and these are all compounds that I mentioning that when you look at the individual ingredient, it doesn't take you long to find in the literature that these individual ingredients, upwards of between 20 or 30 of them, have a little body of literature of their own, as to their anticarcinogenic potential. And so, I think what we've got here among the flavonoids, the phenolic acids, and I should mention also some terpenoid derivatives, of course solic acids in there as well as some iridoid derivatives. When you put all those together, and each of them have an anticarcinogenic potential, the complexion of the botanical is one that seems well suited for its historical use. Gazella: Yes. Especially when you consider a condition like cancer, which in and of itself is so complex. I'm fascinated by the fact that there are all these little compounds, and as you've mentioned, you could probably take one compound, do a scientific literature search and find data to support that one compound, but here we're talking about multiple compounds all within the same plant. Bramwell: Well, that's exactly right. And actually some of the interesting work that's been done, one of the interesting approaches here is to take some of the compounds that occur in the plant naturally and make a fortified extract, if you will. So, that work's been done in vitro and in vivo and in several different places. They've taken out, for example, linolenic acid, beta sitosterol and isovanillin. Those are items, constituents that you can get in a water extract of the plant and then made a fortified product from that... material. And when that material has been tested in the in vitro and animal models, it seems to perform superiorly to the raw extract, and I find that very interesting. It seems that Genzada Pharmaceuticals, Hyatt Life Sciences have done a very good job in the work that's been ongoing here showing an increased potential of this fortified extract approach. Gazella: Yes, that sounds like some pretty cool science. I want to focus, in particular, on a 2018 study that was published in scientific reports. Now in that study, it compared to three different formulations and all of the formulations included Arum palaestinum. What were the results of that study? Tell us a little bit about that particular study and what the objective was and what the results were. Bramwell: Right. So, this is an approach, again, where a fortified... a number of things were tested. One of the things that they tested was combination of the three plant extracts, Arum palaestinum, curcumin longa, which most people are familiar with turmeric, as well as another from the Middle East peganum harmala, sometimes known as Syrian rue. So, those 3 botanicals were studied together and then various combinations of a fortified extract, or in one case, a chemical constituent from each of those was mixed together, and that actually looked the most potent as far as it's anticarcinogenic potential. And in that case, isovanillin, which you would find in the Arum palaestinum, was mixed with harmine, which you would find from the Syrian rue and also curcumin from the turmeric and all three of those plant chemicals were used together. And that actually seemed to have a very potent anticarcinogenic effect in the in vitro and in the animal models that we're studying here, in terms of looking at the invasive potential and proliferation, of the cancer cellulars models that we used. And in this case, the researchers were looking at the head and neck squamous cell carcinoma, which is a very fast growing, aggressive kind of cancer. And, it does appear that the cells that were used here were very sensitive in these models, to that combination. Gazella: So remind us, which combination then performed the best in this particular study? Bramwell: Right. In this particular study, the combination of the three phytochemicals, so isovanillin, Arum palaestinum, and harming from the Syrian rue and curcumin from turmeric is what performed the best. Gazella: Got it. Bramwell: And again, they were able to show the effect on the molecular signaling cascades within the cell. So, there's some definite believable mechanisms of action here as to why the compounds would have the effect that they do. I think we're going to see a lot more about this one in the future as it becomes translated to human clinical studies. Gazella: Right. Yes. Based on that study and other research, it sure seems like Arum palaestinum is best used in combination, potentially with other botanicals versus as a single botanical. Is that true? And if it is true, why is that? Bramwell: That's an excellent question. I think that probably is the case, that either combination of the Arum palaestinium with other botanicals or even compounds, key compounds, from each of several important medicinal herbs. The question is why do we see this additive or even synergistic effect with these compounds or with the botanical blends that seems to manifest in the literature? I don't know all the reasons for that, but I rather think, given as complex as cancer is, being able to affect multiple pathways is probably the breadth of the attack against cancer cells, is probably why we're seeing that synergistic kind of benefit. One way to attack something is with a very narrow focused approach. A deep attack. Another way is with a multitude of effects together. A nice, you know, cover all the bases. And I think that's potentially what we're seeing as this literature sort of declares itself here. Gazella: And now what combination or what product, what Arum palaestinum product do you use in your clinical practice? Bramwell: So right now what I'm using is the Afaya Plus and you can learn about that, consumers, patients, physicians can learn about that at the Hyatt Life Sciences website. But I think that that's the best product certainly than I've seen on the market at this point in time. Gazella: Mm-hmm (affirmative) great. We'll also provide a link to the website too, so listeners can click right over. So, so far, there's been some compelling in vitro and in vivo and we all know that that's kind of the progression of research as we study these botanicals. What about human clinical trials? Bramwell: That's the next step really, Karolyn, and I don't know when those are going to be published or what stage we're at, but we're definitely ripe for what would be called phase one and phase two clinical trials here. From what I can see in the literature. Gazella: Are they underway? Phase one, is this phase one underway or is that still, are we still waiting for them? Bramwell: I think we're still waiting for that, at this point in time. I hope to hear more about that in the near future. But at this point, following the literature and everything we see we like. Gazella: Right. Bramwell: And can't wait for the next human work to actually be published. Gazella: Yes, I mean, the traditional use combined with the preliminary research sure does seem to be compelling. I'd like to talk a little bit about how it's used in oncology in particular. Do you look at this botanical as an adjuvant to be used with treatment or maybe after treatment? What's the clinical application when it comes to oncology? Bramwell: Right. Well that's a very good question and because of where we are in the scientific process here, we're still early on. Although I think Hyatt Life Sciences, to be fair, has done much more work than many dietary supplement companies ever do. But we're not there yet in terms of knowing all we want to know. So at this point in time, I don't think anyone would responsibly say that this is a treatment for cancer. What we would say is, traditionally the syrup has been used by patients who have cancer. It's part of our herbal armamentarium historically, and it seems to make supportive sense. And so, this would be something I would recommend while the patient is going through treatment. Although I tend to leave a space of time between conventional care and herbal therapies, just to make sure that the chemotherapy has time to do its work. So I would tend to leave three or four days, or at least one or two before and after a chemotherapy treatment. I think, from what I see in the literature, at least from the the Middle Eastern region where this is used quite heavily, when oncologists in that area are surveyed, they're not reporting anything really of concern as far as interactions go. But I would still leave a couple of days on either side of treatment, make sure the chemo gets in and does its job. Gazella: Yes, that, Oh, go ahead. Bramwell: No, you're fine. Gazella: Well, I think that that's a good, prudent recommendation and I think that oncologists would agree with that. Now beyond oncology, is the herb safe? You talked about no interactions with chemotherapy that we know of, but are there any other interactions or contraindications that we should know about? Bramwell: You know, not that we can see at this point in time. The only thing I would point out and highlight there, Karolyn, is that even in traditional use, where this has been used as a food, what's been known for a long time is that it's boiled. It's boiled several times in water and that water is decanted several times, taken off, in the preparation of the herb as a food. Or in this case, before it's a supplement. Don't know all the reasons for that, but part of the thinking has been there that there's a high amount of oxalates in the plant and in order to prevent toxicity, that's an important part of the plants preparation as a food/medicine. So, I would highlight that for you. Gazella: Yes, that's interesting. Is there any kind of standardization with this botanical? Bramwell: Yes, it could be standardized. But since we're in the process of learning all that's important about it, I think the closest thing to standardization is the work that was done several years ago with the fortified extract of isovanillin, linolenic acid and beta sitosterol . That complex looked quite promising. And if you wanted to standardize to something, that would be one way to do it, but I'm not aware of a totally standardized extract at this point without fortification, if that makes sense. Gazella: Okay. Yes. Let's talk a little bit about dosage. So what dosage do you recommend and does that dosage change based on the clinical application or if it's for prevention versus treatment? Bramwell: I would tend to be more aggressive with a patient who's using this as a supportive. Make it a supportive care during cancer. And the Afaya Plus, two capsules [inaudible 00:23:07] of that is going to give about 900 milligrams, of a combination of vanillin powder, tumeric powder, harmala powder, the Syrian rue and Arum palaestinum. I would tend to go at least two capsules, twice a day on that. But again, when you're working with a patient with cancer, you're going to have to titrate the need, titrate the dosage that they can take. Some patients going through treatment have a difficult time getting food in. And one thing we always have to remember with a patient with cancer is that we want to feed them first. And we don't want capsules to take the place of food, and so it's going to depend on what the patient can tolerate. But I would start off with a two capsule b.i.d. kind of an approach. And if they can tolerate that well, even up to two capsules t.i.d. As a maintenance kind of thing, for general health, I could see taking a single or two capsules a day, single serving. Gazella: Do you feel like it has a good application? Like for example, somebody, a patient who may be at high risk of developing a type of cancer. So as a way to kind of help reduce risk, do you feel like there's an application for that? Bramwell: We don't really know at this point, but I would suspect so. There again, I'm not one to, I don't necessarily subscribe to the philosophy of more is always better. But I think it's something that I would carry in my mind. You know, if dad and grandfather both had prostate cancer and I want to take something and it's kind of a daily maintenance to keep as healthy as I can, to maintain that prostate tissue in a good state, I would think of serving of this a day would make a lot of sense. Gazella: Okay, great. Now, we talked a lot about oncology, but we also mentioned skincare, infections, kidneys, bones, when you're looking at the clinical potential of this botanical and the clinical application of this botanical, does oncology bubble to the top over everything else? Bramwell: I think it definitely does. In fact, there are many other applications that we've mentioned here. And we're going to learn more about those over time. I think this is something that naturopathic physicians and other integrated healthcare practitioners are going to learn about as they go. And that's okay, really. We're using something that's been in traditional use for a very long time. But it would be something that for other conditions like skincare, I would just try it clinically and see what we see with it. But I think the biggest, biggest application, Karolyn, is going to be oncology. Gazella: Yes, I would agree based on what we've discussed today. For sure. Now, Bramwell, I'd like you to pull out your crystal ball and kind of look into the future as a clinician, what would you like to see happen with this botanical as it relates to oncology specifically? Bramwell: Couple of things and I think already some progress has been made in terms of what formulations are the most effective, but I'd like to see a little bit more work in that regard, with various combinations. I think that we will see, in the next few years, based on what's already been done, phase one and phase two clinical trials. And I hope, based on what's done that that includes work in both patients with prostate cancer, as well as patients with head and neck squamous cell carcinoma and some of the other lines that have shown promise. I mean, there's been some work that's a promising in glioblastoma cell lines as well as lung cancer. So we'll see where it goes in humans first, I hope with patients with prostate cancer and patients with the head neck cancer especially. I also am intrigued, in that 2018 paper that you referenced, there was some work indicating that it may go very well in combination with Cisplatin. Bramwell: Platinum chemotherapy is very commonly used in colon cancer treatment, as well as other cancers. And boy, if there would be something that would help the platinum chemotherapy be even more effective than it is, I think that would be a wonderful combination and as I kind of look to the future, that one comes to the front of my mind, Karolyn is, is this an adjunctive therapy that could actually make the conventional therapy a little more effective? And I would really hope that the future upcoming human work will really hone in on that and help to answer that question. Gazella: Yes, and it would also be kind of interesting to see if this botanical could help reduce some of the side effects that come with conventional chemotherapy. I think that would be kind of an interesting... I'm curious as to why prostate and head and neck. I mean, head and neck, that's a tough one and I would love to see it be effective, but why are those two ones kind of standing out in your mind as to where this botanical may help? Bramwell: Right. Well that's based on the work that's been done so far. So yes, there's going to be a great, great question. The 2018 work was primarily done in head and neck squamous cell carcinoma, and the work before that, in 2015 that was published, was quite focused on prostate cancer cells. So, it makes sense to build on what you have there. But, you know what? Here's the great thing about Arum palaestinum, from everything I'm reading, it looks like the mechanisms of action, and there are multiple of them, could be applicable across many kinds of solid tumors. So this would be the kind of thing where you can build on your in vitro and animal work and human studies, but you might quickly branch out and other areas of exploration as well. It could be something that could be beneficial to many patients. We don't know yet, I don't think. But, when I read this literature, the question I asked myself is, could this be the next [00:30:30] ? Could Arum palaestinum be that botanical source for a cocktail of phytochemicals that really finds broader use and helps many patients live longer and much better lives. I hope so. Time will tell. Human data will certainly inform things from here, but what we see so far is it's highly encouraging and kudos to the Hyatt Life Sciences for getting this out there. Gazella: Yes, I hope so as well. It sure sounds like there's a lot of potential here and we're going to definitely, The Natural Medicine Journal, will definitely be following this research on this interesting botanical, Arum palaestinum. Well, once again, thank you Bramwell, for joining me today and I'd also like to thank the sponsor of this topic, Hyatt Life Sciences. So, thank you for the interesting information, Bramwell, and I hope you have a great day. Bramwell: Well, thank you, Karolyn. Pleasure to be with you.

Natural Medicine Journal publisher Karolyn A. Gazella talked with Kristie Ebi, PhD, from the Center for Health and the Global Environment with the University of Washington. The two discuss Ebi's research using new technology to model growing conditions as they will be in the coming decades if we don't curb climate change.

In this podcast interview, we speak with neuroscientist and physician Leanna J. Standish, ND, PhD, LAc, FABNO, about her naturopathic oncology research. Standish has been involved in original research at Bastyr University since 1987, where she continues to teach and serve patients. We discuss the research she's currently working on—the Canadian US Integrative Oncology Study (CUSIOS)—and its focus on understanding how integrative oncology care affects outcomes for people with certain advanced cancers. In addition, we discuss the use of psychedelic drugs like psilocybin in cancer care—especially for people who have a history of trauma. About the Expert Leanna J. Standish, ND, PhD, LAc, FABNO, is a neuroscientist and physician living in Seattle. She has faculty appointments in the University of Washington School of Medicine Radiology Department, the University of Washington School of Public Health, and Bastyr University. She is working toward obtaining approvals to conduct ayahuasca clinical studies in the United States. She uses functional magnetic brain imaging to study brain-to-brain communication and the ‘entangled minds’ hypothesis. As a physician she specializes in naturopathic oncology, with special interest in the treatment of stage 4 cancer. Standish earned her PhD in neuroscience/biopsychology from the University of Massachusetts in 1978, her ND from Bastyr University in 1991, an MS in acupuncture and Oriental medicine from Bastyr University in 1994, and became board-certified in naturopathic oncology in 2006. Transcript Tina Kaczor: Hello, I'm Tina Kaczor, Editor-in-Chief here at the Natural Medicine Journal. I'm talking today with Dr Leanna Standish about ongoing original research in naturopathic oncology. Dr Standish is a neuroscientist and naturopathic physician with a master's in acupuncture and Oriental medicine and board certification in naturopathic oncology. She's been involved in original research at Bastyr University since 1987, where she continues to teach and serve patients. Dr. Standish, thank you so much for joining me. I want to go- Leanna Standish: Hi, can I just say hi to everybody and especially you, Dr Kazcor, and just express how delighted I am to talk to all of you. Kaczor: Yes, and so yeah, it's very exciting to have you one on one to get to know a little bit of what's going on in the front lines of research specifically. What prompted this was your update at the recent oncology conference. The Oncology Association of Naturopathic Physicians had their annual conference in February where you spoke. I'd like you to kind of start at the beginning. What was really compelling is some of the research on both non-small and small cell lung cancer as well as breast cancer studies. So, if you could kind of update us about a little bit of what ... update us on what's going on with your research in those areas. Standish: Yes. Well, since 2009 working at Bastyr University with Paul Anderson, we started collecting data on survival outcomes in our advanced cancer patients and have a big enough database that we can start summarizing survival outcomes, which is I think of great interest to both patients and their physicians. What we found, our first study was in breast cancer, stage 4 breast cancer, that our median overall survival in our patients, they were 54 consecutive women with breast cancer. The median overall survival is 47 months. When I first got those data, I was very upset because it means that half of my patients were dead at 47 months. But then I thought, well, how does that compare to other studies that were being published at the same time that we were doing our work? What we found is that the best study that we could find in terms of median overall survival in stage four breast cancer was an Abraxane trial that happened in the early part of the 2000s. Just getting some tea here, hold on. That study showed a median overall survival of 36 months. So the conclusion to me was yeah, this is an uncontrolled study. The kinds of patients that we see are the kind of people that are very proactive. They may be survivors just in their very being, but in any sense that you can think about this, that those are pretty good results in advanced cancer. Then we did a similar study in advanced non-small cell lung cancer, and that was with 18 consecutive patients, stage 3 and 4, and the median overall survival there was 43 months. Then we surveyed the literature and did a systematic, I should say systematized review to find that the median overall survival for all the chemotherapy drug trials and even the new immunotherapies that were coming out in just the last say 5 years, the median overall survival of all those studies when averaged together was only 13.3 months. It's kind of astounding to me how poor results in advanced cancer continue to be. That's the summary. Just one more thing I want to say is that this is why we started the Canadian and US study of integrative oncology outcomes. This is 12 clinics all over Canada and the United States that are doing what we call advanced naturopathic oncology, and we're tracking survival and treatment data from 400 people. That probably will be published, it will probably be at 2 years before that study is published. Kaczor: Are there any intermediate points where you've looked at that data? Do we have any idea of what's gong on with that study? Standish: Which study do you mean? CUSIOS? Kaczor: Yeah, that last one you just mentioned, which I think you called- Standish: Yeah, we called CUSIOS, so Canadian US Integrative Oncology Study. What we know is that we've been able to recruit. We're about 85% done recruiting the 400 patients. We have a good diversity of the patients that we recruited for, which was stage 4 breast cancer, stage 4 colorectal cancer, and stage 3 and 4 pancreatic cancer, and stage 3 and 4 ovarian cancer. We wanted to narrow our study to those 4 conditions. We're recruiting. We're able to collect death data, and the most exciting and problematic thing is what do you compare our naturopathic oncology survival data to? Here I've just talked about a breast cancer study, 53 women, their median overall survival is 47, but what does that mean? Compared to what? Right now there is a tremendous amount of intellectual work going on at Bastyr University and also at Canadian College to figure out what the best statistical method is, and fortunately we've been able to collaborate with some very sophisticated big data scientist with statistical ability that have access to this marvelous database in Canada. We will be able to use the SEER database too, and what we're doing is trying to figure out how to match naturopathic oncology cancer patients to patients that are just like them in these registries and then watch them over time with the hard endpoint of date of death. We're also of course very interested in quality of life. We're also interested of course in what therapies each patient got, not only what they were recommended, but also what therapies they received. For example we're tracking Dr Gurdev Parmar's clinic where they're doing locoregional hypothermia. Another clinic is using mistletoe therapy intensively. Another clinic, such as ours at the Ames Institute in Seattle, we're focusing now on the utilization of what's being called metabolic therapy, which is the idea of the cliché is starving cancer using FDA off label drugs that is all the rage these days, very interesting approach. We're using intravenous vitamin C along with chemotherapy. We've sort of abandoned the idea that as a monotherapy it does much. We're starting to explore the safe use of quercetin as a botanical medicine that really needs to be given intravenously to be bioavailable. But I think the most important thing we're doing is taking seriously the idea that trauma, childhood trauma in particular, is a risk factor for development of cancer. And I'm referring of course to the famous ACEs study, Adverse Childhood Events study, that linked in a dose-dependent way the number of adverse childhood events like neglect, foster child, abandonment by parents, alcoholism, violence, etc., war, that the number of these events is correlated with the risk of cancer later in life. And so we at Ames Institute are saying well okay, if that is an important causal feature of why we get cancer, then let's get to that. We're using now psychedelic assisted psychotherapy to be able to do the deep work that is required to help people heal from posttraumatic stress disorder, which not only can come from childhood, but just the very experience of having cancer, being diagnosed with cancer, going through cancer treatment produces posttraumatic stress disorder. What we're hoping is all these therapies combined are going to improve the median overall survival of our patients. That's what we're doing here in my clinic. Kaczor: Tell me a little bit more about this. Is this low-dose psychedelics? I think we're talking about it here in Oregon from a state level. I think there's going to be actually some kind of referendum vote to see if we can legalize such things here, so I'm curious about this. Standish: Yes. The initiative that will be happening in Oregon in 2020 is about permitting psychotherapists, certified licensed and fully trained psychotherapists, to utilize psilocybin in the treatment of posttraumatic stress disorder and also in end-of-life care. That's very exciting. But in the meantime, right now there are no legal psychedelic drugs available for physicians with 1 exception, and that is ketamine. Ketamine is a drug that comes from anesthesia. It's been very well studied as both an anesthetic, but in low doses, it produces a state of consciousness that some people would describe as psychedelic with a dissolution of the sense of self, a connection with higher realities, a connection with one's ancestry, an ability to do deep work in the presence of a physician and a nurse who are overseeing the treatment. What we've found is a 3-hour ketamine session that's led and facilitated in an excellent way can help enormously relieving the depression and the anxiety that is part of all of our lives, but especially if you've been diagnosed with cancer, and especially if you have the kind of trauma in your childhood that is a risk factor for cancer. Kaczor: Is there already clinical data on the use of this? Standish: On what? I'm sorry, clinical data on what? Kaczor: On ketamine or psychedelics being used in this fashion. Standish: No. What there is, this is translational science, and the reason I love naturopathic oncology is that we are people who take science and translate it into other domains of medicine. We know without a doubt now that the state of consciousness, emotional states and brain states associated with those emotional states, have direct effect on the autonomic nervous system, which has direct effects through a cascade of physiology and biochemistry that affects the behavior of cells in the tumor bed. And there's tons of work on that. Is there work on the use of psychedelics for healing cancer? No, but it will be coming, and I hope that we can show some leadership in that area here in Seattle because I think it's an extremely important area. The reason psychedelics might be important too is that most of them have very strong serotonergic effects. What we've found in immunology is that the kinds of cells that are involved in the immunological response to cancer, T-cells in particular, are loaded with serotonin receptors. It is not a far stretch to imagine that one of our future immunotherapies will be psychedelics, and there's now kind of a rage around doing low dose psychedelics, all of which are considered by the drug enforcement agency to be controlled substances, but there's huge interest in this field. Most of us have probably seen Michael Pollan's new book How to Change Your Mind. Kaczor: Yes, yeah. It's a fascinating read. It definitely had more data behind the use of it for emotional states than I had ever realized before reading that book. So let me ask you this because our listeners are often clinicians themselves. Sometimes they are the lay public. In any case, if people want to look further to see if they are appropriate to enter a study or they have patients that might be appropriate, because what I hear you saying is some of these tough-to-treat cancers, whether it's stage 4 disease or lung cancer in stages 3 and 4, they're tough to treat, and we all want to help our patients as best we can. So where would someone go to find you or one of the other 14 clinics involved in CUSIOS study? We'll put a link here with the podcast, but otherwise, where do we find you? Standish: Oh, okay. Yes, please to go the Bastyr University website, and look at the research, and then look for CUSIOS [https://bastyr.edu/research/studies/canadianus-integrative-oncology-study-cusios-advanced-integrative-oncology]. Everything is updated there. It's also listed on the national NIH clinical trials .gov site, and all the clinics are listed there [https://clinicaltrials.gov/ct2/show/NCT02494037]. Kaczor: That's great, and I think what we have is more of a full whole-systems research, outcomes-based research is what I hear you saying. All of these are taking into account large plants, not single agents, which is why we often have weak data when we use single agents in our medicine. Kudos for mastering the complexity of figuring out how to get this data going and inform us. Standish: Yeah, I think that one of our fundamental hypotheses is that natural medicines, those that are known and those that are not known yet, have a potential when they're used in the correct sequence and at the right time and in the right patient who has the right genetics and the right epigenetics at the time that you see them, that our therapies have a chance of really extending high quality life and making cancer into what we hoped for AIDS in the old days as a chronic manageable condition. I think that that day is coming, and we're certainly not there yet. That's for sure. Kaczor: Yeah, yeah. I'm excited because I think that we can track the data much better than we have been able to, so that's certainly helps our cause as well. I thank you for carving out some time in your day and speaking with us today and updating us on what's going on. It's all very exciting, and thank you for all of your ongoing work. Standish: Okay, thank you, Tina. Thanks, everybody. See you soon.

This podcast interview features integrative health expert Russell Jaffe, MD, PhD, CCN, who shares his philosophy about addressing men's health issues in clinical practice. Jaffe discusses hormonal balance, prostate health, gastrointestinal health, cardiovascular health, and inflammation. About the Expert Russell M. Jaffe, MD, PhD, is CEO and Chairman of PERQUE Integrative Health (PIH). He is considered one of the pioneers of integrative and regenerative medicine. Since inventing the world’s first single step amplified (ELISA) procedure in 1984, a process for measuring and monitoring all delayed allergies, Jaffe has continually sought new ways to help speed the transition from our current healthcare system’s symptom reactive model to a more functionally integrated, effective, and compassionate system. PIH is the outcome of years of Dr Jaffe’s scientific research. It brings to market 3 decades of rethinking safer, more effective, novel, and proprietary dietary supplements, supplement delivery systems, diagnostic testing, and validation studies. About the Sponsor PERQUE Integrative Health (PIH) is dedicated to speeding the transition from sickness care to healthful caring. Delivering novel, personalized health solutions, PIH gives physicians and their patients the tools needed to achieve sustained optimal wellness. Combining the best in functional, evidence-based testing with premium professional supplements and healthful lifestyle guides, PIH solutions deliver successful outcomes in even the toughest cases. If you are interested in delving more deeply into this and other integrative health topics, we invite you to join the PIH Academy. Transcript Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Thank you for joining me today. Our topic is men's health, and my guest is integrative health expert, Dr Russell Jaffe. Before we begin, I'd like to thank the sponsor of this topic, who is Perque Integrative Health. Dr Jaffe, thank you so much for joining me. Russell Jaffe, MD, PhD, CCN: Thanks for the invitation. Gazella: Well, before we dig into the specific health issues that men face, you believe in a philosophy first approach. I'm sorry, physiology first approach. What do you mean by- Jaffe: The philosophy is physiology. Gazella: Exactly. Jaffe: So, that was appropriate. Yeah- Gazella: So, what do you mean by that? Jaffe: Right. It's a high level, brief, 2 words, physiology first. What we mean is, physiology before pharmacology. We mean physiology first because it seeks an upstream assessment of the causes of risk or symptoms, in contrast to most conventional care today, even holistic or not, that remains rooted in downstream symptom management. Physiology first uses global evidence to reduce risks and prevent people from falling into the river of disease. Physiology first uses nature's nutrients in supplements, with enhanced uptake and chaperone delivery, for safer, more effective, essential replenishments, items we must take in since our body doesn't make them. Physiology first urges organic or biodynamic or locally grown sources of nutrient-dense whole foods, as minimally contaminated as possible. Physiology first focuses on underlying causes. For example, too little of essential needs being met, which are eating, drinking, thinking, doing—those are the 4 headline categories—rather than working back from symptom-reactive case management. And finally, physiology first uses predictive biomarkers interpreted to their best outcome goal values. Now, this is a paradigm shift for many colleagues but we now can impersonalize predicted, proactive, primary prevention practices, save individuals probably a million a year just by applying physiology first. Gazella: Yeah. Well, that's exciting so I'm glad that we went over that. Now in general, what should be on the radar of clinicians when it comes to addressing the special health needs of their male patients? Jaffe: Yes, and here again, now that we've kind of gotten the hundred thousand–foot level, we start and recommend colleagues start with self assessment. This includes transit time, urine pH after rest, hydration, and a sea-cleans as overall global self assessments, very inexpensive. The individual does much of it themselves, brings it to the expert who interprets it so that we get a snapshot of the metabolic or metabolon/microbiome, the digestion and metabolism. You interpret that to best outcome goal values. You use that to inform and inspire and motivate people to put it in effort for the 6 to 7 weeks that it takes to change a habit of daily living and you can add years to life, years of quality life and life to years. In people with chronic symptoms, well. Take a careful family history although family history is highly relevant if you have the same behavior and environmental factors. If you change your behavior, your habits, your environment, then your family history to a very large extent disappears into the midst of history. If there have been prior treatments and treatment failures, it's important to assess that. We use the predictive biomarkers to help people celebrate when they are at their best outcome goal value and take action when their risks increase. Now, men and women at all ages need activity, at least 45 minutes a day of walking or equivalent. Sitting is the new smoking. Weight-bearing exercise or cardio exercise 2 or 3 days a week and knowing about it or preaching about it is one thing. It's when you actually do it. I'm glad to tell you that I had just enough glimpse of the consequences of not doing that I do what I'm recommending. Now we want to teach men to prepare for sleep, achieve restorative sleep, using physiology before pharmacology, using salt and soda baths, Epsom salts and baking soda, plus or minus aroma oil, essential oil. The baking soda alkalinizes and relaxes muscles in the pores of the skin, and the Epsom salts, which is magnesium sulfate, allows the magnesium to come in and that's often very helpful. We recommend that teaching people, particularly men who have sleep issues, about abdominal breathing and active meditation and green dichromatic light, along with nature's sources of serotonin and melatonin, which is tryptophan. We ask about changes in urine stream flow and quality after urination. Is there any dribbling? How many times do they get up at night to urinate? And we make lifestyle suggestions tailored to the individual at their phase of life. We want to be proactive with prostate support nutrients, such as micellized soft gel that contains all of active saw palmetto, [inaudible 00:06:03], lycopene. Free lycopene, not just some ketchup. Hygeium, with 14 or 15% beta sitosterols. Urtica dioica, also known as stinging nettles. Zinc, in the picolinate form. And selenomethionine, selenium in the selenomethionine, healthier, safer form. And all of this micellized in pure pumpkin seed oil to enhance uptake in retention, to improve function. And we think people can be pleasantly surprised at how effective and synergistic the above prostate health support is, available in a single, easy-to-swallow soft gel. Ask about adult beverages. If they consume more than 5 a week, provide comprehensive liver support and recommend a glass of water above the four quarts or four liters a day that humans need to avoid marginal dehydration—1 or 2 or 3 percent dehydrated is a big stress on every organ in your body. So this is, again, at a headline level, how our comprehensive approach actually works. Gazella: Perfect. Now I'd like to kind of narrow our conversation and I want to stay on the prostate because you mentioned the prostate. So, what are the roles that testosterone plays when it comes to prostate health and men's health in general? Jaffe: Right. Both men and women need testosterone. They need a balance of free and bound testosterone. They need good and not bad testosterone. Now, what does that mean? Well, you can measure in saliva or in plasma. The free and the bound, free and total testosterone. You can measure the dihydrotestosterone. You don't want much of that, maybe zero. You can measure oxidized testosterone. You want zero of that. And you want to enhance the good T, the good testosterone and reduce the bad T based on testing results because testosterone is needed for brain and muscle and organ and joint and bowel renewal and many other functions beyond just being a male hormone. You want to enhance healthy testosterone production through healthy microbiome and metabolon functions, especially the family of the central antioxidants. Vitamins, minerals, and cofactors that along with good hydration optimize your healthy testosterone, which is one of the vitality factors in the body and minimize the bad testosterone that causes everything from hair loss to loss of erections. Gazella: Okay, perfect. So before we leave the prostate, remind us what the significance is of the PSA test. Jaffe: That's a very important question and I think we're finally, after half a century in laboratory medicine and I've been following the issue all of that time. The PSA test is a measure of prostate repair. So, the PSA goes up if you have prostatitis. For example, if you just sit in your car too long and hold your urine in too long. And the PSA goes up in some but not all prostate cancers, and you can fractionate the PSA, free and bound, and that usually but not always helps distinguish the prostatitis from the cancer risk. If you had concern about the prostate and about PSA levels and have a biopsy, after a single biopsy—often there are multiple biopsies—the future PSA has no interpretable value that I know of except for population, but we're talking about 1 man at a time. And so many review articles that I have seen in the last few years say do other tests of prostate health and don't even do the PSA because if you don't need the test, you wouldn't do the test. If it's a question, it's a gray zone, that's exactly what the test is not very sensitive or specific. Gazella: What about enlarged prostate? Jaffe: The first thing I would do and have recommended for many years for enlarged prostate is to take that combination of prostate vitality factors and we have had men whose prostate was double or triple than usual size come back to that of a 40-year-old by following for about 6 months a program that includes the supplements that I recommended just a few minutes ago, along with eating foods that the man can digest, assimilate, and eliminate without immune burden, and that means the lymphocyte response assay test that measures T and B cell function and that then says eat this and don't eat that, take the supplement and don't take that, follow this mental and physical plan because in the 80,000 cases that we put in our database, we've evolved a very personalized approach to, say, prostate size. Gazella: Okay, perfect. So, let's move on. What does it mean when a man wakes up with an erection or doesn't have an erection? Is that significant? Jaffe: Oh, absolutely. The headline is that every healthy man should wake up in the morning with an erection. In essence, it's the quality control check of the distinctive male. Too often and very commonly, when a man does not wake up with an erection, that's a sign that they have pregnenolone steal, that they have high stress cortisol levels and low DHEA, which is the antistress hormone, usually with low free healthy testosterone, often with a sluggish thyroid and an exhausted adrenal gland, due to lack of adequate intake of the essential antioxidants, minerals, cofactors that are necessary. In addition to prostate health nutrients, I would recommend checking the thyroid, TSH, 3T3, 3T4. That can be done on a blood spot or in many different ways. But you must, by my recommendation, get the 3T3, 3T4, TSH all at the same time, and the healthy range for TSH is .5 to 2.5, not above. The usual range has too many unwell people. (Usual lab range.) You want to check adrenal stress hormones, cortisol and DHEA at four times during one day. And at the same time, in the same saliva or plasma specimen, you can measure male and female hormones and their sources, their precursors to see if the body has learned a distress response that steals the healthy progesterone and pregnenolone and produces too much distress hormone cortisol and too little healthy male and female hormones. They come from the same source. You want to get both and in balance. Now in regard to male sexual performance, there are natural solutions to erectile dysfunction. The following vitamins, minerals, and amino acids work as a team to improve the quality and duration of erections B complex. One phrase is 'B complex is for boners'. Keep the urine sunshine yellow and feel the difference comprehensive B complex means. C, it is ascorbate vitamin C, always fully buffered, fully reduced and we recommend based on the C cleanse, taking that amount is associated with healthier and the more robust erections. Vitamin D is really a neuro hormone and it does a lot of things, including improving cell function and providing cell energy to sustain the generally sixfold increase in blood retention during an erection. Then magnesium choline citrate. Magnesium is essential for a lot of different things, including a healthy sexual function, and choline citrate at the same time, say 220 mg of magnesium solves and a teaspoon of choline citrate. That enhances the uptake dramatically. It enhances the retention because it is an alkalinizing, rather than an acidifying source. Most magnesium solves and magnesium products have very low bioavailability and are in the acid form, which makes the magnesium run out almost as soon as it comes in. And then last is L-citrulline and L-arginine, and these are 2 amino acids. They both enhance nitric oxide production inside cells, and when you take about a gram of L-citrulline and 500 mg of L-arginine 30 minutes before adult activities, most men notice the difference, especially men over 40. Foods that are rich in these amino acids include nuts, seeds, chickpeas, and other legumes, also known as garbanzos, and meats. Making an avocado and chickpea hummus with some mustard seeds or black and white sesame seeds added plus or minus some toasted pine nuts with fresh ground black peppers and your favored high-quality salt, that can blend into a nutritious, delicious, amorous and traditional food. Gazella: That's great and it sounds yummy as well. Jaffe: It is. It should be nutritious and delicious. Gazella: Exactly, exactly. Well, let's now move onto the gastrointestinal tract. What should practitioners focus here when it comes to their male patients? Jaffe: Well, in the 21st century it is a pretty fair assumption that the person sitting across a professional has mild digestion dysbiosis, some degree of atrophy known as enteropathy, a long transit time. Transit time should be 12 to 18 hours. We recommend doing that with charcoal. We have an online instruction if folks are interested because you want to assess what's called the microbiome, which is the digestive tract in its fullness, or the GNS, known as the gut nervous system, which is in constant conversation and communion with the reigning central nervous system. And so we recommend focusing on a full complement of personalized native antioxidant, minerals, and cofactors in their safer higher uptake forms based on the assessments and the predictive biomarker tests that we recommend. We want to pay attention to hydration because even a little bit 1, 2, 3% dehydrated puts a stress on every part of the body. We want to have prebiotics. That is unprocessed fiber from diet or supplements, 40 to 100 grams a day. That's what Dennis Burkitt taught me and the most knowledgeable nutritionists that I know recommend that much fiber a day. Probiotics, 40 to 100 billion healthy by a mixed bacteria, bugs. Then synbiotics, which is really recycled glutamine to energize and repair the lining of the digestive tract. Then you want to eat what you can digest, assimilate, and eliminate without immune burden. So, you've done some functional immunology testing like LRA, lymphocyte response assay. Take in no empty calories. You are sweet enough as you are. If you feed parasites and pathogens, fungi and yeast, they will grow. Improve the digestion, the microbiome and metabolon, the innate biological detoxification competencies and enhance your digestion by eating what you can digest, assimilate, and eliminate without activating your immune responses. We teach people to stop feeding the pathogens and they disappear as digestion improves, repairs improve, resilience is restored, and habits of daily living are improved. Then you want to look at the secretory IgA if you're concerned about the interface between digestion and the body. It's called SIgA, secretory IgA. You can measure that in saliva. There should be protected mucins so that if partially digestive materials get near the wall of the body, they don't become foreign invaders if you have healthy mucins and healthy secretory IgA. And there are other elected protected digestive functions that healthy people have that are lost when people lack the essential nutrients or the essential minerals when their cellular metabolism becomes acidic, when their body is reaching out, calling out, actually crying out for repair enhancement essentials, things you have to take in that you can't make in the body. So, we wanna taper or possibly discontinue medications that impair digestion. We want to use prebiotics, probiotics, and synbiotics, especially in people who have had antibiotics and other digestive-interfering medicines. We want to check transit time, should be 12 to 18 hours. When I have roast beets as a main part of my dinner, I expect to see red in the commode in the morning. But I can tell you after all these years when I see that red, my first thought is never, "Oh, I had beets last night" so that's why we use charcoal. Now, avoid fat-binding medications and supplements that reduce essential fat-soluble vitamin uptake. That's vitamins A, D, E and K. And you need bile from the liver to do that and for that you need phosphatidylcholine-rich foods and/or supplements, and we happen to micellize all of our soft gels with this PC, with this—not politically correct—phosphatidylcholine. Now, many men have atrophy of their intestinal lining because of stress and toxin exposure and it's the 21st century, and maybe less than perfect eating, breathing, and drinking. So, getting the essential needed nutrients restored may mean intensive supplementation for a few months, followed by maintenance supplementation for a long, healthy life, and I personally plan to be dancing at 120 and I would like you to join me. Gazella: That sounds perfect. So, you mentioned tests to assess the microbiome and you also mentioned secretory IgA. Are there other tests that you recommend in terms of assessing the microbiome? Jaffe: Right. So, the transit time we talked about, it's one of the self-assessments, 1 of the 4. Then this SIgA, the secretory IgA, in saliva or serum, with the comprehensive lymphocyte response assay, if there's any indication that the person has shifted from elected protected mode into survival mode, which means all the protective and repair functions are down regulated, that's called chronic illness to happen, or hormone tests that include cortisol and DHEA at 4 different time points, male and female hormones can be measured in their precursors on the same saliva specimen. You can use plasma if you wish. Adrenal and thyroid adaptogenic supplementation is recommended either based on clinical history or these test results. By all means include some way of determining how much ascorbate that person needs because ascorbate is the maternal antioxidant that sacrifices yourself that all others may be presode. And then the magnesium with enhanced uptake choline citrate. The choline helps build acetylcholine, an important neurotransmitter and neurochemical. It also helps build the choline-rich biosalts that are more soluble and help get the thicker bile out of the gallbladder and into the digestive tract, where that helps emulsify fat to be taken up into the body. And then based on the urine pH, we would adjust how many doses of the magnesium choline citrate you take. Do a regular hydration assessment and when in doubt, what I recommend is that you have a carafe of water in front of you and a glass. If the glass is full you drink it and if it's empty you fill it, and you just keep doing that. And personally my goal is to go to the bathroom at least every couple of hours and then I cut down the amount of liquid I take in after 7 or 8 PM so then I'm not overhydrated when I go to bed. But underhydration is a much more common and unappreciated problem. Monitor the breadth of our little chemicals, and this can give very interesting insights that are both diagnosis-specific of mild digestion dysbiosis enteropathies and so forth. But in addition that information often makes it very clear to the individual that this is true for them and not in general. And the last is a zinc taste test. Developed by Harry Henken, you drop a zinc solution on the tongue. The people who need zinc can't taste it. The people who say the zinc tastes strong have enough. And it's a pretty good one-dollar type assessment of a critical mineral and specifically for men, men need lots of minerals but especially zinc. You lose about 25 mg per every ejaculation. Gazella: Yeah, that's good. That makes a lot of sense. So, now it's time to discuss inflammation. Is inflammation really repair deficit and how does that change clinical practice? Remind us why that's such a big deal. Jaffe: Right. Well, we started with the physiology-first concept. Now I'm a doubly board-certified pathologist. I know the 5 aspects of inflammation. I know it's taught as a fire to be fought, something that has to be suppressed with anti-inflammatories. And now I pause and say: Anything that starts with 'anti' is using pharmacology before physiology. Inflammation is repair deficit. What my pathology colleagues see as inflammation is the cumulative lack of repair when your immune defense and repair system is doing too much defensive work because of foreign invaders from the breath or the skin or the gut, and if you enhance the innate immune system's ability to repair, your infrastructure is reborn, your bones get rebuilt, your joints are renewed, your mood is better. Your ability to get restorative sleep and meaningful relationships all are improved when you recognize that repair deficit is an opportunity. You use the hsCRP test as a predictive and validated biomarker. It's also an all-cause mortality, morbidity marker. The healthy goal value—and this is, again, where we have the reframing. I don't even look at the lab range because that includes too many unwell people. You know the goal value for this test, hsCRP, and it's less than 0.5. Ignore statistical lab ranges unless you're treating statistics, and knowing the best outcome goal value we add ascorbate based on the [inaudible 26:350, magnesium choline citrate based on the urine pH, and other similar kinds of monitoring so that the person gets more safely the forms that are more effective because of their enhanced uptake and retention and therefore the deficits get corrected more quickly. I mentioned hydration. I keep mentioning it only because every part of your body is healthier and more resilient and more able to repair when you take in healthy water, 4 liters a day or more of either mineral-rich, I happen to have well water but some mineral-rich water that's not contaminated and/or sparkling water. I happen to like Pellegrino but there's also Gerolsteiner and Apollinaris and actually every culture has a mineral-rich water known as a therapeutic or beneficial or health-promoting mineral water. So, you want to drink hard water, so water softeners are not recommended, at least not total home water softeners. If you want to soften the water in the pipes, I don't care, but your blood vessels are not pipes and now I care about the quality of the water that you take in. Gazella: Perfect. So, I love your perspective about looking at repair deficit as an opportunity. Are there other ways to kind of take advantage of that opportunity to reduce oxidative stress and reign in inflammation? Jaffe: Yes. And again, in a physiology-first point-of-view in regard to, say, blood fats. Cholesterol and triglycerides and blood fats and [inaudible 00:28:14]. If you keep the oxidation of those fats, if you keep oxidized cholesterol to zero, if you keep oxidized LDL to zero, because you're taking enough antioxidants and especially ascorbate. Now, the fat-related cardiovascular risks just went away. What remains is understanding your hemoglobin A1C, your hsCRP, your homocysteine, your LRA (lymphocyte response assay immune responses), your vitamin D, your first morning urine pH, your omega-3 index, and [inaudible 00:28:51]. Those are the eight predictive biomarker tests and we have online for folks to peruse and/or download or watch on YouTube discussions of why these eight predictive biomarkers cover all of that genetics, which is 92% of your lifetime quality of life and health. And yes, you can blame mom and dad for the other 8%, and yes transgenerational influences on RNA are a big scientific field but not yet ready to measure clinically. Live in the moment, do one thing at a time, practice gratitude and random acts of kindness, breathe abdominally for at least 5 minutes a day, and make enhance repair your practice and banish inflammation. Gazella: That's perfect. It's a very integrative approach that includes lifestyle as well. I'd like to end with heart disease because heart disease remains the leading cause of death for men in the United States. So, what do you recommend when it comes to protecting heart health for male patients? Jaffe: Yes, and as I think you know part of my primary research when I was in government service at the National Institutes of Health Clinical Center was collaborating with the Heart Institute on animal models of heart disease. Now, Paul Dudley White in the 1930s was a famous cardiologist. He helped invent the electrocardiogram. He taught when I was a young student that in the 1930s at Mass General Hospital in Boston, Massachusetts if they had 1 heart attack a year, they published the case. And yet 40 years after that, cardiovascular disease was the major killer of Western civilization. That's not a genetic change. It's too quick for genetics. A lot has to do with smoking and sitting, sedentary lifestyle, processing of foods, and all that goes with that. Jaffe: So, cardiovascular disease. If your heart attacks you, if you have a clog in a blood vessel, an artery, if you have a stroke, you didn't pay attention to the upstream warnings that you would know about if you did the self-assessment, if you did the predictive biomarker tests because these change. Your risk goes up dramatically decades before catastrophe. And if you change your consumption and attitude, if you change the environmental toxin exposures and by the way 80% of the toxins that people have in their body are of recent exposure, and you can dramatically reduce that by certain simple lifestyle changes. Include 1 to 300 mg a day of micellized CoQ10 in 100% rice-brand oil, and no glycose. No antifreeze in your CoQ10. Keep the 8 predictive biomarkers at their best outcome goal value and when they are, when those 8 tests are at their best outcome goal value, you have a 99% chance of living 10+ years, even if you're 100 at that point, and my main teacher Buntey was 110 when he passed and as I mentioned before I plan to be dancing at 120 by following this lifestyle, and I urge anyone who is willing and interested to join me. Gazella: That's perfect. Well, Dr Jaffe, we covered a lot today. Before I let you go, I'm just wondering if there's any final thoughts or anything else that you'd like to share with our listeners today. Jaffe: Yes. In essence, the physiology-first, the epigenetics is 92% of your life quality has to do with consumption, which you eat and drink and how you think and what you do. Now whatever season of your life is as a man, that may be different. When you're young and immortal, that's one thing. As soon as you're beyond young and immortal, be prudent. Cardiovascular disease starts in teenage years. Cancer risks goes up dramatically when your innate anti-cancer mechanism is turned down because you're eating foods that are causing too much defense burden in your immune defense and repair system. So, just follow through on this physiology-first approach looking at your individual needs for personalized health promotion and put pay to chronic ill health. Gazella: Perfect. Well, once again I'd like to thank today's sponsor, Perque Integrative Health, and Dr Jaffe I'd like to thank you for taking the time and sharing so much information with us today. Jaffe: Well, thanks for inviting me and for making it such an enjoyable time. I hope the listeners will take away much that will be of value, and it's my pleasure. Gazella: Well, thank you and I hope you have a great day. Jaffe: You the same, Karolyn. Always a pleasure. Gazella: Yes, it is. Bye-bye.

During this interview Russell Jaffe, MD, PhD, CCN, will share his thoughts on how to safely and effectively enhance and protect bone health. Listeners will learn how acid-alkaline balance impacts bone health, as well as key nutrients that can help support bone density.  About the Expert Russell M. Jaffe, MD, PhD, is CEO and Chairman of PERQUE Integrative Health (PIH). He is considered one of the pioneers of integrative and regenerative medicine. Since inventing the world’s first single step amplified (ELISA) procedure in 1984, a process for measuring and monitoring all delayed allergies, Jaffe has continually sought new ways to help speed the transition from our current healthcare system’s symptom reactive model to a more functionally integrated, effective, and compassionate system. PIH is the outcome of years of Dr. Jaffe’s scientific research. It brings to market 3 decades of rethinking safer, more effective, novel, and proprietary dietary supplements, supplement delivery systems, diagnostic testing, and validation studies. About the Sponsor PERQUE Integrative Health (PIH) is dedicated to speeding the transition from sickness care to healthful caring. Delivering novel, personalized health solutions, PIH gives physicians and their patients the tools needed to achieve sustained optimal wellness. Combining the best in functional, evidence-based testing with premium professional supplements and healthful lifestyle guides, PIH solutions deliver successful outcomes in even the toughest cases. Transcript Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Thank you for joining me. Today, we're talking about bone health with pioneering integrative health expert, Dr. Russell Jaffe. Before we being, I'd like to thank the sponsor of this podcast who is Perk Integrative Health. Dr. Jaffe, thank you so much for joining me today. Russell M. Jaffe, MD, PhD: Thanks for the invitation. Gazella: Well you know when we think of our bones, we often think of osteoporosis. Let's start there. How common is osteoporosis in particular? Jaffe: Oh, far too common. Depending on how you make the measurements, somewhere between 50 and 100 million Americans are at risk. One in 4 women over the age of 40 will have a fracture of their bones due to the osteoporosis or osteopenia. Maybe 1 in 5 or 1 in 4 men, maybe more, the precision of diagnosis probably understates the issue. The point is that bones, whatever your birth date might be, your bones should be young. Bones turn over every 10 years, which means no part of any bone that you or I have is more than 10 years old. Remember when we were 10 years old, we could jump around, we could leap around. I don't recommend behaving like a 10-year-old. What I'm saying is, your bones should be resilient, and flexible, and not brittle, and not being leeched by the stress and dietary choices of modern living. Gazella: Yes. It's hard for me to even imagine a 10-year-old, but it would be fun to have bones like a 10-year-old, for sure. Now is the DEXA scan still the gold standard for measuring bone density? Jaffe: Yes. D-E-X-A, DEXA is the "gold standard" reference standard. There are other measures that are coming along. There's N-telopeptides which are a little hard to interpret. There are other measures, but to the best of my understanding, the expert experts in bone say that you can measure DEXA changes over 2years. My colleague, Susan Brown and I did an anecdotal prospective study with 11 people, 10 of whom had between 2% and 10% or 11% new bone growth, unprecedented new bone growth by following this approach to Alkaline Way bone health. Gazella: Yes. How often do you recommend that patients get a DEXA scan? Jaffe: Well, let me come at it 2 or 3 different ways. In regard to the usual and customary use of the DEXA scan, it's a 2-year waiting period. Now many doctors will do a DEXA after one year and try to compare, and interpolate, God bless. Other people will use other measures, including bone mineral protein and how much of that there is in say the urine. You asked the right question, which is what is does the measure that almost everyone agrees, or that about which there is reasonable agreement and consensus. The answer there, DEXA. Until something better is really validated and yes, new things come along all the time, but I'm seeing a lot of them go 'cause as you know, my PhD was in collagen and elastin cross-linking, and how you regulate that. That was half a century ago and learned a lot since then. But collagen has a lot to do with bone health and bone turnover. Then there's certain other unique characteristics contributed by the liver that allow the minerals, not just calcium, but all of the minerals that are necessary to align properly to form what we call a bone. Gazella: When it comes to bone health, what do you mean when you say physiology before pharmacology? Jaffe: Well I mean the fact that bone is piezoelectric, which means when you walk, when you move, actually stimulating tiny electrical flows that say to the bone rebuilding cells, the osteoblast and osteoclast, "Do your job." Moving is a good thing, at least 45 minutes a day of walking. Yes, sitting is the new smoking, but if you get up at least 5 minutes an hour, you can undo most of the adverse effects of cutting off your circulation when you sit in most chairs. Now if you happen to have one of these recliner chairs or something like that, more power to you, but you still have to get up out of the chair. Walk for at 45 minutes a day. [inaudible 00:05:24], to the extent that he had a doctor was me, and [inaudible 00:05:29] very active now, they both agree. Now walking is a terrific way of human beings stimulating bone growth because of this "piezoelectric" or tiny electrical flow that nurtures and nourishes the bone. That's an example of physiology before pharmacology. Gazella: A great example. When it comes to your integrative approach, I want to dig into certain aspects of how we can enhance or protect bone health. You often talk about the acid alkaline balance. How does acid alkaline balance impact bone health? Jaffe: Well in essence when your diet or your environment contributes acid, your bones melt slowly away and sometimes not so slowly. On the other hand, when you have a mineral rich environment that bathes the cells and renews the cell's mineral buffering abilities, now you build new bone. We want to build new bone. We don't want to melt the existing bone. Gazella: Right. That makes a lot of sense. Let's stay on this topic for a bit because I know that most of our listeners understand how to support the acid alkaline balance, but what are some of your foundational aspects when it comes to supporting proper acid alkaline balance? Jaffe: Well as you know, we start with the self-assessments. The assessment we want to start with measuring the pH, that means how much acid or how much mineral is in your urine after 6 or more hours of rest. It's the one time of day when you get a meaningful measure in a non-evasive way of the cellular mineral status, 'cause after 6 hours, the fluid in the bladder equilibrates with the lining cells, and lining cells, if they need magnesium then they put the extra acid into the urine. If it's below a pH value of 6.5, then you're too acid. You're deficient in minerals, particularly magnesium at the cellular level. You should take 2, 3, 4 more doses a day of magnesium, but enhanced uptake magnesium with choline citrate. It must be choline citrate, it cannot be choline bitartrate. Try to fool mother nature and she'll come back and slap you on the tush. You want to enhance the uptake and chaperone delivery of magnesium based on [inaudible 00:08:14] chemistry, and for your listeners who are technical, these are inverted [inaudible 00:08:20] droplets. I really am a biochemist. What that means is tiny little droplets that are taken up by [inaudible 00:08:28], that easily enhance the uptake. In recent studies near 100% comes in and then goes to the cells that are [inaudible 00:08:37]. Gazella: You know it seems like bone broth has been the rage for a while now. What are your thoughts on bone broth as a way to boost bone nutrition? Jaffe: Well I'm a big advocate for broth, but not bone broth. Why not bone broth? Bone broth turns out to be far too rich in glutamate, and why is it rich in glutamate? You wouldn't think there's much glutamate in bone, it's glycine, and proline, and something else. No. What the industry calls bone broth includes skin, it includes things that have no other commercial value that are left after you "render" the animal, or the chicken, or the whatever, [inaudible 00:09:27] bone. Bone broth, no. But meat broth, vegetable broth, fish broth, broth you make at home, or broth that's organic or biodynamic, yes, yes, yes. Broth is a very good source of minerals, and I mean vegetable broth, fish broth, meat broth if you want, but real meat made into a broth, which means you very slowly simmer it until it falls apart, and then you have more or less a broth, especially if you either whisk it or put it in a blender. Broth, yes. Bone broth, no. Gazella: Okay, good. That's a good distinguishing factor. Now we also hear about MSM and hyaluronic acid for bones and joints. I'm wondering what you think about these 2 ingredients when it comes to bone health. Jaffe: Well MSM is a sulfur source. Sulfur sources are very important in protecting and enhancing bone vitality and renewal. Now we recommend that physiology before pharmacology approach, which we use garlic, ginger, onions, brassica sprouts and eggs. G-G-O-B-E, garlic, ginger, onions, brassica sprouts. All sprouts are good, but broccoli sprouts, brassica sprouts especially, and eggs. Why not MSM? 'Cause it's pharmacology. It is water soluble DMSO. DMSO makes you smell like a fish. Not a very healthy fish or a decomposing fish actually. MSM is a supplement that's been around for 20 plus years. It has a certain [inaudible 00:11:04] that comes and goes, but it's pharmacology. We want to start the physiology, the G-G-O-B-E, garlic, ginger, onions, brassica sprouts and eggs. Then if a particular practitioner feels that additional MSM is helpful, I think they make the final decision along with their client. As you can hear from my comments, we want to use nature's pharmacy, which means you generally have to cook the food the way it's traditionally done. If you just chop up an onion, the cell walls will prevent you from getting the good stuff. But if you sauteed the union until it's clear, now you have a nutritious and delicious detoxifying physiologically helpful bone joint and vitality enhancing material that you can make into any broth you want. However, you want to eat the foods you can digest, assimilate and eliminate without immune burden. If your body reacts to one or more of the G-G-O-B-E foods, then substitute with the other 4. Thomas Jefferson said they should be stables in the diet, not condiments. I'm a Jeffersonian democrat, which means I'm a grieving optimist. I believe that we should make these staples in our diet again. Gazella: Yeah, that makes a lot of sense. What about hyaluronic acid? Jaffe: I'm glad you asked that too. Hyaluronic acid is different. It is physiologic, so when you take ... I'm a pathologist, [inaudible 00:12:40] certified pathologist. When you look under a microscope at a joint, more than at bone, but at the joints you do see what are called water absorbing compression-friendly molecules, hyaluronic acid among them. Hyaluronic acid goes back to the early '80s, when a Canadian company thought that this was going to be the answer to joint erosion, to the kind of bone-on-bone pain that very commonly occurs to people who haven't walked enough, and have sat too much, or have been on planes too much, as I have been from time to time. Hyaluronic acid has a medical application. It's an injection. I think after you use nature's pharmacy, after you engage, when you eat and think, drink and do in a comprehensive and holistic way, that injections in hyaluronic acid in the right hands, in experienced hands, are an option. It does provide relief to some people for a period of time while other renewal should be engaged in. Gazella: Okay, that makes a lot of sense. Now let's dig into some of your other go-to nutrients for healthy brains. I'm sorry, health ... Jaffe: Bones. Gazella: Bones. Yeah. Jaffe: That applies to brains too. Gazella: Yeah, yeah. That's good. When it comes to bones, what are some of the nutrients that you like to recommend? Jaffe: Well in regard to the nutrients, there are over a dozen and a half. You can divide these into vitamins, minerals and co-factors. It's mostly about a family or a symphony of minerals. Remember a symphony has many different instruments, each of whom plays a slightly different tune. We recommend, in addition to vitamin K1 and K2, in addition to vitamin D3, we recommend biotin necessary for healthy bone. We recommend half a dozen forms of calcium, half a dozen forms of magnesium. Specialized bio available forms, low contaminant forms of zinc and magnesium, and chromium and selenium, methionine. Copper is the sebacate, iodine and iodide, you need both. Boron, acid citrate, vanadium, which balances out blood sugar and chromium. Silica, but from horsetail. Stable strontium is the gluconate, and fiber, croscarmellose fiber to enhance the easing digestibility making it food-like. Those are the over 18, 19, 20 essential bone building nutrients. Now vitamin D should be the D3. There should be some vitamin C to keep everything reduced and happy. Gazella: 'Cause this does seem like a big list. These all work synergistically? Jaffe: And they're all essential. If you lack any one, your bones won't renew properly. It's amazing how many co-factors, how many minerals and necessary nutrients that allow for bone health. But Dr. Susan Brown and I published an article a decade ago, we're working on an update now, which basically says the more tonic, or soda, or acid beverage you consume, the more quickly your bones will dissolve, the more quickly your bones will melt away. Then on the other hand, when you have a healthy traditional diet, rich in minerals, the Alkaline Way, the joy of living the Alkaline Way, documented by morning urine pH, keeping it in the 6 ½ to 7 ½ range, that's green rather than sandy color which is acid, or blue which is too alkaline, you want to keep it in the green zone. It's Goldilocks scenario. Not too much, not too little. Just right is just right. Gazella: Now before I move on, I want to talk about this combination of vitamins, minerals and co-factors. Are these in one product? What will be ... Jaffe: Oh, yes. This is what Dr. Brown and I used in our prospective study. When I say gaining 2% to 11% new bone, by DEXA in just 2 years, I'm saying people taking this formula and also following a healthy lifestyle of foods they can digest, assimilate and eliminate. Gazella: Okay, great. What's the name of this product and what's the recommended dosage of this product? Jaffe: Well the recommended dosage is 4 tabsules a day to build, 2 tabsules a day to maintain, 6 tabsules a day if you have osteopenia or osteoporosis. Gazella: Okay, so 4 per day, 2 per day. Then, I'm sorry, that was 6 per day if there is osteoporosis or osteopenia? Dr. Jaffe? Jaffe: Oh, I'm back. Sorry. Gazella: Okay, perfect. The dose for osteoporosis or osteopenia is 6 per day. Jaffe: Yes, that would be 6 per day. What I would say would be 3 in the morning, 3 in the evening, so a twice a day dose of 3 tabsules, these are fully active, fully available, and they contain all of these different nutrients, each one of which is necessary, and together they form a symphony or a bone building team. Gazella: Okay, perfect. Great. Now I want to switch gears a little bit. What's your view of bone morphogenic proteins and the long-term effect on bone status? Jaffe: Well you're absolutely up to the minute. Bone morphogenic protein is being studied as we speak. It's promising, but we really don't, in my opinion yet, have enough information. What we know is it's built upon something called 2-Beta Coxatene, for those of you who are technical. This is bone mineral protein precursor. Dr. Brown and I are, at this moment in time, encouraged by what we have heard about this. She and I are collecting information as we speak, and stay tuned for bone [inaudible 00:19:21], as they say. Gazella: If we were going to look into the future when it comes to integrative health and bone support, bone building, is this where we're headed with the morphogenic proteins? Is this an exciting area? Jaffe: Well yes, definitely an exciting area. The question is, how much do you need for each person because, as you can imagine, given that you started with a really healthy organic or biodynamic bone, and then you somehow got out of it, this magic complex, how much do you need, and how much does it cost, and how long will it take before you really confirm what is asserted by some clinicians based on their observations? The observations are encouraging, but stay tuned for the bulletin. Gazella: Okay. Perfect. Now I want to dig into diet and lifestyle. I want to circle back with your G-G-O-B-E, the garlic, ginger, onions, brassica vegetables and eggs. Explain it again or in more detail as to why these 5 dietary items are foundational for you. Jaffe: Right. They're foundational because in traditional societies they are sulfur rich. You can think of sulfur as a fire that burns away bad stuff and toxins. That's a metaphor, but biochemically it's not far from the case. For those of you who are technical, they form thioethers. This makes compounds that would otherwise be free radical generating harmful compounds more water soluble and less harmful, so once they're complex, what these sulfur rich foods, or the sulfur in the foods, then they can be treated in urine, sweat and stool more safely and effectively, and it's been used for millennia in traditional societies. We just have rediscovered it in recent times. Gazella: Perfect. Well I want to stay a little bit with eggs because I've done a lot of writing about eggs, and I had the belief that eggs have gotten a bad rap. I personally eat eggs almost every morning. Explain to us about why eggs got the bad rap, and why eggs are actually good for us. Just remind us of that. Jaffe: Yes, eggs got a bad rap because Levy and Fredrickson had the idea of the diet-heart hypothesis that the amount of fat or cholesterol you ate was determinative or it actually determined how much blood fat you have. Now it turned out to not be the case, but Levy ran the Heart Institute and Fredrickson ran the NIH. They had the dominant ... in their time. At that time, there was a man named Olson, and he pointed out that eggs are the perfect food when you combined the white and the yolk, when you make a gently coddled or gently cooked egg you have a near perfect food in regard to easy to digest, assimilate and eliminate for people that have healthy digestion. Now implied in what you said, I think, is getting a healthy egg. My preference today are goose and duck eggs, or quail eggs because they haven't been messed with very much. If you put in front of me a biodynamic chicken egg, or a home harvested fresh egg, I'll be delighted. Commercial eggs I'm not so sure of. I'm concerned about what the chicken ate the got into the egg and that's what she wrote, as they say. Gazella: I would have that same feeling as well. Let's talk a little bit about what we should not eat if we're trying to protect and enhance bone health. What do you tell your patients not to do from a dietary standpoint? Jaffe: Well as you know, I don't have a private practice. I get to influence other doctors and their probable cases, but what I do recommend is stay alkaline. Stay alkaline means eat foods that are mineral rich, eat foods that are antioxidant rich, eat foods that are nutrient dense and rich, and you are sweet enough as you are, do not add sugar to your diet, do not use edible oils. I think edible oils is an oxymoron. What I mean by that is you avoid packaged goods, shipped foods, crisp foods, extruded foods, things that have been processed because processed means you lost the good stuff and you gained the bad stuff. Do a makeover in your kitchen, eat the foods that are whole, eat more fruits and vegetables that are vying ripe. If you want to have healthy fat in your diet, have an avocado, a whole one. Once you separate the oil from the seed, you know, like the olive oil, once you separate the oil from the seed the protective material is now gone and what you have are dense calories. Fat are dense calories, but those fats, those edible oils are easily oxidized, damaged and rancid. Then they get masking agents to make sure that your tongue and your brain get addicted to wanting those rancid processed fats. I don't think that's a good idea. I can tell you lots of reasons why [inaudible 00:25:15], who taught me about this in the early '80s, late '70, [inaudible 00:25:19], why Patty Deuster is so correct about these issues, but slowly we turned in regard to nutrition [inaudible 00:25:26]. Gazella: Let's talk a little bit about lifestyle factors. Now you mentioned movement and exercise in a scientific literature is so clear that that's protective of bone health. What about other lifestyle factors, like if we're looking at stress, or sleep, or just other things that we do? What do you tell your doctors to tell their patients? Jaffe: Well what I learned from [inaudible 00:25:52] and the Dalai Lama was that afflictive responses, that is the traumas of early life or the traumas of daily living that contribute stress hormones, afflict us, they erode us, they reduce new bone formation. By the way, no one gains from any of that. In the famous words of Bobby McFerrin, "Don't worry, be happy." I don't mean live by denial. What I mean is practice relaxation response. Know that your breath is a refuge and know that stress hormones only come out when you feel under attack. You may have heard about fight or flight, but there's also fortitude, there's also gaining the resilience to know that when you go to your breath, you can stay at ease even if everyone around you is hysterical. I can tell you from personal experience, in my family, if you didn't shout, no one paid any attention to you because everyone else was shouting. They just didn't know it. Gazella: Yeah, that's true. The relaxation ... Stress is a big deal. What about sleep? I know often times, sleep and stress go hand in hand, and one can lead to the other, and vice versa. What's your philosophy on sleep? Jaffe: Yes, my philosophy on sleep is that it's really important, restorative sleep, and how do I prepare for restorative sleep? Well I take a salt and soda bath. I put half to a cup of baking soda and Epsom salts in a warm tub of water, and get in for 20 minutes. First 5 minutes I breathe like a baby into my abdomen, the next 15 minutes I pray that my heart won't attack me, and whatever active mediation you want to do, then I get out and I dry off before I get into bed, and I stretch when I'm in bed before I fall asleep. Then I might even ask myself a question that I would like my dreams to answer if I'm inclined to do that. [inaudible 00:28:03] dreaming myself. In the morning I wake up and I stretch. I got to bed early enough that I get up early enough that I don't need an alarm clock. There is no screen, there is no clock, there's no unnatural sound. Occasionally I'm woken up by a wind chime or by a bird, but that's a nice thing to get woken up by. Then I stretch before I get out of bed, and then I get in the shower and I stretch when I'm in the shower, 'cause if you're not stretching a lot, you'll contract. Look at most old people, they slow down and contract. I am how you say old, but not that old, and I'm not yet contracted. Gazella: That's a good thing. Jaffe: That's a good thing. I'm working on it. Gazella: It's perfect. What would you like to be the most important bone health message that our listeners of health care professionals receive today? What's the most important thing that you want to get across? Jaffe: Most important is that bone health is a choice. It is about what you eat and drink, think and do. When you put it together in this proactive way, you have healthy bones for life. If you follow the "Conventions of modern living and pharmaceutical pill-based solutions," you end up slowing the loss but creating brittle, more fragile bones. In the famous words of Mel Brooks, the 2,000 Year Old Man, "Don't do that." Gazella: Right. Yeah, the physiology before pharmacology, I think, is such an important message. Well this has been very interesting, Dr. Jaffe. Once again, I would like to thank the sponsor of this topic, who is Perk Integrative Health. Dr. Jaffe, once again I'd like to thank you for joining me today. Jaffe: Pleasure to be with you as always. Gazella: Yes. Have a great day. Jaffe: You have the same.

Research is confirming that there is a direct link between the gut and the brain. In this interview, probiotics expert Ross Pelton, RPh, will describe the research associated with probiotics and brain health. The focus of the interview is on cognition and mental health issues such as depression and anxiety and how probiotics may help patients with brain issues. Approximate listen time is 31 minutes About the Expert Ross Pelton, RPh, CCN, is Essential Formula's director of science, in addition to being a practicing pharmacist, clinical nutritionist, and health educator in Southern Oregon. Pelton earned his bachelor of science in pharmacy from the University of Wisconsin. A certified clinical nutritionist, Pelton was named as 1 of the Top 50 Most Influential Pharmacists in the United States by American Druggist magazine for his work in natural medicine. Pelton teaches continuing education programs for healthcare professionals to use natural medicine and integrate it into their practices. He also has authored numerous books, including The Drug-Induced Nutrient Depletion Handbook, which is a gold-standard reference book for health practitioners. About the Sponsor Essential Formulas Incorporated (EFI) was established in 2000 as the sole US distributor of world-renowned microbiologist Dr. Iichiroh Ohhira’s award-winning probiotic dietary supplements and skin care products. Always an innovator, EFI introduced REG’ACTIV in 2015, containing ME-3, a probiotic catalyst that produces the “master’” oxidant glutathione inside the body's cells. A family-owned and operated business, EFI was founded on the philosophy of providing high-quality preventative, supportive, and comprehensive pro-health products for the entire family. EFI continues to flourish and grow through a strong company and product integrity and the knowledge that they’re providing scientifically proven products that positively impact the health and well-being of their customers. Transcript Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we're talking about the gut-brain axis and how probiotics can help with brain function, including mental health issues and cognition. Before we begin, I'd like to thank the sponsor of this topic who is Essential Formulas Incorporated. My guest is probiotics expert and registered pharmacists, Ross Pelton. Ross, thank you so much for joining me today. Ross Pelton: Hi, Karolyn is really nice to be with you and your audience again. Appreciate it very much. Gazella: Yeah, this is a really interesting subject. We've covered it a little bit in the Natural Medicine Journal, but I'm really anxious to kind of dig in a little bit more deeply with you. So let's just jump right in. How much do we know about the connection between what's going on in the gut and how that can influence the brain? Pelton: Well, we're starting to learn a lot more about it and I would say that we're still in the infancy of this learning curve, but we now understand why we call the gut your second brain. There's an enormous amount of neurons in your gut. There's over a hundred million neurons and your probiotic bacteria and the compounds they produce, interact with those neurons in your gut and send signals to your brain up what's called the vagus nerve, and so that's how the gut communicates with the brain, through this super highway of nerves called the vagus nerve. It's the longest nerve in the body. What's really interesting to me, Karolyn, is that they've figured out that about 20% of the vagus nerves are sending information from the brain into the stomach or the gut. But 80% of these nerve fibers in the vagus nerve are sending information from the stomach to the brain. So the majority of this information, this communication between the gut and the brain is really the gut communicating with the brain. Gazella: Wow. That's pretty cool. So let's talk a little bit about the scientific literature then. What does the scientific literature tell us about the link between the gut microbiome and mental health issues like depression and anxiety? Pelton: That's getting to be a big topic also and there's a tremendous amount of work being done in that area. In the cover, on the cover of the magazine Psychology Today, in April, 2014 their lead article was the psychobiotic revolution, how your gut bacteria control and influence your emotions and your state of mind. So a mainstream journal, Psychology Today, is referring to what they call a psychobiotic revolution. There's more and more studies that are starting to tease out how this happens. One study I found that was very interesting, mice who were infected with a very small of a toxic bacteria called campylobacter, but it was such a small dose, it did not cause any immune system activation. So the body really didn't know it was there. There was no immune alarm reaction. However, several tests revealed at the mice exhibited greater levels of depression and anxiety-like behavior. So the brain knows, even though the body wasn't responding with an immune reaction, the brain could tell that there was some bad bacteria, very small amount in the gut. In a human trial, it was chronic fatigue patients. It was a placebo controlled trial so some of the chronic fatigue patients were getting probiotics and some were getting a placebo and they did stool samples and they did a number of tests of depression and anxiety and the people taking probiotics were calmer, had less anxiety and claimed they were better able to cope, they got better sleep and they had fewer heart palpitations. So animal studies and human trials are also kind of combining to give us more and more information about this gut-brain communication. Gazella: Great. Now what about other brain issues like cognition and concentration? Does the gut-brain axis cover those issues in the scientific literature as well? Pelton: Well, it really does and it starts at birth and there's a real strong and important relationship between the early microbiome and child cognitive development. You find out that when children are born with a Cesarean birth, the mother has to give a C-section birth, then there's a difference in the microbiome. They've studied infants between C-section births and healthy natural vaginal births and they find out that the infants that are born via C-section for cognitive development through the ages of 4 through 9 is what this particular study looked at and they called it a cognitive gap. So it's just more information that's detailing that an infant's microbiome plays a real critical role in cognitive development. Now, we're learning more and more about the relationship between microbiome and psychology and neuroscience and normally you'd think that the fields of psychology and microbiology are not really connected, but now they're starting to be strongly connected because we're finding out how strongly microbiology and the influence of your bacteria communicate with your brain and affect your mental, emotional states. So gut health affects mental health is the stronger and stronger message that's coming out from the scientific community. Gazella: Yeah, it's really true. I have to tell you, there was an interesting study that I read while I trying to prepare for this interview and it was involving traumatic brain injury. Now, I understand that that connection is preliminary, but it's pretty promising to make the connection between traumatic brain injury and the gut. How can probiotics help someone who has experienced traumatic brain injury? Pelton: Well, there's several studies that have been done on this now. The gut-brain axis is a communication between the gut and the brain and it's the nervous system that does the communication, and when you upset the nervous system, you're going to upset the communication between the gut and the brain. So the gut microbiome has a central role in this pathway of humidification and it's really altered. They find out that the gut microbiome is significantly altered following a brain injury. It reads to more inflammation in the central nervous system and that affects the brain. You get brain inflammation. So that's 1 of the studies that talked about this traumatic brain injury microbiome relationship. In animal studies, it's not nice to talk about these studies because they do some nasty things to the animals, but that's the way we learn about a lot of these things. So they took some male rats and divided them into 2 groups. One group received a brain injury and the other didn't. But they looked at their microbiome before and after and they started a pre-traumatic brain injury incident and then they rechecked the microbiome in day 2, day 7, and day 14. They found that the mice that had received the traumatic brain injury, there was a definite significant change in the composition of their microbiome and it got worse as time went on. They started looking at the microbiome before the injury and then checked it at 2 hours after the injury and then 1 day, 3 days, and 7 days afterward. The change in the microbiome continued to worsen after that traumatic brain injury. So when we learn more about this, we see that the faster you can intervene, the more help that you can provide in this type of a situation. Gazella: So the scientific literature is clear that in cases of brain function, mental health, like depression, anxiety, and even in cases of traumatic brain injury, that the gut microbiome is altered. Does the scientific literature tell us that a probiotic intervention can reverse, change or influence the gut microbiome in such a way that the brain will be positively influenced? Pelton: Well, yes. That's what we're learning is that if you supply probiotics, you will change the gut and you change the electrical and chemical communication between the gut and the brain and you can influence the brain in positive ways. There's a number of researchers that are really documenting the changes in the brain from microbiome probiotic administration. There's a scientist by the name of [Christine Tillich 00:09:11] and she does brain imaging scans on people, these are human clinical trials. She had a group of women who had no previous gastrointestinal complaints and no previous psychiatric problems. She gave them probiotics twice a day for 2 weeks and she conducted functional MRI brain scan on these women and they were looking at the brain activity when the volunteers were viewing faces that contained different emotional expressions and they found changes in the brain regions that control the central processing of emotions and sensations. So this is a placebo controlled trial. Some of the women who were taking something but wasn't a probiotic and then the other women had probiotics and the women that had probiotics, they found positive changes in the brain areas that process emotions and sensations. So really interesting work that's being done. Gazella: Yeah. Very exciting to know that we have this intervention. Now, last year I read about a very small study that got some publicity and it was actually negative towards probiotics and it stated that probiotics can actually cause brain fog. I'm not sure if you had a chance to read that study or what's your take on this issue if it's come up in your pharmacy practice that probiotics can actually cause negative brain issues? Pelton: Well, I'm familiar with that study and my take on that is that this has to do with SIBO, small intestinal bacterial overgrowth. When people have SIBO, then yes, probiotics can cause a problem because SIBO is a situation were bacteria that are normally resident in the large intestine and the colon have translocated. They backed up into the lower portion of the small intestine. So it's not necessarily bad bacteria, but it's just bacteria that are now in the wrong geographical location in the GI track. Those bacteria can digest the fibers in food and cause gas and bloating and a great deal of discomfort. They produce a compound called D-lactate and that can produce brain fog. But the scientist that reported this, I think, really didn't report it correctly, or at least how I would like to report it because he's just saying that taking probiotics cause brain fog. Well, you have to understand that this is in SIBO and many people with SIBO should not be taking probiotics because the bacteria will digest the fibers and cause a great deal of gas and bloating and discomfort. So SIBO is a unique situation and needs to be dealt with separately. Gazella: Yes. Now, that makes a lot of sense. I'm glad that you clarified that. So when it comes to using probiotics in clinical practice for brain health, do you recommend probiotics as a sole treatment or as a part of a more comprehensive protocol? How can clinicians best use probiotics in clinical practice for this particular application? Pelton: Well, I'm always in favor of a more comprehensive approach to health, so I wouldn't advocate just probiotics. It's really important to understand how important a healthy diet is and exercise and good sleep. I also advocate a wide range of different types of nutritional supplements. But probiotics are 1 of the things I do recommend on a regular basis and it's kind of like insurance where you might not need it, but if you get in this situation where you need it, you're darn happy that you have it. I would say that there's certainly a range in how important probiotics are to people. Some people can maintain a microbiome when they're eating a healthy diet and they do pretty well long term and they might be less in need of probiotics on a regular basis. But I would say the majority of Americans, in fact, I've got 1 study that said that 90% of adults and children in America do not consume the recommended amount of fiber in their daily diets and fiber is what feeds your good bacteria. So if you're not getting adequate fiber in your diet, then you're not supporting the growth of your microbiome and your need probiotics. But I really emphasize the people, Karolyn, probiotics alone are not enough. You have to feed your probiotics well, otherwise they won't thrive and survive. So it's a combination of a fiber rich diet with lots of fruits and vegetables, especially the multicolored vegetables. That fiber will feed your microbiome and promote growth and proliferation of a more diverse microbiome. So it's probiotics plus fiber in the diet. Gazella: How do you counsel your patients about getting more fiber in the diet? Because I think you're right. I think that this is a big issue and the statistics are pretty clear that people aren't getting enough fiber and fiber and probiotics go hand in hand. How do you teach them to get more fiber in their diet? Pelton: Well, I encourage people to Google my YouTube video. It's an 8-minute youtube video, just Google Ross, R-O-S-S, and and salad buzz, B-U-Z-Z. It is an 8-minute video that I teach people how to save a lot of time making salads. One of my theories is that people don't eat salads often enough because they're time consuming. But I teach to process all the vegetables all at once and then the secret to the whole process is squeeze a lemon over all of your processed vegetables and toss that lemon and lemon juice in your vegetables and the vitamin C in the lemon juice will preserve your precut vegetables. So I put it in a Tupperware and it stores easily for a week and then every night when my wife and I have our big salad, I take a handful of lettuce and a handful of vegetables that I've already processed and put some wild caught salmon on there. It takes me like a minute to make supper. So it's a way to get a wide range of vegetables because I've got about 14 different types of vegetables in my salad mix and it saves time in the process. Gazella: Yeah, it's a great idea. I'm sure that practitioners may want to share that with their patients. So that's Ross salad buzz. Go ahead and search that. So now let's talk about probiotics. I mean, this is a field where there are a lot of different types of probiotic products. So what do you feel clinicians should look for when choosing a probiotic to recommend to their patients? Pelton: Well, that's a really broad topic, Karolyn, and there's a lot to talk about there. Turns out that humans have somewhere between 500 and a thousand different species of bacteria in their GI track and we're just beginning to learn what these are and there's a wide range between your microbiome and my microbiome. But generally you want to have a strain that has been prepared well in manufacturing so they good shelf life. That's a critical factor whether or not they need to be refrigerated. But 1 thing I'd like to talk about is what I call the new frontier in microbiome science. This is the term postbiotic metabolites. Now, some of your listeners might not be aware of this term, but it's really in 1 of the most important new understandings about probiotic bacteria and the microbiome. We're starting to learn that it's not so much the bacteria that are important, but it's the compounds they produce and we call these compounds postbiotic metabolites. So the process goes like this. You ingest fiber rich foods, your probiotic bacteria break down those fibers and produce secondary compounds that we call it postbiotic metabolites. These are the compounds that are the master health regulating compounds for the entire body. These postbiotic metabolites influence the functioning of every single organ system in the body, especially your immune system in your brain. I use the analogy of NASA's mission control center, controls our space flights. There's dozens and dozens of scientists and engineers but it's really the hundreds of computers making millions of decisions every second that guide and regulate our space flights. So in my analogy, your probiotic bacteria are kind of like the scientists and engineers, but it's your postbiotic metabolites that are really doing all the work, controlling and regulating all the signals that are having an effect on virtually every single organ system in your body. So that's the real important message and the new frontier and the microbiome, learning what bacteria produce these compounds, what strains of bacteria are more efficient at producing some of these compounds and as we get farther into this whole topic, science will start to tell us what types of fibers and what types of food will primarily or preferentially feed different types of bacteria. We know that diversity is important for a healthy microbiome and that means a wider range of different types of bacteria. The way to get a wider range of different types of bacteria is to consume a wider range of different types of fiber. So it's not just the quantity of fiber, it's also the the different diversity, different types of fiber is what's required to get a diverse microbiome. Gazella: Now give us some examples of the postbiotic metabolites that are produced that are so important to our health. Pelton: That's a big topic and I'm glad you've asked me because it's fascinating to me. Our probiotic bacteria are fascinating little chemical factories and so some of the postbiotic metabolites, all the B vitamins are produced by your probiotic bacteria. Several of the amino acids, they make a lot of the neurotransmitters and lactobacillus fermentum ME-3 produces glutathione. Some of the strains produce hydrogen peroxide, which is active against some of the things like Candida yeasts and short chain fatty acids are 1 of the big, most important categories that we know about. These short chain fatty acids are active against pathogens. They rebalance the acid base level. They have antiinflammatory activity. So that's why these postbiotic metabolites are so important because these are the compounds that have all the activity to regulate the microbiome ecosystem. So again, it's not just the bacteria, it's all these compounds that they produced. These compounds are produced during fermentation. The bacteria ferment foods to get access to the fibers and then they change these fibers into these secondary metabolites, the postbiotic metabolites. So fermentation is the process that creates the postbiotic metabolites. For years, and in fact for centuries, fermented foods have been a primary way that we preserved foods and it's the postbiotic metabolites, especially the short chain fatty acids that are produced during fermentation that create an acidic environment to suppress the growth of pathogens. So that's how fermentation works and that's an important part of your immune system because in your gut, the bacteria go through fermentation process and produce these short chain fatty acids that will suppress the growth of pathogens. Gazella: Yeah. When you're describing this, you're describing this combination of fiber plus bacteria. So you're actually describing more than a probiotic. You're describing more of a whole food extract or what's sometimes called a symbiotic. Is this where we're headed? It seems like there's not a lot of probiotic products that have fiber rich foods combined with the bacteria to create this whole food combination, which then creates the posts by attic metabolites. So it seems like this is unique. Pelton: Well, you're right. Although you will see some probiotic products that have a prebiotic in them, like fructo-oligosaccharides or FOS. I mean, some of them had things like inulin in them. But keep in mind, we want to strive for a diversity of fibers and so these products just have one type of fiber or 1 or 2 types of fiber. A product that I'm very familiar with because I'm the scientific director with Essential Formulas is called Dr. Ohhira's Probiotics. They're made in a fermentation process. It takes years to produce the product. They have large fermentation vats where they start out with 12 strains of bacteria then they had dozens of different types of organically grown foods and the bacteria are given 3 to 5 years to break down and ferment all of these foods, and during the process they're producing a wide range of postbiotic metabolites and scientific research has determined that Dr. Ohhira's Probiotics contain over 400 different postbiotic metabolites. So Dr. Ohhira's is really not primarily a probiotic. It's primarily delivering postbiotic metabolites directly and it's a much faster way of effecting change in the microbiome because if you just take probiotic bacteria, those bacteria, when they reached the gut have to find fibers and begin the process of breaking those fibers down and transforming them into the postbiotic metabolites. But Dr. Ohhira's is directly delivering these postbiotic metabolites so you get a really rapid microbiome restoration because they immediately, as soon as they hit the gut, they start to produce the antiinflammatory effects and accelerates the regrowth of healthy new cells that line the GI track. It's just a really unique fast way to create change and correct things like dysbiosis. Gazella: So you mentioned that there are dozens of forwards in the Dr. Ohhira's product that are fermented and combined with the 12 strains. What are some of the types of foods that are in that product? Pelton: They have a wide range of fruits and vegetables and mushrooms and seaweeds, all healthfully raised. They have different standards in Japan, so they're not what we would call organically grown by our standards because they just don't have those standards. But they're healthfully grown. They use pure spring water. There's no pesticides and insecticides and artificial fertilizer or anything, and they're allowed to grow naturally and then there are harvested at their peak of ripeness. So the nutritional content is at its peak and then they shred these foods and add them to the fermentation vats so that the bacteria can start to break them down and do the fermentation process that allows them to produce the postbiotic metabolites. Gazella: Now you mentioned that you don't have to refrigerate Dr. Ohhira's. I mean, as a consumer, I actually find that really appealing, but some practitioners are pretty focused on the refrigerated probiotic products. Why don't you have to refrigerate Dr. Ohhira's? Pelton: Well, Dr. Ohhira's, this fermentation process that I've spoken about, the bacteria learn to thrive and survive in the fermentation vats at room temperature. So they have adjusted to survive in a room temperature and then the capsule for Dr. Ohhira's Probiotics is a patented capsule design that's as hard in the harsh acidic environment in the stomach and then preferentially releases all the contents in the small intestines. So it's a user-friendly product where food is not an issue, it could be taken on an empty stomach or with food and refrigeration is also not an issue. Gazella: Then what's the dosage of the Dr. Ohhira's if you're just going with regular maintenance and there's not really a therapeutic application? You just want to recommend it to your patient for optimal health. Pelton: Sure. The recommended dose is 2 capsules daily on a ongoing regular basis. Gazella: Perfect. So I'd like to talk a little bit about the future because it sounds like what you've just described with this whole food extract and this fermentation process at room temperature and the paste that's created and it's put into this special gel cap that can survive the stomach. It sounds like that we're headed to the future. So bring out your crystal ball and tell us 2 things. First of all, what does the future hold when it comes to probiotic research and advancement and then what does the future hold when it comes to this gut-brain axis and where we're headed with that? Pelton: Okay. Well, I think that in the future we'll see more and more recognition of the benefits of these postbiotic metabolites. I think more companies will start to try to develop products so that they can directly deliver postbiotic metabolites. In fact, the pharmaceutical industry also sees the handwriting on the wall. I've looked at a number of different reports where pharmaceutical companies are starting to develop new products that contain postbiotic metabolites. The pharmaceutical industry realizes that rather than trying to develop more antibiotics, they can start to develop products that contain postbiotics and these new products will be less expensive to produce. They'll have fewer side effects because these are compounds that are naturally produced in the human body. So it's a new frontier for the pharmaceutical industry also. The postbiotic metabolites is a new frontier all the way around. Your other part of your question is how do I see the whole industry of probiotics going? We'll continue to discover new strains of bacteria, but I think there will be more emphasis focused on trying to discover what are the compounds, these postbiotic metabolites, the different strains of bacteria produce. So it's not so much trying to just discover different strains of bacteria and name them, but what are these compounds that they're producing and which strains of bacteria are more effective at producing these compounds for us. I think we'll also get into in the future much more personalized microbiome understanding so that different people will react differently or more favorably to different types of probiotic products and even different types of postbiotic metabolites will probably be more effective and more important for different types of individuals with different types of problems. Gazella: Yeah. I have to say that this does lend itself to that personalized medicine that practitioners and researchers are talking about. So I would agree. I think that's a great direction to go in. Now when it comes to the gut-brain axis, I know a lot of the research that we talked about today is a bit preliminary. Are you expecting to see some more formalized larger clinical trials, human trials, double-blind, randomized placebo-controlled trials in the area of mental health, potentially dementia, Alzheimer's, concentration, maybe chemo brain? I mean this is just such a big topic. Pelton: Well, yes, Karolyn. That's another huge frontier for the microbiome. Some studies are calling the microbiome the missing link in the gut-brain axis and they're starting to focus more on the microbiome's role in the link between gastrointestinal health and mental health. So we'll see a lot of that happening in the future. I can share 1 study with your listeners that's really quite amazing that talks to the mental health issue and the relationship between the microbiome and mental health. Scientists started out with 2 strains of mice. One strain of mice is specifically bred to be highly timid and anxious and the second strain of mice are bred to be highly courageous, bold, and exploratory. So then the researchers just took the bacteria from the GI track of each strain of mice and implanted them into the opposite strain. It completely reversed their behaviors, just by changing the bacteria and their microbiome, taking it from the bold, courageous exploratory mice and transplanting those gut bacteria into the strain that was timid and anxious. It just totally changed the behavior from being bold and exploratory to being timid and anxious and did the reverse in the opposite of mice. So fascinating information to see how just the gut bacteria have this direct influence on behavior and emotional activity and so forth. I'm sure we'll see many more studies in the future that are starting to unravel how this all works for us. Gazella: Yeah, I would agree. This is going to be fun to keep an eye on and to follow because it's really exciting and it can really make a difference in patients' lives. So once again, I'd like to thank the sponsor of this topic was Essential Formulas Incorporated, of course, the distributors of Dr. Ohhira's Probiotics. Thank you, Ross, for providing us with such a great amount of interesting information for us to consider. Have a great day. Pelton: Okay, Karolyn. Nice to be with your listeners. I want to just encourage everybody, every time you eat, you're feeding 100 trillion guests, so feed your probiotics well. Gazella: Absolutely. That's great ending advice. Thank you. Pelton: All right.

Statistics indicate that hearing loss is on the rise. In this interview, board certified otolaryngologist Dr. Ford D. Albritton IV describes the magnitude of the problem, as well as the research associated with key nutrients that can help reduce the risk of hearing loss. It's critical that all practitioners, not just hearing specialists, put this topic on their radar so they can help patients who already have hearing loss and those who are at risk.   About the Expert Ford D Albritton IV, MD, FACS, is the director of sinus surgery at the Sinus and Respiratory Disease Center at the Texas Institute for Surgery. He has served as chairman of the board of directors at the Texas Institute for Surgery and chairman of the Department of Otolaryngology-Head & Neck Surgery at the Texas Health Presbyterian Hospital of Dallas. Innovation and creative solutions to long standing problems in his field have been a focus of his practice since completing his training at the Emory University School of Medicine. He holds patents in the fields of nutritional compounds for targeting prevention of sensorineural hearing loss based on research initiated in the early 2000s. He also holds patents and expertise in the field of sinus disease and surgery with several publications to his credit. He remains active in clinical research and has been requested as a lecturer on the subject for surgeons domestically and internationally. Current interest exists in linking dietary methods of hearing preservation to cognitive function maintenance in patients with hearing disability, defining intervention strategy, and establishing modes of prevention. Transcript Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we have a fascinating topic. We'll be talking about how certain nutrients can help reduce the risk of developing hearing loss, and we have the perfect expert to help us with this topic. Dr. Ford Albritton, IV is a board certified otolaryngologist with the Sinus and Respiratory Disease Center at the Texas Institute. Dr. Albritton, thank you so much for joining me. Ford Albritton, IV: It's my pleasure, Karolyn. Thanks for having me. Gazella: Yeah. So, how common is hearing loss, and have we actually seen an increase over the past decade or so? Albritton: Hearing loss is incredibly common, and it's been pretty consistent if we look at the prevalence. The National Institutes of Health actually has its own group that looks at communication disorders, and they estimate the prevalence of about 15% of residents in the US having a diagnosis of hearing loss, and currently that puts us at about 38 to 40 million. And you asked the question has there been an increase, and it's sort of a tricky answer. Yes, there's been an increase, but so has the population increased. In 1971, that number was 13.2 million and basically one third the current number. So, why are we seeing such an increase? Well, it's a combination of population growth and the basic dynamics of our population age. If we look at aging as a criteria for hearing loss, we can compare people that are between the ages of 45 and 54. Only about 2% of those people are going to have a diagnosis of hearing loss, but if we go up to 75 years or older, almost one half to two thirds of the population will be having a hearing loss diagnosis depending on the studies you look at. And the World Health Organization has currently estimated hearing loss at about 466 million, but by 2050 they do predict that number should hit 900 million. So, there's certainly an increase, but it's tricky to say that that's because of something changing in the environment or our susceptibility is increasing, and their point of fact is a few years ago, pediatrics journals documented that adolescents were having an increased rate of hearing loss from comparing data between '94 and 2006. They reviewed that data again in 2010 and found that that was just simply a statistical error and that they had erroneously just compared two points of data instead of contiguous and that actually the rate of hearing loss has not increased in that age group. Gazella: Okay, that's interesting. So, what is considered a normal hearing range, and at what range does there begin to be a problem? Albritton: The way we measure hearing is using something called an audiogram or audiometry, and it measures sound intensity. The official measurement unit is called the decibel, which is a logarithmic measurement of sound intensity, and we define normal hearing as a threshold where a subject can recognize a presented tone at a specific frequency less than 20 decibels. So, if you're presented a tone at a low frequency or a high frequency and you can perceive it, recognize it at a sound energy level quieter or equal to 20 decibels, that's normal. Furthermore, we use some tricks of averaging and statistics to have some simple ways of measuring. Like we will average two tones or three tones or pitches on the hearing test and come up with a number of sound intensity, and we consider anything less than 20 normal, and anything above 25 we start to believe is abnormal and probably would benefit from some sort of intervention. Gazella: Okay, great. So, let's talk a little bit about risk factor. Who's at risk of developing hearing loss? Albritton: Probably a number one factor is family history. So, genetics play a larger role than we really can appreciate at this point in our mapping of the human genome, but family history is probably the most important question we ask patients into mapping their risk for hearing loss. The second one would be noise exposures, people with a high occupational noise exposure. OSHA measures that as greater than eight hours exposed at 90 decibels, so noise exposure at that rate can cause hearing loss. And then drugs; certain chemotherapy agents, some antibiotics are notorious for being toxic to the inner ear. Certain infections; one of the great benefits of immunizations and the reason we recommend immunizations is to prevent some of these preventable causes of hearing loss. Maternal infection of mumps, measles, rubella, for instance, can have devastating consequences on a fetal ear development and could have consequent hearing loss. And then finally, sort of our chronic illnesses, diabetes, hypertension, heart disease can compromise blood flow and health to the inner ear causing problems. Inflammatory conditions such as rheumatoid arthritis, certain inner ear inflammatory conditions can also cause problems. So, it's a pretty broad area of the things that can cause hearing loss, but the biggest risk, again, being family history. Gazella: So, when we think of hearing loss, it's understood that it obviously affects communication and how we communicate with each other, but does hearing loss have any physical impact on a patient's life? Albritton: That's an interesting question, and I think that 20 years ago we probably would not have directly thought so. It obviously does affect sense of wellbeing and ability to interact with others, but it can affect a lot of other things. An interesting study from last February demonstrated a correlation of hearing impairment severity and the incidence of fractures to the radial forearm, to the hip, to the spine, and it showed that patients with severe hearing impairment actually had an increased risk of fracture that was greater than the normal hearing group, and basically you had 1.4 to 1.6 greater risk of having one of those types of fracture from a fall if your hearing was severely affected. There's lots of further digging that needs to be explored such as severe hearing loss also contribute to injuries to the balance system. That's sort of outside the scope of the research at this time. But really the most newsworthy research in the past decade is focused on the correlation of hearing loss, severity of the hearing loss, with cognitive impairment and dementia. In 2013, a paper out of Johns Hopkins authored by Dr. Lin out of their department of otolaryngology and his colleagues demonstrated in just under 2000 patients that patients with a pure-tone average, that's that average we discussed earlier, of several frequencies of over 25 decibels, they had rates in decline in their cognitive function testing that was 30% to 40% greater than their normal hearing peers. And not only that, there was a linear relation between the hearing loss severity and the degree of decrease in their cognitive function test scores. So, that data really set off alarm bells, and health organizations throughout the world, the British health system, the French health system, Danes, Italians began looking at their population, and probably the most robust examination has been the English, many thousands of patients, have agreed with this information. They put a cognitive impairment risk of 1.6 times greater than normal hearing population with hearing impairment. Interestingly, some of these studies took the next step and tried to assess, well, if we do something for the hearing, such as a hearing aid or a Cochlear implant, something that will restore hearing, does that make a difference in the cognitive impairment testing? And it actually does. An Italian study was one of the preliminary studies to look at this, and they demonstrated that either a hearing aid or a Cochlear implant could actually reverse some of this cognitive impairment seen on the testing with improved scores. The French study was pretty astounding in terms of its result. Greater than 80% of their lowest scoring cognitive impairment patients tested, they showed improvement after the Cochlear implant, which was quite surprising. So, there's a question as to how hearing loss, how is this leading to dementia? And I don't think we fully understand that yet, though there are some hypotheses, and Dr. Lin laid out about four of these. First one being is there some common physiologic pathway that's contributing to both brain damage and inner ear damage? Something like blood pressure elevations where we see some chronic ischemic changes to the brain on MRIs or diabetes or something along those lines. The second theory is something called the cognitive load theory. Basically, it surmises that the effort of constantly trying to comprehend what is being heard takes memory resources, whether it be a neurotransmitter or other nutritive resources, and the chronicity and cumulative nature of this leads to issues and errors in ongoing brain function, the ability to maintain memories in an ongoing manner. A third theory is that hearing loss may affect brain structure. We do know that in brains of patients without stimulation, stroke patients, et cetera, that there's certain areas of the brain that shrink, and it isn't necessarily that we lose cells there, but there are some changes in the simple [inaudible 00:11:38] of those cells and that hearing loss patients do appear to show some of those similar findings on their MRIs. And then finally, social isolation. We know that social isolation happens with hearing loss, and we also know that social isolation is a known risk for cognitive impairment. One theory that a lot of fellow ENTs and otolaryngologists specializing in ear have known about since the '90s is that if we fit a patient with hearing aids earlier, they do better long term, and a large study in the VA looking at World War II veterans in the '90s established that patients that obtained hearing aids earlier did better with those hearing aids long term. They were able to accurately repeat words presented to them at a higher rate than their peers who had not obtained a hearing aid and had similar hearing test results. They would have basically the same level of hearing loss, but their ability to interpret speech was impaired, and the ability for the hearing aid to function with those patients was just suboptimal and were not able to get the same level of functionality from their hearing aid. And what the theory was is that the stimulation of certain areas of the cortical brain kept those areas healthy and functioning and that the old use it or lose it hypothesis, the patients who weren't using it did not maintain that brain and it therefore degenerated, never to really fully improve. This takes it to another level and seems to suggest that it's not just those areas of brain corresponding to speech recognition; it's rather the brain as a whole that is suffering from the lack of input. Gazella: Yeah. Early intervention is always best, so that makes a lot of sense. Now, you mentioned social isolation. Are there other areas that are affected with hearing loss that negatively impact the quality of the life of the patient? Albritton: Well, I'm sure that there are, and I'm sure that we're going to discover more, but I think the most obvious is isolation and its consequential potential for depression. People that can't hear, they eventually will isolate themselves in social situations because it just becomes too embarrassing or futile for them to continue trying to participate in a conversation they can't hear. And I think we all can appreciate what that feels like. If we've ever been to a noisy restaurant and we can't hear the conversation across the table or slightly away from us, we tend to withdraw. Imagine that for patients with significant hearing loss being a daily ongoing issue, and that ends up contributing to further self-isolation, but depression, and several studies have demonstrated that there is an increased incidence of associated depression with hearing loss. Gazella: Yeah, that makes a lot of sense. Now, you mentioned genetics. So, what is the difference between hereditary hearing loss and age-related hearing loss? Albritton: I would suggest that almost all forms of hearing loss that we attribute to age probably have some genetic component. As we look at just genetic programming for your resilience, your resilience of your skin, your eyes, your hair, your ears, all of those things are sort of pre-programmed, and most people accept multi-hit hypothesis to hearing loss. In other words, that it's not one thing; it's a multitude of things over time that lead to the cumulative and irreparable damage and that there are certain susceptibilities imparted by our genetics. So, we would guess that most age-related hearing loss does have some genetic, if not total genetic, predisposition, and the fact that it's not 100% of patients over the age of 75 with hearing loss, rather one half to two thirds, sort of backs that up. But in terms of congenital or hereditary hearing loss, there are certain conditions and syndromes which we know are hearing loss related, and we can diagnose those fairly young. It's the patients over the age of 40, 50, 60 that we're less able to determine. And there are some studies, though, that have looked at what we term age-related hearing loss and looked at their genetics and have identified some mutations that are fairly specific for a family group but not universally represented in other genomic studies, and they show up in certain areas of the gene pool where we know that genes dedicated to hearing messaging are present. So, there's probably a multitude of issues with mutations over our family histories that does lead to the age-related hearing loss, so I would look at them mostly in the same way. Gazella: Yeah. It'll be interesting to see how that research kind of plays out from an epigenetic standpoint. Now, there's early evidence showing that antioxidants, specifically beta-carotene, vitamins A, C, and E and magnesium can be protective. Tell us about that research. Albritton: Sure. I want to add one more little point to the last question as it'll tie into this. We do know that insulin-like growth factor 1 is something that's important in our homeostasis and our ability to fight off reactive oxygen species or free radicals, and some studies have demonstrated that this decreases with age, and some other studies have taken it a step further and looked at does this have a role in some of the age-related hearing loss, and it does appear to have some role in that. So, it's been a natural thing for antioxidants to have been targeted as a potential therapeutic arm against the aging of the ear. You mentioned vitamin A, C, E, magnesium, and I would caution drawing conclusions to these individual compounds at this time because the data is really all over the place. There are numerous studies in mice that have demonstrated some general improvements using a group of different antioxidants versus control groups. Some of those antioxidants include things like cysteine or acetylcarnitine. Longitudinal studies, though, looking at humans with vitamins A, E, C, B12, folate have showed different results. For instance, in men, they didn't find any difference with any of those vitamins used except in men over the age of 60 they did note that folate may have given some protective benefit. In women, they found that vitamin A and folate also helped not necessarily an age dependent result, but this is interesting; vitamin C, which has been shown to be helpful in some animal models, was actually harmful and actually worsened things in some women studies. We know that folate is an effective cofactor. We know that it helps balance out homocysteine levels, which can protect ischemic vascular damage, so that makes sense to us that it would work. The roles of vitamin C are just straight antioxidant properties, so that suggests that there's something more than just straight antioxidant benefits. One interesting study in Finland that was done about 10 years ago, and they call it the disco study, and it wasn't a very large study; about 20 people were given either an antioxidant vitamin or a placebo. They had their hearing tested before a night exposed to loud music and then they had their hearing tested short term and long term afterwards, and they definitively showed that the group with the antioxidants had less impact from the noise exposure than the control group. Gazella: That's interesting. I like they called it the disco study. That speaks to the era or the timing of that study, I think. So, when we're talking about studies, the research that I read I believe also included magnesium. What would be the connection with magnesium and why would magnesium help our ears? Am I correct? Was magnesium a part of that study? Albritton: Magnesium's a part in several of these studies, and magnesium and the metals probably have a bigger role in enzymatic cofactor, enzymes that can control either the release of certain natural antioxidants or enzymes that have some role in keeping a biochemical process in its favorable state as opposed to going to its unfavorable state. Those metals are essential to these enzymes functioning theoretically, and yes, in some military studies, the use of magnesium has been shown to be effective. Gazella: Now, you mentioned a lot of nutrients, A, C, E, just talked about magnesium. Is the combination of nutrients important and are there other nutrients that you wish researchers would be looking at? Albritton: Now, you're getting to what my interest is. I think yes. I think very much there is combination therapy that makes a difference. I think we're still trying to figure out what that precisely is. There are a host of readily available organic compounds that are something we may have picked up through ethnobotany or traditional Chinese medicine or just from the vitamin industry at large, but we have found that several of these compounds do appear to help in the protection of the inner ear, the heart, the kidney, et cetera. One of those is N-acetylcysteine in rat models, which has proven to be effective at protecting the outer hair cells of the inner ear, and one of the methods we think it works is just by scavenging the free radicals, but it does turn on the body's natural production of glutathione synthesis. So, it doesn't just target the free radicals with its own ability to neutralize them. It actually turns on the body's ability to keep producing those free radical fighters. But there's something else that goes on. It seems to regulate the nitric oxide in the inner ear, and one of the things that nitric oxide can do is, depending on its concentrations, it can trigger a cell to commit cell suicide. We call that apoptosis. In damage that may be sublethal, damage that shouldn't cause a cell to destroy itself, sometimes that misregulation allows the nitric oxide to get so high that it ends up allowing that cell to die. And as you may or may not know, these cells can't regenerate at this time, and so that regulation of the nitric oxide is one unexpected benefit of the N-acetylcysteine. And that's something we see in several other compounds. Some compounds, for instance ... I'm just going to give you a brief list. Resveratrol. We know resveratrol as a miracle compound that has some anti-aging properties in animals, turns on some anti-aging genes, but we found in several studies that it has a highly effective role in reducing inner ear damage in animal studies. It has not been studied in humans to date. We believe that's a real key chemical. CoQ10 has been also very effective in guinea pig models. We know that the mitochondria stabilization appears to be important, and CoQ10 is important in the function of our energy production in the mitochondria. Replacement does appear to have beneficial effects. One independent observation as I see patients in my office all the time with a balance disorder that we can attribute to a medication being used for their high cholesterol, and a class of medications HMG-CoA reductase inhibitors, such as the statin drugs, are notorious for depleting the body's natural production of CoQ10. So, replacement of that in patients has helped with balance preservation, and anything that helps balance preservation we can assume is also working in other areas of the inner ear as well. There are a number of elements and compounds that we discussed. We put together in 2006 a group of compounds we thought were going to be important that included the resveratrol, the N-acetylcysteine, N-acetyl-carnitine, alpha lipoic acid, green tea extracts, flavonoids from citrus, the CoQ10, B complex, and the trace minerals such as selenium, manganese, magnesium, and have found that to be effective in some pilot studies that we have performed on patients with their hearing loss showing some actual improvement in their hearing using the compound versus not using the compounds. We've not had the opportunity yet to complete a double blinded study at this time, but there is certain promise with this. I think the holy grail is a compound that would be able to be taken on a daily basis that would offer protective benefits to the whole body, not just the inner ear. Gazella: Right, and when you're talking about protection, you're even talking about protection in a patient that has some hearing loss; that it can also work in that patient population. Albritton: Yes. In fact, our pilot study really only targeted patients with hearing loss. We compared patients that had many years of hearing loss, and we had multiple hearing tests on them and then started therapy with them and measured several hearing tests on the medication, were able to compare their hearing test pre and post, and were able to make those comparisons based on a preexisting condition. And so we did see some improvements in patients with existing hearing loss. Gazella: What about reversal? Is that on the radar or is that a little bit too pie in the sky to actually reverse damage, to have a hearing be regained? Albritton: There's research being done in terms of hair cell regeneration. That's several decades away at best. That, if it does prove possible, would reverse it. Now, in terms of nutritional therapy, that's an unknown. We don't have the data yet to determine that. I think it is promising that we can see improvements in cognitive function with hearing aids and with Cochlear implants, but we can't know that by correcting some of the metabolic issues or protecting the interior from damage from its own physiologic stressors or noise exposures whether that's going to actually reverse the hearing loss that has occurred. I think that's probably pretty hopeful on our parts, but never rule anything out. Gazella: Yeah. Yeah, that's for sure. Now, given how common hearing loss is, it's likely that the readers of our journal have patients in their practice who are at risk. So, in addition to the nutrients that you mentioned, what else should doctors be recommending to their patients to help protect hearing? Albritton: I think first and foremost is recognize how common of a condition this is and screen for it. Ask patients, "Have you had any problems hearing? Has your spouse indicated that you may be having trouble hearing you?" It's interesting that spouses tend to be the ones that send patients for hearing tests more often than the patient seeks testing on their own. And it's a known fact that only one in five patients with hearing loss is going to seek help for it on their own typically. It can take 10 years or so before patients seek help for the symptoms. So, it can lay dormant, it can be hiding and be attributed to mumbling or volume not being turned up loud enough before a patient truly begins to embrace there may be a problem they need to evaluate. Refer patients for hearing tests if there is a presumed hearing loss or if there's a family history of hearing loss. Any patient that is on those medications, chemotherapy drugs, certain types of antibiotics, those patients should be monitored. One other thing that I think is very important and I think most practitioners are very good about doing, but let's remind them that noise exposure can be prevented. If you can't prevent the noise exposure, then protect yourself from it and that people that have hobbies or occupational risks should be wearing some degree of hearing protection, and just like smoking cessation's important for us to counsel, the use and adoption of protective devices should be something we continually discuss at our meetings with these patients. Gazella: Yeah, it's such a good point that you bring up that one in five seek help on their own and a lot just kind of let it go, let it go, and yet early detection, the earlier it's caught, the better off they'll be. So, I'm so glad that we're putting this on the radar of the doctors who are reading our journal. This has been very interesting, and I really appreciate you for joining me today. Albritton: Well, thank you. It's been a pleasure. Gazella: Have a great day. Albritton: You as well.

The Centers for Disease Control and Prevention has called insufficient sleep a public health epidemic. And yet, many of the commonly prescribed medications are not helping most patients. In this interview, John Neustadt, ND, explains why an integrative approach to treating insomnia provides a much more effective alternative to commonly used sleep medications.   About the Expert John Neustadt, ND, received his naturopathic doctorate from Bastyr University. He was founder and medical director of Montana Integrative Medicine and founder and president of Nutritional Biochemistry, Inc. (NBI) and NBI Pharmaceuticals. He’s a medical expert for TAP Integrative, a nonprofit organization educating doctors about integrative medicine. He has published more than 100 research reviews and was recognized by Elsevier as a Top Ten Cited Author for his work. Neustadt’s books include A Revolution in Health through Nutritional Biochemistry and the textbook Foundations and Applications of Medical Biochemistry in Clinical Practice. Neustadt is an editor of the textbook Laboratory Evaluations for Integrative and Functional Medicine (2d Edition). He was the first naturopathic doctor ever voted Best Doctor among all physicians in his area. Neustadt received 15 Orphan Drug Designation by the US Food and Drug Administration for the use of natural products for the potential treatment of rare diseases. About the Sponsor Nutritional Biochemistry, Inc. (NBI) formulates and manufactures products that give results. Started by John Neustadt, ND, in 2006 when he couldn’t find formulas he needed to help his patients and family, NBI products solve 2 problems he was having. Existing products didn’t contain the dose or combination of nutrients used in clinical trials and actually shown to work. Equally frustrating, other companies would cite studies on their websites, but then use lower amounts of nutrients than what was used in the study, or use entirely different nutrients that weren’t supported by the research. Neustadt’s latest creation is Sleep Relief. NBI’s Sleep Relief is a breakthrough in sleep technology. Its bi-phasic, time-release technology delivers NBI’s proprietary formula with clinically validated nutrients in two stages—a quick-release first stage and a slow-release second stage to help you gently fall asleep, stay asleep and wake refreshed and ready for your day. NBI's Osteo-K delivers the clinical dose of nutrients shown in more than 25 clinical trials to grow stronger bones and reduce fractures more than 80%. NBI is and always has been a family-owned company. We don’t manufacture anything we wouldn’t take ourselves or give to our own family. No matter what we do, our promise to physicians using our products is to help their patients, and to customers purchasing directly from NBI, is uncompromising quality. NBI is a name you can trust. But don’t take our word for it. Spend some time on our website, learn about our products, and educate yourself on the hundreds of research citations and studies that they’re based on. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, publisher of the Natural Medicine Journal. Thank you so much for joining me. Today, our topic is the integrative approach to insomnia. During this interview, we will learn that insomnia is a significant problem for many patients that can have far reaching physical, mental and emotional health ramifications. We will also learn how to successfully treat this condition by using a combination of diet, lifestyle recommendations, and dietary supplements. My expert guest today is Dr. John Neustadt. Dr. Neustadt received his naturopathic doctorate from Bastyr University and he was the founder and medical director of Montana Integrative Health. Before we begin, I'd like to thank the sponsor of this topic who is Nutritional Biochemistry Incorporated, or NBI, manufacturers of high-quality dietary supplements for health care professionals. Dr. Neustadt, thank you so much for joining me today. John Neustadt, ND: Thank you for having me on. Gazella: Well, so the Centers of Disease Control and Prevention calls lack of sleep a public health epidemic. Now, that seems pretty significant so today we're going to talk specifically about insomnia. How common is insomnia in particular? Neustadt: Well, the CDC is absolutely correct. It is a public health epidemic. Up to 80% of people struggle at some point with what's considered transient insomnia, less than two weeks of duration and insomnia effects 10 to 15 percent of the general population. In primary care settings, it's estimated that up to almost 70 percent of primary care patients have insomnia so it is incredibly common. Gazella: Oh, yeah that is. So how does lack of sleep impact a patient's overall health from like a physical, mental, emotional standpoint? Neustadt: It has devastating impacts. There are two ways to think of it. One is short-term impacts and the other are the long-term impacts. So, short term it can impact decreased job performance, impact social and family life by creating greater fatigue. I mean, just you're more tired during the day. Decreased mood and depression, increases in anxiety and stress. Decreased vigor and just not being able to cope with the demands of daily life and be able to complete tasks. That's only short term. Devastating just in the short term. But in the long term, it can be a killer. There, if people are sleeping an average of less than six hours per night, it can increase the ... or decrease the quality of life at the same magnitude of a similar condition such as congestive heart failure and major depressive disorder. It's an early symptom for Alzheimer's Disease and Parkinson's Disease and Huntington's Disease and there's a sweet spot for sleeping of about eight hours. That research shows is the healthiest, and if you're sleeping less than six, or longer than nine hours, it increases your risk for diabetes, metabolic syndrome, and death and, in fact, for metabolic syndrome, there's a 45 percent increase in risk compared to people who are sleeping seven to eight hours a night. Gazella: Wow, so yeah, so this is a very important topic for clinicians to have on their radar. So, when you're evaluating a patient with a sleep disorder such as insomnia, how do you approach the work up? Neustadt: Well, insomnia's really a qualitative diagnosis. It's how are they ... how do they feel that they're sleeping? How do they feel that it's impacting their health? Now the DSM official diagnosis, there is a quantitative or a couple of quantitative aspects to that and that is it's occurring at least three nights per week, and present for at least three months. So understand the difference between transient insomnia, less than two weeks, versus the diagnosis, official diagnosis, needs to be going on for greater than three months. So there's a huge discrepancy there and in time periods and clinically it's important to be aware of that because these detrimental and dangerous effects of insomnia and sleep deprivation definitely are occurring in shorter than three months period of time. They're happening pretty quickly if someone's not getting enough sleep and even over a few days the short term consequences. And so what I ask people about is how many hours, on average, do they think they're sleeping a night? Do they have any difficulty with falling asleep or staying asleep called sleep phase delay or sleep phase advance? Are they waking refreshed in the morning? What's going on with them psychosocially? Are there any stresses going on at work or in relationships or financially that's increasing their anxiety and could be impacting their sleep? Are they are risk for any hormonal abnormalities or imbalances because the research is clear that low estrogen, low or high testosterone, elevated TSH, those are all things that can create insomnia. Abnormal progesterone, as well. And then looking at medications because there are some medications that can impact sleep, as well. Gazella: Yeah, let's talk about the medications that can impact sleep. What are some of those medications that can impact sleep? Neustadt: Well, prednisone, that can cause hyper-arousal, or can cause somebody to not sleep, not be able to fall asleep, or have fragmented sleep. Beta-blockers, very common heart medications, can decrease melatonin production. So we know what the mechanism of action ... their interaction of sleep is they decrease melatonin and can cause poor sleep. Some antidepressants, actually, can cause poor sleep. Antidepressants can, depending on the antidepressants, can either cause somebody to not be able to sleep enough or can cause hypersomnolence, somebody to be sleeping too much. So looking at those, looking up ... it's very easy to look up whatever medication they're taking quickly and see, besides the ones that I mentioned, could it be potentially interfering and impacting with their sleep. Gazella: So I've been hearing about hyperarousal, or the hyperarousal hypothesis, which I find quite fascinating. What is the hyperarousal hypothesis and how can it affect what is recommended to patients? Neustadt: Great question. So the hyperarousal hypothesis I like to refer to as "wired-but-tired." And it occurs to people typically who are under a lot of stress, they have elevated cortisol, and when they end up trying to fall asleep they just can't turn their mind off, or even if their mind isn't racing, they just can't calm down. Their body can't relax and settle into sleep. They're staring at the ceiling, it can cause fragmented sleep. And that wired-but-tired, again, typically occurs in people who are under chronic stress. Gazella: Yeah. And you know the other day when you and I were talking as it related to the hyperarousal hypothesis, you were telling me about something else that was new to me and it was called social jet lag. Talk a little bit about social jet lag and the research associated with social jet lag. Neustadt: I'm so happy you brought this up because I love this as well. Fitbit, that maker of the wearable tracking devices, and tracking people's sleep as well, they had access, because of their users, to over six billion data points of sleep. And they looked at those. And they looked at the data and determined that the biggest predictor of healthy sleep, restful sleep, is going to bed at about the same time every night. Basically training our body that it's bedtime, getting that routine. Social jet lag occurs when people are going to bed at about the same time every night during the week but then the weekend comes. Friday night they go out, hang out with friends, stay out late. Saturday night maybe do the same thing, and then Sunday comes around and they try to go to bed again at their weekday, or their work week time, and they can't fall asleep. And essentially what they've done is it's as if they've flown to another time zone and their body thinks that it's not time to go to sleep yet. And they've induced their own jet lag called social jet lag. And so one of the things that Fitbit found, and I think one of the most impactful things, is showing that getting that regular bedtime, being in that routine, going to bed at about the same time every night is one of the best things people can do for improving their sleep. Gazella: And even on the weekend, and I'll tell, you, when you put this on my radar I, of course, had to do a little research and there's a lot of studies on this that actually show that the physical effects that you talked about with sleep deprivation earlier also occur with this social jet lag. So I think it's really important for clinicians to be aware of that. So thank you for bringing this to my attention. So now doctors often prescribe benzodiazepine or benzodiazepine-like drugs to help patients sleep. What are some of the potential risks of these particular medications? Neustadt: Well, the potential risks are very well documented and they increase risk for falling, dizziness, light-headedness, those risks are increased in people who are 60 years or older because their ability to metabolize the drug tends to decrease. And so because it increases the risk for falls and dizziness and light-headedness, it then increases the risk for fall-related injuries, such as osteoporotic fractures, such as concussions, such as death, even. But even beyond those risks associated with increased risks for falling, the research has shown that cancer risk is actually increased in people who take over about 132 doses of benzodiazepine a year. So that's even ... that's less than half of a year worth. And in fact some of these risks are increased with very small and limited exposure. So you know from half a dose to 18 doses per year, the hazard risk for death is increased 3.6 times. 18 to 132 doses, the hazard risk for death increased 4.43 times in a study that looked at this. And for greater than 132 doses, it increases 5.32 times. That's 532 percent greater than somebody not taking these medications for death. And the research has shown to actually get one benefit, the number needed to treat, to have one patient benefit is 13 patients. But the number to treat to create harm is only 6 patients. Gazella: Yeah, that's problematic. So what about the newer class of medications, like the orexin receptor antagonist Belsomra? Neustadt: Belsomra came on the market in 2015, it's a schedule 4 drug and it's a CNS depressant. So, like other CNS depressants, like benzodiazepine, it can have similar adverse effects. Some of the benzodiazepine drugs like Lunesta or Ambien can also cause, like Belsomra, can cause daytime impairment including impaired driving skills, risk of falling asleep while driving, abnormal thinking and behavioral changes are part of the adverse events spectrum, including amnesia, anxiety, hallucinations, other neuropsychiatric symptoms, even complex behaviors like sleep-driving. I mean, you're driving while not fully awake, after taking the hypnotic. Or other complex behaviors have been documented, like preparing and eating food, making phone calls, or even having sex, without remembering it. And so the drug has some serious risks, including worsening of depression and suicidal ideation, and the benefits of that, it can increase ... or the benefits of the medication, because all medication, it's a risk-reward calculation ... it can decrease sleep latency, that is, the amount of time to fall asleep by about eight to 10 minutes and increase sleep duration by 17 to 20 minutes. So at the most beneficial end of that, maybe it's 30 extra minutes of sleep. But you get all of those risks associated with it. Gazella: And are patients getting good sleep when they're on these prescription and over-counter medications? Are they getting good quality sleep? Neustadt: Well, you raise a great point. That's one of the problems with all of these medications is they tend to increase sleep duration, sleep quantity, but they're not increasing sleep quality. They're not getting patients into that deep, restorative phrases of sleep, the slow-wave sleep, phase 3 and into phase 4, to get that good, restorative sleep. So the quantity of the sleep may be increased but the quality has not been shown to be increased. Gazella: So you've made a pretty compelling case that a more integrated, holistic approach is needed. And integrative practitioners often recommend melatonin for insomnia with their patients. Can you talk a little bit about melatonin and why for some patients, many even many patients, it may not be enough? Neustadt: Melatonin is one of the first things I find that people with whom I speak, they've tried. They've reached for that. If they're going to try a natural product, they've reached for the melatonin, you know, first, almost universally. The challenge with melatonin is that it's got a very short half life, 40 to 50 minutes. And so while melatonin is considered a circadian modulator, meaning it helps the body recognize day from night, and it is a natural hormone, a natural product that our body uses to help us fall asleep, it's not really used for sleep maintenance. And so when somebody takes melatonin to help them fall asleep, because it's got such a short half life, well 50 percent of the melatonin is eliminated from the body in less than an hour, so let's just be generous and say an hour for easy calculations. So common doses out there is a 3 mg dose. So in an hour, they've got a one and a half milligrams left. An hour later they've got .75 milligrams left. And on down. And so 3, 4 hours later, essentially most of that melatonin is out of their body and they wake up again. I hear so often people who take melatonin, they end up waking up in the middle of the night, still. And so what do they do? Well, they might need more melatonin. And so they keep taking higher and higher doses until they're sleeping through the night and then they wake up feeling drugged in the morning. Groggy, hungover and it takes them hours to actually feel fully awake. So the natural rhythm of melatonin in our body is that the rise in melatonin occurs around 10 PM and then it peaks at about 2 AM in the morning, and it declines at approximately 6 AM, it's declined back to baseline. And that makes sense because that's sort of the rhythm of when we start to fall asleep and when our body then starts to wake up. Of course melatonin is balanced with other hormones as well that the body is producing during sleep, but the immediate release of melatonin that people are taking is not mimicking the body's cycle of melatonin production during the night. And it's also not a complete solution because it's not dealing with the other phases of sleep, we're looking at the other hormones in sleep, GABA for example. Or the other variables that can impact sleep such as poor blood sugar. When blood sugar can drop, hormones are secreted like cortisol and epinephrine to increase the body's blood sugar and we wake up. And so that's why melatonin for a lot of people doesn't work, because it's just not a complete enough solution. Gazella: I think that's a really good point, that it's not a complete solution for many people and that's why you use such an integrative approach. So I'd like to really dig into your integrative approach, I'd like to talk about dietary supplements, diet, and other lifestyle factors. So as long as we're talking about melatonin, let's keep on that subject and talk about dietary supplements. Are there specific dietary supplements that you use in your clinical practice specifically for insomnia? Neustadt: There are and it depends typically on the clinical picture. So for example if somebody has muscle aches or tight muscles that's keeping them from sleeping, magnesium can help, that can be a gentle muscle relaxant. If there's some anxiety that may keep them from sleep, well, glycine is an amino acid that's also an inhibitory neurotransmitter, that can be helpful. GABA also an inhibitory neurotransmitter used in the body available as a dietary supplement. That can be helpful. Botanical extracts such as alphianine increases alpha-wave production in the brain which is associated with calming, alert calmness. Then there are some sedative botanicals that can be helpful such as hops or skullcap, also called Scutellaria. And others. So that's part of it and for potential, looking at decreasing the response to stress, I like using, if they're under a lot of stress, some adaptogenic herbs like ashwagandha, or jujube, magnolia bark extract. If there is vaso ... if there's an issue with hot flashes and perimenopause, pine back extract. There's a clinical trial on that showing that it improved sleep quality and sleep quantity. And so I typically, you know, this monotherapy approach of one symptom, 1 pill, it really doesn't work when we're looking at complex pathologies like insomnia or many other chronic issues. And so I tend to like products that combine those different nutrients shown in clinical trials to work that target the underlying pathology, the underlying biochemical pathways at work and sleep and affected by insomnia in a time release or a biphasic time release delivery system because it more closely mimics the body's natural rhythm of the 2 major categories of your sleep. One is helping somebody fall asleep, you know how do we do that, and the other, over ... you know, the subsequent 6, 7 hours later after they've fallen asleep, how do we help them stay asleep? And so that's how I conceptualize it and that's the overall approach with dietary supplements when they're indicated. Gazella: So before I move on to diet, I know that you helped formulate and create a specific sleep supplement. I want you to tell me the name of that supplement but I also want you to tell me why you created it, because let's face it, there are a lot of sleep supplements in the market. So why did you want to create the supplement that you created? Neustadt: So the name of the product is NBI's, my company, NBI's Sleep Relief is the name of the product. And I created it for a couple reasons. One, just like all the products that I've created in NBI and formulated, I couldn't find the combination of nutrients or the dose and form of nutrients in a product shown in clinical trials to actually work. And I personally suffered from insomnia for years and years. And I tried a lot of different things. It wasn't helping me. I'd work with a lot of my patients trying to different things, having to dispense different bottles of products, in addition of course to working with diet and lifestyle and other psychosocial factors involved. And I couldn't find something that worked consistently. And so I started digging into the sleep research, the pathophysiology of sleep, the clinical trials, what are the underlying mechanisms affecting sleep. And after over a year of research and formulating and working, trying over a dozen different combinations and doses, that's when I created Sleep Relief. Gazella: Okay perfect, Sleep Relief. So now let's talk a little bit about diet. What are some of the things that you recommend to your patients when it comes to sleep, associated with diet that may not be on the radar of some practitioners? Neustadt: So one of the big things that I see over and over is a lot of people have, may have acid reflux and they don't know about it. And because maybe it's not ... maybe they have a cough when they lay down, maybe they are just not aware that that's going on. And so evaluating for that because that can wake people up. The other thing that I find with diet that's very important, and with acid reflux, you know, that can be diet related. There are 5 most common foods that can contribute to that and interrupt sleep, that's raw garlic and onion, chocolate, coffee, and citrus. Although other things can do it for other people. An infection can do that, H. Pylori can cause that as well. And then if they have a hernia, a hiatal hernia, that can cause it as well. So looking at that, looking at those underlying potential causes if that is involved. The other thing is poor blood sugar control which I already mentioned. And one of the things I like to ask that can indicate if they might have poor blood sugar control is if they get that afternoon, postprandial tiredness. You know, about 3, 4 o'clock in the afternoon, a couple hours after lunch do they just get that energy slump. And that can be an indication that they're having a little bit of blood sugar control issues. Or are they waking up at the same time every night. Both of those questions can give clues. And if that does seem to be involved, one thing that I love to try with patients ... it doesn't work very often but when it does, it's really a home run, and that is ask them to eat 8 to 10 grams of protein before bed. Protein's one of the best ways to regulate blood sugar. And so if they do that and it stabilizes their blood sugar and they then are sleeping through the night, well, again, it's a home run. I mean, there are no pills, no powders, it's just natural doing it with food and it also opens the door for even more discussions with helping them understand how they can improve their diet during the day to help, to eat, to promote ... to help them understand how they can eat, changes they can make to eat, the promote their health for the rest of their life. Gazella: Yeah, those are some great suggestions when it comes to diet. Now let's talk a little bit about lifestyle. What are some things that may not be on the radar of some practitioners when it comes to lifestyle aspects? Neustadt: So we talked about going to sleep at about the same time every night, that's really important. The other thing is ... and most practitioners, or hopefully all of them have heard of sleep hygiene. The research shows that about the 69 to 70 degrees for most people is the ideal temperature for sleep. Some people who, if they're in a relationship with their partner, they may like different temperatures may be most comfortable for them. So there are wonderful things out there now, it's call the ChiliPad, that you can get, it's a pad you can put on your bed, where you can control the temperature on each side of the bed. So that can be really helpful. Stress of course is a big issue in our society, a lot of people are under chronic stress, so anything that we can do to help people decrease their stress or better deal with stress is really important. And a fantastic study came out recently that showed that a lot of the impact of stress is not the actual event happening to us, it's how we view it. So if people view stress as a good thing, meaning "I gotta learn something from it and what can I take from this," the health impacts from stress are mitigated. If somebody sees a stressful event and they're internalizing it and they're not seeing it as a growth opportunity, then it magnifies the negative stress impacts. So, A) getting them to just understand that mindset is really important, just when it comes to stress happening, and then what can they do to have more control over those events that may be causing them stress to decrease that stress. And that could mean creating healthy boundaries for themselves. That could mean doing any yoga or mind-body techniques. You know there's lots of things that we can offer to patients that can be incredibly, incredibly helpful. Gazella: Yeah, I would agree. And now your approach focuses on diet, lifestyle, and dietary supplements. How important is it to focus on all 3? So some practitioners might be really focused on the person's diet, or some might be looking at their stress level, and some might be focused on just melatonin. Why is it so important to look at this from an integrative standpoint? Neustadt: Well I think if we want to do the best job we possibly can for our patients and give them the best results, looking at it through a more integrative approach is important. And I like the approach of trying dietary supplements to give people benefit quickly. So if somebody is sleep deprived, it's gonna increase their tendency to reach for those comfort foods. I think we've probably all experienced that. And especially because what happens with insomnia and sleep deprivation, it decreases mood. It can cause depression. And sugary foods, for example, when we reach for those, it can increase our serotonin production and temporarily lift mood. But it causes this rollercoaster of insulin and blood sugar that's hard to get off of. So just getting people sleep can help improve their mood. So I like the dietary supplement approach for triage to get them feeling better so they can make healthier decisions, have a more present mindset, be more proactive instead of reactive, while I'm working with them also on improving their diet. Transitioning to a healthier way of eating, which, the research has shown, unambiguously is the Mediterranean pattern of eating. And also stress reduction and exercise and those things as well. Gazella: Yeah, I mean that all makes a lot of sense. And this is a very important topic and I want to thank you, Dr. Neustadt for a very interesting conversation and once again, I'd also thank today's sponsor, Nutritional Biochemistry Incorporated, or NBI. Thanks again, Dr. Neustadt, for joining me. Neustadt: Thank you for the opportunity. Gazella: Have a great day. Neustadt: Thank you. Gazella: I'd like to remind readers of the Natural Medicine Journal that we now offer free continuing education credits for naturopathic physicians. Our list of podcasts and research guides that have free CE credits is growing. For more information, just click the Continuing Education tab at the top of our Natural Medicine Journal website.

When it comes to testing, you can always count on a lively debate about how to best identify food sensitivity and intolerance. In this interview we review recent clinical and mechanistic research on the ALCAT test, including studies conducted by Yale School of Medicine and other institutions. In addition, general advice will be given about how food testing can help integrative practitioners create personalized diets for health and performance for their patients. About the Expert Roger Deutsch is the CEO of Cell Science Systems, where he oversees research and general management. He has been involved with all aspects of the development of ALCAT technology for 34 years. He previously studied psychology at the State University of New York, Purchase and Chinese medicine at the International College of Oriental Medicine in the United Kingdom. He is coauthor of the book, Your Hidden Food Allergies Are Making You Fat, and has lectured in more than 25 countries on the topics of food, inflammation, and the aging process. He is deeply involved in supporting free education for impoverished girls and free healthcare in rural India. About the Sponsor Cell Science Systems, Corp (CSS) is a CLIA licensed lab and an FDA registered medical device establishment that has developed the ALCAT test for food and chemical sensitivities, as well as GI function assays, telomere length assessments, molecular diagnostics, and this month will also be launching cellular tests for the assessment of functional micronutrient deficiencies and antioxidant status. CSS received the company of the year award in 2016 for Food Intolerance Testing, North America, by Frost & Sullivan. The ALCAT test has been clinically validated in research at the Yale School of Medicine, where mechanistic studies were also conducted. Those studies have led to new discoveries regarding the pathogenic mechanisms underlying food sensitivities. CSS will continue to participate in industry grant–funded, cross-border, translational research that focuses on the role of food-induced release of DNA and its role in pathology. CSS is located in Deerfield Beach, FL, and also operates a wholly owned subsidiary lab in Potsdam, Germany. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, our topic is Identifying Food Sensitivity and Intolerance. I'd like to thank Cell Science Systems, who is the sponsor of this topic. My guest is Roger Deutsch, who is one of the pioneers in the field of food and chemical sensitivity testing. Roger, thank you so much for joining me. Roger Deutsch: Thank you, Karolyn. Pleasure to be here. Gazella: Well, historically, it's been kind of challenging to identify food sensitivities and intolerances in patients. Generally speaking, I'm just wondering, why is that? Does the research you've participated in offer any new understandings? Deutsch: Yeah, the research that I've been involved in certainly does offer a lot of new understandings. Just to put this in context, and just to repeat, I'm sure most people are very clear on this distinction between allergy and intolerance. Just for sake of brief review, the term allergy was coined by a physician named von Pirquet in 1906 to denote an altered reaction. Then there was quite a bit of debate amongst allergists in Europe during the '20s and '30s as to what should be included in that definition of an altered reaction. At the end of the day, they settled on including only those types of reactions that induced an immediate symptom onset, because those are more definable. Just through some research in the '30s where they transferred serum from an allergic patient to a non-allergic patient and then scratch test the area where the serum transfer took place, and they would induce the wheal-and-flare. They knew that there was some factor in the serum that caused allergy. They didn't know what it was. They called it reagent. Then, years later, in 1969, they found out reagent was IgE. Then they found out all the events that were preceding the IgE molecule and then how the IgE molecule bound to mast cells and then cross linked, which caused degranulation and release of histamine and medium symptoms and so forth. Later, interestingly, they found out that's the same pathway the body uses to protect against infections with worms. So they called that allergen. Of course, worms are large compared to a cell, so when the immune system has to combat such a big pathogen, it's a very dramatic reaction, so there's a very dramatic release of histamine. The symptom onset, then, is very dramatic and very rapid. Then that being as clear as it was, by contrast, intolerances or sensitivities due to an enzyme deficiency or some other part of the immune system, the innate immune system underlining a sensitivity was more difficult because the symptom onset wasn't immediate. The linkage between cause and effect was ambiguous, obscure, and the pathway was unknown, so what do you look for? A lot of different things were proposed. Before too long, people proposed looking at the white blood cell. In the 1950s, an allergist in El Paso named Black reported his usage of looking at white blood cells through a microscope, being challenged with an allergen and seeing morphological changes that then were correlated with clinical symptoms. Then that work got picked by some researchers from Washington University named, gosh. I forgot what their name is. I don't know. It will come to me later, but anyway, they gave it the name cytotoxic test. They published about three or four papers, and it became very popular and broadly used. There was a lot of political upheaval because it's something that came on that proposed a solution to a lot of problems. People don't like huge paradigm shifts, so it fell a little bit by the wayside. We knew that there was a white blood cell component to the thing, which is logical. The immune system would underline an immune reaction. It's no mystery. When we came along, we thought, "Look. The allergists don't like the cytotoxic test." Bryan was the name, William and Marian Bryan brought out the cytotoxic testing. Allergists get upset about it, because it maybe changes the paradigm in ways they were afraid of. It was subjective, because it required a technician to look at cells under a microscope and make a judgment call as to whether or not there was a reaction. We came along in that period of time, in the mid-'80s and applied electronic instrumentation to the measurement of the cells and introduced some other standards, better controls over the allergen presentation and used the computer to interpret the degree of change in the white blood cells. We went along quite a long time observing and making the clear association that when the white blood cells would expand or degranulate or didn't become [inaudible 00:05:48], now we know undergo apoptosis or necrosis or pyroptosis, there was good clinical correlation. We did studies in the late '80s with people who were pioneers, and had backgrounds in research and drug companies even that were interested in this field. We found that when you had an ALCAT, the name of our technology was ALCAT. When you had an ALCAT positive and if you challenged the person with the food that was positive under double blind conditions, you would get correlation about 80% of the time. When there was an ALCAT negative, you would get correlation, in other words, no clinical response from a double blind challenge, about 85% of the time. That was good clinical validation. It was building the mechanism. If you fast forward to earlier this year and last year, there had been a number of clinical studies in between, of course, but we gave the technology to be investigated to some very smart people at Yale School of Medicine. They did a clinical study that they know how to do, a randomized, controlled, double blind, placebo-controlled trial, feeding patients either a diet that was based on the ALCAT test, eliminating positive foods or placebo group, and nobody knew who was in what group except the one coordinator who didn't tell until the end, a placebo diet based on an ALCAT test where they kept the positive foods in. They just looked at change in symptom scores over time. They saw a huge difference between the people following the true experimental diet versus the ones following the placebo. Then they looked at some chemistries. They actually banked serum at the beginning of the study, knowing that retrospectively, they'd see who had done well. Then they could go and evaluate what might have happened amongst that population that had a strong response. They did find that, out of about 1,200 or so peptides and proteins that they assayed, that neutrophil elastase would drip precipitously in those people. Clearly, the neutrophil seemed to have some effect. They went on and did some look into what's happening inside the cell, and which subtypes of leukocytes were most involved. They did immunological studies using flow psychometry and they found that eosinophils were activated most of the time. Neutrophil elastase was being released, so obviously, there was some orchestration between these two classes of granulocytes, but the other thing they found, which is very interesting, is that there was greater release of DNA from the cells that had reacted in a positive way than there were, excuse me, reacted to a food that was tested as positive versus when there was no food in that sample or an ALCAT-negative food. Somehow, the positive reaction would induce the peripheral leukocytes to undergo some sort of process that would result in the release of toxic mediums like neutrophil elastase and others, but would also cause a release of cellular DNA. That's an interesting finding, because over the last few years, most people are not familiar with this yet, but common sense tells you DNA doesn't belong outside the cells. It belongs either nicely tucked away in a eukaryotic cell in the nuclei or in the mitochondria. When it gets out, it can cause problems. We could talk all day about how it gets out, but there's some very smart research from Max Planck Institute, which shows that these neutrophils and macrophages and other granulocytes use, as a strategy to kill pathogens, something called ETosis. When it applied to neutrophils, it's called NETosis. Even after this cell has released free radicals, then it's to try and defend against invaders. Even though the cell is dead, a lot of the nuclear material, the histones, the DNA, merge with granules and the toxic mediators inside and the plasma membranes and the internal membranes and strip out, form these nets. That can trap pathogens, and the DNA is toxic, and kills them. That's occurring, but if too much of this goes on and the body's mechanism for cleaning up the mess, which is mostly DNA's want, and you have the persistence of this toxic DNA in the circulation, excuse me. It causes all sorts of problems, like metabolic problems, like lupus, like arthritis, and even cancer. It's a new area of medicine, so it's interesting. We've found that the ALCAT predicts the foods that trigger the release of DNA. Now we have the next step ahead of us, using a grant that we received from one of the larger industry players, we're going to characterize the nature of the DNA that's released, because the nuance here is that if the DNA is methylated, it's not toxic. If the DNA is unmethylated, it is very toxic. We want to look at that. The expectation is that we'll find that it is mostly unmethylated, because the release of DNA is kind of chaotic and not controlled. Gazella: That is fascinating. I have you tell you, you're talking about the 2018 study that was published in Alternative and Complementary Therapies? Deutsch: No, this study was, it came out Yale. Gazella: It was earlier this year? Deutsch: Yeah, I can't remember the actual name of the journal right off the top of my head. Gazella: Okay. Deutsch: If people go on to CellScienceSystems.com, there are a couple of papers from Yale. The first one I spoke of was a clinical paper. That was published in EMJ Gastroenterology. The other one was another nice, international journal. Gazella: Great. I do want to talk about the study that was published in Alternative and Complementary Therapies, but I want to stay on this topic that you just introduced, because honestly, it's fascinating to me. I think our readers will find it fascinating as well. Right now, can we draw clinical conclusions that ALCAT can be used to predict which foods might increase the release of potential unmethylated DNA, or is that down the road? Is that a clinical application right now, or is that something that is down the road? Deutsch: I think the clinical utility has been established a long time ago from the studies from back in the late '80s where they did these double blind and placebo-controlled oral challenges very carefully and found overall efficacy of the test at 84-plus percent. There's been other studies, one that you just mentioned that also came out in last month's Complementary and Alternative Medicine with some work done at University of Northern Illinois. There, of course, they found some other pathways and some other mechanisms. They found that Serum Amyloid A, which is reflective of overall body inflammation, also drops precipitously in people who have clinical improvement when they alter diet based on ALCAT, much more so than control groups, where you have blinded sham diets being implemented. Another validation just came out last week. This was on European Society of Clinical Nutrition and Metabolism. There was a group from the University of Pavia, which is northern Italy. The University itself was established in the 900s or the 800s. It's a very old institution, very well-respected in Europe. They found that with respect to gluten, isolated gluten, the 33-mer peptide that you can buy from chemical companies that are used in a lot of tests, some tests, and gluten-containing grains, wheat, oats, barley and rye, that the ALCAT test and double blinded placebo-controlled oral challenges with gluten and grains was also very highly correlated. They proposed, at the University, that ALCAT actually be used as a new diagnostic criterion for non-celiac gluten sensitivity. Gazella: Yeah. There's a lot of solid research showing the clinical efficacy of using the ALCAT test. That's what I'm hearing from you regarding the research that's been done up to this point. Deutsch: Yep. It's pretty clear. Gazella: Great. Good. I want to step back a little bit. How common are sensitivities and intolerances to specific foods? Deutsch: That's always a challenging question, because we don't have a clear-cut definition. Intolerances are generally induced by a lack of an enzyme to break down some component of a food, and we have an adverse reaction that may not be that severe, so lactase deficiency can induce lactose intolerance. If you bring those in, but then you get into the more nuanced types of intolerances where there's a chemical that is naturally occurring in a food or could be added in processing where the person lacks the enzyme to break down that toxin. Again, keeping in mind that all plants produce natural toxins in order to defend against pests. Nowadays, I think we see the inability of individuals to break down some of those toxins and the innate immune system comes into play, because we're increasingly depleting and compromising our ability to detoxify. Again, because of some overall changes in diet and how food is produced, the industrialization of farming and so forth. You might find that because the body is not as efficient as it should be, breaking down a toxin the food with which the person has not had, through his ancestry, the development of those detoxification pathways, that if they have a little bit, it's okay. If they have too much, it becomes a problem or if it's the wrong time of year and there's too many other co-factors or they visited Mexico and have a disruption in their diet, then they have more of an issue with it. It's not as clear-cut as, say, an allergy where just a few molecules of the offending substance can trigger a very dramatic response. It actually gets amplified by things like Substance P in the body and spreads out, because it's a whole different pathway and a whole different animal entirely. It depends how you want to try and define these intolerances and sensitivities. People fluctuate, depending on season, detoxification pathways, intestinal permeability, overall level of health, cofactors and so forth. If you are comfortable with a generalization, I'd say that it's very rare. We have found some, but we've had to look hard. It's very rare to find a person who doesn't have any sensitivities or intolerances. In how many? Again, it depends how you operationally define them, but it's highly relevant. It underlies a lot of inflammatory problems, metabolic syndrome and all the health issues that can come from that. It's extremely common, but I don't want to put a number on it, because we're all guessing. Gazella: Yeah. That's interesting. It's rare to find someone who doesn't have a sensitivity or an intolerances. That's a pretty big statement. I'd like to talk specifically about celiac disease and non-celiac gluten sensitivity. Tell us about testing regarding those issues. Deutsch: Celiac disease is an autoimmune disorder where cytotoxic T lymphocytes attack the enterocytes in the small intestine. In order for that to happen, the T lymphocytes have to recognize the allergen or trigger. The trigger, it's not really an allergen. The trigger is gluten. It's presented to the T lymphocyte by an antigen-presenting cell, mostly dendritic cells, which absorb the trigger, break down the peptides internally and lysosomes, transport it by an MHCT molecule to the surface where if there are T cells that recognize that complex, will become activated and may lead to celiac. Celiac depends upon the ability of the T lymphocytes to recognize the combination of that MHCT molecule with the gluten and gliadin peptides. If you're not genetically, if you don't have the genes to produce that specific variation of an MHCT molecule, you can not get celiac disease, so the tests for those genes, which are human leukocyte antigen GA DQ2.5 and H. They're very easy to test through PCR. We also do that testing. That test has phenomenal negative predictability. If you don't have those genes, you cannot get celiac. However, you could still have an adverse reaction to gluten, which is not mediated by the T lymphocytes and that pathway, but it is a function of the innate immune system, which means neutrophils, eosinophils, mostly neutrophils. That's what we call non-celiac gluten sensitivity. That's what they studied in Pavia and found that the ALCAT test is measuring the activation of the granulocytes, which are mostly peripheral granulocytes, mostly neutrophils. The same thing was seen years ago with Fezzano and Stroup, working with the people at NIH in leukocyte biology labs where they challenged with gluten in experimental animals in transgenic mice whose neutrophils would glow when they became activated. They saw all this activation. It's the same pathway, but it goes further in those people who are genetically predisposed. If you go past the first lines of defense of the innate immune system and reach into the specific immune systems, T lymphocyte population becoming active, that causes the real problem. Gazella: I see. ALCAT is actually effective for both food sensitivity and food allergy. Deutsch: I wouldn't say it's effective for food allergy, because I wouldn't call celiac disease really a food allergy, because there's no IBE molecule. Again, the allergists only like to use the word allergy when there's IgE involved or there's an immediate symptom onset. Here, you do have other immunological reactions, more like a Type 4 reaction, whereas an allergy, in the Gell and Coombs system, is a Type 1 reaction. ALCAT will let you know whether you're going to have a problem with gluten. Exactly how that problem will manifest will depend upon many factors, your genetics and also your microenvironment, your ecology in your gut. The ALCAT will tell you both those issues, but not what we call a true food allergy with a Type 1 type of reaction. Gazella: Right, okay. Good point. Good clarification. Let's dig into that 2018 study that was published in the Journal of Alternative and Complementary Therapies. Can you describe the objective, the method, and the outcomes of that study? Deutsch: Going from memory, I don't have that in front of me. It was basically, again, a double-blinded, randomized trial looking for improvement in symptoms that are typically related to sensitivities, food sensitivities. We were looking at various inflammatory conditions where the control diet was, again, a sham diet where foods were taken out, but they were not ALCAT test positive foods. The test subject didn't know that their new diet instructions were excluding ALCAT test positive foods or ALCAT negative things. Then just looking at the outcomes and some biomarkers, and specifically Serum Amyloid A and body composition. There were differences seen that were pretty distinct between the two groups. There was a much greater improvement in the symptoms in the report, which is also on our website. It was, again, the University of Northern Illinois. Dr Lukaszuk led the research project, showed that there was much greater reduction in symptoms amongst the people who were following the ALCAT test and the significance was significantly high. It wasn't something that could have happened as a function of [inaudible 00:26:01]. There was a very sharp drop in Serum Amyloid A, which a lot of people are beginning to look at more than high-sensitivity C-reactive proteins as an indicator of total body inflammation. It puts together a nice picture of that. Biochemistry is changing. The new system is less reactive and people are improving body composition and reducing their symptoms. Gazella: Yeah. It sounds like you've got some great research going on, but I'd like to talk a little bit about the future. Can you tell us about cellular technology for identification of functional nutritional deficiencies? Deutsch: One of my favorite topics. I used to live in Austin for 14 years. During that time, there was a lab. There was a charitable organization named the Clayton Foundation that backed a researcher of Experimental Biology Department, University of Texas in Austin named William Shive. William Shive was a protégé of a gentleman who wrote the book in the 1950s called Biochemical Individuality. That book basically explained that we're all quite different, and his experience was that he went in. Prior to the 1950s, he went in for a surgery the night before. They gave him morphine to help him sleep, and it kept him awake all night. That kind of reaction caused him to think over about how we're all a little bit different. A paradoxical reaction like that was quite pronounced. He did a lot of research just in animals and humans, looking at how we're different, and extended that concept to the idea that nutritional needs are also unique. In the 1970s, a group basically challenged, recognized that we needed, as a profession, to have a test for nutritional deficiencies that took into account individuality. William Shive was proposed as the person to help develop it because of his knowledge in the field. He got backing from the Clayton Foundation. The Clayton Foundation, by the way, was a gentleman named Clayton who was in partnership with MD Anderson there in New Orleans. They would support research in nutrition and cancer. One of the things they did was to try and recycle the funding. As soon as something was developed, they would try and commercialize and monetize it, license it out, and recycle those funds for new things, because philanthropists want to see more and more benefit happen. I got to know Dr Shive, and he was doing his evaluations in using the classical way of looking at lymphocyte proliferation, using incorporation of radioactive [inaudible 00:29:27] into the DNA and then extracting that after five days and measuring radioactivity and therefore inferring how much new DNA there was, what DNA synthesis levels occurred and being able to infer growth of lymphocytes, which we spoke about before. When they were stimulated by a mitogen, where a mitogen could be a plant lectin like phytohemagglutinin, which would universally induced EMD cells to multiply. Remembering here what I was speaking to you about the difference between gluten sensitivity and celiac disease. Celiac disease is, again, involving T lymphocytes, meaning it's a function of the specific immune system, so only certain T lymphocytes will recognize a pathogen's peptides being presented to it, and others won't, which is why it's not really a great test for looking at particular allergies because there's too much background noise. 99% of lymphocytes don't react to a pathogen, but 1% of them do. After an infection or during an infection, a small number of lymphocytes that recognize the pathogen will divide in the circulation and in the lymphatics and multiply themselves, which is obviously not something that granulocytes to. He's stimulating lymphocytes with a mitogen. You want them to divide, because the ability of these cells to divide and clone rapidly enables you to produce the antibodies and the lymphocytes that will kill the pathogens. What they need to divide are nutrients. If you stimulate them, and they divide very slowly, you might look at adding nutrients into the culture. There was research done on that in the 1930s where people would take mold spores and radiate them and see that they no longer would divide. Then they one by one added back specific nutrients to see what would restore metabolic machinery. In fact, a group from the University of Chicago got a Nobel prize for that in 1958, so the idea was out there that lymphocyte proliferation could be a good marker for measuring a functional response to changing nutrients in a culture. My early discussions with Dr Shive were, "Dr Shive, the concept is great, but why are you using this old-fashioned method that involves radioactivity if you want to count cells?" Use a cell counter. He agreed. We started to do some work together. Unfortunately, Dr. Shive passed away, but I always was fascinated by that area, and continued to work on it for maybe 15 or 20 years, looking at using cell counters to measure lymphocyte response when stimulated with a mitogen when you alter the culture medium to add another nutrient, one by one. If you found that the adding of the nutrient induced a more robust lymphocyte proliferative response, you can infer that for whatever reason functionally, that nutrient was not at optimal levels, and there should be repletion of that nutrient through foods that contain it or even supplementation. After many years, we kind of looked at that, but we thought that even a cell counter, we're in the cell counter manufacturing business. Some people don't know it, but we're a CLIA lab, and we do these tests, but we also build cell counters and sizers that are used in our tests, because we want them to do very specific things. We found that there were other methods that we looked at that could be done more rapidly and more simply, and correlated with the cell counts. We've been validating that over the last couple of years, and we're actually going to release that testing this month, in January, to look at the levels of improvement of specific immune function when you add specific micronutrients to cell cultures. We're also looking at doing the same kind of testing under conditions of oxidative stress to see which antioxidants improve the survival of the cells when there is an oxidative stress situation going on. Gazella: That's awesome. There's a lot of integrative practitioners who are interested in that type of personalized medicine. When you say it's available in January, is it clinically available to practitioners in January? Deutsch: Yes. Gazella: Awesome. That's great. Deutsch: Yeah, we're making it available. Gazella: I have one final question. I've been researching Cell Science Systems, and it seems like it's not just about delivering a test for your company. It's about helping clinicians personalize the diet for their patients, but then providing support regarding compliance and sustainability. Why is that so important to your company? Deutsch: Our company is here to help. I've done this for coming on 34 years now, and I had health problems in my earlier years. I worked through it. I was an athlete as a kid and all that, played on teams and all that, but I had bad allergies. Finally, when I was in my 20s, with the help of some naturopaths in Australia, figured out that my issues were basically diet-driven. I got interested in this field. I know how, from firsthand experience, what a problem it can be if you don't know that you're eating something which causes your eczema, your respiratory problems, your fatigue, your arthritis, your migraines, so on and so forth. I want to do everything possible to have an impact. I know that's the way most people in the naturopathic community are as well. We've created some tools to help educate patients, to help them comply, to help them understand how to substitute certain things, to be able to take an ALCAT test result and have it reflect into a several-hundred-page personalized book of recipes, and then just make this all available. We created an educational course, which actually, we'll have to go to the Naturopathic Societies and see if they'll accredit it, but we have accreditation for this from the dietitians and nurse practitioners, so it's a course that we offer. Again, we're going to present this to the naturopaths. It costs $199. Then when people go through that, then they can purchase from us these meal planning tools and other things for their patients. We're going to put a lot of this online, so it'll be very convenient, at our website for this purpose, called GutHealthPartners.org, and just make compliance a lot easier so people stick with it and get the benefits. That's what we're doing. Gazella: That's great. We also have a lot of dietitian and nurse practitioners who are readers of the Natural Medicine Journal, so I'm sure that they'll appreciate that. That sounds like a wonderful mission for your company. This has been very interesting. Thank you again, Roger, for joining me today. Once again, I'd also like to thank our sponsor, of course, Cell Science Systems. Have a great day, Roger. Deutsch: Thanks. Thanks for having me, Karolyn.

In this interview, Ross Pelton, RPh, PhD, CCN, describes the new science associated with postbiotic metabolites and their impact on health. Listeners will also discover what postbiotic metabolites are and why they are so important to the human microbiome. About the Expert Ross Pelton, RPh, PhD, CCN, is Essential Formula's director of science, in additino to being a practicing pharmacist, clinical nutritionist, and health educator in Southern Oregon. Pelton earned his bachelor of science in pharmacy from the University of Wisconsin and received his PhD in psychology and holistic Health from the University for Humanistic Studies in San Diego, California. A certified clinical nutritionist, Pelton was named as one of the Top 50 Most Influential Pharmacists in the United States by American Druggist magazine for his work in natural medicine. Pelton teaches continuing education programs for healthcare professionals to use natural medicine and integrate it into their practices. He also has authored numerous books, including The Drug-Induced Nutrient Depletion Handbook, which is a gold-standard reference book for health practitioners. About the Sponsor Essential Formulas Incorporated (EFI) was established in 2000 as the sole US distributor of world-renowned microbiologist Dr Iichiroh Ohhira’s award-winning probiotic dietary supplements and skin care products. Always an innovator, EFI introduced REG’ACTIV in 2015, containing ME-3, a probiotic catalyst that produces the “master’” oxidant glutathione inside the body's cells. A family-owned and operated business, EFI was founded on the philosophy of providing high-quality preventative, supportive, and comprehensive pro-health products for the entire family. EFI continues to flourish and grow through a strong company and product integrity and the knowledge that they’re providing scientifically proven products that positively impact the health and well-being of their customers. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we have a fascinating topic. We'll be talking about post-biotic metabolites with probiotic expert Dr Ross Pelton who is also an integrative pharmacist. Before we begin, I'd like to thank the sponsor of this interview who is Essential Formulas Incorporated. Dr Pelton, thank you so much for joining me. Ross Pelton, RPh, PhD, CCN: Hi, Karolyn. It's nice to be with you. Gazella: Well the research regarding the human microbiome is really exploding. Why is this so significant? Pelton: Well I like to give people a little historical overview which I think gives us an understanding of how and why this incredible acceleration of research into the microbiome has taken place. I'd like to go back to the Human Genome Project. It took 13 years and billions of dollars to sequence the first human genome. After sequencing the human genome, one of the primary goals of that whole scientific endeavor, they thought once they sequenced the human genome we would be able to get cures for many of our chronic degenerative diseases. That primary goal of the Human Genome Project was a total failure. We did not get any cures for human diseases from the Human Genome Project, but one important thing that we did get was the development of incredible technology and incredible equipment that allowed for much faster and much cheaper sequencing of genomes. That's when scientists started to use this new technology to sequence the genomes of bacteria in the human gastrointestinal tract. They were astounded with what they found, this whole massive population of organisms in the human gastrointestinal tract. Fortunately, our government then went on to fund the Human Microbiome Project. The funding for the Human Microbiome Project coupled with the incredible technology developed in the Human Genome Project allowed scientists to make tremendous progress in exploring and identifying many of the different species and strains of bacteria in the human microbiome. Now, a little historical overview. Bacteria were discovered several hundred years ago, and scientists like Louis Pasteur had a major impact on the development of microbiology and the study of bacteria. But Louis Pasteur was responsible for the gene ... Excuse me. The germ theory of disease. He solved most of the serious diseases of his time. He developed vaccines for them and taught people how to avoid them or limit their problems. He was a global rock star in his lifetime because he solved most of the common diseases of his time. It would be similar if one person today solved Alzheimer's disease and cancer and diabetes and autism or something. It's amazing what he did, but he set in motion this germ theory of disease. For a couple of centuries, most people had the concept that germs or bacteria were bad. They're causing disease and we need to eradicate them. Well another thing that happened along the way is that the only way scientists could study bacteria was extract them from the body, put them on what's called a Petri dish on an auger plate that allows the bacteria to grow, and then they watched them and observed it. A couple hundred years, that's the only way we could study bacteria, but we've recently learned that over 99% of your bacteria are anaerobic which means they can't stand oxygen. For a couple of hundred years, scientists would extract bacteria, put it in the lab to look at it, but it would get exposed to oxygen and die. For several hundred years, we could not study over 99% of the bacteria in our microbiome, but the development of this incredible technology from the Human Genome Project allowed scientists to start to dive into this new area and sequence the genomes of the bacteria and start to learn what they are and how they function. That's what started to kind of explode the research into the human genome, the human microbiome. Also a very interesting thing happened. There's a thing that I refer to as the genome complexity conundrum. This is a fact that, when the human genome was sequenced, we found out that humans have about 23000 genes which is significantly less than scientists thought they would find, but the conundrum is that the common rice plant has around 45000 genes. Scientists are scratching their heads. How could we as evolved beings as we are have only 23000 genes and the common rice plant has over twice as many genes as we do? The answer to this conundrum is the fact that, although we only have 23000 genes, the bacteria in our microbiome have millions of genes. In fact, over 99% of the DNA in your body is the DNA of your bacteria. This starts to open up an understanding of how important it is to create and maintain a healthy population of these bacteria in your microbiome so that they are doing good work for you. Because if you have pathological bacteria, their DNA and their genes are creating bad compounds that cause inflammation and poison you and create all sorts of diseases. This ... We're starting to understand why it is so important to create and maintain a healthy microbiome because your bacteria in your gastrointestinal tract are controlling and regulating vast amounts of your health. Gazella: Well I have- Pelton: It's kind of a little overview for starters. Gazella: Yeah. I have to say I love that historical perspective because it provides the perfect backdrop for today's conversation. Thank you. It was very thorough. Pelton: Sure. Gazella: Now today, I'd like to focus on post-biotic metabolites because, as you have referred to in your recent presentation, this really is a new frontier in probiotic science. Remind us. What are post-biotic metabolites? Pelton: This is another fascinating area, Karolyn. It's just starting to be explored, but it's extremely important when it comes to microbiome science. [inaudible 00:06:39] say in my lectures and seminars the reason probiotic bacteria is important is because of the work they do. The work that they do is that their metabolic processes digest the food that you give them and break it down and, in turn, their metabolic processes produce a wide range of compounds that we're referring to as post-biotic metabolites. What's really important for people to understand is it's these compounds that the bacteria produce that regulate vast amounts of your health, not the bacteria themselves. We're shifting our focus a little bit from putting all our research efforts and all of our money into just identifying and naming different strains of bacteria. Now, we're starting to realize it's probably more important to identify what are the compounds that these bacteria produce, what are the health regulatory effects of these compounds, which strains of bacteria are more efficient and more effective at producing some of these compounds. That's the new frontier in microbiome science. Two months ago, I gave a presentation at the International Probiotic Association's annual convention in Miami. The title of my presentation was Post-biotic Metabolites: The New Frontier in Microbiome Science. This is what we're starting to explore and understand now. Gazella: Yeah. It sees like it's taking this science ... It's giving it a whole new level of complexity. Let's talk a little bit about practical things like what functions do these metabolites serve as it relates to the human microbiome and health in general. Pelton: Sure. That's a good segue here. I'm emphasizing these post-biotic metabolites. What do they do? Well they have a vast number of functions, and in fact, a very highly respected author and scientist in the microbiome arena—his name is Dr Emeran Mayer—wrote a book called The Mind-Gut Connection. In his book, he tells us that your bacteria with their millions of genes will digest your food and produce hundreds of thousands of metabolites. We're just beginning to understand what all these metabolites, these post-biotic metabolites are. Some of their functions, they have antiinflammatory activity. They adjust the acid-base balance in the GI tract. They have cell signaling capabilities. They have detoxification capabilities. They can directly fight and kill pathological bacteria. There's just a wide range of functions. Let me just mention one major class of these post-biotic metabolites. They're called short-chain fatty acids. This is a class of really important post-biotic metabolites produced by your probiotic bacteria. Since they're acids, short-chain fatty acids, they're weak acids, but they create the proper and optimal acid-base balance in the gastrointestinal tract. The optimal acid-base balance is just slightly acidic, but when people have dysbiosis ... That's the term for different types of gastrointestinal problems or you have gas or bloating or diarrhea or constipation or inflammation or pain or whatever. Dysbiosis is the term for these general conditions. When people have dysbiosis or gastrointestinal problems, the acid-base balance goes anywhere from 10 to 100 times too alkaline. If you're going to get the GI tract back to good health, you have to bring it from it's alkalinity back down to its slightly acidic condition, and these short-chain fatty acids produced by the probiotic bacteria readjust and create that optimal slightly acidic acid-base balance. Short-chain fatty acids also have antiinflammatory activity. If you have dysbiosis and gut problems, you've got inflammation. They'll help to dampen that inflammatory fire. Also another really important part of this in the story with the short-chain fatty acids is the fact that the cells that line your gastrointestinal tract have the most rapid rate of turnover of any cell in the human body. People don't realize this. Most people don't, but you create a whole new digestive tract every 6 to 10 days. It takes an enormous amount of energy for the body to continually generate these new cells in the lining of the gastrointestinal tract, and you do not get the energy to produce these new cells from your blood supply. The energy comes from short-chain fatty acids like butyric acid that are produced by your probiotic bacteria, these post-biotic metabolites. These are just some of the ways one class of post-biotic metabolites, the short-chain fatty acids, contribute to a wide range of health-related things related to your gastrointestinal tract. Gazella: Now, can you expand a little bit more on the mechanisms of action and how these metabolites kind of work on our behalf? I mean the short-chain fatty acids is a great example. Pelton: Sure. Again, there's a wide range of these different compounds, and so there's different mechanisms depending on what post-biotic metabolite the particular strain of bacteria are producing. This gives me a chance to emphasize a really important point, Karolyn. A healthy microbiome is a widely diverse microbiome. By diversity, I mean a lot of different types of probiotic bacteria. It's not enough just to have high numbers but only a few different types. You want to have lower numbers but a wide range of different types of bacteria. If you have diversity of bacteria, you'll have a lot more bacteria producing different types of health regulatory compounds, and the way to create a diverse microbiome is to consume a diverse diet. You have to consume a wide range of different high-fiber foods because these are the foods that your bacteria require. The fibers in multi-colored vegetables especially, that's the number one food group for your probiotic bacteria. Then there's also multi-colored vegetables and various other types of foods that are high in fiber, but our human body cannot digest these fibers. They go through your system into your colon, your large intestine, and that's where your probiotic bacteria start to digest them. That's the food for your probiotic bacteria. Yes, it's important to take probiotics, but you have to learn how to feed your probiotic bacteria well. If you don't, they will not thrive and survive. Here's a couple of examples of some other mechanisms and how they work on our behalf. Some probiotic bacteria produce a wide range of compounds called antimicrobial peptides. Scientists just abbreviate these as AMPs, but antimicrobial peptides are very small amino acid chains or I describe them as small fragments of proteins. They specifically have antibiotic effects, but they have a narrow range of effectiveness. They are only damaging to pathological bacteria. They don't harm your good bacteria whereas prescription antibiotics are called broad-spectrum. They kill everything, your good and your bad, but the natural antibiotics produced by your microbiome and your probiotic bacteria as antimicrobial peptides are only going to function or be active against pathologic organisms. It's an important part of your immune system. These natural antibiotics being produced in a healthy microbiome are sometimes suppressing the growth of any bad bacteria that happen to be resident in your gut. Another example, there's lactobacillus fermentum ME-3. It's a very unique strain of probiotic bacteria that synthesizes glutathione. Glutathione is a post-biotic metabolite of that particular strain of probiotic bacteria. I could go on and on. There are many different types of post-biotic metabolites. Just a couple of general classes, your probiotic bacteria are little chemical manufacturing plants. They make all the B vitamins and Vitamin K and some of the critical amino acids. They make some of our most important nutrients. That's really a source of some of our nutrition. That's a little overview of some of the things and some of the ways that some of these other post-biotic metabolites are helping us. Gazella: Yeah. Those are some great examples. I have to say, when I knew that I was going to talk to you about this topic, I jumped online to do a literature search and I was actually quite surprised at the amount of research specifically about post-biotic metabolites. Can you tell us about some of the more recent studies that you have enjoyed reading about in the scientific literature? Pelton: Sure. Well I'm very excited having learned that a strain of bacteria called lactobacillus fermentum ME-3 can produce glutathione. Glutathione is one of the most important compounds in the human body. We call it the master antioxidant. It's produced in every cell in your body, and glutathione probably protects more of your body than all the other antioxidants combined. Glutathione also is the master regulator of all your detoxification. Being able to boost your glutathione levels by taking a strain of probiotic bacteria everyday is really a breakthrough in health and medicine. That's a pretty unique, new understanding of one particular strain of probiotic bacteria. Another thing that's very exciting to me is that, last year in Japan, there was some independent research done on Dr Ohhira's Probiotics which is a brand of probiotics that's produced in a fermentation process that's different than all other types of probiotics on the market. The fermentation process used in the production of Dr Ohhira's Probiotics allows the final product to contain over 400 post-biotic metabolites. This is a real interesting, new viewpoint and insight into how probiotic bacteria work where you've got a probiotic, Dr Ohhira's Probiotic by brand name, that's produced in a multi-year fermentation process -- and I'll explain that in just a moment -- but the end product contains 400 of these post-biotic metabolites. Let me explain this fermentation process and how these post-biotic metabolites are produced. We start out with big fermentation vats in a sterile warehouse. They start out with 12 strains of probiotic bacteria. Then they, at seasonally appropriate times, harvest and shred dozens of different types of organically grown foods: mushrooms, vegetables, seaweeds, fruits, and so forth. Then the bacteria get to grow and digest and ferment these foods for 3 years before the product is ready for encapsulation. During that 3-year fermentation process the bacteria in those fermentation vats are breaking down the food and producing this wide range of post-biotic metabolites. With Dr Ohhira's Probiotics, we are not so much impressed by the probiotic bacteria we're delivering. We're really focusing on the delivery of these post-biotic metabolites. We get what we call rapid microbiome restoration because we're not just supplying somebody with bacteria in a capsule. We're directly delivering these post-biotic metabolites. Other companies that supply probiotics, you have a capsule with bacteria in it. Those bacteria haven't done any work yet. It's like a starter culture. When you take those bacteria, they have to go into your system, start to try to find the proper foods that they need so that their metabolic processes can begin to start to produce some of these post-biotic metabolites that are responsible for improving the health of the gastrointestinal tract. But with Dr Ohhira's, we're directly putting in over 400 post-biotic metabolites. We quickly readjust the acid-base balance and suppress inflammation and start to heal the leaky gut or intestinal permeability problems and have some detoxification capabilities and start to work against some of the allergies that might be present in the GI tract. It's a very fast, rapid way of addressing gastrointestinal problems. Gazella: Yeah. I'll disclose to our listeners that I actually have been taking the Dr Ohhira brand of probiotics for a lot of years actually now. I have been impressed with the product. You're telling me something very, very new though. I had no idea about the 400 post-biotic metabolites and this delivery of all these post-biotic metabolites. I've always loved the fermentation process and all the organic foods that are put in there in a 3-year period, and there's just so much that I love about the product. This kind of adds a new level of complexity to this particular product. I'd like to stay on the Dr Ohhira product just because I always like to clarify dosages and ... Now, how many strains, again, are in the Dr Ohhira product? Pelton: There's 12 strains that we use to start the process, but again, I want to kind of emphasize that our product is really what we call a complete microbiome product because it doesn't just have probiotic bacteria. It's got probiotic bacteria plus some of the prebiotic food supply that was present in the fermentation process, and most importantly, it's got this wide range of post-biotic metabolites. We just redesigned the packaging for Dr Ohhira's Probiotics, and on the new package, there are 3 different arrows that go in a circular direction. The 3 individual areas, the words inside the arrows say probiotics, prebiotics, and post-biotics. The post-biotic arrow is right front and center on the package. We're trying to emphasize to people the importance of this topic of post-biotic metabolites and Dr Ohhira's specifically delivering post-biotic metabolites. There is no other probiotic in the world that we know of that is produced in this multi-year fermentation process that allows the direct delivery of post-biotic metabolites. Gazella: So as a result, do you dose this differently than you would a typical probiotic? Am I able to maybe use less? How do you handle the dosing of this? Pelton: Sure. The recommended dosage is 2 capsules daily. I'll give just a little recommendation on some other uses of it. If people have food poisoning and it's very common when people travel, get some bad food, and get sick pretty quickly, then I advise them to bite and squeeze the contents out of Dr Ohhira's and swallow it that way because the capsule in Dr Ohhira's is a patented delivery system where the capsule actually stays hard in the harsh acid environment in the stomach and then it becomes porous in the more alkaline pH in the small intestine. So it preferentially releases the contents in the small intestine. But if you've got food poisoning, if you've got bad bacteria directly in your stomach, you want to bite the capsules, squeeze the contents out so it gets directly into your stomach and start to fight the bacteria locally in the stomach. I have people who chew 5 to 10 capsules and do it every 20 or 30 minutes, and it clears food poisoning out very quickly for most people. Another thing to emphasize is that, in the fermentation process, the bacteria learn to grow and thrive and survive at room temperature. Dr Ohhira's does not need to be refrigerated. That's a very nice user-friendly part of Dr Ohhira's. Also because of this patented capsule design, you don't have to worry about food. It can be empty stomach, can be with meals, after meals, makes no difference. Main thing is everyday get them in. If I'm working with somebody that has Crohn's disease or colitis or irritable bowel syndrome, some of these really serious GI problems, I personally suggest they try taking 5 to 10 capsules daily, maybe 5 capsules twice a day for a period of 10 days or longer until you start to get improvement because you want to power these post-biotic metabolites and start to accelerate the change. Some relatively new information, SIBO is a condition that is getting a lot more press these days, becoming more recognized as a fairly widespread condition. SIBO stands for small intestinal bacterial overgrowth where you have bad bacteria that normally reside in the colon, but they backed up into the small intestine and then they digest foods there. They're in the wrong location in the GI tract. They produce a lot of gas and bloating and diarrhea. So a lot of people with SIBO can't tolerate probiotics, but with Dr Ohhira's Probiotics, we're not primarily delivering probiotic bacteria. We're delivering the post-biotic metabolites. Many people on SIBO will find that Dr Ohhira's is very helpful. Gazella: Interesting. An interesting note too, it doesn't taste bad. I've actually opened up the capsule and put it on a little part of my gum. Pelton: I'm glad you brought that up, Karolyn, because that's another recommendation I make. There are a couple of dentists that make this recommendation, and I myself do it personally. Several nights a week at bedtime, I will take one capsule and bite it in my mouth and squeeze the contents out and swish it around in my mouth before swallowing it. This helps support a healthy oral microbiome. It helps to suppress gingivitis and periodontal disease and things like that. We're not calling it a treatment for these conditions. You're just trying to support the health of your oral cavity and a good healthy oral microbiome. Gazella: Yeah, absolutely. Probiotic supplementation and probiotic science has really come a long way. There was a time when we thought that all you had to do is eat a little yogurt and you're good to go. Then there was the exciting research regarding prebiotics and synbiotics. Now, there's this topic of post-biotic metabolites. What does the future hold when it comes to this exciting area of study that seems to be moving quite rapidly? Pelton: Well I think the future is in post-biotic metabolites because ... In fact, even pharmaceutical companies, drug company industry is starting to look at post-biotic metabolites and realizing that there's potential for them to develop new drugs on these naturally occurring compounds that are produced by your probiotic bacteria. These are compounds that are natural to the human body. It's not like they're putting a foreign chemical into your body. As I mentioned earlier, Dr Mayer, in his book The Mind-Gut Connection. He's telling us that your probiotic bacteria produce hundreds of thousands of metabolites. I think the future will be less emphasis on just trying to name and identify strains of bacteria, but learn more about what are the compounds, what are the post-biotic metabolites that these bacteria make, what are the health regulatory effects of these compounds, which bacteria are more efficient at producing these compounds. I think that's really the new area, new era, new frontier of microbiome research. It really is very exciting because we're really starting to understand that the microbiome is the foundation of your health at all levels. There's a physician by the name of Alessio Fasano who discovered the primary cause of leaky gut and intestinal permeability which happens when you have inflammation, it opens up your tight junctions in your GI tract and allows toxic things to leak into your system. Dr Fasano says that 2 main causes of inflammation and leaky gut are gluten and bad bacteria. I recommend that everybody be on a gluten-free diet. Then we need to clean the gut up. I did a presentation a month ago at the American Association of Antiaging Medicine Conference, and my topic was Natural Therapies for ADD and ADHD. One of my primary messages is scientists are looking for the answers for autism and ADD and ADHD in the brain. Don't look in the brain. The answer is in the gut. We have to heal the gut and heal this intestinal permeability problem because if you have leaky gut, you have leaky brain. We mean your blood-brain barrier is leaky and some of these toxins are getting into your brain. You have gut inflammation. You have brain inflammation. We have to focus on the gut, and one of the most serious worldwide health dilemmas right now is the rapid rise in antibiotic-resistant bacteria. Many of the people listening to this probably are familiar with MRSA, methicillin-resistant Staph aureus. There's hardly any antibiotics that are effective against it anymore. Now, we've got antibiotic-resistant [inaudible 00:29:33] and antibiotic-resistant tuberculosis on the rise. We have to understand that we have to reduce our reliance on antibiotics and increase our reliance on good bacteria. We need more bugs, not drugs. The rise of antibiotic-resistant bacteria is a global health crisis, and you don't want to have a weak immune system and wait until you get sick because scientists are talking about a post-antibiotic era where antibiotics are not going to be effective anymore. We won't be able to have Cesarean births and we won't be able to have our appendix out or our teeth cleaned because, if you get an infection, you're dead. The answer to the problem is to have a good healthy diet with lots of fiber-rich foods to create a diverse microbiome which gives you a healthy immune system. That's the way to stay away from all these antibiotic prescriptions. That's my little rant on that topic. Gazella: No. It makes a lot of sense. I have to say that human microbiome research is fascinating and so important. This new research on post-biotic metabolites resulting from probiotics just really adds a lot to the conversation that we need to have about -- excuse me -- the human microbiome. Don't you agree? Pelton: I agree totally. I think this is the next level of understanding of how and why the microbiome is important and gives people a little bit more insight into why it's so important to learn how to create and maintain a healthy microbiome so you can have many different types of bacteria producing all these health regulatory post-biotic metabolites so that, in turn, you will have a healthy immune system. Gazella: Absolutely. Well this has been a great interview with a lot of great, important information. Once again, I'd like to thank the sponsor of this interview who is Essential Formulas Incorporated. Thank you, Dr Pelton, for joining me today. Pelton: My pleasure. Nice to be with you, Karolyn. Gazella: Have a great day. Pelton: You bet. Bye-bye.

This paper is part of NMJ's 2018 Microbiome Special Issue. Download the full issue here. In this interview, naturopathic physician and probiotic expert Donald Brown, ND, discusses the role of probiotics in supporting the gut microbiome. Brown also describes the mechanisms of action and clinical applications of probiotics, as well as strains, dosages and potential contraindications. About the Expert Donald J. Brown, ND, is one of the leading authorities in the USA on the safety and efficacy of dietary supplements, evidence-based herbal medicine, and probiotics. Brown currently serves as the director of Natural Product Research Consultants (NPRC) in Seattle. He is a member of the Advisory Board of the American Botanical Council (ABC) and the Editorial Board of The Integrative Medicine Alert. He was a member of the Board of Directors for the International Probiotics Association (2008-2010) and its Scientific Advisory Board (2006-2008). He has also previously served as an advisor to the Office of Dietary Supplements at the National Institutes of Health. Brown is the author of Herbal Prescriptions for Health and Healing (Lotus Press, 2002) and was a contributor to The Natural Pharmacy (Prima Publishing, 2006), the A-Z Guide to Drug-Herb-Vitamin Interactions (Prima Publishing, 2006), and The Textbook of Natural Medicine (Churchill Livingstone, 2006). About the Sponsor Founded in 1979 by molecular geneticist Stephen Levine, PhD, Allergy Research Group® is one of the very first truly hypoallergenic nutritional supplement companies. For nearly 40 years Allergy Research Group® has been a leading innovator and educator in the natural products industry. Our dedication to the latest research about cutting-edge nutritional supplements continues to this day. Our purpose is to provide customers with products they can use to improve their patients’ quality of life, through scientific based innovation, purity of ingredients, education and outstanding service. ARG is proud to be a sponsor of the Clinical Education LinkedIn Forum, a closed peer-to-peer group on LinkedIn where healthcare professionals can ask clinical questions and receive evidence-based and clinical-based responses by experts in their field. Visit www.clinicaleducation.org/linkedin for more information & to sign up for free! Visit www.allergyresearchgroup.com for more information on ARG and our products. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we are exploring the impact that probiotics can have on the gut microbiome. Before we begin, I'd like to thank the sponsor of this topic who is Allergy Research Group. My guest is naturopathic physician and a leading probiotic expert, Dr. Donald Brown. Dr. Brown, thank you so much for joining me. Donald J. Brown, ND: Hi Karolyn. It's a pleasure to talk to you. It's been a long time. Gazella: I know. Brown: How are you? Gazella: I'm doing great. I know. This is like old times. And you know, before we dig into this topic, I have to tell you that I am just fascinated by the human microbiome, and it seems like the research in this area has really exploded. Why is that? Brown: Well, I think, again, it's ironic as a naturopath talking about it because we've always talked about the impact that the intestinal tract has on health in general. Immune health, skin health, so forth and so on, and I think that what's happened is that particularly probiotic research has led us to realize that there's these microbes on our body. And we have a tendency in probiotics to focus on bacteria, but what's exploding in this area is that we have resident microbes that are viral microbes. We have fungal microbes that are natural inhabitants of our body. So looking at this, we're really talking about 40 trillion microbes, predominantly bacteria, and sort of the balance that we have with these microbes which are part of our body. And it's funny because the research [inaudible 00:01:54] dramatic, and we have 10 times more microbes on us and in us, mainly in us, than we have cells. And the new data is really indicating that that's not the case; it's about 1.3 to 1. So people who get itchy when they think that they have more bacteria on them than cells, it's not quite as dramatic as we thought. Again, I think it gets back to the fact that we're recognizing the fact that these things play such an interesting part in our health and our wellness, and when it tips in the wrong direction, our illness too. So expanding it out so we're not just looking at the microbes in the GI tract, but the microbes in other parts of our body as well. Gazella: Yeah, I think that's really some of the most interesting parts of this research is that it does expand beyond the intestinal tract. So as it relates to the human microbiome, remind us of the mechanisms of actions that probiotics have. How and why do probiotics even work? Brown: Well, probiotics ... When you think about the GI tract, the analogy I like to use, especially when I'm talking to the public ... talking to healthcare professionals here ... is it's sort of like a busy parking lot. And you have organisms that are health promoting, and then you have organisms that are potential pathogens, and they're looking for parking spots. Remember that bacteria ... viruses are the same way ... have to adhere to cells to be able to be either health promoting or disease promoting. So that's one of the first things that probiotics are doing is they're competing for spots. And once they actually set up house, they then start creating a micro-environment that is inhospitable to potential pathogens, producing things that are anti ... compounds that are antimicrobial. They alter the pH slightly to make it inhospitable for these microbes and really create a situation where, "Hey, this is our home. This is our neighborhood, and you're not welcome here" kind of a thing. The other thing that should resonate with most of the doctors on the phone is the whole idea of leaky gut and intestinal barrier function, too. It's one of the things that probiotics do once they set up house is they're also helping to produce mucin and to sort of keep those tight junctions in the intestinal tract, the cells healthy and intact. And that's very, very important. The other thing that they do is they also, in the colon, are producing short-chain fatty acids which are associated with reducing risk of cancer as we age. Production of short-chain fatty acids act to help with digestive health as well. And then one of the really interesting things that's really been discovered over the last, I would say, eight to 10 years, is that when these little bacteria actually bind, they're communicating through the intestinal wall with what are called dendritic cells which are funny-looking, little, sort of odd-looking starfish type things that send little feelers up through the ... into the epithelial cells. And the probiotics are actually communicating with them to sort of modulate the immune system. So they produce a little bit more of this, produce a little less of this. Inflammatory responses are also modulated through it. And then the last thing and one of the really, really interesting things right now is we're beginning to realize that the intestinal tract is communicating with the brain. So the gut-brain axis is what that's called, and we know that stress, for instance, can actually negatively impact the probiotics in the GI tract, the healthy bacteria in the GI tract, and in turn, through the vagal nerve going up to the hypothalamic-pituitary axis, actually modulates that response. So we're now finding out that probiotics may actually be involved in ... I'm sure you've done interviews where you talk about the HPA axis and stress response. We're now finding out that the GI tract is very, very directly involved in that. So it could be negatively impacted by stress but can also positively impact the HPA axis, which is a whole new mechanism of action which is wild. So we've got gut health, digestive health. We have immune health based on responses with the GI tract. Now we're finding out that there's actually effects on mood, stress response, that sort of thing. And that's not even covering the female genitourinary tract which has its whole population of probiotics that are positively affecting genitourinary tract health as well, so it's big. It's a vast influence on the body. Gazella: Yeah. There is a lot going on here with probiotics. I think that's why I like the topic so much because there's just so much to talk about. So when we're looking at the scientific literature and the research, what conditions have the most compelling research in terms of improved outcomes? I realize that this may be a pretty long list, given the mechanisms that you've just described, but take us through that list from a research perspective. Well, I think what I like to do is I like to start with the things that are accepted by the larger medical community. And one of those is the fact that we've known for a long time that probiotics have a positive effect on prevention of antibiotic-associated diarrhea. So I would put that probably at the top of the list of, hey, if I'm in a room and I've got people who are skeptical of alternative medicine, integrative medicine, that's always a good starting point because we have really solid data that antibiotics definitely are good at preventing that. My background is in pediatrics, and I think another area that has sort of reached a critical mass is actually ... it's fascinating ... is the prevention of atopic dermatitis in children who are potentially at risk. The studies started ... First one was in the Lancet in early 2000s, and basically the studies are looking at mom particularly but also whoever the partner is, and risk of ... that have a background of atopic diseases, allergic diseases, and actually starting to give mom probiotics during the second half of her last trimester. And then once the baby is born, if mom's nursing, continuing to give the probiotics to the mom until she stops. And then, anyway, it varies on the study, but usually then the infant starts to take the probiotics. What they're finding is that it's reducing the incidence of atopic dermatitis by about 50%. That's amazing to me because if you look at sort of tracking the use of the antibiotics in children on a graph and you look at the increase in atopic diseases, so you're looking at eczema, atopic dermatitis. You look at asthma. They track almost exactly if you look at from 25 years ago to now, they track almost exactly. And also cesarean births contributing to that as well where the microbiome, so that's really fascinating to me. I would say the other area, sort of shifting gears, that I think has reached a critical mass is also adjunctive use of probiotics in female genitourinary tract health. So treatment using standard treatments for things like bacterial vaginosis would probably be the top area, but also prevention of recurrence of urinary tract infections. We're, particularly in the bacterial vaginosis area, I think really reaching a point where we have enough data to sort of suggest that, hey, using these things really can help with prevention. And then I would probably put the last one, as we move into the immune system and we really have reached a critical amount of data. Not a lot of pediatric data but adult data now that suggests that routine use of probiotics seems to reduce the incidence of upper respiratory tract infections. So, again, I could go on and on and on. Gazella: Right. Yeah. Brown: There's a lot of stuff. There's a lot of stuff that's emerging and that we're sort of on the edge. But one of the things I think the listeners need to know about is the fact that I think we like to think about alternatives too, but one of the great things about probiotics is that adjunctive use. Obviously it's antibiotics, but Helicobacter pylori, for instance. The standard treatment of that is very rough on people. Recurrence rates are really high, so one of the themes that I always like to talk about when I talk in my lectures to healthcare professionals is that remember that a lot of the treatments that we use for ... Let's take urinary tract infections. E coli are really good at setting up what are called biofilms that are these little bits like taking a Visqueen sheet and putting it over themselves so that you can get to use the antibiotics. You can get to the ones that are not underneath the protective shield, but the ones that are under there don't get affected. So one of the things that probiotics are great about is going in and helping to break up that biofilm and actually make standard treatment perform better, and then continuing to use the probiotics actually reduce recurrence rates. So, and there's reduced recurrence rates, and there's a whole litany of examples of areas where if we use probiotics. I mentioned helicobacter pylori but also UTI's, bacterial vaginosis, where probiotics actually help the treatment go better, outcomes are better, and then really reduces recurrence rates. Gazella: Yeah. That's such a good point and you know, you mentioned antibiotics and how they disrupt gut flora and how probiotics can help reverse that dysbiosis. Are there other medications that kind of do the same thing as antibiotics where they disrupt that gut microbiota diversity and that probiotics may be able to help reverse that? Brown: We're thinking that some of the more aggressive inflammatories that people take may have an affect. That's still sort of in the early phases. One of the early ones, interesting ones that there's still a limited amount of data, but I actually reviewed it, was a study with a proton pump inhibitor, so things that we're using for reflex and that sort of thing, having a very negative effect on the microbiome. So, we're sort of still in the early stages of learning what specific drugs and the effects are. Obviously antibiotics would the be the easiest case study, because we can actually look at the what affects. They've done studies with people who are getting the triple therapy for helicobacter pylori and realizing that during that therapy, the healthy bacteria in the G.I. tract can be reduced by as much as 80%. If we use probiotics, during that treatment, it reduces that to 40 to 50% and then if we continue to use it after, people tend to bounce back quicker. There are other drugs that we know are beginning to emerge that have negative effects, but stay tuned on that one. Gazella: Right. Right. Now, let's switch gears and talk little bit about strains, because I know that that's a hot topic. So, specifically for the conditions that you mentioned in helping to restore gut microbiota that's been disrupted by medications like you were just talking about, what are the more common strains used for these types of clinical applications? If you don't mind my backing that up, I am very, very disturbed when I hear people lecturing who say that strains don't matter. I go to a lot of international conferences. I sit on committees that set standards, international standards for probiotics and it is something that experts who know a lot more about this area than I do are upset about, because there are people out there who are saying that it's species specific and strains don't matter. I beg to differ. I think that it's very, very important that health care professionals realize that, particularly health care professionals realize that ... and Karolyn, you've known me for a long time. We've done interviews about [bontanical 00:16:20] medicine that I'm an evidenced based person. I like to see the ... particularly if we're talking about treating a condition. And so when we go from species level where there's very little research to strain level, we emerge into an area where we know what the dosage was, that was used in the study. Particularly when we talk about pediatrics, we talked about people who might be immune compromised. We talked about older folks like myself. It's important also to ... safety is pertinent too and that's one of the areas that is a little bit of a red flag for me with the whole probiotic area. Particularly on the commercial side where we have this race to do all these different things and some of the species level stuff that's being sold has not been clinically studied. And so, very, very important that people realize that some of the standards that go around a strain or viability is the lack of bacillus or the bifidobacterium strain that you're using shown to be viable. Does it actually adhere in the intestine is one of the things that we now have the ... within the persons body, but we now have technology that can actually show that these things sort of do adhere, and how long they adhere, and how long they stick around. Another thing that's really important that I've given many lectures to health care professionals is they don't think about is that we also don't want these strains, what's called trans located, we don't want them to go from the intestine to the blood stream. And they're having case studies. There was a paper published a number of years ago on people who were really severely immune compromised where the probiotic that was being ... it was a specific strain actually trans located into the blood stream and caused sepsis. People then had to be treated with very aggressive antibiotics. So, we don't want them to go from the intestinal tract into the blood stream. Another one that's [inaudible 00:18:39] ... we're talking about antibiotics, I always chuckle when I remiss on this one is also we realized that hey, probiotics are good for people who are taking antibiotics, but we also want to be sure that the probiotics strain has been tested for not blocking the ability of the antibiotic to do it's job. So, it's called antibiotic resistance. And it can be transferable. They have run into organisms that we think are probiotics that actually have a negative effect on an antibiotic doing it's job, so that's important. I already talked about safety and efficacy. I'm all about that. A silly one that I just want to toss in that's talked about internationally, that I still bump into in the U.S. more so than in other areas is the fact when we talk about being a probiotic supplement, we want to look at the label, and we want to be sure that these stability, or the shelf life of the product is actually been proven to the time expiration. There are still a lot of probiotic products that are sold in the United States that actually declare their potency at the time of manufacture, which is like, well okay, but I have a vitamin C product. They told me the potency when it was manufactured, but it says it has a two year shelf life. Have they actually tested that? Has that actually been proven? And so, remember, these are living organisms. Very, very important that stability or shelf life be proven for these as part of the choice of picking a supplement.  Gazella: Well, I was just going to say, do you have some go to strains that you like to focus on when it comes to recommending probiotics? Brown: I think there's a lot of them right now, actually. That's another area where we could probably go on and on about. There are what I like to call legacy strains that have been around for a while that have a lot of research on them that have ... and we also understand their mechanism of action really well. The one that people probably know the most is lactobacillus GG, which is a rhamnosus strain that was discovered by a couple of guys in Boston. I always like it when they give their own name to the strains. It was Gorbach and Goldin I think were their names, so they named it lactobacillus GG. But anyway, that one has been around for a long time. A lot of really, really excellent research. Some of the bifidobacterium strains from Japan from [Morinaga 00:21:24] is the name of the company, have a lot of research, particularly in the pediatric area. Been around really since the ... lactobacillus GG, since the early '60's, the Morinaga [inaudible 00:21:38] really since the '50's. The Japanese were doing isolation in human studies long before we were doing them here in the U.S. Brown: Another one that I really like is lactobacillus acidophilus DDS-1. It's an interesting strain that was discovered by a guy named Dr. [Shahani 00:21:56]. By the way, all of these strains that we're talking about are derived from humans. These are human derived strains and this one was actually discovered and isolated first in 1959. And like the lactobacillus GG and some of the Morinaga strains has a lot of clinical research. It also ... in vitro research that shows that it adheres, that it survives. And then human trials, actually looking at it's ability to treat things like travelers diarrhea, prevent antibiotic associated diarrhea, those sorts of things. When I look at products, I always look at what's the indication? What's been studied? There's commercial strains the lactobacillus, I'm sorry rhamnosus HN001, for instance, in the atopic dermatitis prevention area that has phenomenal studies. And so there are a number of strains out there that have reached that critical point of whether its specific to one condition or have been looked at in other areas that have really excellent data. And again, being somebody whose background was in pediatrics, I'm always also looking at what's your safety data as well. That would be an example of a few strains that I think have really excellent data. Gazella: Yeah. That's good. And you know, not that long ago, we were seeing maybe just one or two species, one or two strains. Now we're seeing multi species, multi strains in these formulations, sometimes six, nine, twelve different species or strains in one formulation. Is that a good thing? Brown: Sometimes it's a commercial thing. Here's my theory and I could easily be misproven [inaudible 00:23:58], but or unproven. Are you misproven or unproven? Which- Gazella: I'm not sure. Brown: Called out for my lack of proof. My answer to that, when I get asked that, and it's more common when I'm lecturing to the public or to managers of supplement sections is that probably for wellness purposes. So if I'm taking a probiotic or if I'm a doctor and I'm recommending a probiotic supplement to be taken daily, I probably would use something that's a little bit more of a multi strain. Sort of a balance between the lactobacilli family and the bifidobacterium family. That's a sort of my go to. And as you get into the senior population, seniors have a tendency to have a drop in the bifido. That's probably dietary related, because fiber and that sorts of things, they like to feed on ... They're probably eating less fiber in their diet. But anyway. Having a balance of a number of strains, is there a magical number of strains? I don't think so at this point. I don't think anybody's proven that. I think the difficulty ... what I say to people is, is that when you shift, it's much easier to talk about a single strain or a combination of a couple strains. You know, in irritable bowel syndrome, inflammatory bowel disease, BSL-3 has eight different strains in it. I mean, that's a lot of strains. It's been around for a long time. They use very high doses, but its easier to look at disease endpoints when we do a clinical trials, because we have very clear outcomes that we're looking for compared to what's a placebo, for instance, Wellness studies are really hard to do, so I don't know that there's an easy answer to your question because I don't know if the company after I ... know a lot of them, and some of them have a lot of ... have deep pockets. I don't know who's gonna do a wellness study that shows that, "Hey, if you do this many strains at this potency, that it works better than if you only do one strain at this potency, or if you do nothing." 'Cause those are expensive studies to do. Gazella: Yeah. Totally. And I'm gonna ask you another unfair question, and it's regarding dosage. You know that can be somewhat controversial, still debatable. How do you dose probiotics or recommend ... What's your philosophy on the dosage? Brown: Well, I always start with what is the clinical. If I'm treating a specific condition and I'm using an evidence-based strain I dose it at the dose. And it's interesting, 'cause there's extremes and that's one of the issues when we look at meta-analyses that have been done, so stuff like say, not only was there this cacophony of strains that were used, going from one strain to five strains. That sort of thing. But the dose, the potency and we measure the potency of probiotics, what are called colony forming units so we talk about milligrams or gram amounts of these things. So I always try to look up with what the research showed. Again, leading back to wellness and sort of, regular use. I have a patient who's take a multi-vitamin, who's taking fish oil every day and I say, "Hey, one of the things you should think about is keeping your intestinal tract healthy and probiotics are gonna contribute to that, keeping your immune system healthy." I don't have an easy answer for that. I typically use multi-strains and I'll probably usually go in the 10 to 50 billion CFU per day. Is that correct? Is there clinical data to back that up? The answer is no, I don't know for sure. But that's sort of how I think. The one thing that I can tell you is that I remember a client who decided to go high potency and high potency is definitely [inaudible 00:28:23] was like 25 billion CFUs per instance, it was like a shot across the balance. It was 12 years ago. And I'm freaking out because [inaudible 00:28:33]. You can't go run 5 billion CFUs per day or people gonna be having a [inaudible 00:28:41] reaction or getting thrown out of dinner parties 'cause they're farting and having to go to the bathroom all the time. So what I can tell you is that we have enough data now in healthy people that if we go to, even, 100 billion CFUs per day that we're not seeing any adverse effects. We're usually with this ... How much of that is actually ... adhering how much of it is actually having an impact versus 40 billion, 50 billion or even 10 billion for that instance. So that's another one that's gonna be interesting to see how that evolves. There's obviously, particularly on the retail side in this race to see who can come out with the highest potency with most strains and we'll see how that goes. Gazella: Right, yeah. Well, I think that was a difficult question and you answered it brilliantly. So now it seems like many probiotics on the market are actually synbiotics because they combine pro and prebiotics. Now, what's your view about this combination and why are more companies going in that direction? And am I right, are companies going in this direction? Brown: Well, here's my criticism of that and I like synbiotics. I think the whole concept is an interesting one. On the retail commercial sense, it's been difficult for consumers to wrap their head around a probiotic and then also there's this concept called prebiotics and then again for people who are listening, a prebiotic is basically something that acts as a food for probiotics to feed on and grow and encourage growth even on their own. The issue that I have with a lot of products that combine probiotics and prebiotics, whether it's FOS, GOS, XOS now is another one that's used. Now these are basically complex sugars. Really, for all intents and purposes, kind of fibers. All of the FDAs now said that they are probably not gonna qualify to make the cut. The problem is that if you look at the studies on the prebiotics, the dosages are way higher than what you're gonna put into a capsule. There are some probiotic products that I've seen that have ... that are powders or that are in the sachets where you can actually get the prebiotic up to a dose that actually has any meaningful effect clinically. So remember with prebiotics, we're rack out a low of a gram and many of the studies were as high as 10 to 15 grams. So again, really important to sort of ... And I know this is a challenge for people who are in clinical practice because they're trying to treat some patients with what they think is the best, but it's really an issue of, again, getting back to sort of ... Does the company make an attempt to sort of match up the dosage of the prebiotic that actually showed an effect, a positive effect on probiotics? And that's a challenge. That your delivery yet [inaudible 00:31:50] in capsules, it's under dose. You don't get enough of the prebiotic. Gazella: Yeah, that's really interesting because I was not aware of that. So, that's a good heads up there. Now you talked about safety, but are there any contraindications that clinicians should be aware of? Direct contraindications that says, "This patient should not be on probiotics"? Brown: The area that I'm most cautious about ... I used to think it was premature infants, very low growth weight infants, but there's been enough research. When you ask, probably why the other thing too, that would be our [inaudible 00:32:24] list of things that have really reached critical masses, prevention of what's called Necrotizing Enterocolitis and in very low growth rate entrance ... fascinating and it worked. It's basically saving lives is what we are talking about. The death rate from that is quite high. So used to saying, "Hey, these kids are born ... GI tracts not really developed." That's a potentially dangerous use in that population. The answer to that is "No, actually. It's actually good." I would still continue to encourage on healthcare professionals to be very selective in strains that they use in people ... HIV positive, AIDS, people with really severe immune deficiencies. Cancer patients who ... technically more advanced cancer. Be very selective and try to get to the best of their possibility, look at the data and say, "Okay, this is strain that actually was used in that population and works." That would not ... Those two populations are ... that collection of population severely immunocompromised people is not one that I could, probably just use any probiotic supplement. Particularly multi-strain, high potency without doing any sort of research. I'm very selective and usually do one strain or two strains in that population that I feel have enough safety data. Gazella: Yeah, that's good advice. Anything else that you'd like to add on the topic of probiotics for listeners that you'd like to leave them with? Brown: Again, I just think that it very, very important to first and foremost, and I'm repeating myself. First and foremost look at if you're using it for specific use. We didn't even get into female genital urinary tract health nursing. Really amazing stuff going on in that area. Your oral use of probiotics to actually, finding that they're populating in the vagina and that you're getting significant effects, which is amazing. We used to think you'd have to use everything with ... through a vaginal, pessary type of an effect. So that's it. I think again, trying as much as possible to deal with companies that are trying to ... that are working with strain suppliers or strain suppliers that are manufacturing products for them that are looking at the essentials that we talked about at the beginning. It's really, really important to me. And also again, trying to insist that companies refer back to the data on specific strains as opposed to just saying "It doesn't matter, you can use anything you want." I'm horrified when I go to professional lectures and I hear ... For instance, medical doctor getting up and saying that it's [inaudible 00:35:14]. So it goes against every thing that is accepted in the probiotic world. So, again, a lot of white noise in this area. Healthcare professionals are going to be as susceptible to it as consumers are but that's a couple of areas where I think you can sort of cut through that and try to get to what really has been shown to be effective and safe. Gazella: Yeah. I mean, it's a big topic for sure. We're going to have you back to dig in a little bit more deeply on some of these topics, but I want to thank you for definitely shedding some light on this important topic, and helping us get through it. And I'd also like to once again thank the sponsor of this topic, who is Allergy Research Group. So Dr. Brown, thank you again for giving us all this wonderful information and I hope you have an awesome day. Brown: Thank you Karolyn.

This paper is part of NMJ's 2018 Microbiome Special Issue. Download the full issue here. In this interview Natural Medicine Journal's editor-in-chief, Tina Kaczor, ND, FABNO, and Steven Sandberg-Lewis, ND, DHANP, discuss the integral role of the gut microbiota in mood and cognition. A review of how the gut and brain communicate through both the nerves and gut microbial metabolites is discussed. They also talk about how intestinal permeability and brain permeability are associated and what you can do about it. As a naturopathic clinician with over 40 years' experience, Sandberg-Lewis shares some clinically useful pearls along the way.  About the Expert Steven Sandberg-Lewis, ND, DHANP, has been practicing since 1978, teaches gastroenterology at National University of Natural Medicine and has a private practice at 8Hearts Health and Wellness in Portland, Oregon. He lectures, presents webinars and interviews on issues of digestive health. He is the author of the medical textbook Functional Gastroenterology: Assessing and Addressing the Causes of Functional Digestive Disorders, Second Edition, 2017. His column Functional Gastroenterology Bolus appears regularly in the Townsend Letter. Within gastroenterology, Sandberg-Lewis has special interest and expertise in inflammatory bowel disease, irritable bowel syndrome, small intestine bacterial overgrowth (SIBO), hiatal hernia, gastroesophageal and bile reflux (GERD), biliary dyskinesia, and chronic states of nausea and vomiting. He lives in Portland with his wife, Kayle. His interests include mandolin, guitar, writing, and lecturing. Transcript Tina Kaczor, ND, FABNO: Hello, I'm Tina Kaczor with the Natural Medicine Journal. I'm speaking today with Dr. Steven Sandberg-Lewis and our topic is the gut-brain axis. Dr. Sandberg-Lewis has been a practicing clinician for over 40 years now and he is the author of Functional Gastroenterology: Assessing the Causes of Functional Gastrointestinal Disorders, and that has come out in a second edition as of March 2017. He's also adjunct full professor at the National University of Natural Medicine. Dr. Sandberg-Lewis, thank you so much for joining me today. Steven Sandberg-Lewis, ND, DHANP: You're welcome. Kaczor: Alright, so I think our talk about the gut-brain axis is extremely timely because of the media attention now given to the bacteria and the effect of our microbiome on our physical ailments and I think it's beginning to look at how it effects the brain both cognition and mood as well. And so, what I'd like to do is really start at the beginning and can you just give us a quick overview of what exactly do we mean when we talk about the gut-brain axis? Sandberg-Lewis: Yeah, naturopathic medicine seems to always be at least 30 years ahead of the rest of medicine. We've been talking about this a long time but now we have a lot of research to back up what we talk about. So, the gut-brain axis probably has many more players than we're aware of but the ones we know about are, of course, the microbiota, a lot of people call that the 'microbiome'. But it's the bugs. About 100 trillion of them and they are, of course, not just in the colon but in the small bowel, in the stomach, which is not sterile and the oral and esophageal areas. The true meaning of microbiome is the genome of the gut floor which has way more, at least 100X more genes than the human genome, which is 26,000. And when you put the two together, you call it the 'holobiome', which is the human genes and the microbial gene. But really, you need to do that because they interplay so much and the bugs really control our genome so intensely. Then there's that whole genetic piece then there's all the, what we call the metabolon. What the bugs and the enteric cells make, all their metabolic products and that includes secretory IGA, short chain fatty acids, lipooligosaccharide, bacterial hormones and neurotransmitters and cytocinesis. We can talk about all those kind of details. And then of course there's the enteric nervous system speaking to the vagus and the vagus speaking back. And there's the HPA axis and then there's the immune system and the gut. So, it's huge. It's so much talk it's deafening crosstalk. Kaczor: It is interesting and one of the pleasures, I think, I've been practicing nearly 20 years and I know that you've been practicing over 40 eyras so, it's quite a long time to watch the evolution of thought processes in medicine as well as the population at large. And in some of the folk medicine even, naturopathic medicine, but good old folk medicine, an apple a day and staying regular and keeping the bowels moving, it's amazing how that comes back at us and now we're talking about it in scientific terms which is fascinating to watch the pendulum swing. Okay so, when we talk about how they communicate, you gave a little overview of some of the ways, when you mention the vagus system, what do you mean exactly? Sandberg-Lewis: On every new patient, I like to have them open their mouth, stick out their tongue, take a look at their palatal arch and their uvula and then have them say 'ah'. When they phonate, we've all done this, check the vagus nerve. The place you can check the vagus nerve directly is there in the palate because the levator palatini muscles on either side raise the palate when you say 'ah' and when you phonate. So, I'd like to see both arches go up symmetrically and not an asymmetrical rod. Occasionally you see nothing. The patient says 'ah', nothing happens. There's no palatal rise and you can have them do it over and over and nothing happens. So, that's a sign that the vagus isn't really firing the way it's supposed to and there are lots of ways to try and improve vegul tone. But that's a good thing to know about your patient. The next thing is the vagus nerve gets sensory information from the enteric nervous system and the neuroendocrine cells in the gut as well as the epithelial cells. It gets input in actually 90% they assume, 90% of the crosstalk is from the enteric nervous system to the Brian through the vagus. So, it's mostly the gut talking to the Brian and then the brain through the vagus talks back about 10% of the time. So, there's direct transmission through the nerves and then there's all the cytocinesis and other factors and neuro peptides that also speak through the humoral method. Kaczor: So, what you're saying is the gut itself is sending signals through the vagus nerve to the central nervous system and effecting what exactly? Sandberg-Lewis: So, yeah. It's pretty interesting what the gut is interested in talking about. Yeah, you wonder, what does my gut have to say? What does it care about? So, what the gut is saying, the 90% of impulse is going from the gut to the brain, it's talking about the shape and the consistency of the bowless of food moving through and scraping up against the ... rubbing up against the mucosa. The sheering forces of the bowless against the mucosa. That's stimulating serotonin locally but there's also this ... That's what the gut's interested in. Is, what kind of food is it, what's the shape, what's the consistency and what does it feel like as it rubs against the enteric cells? This seems to stimulate taste receptors on the antero endocrine cells that are scattered throughout the mucosa and give information about the composition of the food, there's, again, there's all these neuro peptides and hormones, GI hormones that are released as well. But directly through the vagus nerve, we think it's mostly the gut talking about it's scratchiness of the food and the size and the consistency and the kind of food. Kaczor: Okay. And I have to clarify for my own self, when you say 'taste receptors', you're going beyond the tongue? Is that what I hear you saying? Is this "taste receptors" that you say along the GI tract, how does that work? Sandberg-Lewis: Air quotes, well, our genius in our midst, Paul [Calmens 00:08:18], he's been telling me for years that there are taste receptors throughout the entire gut. And especially most pronounced is the bitter, bitter receptors. And I've tried to go into the research and find out what exactly they do. We don't know a lot about what they do but we know that bitter receptors are not just in the tongue and the mouth, they're throughout the whole gut and they seem to trigger the release when they're stimulated. They trigger the release of ghrelin and glucagon peptide one which have to do with blood sugar balance and hunger and my guess is, Flip Wilson used to say, "The devil made me do it" when he did something that he thought was nasty. But I really think that in many ways, the GI flora and the food that we eat interact to create cravings so that the body can get what it needs. And if you get more ghrelin, you get hungrier. And certain other, like GLP, maybe you're gonna create more sugar. It's really important, of course, to eat food ... I think this is why Indies think it's so important to eat foods that's close to nature because once you get these synthetically modified foods or their consistency and their flavor and their compositions is altered, it probably throws off these natural mechanisms that tell us when to eat, when not to eat, when our blood sugar is fine, when it needs to go up or down. So, these are really finely tuned things. Kaczor: Yeah, it's interesting in context, again, of traditional medicines because it automatically makes me think of Ayurvedic medicine and other traditional practices that naturally balance the flavors on the plate, that's a big part of making sure each meal is healthy in that tradition. So, let's talk about the microbiotas some more. You mentioned briefly that its metabolites are part of the talk between the gut and the brain, can you elaborate on that? Sandberg-Lewis: Yeah. First of all, I wanted to mention that the metabolic byproducts, the products of the microbiota, it's huge, it's huge. And Emerson Mayor's book, the gut-brain connection, he makes a quote that 40% of the metabolites in human blood are derived from gut flora, which blew my mind completely. And so, I said, "Where is he getting that?" And I looked, I found it in two or three different articles. And so, to me, that means 40% of our blood chemistry is derived from the intestinal flora. And that makes sense since there are at least 10-to-1 more of them than there is of us in terms of cells. But I never really put that together. So, there's these metabolites in our blood derived from the flora that do fine tuning of eating behavior, mod, blood glucose, digestive secretion, absorption, motility, just it's mind blowing. It's so important and it makes sense. You can understand that when you go ahead and even just take a broad spectrum antibiotic, we know that greatly increases the risk of kids and even adults, getting inflammatory bowl disease, especially Crohn's. Just so many effects on immunity and the balance within the body if we knock down the bacteria or alter them or decrease their diversity. So, pretty important, pretty major stuff that everybody's been messing around with since the 1920s and '30s with antibiotics. Kaczor: Mm-hmm (affirmative). Yeah and you mention a metabolite that caught my attention because I think it's at least in our naturopathic circles, we're paying a lot of attention to the role of that lipopolysaccaride and the LPS, for short. Can you talk a little bit about that? Because I feel like that's, as far as I can see, getting a bit of attention these days in how the gut and brain effect one another. Sandberg-Lewis: Yeah well, I'm glad it's getting attention, it deserves it. You know, every physician knows about LPS in one particular way and that is, it is the cause of septic shock. It kills people if the LPS is high enough. What we don't usually hear about and we're starting to get more and more research on is, what about physiological levels of LPS when it's not super high? Sandberg-Lewis: LPS is used in research, they inject it into lab animals to activate the NF kappa B pathway of inflammation and there's a tremendous amount of it. These are from the gram-negatives. The gram-positives also have an inflammatory precursor like this, which is the peptidoglycan. But, mostly we talk about the gram-negative because it's so potent and there were a million copies or so of LPS in each gram-negative microbe and it's not just something that gets emitted when the bug dies, it's also just when it's replicating or if you take an antibiotic and weaken it a little bit, they don't have to die to give off LPS. And it's thought that in the adult human gut, you have up to a gram of LPS, a thousand milligrams at any one time. So, it's a major player. There's a lot of it and it can trigger the Zonulin pathway, which leads to intestinal permeability, hyperpermeability, which we know is related to autoimmunity and allergies. Obese humans have up to a three fold increase in LPS compared to lean and maybe some of that also dove tails with the fact that obese adipose tissue has 10X as many macrofacies. So, you got a lot of esocine activity, a lot of TNF alpha. Kaczor: Mm-hmm (affirmative). Sandberg-Lewis: And different types of enteric flora have different amounts of LPS. Or even different potentiates. So, antero bacter are thought to have some of the most potent LPS that can be up to 1,000X more potent than some of the other gram-negative bacteria. So, this is a major toxin, it's a major provoker of inflammation and pre radical activity in all kinds of changes. Kaczor: So, how does LPS effect the brain directly? Since, I hear what you're saying and I know even in experimental animals LPS is a common way to reliably instill an inflammatory process in a lab animal. So, it's clearly a very potent, inflammatory molecule. How does it effect the brain? Sandberg-Lewis: So, the bacteria, we get some bacteria trans locating into the blood but they usually get called out after they travel through the portal vein to the liver by the cooper cells. At least if the liver's working well. You're not gonna have a lot of bacteria in the blood but the bacteria can still effect the central nervous system, even if they don't cross the blood brain barrier and never even get there. First of all, one mechanism is that LPS and the inflammatory cytocinesis that it induces include interleukin one, interleukin six and I mentioned TNF alpha and they can actually up regulate the transcription of these cytocinesis in certain discrete areas of the brain. And then one of the things that happens with that is, within the brain you get an up regulation of indoleamine dioxygenase, which is that enzyme that converts tryptophan to kynurenine and that can move further to quinolinic acid, which is neurodegenerative. Although, there's quinolinic acid, which is also has a positive effect. So, depending on how it goes through the pathways, you can have neuro degeneration up regulated. And studies show that depression, anxiety and insomnia can issue from high levels of quinolinic acid. So, there's that. There's also cognitive deficits and in my book, very important, is increased visceral sensitivity. All the functional disorders of the GI tract, there is increased visceral sensitivity meaning, people perceive their own motility and movement within the gut as pain or strong discomfort. And man, those patients are strong to treat because if you start to activate their GI tract and get it moving again after it's been atonic for years, then they're complaining that they're up all night with abdominal pain. And that's a tough one, we're trying to learn more about how to deal with visceral hypersensitivity. But, it's thought that LPS is one of the things that triggers that too. Kaczor: So, I have a two part question. I guess, in our clinical assessment of LPS, is there a means, I mean, I know that we could do testing for small intestine bacteria overgrowth through breath testing but, is there any blood test, I guess is what I'm thinking? Can you tack on any blood test to gauge LPS levels and the second part of this question is, what do we do about it? I suppose treating the gut in a totality dysbiosis present, is the short answer. Any clinical pearls are certainly welcome. Sandberg-Lewis: Yeah. So, you can, this is available, you can measure LPS. You can measure LPS binding protein, I believe as well. And you can, in your patients, you can, of course, measure zonulin, which gets up regulated by LPS. So, yeah. By all means, start experimenting with that and then see if you can get the levels down. Now, yeah. I'm known for spearheading along with some other really busy physicians and researchers. The treatment and in our case, more the natural treatment, of small intestine bacterial overgrowth, you just can't get away from it. It's so key to, we used to say, "Death begins in the colon" when I was in school in the 1970s and now, I think it makes sense to say, "Disfunction and autoimmunity begins in the small intestine". It's just associated with so much and that includes neurodegenerative diseases, like Parkinson's as well. A practical thing, yeah. Learn how to test for, interpret and treat ... Use your testing and learn how to treat SIBO. Both the hydrogen, methane and hydrogen sulfide types. And don't throw out the yeast with it either because they often go together and get that metabolite base 40% of the blood. Get it into a functional mode instead of a dysfunctional mode. Kaczor: Mm-hmm (affirmative). Mm-hmm (affirmative). Yeah. And I know, I will say that, you lecture and write a lot on the clinical aspects of this. So, anyone who wants further information can certainly start Googling you and find lots and lots to followup on. I do want to ask another question because this issue that we are in for the Natural Medicine Journal this month is a special on the microbiota and the microbiome. How do probiotics specially effect the gut-brain axis? Sandberg-Lewis: I don't know that we have enough yet to really have a great answer. Although, there are some docs out there that really have a strong handle on the strain specific effects of probiotics and people like Jason Hawrelak who is a ND and teaches at Western States and practices in Australia, he has totally got that covered. So, I would highly recommend looking at his website Jason Hawrelak, Hawrelak. But I mean, we know that there are studies that show that fermented foods significantly reduce anxiety, especially social anxiety. And there's a lot more research going on on strains, specific things that show that there are specific effects on anxiety and depression. But it's still really early so, I can't say I have a really good picture of that. When people ask me about probiotics, I usually say, "I don't know anything about probiotics". They don't believe me but, yeah. Kaczor: So, is it accurate to say that you advocate the whole foods diet, plenty of prebiotics in the form of fibers and resistant starches and things like that and then trust that if that is done well and consistently and then, of course if there is other treatments to kill undesirable bacteria etc. but complimenting ... I mean, the way to encourage the good bacteria is to give the prebiotics more in your view? Sandberg-Lewis: Well, the problem is a lot of my patients, because they have overgrowth, they can't tolerate prebiotics and fiber. So, when I first start working with them, we can't really use those things except very specific types. We know that partially hydrolyzed program seems to be actually beneficial for people who have overgrowth, sometimes used along with rifaximin in treatment of hydrogen SIBO and it increases the effectiveness of that. But, there's some GOS's that that may also be well tolerated. But that's a problem in the beginning because if you have overgrowth and then you feed them with a prebiotic, then it just increases symptoms and problems. So, it's a fine balance, it's a fine balance. But, yeah. I really encourage my patients to eat whatever fermented foods, probiotic foods that they tolerate. So, we use lactose-free, fermented dairy products, we use pickled items like kimchi or sauerkraut, the real stuff not the fake stuff. The refrigerated kind. Or homemade. And things like that. I think all traditional groups of people around the world have their own probiotic foods. Some of them pretty hard to even relate to, like haggis in ... where is that? Scotland. Where they eat the goat stomach that's fermented. Fish and rotten fish in the northern areas of Europe. There are some really interesting things you'd think, "Why the hell would people ever invent that food?" But these things have tremendous fermentative capabilities. And one thing that I'm sure NDs understand this but it comes up a lot with patients asking, they'll say, "So, you don't want me to eat any fermented food, right? Because I already have ... You want me on a low fermentation diet". And I say to them, "Well, no that's not what I want you to do". Unless you have a histamine sensitivity and you can't handle foods that are fermented, I want you to use those things because if you eat a high fermentation diet that has carbohydrates that are easily fermented, that produces gases. Hydrogen, carbon dioxide, maybe ethanol, methane, hydrogen sulfide in the gut and causes distention and pain and changes the stools and can cause bloating. But if you eat a food that is a fermented food, the gases have already come off into the atmosphere in the process of fermentation and now you're just getting all the bacteria and the great metabolites without the gas that causes the symptoms. I think that's an important differentiation. Kaczor: Well, yeah that's a great way to put it. To help them and us understand it a little bit. One last question, we'll end on a fun question, when you hear the term 'gut reaction to something', because we're talking about the gut-brain axis and someone says, "I used my gut" or gut instinct, gut reaction, what do you think? Sandberg-Lewis: Well, I'll bet physicians with different backgrounds have different ways of interpreting that but clearly if 90% of the input in the gut-brain axis is coming from the gut and if you think about it, if virtually every neuro peptide and GI hormone that's produced in the gut effects insulin and blood sugar and we know the brain suffers within minutes from blood sugar that's too low whereas the other organs may not care for quite some time and oxygen as well, of course, to the brain within three minutes. There are major effects on life and death related emotions that take place when the gut is feeling like something is wrong and it's gonna make more jittery molecules instead of more serotonin and gaba. And that's gonna have very rapid effects on the mood and on the functioning of the person's nervous system. Kaczor: Mm-hmm (affirmative). Alright well, I sure do appreciate the time you took to talk to us today about this. It is a huge topic and I am excited, as a naturopath that everything is coming back to a source, the GI tract, I mean and we've always been taught that we have to remedy the gut and get that in order before we can really keep someone in an optimal health state. So, sometimes that's harder than others and I do appreciate the time it took to enlighten us today with the gut-brain axis and it look forward to talking to you probably in the realm of gastroenterology again in the future. Sandberg-Lewis: Great, let's do it. Kaczor: Alright, take care. Sandberg-Lewis: Alright, bye.

Daniel Chong, ND has been a licensed naturopathic physician, practicing in Portland, OR, since 2000, where his primary focus is on risk assessment, prevention, and drug-free treatment strategies for cardiovascular disease.  He is also founder and lead coach at The Healthy Heart Academy, LLC, an online platform created to help eradicate heart attacks via direct consumer coaching, and health practitioner education.  Dr. Chong has completed training in cardio-metabolic medicine from The American Academy of Anti-aging Medicine, is a member of the Society for Heart Attack Prevention and Eradication (SHAPE Society), serves as a clinical educator for Boston Heart Diagnostics Lab, and is a contributing editor in cardiology for The Natural Medicine Journal. In this conversation, Dr. Chong and I focused on the number 1 killer in the US, heart disease. Dr. Chong talk about the foundation for preventing and reversing cardiovascular disease with diet and lifestyle. We talk about some of Dr. Chong's favorite foods for heart health, as well as those to avoid. We also discuss the hot topic of supplementation and what most humans may need, even when consuming an optimal diet. I know Dr. Chong will be back on the podcast some day to expand and deepen into some topics we skimmed over!   Links to learn more - Show notes and resources: https://alter.health/episode4/ - Get a copy of Dr. Benjamin's book: https://amzn.to/2tmiOz3 - Apply to work with Dr. Benjamin: https://alter.health/membership - Connect on Facebook: https://fb.me/alterhealthinc - Follow Dr. Benjamin on Instagram: https://www.instagram.com/drbenjaminalter

In this interview, naturopathic physician Carrie Decker, ND, describes some of the actions she takes with patients to help reduce the risk of developing dementia and cognitive decline. Her integrative approach includes nutritional and lifestyle assessment, assessment for common risk factors or other potential exposures, and nutritional supplementation to meet her patients' individual needs. About the Expert Carrie Decker, ND, is a certified Naturopathic Doctor, graduating with honors from the National College of Natural Medicine (now the National University of Natural Medicine) in Portland, Oregon. Decker sees patients at her office in Portland as well as remotely, with a focus on gastrointestinal disease, mood imbalances, eating disorders, autoimmune disease, and chronic fatigue. Prior to becoming a naturopathic physician, Decker was an engineer, and obtained graduate degrees in biomedical and mechanical engineering from the University of Wisconsin-Madison and University of Illinois at Urbana-Champaign respectively. Decker continues to enjoy academic research and writing and uses these skills to support integrative medicine education as a writer and contributor to various resources. Decker supports Allergy Research Group as a member of their education and product development team. About the Sponsor Founded in 1979 by molecular geneticist Stephen Levine, PhD, Allergy Research Group® is one of the very first truly hypoallergenic nutritional supplement companies. For nearly 40 years Allergy Research Group® has been a leading innovator and educator in the natural products industry. Our dedication to the latest research about cutting-edge nutritional supplements continues to this day. Our purpose is to provide customers with products they can use to improve their patients’ quality of life, through scientific based innovation, purity of ingredients, education and outstanding service. ARG is proud to be a sponsor of the Clinical Education LinkedIn Forum, a closed peer-to-peer group on LinkedIn where healthcare professionals can ask clinical questions and receive evidence-based and clinical-based responses by experts in their field. Visit www.clinicaleducation.org/linkedin for more information & to sign up for free! Visit www.allergyresearchgroup.com for more information on ARG and our products. Transcript Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we're talking about maintaining healthy brain function with naturopathic physician, Dr. Carrie Decker. Before we begin, I'd like to thank the sponsor of this podcast who is Allergy Research Group. Dr. Decker, thank you so much for joining me. Carrie Decker: Thanks Karolyn, I'm glad I'm able to be with you today. Gazella: So we're going to start by having you remind us of the medical definition of dementia, and then tell us how common these conditions are. Decker: Yeah, so dementia basically is the mental decline and associative changes in memory, mood and even personality which can occur from an acute incident, such as a vascular event or head injury, or be the progressive changes we see with conditions such as Alzheimer's and Parkinson's Disease, or even alcoholism. There are other less common causes of dementia as well. Not surprisingly, many of these conditions can overlap, particularly vascular and Alzheimer's dementia. The main difference with vasculars and Alzheimer's dementia, is that with a vascular event there will be a more sudden decline and then a fairly stable period compared to the typical slow decline of Alzheimer's disease. With a vascular event you might see a sudden change in personality, mood, language or even motor symptoms. Personality, mood and motor changes also may occur with Alzheimer's disease, but are generally in the later stages and occur gradually. Vascular or stroke related dementia accounts for 10 to 20% of dementia in the US and Europe. And the most common type of stroke is ischemic stroke which represents roughly 80% of all strokes in the US. There actually is a region in the US known as the stroke belt in the Southeast, which I was unaware of. Multiple studies have found a higher incidents of stroke in this region. Even in well characterized populations such as healthy male physicians and patients born there. There are many subcategories of ischemic stroke and, of course, all are associated with conditions such as a clot or vessel disease which leads to obstruction and reduced blood flow. And with this oxygen, the nutrients to a focal region of the brain. With a hemorrhagic stroke, which is often associated with hypertension and trauma, blood leaks into the brain and locally increases pressure in the surrounding region. Changes with a hemorrhagic stroke may occur somewhat gradually over minutes or hours, where the intracerebral hemorrhage are very suddenly with a subarachnoid hemorrhage. Clinically, the course of events helps to diagnose which type of stroke someone had, but brain and vascular imaging is required for diagnoses. Incidents of cognitive impairment in dementia after stroke ranges from six to 32% which becomes clouded with factors contributing to other types of dementia the longer the patient is followed. Alzheimer's dementia is most common type of dementia. In the age specific incidents ranges from less than 1% in an individual 65 to 70 years of age, to as high as 8% in individuals 85 years in age and older. Early onset Alzheimer and dementia can occur in individuals as young as 30, however this is far less common and usually genetically related or many misdiagnoses and other conditions which can cause cognitive changes. Gazella: Perfect. So what I'd like to do, is I'd like to focus on Alzheimer's a little bit, because it is the most common form of dementia as you mentioned. So what are some of the hallmark changes that take place in the brain, that can indicate Alzheimer's has set in? Decker: So all this again is pretty gradual, but the key things that occur in the brain with Alzheimer's dementia, which many people ... the physicians out there, at least will remember from cramming for pathology tests, are extra cellular deposits to amyloid beta peptides near fibrillary degeneration and associated tangles and neuritic plaques. These are not specifically seen with imaging, but analysis techniques and tracers are constantly being developed that can help us see these changes more specifically. Additional biomarkers that assess for changes in markers related to tau and amyloid beta in the cerebral spinal fluid are also being developed to help determine the risk of cognitive decline and assess for Alzheimer's disease, but are not yet recommended for routine diagnostic purposes. Brain imaging with an MRI is indicated in the evaluation of dementia and is capable of identifying alternative diagnoses such as the cerebral vascular types of events. Contrast may be used, excuse me, to help visualize the regions of vascular compromise or even an altered blood-brain barrier. Structural changes seen in an MRI with Alzheimer's dementia include general and focal atrophy, as well as white matter lesions; however, these findings are non-specific. The most characteristic finding with Alzheimer's disease is reduced hippocampal volume, or medial lobe atrophy, which must be evaluated relative to one's age, as a decrease in volume is normal with aging, as well. At times, there might be a dramatic reduction in hippocampal volume of over 40%. Positron Emission Tomography, which is commonly called a PET scan, with amyloid tracers can help us determine if there's an amyloid burden on the brain and this helps rule out the likelihood of Alzheimer's dementia if they're not found. But, it's not diagnostic if they are found, because you still have to rule out other types of pathology. Gazella: Okay, perfect. Now what are some of the symptoms of Alzheimer's disease? Decker: As most people ... even an untrained non-professional would know, the cognitive impairment is one of the most common signs that we see. Especially, initially, with Alzheimer's dementia. But it may be accompanied by executive disfunction and visual spatial impairments. Executive disfunction may manifest as difficulties in things like problem solving, multi-tasking, and abstract reasoning. Visual spatial impairment can manifest as changes with difficulties with reading, discriminating form and color, perceiving contrast, and detecting motion. For the most part, these deficits and changes manifest insidiously. The memory changes with Alzheimer's dementia involve significant deficits and declarative episodic memory, that is the memory of events occurring at particular time and place, which relies heavily on the hippocampal function. Memories for recent events are also impaired early in Alzheimer's disease, whereas the ability to recall something that's mentally rehearsed, like an address, is kind of spared early on. Longer term memories, which have been consolidated and in essence kind of rehearsed over years, are also spared because they don't rely on the hippocampal function. The deficits in immediate recall of rehearsed items, as well as semantic memory, the knowledge and facts we accumulate through our lives, gradually develop with time. Procedural memory, like knowing how to tie your shoes, can become affected in the later stages. Generally, the earlier changes are described overall, as recent memory impairment. Kind of avoid confusion and language that's often over a patient or caregiver's level of understanding. Also, with this we might see neuropsychiatric changes, particularly in the mid to late stages of the disease. This can include apathy or depression, irritability or related disengagement. More severe behavioral disturbances, such as aggression, wandering, and psychosis or hallucinations, also can be seen but really should be evaluated for further other possible causes, such as infection or medication-related toxicity, which is also more common in the elderly. It is not uncommon for patients to underestimate their deficits and offer alibis or explanations for them when they're pointed out, which kind of contributes to some of the mood-related symptoms, such as irritability for people. Loss of insight also occurs with time. And, interestingly, those with more insight into their condition are more depressed. While those with less insight are more likely to become agitated, experience psychotic features or perform actions like leaving the house, wandering in their pajamas. Which, if someone had the insight, they were less likely to do. Seizures may also occur in 10 to 20% of individuals in the later stations of Alzheimer's disease. The seizure type isn't so much a motor one, it's more of a focal non-motor seizure which manifests with impaired awareness, confusing amnesia spells, unexplained emotions, and experience of a metallic taste. Sleep disturbances are also common with Alzheimer's disease and may occur early in the disease process. This includes the fragmented sleep. It also may manifest as longer sleep. Sleep time generally decreases by 30 minutes per decade, starting at mid-life. So some sleep changes are also normal with aging. Poor sleep also happens to be a risk factor for cognitive decline and dementia, which is important to note. Gazella: Yeah, it's a devastating diagnosis, there's no question about it. And today we're talking about reducing risk. How do we even know that's possible? Decker: Whenever I think about risk for any type of disease, I think about, "Well, what are the risk factors?" And if we can associate it with a risk factor, if we deal with those risk factors then we're reducing your risk. So, from the Alzheimer's disease, specifically risk factors are hypertension, dyslipidemia, and altered glucose metabolism. Each, of course, is treatable. Individuals who are physically active have a reduced incidence risk of Alzheimer's disease and cognitive decline. Exercise, of course, also reduces the risk of these other things; the hypertension, dyslipidemia, and hyperglycemia. So we really can't say enough about that. Long-term use of certain medications, such as benzodiazepines, anticholinergics, antihistamines, opioids, and proton pump inhibitors, may be associated with increased risk of Alzheimer's disease. So working with patients to discontinue these, if not needed, may really benefit brain health. Exposure to environmental pollutants, including air pollution, second-hand smoke, or pesticides may put someone at increased risk for Alzheimer's disease. Chronic infections, such as Lyme disease, also may put someone at risk for developing dementia. That can be mistaken for Alzheimer's disease, but the inflammatory aspect of any type of chronic condition also may play into something that may later manifest as Alzheimer's. Cigarette smoking contributes to cardiovascular disease and hypertension, both of which are risk factors for Alzheimer's disease. The high-sugar diet, of course, contributes to the development of diabetes and hyperinsulinemia, which increases the risk of Alzheimer's. Excessive alcohol use contributes to dementia in its own right and affects memory acutely. Chronic use of alcohol in excess also contributes to hyperglycemia and the nutritional deficiencies, which may also be contributing factors to longer-term memory problems, as well as Alzheimer's. So, with so many things that are risk factors that are associated with Alzheimer's disease, correcting them inevitably reduced the risk. And then when we start to eliminate many of these factors that are known risk factors for Alzheimer's disease, or at least associated with it, the reduction in risk, of course, compounds as well. Genetically, there are definitely some things that we're unable to change, per se, but we can still influence the phenotype by addressing environment, nutritional, and other factors which impact it. Gazella: Well, that's great. And I would like to talk about nutrition and specific diet. You mentioned high-sugar diet as being a possible risk factor. When it comes to reducing risk, what do you like to emphasize and why? Decker: For me, really that's one of the biggest places to start. Reducing the high intake of high glycemic foods, like the breads, pastas, desserts and sugary snacks, often is one of the first changes that most people need to make. So often, people are grabbing these things for a quick energy fix because they're easy. And they also come with a blood sugar spike and then a blood sugar crash. Good brain food really includes foods that provide the essential vitamins and minerals, proteins, and healthy fats. Eating a diet that has lots of color, and not the artificial variety, helps people to take in the necessary vitamins and minerals, as well as many other phytonutrients found in fruits and vegetables. Nuts like walnuts, which provide healthy fats, protein, Vitamin E, as well as other nutrients and salmon, which provides a lot of Omega-3 fatty acids, are particularly good things to routinely include in the diet. A higher total intake of Omega-3 fatty acids, particularly DHA, is associated with a reduced risk of Alzheimer's disease. DHA helps reduce the amyloid beta peptide accumulation, as well as oxidative damage, which also is a contributor to Alzheimer's. One more part of that, when you dial really into the diet more, on an individual basis there might be other things that come up, things like the food sensitivities, the allergies, different types of things that cause inflammation. And for some sensitive people, even things that are high in histamine might be something to reduce. Histamine is an inflammatory mediator, which released from basophils and mast cells in the body, like when we have an allergic response, but it's also found in certain [inaudible 00:11:40] like fermented meats and wine. People can become more sensitive to foods like this when the lining of the gut is damaged, or if they have certain genetics related to the breakdown of histamine. Histamine increases the blood-brain barrier permeability, which can contribute to neuroinflammation and neurodegeneration. Gluten absolutely should be out of the diet for people with celiac disease, as it's been determined in this population, specifically, to contribute to cognitive impairment, as well as nutritional deficiencies. But, not only them, the people who are not affected by celiac disease also can have an inflammatory response and with this foggy thinking, however we don't have research that I'm aware of that specifically connects it with Alzheimer's yet. Gazella: Okay, so it sounds like a really solid anti-inflammatory diet. In addition to diet, you mentioned exercise. You mentioned sleep. But what other lifestyle factors are critical to look at when it comes to reducing risk of dementia in the patient population? Decker: Yeah, like I said, exercise is one of those things that just is important for so many aspects of metabolic health, but also has other ways that it improves cognitive function. It's something that supports the levels of brain-derived neurotrophic factor in the body. We shorten that up, calling it BDNF. And that improves neurogenesis and cognitive pathways in the brain. Exercise also has been shown to increase hippocampal and total brain volume, which we already talked about as being something that happens with Alzheimer's disease. Cognitive stimulating also benefits cognition, and that's been shown in studies. Just something people talk about. So whether this includes reading a book, playing a game of cards, or learning a new musical instrument or other skill, it's important to include. Eliminating smoking and excessive alcohol intake also should be a part of a dementia protocol. But, also general health promoting advice. Healthy sleep is important for cognitive function and preventing dementia. So working with lifestyle to make adaptations, such as new blue light or other stimulating things at least an hour before bed might come into play with people if the sleep is poor. Gazella: So Let's talk a little bit more specifically about nutritional factors and how they might contribute to cognitive decline in Alzheimer's disease. Decker: Nutritionally, deficiencies or lower levels of certain vitamins, minerals, or other essential nutrients have been shown to be associated with Alzheimer's disease. This includes the B vitamins; B-12 and folate, Zinc, Vitamin D, as well as tocophorols, and tocotrienols. Lower levels of CoQ10, which our body produces, have also been shown in some studies to be associated with an increased risk of dementia. I believe it's critically important to start with the necessary nutrients, such as these, because their impact in the body extends far beyond just the brain. Zinc has a critical function in the brain and lack of zinc can cause neuronal death. Low zinc levels are associated with a poor ability to smell and depression. So if these symptoms are also mentioned, screening should be considered. Homocysteine levels have been observed to be significantly higher in patients with Alzheimer's disease and also can be deficiencies in the B vitamins; folate, B-12, or riboflavin. Homocysteine elevation also is commonly seen in cardiovascular disease and depression. So if these are also an issue for a patient, and even if not really, this should also be considered. Vitamin D access in your [inaudible 00:14:45] hormone and also impacts genetic expression. Vitamin D levels should be at least 30 nanograms per milliliters and I would recommend even higher, really around 50 nanograms per milliliters. Low levels of vitamin D are also often seen with cardiovascular disease and should be a part of screening for that. Tocophorols, tocotrienols, and CoQ10, they're all fat-soluble, neuroprotective antioxidants and they're also cardio-protective. They support not only a healthy brain, but they reduce the risk of cholesterol oxidation and they support health vessel function, which can help reduce the risk of the vascular dementia, which we talked about earlier as well Gazella: What about other botanicals or natural substances? Are there any others that have evidence supporting cognitive function and helping reducing risk? Decker: Yeah. There's so many that I kind of got into thinking about some of them and there's way too many to discuss. But, I'm looking at ... I wanted to talk about some of them with the biggest evidence that I've seen. So because inflammation plays a role with Alzheimer's disease, we talked about that with diet. Some different therapies, which can help reduce inflammation like oxidative shots, can be helpful. But some other mechanism-like things like essential fatty acids also may improve dementia. When we talk about managing inflammation with natural substances, curcumin, the active compound found in tumeric is often at the top of the list. And it comes into play here, too. Curcumin has been shown to improve working memory, attention, and reduce cognitive decline in healthy elderly patients. Curcumin has clinical evidence it helps reduce depression, as well. Which, again, is common with Alzheimer's disease. Mechanistically, it has been shown to reduce oxidative stress and accumulation of the beta amyloid plaques, at the same time reducing our increasing levels of protective antioxidants, such as superoxide dismutase. Of course, making sure the curcumin is bioavailable is very important. The best data I've seen comparing a lot of the [inaudible 00:16:35] curcumin preparation suggests that the best bioavailable can be obtained with a molecular dispersion process that then answers the water solubility and dispersion of fat-soluble ingredients, like curcumin. With this type of preparation, it's been shown to be even six times higher absorption than the more commonly used curcumin phytosome that's found in many supplements. Another one that has a lot of evidence behind it is Huperzine A. Huperzine A is an extract from the club moss and it acts as an acytlcholinesterase inhibitor, which also happens to be one of the mechanisms of many drugs which address dementia. Huperzine A also may help reduce dementia by regulating production of beta amyloid precursor protein, protecting the cells from oxidative stress, mitochondrial disfunction, as well as damage associated with glutamate induced toxicity. Glutamate's an excitatory neurotransmitter in the brain, and when in excess, it promotes some of this neuroinflammation and neurodegeneration that we see with a lot of chronic nervous system diseases. There've been multiple randomized, placebo-controlled trials looking at the impact that Huperzine A has on both Alzheimer's disease, as well as vascular demential. It's been shown to significantly improve cognitive function in patients with mild to moderate vascular dementia and significantly improve cognition, mood, and activities of daily living scores in patients with mild to moderate Alzheimer's disease. The benefits of Huperzine A have also benefits in other populations with findings of enhanced memory and learning in adolescence and improved recovery in elderly patients from general anesthesia. Ginkgo Biloba has been studied in many clinical trials, as well as in the studying of dementia. As a botanical, we always think of it as being this go-to for supporting microcirculation, kind of in the fingertips, the toes, the eyes, the kidneys, but the brain is also a part of that. Ginkgo's protective, in part, due to its antioxidant effects and supports circulation in the small vessels by reducing platelet activation and aggregation, as well as stimulating the release of endothelium-derived relaxation factor. In double-blind, randomized, placebo-controlled studies in patients with mild cognitive impairment, Ginkgo has been shown to improve cognitive function and reduce dementia conversion rate, improving episodic memory and even improving activity challenged gait, which is something that can be an issue with people with dementia. In a double-blind, randomized, placebo-controlled study in patients with mild to moderate Alzheimer's or vascular dementia who also had the neuropsychiatric aspect of that, Ginkgo was shown to significantly improve cognition, neuropsychiatric symptoms, functional abilities, and the quality of life in patients, as well as their caregivers. In healthy populations of middle-aged and older volunteers, Ginkgo has also been observed to positively impact memory, improving recall performance, as well as speed of processing abilities. Lipids are also very important for the brain, which is not very surprising, as the brain is very fatty tissue. Brain cells are especially rich in phospholipid choline, which the body can synthesize from a substance called citicholine, also known as CDP choline. Citicholine and phospholipid choline both support the integrity and functionality of the neuronal membrane, as well as the mitochondria. Citicholine provides choline, and enhances the synthesis of acetylcholine, the neurotransmitter that plays a significant role in memory and learning. Citicholine has been studied in multiple clinical trials with populations experiencing memory-related issues ranging from mild cognitive impairment to vascular dementia and Alzheimer's disease. A Cochrane review assessed the effectively of citicholine in 14 double-blind, randomized, placebo-controlled trials in patients with cognitive impairment due to chronic cerebral disorders, which can include both the vascular and Alzheimer's disease and found that, in patients with cognitive impairment due to these disorders, that citicholine has positive effects on memory and behavior in at least short to medium term and they recommended that studies of longer duration be conducted. Significant improvements in mental performance have even been seen in patients with early-onset Alzheimer's disease treated with citicholine, as well. In a population of patients with the apolipoprotein protein, E epsilon four allele, which increase the risk of dementia, including that of the early-onset dementia as well as vascular dementia, citicholine has been shown to significantly improve cognitive performance, also improving the parameters of cerebral blood profusion in brain bioelectrical activity patterns. In patients who had their first recent ischemic stroke, citicholine was shown to improve attention, executive function, temporal orientation, cognitive status, as well as quality of life, many of which often decline in this post-stroke period. Lion's mane mushroom is another one that's worthy of mention in a discussion of dementia, as well as in the other changes that occur with aging. Lion's mane has a long history of traditional use for supporting nerve growth and we now know it induces the secretion of nerve growth factor. In recent randomized, double-blind, placebo-controlled studies, lion's mane has been shown to significantly increase cognitive function scores in patients with mild cognitive impairment, as well as reduce depression and anxiety. In animal models, lion's mane has been shown to improve spatial short-term and visual recognition memory impairments induced by amyloid beta peptide. Peripheral neuropathy is not uncommon at all in the aging population, whether it be due to diabetes, nutritional life deficiencies, or idiopathic in nature, and lion's mane can also be a benefit for this, because of the fact that it promotes nerve growth factor again. Lion's mane, like many of the medicinal mushrooms, also may have protective effects against certain forms of cancer. Gazella: I was gonna say, there's a long list here. Decker: I know. I just have to throw this last one in. French maritime pine bark extract also is another one that's been the topic of several clinical studies related to cognitive function. Although, this one hasn't been studied in the population with Alzheimer's or the decline already, it's been studied in several different healthy population ... in different clinical studies. In population ages ranging from kids to older adults, even including 60 years in age and above, it was repeatedly shown to improve cognitive function, as well as additional memory retention, mental performance, and working memory in some of the studies. And beyond cognitive function, it is also one of these that can positively impact blood pressure, cholesterol balance, blood sugar, and has positive impacts on these other diabetes-related microvasculature complications. So it's really excellent for use in individuals who also experience these other challenges. Gazella: So that is a long list. You've identified lots of choices when it comes to nutrients and botanicals. Now, are there any safety issues or contraindications associated with this long list that you've just mentioned. Decker: Yeah. Well for the nutrients, of course, some of them such as zinc and vitamin D are appropriate only if there's a deficiency. As an excess, they can cause problems. But, things like CoQ10, tocotrienols, and essential fatty acids are really very safe and are used in part to help reduce cardiovascular disease risk, as well. The side effects that some people might experience with agents that help increase blood flow to the brain, like Ginkgo, is a slight headache. And, of course, if this occurs the dosage should be diminished or supplement discontinued if it doesn't subside. Some people might find cognitive support formulas, and even things like CoQ10 and phospholipids alone, to be somewhat stimulating. Not like the jitters type of thing, life coffee, but feeling like a little supercharged. A little of this sounds positive. It can be really problematic if you're not able to do something with that energy or need to go to sleep. I've also seen people have more vivid dreams when taking something like Huperzine A, and that tends to usually be more transient. But if it's troubling and doesn't dissipate with time, an alternate supplement should be selected. I generally instruct people to start with low dose, especially if you using combinations of these nutrients, because they really can be very potent. Although some of the nutrients can be taken at night, I generally tell people to take anything that's intended to support cognitive function in the morning. Because we really want it to be something that helps us fly through the day and be as productive as we can be. But really, with all supplements, it is important to screen them with your doctor to make sure they don't have interactions with other medications you may be taking and to make sure they're something for you, individually, that is correct. Gazella: Yeah, that makes a lot of sense. And, it occurs to me that you mentioned formulas for brain health ... probably a lot of these ingredients that you mentioned are used in combination to be more effective. So there's a synergistic effect. Is that accurate? Decker: Yeah. Some things more than other. Different supplement companies put different combinations together and a lot of the companies look to the research, just like I'm talking about today, and see what might be appropriate to put together. When I work with things, I often use a B vitamin complex or other specific combinations meant to address homocysteine elevation, if that's an issue. Essential fatty acids and moderate doses of vitamin E, if not part of the diet routinely, should also be included. CoQ10, Vitamin E, and essential fatty acids - the fish oils, sometimes you can find those in combination because they're all a fatty substance. They often combine very well. Vitamin D and zinc tend to be single nutrient therapies that people are on because we use them for all sorts of things, including immune support as well as mood. So those will be things, individually, people take. Generally, if someone's healthy and not experiencing cognitive decline, that's kind of a good combination package of nutrients to just prevent the nutritional decline-related issues. But, some of the combinations ... I've seen a combination that has the lion's mane mushroom, the phospholipids, citicholine, as well as a substance called coffee fruit extract that really supports cognitive health quite well on both a short-term and long-term basis. The coffee fruit extract, which contains less than 1% caffeine, has been shown in multiple studies to increase levels of brain drive neurotrophic factor, which I kind of talked a little bit about with exercise. The brain drive neurotrophic factor promotes neurogenesis and is naturally increased in the brain when someone's working on learning something. I like the combination again, because it's so potent and it's something that someone feels the effects of in the day they take it, yet it has long-term benefits because of the fact that both lion's mane mushroom and coffee fruit extract have of promoting neurogenesis. It also contains American ginseng, and that in combination with the phospholipids, has a pretty dramatic on energy levels as well. You know, we see a decline in energy with aging populations, which also can be an issue. I've also found this combination to be really helpful with patients with depression, which makes sense. There's a common overlap with some of the things we talked about in many ways with depression. So you might want to consider it for that, as well. Gazella: Yeah, sounds like a good combination. Well this has been packed full of great information, but I'm wondering if you have any other advice for practitioners who might be listening, who are trying to help protect cognition in their patients. Decker: Yeah, and this one doesn't maybe fit in with everything I've been talking about, but I'm a naturopath and I think about things in a very whole-minded fashion ... and I live in Portland, so maybe that influences it as well, but I think it's really necessary to look at the impact of community and how being happy can really impact the overall health of our patients. Particularly in older patients, a lot of them might be alone and if they get stuck in grief ... say they have the passing of a loved one or so many people pass the more we age, and often that will be people in the family. A partner. A spouse. And that contributes to loneliness and these things don't really just eat away at the mood, but they bleed into the health in so many other ways. Community really gives people life. It gives them purpose and meaning. And being active and finding community, which someone resonates with, really serves a far greater purpose than just being an event on their schedule. And with the elderly or aging population, whether this is a local community center, a church or some other group, it can really help people find a fulfillment and happiness and that goes far beyond just that. It improves the mood and the health of the brain, as well. Gazella: Yeah, that's such an important point and I'm glad that we're ending with social support, because it has far reaching benefits. Well, once again, I would like to thank the sponsor of this topic, who is Allergy Research Group. And I'd like to thank you, Dr. Decker, for this wonderful information and joining me today. Decker: Yeah, it was great to be able to do so. Gazella: Well have a great day. Decker: Thank you, you too.

In this interview with Natural Medicine Journal's publisher, Deborah Yurgelun-Todd, PhD, and Perry Renshaw, MD, PhD, MBA, discuss the research they are conducting at The University of Utah in the Neuroscience Department. They specifically describe research associated with the safety and efficacy of supplemental citicoline, as well as evaluate emerging research in this area. Approximate listening time: 30 minutes About the Experts Deborah Yurgelun-Todd, PhD, is director of the Neuroscience Initiative and a USTAR Professor of Psychiatry at the University of Utah School of Medicine. Her research focus is on identifying the neuropsychological and neurobiological bases of human behavior. Yurgelun-Todd is an expert in the application of structural and functional magnetic resonance imaging, the administration and analysis of neurocognitive tests, and the integration of the results obtained by these multiple modalities. She has examined the etiologic bases of neural models of dysfunction in psychiatric disorders including depression, bipolar illness, substance misuse, and schizophrenia. She is also recognized for applying imaging techniques to study cortical changes during development in healthy children and adolescents, and during treatment intervention in adult patients.   Perry Renshaw, MD, PhD, MBA, is a USTAR Professor of Psychiatry at the University of Utah School of Medicine and a Medical Director of the VISN 19 Mental Illness Research, Education and Clinical Center (MIRECC) at the Salt Lake City Veterans Affairs Medical Center. His training as a biophysicist and psychiatrist has led to a primary research interest in the use of multinuclear magnetic resonance spectroscopy (MRS) neuroimaging to identify changes in brain chemistry associated with psychiatric disorders and substance abuse. Current clinical trials are focused on the use of citicoline as a treatment for methamphetamine dependence, creatine as a treatment for depression, and uridine as a treatment for bipolar disorder. Renshaw’s recent work focuses on brain chemistry changes that may increase depression and suicide for people living at high altitudes. Transcript  Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, I'm thrilled to be joined by two highly respected brain researchers from them University of Utah Neuroscience Department, Dr. Deborah Yurgelun-Todd and Dr. Perry Renshaw. Now, before we begin and dig into today's topic, I'd like to have each of you describe the focus of your research. So let's start with you, Dr. Yurgelun-Todd. Deborah Yurgelun-Todd: Yeah. Well, my research is initially started to focus on cognitive function and the neuropsychological, or brain, pathways that mediate how we think and how we feel. And then I became very interested in the application of brain-imaging to help us understand exactly how those pathways worked and give us some insights into how the brain does things well, and how it does things less well. Gazella: Perfect. Now, Dr. Renshaw, how about you? Can you please describe your research focus? Renshaw: Well, sure. Well, I'm sort of confused soul. I'm a psychiatrist/biophysicist, and the way in which I merged these techniques together is to do brain-imaging studies that focus on, how is brain chemistry altered in, particularly, diseased states that psychiatrists might be interested in. And based on identifying unusual patterns in brain chemistry, my research group likes to focus on identification and development of novel treatment strategies. One of which is a molecule, I guess we'll be talking about today, CDP-choline or Cognizin. Gazella: Perfect. And you're absolutely correct, I'd like to talk about citicoline in a lot more detail. Now, Dr. Yurgelun-Todd, why did you become interested in citicoline for the brain, and why did it catch your attention? Yurgelun-Todd: Well, they've done some work looking at why the brain was not working very well in mood disorders, and why attention, in particular, was a problem in individuals who had depression and other mood disorders. And when citicoline was brought to my attention, there seemed to be interesting potential for that to alter attentional systems. So I became very excited at the possibility of that becoming a treatment for individuals who may not have optimal brain functioning. Gazella: Perfect. I love the fact that attention actually is what caught your attention, so that's brilliant. That's brilliant. Now, Dr. Renshaw, what does the scientific literature tell us about the safety of citicoline, and are there any contrary indications or risks associated with its use orally? Renshaw: You know, that's a great question because we have a really well established answer that citicoline has been used millions of times around the world. In some countries, particularly where they use it as an intravenous administration as a drug. In other countries like the US and Canada, it's a nutritional supplement. We've done studies, or rather, Dr. Yurgelun-Todd has done studies looking at the effects of citicoline on adolescents and she can describe what she saw. But, by and large, you have to take a whole lot of citicoline before you notice anything adverse. And in the few instances where we've seen that, it's been people feeling like they've had too much Starbucks coffee and that goes away over about a half an hour. Gazella: Yeah, and I would like to hear about the studies on children, Dr. Yurgelun-Todd. What does your research tell you about safety, especially in that population? Yurgelun-Todd: It's very interesting because we, as I mentioned, I was interested in potential ways to improve thinking and so we decided we would look at the developing brain in individuals who were adolescent. And we found that when we supplemented with citicoline, they actually improved their attentional span and could do—and had some improvement in their psychomotor function as well. So this was in healthy adolescence, rather than anyone who actually had a documented impairment. The fact that you could see improvement in cognitive functioning and psychomotor functioning in healthy individuals without a documented impairment was actually quite remarkable. The other thing that was remarkable was that the dosing was very low, and in fact, this was a new area to explore. How low could we dose and still see an effect on the brain? So we were quite enthusiastic about those finding and think they have important implications. With regard to safety, we also were very rigorous in the documenting potential side effects associated with the administration of citicoline and we really saw essentially no side effects in the side effects profile that we did document. Looked very similar to the placebo, in fact, was not statistically different between placebo and the treatment arm. So we were really reassured that even with the rigorous assessment for side effects, there was nothing that was documented in this trial. What's really compelling, however, is that most treatments for cognitive changes or for any neurologic disorder, neuropsychiatric disorder do end up having side affect issues, some of them being more visceral, like stomach or headache or things like that, but also some of them actually diminishing your cognitive functioning. So this was rather remarkable that we could enhance cognitive functioning with no side effects. Gazella: Yeah. I mean, it's good to hear that the safety profile is good. And I may want to come back on that topic of children, but Dr. Yurgelun-Todd, I'm going to stick with you here. There's a wide variety of brain functions and cognitive issues that have been researched associated with the use of citicoline, like focus, attention, dementia, and other issues. Which area, presently, has the strongest, and most compelling research? Yurgelun-Todd: Well, that's a very interesting question because there's a biased based on what science you happen to love. I think some of the most compelling research has been associated with the fact that there's a repair mechanism associated with the administration of citicoline, that is, cellular biochemistry is actually altered and phospholipid synthesis is improved when you have an administration of citicoline, therefore, individuals who have neurological insults, such as strokes or mild traumatic brain injury, things like that can see rapid repair in their cells with citicoline administration. That is the area that's more involved in the patient or the real neurological insult area. Within the healthy individual, I think the most compelling research really falls on two ends of the lifespan, that is the elderly or middle-age and above, and also then some of the work we talked about in adolescence, where both when your brain is growing rapidly and also when your brain is aging, it seems as if the supplement with Citicoline can make a substantial difference. Gazella: Yeah, that's interesting. Now, Dr. Renshaw, there's preliminary research demonstrating that citicoline may be able to help with cocaine dependence and addictions. I find that pretty fascinating. How promising is that research, and do you see that as a viable application in the future? Renshaw: Yeah. No, that's a great question. Citicoline, broadly speaking, has 2 effects. One that Dr. Yurgelun-Todd just touched on. Brain repairs is probably more well established and been investigated for probably 30 or 40 years. Our work, to a first approximation, looks at the effects of citicoline in terms of increasing the levels, brain levels, of neurotransmitters, particularly dopamine and norepinephrine in the brain. When someone is using cocaine or methamphetamine, they often have a depletion of dopamine within their brain, as well as, in the case of methamphetamine, some damage related to decreases in blood flow. From that perspective, citicoline is almost a perfect fit in terms of what it can do an active user, increasing the level of dopamine in the brain, makes them feel, I think, more intact and, perhaps, less inclined to continue using drugs. And the brain repair mechanism because the mechanism on which stimulants cause brain damage is often related to ischemia. It's just a really good fit. Where we're going now in this research, is that we've broadened our scope from cocaine to methamphetamine to stimulants that are used to treat ADHD. In fact, we are in the middle of finding a study supported by the National Institutes on Drug Abuse, we're working with in Salt Lake City and Seoul, South Korea. And what we're looking at is adolescents who are using stimulants, not necessarily as a drug of abuse, as a way to approve their attention, focus, and do better on very rigorous South Korean college entrance exams. Some estimates suggest that close to a quarter of all high school students in South Korea are taking stimulants, which is probably not good or the long-term outcome of which is not good. We think citicoline may be a way to help people feel better and get off the use of stimulants. Which is better avoided, unless you have a really good reason for continuing treatment with that class of medication. Gazella: Yeah. That's actually one of the questions I was going to ask. When you're talking about using citicoline in healthy children, I was curious ... and Dr. Renshaw, I'll stick with you on this one ... I was curious, I have not read any studies using citicoline for children with ADHD, but I think what you're saying is you're evaluating whether or not this could be a viable alternative to the pharmaceuticals that are being used for ADHD. Is that what I'm hearing? Renshaw: There's a real divide, at least in the United States, between things that are approved as natural products, nutritional supplements, and pharmaceutical agents. The natural product industry lives in fear of having their products considered to be drugs because the amount of testing, and safety monitoring, and efficacy, and evaluation that goes into getting something onto the market as a drug is really very expensive and onerous. So for us, any research that we do, we have to have it paid for itself. It's been a lot easier to look at the use of citicoline in healthy populations, and certainly the sponsors of the work that we've done, which have been certain large natural product companies, who are much, much happier without us in approach. That's said, if I take off my sort of business man's hat and put on the scientific garb, what we believe is that, in fact, citicoline would likely have good effects for treating ADHD. In Europe, it's been used as a drug to treat Parkinson's disease with good outcomes, and Parkinson's disease is, as you may know, is also a disorder associated with decreased dopamine in the brain. The ability to increase focus and attention is generally quite good. The difference between citicoline and the stimulant per se, is the effect of citicoline is to increase the brain's concentration of dopamine, that you're encouraging the brain to make dopamine when it otherwise might not do so. Stimulants just release dopamine from the brain and tend to deplete it, so they are very different mechanisms, and there's every reason to think that they'd both be affective. They probably have different safety profiles. Gazella: That's fascinating. And Dr. Renshaw, I'm going to stay with you one more time. What about autism, autism spectrum? There's numerous conditions that are in that category. Any preliminary research in that or are we pretty much leaving that alone for now? Renshaw: We haven't been involved in that research. There was a company we did some research with in the Boston area, that was very interested in a related compound from the treatment of autism. They got involved in a big patent dispute with the University of California in San Diego that was resolved in UCSD's favor. So I don't think there's ever been a trial. But, there certainly is a suggestion in the autism literature to treat with pyrimidines, as the effect of either cytidine or uridine on the brain might help some individuals with autism spectrum disorders, but I think in fairness, it's really quite preliminary and that we'd have to do studies to understand what the effects were likely to really be to a population. Gazella: Yeah. That makes a lot of sense. Now, Dr. Yurgelun-Todd, I'd like to stay on this topic of exciting new research in the area of citicoline use. Another area of research that's pretty interesting, and could be significant, is the use of citicoline for appetite control. I mean, obviously we have an issue with obesity in this country. Is it too early to tell is this may be a promising application of citicoline in the future? Yurgelun-Todd: You know, I don't think it is. We've noticed some years ago that in looking at the response to food cues, individuals who had received the supplementation of citicoline actually showed significant decreases in appetite and that this was related to dose of citicoline that they'd received. And the thing that was interesting about that data, was it wasn't just that the individual said, "Oh, I feel like I have a reduced appetite." They actually showed differences in the way their brain responded to the cues, such as food items, ice cream, donuts, things like that when they viewed them in the magnet. So we had documentation that neural activation was altered in food-processing related areas of the brain, as well as having a decrease in appetite, which really suggests that there is some mediation of brain responses to appetitive cues, which is really one of the problems with obesity. And within weight control, that's just sort of having an over-reaction to these kinds of cues. And thinking about it further, it didn't really surprise us because it goes back to what Dr. Renshaw just mentioned about the dopamine system, the dopamine system in addiction are part of the reward system in the brain and the ... although we initially focused on the impact of citicoline on cellular function and phospholipid metabolism, we recognized as we thought about it further, that the concentration of dopamine is being changed with the supplementation of citicoline as well. So we're changing neurotransmitter balance in the brain and that had a really positive affect in terms of response to food items. I don't know if Dr. Renshaw wants to comment. Renshaw: No, I think that's right. When stimulants have been used for this purpose, in fact, that's why many of them were developed initially, but they sort of force the brain to release all the dopamine that it's already made. What we really like about citicoline or pyrimidines as a strategy for increasing brain dopamine is that A, it's really encouraging the brain to speed up synthesis, which is sort of what you'd like to do, and again from a safety perspective the latter approach should be much safer for individuals taking a supplement or another medication over time. Yurgelun-Todd: To go back to your question on is it too soon. I don't think so because I think most studies that we hear about are really just using self-report and don't have the documentation of a brain response. You couldn't really fake a brain response in terms of metabolic activations, so that is a really, I think, robust piece of research that will support this as an appetite moderator. Gazella: That's fascinating. Now, I want to stick with you, Dr. Yurgelun-Todd because I do want to go into dosage. But specific to appetite control, what was the dosage used? Yurgelun-Todd: 2,000 milligrams in the study that we did. Although, we did not ... we've not had the opportunity to see how low we can go to have this effect. And this was in middle-aged individuals. So we were looking at people, 40 to 60 years old, and they were looking at the extent to which having a 6-week supplementation could impact the brain. And that's what we saw. Gazella: And 2,000 milligrams, is that divided doses? Yurgelun-Todd: Yes, it was. It was morning and evening. Gazella: Okay, perfect. Now, Dr. Renshaw, I want to dig a little bit deeper into this issue of dose. Now, does the dose of citicoline vary depending on the application or is there a consistent dosage range that is affective across most conditions? Renshaw: That's a great question, and citicoline has a funny history that was used most extensively first in Europe. And there, after an injection of citicoline, they had a lot of trouble showing that there was any citicoline or cytidine in the bloodstream. When they went to oral ingestion, that became an even bigger problem. And it turns out, that the stomach plays tricks with citicoline, it turns the cytidine, that's part of it, into a molecule called uridine, which is the predominate pyrimidine in the human central nervous system. Because of that, it's been a wide spectrum on the views on how bioavailable, that is how much citicoline gets used by the body. It turns out that if you measure uridine, essentially all the citicoline is absorbed and gets distributed across the body, but it took a long time to figure that out. This was sorted out by a scientist at MIT, Richard Berkman, who's also studied citicoline extensively. If you look at the clinical indications, a lot of the ones we look at, mood disorders, attention-deficit disorder, probably require lower doses. In the United States, the most recent trials have really looked at serious brain injury conditions, like stroke, and so there have been trials that are conducted with oral administration of citicoline to treat stroke. The problem there is that in the context of someone who's found out a real metabolic stress affecting the brain and the body, it just sort of absorbs things effectively from your stomach, plus you've got a problem with the area you want to impact has got decreased blood supply due to the stroke. And doses went up to something like four grams a day in those instances. We've been ... most of our indications using somewhere between 500 and 2,000 milligrams of citicoline. The effects of citicoline last for about two, or three, or four hours just depending on the individual. So taking it twice a day works reasonably well. There is, for many normal people, a self-correcting mechanism, which if you're taking more than your body needs, you will feel anxious and jittery. That's relatively uncommon. Anyone taking less than 2,000 milligrams a day is unlikely to have side effects. This is obviously important in figuring out what to do. Studies in children, for example, as Dr. Yurgelun-Todd has done. Children come in a variety of shapes, sizes, and weights. It's probably going to be important to adjust the dose to reflect the weight of the child. Gazella: Yeah. I think one of the fascinating things for me with citicoline, is that it does, in fact, have efficacy at what could be considered a fairly low dose, even as low as 250 milligrams. But even at 500 milligrams, that's a pretty low dose, and it's still showing affect, correct? Renshaw: That's right. From that perspective, it's really important to recognize that one of the most established effects of citicoline is to speed up membrane synthesis, and this is true in every cell in the body, and we all travel around with CDP-choline in our cells. For that reason, because it's highly important in controlling this fundamental process, the body tends to keep the concentration of CDP-choline low. So that relatively low doses, especially for natural product, work much more effectively than is true of almost any other type of natural product. And again, we think that that has a lot to do with the fact that it's a really important regulatory control molecule within the body. Gazella: Right. Now, Dr. Yurgelun-Todd, we've talked about a lot of different conditions, and application, and some pretty exciting emerging research associated with the oral use of citicoline. Out of all of that, what do you feel shows the most promise? Yurgelun-Todd: I think I'm going to relate that to where I think there's a great deal of need. And that is in our children, and our adolescents, and young adults. And specifically, I think the fact that we can provide a very safe, minimally, essentially no side effect treatment to improve attention, and you touched on this earlier, I think is very significant. We've not done studies in ADHD or populations, such as a diagnosed ADHD population, but I'm quite sure that this would be a supplement that would make a significant difference for many of those and not have any long-term or short-term side effects. So I think that's a very important point. The other thing that hasn't been as well explored, but I think is important, is the area of concussion or sports injury. Where, I believe, because of the data that we've seen in stroke, and in other neurologic disorders there's every reason to believe that citicoline could actually provide a preventative capacity, like in a sports drink or a bar, something to that effect, prior to concussion. And then also supplementation during the season could be very helpful. So I think that ... well, that hasn't been an area that we've focused on so much. I think given the attention now in the sports of our children and college students, that this would be an area that could be really important. And then, of course, my original reason for wanting to get into this work, which is mood disorders. I think that we hadn't really capitalized on the impact of Cognizin on improving mood disorders. And I think there are many individual, particularly, in the perimenopausal age group who have found that this has been a very important supplement in their life and has helped them significantly in feeling that they can think more clearly and feel better overall. So those are my favorite areas to think about. Gazella: Yeah. That concussion, that is really fascinating and it would be great if there could be some studies done there. Dr Renshaw, do you agree? Anything to add to that list? Renshaw: Yeah. There's a substance abuse investigator at the University of Texas Southwestern in Dallas, Sherwood Brown, who did a study of the individuals who had both, cocaine dependence and bipolar disorder. And what he found was citicoline was actually much more effective in treating the bipolar disorder than the cocaine dependence in the patients that he was working with. We have a colleague here in Utah, Doug Hondo, who looked at that and said, "Why would something like citicoline be effective in treating bipolar disorder?" And he's developed a theory that suggests that citicoline may have a really potent antisuicidal effect. And it shares, to an unbelievable degree, many of the same effects on the human brain that both lithium, which is known to antisuicidal and ketamine, which is the antidepressant for those of us in psychiatry. So he's about to begin a study looking at whether or not, and this has been funded by the Veterans Administration, Citicoline reduces suicidality with treatment for only the first week. This is very exciting, and is something that will get underway, it's a 4-year study, in a couple of weeks. And if that's really true, and you could get the same protective effect without having to take Lithium or Ketamine, both of which have pretty significant side effects, that would be a real advance. The compound that Doug will be using in the study is uridine, which is the major metabolite that citicoline provides through the body in [inaudible 00:25:19]. Gazella: Dr. Yurgelun-Todd, because we're talking about bi-polar mood disorders, a lot of these folks are on some heavy duty medications as Dr. Renshaw just mentioned. Do we know anything about interactions? I don't know that there's been any studies, but if somebody is on a Prozac, or an antidepressant, or some of these other, Lithium and whatnot, can citicoline be taken with that or is that a no-no? Yurgelun-Todd: Thus far, I don't know of a clinical trial that examined that specific question, however, everything that we know about citicoline would suggest that because this is found in normal diets and is a part of the human body, that it would not have any interaction effect with the treatments that have been provided. So it should be perfectly safe. Gazella: Yeah. That makes some logical sense. Yurgelun-Todd: But with the caveat that we don't have that empirical data. Gazella: Right. You're basing that on logic and mechanisms of action and ... Yurgelun-Todd: Exactly. Gazella: Now, Dr. Renshaw, I'm going to put you on the spot here, but this is your area of expertise, your background is with addiction. I would love to hear your thoughts on our present opioid epidemic. I realize that this is a huge topic. This might be an unfair question, but can you give us a snapshot from your perspective as a researcher with this type of expertise, what needs to happen to get this issue, this opioid epidemic under control? Renshaw: Boy, if I knew the answer to that question, I'd have a really high profile job. We're very interested in addiction as you know, we live in the Rocky Mountain states, and so one of the things we study is, what happens when someone moves from a lower altitude to higher altitude, and what we find is that people often get more depressed and more anxious and, curiously, use more different kinds of drugs of abuse. So I guess you could say, flatten out the Rocky Mountains states, but that's not actually our strategy. We're looking for molecules like citicoline that may have an effect in changing brain chemistry in ways that are effective in treating some of these high altitude related conditions. The fact that this is something you can do that changes the use of drugs across a broad variety of categories suggests that these may be molecules that are really valuable in treating a range of different addictive disorders, but clearly you've figured out by now, that I'm sort of waving my hands because I think there are a lot of very smart people who are struggling with the question of how do you prove the problems of opiate dependence in this country. And it's really shocking how we have a problem that's occurred over a short period of time. Gazella: Right. We've covered it in the Natural Medicine Journal, so it's definitely in our radar as well. Now, I think we covered everything, but Dr. Yurgelun-Todd, is there any final thoughts that you'd like to add on this subject? Yurgelun-Todd: Yeah, just one final thought, which is that I think that the impact of citicoline and particularly Cognizin citicoline has not been fully appreciated yet. It's come a long way since we began working with it and I think we've appreciated that it has multiple types of impact on the human brain and body, but I think we have even more potential to see it improve the quality of our lives. So I'm excited to continue working with it. Gazella: Yeah. That's kind of why I wanted to focus on the emerging research because I think that that's very exciting, and I think that this can be a really positive clinical tool for healthcare practitioners. Dr. Renshaw, anything else to add to that? Renshaw: Just one comment and then a tantalizing tidbit if you will, we can edit this out, I guess. But one of the things that we think is going be an important trend, is the combination of citicoline with other natural products as a way to boost its efficacy. And that's something that hasn't happened yet, but we have some combinations that we're exploring now. One of the things that Dr. Yurgelun-Todd didn't share with you, is she has, across 3 different studies, evidence that citicoline also improves complexion. It has effects on skin tone, which makes some sense when you think that both the brain and the skin are rapidly turning over cells. So that's an area that's a little bit outside our area of clinical expertise that merits investigation as well. Gazella: Wow. Yeah, that is pretty interesting because that could then ... it could be a topical ingredient. Yurgelun-Todd: Right. Exactly. Renshaw: Exactly. Gazella: Yeah. Wow. That's pretty interesting. Well, I want to thank you both for joining me. This has been fascinating and information-packed. I'm so pleased that you took time out of your schedule to join me today. And I hope you have an awesome day. Yurgelun-Todd: Well, thank you so much. We were delighted to join you. Renshaw: Yeah, you too, Karolyn.

In this podcast episode, we talk about cardiovascular labs with naturopathic cardiology expert, Daniel Chong, ND. Chong discusses the use of cholesterol panels and other tests he uses in practice. He dispels some common myths about how to interpret different lab results.   About the Expert Daniel Chong, ND, has been a licensed naturopathic physician, practicing in Portland, Oregon, since 2000 and focusing on risk assessment, prevention, and drug-free treatment strategies for cardiovascular disease and diabetes, as well as general healthy aging, and acute and chronic musculoskeletal injuries. Chong has also completed certificate training in cardio-metabolic medicine from the American Academy of Anti-Aging Medicine and is an active member of the Society for Heart Attack Prevention and Eradication (SHAPE). In addition to his clinical work, Chong serves as a clinical consultant for Boston Heart Diagnostics Lab. Tina Kaczor, ND, FABNO: Hello I'm Tina Kaczor editor-in-chief at the Natural Medicine Journal. I'm speaking today with my friend and colleague Dr. Daniel Chong a naturopathic physician and specialist in cardiology specifically. Dr. Chong is a founder and lead consultant at healthyheartacademy.com as well as a consultant for the cardiology industry. Dan, thanks for joining me today. Daniel Chong, ND: Hello Dr. Kaczor, it's nice to be here. Kaczor: We have talked informally, and I thought this would be a great opportunity to talk specifically for our audience, about the use of cholesterol panels, and we'll go into specifically some breakdown of the usefulness of common cholesterol panels, and then break that out into more particular cardiology panels. There's a lot out there right now about whether cholesterol is or isn't even linked to heart disease, so let's just start at the beginning. Can you give us a little bit about the roots of the cholesterol theory? We'll branch off from there. Chong: I can try. It definitely is a relatively long-standing theory now. As I understand it, the first thoughts as to whether or not cholesterol had anything to do with cardiovascular disease came in the early 1900s on animal research with rabbits, but at that point it was dismissed because people were still not clear whether or not you could make any correlations between findings in rabbits and extrapolate out to humans. The major real focus on the connection between cholesterol and heart disease started more in the mid-1900s almost simultaneously in a way with Ancel Keys and the Framingham study, so they started around the same time. Ancel Keys was one of the first people to really make a point of saying, "We should really research this because we repeatedly are seeing this potential connection," and so he was one of the first people to really start trying to splice it out. Then, the Framingham study started simultaneously. They don't come out with any of their more definitive conclusions until a little later than him with that. That's where it all began as far as I understand it. Kaczor: In the Framingham study specifically I know that there has been ... The broad interpretation in the professional world has been high cholesterol equals risk of heart disease, LDL being the "bad cholesterol," in general. Is there particular subpopulations that this is more true for? In other words, can we say if you are a 40 or 50 something-year-old male this is more true than if you're a 80-year-old male, or a female? Is there any way to delineate that with just looking at broad generic cholesterol levels, nothing too specific yet? Chong: Hopefully, it will be answering your question by saying this, but to me one of the most fascinating pieces of information I heard come out of the Framingham study in particular is that over the course of however many years ... this was a statistic we heard about maybe five or so years ago. The Framingham study had been active for well over 50 years and they had well over 50 years of data on how many thousands of people, and the statement was made by the former director of the Framingham study, so it was certainly legitimate. Essentially what they said was, one of the key pieces of information that they saw in terms of the relationship between at least total cholesterol and cardiovascular disease was that it appeared as though if a person's total cholesterol was at or below 150 naturally, so throughout their lives without necessarily an intervention with a drug or whatever, just the people in the study who had naturally low cholesterol did not get heart disease period. Of course, you can't then take that and make any truly definitive statements, but there is, in terms of a general viewpoint that was one of the things that came out. In other words, nobody with cholesterol under 150 naturally got a heart attack in their study. Again, there would still need to be more done to splice that out and figure out what exactly is going on there and why that is, but there's definitely something to be said. You can see the same exact type of finding if you look at epidemiological research on different cultures of people in history who did not get heart disease or got very little heart disease, all of those people regardless of where they were on the planet, what types of specific foods they were eating, even to some extent what their lifestyle was some of these people smoked, et cetera, the cultures of people who were known and found not to get cardiovascular disease all had cholesterol at or below 150. Kaczor: You're talking about total cholesterol? Chong: Correct. Kaczor: Let's move over to talking about the bad cholesterol. LDL- Chong: Can I pause you for one quick second? Kaczor: Yeah. Chong: Just to say one other thing about that. There's a lot of questions that would be immediately raised from those statements that I just made. One other way that I look at things is, and I know we'll get into it more, but cholesterol in of itself, I will say right from the beginning, has to be involved. It is not a worthless thing to measure, it is not something to just disregard and only focus on information. Time and again it has to be involved, technically it has to be involved. You can't make plaque without it, but it's just an important way to think about it. It's just whether or not it's the primary causative factor and we'll get into that. Kaczor: Yeah, that's an important point. I don't see many people with total cholesterol below 150, but we'll put that aside. It's pretty uncommon. I don't know about other people. Let's break it down- Chong: In modern times it absolutely it is. Kaczor: Let's talk about LDL specifically and just start out with there's a lot of more specific labs that are looking at LDL particle size rather than total LDL. Just a brief primer, if you would, on the difference between LDL- Chong: I like your emphasis on brief. Kaczor: Yeah. Chong: Sorry, go ahead. Kaczor: On LDL calculated as it is in a common cholesterol panel and the particle size as it is measured by several different labs now. Chong: I'll do two separate simple ways that I look at it. One is technically LDLC or "LDL cholesterol" measurements that are most commonly done in the average physicians' offices et cetera is technically measuring the mass or total amount of cholesterol being carried around on LDL molecules. Just as a reminder to people, these LDL molecules are protein-based particles that are essentially like cargo ships carrying around different substances, one of the main ones being cholesterol. When you are getting an LDLC you are getting an estimate of the mass of the total amount of cholesterol being a carried around by all of the LDL particles in the system whereas, an LDLP is specifically getting a count of the LDL particles floating around in any one measurement of blood. From an analogy perspective it's like you're counting either the cargo that's being ... The Pacific Ocean has a certain amount of cargo ships out in it carrying cargo and LDLC is like, "Okay, what's the estimate of total cargo being carried around by all of those ships?" Whereas an LDLP would be like, "Okay, we're going to go into the ocean, we're going to count each one of those ships and see how many there are." Depending on some different factors this is why you could theoretically ... Let's say a cargo ship could technically carry 100 pounds of cargo, you could technically have two ships carrying 200 total pounds of cargo or you could have 20 ships carrying 10 pounds of cargo each. In both cases the LDLC would be the same and yet one, there's 20 ships and the other there's two ships, if that makes sense. The reason why that's so important to make the distinction is that what we know now is that risk specifically goes up with ship count or particle count—not necessarily total mass or total cargo. If you have a way of identifying, "Aha, there is actually only two ships in this ocean versus 20," that can significantly impact risk level. Kaczor: Looking at the LDLC, which is the calculated one, it may or may not correlate with cardiovascular disease is what I'm hearing you say, and LDLP we can use as a more specific correlation with cardiovascular disease. Chong: Right, that is correct. In the grand scheme of things when we're also potentially considering other factors like inflammation, and oxidative stress, et cetera, it's still relative ... we're just talking about cholesterol-related markers and their impact on risk, so there are obviously ... I don't want to discount the fact there are other factors involved here, but when we're just talking about the cholesterol and its impact on future risk or not the particle count is what trumps everything. Again, just in the realm of the cholesterol markers. Just for an example, there's a research study I've seen where they looked at 16-year survival, from year 0 to 16 and measured LDLP and LDLC in each person. This is a very large study, and what they saw is a distinct difference between particle count and future event risk for cardiovascular disease. In other words, you had a distinct increase or higher rate of survival in people who have low particle counts regardless of what their LDLC or mass was. Whereas the people with worse outcomes all had high particles even though some of them technically had low LDLCs or low amount of total mass or cargo. Kaczor: It's been- Chong: It's been clearly seen that there's a distinct difference. It's also important to mention here, it is unfortunately true that there are some people out there who are still saying, "If I have large puffy LDL (i.e., my LDL particles are loaded with a lot of cargo per particle) and yet not necessarily ..." If you have a high LDLC, but all of your LDLs are large and puffy, and you also have a high LDL particle count you will still have an increased risk. There are some people out there who are under the misconception that if LDL particles are large and fluffy or large and puffy enough they can't cause problems, that's totally inaccurate. Bottom line, when we're talking about LDL, particle count trumps everything. Kaczor: Let's move on to HDL. That's really good points on the LDL because I do know that the size and the type, the fluffy or the dense, that idea is very much part of the verbiage that patients use when they come through the door- Chong: I'm sorry, I will say one other thing quickly about that. I don't mean to say that it's worthless to check LDL particle size because it's still true that LDL particle size, the smaller the particles the higher the potential is for future risk, but it's not just because of the mechanism itself. It's like just because there is a strong relation between what causes LDL particle sizes small and what causes cardiovascular disease. As an example, typically people with poor insulin sensitivity, or insulin resistance, diabetes, et cetera tend to have smaller particles, so it's still important to look at particle size because it does add to the predictive value of the test you're running. I don't mean to say that it's worthless or anything like that, you just can't say, "If my particles are large and puffy, I don't care how many there are." Kaczor: Got you. Okay. Let's go back and just come back to HDL, the high density lipoproteins. This we don't harp on as much, the drugs aren't targeted towards it as much. We tend to know that higher is better. How do you use HDL in your interpretations? Chong: One of the reasons why the drugs aren't targeted as much is because they keep trying and failing. Pretty much every study that's ever been done on a drug that it raises HDL shows that they clearly work and then oftentimes the people die sooner, so they have to stop. The bottom line is it's not a cut and dry direct simple relationship where the higher the HDL the better necessarily. Especially if you make a change in somebody, so like diet, lifestyle, et cetera, and their HDL goes up it is absolutely not a guarantee that they are getting better or that they are more cardio protected than they were beforehand. It might be the case, but it's not a certainty. From that perspective, at least personally, when I'm looking at HDL I'm always looking at the whole picture. If I see a relatively low HDL and yet this person might happen to be one of these lifelong naturally low in total cholesterol, naturally low in LDL people I'm not as concerned about that low HDL as I am in somebody who has really high LDL, really high total cholesterol, insulin resistance, et cetera, and they have low HDL. There's a definite difference. Those two people might both have the same HDL number, but one is way more concerning than the other one, and it just has to do with the role of these particles, these molecules, and what are they doing for us? If you really simplify it down HDL does a lot of complicated things, we still don't even know everything that it does, but definitely one of its main job is reverse cholesterol transport where it's helping to remove excessive cholesterol deposited in the periphery so to speak. I like to look at it as a garbage truck or a garbage collector. It is very true that if you do have a lot of "garbage" in the system, you have a high total cholesterol, a high LDL there's lots of cargo, or garbage, or whatever you want to call it being shipped outward you would hope to see the body responding to that by increasing garbage truck count to pick up the extras. You commonly see that on people who go onto low-carbohydrate, high-fat diets. Oftentimes you will see, hopefully, an elevation in HDL as the body is literally just adapting to the additional load on the system that you're putting on it. It does not, however ... Unfortunately, you can't take that response and then conclude that the low-carbohydrate diets are cardioprotective because they cause HDL to go up. It's not that cut and dry, it's more just that the body is responding and having to increase its HDL to adapt and make up for the extra amount of cholesterol in the system, if that makes sense. It's quite complicated. You do see HDL go up for that reason. The other thing is sometimes you'll see high HDL in somebody who's got disease, especially if they're inflamed or they have chronic inflammation. In those situations, in all likelihood, what's going on is that inflammation is known to hinder HDL function. The body always trying to adapt, always doing the best that it can to deal with the cards it's being dealt, if it has poorly functioning HDL it's going to spit out more of them in an effort to continue doing the job that needs to be done. If the HDL are dysfunctional as a result of oxidative stress, inflammation, et cetera in the system if the person has the capability you may sometimes see HDL production go up or HDL number go up on the person's lab because each one is not working as well as it should. Kaczor: That's an interesting idea, that it's a reaction. Chong: Absolutely. It's a fluid, functional system. Again, people just think, "Oh, HDL went up, that's good," or whatever. It's not like that. You have to think about why is the body doing that? What is the response going on? The body's always trying to maintain homeostasis, which would include not having cholesterol collect in the walls of the arteries. Kaczor: That's awesome. I appreciate that perspective. I think it's really helpful for us because we want the quickest most linear path to a conclusion, so it's good to remember to step back once in a while. Chong: For sure. Kaczor: We don't have time to go into labs, other labs in great detail, but what other laboratory parameters would you consider must haves? I'm going to give you a typical case, a patient comes to your office, they themselves have no history of cardiovascular disease. They have both sides lots of cardiovascular risk, so they believe that maybe there might be something going on there. What's your bare minimum of labs? What would you do? Chong: Especially in today's world where we're not necessarily billing insurance or whatever personally, for me, if I'm trying to get the most bang for my patient's buck in the realm of cholesterol I'm going to measure an apo A1, or apolipoprotein A1, I'm going to measure an apolipoprotein B, which for those people that aren't fully aware it's essentially like getting more precise HDL and LDL. Apo A1 is like getting a bit more precise HDL count and apo B is like getting a more precise particle count. Again, that's the name of the game, especially looking at the ratio between those two. I'm also going to measure a lipoprotein a, which has its own independent impact on things and is not necessarily going to be responsive to medications or dietary changes that do impact these other markers. It's a very important marker to assess and you can never really predict whether or not somebody's going to have high levels of that or not, but definitely the potential goes up with a strong family history. Then, beyond that in the realm of inflammation I'm at least going to want to see an HSCRP, I'm at least going to want to do some fundamental blood sugar metabolism related markers. I personally like to check a fasting insulin, and then potentially a hemoglobin A1c as well, although that sometimes has some questionable value depending on each patient. Beyond that, it starts getting a little bit more spliced out and potentially, depending on each patient, what you might go from there. I do check vitamin Ds pretty often, I check ferritin, and iron binding capacity pretty often at least screening that once to make sure there's no hemochromatosis going on. Those are probably the main ones I'm going to want to see. I will definitely do a CBC as well. Kaczor: The one I didn't hear you say, and I'm curious if you do, is homocysteine. Chong: Sorry, thank you Dr. Kaczor. Yes, absolutely homocysteine as well. Again, whenever I have the opportunity especially if there is a strong history and there's good reason to want to delve more deeply than average there are definitely some other markers I would typically run with people, but those would be a great starting point. I don't know if we're going to talk later about going outside of blood tests, but just long story short I don't consider an assessment truly complete without some type of imaging at least on the high risk population. Kaczor: By that, you mean? Chong: Sorry, carotid ultrasound, IMT, or a coronary calcium score. Kaczor: I can vouch for that. I've had several patients with cholesterols that didn't look too impressive, but their coronary calcium scores came back very, very good, and so they didn't have any [inaudible 00:24:42]. Chong: I will say one pearl type of information about that, the value of coronary calcium scores specifically goes up with age. The value of risk assessment using that test goes up with age. In other words, occasionally if a person is still relatively young, typically under about 55, you may have a situation where that person has a decent amount of soft plaque that has not been calcified yet and it will make their calcium score looks pretty good, but then if you check a carotid ultrasound it doesn't look so good. I have seen some mismatches in that regard with some of the slightly younger people, so my tendency is to measure carotid ultrasound, IMT tests with the understanding, obviously, that you're not checking the coronary arteries, but there's an over 90% correlation between the two. To me, a carotid ultrasound is a little pickier, a little more fine-tuned than the other one, but absolutely the high calcium score is a very powerful risk predictor. It's just whether or not you're going to catch everybody that way. Kaczor: Great. Dr. Chong, thank you so much for joining me today, I appreciate your expertise, taking the time. I think this is a to be continued type of thing because we didn't talk about what to do. Chong: I would love to keep talking, yes because I feel like we just started scratching the surface. Happy to delve more into some of these other details because there's a lot of other things to consider. Kaczor: We'll talk about treatments and we can talk a little bit more about imaging techniques next time. Thanks again. Chong: Super, yeah. Thank you.

In this interview, nutrition expert Jolie Root describes the health benefits of the Mediterranean diet and how practitioners can enhance compliance with their patients. Listeners will learn how to effectively utilize this diet in clinical practice. Approximate listening time: 32 minutes About the Expert Jolie Root, LPN, LNC, is a nutritionist, health educator, nurse, medical journalist and well-known radio personality. She travels North America attending medical conferences and educating the public about the roles of nutrition in integrative medicine. She also spreads the word through informational articles published in magazines and newsletters across the country, including Alternative Medicine, Whole Foods, Taste for Life, and Senior Living. In addition, she hosts a weekly talk show called “Food for Thought,” which can be heard Fridays at 10:00 a.m. Eastern Time on AM 1160 WVNJ. About the Sponsor Since 1965, Carlson has produced pure, quality, award-winning vitamins, minerals, omega-3s, and other nutritional supplements. Carlson began with a single vitamin E product, helped launch the omega-3 market in North America in the early 1980s, and now offers a product line with more than 200 nutritional supplements. Carlson is most renowned for the high quality of their award-winning omega-3s, and now they’re available in a premium olive oil. Olive Your Heart® blends cold-pressed Greek Terra Creta extra virgin olive oil with premium Norwegian marine oil sourced from deep, cold-water fish and is available in basil, lemon, garlic, and natural flavor. Each serving provides 1,480 mg of omega-3s, including EPA and DHA. Olive Your Heart® is mild and smooth, and makes it easy and delicious to add heart healthy nutrients into your diet. Transcript Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we are going to explore the efficacy of key components of the Mediterranean Diet. We'll also be talking about enhancing patient compliance to this diet. Before we begin, I'd like to thank the sponsor of this topic, who is Carlson Laboratories. My guest is nutritionist Jolie Root. Jolie, thank you for joining me. Jolie Root, LPN, LNC: Oh. It's a pleasure to be with you, Karolyn. Thanks for the opportunity. Gazella: Well, this is a great topic. We've actually written about this topic a lot in our journal, and I am a big fan of the Mediterranean Diet. I think most practitioners know what makes up the Mediterranean Diet, but can you remind us what the key components of the diet are that contribute most to its health promoting aspects? Root: Yes. It is a diet that is high in plant foods, so that means fruits, and vegetables, and whole grains, and whole grain breads, legumes, and nuts, and seeds. They also use hefty amounts of extra virgin olive oil, and it may or may not include moderate amounts of red wine, and also fish, and poultry, dairy, and eggs are featured, and red meat is minimized. It's only very occasionally that there will be red meat in this diet. It's a plant-based diet with a variety of fruits and vegetables, fresh foods, and whole grains, legumes, nuts, and seeds, and olive oil. Gazella: Now, let's talk about the olive oil, because it seems like the healthy fats are a big component of this diet. What are some examples of the healthy fats in the diet, and why are these fats better for patients? Root: Well, I think that you could say that part of the overarching benefit of walking away from unhealthier fats and towards healthy fats in the diet has to do with inflammation. We know in Western culture that we have an imbalance of fats that promote inflammation relative to an inadequate intake of fats that help to balance inflammation, so specifically I'm saying that one of the really I think imminent qualities of the Mediterranean Diet is that it relies on olive oil and then omega-3s from nuts and from fish, and it's low in omega-6s. That's the problem when you contrast that to the Western pattern diet, which is much higher than it should be in omega-6 relative to omega-3, and in the US, in North America, people rarely use olive oil as their main cooking oil. Here in the West we eat a diet that promotes inflammation, and it's not just inflammation. It also promotes an unhealthy level of clotting in the blood and constricted blood vessels, so the result of that is high blood pressure and arterial stiffness. The Mediterranean approach, using olive oil and omega-3s from nuts and from fish oil, relaxes the blood vessels, helps to govern excess inflammation, and promotes health in areas from heart disease all the way to cognitive function. Gazella: Now, I'd like to continue to deconstruct the diet a bit more, but let's stick with the conditions that you just mentioned, and I'd like to talk about first prevention and then treatment. Let's talk first about prevention. Purely from a preventative standpoint, which conditions benefit most from the Mediterranean Diet? You mentioned heart conditions, but can you expand on that a little bit more? Root: Well, cardiovascular disease, so disease of the heart and the blood vessels, so that would mean not just heart disease with its inherent health risks, but cardiovascular death as an endpoint is something that has seen reduction in the double-blind, randomized, controlled studies and even in single-blind, controlled studies with the Mediterranean Diet, so the Lyon Heart Diet Study and the PREDIMED Study are studies that practitioners can look up and read. They saw a reduction in heart disease and a reduction in heart disease deaths as an endpoint, but along with that we also see blood vessel issues, so hypertension and endothelial function as components of heart disease, are improved on the Mediterranean Diet, because some of the elements in the Mediterranean Diet relax the blood vessels, and that allows for supporting blood pressure in a normal range. The other thing is when you look at the heart, before we have heart disease, we may have diabetes or metabolic syndrome, conditions leading up to sometimes an increased likelihood of an endpoint of heart disease. The Mediterranean Diet helps with blood sugar stability and some of the issues that contribute to the metabolic syndrome, such as derangement of lipids, so cholesterol numbers that are not where we want them, triglycerides that are elevated, and that blood sugar control, and higher than what would be optimal inflammatory markers, and then that's metabolic syndrome, which also sometimes we might call pre-diabetes, but also diabetes itself is something that we have seen benefit in reducing risk of with Mediterranean Diets. That's kind of in the cardiovascular realm, but if you want to go to the cognitive realm, we have seen improvement in cognition in elderly people who followed a Mediterranean Diet with either additional nuts or additional olive oil, and we have even seen some changes in some of the suspected markers of Alzheimer's risk, things like amyloid deposits and amyloid protein. So, earlier in life we're concerned about heart disease. We're concerned about metabolic syndrome, diabetes. Later in life we start thinking about dementia and ultimately with the worst endpoint there, which would be Alzheimer's. Gazella: Yeah. I mean, that's a pretty broad range of conditions. I'm curious. When we switch over to treatment intervention, can the diet be used as a treatment intervention for many of these same conditions? Root: Well, I wouldn't go so far as to say that it would be a treatment for Alzheimer's. We don't generally find that treating Alzheimer's works particularly well once that disease itself has set in, although I would urge practitioners to look up Dale Bredesen and the work that he's doing. However, the cardiovascular disease? Yes. I would recommend the Mediterranean Diet as a treatment if someone were to come to me and ask for a recommendation, because of the ability to change the inflammatory markers, the lipid balances back to a more favorable profile. There is, for example, one of the elements ... I know we're going to talk about this in more depth as we go forward, but think about resveratrol, which is known to enhance nitric oxide production, and that means relaxing blood vessels and promoting endothelial health. In those cases, people that are in pre-diabetes, metabolic syndrome, or actually know that they have cardiovascular disease are looking to improve these factors, and Mediterranean Diet has shown to do exactly that. Gazella: Before I leave this subject, are there any studies on obesity? It seems like obesity can increase the risk of so many things, not only heart disease, but also some cancers, and of course diabetes, and metabolic syndrome, and some of the other things that you've mentioned. Are there any studies showing that the Mediterranean Diet will help people lose weight? Root: Yes. They weren't looking at that as an endpoint, so I'm not aware of studies, Karolyn, where they were specifically looking for weight loss as an endpoint in the study, but they have seen, as an aside, the additional benefit in some of the big studies of Mediterranean Diet of weight loss, although that wasn't really what they were after or what their intent was. People do seem to lose weight when they follow, when they adhere to a Mediterranean Diet. There's the key. Gazella: Right. Root: You know, that's the key in everything that we do, either successfully or not, when we talk about integrative health. But the weight loss factor seems to be more pronounced than in people who follow something like a low fat diet. I think that it's a happy additional benefit of following a Mediterranean Diet. Gazella: Well, that's good. Now, is there anybody who should not be on the Mediterranean Diet? Are there any contraindications or safety issues? Root: I can't think of any. I thought about that. I expected you to ask me that question, and I thought about that. I can't think of any, because the factors in Mediterranean cooking and following that approach are varied enough that if you had ... Let's say, okay, one caution is always what if you have a really strong food sensitivity or food intolerance, so a gluten issue, or what if you have a real sensitivity to nightshades? You could avoid those foods and still follow a Mediterranean approach, so there's enough variety I think in the foods in a Mediterranean lifestyle, a Mediterranean Diet, that I can't think of anyone that really would be a problem. If you choose to be a vegetarian, omit the fish and include more olive oil and nuts for healthy fats. If you are avoiding gluten, then don't eat the gluten containing foods that are part of the diet. There's no hard and fast rule that says that you absolutely must include every element of the diet. If you have an issue with alcohol, you do not have to have the red wine. But as far as just a strict avoidance, I can't think of anyone. Gazella: You know, I would agree. I have not seen anything ... I mean the diet is so fluid and so varied, so I think that that's definitely one of the benefits. I'd like to continue to kind of deconstruct this diet a bit more. You know, you mentioned healthy fats. You mentioned resveratrol. This diet includes a lot of key nutrients. It comes from the spices and the other foods that are featured in the diet. Can you give us some more examples of the specific polyphenols and other compounds that we can find when we break down this diet? Root: Definitely. Let's say tomatoes, which are certainly something that people in Italy, and people in Spain, and France, and most of the Mediterranean countries enjoy, so with tomatoes we have lycopene, and lycopene is one of the dominant antioxidants in the bloodstream when people do eat a Mediterranean Diet. Lycopene itself has been associated with protecting the prostate health in men, reducing certain aspects of risk factors for health disease. So, lycopene from tomatoes is an example. If you look at the leafy greens that are in the diet, then we can talk about lutein and zeaxanthin, and we'd also have to talk about the magnesium that is a very strong element benefit of leafy greens, and the carotenoids, the betacarotene, but lutein has been shown to be very beneficial for the retina. You know, dating back to the 90s, more lutein, even a single serving of spinach a day, reduced macular degeneration by more than 40% in men who were eating a healthy diet including spinach on a daily basis. Lutein is there in the leafy greens. Think about garlic. You've got allicin, and you've got a lot of phenolic compounds in the garlic. Garlic is a benefit for being, first of all, an antioxidant, but also an antifungal. It's just a very healthy food. It also helps to normalize lipids. It helps with blood vessel expansion, so garlic is another element. I mentioned the resveratrol in the red wine. You wouldn't need to do red wine. You could get resveratrol from the purple grapes and from other red foods that are in the diet. If you eat blueberries, you could get pterostilbene, which is another very potent blood vessel health supporting antioxidant. Let's not even get started on the dark chocolate, which is one of the elements, and we love that part, in moderation, meaning about an ounce a day of a good dark chocolate, full of flavonoids, beneficial for the blood vessels. Turmeric, so in the spice cabinet we have the turmeric, which provides us with the curcumin, which is an antioxidant, protects the lining of the blood vessels, associated with benefits in the brain, associated with a reduction in the amyloid deposits. You know, those are just some that come to mind. Then the olive oil, which is certainly a big part of this. There's the oleuropein. There's the oleocanthal. These are antiinflammatory. When you get a good olive oil, you get a little sting in your throat if it's a really good one. Antioxidant, antiinflammatory. We're always a little reluctant to talk about cancer, but anti-proliferation. There are some studies that have shown the biological activity of oleuropein too, and that's an olive oil compound, antimicrobial, antiviral. So, you could apply that to heart disease, absolutely, diabetes, but also neurological diseases. There are just so many mechanisms from the specific compounds that would benefit almost the entire lifespan. I can't think of ... Even children would benefit from having these very nutritionally potent foods as the centerpiece of their diet, rather than pop tarts. Gazella: Yeah. Exactly. It is a long list. I have to say that I've only heard one complaint about the Mediterranean Diet from a clinical perspective, and that is that sometimes practitioners feel like it's not specific enough. You know, the DASH Diet and some of the other diets, they have very specific directions on how to follow the diet, X number of this and X number of this. Now, how do you describe the Mediterranean Diet in very specific terms to ensure proper adherence to the diet? Root: Well, I try to describe the things to include and the things to avoid in order to hopefully be following it quite well. So, we don't include added sugar, for example. I say get rid of that. I talk about limiting and hearty limits on red meats, and instead fish, and also feel free to have days where you don't have an animal protein or the animal protein might be cheese or eggs, but that we keep eggs even limited somewhat. What we're doing is changing out saturated fats for unsaturated fat. I'm not one of these that thinks that saturated fats are all bad, but this is a diet that emphasizes olive oil, rather than butter. When we start to make these changes and we begin to develop a taste for these more natural and less processed foods, your taste buds change, and you begin to find it easier to embrace this more ... It's a simpler approach to cooking, so very few things from boxes, for example, in the Mediterranean Diet. People always say, "But what about pasta?" I say, "Well, what about whole grains? What about exploring using bulgur wheat? If you're going to do a pasta, do something like a couscous. You know?" Fewer things from boxes, fewer things from cans, although tomatoes from cans I think are okay. More fresh herbs, less salt, and more fresh herbs and seasoning as spices. As far as adherence goes, I recommend cookbooks, Karolyn. I think that it's easier to take a kitchen table approach to this. I find a lot of times when diets are specified very strictly, people get very frustrated and overwhelmed with the weights and measures of it all. How do we actually keep ourselves to 200 milligrams of cholesterol in a day, for example? How many milligrams of cholesterol are in an egg? I take a different approach as far as specificity and try to encourage a variety of colors of fruits and vegetables, less canned and boxed and more fresh. Shop more often, not less often, so that you're going and you're getting some fresh produce, and you're going home and having it in the next couple of days. Several meals a week that don't feature meat. At least two or three meals a week that do feature fish, so that you're getting those omega-3s. If you're going to do the eggs, get the omega-3 eggs, because those are full of a very absorbable form of DHA, and also lutein, and other nutrients, the choline that your brain needs. I take more of a Food Network approach to it than I do an American Medical Association approach to it, and I recommend cookbooks. I have a favorite cookbook. It's the Complete Mediterranean Cookbook, and it's done by the people that do Cooks Illustrated Magazine, so it's America's Test Kitchen. I got it from Amazon. It's got 500 recipes in it. I haven't found one that I haven't liked. Gazella: I love that kitchen table approach. You bring up so many good things. When you're describing it to patients, you're talking about ... Just by telling them what to avoid, it's going to automatically be including healthier options in their diets, you know, like swapping out butter for olive oil and shopping more often. That's a great piece of advice as it relates to a Mediterranean Diet. I think those are some great tips. Now, in addition to describing the diet in those specific terms, is there anything else that healthcare professionals can do to improve compliance? Root: I think there is. I think it brings up a piece of the Mediterranean Diet that we don't talk about enough, and that is imagine yourself in the South of France. Imagine yourself on the Island of Crete. Think about the way that they approach their day, their meals, their habits. These are people that are moving at a slower pace than we do here, so it's not as much about convenience as it is about community. The meals are a point of shared experience for the family, the extended family, your neighbors, people that you ... Even when you're doing business with people, you bring them to your table, and you break bread, and you have a glass of wine. It's a much more relaxed, chill approach to things than in our zooming from point A to point B, and running into the deli, and grabbing something, and running back out kind of approach to life. You saunter through the market with a basket over your arm and pick up some fresh veggies, and some fresh fruit, and maybe a nice piece of fish, and maybe they've just baked some crusty bread, and you're going to take that home and break the bread, and dip it in some of that olive oil, which you've ground some seasoning and some spices in, maybe a little balsamic vinegar. You take a very slow approach to that meal. Maybe you're all cooking it together and having it a little bit at a time, but there's this sort of attitude, and this piece of mind, and this slow approach that they take. I think that that is as important to adopt that mindset as it is to be aware of the nuts, and the bolts, and the mechanics, and the ingredients of the diet. Gazella: I am so glad that you brought that up, because you're right. A big part of the Mediterranean eating is social and communal. Honestly, I don't hear a lot of doctors talking about that benefit. I would agree with you. I think that does add to the health promoting aspects of the diet. Yeah. I think that's a great thing to emphasize to patients. Now, for those people who are having difficulty consistently following the Mediterranean Diet, do you recommend dietary supplements. If you do, take us through some of ... I know this might be kind of an unfair question, because it's not a one size fits all, but are there maybe your top three recommendations that would probably be good for 90% of the people? Root: Well, of course, you know, I have my favorites, but fish oils, so a good, high quality omega-3 supplement. Obviously you want a trusted company, because you want it purified. These days, with the omega-3s we are taking the approach of reaching an optimal intake, and that's measurable now. There's actually a little finger stick blood test that we can do now to see where you stand as your omega-3 score is concerned. For most adults we actually need a little more than what had been the recommendation. High quality fish oil that provides somewhere around 1,500 milligrams of the active components, the EPA and the DHA, is one thing, fish oil and with olive oil as your main cooking oil. There's even a functional food supplement now that is even a combination of the two that you don't actually heat up to cook with, but you could use it for salad dressing, or you could use it to do that dip the bread in thing that I described, which is the first course of so many Mediterranean meals. So, that's a place to start is a good, high quality omega-3 or a combination omega-3/olive oil supplement. Then I think something that not enough people are taking that more people probably would benefit from is a good curcumin supplement. It's made from turmeric. The curcumin itself is not really well absorbed, so you want to take it at mealtime. Get one that is CurcuWIN or one of the trademarked turmeric supplements, because the manufacturers have helped with the absorption. Always in a meal with fat is the best way to take either a fish oil supplement or the curcumin supplement. Those are the first two things that come to mind. Then if I were going to pick a third thing for Mediterranean Diet, it would probably be a resveratrol or a pterostilbene. Those are things that maybe people aren't getting enough of in their diet, and especially teetotalers. If you're not drinking red wine, then you may not be getting much resveratrol, and there really does seem to be some longevity associated with that. Gazella: Yeah. I was going to ask you about resveratrol, because even if you are drinking maybe a glass or two, I think that enhancing the resveratrol amount in the diet is probably a good idea. It's such a powerful nutrient. Root: Me too. There are a lot of people that a glass or two is absolutely as much as they ought to do, women. Really you've got to keep alcohol at a small to moderate level, because extra is so bad. So, we've just seen a look at early onset dementia with chronic, heavy drinking, and it was much worse in men, but that's because men are more likely to be the chronic, heavy drinker, but it was scary when I was reading about it, because these men that it's four to five drinks a day ... So, this is a see something, say something for family members. If you know somebody that's drinking that much, it's intervention time. It takes 20 years off of their life. With the resveratrol a little bit of red wine, great, but I wouldn't do more red wine in order to meet my resveratrol goal. I would take a resveratrol supplement. Gazella: Yeah. That's such a great point. Well, before we wrap up, Jolie, I'm wondering if there's anything else that you'd like to share to our listeners about the Mediterranean Diet and how they could or should be using it in their clinical practice. Root: I would encourage physicians to use any kind of teaching tool that they can. There is now the ... I'm drawing a blank on this. The Department of Agriculture makes dietary recommendations, and they actually have one now that talks about Mediterranean Diet, and they help people follow it, a Mediterranean style diet, but there is a wealth of information on the internet from trusted sources that can help with sort of the guidelines for the Mediterranean Diet. I think Oldways has a Mediterranean Diet pyramid. Maybe even keep some good cookbooks in the office, and hold them up, and say, "Here is a great way to get started," and they can order them, or you can give them a gift or something. People need practical advice, and remind them of the community benefit, the gathering the family around the table, because that's not just about the Mediterranean Diet. That's something that really is missing in our busy culture, and everyone I think would be healthier if they were able to do more sharing over meals. Gazella: Yeah. I would agree. I think the Mediterranean Diet is such a powerful clinical tool that practitioners can use. Well, once again, I'd like to thank today's sponsor of this topic, Carlson Laboratories, and I'd like to thank you, Jolie, for joining me today and sharing this information with us. Root: It was a treat, Karolyn. It was so nice to talk to you. Gazella: Yeah. Well, great. You have a great day. Root: You too.

Sponsored by Perque Integrative Health By Natural Medicine Journal There is a significant link between lack of sleep and hormonal, inflammatory, and immune system health. In this interview, Russell Jaffe, MD, PhD, describes the connection and then provides information about his comprehensive, integrative approach to sleep issues. About the Expert Russell M. Jaffe, MD, PhD, is CEO and Chairman of PERQUE Integrative Health (PIH). He is considered one of the pioneers of integrative and regenerative medicine. Since inventing the world’s first single step amplified (ELISA) procedure in 1984, a process for measuring and monitoring all delayed allergies, Jaffe has continually sought new ways to help speed the transition from our current healthcare system’s symptom reactive model to a more functionally integrated, effective, and compassionate system. PIH is the outcome of years of Dr. Jaffe’s scientific research. It brings to market 3 decades of rethinking safer, more effective, novel, and proprietary dietary supplements, supplement delivery systems, diagnostic testing, and validation studies. About the Sponsor PERQUE Integrative Health (PIH) is dedicated to speeding the transition from sickness care to healthful caring. Delivering novel, personalized health solutions, PIH gives physicians and their patients the tools needed to achieve sustained optimal wellness. Combining the best in functional, evidence-based testing with premium professional supplements and healthful lifestyle guides, PIH solutions deliver successful outcomes in even the toughest cases. Transcript Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of The Natural Medicine Journal. Today, I have one of my favorite guests, Dr. Russell Jaffe, with me. Our topic is sleep. But before we begin, I'd like to thank the sponsor of this interview, who is PERQUE Integrative Health. Dr. Jaffe, thank you so much for joining me. Russell Jaffe, MD, PhD: A pleasure to be with you, Karolyn. Gazella: Yes, it's always a pleasure. This is an important great topic. Now, the CDC has said that lack of sleep is a significant national health problem. It's reached epidemic proportions. Now, why do you think so many people today don't get enough quality sleep? Jaffe: Well, first I commend my colleagues at the Center for Disease Control for waking up. Yes, sleep deprivation in our time, in this 21st century, it is at least epidemic, and it may be endemic. Endemic means beyond epidemic. If it becomes so usual that it's like the normal, we don't notice it. Fortunately, CDC has noticed that sleep deprivation causes all sorts of "tsuris." That's a Yiddish word for problems. It causes all sorts of amplifications of dispositions to ill health. Not necessarily the sole cause or the single bullet in the problem that a person has, but anything you have will be made better by good restorative sleep. Anything, any health challenge you have, any performance issue, any life quality issue, will be made better by good quality of sleep and worse by a lack of restorative sleep. The emphasis here is on restorative, not just on being unconscious. Gazella: Right, I would agree with that. I want to dig into some of the technical aspects of sleep. Can you first explain to us the intricacies of the hormonal regulation of sleep? What's going on? Jaffe: Well, half a step back if you permit me, which is in biology, in life, it's always about proportion, or ratios, or balance or imbalance. We can, and I'm happy to talk about the hormones and the neurochemicals, and the sources of these neurochemicals that are amino acids. The sources of some of these neurohormones that are either a vitamin or a fatty acid, a dietary source again. As Hippocrates said several millennia ago, "Let your food be your medicine. Let your medicine be your food." If you start with a healthy, all foods diet that you can digest, assimilate and eliminate, you will then take in a healthy balance of the precursors to all of these neurochemicals, neurohormones, et cetera, and the body will figure out how to utilize them in an efficient and effective way. Now I know that's a kind of high level view. But when we talk about these rhythms, which sleep is a particular example of biological rhythms in action, we do know certain things. There are four phases to sleep. At the end of the fourth phase is the time when a release of growth hormone, a release of neurochemicals, a release of neurohormones occurs, and abnormal cells are identified and eliminated. It's called apoptosis for those of you who speak Greek. But it means that everybody makes abnormal cells, abnormal cells you could hear as cancer. But everyone makes abnormal cells every day. The reason we don't all have cancer is because at night we have a restorative and reparative system that also identifies abnormal cells and eliminates them. Now I mentioned the importance of rhythm, and you asked me about hormones, which is the right question to ask for sure, one of them. One of the hormones we know in relation to stress resilience, and stress adaptation and stress response is cortisol coming out of the adrenal under the stimulation of the pituitary, which in turn is controlled by the pineal, and we'll get upstream at some point. When cortisol goes up because we're under stress, if DHEA, the companion molecule on the other side, the source of the androgens and estrogens, if DHEA goes up in proportion to the cortisol going up, we're fine. It's when the stress hormone cortisol goes up and the DHEA is exhausted and cannot go up, that's when we have a first level of problem. That's when people feel invincible, but they're not. They're cruising for a bruising, but they're not aware of it because the cortisol overrides the commonsense of the DHEA and those androgen and estrogen compounds. There are other hormone ... Go ahead. Gazella: Yeah, that makes a lot of sense, and I was going to ask you, but are there hormonal connections, so please continue. Jaffe: Oh. If I may, there are other modulators. One important balance point or ratio is the cortisol to DHEA. But then there are others including the adrenaline to serotonin. Now adrenaline derived from the amino acid tyrosine, derived from our dietary protein, adrenaline says, "Go and you can persevere until the success shall be won." In contrast, serotonin says, "Now hold on there. Maybe we don't have the fuel to go all the way to the end. Maybe we should be a little more sensible here and not get exhausted." Now serotonin comes from tryptophan just like adrenaline comes from tyrosine. Both of these come from the proteins we eat. If we're a carnivore, we'll have more of those amino acids. If we're a vegan or a vegetarian, we'll have less. If you think your engine is burning too hot because of too much adrenaline, if you think that it would be better for you to be more on the calm than on the assertive side, my suggestion is try a plant based diet. You might not want to be a vegan or a strict vegetarian cause I think you should have a wide variety of foods that you can digest, assimilate and eliminate without immune burden, and I'm not making any political statements about ... Although my personal preference is a more plant-based diet cause I think that's healthier. I think that's less polluted. I also think that's better for the planet. But I put my little advertisement in, and now I'll get back to the fact that tryptophan becomes not just serotonin, the soothing counterbalance to adrenaline, but serotonin becomes melatonin in the pineal, this deep control center. We've learned about the pituitary as the master gland, but the mistress or the master of the master gland is the pineal, modulated through the thalamus and the hypothalamus. We can get into all those tracks if you want cause I really am a biochemist and a neuroanatomist. But the point is that amino acids derived from our diet become the neurochemicals whose balance we express in our personality, in our resilience, or in the way in which we're distressed. The people who have mood issues, the people who have endurance issues, the people who are concerned that sometimes they, maybe either overreact, or they're just not in tune with what's going on and people misunderstand. In any of those situations, you have an imbalance of cortisol to DHEA and/or an imbalance of adrenaline to serotonin. Gazella: Right, that makes a lot of sense. I love how you brought adrenaline and serotonin to life. That was perfect. I want to stick with the topic of amino acids here. You know, I've heard varying views about tryptophan versus 5-HTP regarding sleep. Can you clear up that confusion for us? Jaffe: I absolutely can. There was a time when tryptophan was the favorite approach, the more natural approach to sleep, to sleep enhancement, sleep quality. Then it fell under a cloud because of something called Eosinophilia–myalgia Syndrome. At that time ... This was the late 80s, early 90s ... there was voluntary recall of tryptophan. At the same time, interestingly, that serotonin reuptake inhibitors were being advocated on the pharma side. Tryptophan fell under a cloud until it became clear that due to a change in production techniques, one company called Takeda had inadvertently, not intentionally, but they had changed the way in which they produced tryptophan. It was cheaper for them to produce large bulk of tryptophan. But they also included what turned out to be something called Peak E, which was a dimer. It was two tryptophan molecules bridged by a small carbon bridge. The consequence was induction of pain, myalgia, muscle pain, and an allergic-like response, eosinophilia. The FDA, out of an excess of caution, asked the industry to voluntarily recall tryptophan and they did, which was the right thing to do, in my opinion. At the same time, my group published a clinical observation, which is we had uncontaminated tryptophan, and we gave it to people with this Eosinophilia–myalgia Syndrome, and it helped them get better, and we published that. If tryptophan was the real culprit, then giving them tryptophan would have made them worse, and it made them better, and we published that. Now the agency, the FDA did not yet know about the contaminate now known as Peak E, this dimer of tryptophan that somehow jangles things up or messes things up. In fact, we do know how it does that. It bridges across two receptors in a way that makes the cell very unhappy. Out of an excess of caution, the FDA asked the industry to withdraw tryptophan. In the absence of tryptophan, 5-HTP became popular because it's a tryptophan derivative. That sounds okay. Until you learn that it most often goes to quinolinic acid, and a series of excito-neurotoxin consequences that are not so good. You don't get as much of the serotonin to melatonin conversion when you go through 5-HTP. It's actually better to go directly from tryptophan to melatonin and bypass the 5-HTP. 5-HTP is a supplement. It is available in health food stores and online today. It is not my preferred form because I always believed in tryptophan. I still believe in tryptophan. My recommendation is enhanced uptake tryptophan. Because it turns out when you have a little B6, a little B3, a little zinc, a little of the right fiber, then you double, triple or quadruple the uptake from the intestines into the body so you get smoother uptake and better total absorbability, or what we call bioavailability. That is basically what we recommend. Gazella: Interesting. With the tryptophan, is there a dosage range for sleep that you typically recommend? Jaffe: Well yes, in regard to the tryptophan ... And I do recommend the enhanced uptake and the chaperone delivery. But for the tryptophan itself, it's anywhere from 500 milligrams of free amino acid to 1,000, maybe even 2,000. It is absolutely safe for people to start at the lower end, which would be one capsule, say 500 milligrams, and go up anywhere from two to four, depending on their body mass, depending on their situation. Then often people ask me the question, "Well, what if I get up in the middle of the night?" "Well, why did you get up in the middle of the night? If you got up to go to the bathroom, go to the bathroom and get back to bed. If you want, you can take a second dose of the tryptophan because the peak occurs at 30 minutes. It has really done its job after four hours. If you are in a deep sleep and you stay restorative in your sleep, you don't need more. But if you get up, for whatever reason, my suggestion is take another dose. Take another one, two, three, four capsules, whatever dose works for you, 500 to 2,000 milligrams per dose. You can take that two or three times in a night." Now occasionally, people do tell us that if they take more than 500 milligrams, they sleep really soundly. But when they get up, they're a little bit groggy before they really get going. That feels, to me, like a little too much. "Metabolism does play into this individuality," as Roger Williams told us. Biochemical and individual natures of our metabolism, how robust is our liver, how effective is our spleen and kidney at any moment in time, these are important variables. Gazella: Yeah, and I'm glad that you mentioned that about the breakthrough insomnia, because I think that a lot of people are affected by that, where they will wake up at 2:00 in the morning and then they're frustrated, so that's good to know about the tryptophan. Now are there any- Jaffe: Well, let me add if I can jump in on that, cause it is very, very common. It is also very common in people who are more creative, more sensitive and more aware. Why? Because they're worrying. I think you know this, but the Dalai Lama is my daughter's godfather. One of the things he said to me is, "Don't worry." Gazella: Good advice. Jaffe: Good advice, hard to do. You have to practice it and that's the point. Sometimes two, three, four o'clock, maybe even five o'clock in the morning, it may feel early, but that's the preferred time for monks to meditate. They go to bed early, but they get up early. If you're one of those people ... And I'm in that phase of my life. I tend to go to bed early now, and I tend to get up early. I find those few hours before dawn a delicious time to either relax, or stretch or meditate, or just have a few quiet moments to myself where the phone doesn't ring. Gazella: Yeah, I would agree. Now are there any other amino acids that can be helpful with regulating sleep and mood? Jaffe: Well, yes, and there's two parts to this discussion. There are the amino acids related to detoxification. Then there are the amino acids related to mood stability. If I can take those in reverse order, in regard to mood, it turns out that glycine, the simplest amino acid, is also a neurotransmitter. It's a soothing neurochemical. If the nerves are excited, glycine calms them down. If the nerves are exhausted, glycine provides an energy source to wake them back up. Glycine's really very important in the brain, also important in the gut nervous system. In addition, if you combine glycine with methionine, a methylating detoxifying amino acid, and combine those two with magnesium aspartate, an amino acid that in its own right has been studied as a mood modulator, as an antidepressant. But when combined with the detoxifying methionine and the neuro-balancing glycine, that's a very interesting combo of simple amino acids that in combination with the tryptophan can give even deeper and more restorative sleep. Gazella: Perfect. Then now you mentioned the detox side of things? Jaffe: Right. Now the other side is there are three phases to detoxification, phase one, phase two, phase three. Within the detoxification system, you want sulfur containing amino acids like cysteine, C-Y-S-T-E-I-N-E, you want methionine, but you might want a little phenylalanine because in order for sleep to occur, you must have enough adrenaline in the deep brain sleep center so that the adrenaline falls at the same time that the serotonin rises. That's called going to sleep at the cellular, molecular, biochemical level. Now what happens if the serotonin rises cause you're tired, and your body wants to go to bed, but there isn't enough phenylalanine-derived adrenaline to fall, you'll be exhausted, but you'll still be awake. What about the other side? What if the adrenaline falls, but you didn't take in enough tryptophan so the serotonin doesn't rise? You'll be groggy, but you won't have restorative sleep. We need to have the fall of adrenaline and the rise of serotonin at the time when we're horizontal, not vertical. Gazella: Right. I want to kind of circle back to what's going on when we're sleeping because you mentioned previously when we're sleeping, the body is really quite active. I've read studies associated with inflammation for example. If you get six hours or less in just one night, you put your body in an inflamed state. We know that there's a strong connection between the immune system and the inflammatory system. What's going on with those two systems in particular, and why is it so damaging if we're not getting enough sleep? Jaffe: A profound, important question, and a question for our time, our 21st century challenging time. There is so much that occupies people today, so many screens, so many calls, so many distractions, so many attractions, that most people do not appreciate that sleep is essential for quality of life. If you want to add life to years and you want add years to life, you must have a quality of sleep. Most of us, at some point, we become tired and/or exhausted. We do get into bed. Most of us even take our clothes off before we do that. But most people ... And I'm the exception here and I would advocate being the exception. Most people do not have a roughly half an hour or so during which they prepare for a restive, restorative, rehabilitative sleep time. They might even dream. They might even be able to solve a problem and bring a solution back into waking time. It turns out you can do things called lucid dreaming if you're inclined towards that. But the bottom line is that sleep, preparation for sleep, and appreciation of the importance of sleep has been massively devalued in our society. Where we're supposed to go as close to 24/7 as we can and sleeping is somehow either depreciated, deprecated, or seen as a sign of sloth. Now when I was a young doctor in the academic medical world, I can tell you that I slept so little that when Rebecca and I got together ... Cause she's a fine artist who values her sleep, and she's a terrific human being if she gets 10 to 12 hours of sleep a day. At the time, I was sleeping about four hours a day and thought that was just fine, which meant we had to choreograph being together, but we figured it out. My point is that very often the very people who would benefit from mindfulness and restorative sleep don't "have the time." They can't fit it in. They're too driven to succeed. Or, as the Dalai Lama says, "They sacrifice their health to gain wealth. Then they give back their wealth to regain their health and they are so busy living in the past or ruminating about the future, that when they pass in the moment, they have barely lived." That's a classic Buddhist perspective. I'm not particularly Buddhist, although I've done of lot of mindfulness myself. I have found that it helps to not just to feel that I've indulged in sleep, but to know that with wisdom and more years, having the ability now to go to bed early and get up early is delicious. I don't miss going out to the Kennedy Center as much. Occasionally, I still want to go out and socialize. I have friends over. I prefer to cook for them than to go to a restaurant cause when I cook, I know what they're going to eat. I know we're going to sleep better because it's going to be food you can digest, assimilate and eliminate without any burden. I'm even going to take into account what their biochemical individuality might be and sometimes I get it right, sometimes I don't, but I always try. Sleep is our friend. Sleep is to be appreciated for the positive side, not for the absence of usual consciousness. Gazella: You know, I want to get back to specific nutrients cause we've already talked a lot about amino acids. But before I talk about other nutrients, I'd like to talk about sleep medications. There are some pretty potent prescription sleep medications. There are over the counter sleep medications. Do you have an overarching view of these sleep medications and if they're helpful or if you think it's better to try to get patients off of these sleep medications? What's your view? Jaffe: Well, actually it's interesting. My view is more or less the same as the FDA. The FDA's official view is if you can do without them, please do. If you can possibly do without them, do. Because the adverse effects are clearly known. The benefits are also statistically defined. If you absolutely need them, they are beneficial at least within the reductionist frame of our scientific method. But while I agree with the FDA, I often find that if people will follow through on what we're talking about. Including, having a diet that's appropriate for them, that they can digest, assimilate, and eliminate without a burden. When they have enough of the essential vitamins, include vitamin D, which is really a neural hormone and other essential nutrients. So that their cells can deal with the challenges and stresses of the day without being so overexcited or overexhausted, those are two extremes which we want to avoid. Being overexcited or overexhausted. We want to be resilient, we want to be in the middle. Sleep is just really important for all of that. Now with regard to prescriptions, the most common question I get is, can we approach this nature, nurture, and wholeness approach to sleep ... these amino acids and these fatty acids that are the precursors for these complicated molecules. Can I increase nature's sleep balancing, stress balancing molecules? The answer is yes, although in many cases—especially, in the cases of Ambien and other serotonin reuptake inhibitors—when you bring in nature's team, the full valet or symphony of life, very often you can taper the pharmaceutical hypnogogic sleep medicines. Taper them, eliminate them slowly. The importance of that is that it's known and it's been proven in many scientific studies. That you do sleep, however you don't dream and you don't have the normal sleep rhythms phase one, two, three, four. You don't have the normal release of growth hormone, which is so important to identify abnormal cells and eliminate them. So sleep prescriptive medicines are benefits with a cost. I usually find that when we bring in the essential nutrients that people can't make. That they must take in from their diet or supplements, that they can then taper safely and effectively, the pharmaceutical sleep medications. Gazella: Yeah, that's good to know. Certainly long-term use is definitely not indicated with those pharmaceuticals. Talk a little bit about those specific nutrients that practitioners who are listening can use to help improve sleep quality. Jaffe: Well, we've talked about amino acids, so I'd like to note turn towards the fats. Those essential fatty acids, the omega-3 and omega-6 fats are the sources for the prostaglandins. They're the sources for the thromboxanes, which are the really active but short lived molecules inside the body. We can measure the balance of omega-3 to 6 in laboratories. Neil Harris has devoted decades to validating the omega-3 index. My colleague, Artemus Simopolous, has looked at the NHANES National Health and Nutrition survey data. She says that Americans now, instead of having a balance of omega-3 to -6, because of edible oils, and fats in our diet, and these foods that are crisped, and chipped, and so forth. It's typical for Americans to have 20, 30, 50, 80 times more omega-6 than omega-3, which is pro-inflammatory. That makes you feel worse faster. That makes you more inflamed, and creaky, and uncomfortable faster. Folks like me no longer use edible oils. We cook with wine, or we cook with broth, or we cook with beer, and whole foods. When you do that, you can restore a typical four to one ratio and not be so pro-inflammatory. Many people that I meet today look, feel, and function as if their body is under assault, inflammatory assault as if it's not repairing itself. Inflammatory is really repair deficit. When your body can repair itself, you don't have inflammation. So we don't want to have zero omega-6 intake, but we don't want to have 50 times omega-6 to omega-3. There is an omega-3 index test. It's one of the eight predictive biomarkers. It can help you take in the sources of fat that are essential and good. By the way, there is good fat. Omega-3 and omega-6 fats are good unless they're damaged by air and oxygen, in which case they're bad. So you want them distilled under nitrogen. You want them in whole food sources. You want them in the healthier forms so that your body can convert the omega-3 fats into the prostaglandins that repair you while you still have a little bit of omega-6 to activate the system. But not so much that it creates repair deficit commonly known as inflammation. Gazella: Perfect. Now in addition to the EFAs, before I move on to my next question, are there any other nutrients that you'd like to highlight? Jaffe: Well, yes and it's in the broad category of, life is connected at every level with every thing. But when we think about, say sleep, and how the systems that convert these amino acids or these fats into the quality of sleep molecules that we're looking for. We must have enough antioxidant ascorbate in the cell to donate electrons and prevent free radical oxidative harm. We must have enough magnesium, choline, and citrate. We advocate advanced uptake in chaperone delivery of magnesium using choline citrate. So that you can correct the acetylcholine/bile salt deficiency at the same time you've energized and alkalinized the cell, while bringing magnesium into the cell. When very often, there's too much calcium and too little magnesium. In fact, calcium channel blockers are a major category of pharmaceuticals because there is a relative excess of calcium. But there's an absolute deficiency of magnesium. Magnesium in the diet, Dr. [Rah Aleem 00:06:51] has shown, has dropped half, by 50 percent in the last 50 years. While the need for magnesium ... because of stress and medicines that waste magnesium. Like, proton pump inhibitors and H2 blockers, and many chemotherapies, and even hypertensive medicines like diuretics are known to waste minerals including magnesium. So, as my grandmother used to say, the rents are going up and the ceilings are coming down. Gazella: It's true. So, you know the conversation between the patient and the doctor is an important one. I'm wondering for the Healthcare Professionals who are listening, what type of tips do you give patients to help them get a good night's sleep? I know you believe that it's not just a matter of handing somebody a pill and calling it a day. It's a very comprehensive approach that you have to health. So, what type of advice do you give to people who are struggling with sleep? Jaffe: Thanks for asking and yes, as important as I believe diet and supplementation are in the 21st century, it's about what you eat, drink, think, and do. So, let's talk about the doing part of preparing for sleep. Here's what I do, I set aside the half an hour before I'm gonna get into bed. During that half hour, I want to get as much value as I can. So I set a salt and soda bath. I put a half to one cup of Epsom salts and a half to one cup of baking soda. My skin isn't dry, but if my skin was dry, I might put in a drop of Rosemary or some other Emollient oil, an aromatic. I soak in there for about 20 minutes. While I'm soaking, I do five minutes of deep abdominal breathing. If you want to know what abdominal breathing is like, get a video of a baby or watch a baby because they all do it correctly. They breathe abdominally. Then, do about 15 minutes of mindfulness practice, or active meditation, or whatever is your preference to let go of the day. Very often, people fall into bed, reasonably tired and exhausted. But thinking about the stresses of the day and they bring that into the bedroom. In my bedroom, we actually have no screens, we have no clocks, we have no alarm clocks, we have no phones. I know this is hard to believe, but I actually when I go to bed, I don't need to hear the emails coming in on my phone. I believe, if you can, at the place where you sleep should be a place of serenity. That you should give yourself a half an hour to let go of the day and really let it go. Then, have an active time of restoring yourself through sleep. If you want the bonus round, it's the green dichromatic light that I learned about from [Banti Darmawarh 00:09:56]. A rather extraordinary monk. Green dichromatic light is known to go directly from the retina to the pineal gland. In the pineal gland, it says everything is okay. Green is the harmonizing color. This has nothing to do with vision. It has everything to do with the retinal / pineal direct connection, which has been reconfirmed by others. As [Banti 00:10:25] said, well wisdom, new things, millennia ago, and science is catching up and that's a good thing. Gazella: I have not heard of the green light. That's fascinating to me. Jaffe: No, it is fascinating. You may have heard about light boxes. There are people with what's called Seasonal Affective Disorder or SAD? Gazella: Sure. Jaffe: Norman Rosenthal and NIHMINH, showed that if you stay in front of these fluorescent light boxes for three hours a day, it boosts your pineal, and you get a little more melatonin, and you're less depressed. Banti said, people don't have time for that 20 minutes twice a day in front of the green. That's what we recommend. Gazella: Wow, that's awesome. What about other hygiene aspects? Like the temperature of the room? Light in the room? Are those valid? Jaffe: Thanks for asking. The answer to the second question in regard to light. It should be as dark as possible. Now if for some reason, it is not pitch black in the room where you sleep, please get a comfortable eye mask. You should not have photons of light hitting the retina while your eyes are closed during sleep. If that requires an eye mask, please. They're not expensive, they can be comfortable. Take a flight on the Air Singapore, they'll give them to you. At least in business class. That's the question of dark. Now, the nature of the room itself, should be comfortable, cool, this is a situation where warm is not your friend. What I have is a latex mattress which is very firm and lets me float. That's a nice thing. I have a duvet, so I have ... Some goose donated some feathers and somebody sewed this together. In Germany, this is routine. You have this light Duvet on top of you. You have a mattress that will support you. It's cool in the room, you don't want it warm. Does that address your question? Gazella: Absolutely, absolutely. Those are some great tips that our Practitioners can keep in mind when talking to their patients. I'm just wondering, we're about ready to wrap up, is there anything else that you'd like to talk about sleep for our listeners today? Jaffe: No. I thank you for the opportunity to come at it in this way. Restorative sleep is one of essentially components of a life well lived. As someone who didn't think that sleep was important for many decades of my life, I can tell you it was a mistake. I'm correcting that now. But I do also believe there are different phases to a life. I think if you're an adolescent, you have a different sleep rhythm. My understanding today is that young people actually do go to bed later and get up later, although they may or may not be able to do that and still graduate from schools. But I do think at different seasons of our life, we have different relationships between wake and sleep. I want both my wake time and my sleep time to be as productive as possible because this is the only life that I know I have at this time. Therefore, every moment to me is precious. Gazella: Yeah, absolutely. Great point, great way to end. So once again, thank you Dr. Jaffe for joining me. I'd also like to thank the sponsor of this interview, Kirk Integrative Health. Thank you and have a great day. Jaffe: Thank you, Karolyn. A pleasure. There is a significant link between lack of sleep and hormonal, inflammatory, and immune system health. In this interview, Russell Jaffe, MD, PhD, describes the connection and then provides information about his comprehensive, integrative approach to sleep issues.

Skin conditions are common in many clinical practices. In this interview, dermatologist and researcher Raja Sivamani, MD, describes how an integrative approach can help improve outcomes, especially with difficult to treat dermatological conditions. About the Expert Raja Sivamani, MD, CAT, is a board-certified dermatologist and an associate professor of clinical dermatology at the University of California, Davis, and director of clinical research and the Clinical Trials unit. He is also an adjunct sssistant professor in the Department of Biological Sciences at the California State University, Sacramento. He engages in clinical practice as well as both clinical and translational research that integrates bioengineering, nutrition, cosmetics, and skin biology. With training in both allopathic and Ayurvedic medicine, he takes an integrative approach to his patients and in his research, with a focus on the gut and skin microbiome and lipidome. He has published over 80 peer-reviewed research manuscripts, 10 textbook chapters, and a textbook titled Cosmeceuticals and Active Cosmetics, 3rd Edition. He has a passion for expanding the evidence and boundaries of integrative medicine for skin care. About the Sponsor Dermveda is an integrative skin care, beauty, and wellness site dedicated to inspiring and empowering people to develop a healthier, more holistic relationship with their skin. We provide skin education tools and personalized, science-reviewed health content for both consumers and practitioners. Membership is free at Dermveda.com. Dermveda's continuing medical education site, LearnSkin, was developed by leading dermatologists and integrative medicine practitioners to support integrative dermatological education throughout the healthcare community. The goal is to share the latest in scientific research and treatment options in dermatology for both Western and Eastern medicine. We aim to meet the growing demand for high-quality, evidence-based education that bridges conventional and alternative medical approaches. The first eczema series will begin in March at LearnSkin.com. Later this year, Dermveda will be hosting the first annual Integrative Dermatology Symposium in Sacramento, CA, from October 19-21, 2018. Experts from around the world in the practices of Western, Naturopathic, Ayurvedic, and Traditional Chinese Medicine will come together for this special event. The Symposium will feature educational sessions, clinical content, targeted industry trends, practical takeaways, and best practices related to all aspects of skin care. Registration opens in March at IntegrativeSkinSymposium.com. Transcript Karolyn Gazella: Hello. My name is Karolyn Gazella and I am the publisher of the Natural Medicine Journal. Today our topic is integrative dermatology and my guest is Dr Raja Sivamani, an integrative skin care expert. Before we begin, I'd like to thank the sponsor of this topic who is Dermveda. Dr Sivamani, thank you for joining me today. Raja Sivamani: Thank you so much for having me. It's a pleasure to be here. Gazella: Well this is an interesting topic and I have to say that we have not covered this a lot in our journal so I'm super excited to talk to you today. So, let's start with a very basic question. How do you define or describe integrative medicine specifically as it relates to dermatology? Sivamani: Karolyn, I agree with you, this is actually a really exciting area when we think about integrative dermatology. So, to answer the question that you're asking, you know, how does integrative medicine specifically relate. Dermatology really has many facets to it and by in large, many times when you go to see a dermatologist the appointment can be a little rushed and typically you're in there for about 15 minutes or so and many times the conversations will be focused on things like the diagnosis, which is super important and then some basic treatment plans and maybe a surgical treatment plan. When we start thinking about integrative approaches, really then you start to take into all the other aspects of dermatology that are so vital to providing good care when it comes to anything skin related. So things like psychology, preventative approaches, diet, what you're putting on your skin, daily habits. All these things comes together and so, when I think about integrative approaches to dermatology it really is about a team approach and some of that team can be deployed by the practitioner but many times I also think about this expanded team that's working together in a way that, you know, maybe one practitioner's able to provide certain aspects and then another practitioner is able to provide other aspects of care and then them working together. So, that's how I view integrative. And integrative, just as an add-on but I do want to talk about is, is not to say its separated from conventional medicine. I think bringing in conventional medicine, making that just as an equal part of the conversation, I think is really important. Gazella: I would agree and that fits perfectly with the focus of our journal so this is great now. So, what are some of the more common skin conditions that practitioners are faced with in clinical practice? Sivamani: It turns out dermatology is so common. A lot of people see people with skin conditions. They did a study at the male clinic where they looked at how often and what kind of skin conditions, sorry, what kind of general conditions come in and skin conditions were really high. The ones that are common and they tend to be pretty prevalent in the general population are things like acne, of course, these all depend on different age groups as well but, acne is very, very common. When we talk about eczema specifically, atopic dermatitis, that's another one that's common but there's also other conditions that may not be as common as those two but are still pretty common. Things like psoriasis and there's also seborrheic dermatitis, rosacea so, there's quite a few things that come up over and over again. And, another sub-set of eczema, not atopic dermatitis, which is more dealing with pediatric population, and that does extend into an adult population but then there's also just common irritations that come up on the skin on a day-to-day basis that anyone can get. Things that mean to us as contact dermatitis either from irritation or an allergy. Gazella: Now out of all of the skin conditions that are out there and, there are a lot of them, what are some of the more difficult to treat skin conditions that practitioners are faced with and, why are they so difficult to treat? Sivamani: Karolyn, this is such a great question. I really like this question for a couple of reasons. When we talk about difficulty I really break that up into two modes, two facets to what makes a skin condition difficult to treat. Firstly, a skin condition can be difficult to treat just because it's a rare condition and it will require some treatments that sometimes aren't always well studied because it's rare. And so, you can have conditions that just don't happen that often and when they do often and sometimes you know this condition can be auto-immune or other facets to them that really make it more difficult. I think there's a second facet, though, that really is a challenge as well. And that's conditions that are chronic and that require constant management. We really have to integrate in lifestyle and other approaches and symptom management isn't enough. So, you have conditions like acne that, you know, they just won't cure on their own, you need to have some sort of active management to that in a very, what I believe, holistic conversation and things like eczema require so much activity from, you know, if you're a patient and you're taking care of eczema that's one thing but, if you're a baby, then you're really dependent on caregivers and so then it becomes a conversation with the caregivers and managing how they are approaching the treatment. And so, I think that that second group where you have chronic conditions that don't necessarily have a cure but, if you can get really good management then it can make a huge difference. I think that is also a pretty big difficulty because it requires constant conversation and a lot of education. I think education is key in those kinds of situations. Gazella: Yeah, that would make a lot of sense. Now, I find it interesting that you have training in both allopathic and Ayurvedic medicine. I'd like to focus a bit on Ayurvedic medicine. So, for our listeners, what is Ayurvedic medicine? Sivamani: Yeah, so, Ayurvedic medicine is, it was born from a tradition that's very rich in India. It's over 5,000 years old and their approach is really looking at homeostasis, meaning when you're in balance. Just to simplify it, is when are we in balance and when are we in a state of imbalance? And so Ayurvedic medicine has some tendance in how it measures what it means to be imbalanced, what is your imbalance state and I'll just use a couple of cavular terms. One is, prakriti which is your state of balance or what they say your original constitution but then you also have this notion of what's known as Vikrity which is your imbalance state and they use the three doshas which are known as vata, pitta, and kapha in a very broad manner to identify what those imbalances are and, a lot of approaches including lifestyle approaches, dietary approaches, what you put on your skin, believe it or not, you can even describe western medicine from an Ayurvedic perspective and the idea is, can you take this imbalance and move it back towards balance? What I really like about Ayurvedic medicine is that it can really go well in an integrative approach. So, you clearly have conventional approaches that tend to be focused much more on symptom management and then Ayurvedic medicine gives you tools, and I think that's really important, just having this ability to have this conversation to what it means to be in balance so you have these tools to talk about what are different lifestyle changes you can make or what would be an appropriate dietary change that you could make. If I may add, one of the fun things I think about Ayurvedic medicine is that it gives you the opportunity to personalize and in conventional medicine they're really good about research studies that will study a large group of people and then in many ways you get kind of an average outcome and then you can apply that to each patient. So, if you bring the two together you have this really powerful system where Ayurvedic medicine allows you to personalize a little bit more on top of what you're going to do and then conventional medicine gives you the ability to have broad-stroke approaches that might give you a good starting point, especially for symptom management. But, Ayurvedic medicine is really rich on the personalization aspect. Gazella: I think that's important. That really has become a big emphasis, it's no longer one size fits all. I would assume, especially in the area of dermatology and these difficult to treat skin conditions. Can you give us a few examples of how you apply Ayurvedic medicine to dermatology in clinical practice? Sivamani: Sure, you know, that is one of the funnest parts and really interesting parts of my practice. I feel like I get to know my patients better. If I may say, from one of the really key aspects of Ayurvedic medicine is, I have to get to know the patients habits much more and understand what kind of things are they doing in their daily life. That in and of itself gives me a greater connection. So, for example, if I have a patient coming in with eczema and Atopic dermatitis, we're talking about different management approaches. One of the things that can sometimes come up is if we're just taking a pharmacological approach and we're talking about steroids, a lot of people want to know, am I going to be doing these steroids for the rest of my life, is there any sort of way that I could do management that doesn't require the steroids to be used? So then you have this rich knowledge in Ayurvedic medicine about all these different oils and how oils are used on the skin and, there's a rich, rich literature, rich history on different oil therapies and what they call oliation and what's known as abhyanga, so self massage or massage with oils. And it really opens up a conversation because you can start talking about moisturization but bringing in the science of natural oils and, this is an area that's started to really grow in dermatology, what's the role of coconut oil, what's the role of olive oil, what's the role of sunflower, safflower oil, this has now started to hit the medical literature. What Ayurvedic medicine does is it goes one step further and you can do herbal infused oils and I have these conversations with my patients. I tell them, you know, why don't we talk about maybe some simple ways to make a herbally infused oil where you can have a moisturizer that is really based on an oil therapy. And what starts happening is, people start to become very engaged with themselves. Their skin becomes a part of them that they're not afraid of anymore and they're used to touching themselves in a way that's actually very therapeutic and then, you know, funny thing is, when I have these conversations then they realize that there's a holistic approach and then they're okay with using the steroids and they understand why we're using steroids and then it's part of a bigger picture approach to managing their symptoms. So that's one example that comes up very frequently in my practice. Gazella: And now give us an example of a herbal infused oil. Like which herb would you put with the oil for which condition? Is it that simple? Sivamani: It's a little bit more nuanced. Gazella: Okay. Sivamani: What you have is you have different dosha imbalances and different oils, there can be, some oils that are warming in tendency or they can be cooling, I mean, you have to balance that with the doshas but, I'll give you one example, which I think is a pretty good one. Coconut oil is widely used now as a moisturizer and sometimes what we can do is we can infuse, there's a herb called neem. Neem has both anti-bacterial and anti-fungal properties and we've been studying it. Actually, I have a basic science laboratory as well and we've been looking at neem specifically. But, one thing you can do is you can create an infused oil that has coconut oil as the base with a neem infusion and what that does is it gives you this oil that's not only going to be helpful for bolstering the skin barrier and nourishing the skin and, from that aspect but you also get that extra little antibacterial effect. Now, I don't want to claim that it's an antibacterial like something that's been studied through the FDA but that being said, in eczema, sometimes, its smaller shifts in the microbiome and one of the things that we try to do is think about, from a practical perspective, can be infusing oil that might be able to touch upon those kind of aspects and then eventually it would be nice if we could start studying them in controlled studies and really looking at how, what is it doing to, for example, the microbiome? But that's one of the examples of an infused oil that we might use. Gazella: Yeah, that's a great example. Now what advice do you have to healthcare professionals who may be struggling to treat some of these difficult to treat skin conditions in their clinical practice? Sivamani: This is such a fantastic topic to talk about. When it comes to treating conditions that are a little bit more difficult, I think it's important to realize that there's a team available and there's also the patient perspective. But I think the team approach is really important. You're not alone and, what I mean is that, if you have someone that has a really bad itch, for example, we can do our best as a, myself, as a dermatologist, I can talk to them about what are some of the things they can do to help their skin not be as dry or are there some treatment options to help reduce the itch even from a pharmacological perspective. But then, I think it's really helpful to start thinking about the psychology of itch. What are the other approaches that we can take so then, if we can get them to one of my colleagues in, for example, traditional Chinese medicine and they can take an approach where maybe they look at acupuncture, and that can channel in on a different aspect to itch and, you know, focusing a little bit more on some of the other approaches, I think that's where it really becomes important. When you're struggling to treat a more difficult condition that may even be chronic, it's to start thinking about a team approach and I feel like that's the essence of integrative approaches anyway and so if we can start developing teams and developing good partnerships with other healthcare professionals then as a healthcare professional we won't feel alone and as a patient, the patient won't feel alone either and they see that there's a team working for them. Gazella: Yeah, absolutely, and that definitely is in line with the integrative approach that you described in the very beginning. Now, you are an advisor to the company Dermveda. Why did you want to work with Dermveda and how is it different from other skincare companies? Sivamani: What I really like about Dermveda is it's focused on education and, if you look at the founding team, the founding team consisted of people that are really dedicated to dermatology, they're very good teachers and lecturers and, also they have a good education background and, I like education first approaches because I think if you can teach people to start thinking more deeply about their condition, and when I say deeply, not just about maybe the molecular mechanisms or some sort of cellular pathway but really understanding that that's important but, it's also important to think about things that may be affecting you emotionally or psychologically and allowing people the space to see that these are also important and by opening them up to have better conversations with themselves and their practitioners. That's why I'm so passionate about this company. I'd personally really dedicated to education, I like education in all of its aspects and I think its really important to empower patients and practitioners and so, because of that approach, I really am drawn to the Dermveda's approach and also, the holistic and the integrative approach allowing us to learn about, not just conventional medicine but also thinking about Ayurvedic medicine, traditional Chinese medicine. Our naturopathic colleagues have such great insight into the botanicals and into plant based approaches but I think that, giving a platform for this open discourse that's honest and credible is super important so that's why I'm so interested in this whole approach. Gazella: Yes, I was thrilled to see that Michael, Dr Michael Traub is on your team. He is a friend of the Natural Medicine Journal and on our editorial board. A very top-notch doctor so, that was exciting for us to see that as well. And now, Dermveda is also hosting an integrative dermatology symposium this October in Sacramento, California. Can you tell us a little bit more about that symposium and why you feel it may be important for practitioners to attend. Sivamani: We are so excited about the symposium, the integrative dermatology symposium is going to be the first time where we're going to get all the different perspectives into the same room and have a good open discourse and really start talking to each other ina way that we can start building relationships. This symposium is going to really feature a wide variety of things. You mentioned Dr Traub, he's going to be one of the speakers there. I still remember one of the first lectures that I saw with him and I was really impressed by, not only was he able to talk about the pharmacological approaches but it was so nice that he put in things about, and this was with eczema, we were talking about treating eczema, he had a lecture on that and, he put in things about a humor and what does that do for a child at the end of the night when they're about to go to bed, if you can have some way of getting them to laugh, does that make a difference? I think its important to talk about these aspects and what we'd like to do in the symposium is really put that into a situation with all come together in a focused way where we have this combined goal of just making it better for each other to treat our patients and leaning what's new and what's coming out that's in the new literature and realize that any one perspective isn't the full approach. And, if you can start taking a different perspectives it really makes a difference and, I'll give you an example. So one of the things that we're going to be talking about is like one of the lectures is going to talk about emerging approaches to eczema and there'll be conversations about all these new medications that are now coming out but then there's also going to be conversations about what is the latest science on the oils that are being used for eczema. Which oils seem to be the best, which one's may not be the best. And then from there, they'll also swing into a conversation about diet and so, I think one of the things that sometimes we miss out on in just the medical education that we might go through is that you might get pieces and bits but when we start thinking about continuing education, you want to start really have good, honest discourse about all the aspects because that's really what the patient really wants. They want to have a good, holistic conversation about everything. They want to know what can I do with diet or, what can I do with my lifestyle approaches. So, this is going to give practitioners, that attend, the chance to be empowered to understand what is the latest in that but not only that, I think the most exciting part about it is, we're going to get everybody in the same room and you just never know what's going to develop in those kind of situations. What kind of partnership and friendships are going to come out of that and I think that's the way to really push the boundaries of medicine so that when we talk about integrative medicine it really just becomes medicine and it's just the approach that we all would want to take with any patient that comes in. Gazella: Yeah, that's a very good point and it sounds very comprehensive and we have a link to the conference. So, for our listeners who want to learn about more information about the integrative dermatology symposium, you can just click on that link and then you'll be able to find out more information. Well, once again, Dr Sivamani, thank you so much for joining me and I would also like to once again thank our sponsor, Dermveda. Sivamani: Thank you so much and it's been a pleasure to be here with you. Gazella: Great. Have a great day.

About the Interview Tina Kaczor, ND, FABNO, recently sat down with Dugald Seely, ND, MSc, FABNO, director of the Ottawa Integrative Cancer Centre, to discuss several ongoing studies in integrative oncology. Studying integrative oncology has unique study design challenges. They talked about how these challenges are met and how current study designs are attempting to accurately reflect complex in-office care. Seely covered a broad range of topics, from details of specific studies to an overview of the current landscape of collaborating with peers in integrative oncology. He also offered some tips on how private practice clinicians can begin to participate in research. The Thoracic POISE Trial One of Seely’s current research endeavors is the Thoracic Peri-Operative Integrative Surgical Care Evaluation (POISE) Trial. Seely says it’s probably the most interesting and complex study his team is currently working on. The goal of this trial is to explore the impact of naturopathic medicine in addition to conventional usual care at the hospital for patients who have thoracic cancers and are eligible for surgery. The researchers are randomizing a group of these patients into receiving standard usual care at the hospital only, or getting usual care plus an integrated approach delivered by a naturopathic doctor before surgery and for a year after surgery. They’ll be looking at a whole battery of different outcomes, including adverse events related to surgery, quality-of life-measures, immune function, inflammatory changes, cost-effectiveness, and, ultimately, long-term survival and recurrence rate over 5 years. Seely sees this study as an opportunity to investigate the effectiveness of truly holistic, whole-person care. To do that, they’ll be employing interventions in 4 domains: Targeted natural health products Nutritional approaches Fitness improvements (particularly pulmonary fitness) Mind and body medicine and psychological well-being At the end of the study, Seely expects to be able to say whether, as a whole, naturopathic medicine in this setting can make a difference in outcomes related to survival or adverse events related to surgery.  Canadian/US Integrative Oncology Study Another study Seely is working on is called the Canadian/US Integrative Oncology Study. This is being done in partnership with Bastyr University. The other principal investigator is Leanna Standish, ND, PhD, LAc, FABNO. This study, which will be conducted over a 6- to 7-year period, will recruit and observe the interventions given to patients with 4 types of late-stage cancer. The researchers will look at the naturopathic care interventions given to these patients at 11 different clinics across North America. Seely and the research team are looking at clinics with the most innovative and useful therapies in naturopathic oncology. They’ll document the interventions and follow the patients to observe effects on survival rates. In addition, they’ll be looking at cost and quality of life. In the end, Seely hopes the CUSIOS trial will shed light on the outcomes we see with patients who go through these advanced integrative oncology clinics. How Can Clinicians Get Involved in Research? For clinicians interested in getting involved in research, Seely offered this guidance: Build relationships. For him, doing graduate work was key because it automatically caused him to engage and collaborate with others. If you’re interested in research, start by connecting with people at academic institutions and begin the dialog. If you’d like to learn more about the sites currently involved in integrative medicine research, visit Clinicaltrials.gov. About the Expert Dugald Seely, ND, MSc, FABNO, leads the clinical practice and cancer research program for the Ottawa Integrative Cancer Centre. In addition to his clinical role as a naturopathic doctor, he also serves as the executive director of research & clinical epidemiology at the Canadian College of Naturopathic Medicine, affiliate investigator for the Ottawa Hospital Research Institute, and vice president for the Oncology Association of Naturopathic Physicians. Seely completed his master of science in cancer research at the University of Toronto and is a fellow of the American Board of Naturopathic Oncology. As a clinician scientist, Seely has been awarded competitive grant and trainee funding from the Canadian Institutes of Health Research, the Canadian Breast Cancer Research Alliance, the SickKids Foundation, the Lotte and John Hecht Memorial Foundation, the Ottawa Regional Cancer Foundation, and the Gateway for Cancer Research Foundation. Transcript Tina Kaczor, ND, FABNO: Hello. I'm Tina Kaczor with the Natural Medicine Journal. I'm speaking today with naturopathic physician and researcher, Dugald Seely. Dr. Seely is the founder and executive director of the Ottawa Integrative Cancer Center in Ontario, Canada. He has led numerous research projects including the largest integrative naturopathic cancer care clinical trial ever conducted in North America. He has more than 50 MEDLINE indexed peer-reviewed publications. Last but not least, among his many accolades over the years, he has most recently been awarded the Dr. Rogers Prize, which is a prize awarded in Canada for excellence in complementary medicine. Dr. Seely, thanks so much for joining me today. Dugald Seely, ND, FABNO: Thanks so much for having me on to talk, Tina. Kaczor: There are so many things that we could talk about in the realm of research. You're also a practicing clinician, so there's lots we could discuss. I want to start off with a couple projects that are currently ongoing for you, maybe that you're knee-deep in. If you could just start us off with a couple research projects that you have going on these days. Seely: Yeah. Sure. One of the ones that you mentioned, the integrative oncology study, is a big study that we're doing. That's probably the most interesting and complex study that we're running right now. I say running a little bit loosely because we actually haven't started it yet. We're waiting on final ethics approval. We're nearing the runway anyways. This is the Thoracic POISE Trial, which is the Thoracic Peri-Operative Integrative Surgical Care Evaluation Trial. The goal for this trial is to explore the impact of naturopathic medicine in addition to conventional usual care at the hospital for patients who have thoracic cancers and are eligible for surgery. What we're doing in this study is we're going to be randomizing a group of these patients into receiving standard usual care at the hospital only, or getting usual care plus an integrated approach delivered by a naturopathic doctor prior to their surgery and for a year after the surgery as well. We have a whole battery of different outcomes that we're exploring, including adverse events related to surgery. We're looking at quality of life measures. We're looking at some biological surrogates, including immune function, inflammatory changes in the body, and we're looking at some cost-effective outcomes and, ultimately, long-term survival and recurrence rate over 5 years. This study is a long study. It's going to take us probably, by the end of the whole thing, maybe 12 years. We're starting off with a feasibility component to explore the interventions and how effective they can be applied before we move into the randomized component with a much larger population. Kaczor: That brings up a question in my mind. That is, when you talk about the feasibility aspect, are you designing it such that the intervention will be standardized across the patients, or will this be more naturopathic in it being more personalized per patient in a systems-based approach? Seely: Yeah. That's a great question. We've struggled a lot with how to develop the intervention in a way that could be representative of naturopathic medicine in the field. Then, also scalable and standardizable in a way that it could be replicated in another trial. I think we balanced it as much as we can from both ends. It depends on who you speak to I suppose around that. The goal is truly holistic or a whole-person care. We have components that relate to the use of targeted natural health products that we've standardized for this population. We've got a nutritional approach that we've standardized to some degree. We have interventions related to improving fitness and pulmonary fitness in particular. Then we have interventions related to mind and body medicine and psychological well-being. Those four domains comprise the types of interventions that we have. Within each of those, we developed specific interventions that we detailed how this would be applied, and under what conditions, to these patients so that this can be clearly documented. There is a standardized approach that we're using. There is some flexibility in terms of the patients and how they represent in terms of making changes to the intervention. For example, if someone presents with diarrhea, they will be provided with probiotics as well as their core interventions. If they have weight loss, they would get whey protein as well. If they're experiencing mucositis or neuropathy, we'll apply glutamine. There are some things that we can tweak based on symptoms that the patient has. Initially, at least, everyone in the study is going to get a course of intervention that everyone will receive similar. We don't know what is going to be providing what effect. That's the nature of a pragmatic study like this. We'll be able to say, at the end of the day, that this whole-person approach, what effect does it have on the outcomes that we're looking at. These are important outcomes for these patients regardless. It's a bit of a black box at the end of the day. We won't be able to identify what specific intervention has what effect, but we can say, as a whole, naturopathic medicine in this setting can make a difference in outcomes related to survival or adverse events related to surgery. Things like duration of hospitalization after surgery, so we'll have information on that. Kaczor: This particular trial is being done in conjunction with area cancer centers and your center specifically. This is site-specific. Is that right? Seely: It is initially. The feasibility study, which won't be randomized, is going to happen with the Ottawa Hospital as the hospital site. Then, the Ottawa Integrative Cancer Center (OICC) will be the site where the naturopathic care will be delivered. Once we have run in a few of them, when we do the randomization, we do plan on having at least 2 additional sites across the country. We have a couple places identified that will be good sources for recruitment. It will take place in other sites as well. Kaczor: Great. I like the idea of it being a whole-systems approach because that's one of the things that we run into in naturopathic medicine is that the reductionist view of a single agent being studied is never reflective of what we're actually doing. That's great. My understanding is you have another study that has multiple locations. Is that correct? Seely: Yeah. We're doing another study, which is quite different. It's an observational study called CUSIOS. It's the Canadian/US Integrative Oncology Study. This is being done in partnership with Bastyr University and the other co-PI is Dr. Leanna Standish. Really, we're looking at in this study over a 6- to 7-year period to recruit and observe the interventions that are given to patients with late-stage cancer, 4 types of late-stage cancer. We're looking at what the naturopathic care interventions are being given to these patients at 11 different clinics across North America—5 in Canada and 6 in the United States. Each of these clinics are being led by what one would consider to be a naturopathic oncologist or someone steeped in naturopathic oncology. We're tying to look at clinics that have some of the best therapies, the most innovative and useful therapies, in the naturopathic oncology realm being given to these patients. We want to look at what those interventions are and we're documenting that using REDCap. Then, we're going to be also following these patients to see what the survival rate is amongst these patients. Then, we're also doing a substudy within that looking at cost and quality of life. Their experience through the care as well in a more of a qualitative kind of a way. Again, a lot of outcomes that we're trying to track, it is observational so it won't have the same sort of subjective biases for sure. It'll give us, I think, a lot of really good information about what the practice of naturopathic oncology is ostensively at its best, and what are some of the outcomes that we're seeing patients go through these advanced integrative oncology clinics. Kaczor: Yeah. Let me ask you this as far as time horizons. These are both pretty lengthy studies. I have a 2-part question. One, when can we look forward to preliminary results or the first publications coming out of either of these trials? Two, are they registered such that, regardless of how the data shakes out, positive or negative, that it will be published? I understand that once trials are registered in a certain way, the data has to be published at some point. Seely: Yes. For sure, we will publish regardless of what the outcomes are. The CUSIOS study is ongoing. It is registered under clinicaltrials.gov. Thoracic POISE is not yet registered because we haven't got it through ethics yet. We will be establishing that soon. We will be publishing those, no question. We actually have submitted one publication so far and it's been peer reviewed. This is looking at the intervention development process that we used for thoracic POISE, which is really a collaborative effort with physicians at the hospitals, at the hospital pharmacists, the naturopathic doctors as well. That's being submitted for publication. We also have information related to the survey. When you survey the whole profession through the Oncology Association of Naturopathic Physicians (OncANP), we wanted to know what were the best interventions, what were people using. That really helped influence the interventions that are being chosen for this study. That's also being submitted for publication. Hopefully, we'll see those out in the literature in the next few months. Kaczor: Great. I'm going to switch gears just a little bit. You mentioned pharmacists and other doctors at these cancer centers. I guess one question to us out there, whether we're clinicians or we're in the research realm, is collaboration and creating those bridges that are required to really study integrative oncology. My question to you is, how to go about that? Maybe just let me know if, over the years, has it changed? It seems like it would be easier now than say 10 years ago, or even 15 years ago. Can you speak on that a little bit? Seely: Yeah. I think it has gotten easier. There's more of an openness to doing the evaluations and the studies. We're seeing more interest in research, I would say overall, into naturopathic and complementary approaches to care. There's still certainly resistance that exists. Academics and researchers are much more open to looking at these questions typically than clinicians may be. The interest is really in trying to figure out what works from a research perspective. I do believe it's getting more easy to collaborate in that way. Funding opportunities are not easy for sure. I think that, within the naturopathic community, we know that we have a lot of low-lying fruit from our own intervention palate that it should be researched. There's good reason for it, and there's a lot of [inaudible], and there's some early evidence of benefit. [inaudible] have not been researched adequately in many cases. In terms of building relationships and trying to engage with others, I found doing graduate work was really helpful. There's an automatic process that you engage with others. There's an expectation to be collaborative, and reaching out to people who are doing research at institutions to say, "You've got a good idea about an intervention that might have some effect." I think people are surprised when there's really a good openness for those questions. I think finding people in academic institutions that have a focus on research is a good place to start and to try to start a dialogue and a relationship really. Kaczor: Yeah. Let me ask you one last question. That is, if people are interested either in your area geographically or they want to look up the centers that are involved in the US/Canadian collaboration trial, where should they look for more information? Seely: Clinicaltrials.gov will list all the different sites that are involved in the trial. I think there's more information related to that probably on our website, OICC.ca. Yeah, clinicaltrials.gov will have the information related to that. Kaczor: Okay. Great. As far as getting funding, this is usually in collaboration. I mean, you have a research background and a masters degree and such, so your advice to clinicians who just have their clinical degree is to collaborate basically and find others who are of the same passion for whatever question is being asked and maybe try for grants in that direction? Is that correct? Seely: Yeah. I think trying to become part of a team, reaching out to different groups that are involved in research techniques through the colleges. They often have research departments and may have some information related to that. Talking to universities and people there. A really great place to start, I think, in terms of doing research too is publishing case reports. There's more of a drive for case reports in [inaudible]. That's something that is ... I know that the AANP is trying to support more case reports. I think that diving into that and writing up a case report that really clinically just gets someone steep into what the evidence is in the literature around the topic and leads to more investment. It's a more accessible entry point into research I would say. Kaczor: That's a great bit of advice. We, as clinicians, are always ... Everybody has a few cases that are extraordinary over the years, so that's a good bit of advice, especially within integrative oncology when extraordinary cases do happen. It would be great to document that and see if there's commonalities and create studies like yours around those treatments. That would be incredible. I really appreciate your work, your time with me today. I hope we get to talk again in the near future. Thanks, Dugald. Seely: Thanks so much, Dr. Kaczor. I totally appreciate the journal and what you're doing with it. Thanks for having me. Kaczor: Take care.

One in four men over the age of 65 has urinary incontinence, according to the Centers for Disease Control and Prevention. In this interview, men's health expert Ronald Morton, MD, FACS, describes how urinary incontinence is diagnosed and treated. He also provides detailed information about the key medical devices that are available to treat this condition. Approximate listening time: 14 minutes About the Interview Although urinary incontinence is not as common in men as it is in women, it is more prevalent than many people think. According to the Centers for Disease Control and Prevention, one in four men over the age of 65 suffers from it. The underlying causes are often similar in both genders: aging and weakening of the pelvic floor muscles. However, pelvic trauma or prostate disease or surgery can also contribute to the problem in men. Urinary incontinence creates significant quality-of-life issues, so finding effective treatments is very important. In this interview with urologist Ronald A. Morton, Jr., MD, FACS, Natural Medicine Journal’s publisher Karolyn A. Gazella discusses the prevailing treatment options for male urinary incontinence. For some men, pelvic floor exercises alone can provide relief. For others, diet and weight modification are necessary. Others may opt for more advanced interventions, including surgery. Surgical options range minimally invasive to extensive. On the simpler end of the spectrum is the basic urinary sling. In this quick procedure, a sling is inserted to replicate the support lost in previous interventions or trauma. On the other end of the spectrum is an artificial urinary sphincter, which regulates urine flow through a pump. Of course, surgical interventions are not without risks and side effects. Morton addresses those and discusses how to determine whether a patient is a good candidate for surgery. Listen to this interview to learn more about the current treatment options for male urinary incontinence, as well as Morton’s predictions for the future of incontinence treatment. Scroll down for the full transcript. About the Expert Ronald A. Morton, JR, MD, FACS, is the vice president of clinical sciences for the Urology and Pelvic Health division of Boston Scientific, a position that he has held since August 2015. Before joining Boston Scientific, via acquisition, Morton worked for Endo International plc as chief surgical officer, American Medical Systems. Previously, he worked for GTx, a biotech company in Memphis, TN, as chief medical officer. Prior to joining GTx, Morton was chief of urology at Robert Wood Johnson Medical School and director of urologic oncology for the Cancer Institute of New Jersey. He also held an endowed chair position as director of the General Clinical Research Center. Morton holds a BA in natural sciences from The Johns Hopkins University and received his medical doctorate from The Johns Hopkins University School of Medicine. He has board certification as a diplomat, American Board of Urology. Transcript Karolyn: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today our topic is male urinary incontinence and my expert guest is Dr. Ronald Morton. Dr. Morton, thank you for joining me. Dr. Morton: Hi, Karolyn, and thank you for having me today. Karolyn: Well great. Well, let's just start with the basics. How is urinary incontinence diagnosed in men? Dr. Morton: Karolyn, urinary incontinence is not as common in men as it is in women, although it does happen more commonly than people think. The main causes are as it is with women, aging and weakening of the pelvic floor muscles. But more importantly, and the reason for many of the interventions that we have for urinary incontinence in men is it can be due to trauma to the male pelvis and/or surgery for diseases of the prostate. When I say disease of the prostate I mean both benign conditions like BPH, which many men suffer from and are aware of, and then also prostate cancer, which is a very common cause for surgery on the male pelvis. Karolyn: And then what's considered the gold standard of treatment for this particular men's health condition? Dr. Morton: There are many ways to treat male incontinence, as there are many ways to treat female incontinence. The usual approach that will be taken by a urologist is to go from the least invasive to more invasive solutions until the patient is happy. I think that one thing that always has to be kept in mind is that this is really a quality of life issue for most men, especially since urinary incontinence in males is generally a disease of men who are older. The median age of diagnosis of prostate cancer is about 63 years of age or so. Since operations on the prostate are the common cause for this, they're generally older men and it's a quality of life issue. What one male will find satisfactory control of the urinary incontinence might be totally unsatisfactory to another. So the general approach would be to start with exercises, commonly called Kegel exercises. The same exercises that we suggest that women do who have a mild degree of urinary incontinence and see if that won't help. If Kegel exercises won't help and it's not something that can be helped with diet and weight modification, then we go into more invasive treatments for male urinary incontinence. The first level of invasion is a procedure that only takes a few minutes, really, less than a half an hour called a male urinary sling. It's much like the slings that are used in women. It  supports the male urethra and holds it up, providing support that has been lost due to the previous surgical intervention or pelvic trauma in hopes that that will correct the incontinence. Fore more severe degrees of incontinence we often times need to move towards what is really considered, as you say in your question, the gold standard for severe incontinence, which is the artificial urinary sphincter [AUS]. In that procedure, a cuff is placed around the urethra and this cuff is connected to a pressure-regulating balloon, which controls pressure in the cuff, keeping the urethra closed and preventing leakage of urine and also a pump, which is placed in the scrotum. When it's time to urinate, the male can just activate the device. The fluid leaves the cuff and goes into the pressure-regulating balloon, opening the urethra. The male can then urinate and then after a period of lock-out time, the cuff will refill, returning him to a state of continence. Karolyn: So let's talk about these two, the sling and the sphincter. What determines whether or not a patient is severe enough for the sphincter versus the sling? What's the difference between those two patients, the one that gets the sling and the one that gets the sphincter? Dr. Morton: Good question because again, it has a lot to do with personal preference. But there are some general guidelines that one can go by. When we measure incontinence and it can be a difficult thing to put a number on, but most men who have incontinence will use urinary pads in their shorts in order to trap urine leaking. A good gauge of to what degree a male leaks is how many times they have to change that pad. Now, some men will as soon as there's a small amount of urine because of the discomfort it will cause will change that pad right away. Some men tend to allow the pad to get very, very soaked before they'll change it. Everyone behaves a little bit differently. A way to get a handle on exactly how much leakage a man has it to do what we call the pad weight test. So we'll give them all the pads that they might need for a day and a bag that can prevent evaporation and they just collect the pads that they use for the day, put it in this bag, and everything is pre weighed, and then we weigh it to see what the volume of urine leakage is. A rule of thumb, if they're leaking around five pads or 300cc of urine a day, that's severe and is more likely to be treated with the artificial urinary sphincter. Degrees of urinary leakage that are less than that can be and generally might be recommended that they be treated with the sling procedure. Karolyn: Now are there are any contraindications associated with each of these options, the sling or the sphincter? So in other words, are there men who would not be a good candidate for either of these options? Dr. Morton: Well, they have to be able to undergo a surgical procedure, and while the sling procedure is relatively short, it does require at least a regional anesthetic. The artificial urinary sphincter procedure is a little bit longer and requires a general anesthetic so they have to be fit for the surgery. The sling is generally not recommended for men if they have been treated for prostate cancer with radiation. The outcomes there haven't been as good as they have been with the artificial urinary sphincter so in that setting we generally would recommend a sphincter as opposed to a sling, even if they were otherwise a good candidate for a sling. Karolyn: What about side effects? Are there any side effects associated with either of these devices? Dr. Morton: I'll take that question separately for each of the two devices. The side effects associated with the sling are that if you don't choose the patient in the best way, two things can happen. One, the patient can not have their incontinence adequately treated. A second issue is if you put a sling in a patient whose major problem is not one of the urethra but is a bladder issue, and that can be sorted out ahead of time with uro dynamics, but if you did you may render that patient obstructed or in urinary retention. The problem doesn't have to do with external sphincter deficiency for that patient. For the artificial urinary sphincter what we're doing is we're placing this cuff around the urethra. It does over time potentially compromise some of the blood supply to the urethra in that area and you can get what's known as atrophy of the urethra in the area of the cuff. When you get atrophy in the area of the cuff there can be a return to urinary incontinence. Of course for both of these procedures, since you're putting a foreign body in, there's a risk of infection, although infectious problems with these devices have been relatively low. Karolyn: Okay, that makes a lot of sense. Now, I'm just curious because you have a certain expertise in this area as chief surgical officer of American Medical Systems. What general advice do you give to physicians who are treating men with urinary incontinence? Dr. Morton: One, most of the advice that I have is for physicians who have men with incontinence but aren't necessarily the experts in treating them. There's a couple of things. One of the things that our research has shown us is that many men who are subjected to surgery for prostate cancer, for example, and who then suffer from incontinence don't recognize, or aren't made aware that there are treatments for it and they suffer in silence we like to say. So, if we can get anything out to the many physicians listening to this podcast it would be don't let this happen to any of your patients. Make sure they understand that if they do get incontinence after, for example, radical prostatectomy, there are options and there are potential solutions for this. The second message is I spend a lot of time working with the engineers and we're constantly looking at ways to come up with a better mouse trap if you will. What can we do to avoid the complications we spoke of earlier? What can we do to help physicians identify the proper patients so we don't use a sling in a patient who should've had an AUS, or an AUS in a patient who should've had a sling? And what can we do to make the functioning of the AUS a little bit easier so that in this elderly population of men they are always candidates for the device? Karolyn: Yeah, that makes a lot of sense and I'm glad that you brought that up about suffering in silence and information. Obviously, a well-informed patient is the best patient to have. So letting that patient know his options is absolutely critical. So one final question for you Dr. Morton. What is on the horizon when it comes to devices for this particular issue with men? Do you see existing devices just being improved? Do you see new devices? Are we kind of where we should be? Look into your crystal ball and tell me what the future holds for this. Dr. Morton: I don't know if I'm the best person to predict the future, but I think that our efforts are to make sure that A, these are the right solutions. We are constantly looking at, are there other options? Are there other ways to manage urinary incontinence? Could we come up with a less invasive way to place the sling or a less invasive device would replicate the great performance of a sling? On the urinary sphincter side of things it's a mechanical device, so can we simplify that mechanism so that it's easier for the patient to implement? Remember there's a patient interface with the AUS. Most devices that we implant, like when a cardiologist implants a pacemaker, there's no patient interface. The patient doesn't have to decide whether or not their pacemakers work. It's in and it just works. For our device, at least for the artificial urinary sphincter, there's that patient interface. So if we can improve that patient interface with the device and make it as reliable as possible, that's what we're looking to do in order to improve the overall performance of the device and have men have a greater satisfaction with their quality of life. Karolyn: Yeah, that makes a lot of sense. Well, this has been very informative. Once again, thank you, Dr. Morton, for joining me today. Dr. Morton: Karolyn, thank you for having me. Karolyn: Have a great day.

By Karolyn A. Gazella  In this sponsored podcast integrative health expert Russell Jaffe, MD, PhD, CCN, describes a comprehensive approach to identifying immune dysfunction long before illness sets in. He also provides advice regarding diet, lifestyle, and dietary supplements. Jaffe explains why choice is far more significant than genetics and how to counsel patients about reducing immune burden. Approximate listening time: 30 minutes  About the Expert Russell M. Jaffe, MD, PhD, is CEO and Chairman of PERQUE Integrative Health (PIH). He is considered one of the pioneers of integrative and regenerative medicine. Since inventing the world’s first single step amplified (ELISA) procedure in 1984, a process for measuring and monitoring all delayed allergies, Jaffe has continually sought new ways to help speed the transition from our current healthcare system’s symptom reactive model to a more functionally integrated, effective, and compassionate system. PIH is the outcome of years of Jaffe’s scientific research. It brings to market 3 decades of rethinking safer, more effective, novel, and proprietary dietary supplements, supplement delivery systems, diagnostic testing, and validation studies. About the Sponsor PERQUE Integrative Health (PIH) is dedicated to speeding the transition from sickness care to healthful caring. Delivering novel, personalized health solutions, PIH gives physicians and their patients the tools needed to achieve sustained optimal wellness. Combining the best in functional, evidence-based testing with premium professional supplements and healthful lifestyle guides, PIH solutions deliver successful outcomes in even the toughest cases. About the Host Karolyn A. Gazella is the publisher of the Natural Medicine Journal and has been writing and publishing integrative health information since 1992. She is the author or coauthor of hundreds of articles and several booklets and books including her latest book The Definitive Guide to Thriving After Cancer (Ten Speed Press, 2013) that she wrote with Lise Alschuler, ND, FABNO. Together with Alschuler, Karolyn is the cohost of the "Five to Thrive Live!" radio show on the Cancer Support Network and iHeart Radio. She is the co-creator of the Five to Thrive® Plan and the author of "The Healing Factor," a blog on PsychologyToday.com. Gazella is based in Boulder, Colorado.  

Cell phone use is increasing worldwide. We are told that the radiation they emit is safe, but is it really? We have now been using cell phones for over 30 years, and data is accumulating that the radiation they emit, although non-ionizing, has definite biological effects. A couple of Natural Medicine Journal articles on the topic … Continue reading A Primer on the Risks of Cell Phone Use →

Wall Street Journal, New York Times, Prevention Magazine May is Mental Health Awareness Month & highlighted throughout America. According to the National Mental Heath Association, an estimated 22.1 percent of Americans ages 18 and older- 1 in 5 adults suffer from a diagnosable mental disorder in a given year. Mental health disorders can also affect 1 in 5 young people. This segment is for educational purposes only. Please, if you or a loved one is experiencing depression, there is so much help available so reach out. There are people that care, talk to someone. There is hope. If you are being treated for depression, always consult with your own personal physician who can address your medical needs. My guest Cheryl Myers is head of scientific affairs and education for EuroPharma, Inc., a natural medicine company with over 80 products being sold throughout North America and Europe. In this role, Cheryl oversees technical literature development, product research validation, educational outreach and acts as a liaison with thought leaders in integrative health. She has a degree in psychology & worked in the field of psychiatry for 10 years. A recognized expert in integrative health and dietary supplement use, Cheryl has been a featured guest on more than 250 radio and television shows. She is well known as an advocate of bridging the worlds of mainstream and natural medicine to achieve health outcomes neither can create alone. Cheryl has been interviewed by the New York Times, Prevention Magazine, the Wall Street Journal and other periodicals on wide ranging topics such as dementia prevention, menopause symptom relief, cancer care, heart disease and many other aspects of health and wellness. She has appeared on the PBS television show “American Medical Review,” hosted by Morley Safer, to explain coenzyme Q10 and cardiac recovery. She has acted as a technical consultant for many segments of the PBS TV series “Healing Quest,” hosted by Olivia Newton-John. A graduate (with honors) of Purdue University, Cheryl, whose first degree was in nursing, also has clinical certifications in oncology (cancer care) and gerontology (health issues of aging). She has lectured on Alzheimer’s disease and related dementias at TriState University in Indiana. As a member of the editorial board of the Natural Medicine Journal (the official journal of the American Naturopathic Association), Cheryl evaluates scholarly articles and studies illuminating the science behind natural health interventions. Contact Cheryl @ cmyers@europharmausa.com ~ Europharmausa.com Join Me on Facebook @ https://www.facebook.com/BuildingAbundantSuccess

Nat'l Integrative Health Expert ~ Cheryl is head of scientific affairs & education for Europharma,Inc. a natural medicine company with over 400 products being sold throughout North America. In this role, Cheryl oversees technical literature development, product research validation, educational outreach and acts as a liaison with thought leaders in integrative health. Cheryl is also the owner and founder of the natural health information website, HulaGoGo.com. The website motto is: “Think. Care. Act.” and she tries to carry this sentiment forward in all her endeavors. A recognized expert in integrative health and dietary supplement use, Cheryl has been a featured guest on more than 250 radio and television shows. She is well known as an advocate of bridging the worlds of mainstream and natural medicine to achieve health outcomes neither can create alone. Cheryl has been interviewed by the New York Times, Prevention Magazine, the Wall Street Journal and other periodicals on wide ranging topics such as dementia prevention, menopause symptom relief, cancer care, heart disease and many other aspects of health and wellness. She has appeared on the PBS television show “American Medical Review,” hosted by Morley Safer, to explain coenzyme Q10 and cardiac recovery. She has acted as a technical consultant for many segments of the PBS TV series “Healing Quest,” hosted by Olivia Newton-John. In other media ventures, Cheryl served as the technical/medical advisor for the Tony Shalhoub independent film, “Feed the Fish.” With several scenes shot in emergency rooms and clinics, Cheryl helped to insure authenticity, and to assist in creating comedic exaggeration of bandages and medical props. A graduate (with honors) of Purdue University, Cheryl has past clinical certifications in oncology (cancer care) and gerontology (health issues of aging). She has lectured on Alzheimer’s disease and related dementias at TriState University in Indiana. As a member of the editorial board of the Natural Medicine Journal (the official journal of the American Naturopathic Association), Cheryl evaluates scholarly articles and studies illuminating the science behind natural health interventions. Cheryl’s own nationally published articles have addressed a variety of health applications for natural products, including a referenced letter on the safety of taking St. John’s Wort prior to surgery in Aesthetic Surgery Journal and “Therapeutic Herbs for Gastrointestinal Disorders” in the Nutrition in Complementary Care: A Dietetic Practice Group of the American Dietetic Association. Additionally, Cheryl is an expert educator on dietary supplements and was invited to give educational presentations on various topics at the Mayo Clinic, in Rochester, MN; the Jefferson-Myrna Brind Center of Integrative Medicine at Thomas Jefferson University Hospital , in Philadelphia, PA, and at Florida Hospital Celebration Health, in central Florida, amongst others. You may contact Cheryl at: cmyers@EuroPharmaUSA.com Join On Me Facebook ~ http://artist.to/buildingabundantsuccess/