Podcasts about cell metabolism

Send us a textHey my beautiful friends –This week's conversation was sparked by a funny little tech discovery and a box I mailed — both of which got me thinking about food in a new way. You know how people are always quick to tell you what not to eat? Well, this week we flip the script. I'm sharing thoughts from my own journey and a coach that made me laugh and think — and you'll hear why his words still stick with me to this day. We're keeping things simple, kind, and grounded in something real. I'm not handing out rules, I'm sharing a mindset and maybe even a little inspiration for your next grocery run or packed lunch. And as always, we'll close with a little heart lift — this one from Michael Pollan, who said, “Eat food. Not too much. Mostly plants.”Come hang out with me, and let's talk about what loves us back. References:1.    Zhang & Talalay, Frontiers in Nutrition, 20232.    Liu, Nutrients, 20233.    Viguiliouk et al., Obesity Reviews, 20234.    Jenkins et al., AJCN, 20245.    Estruch et al., The Lancet Diabetes & Endocrinology, 20236.    Guasch-Ferré et al., BMJ, 20237.    Yao et al., Nutrients, 20238.    Harvard Nurses' Health Study Update, 20239.    Anderson et al., AJCN, 202410.Simopoulos, Frontiers in Endocrinology, 202311.Ye et al., Nutrients, 202312.Sonnenburg et al., Cell Metabolism, 202413.Mozaffarian et al., AJCN, 202314.Mastrocola et al., Appetite, 202315.Pollan, M. (2009). In Defense of FoodLet's go, let's get it done. Get more information at: http://projectweightloss.org

This episode reveals groundbreaking research from the Journal of Cell Metabolism showing that when you eat matters as much as what you eat for hunger control and fasting success. Dr. Scott and Tommy break down a study demonstrating that consuming 45% of daily calories at breakfast versus dinner dramatically reduces hunger and appetite without changing metabolism or weight loss. Learn why your physiology works against you when eating large evening meals, making it harder to close your eating window and stick to fasts. If you struggle with late-night cravings, can't seem to end your eating window, or find yourself breaking fasts in the evening, this episode provides the meal timing strategy to align your eating with your body's natural circadian rhythm for easier, more sustainable fasting. ⁠Take the NEW FASTING PERSONA QUIZ! - The Key to Unlocking Sustainable Weight Loss With Fasting!⁠⁠ Resources and Downloads: ⁠⁠SIGN UP FOR THE DROP OF THE ULTIMATE GUIDE TO BLOOD SUGAR CONTROL⁠⁠ ⁠⁠GRAB THE OPTIMAL RANGES FOR LAB WORK HERE! - NEW RESOURCE! - December 2024⁠⁠ ⁠⁠FREE RESOURCE - DOWNLOAD THE NEW BLUEPRINT TO FASTING FOR FAT LOSS!⁠⁠ ⁠⁠SLEEP GUIDE DIRECT DOWNLOAD⁠⁠ ⁠⁠DOWNLOAD THE FASTING TRANSFORMATION JOURNAL HERE!⁠⁠ Partner Links: Get your⁠⁠ FREE BOX OF LMNT⁠⁠ hydration support for the perfect electrolyte balance for your fasting lifestyle with your first purchase⁠⁠ here!⁠⁠ Get ⁠⁠30% off a Keto-Mojo⁠⁠ blood glucose and ketone monitor (discount shown at checkout)! ⁠⁠Click here!⁠⁠ Our Community: Let's continue the conversation. Click the link below to JOIN the ⁠⁠Fasting For Life Community⁠⁠, a group of like-minded, new, and experienced fasters! The first two rules of fasting need not apply! If you enjoy the podcast, please tap the stars below and consider leaving a short review on Apple Podcasts/iTunes. It takes less than 60 seconds, and it helps bring you the best original content each week. We also enjoy reading them! Article Links: https://www.cell.com/cell-metabolism/pdfExtended/S1550-4131(22)00344-8

Join our Patreon and get access to monthly bonus episodes and more nutriton content!Can fasting really slow aging? Does calorie restriction work for humans, or just for mice and yeast? And how much protein do you actually need to age well? This week on Your Diet Sucks, we break down the evidence behind the most talked-about interventions in the longevity space, what holds up under scrutiny, what doesn't, and why you might not need a supplement stack to live longer, and enjoy life. We dig into:The actual science on calorie restriction, fasting, and supplements—and where the evidence stopsWhat inflammation, oxidative stress, and telomeres have to do with how we ageThe best-researched dietary patterns for living longer (hint: it's not sexy, but it might include red wine)Why protein becomes more important as we ageThe difference between lifespan and healthspan, and why quality of life needs to be part of the conversation

In this episode of Hema Now, Jonathan Sackier is joined by John Riches, Clinical Reader in Cancer Immunometabolism at the Barts Cancer Institute and Honorary Consultant Haemato-oncologist. They explore how metabolic shifts drive lymphoma progression, the potential of immunotherapy, and what the future holds for treating lymphoid malignancies.  Timestamps:      00:00 – Introduction  01:46 – Riches' journey into haematology  03:42 – What is T cell exhaustion?  07:06 – The key role of metabolism in lymphoma  09:33 - Richter's syndrome  13:17 – Breakthroughs in immunotherapy  20:27 – The challenges of translational research  25:39 – B cells in autoimmune diseases  28:16 – The potential of breath biopsy  32:58 – Riches' three wishes for healthcare 

Follow us on Instagram @yourdietsuckspod!This week, Kylee and Zoë take a deep dive into ultra-processed foods: what they are, where they came from, how they're designed to light up your brain's reward systems, and what role they play in athletic nutrition. We talk about everything from cereal meant to prevent sinning to the low-fat diet craze, the war-time origins of shelf-stable food, and the engineering behind the foods that are hyper-palatable.We also get into the landmark NIH study that showed just how much processing—not just calories or macros—can influence how much we eat, how full we feel, and how our bodies respond to food. This episode is about helping you understand the systems at play, so you can make choices that support your health and performance without getting caught in fear or shame about the food you eat. Because when it comes to ultra-processed foods, context matters—especially for athletes.

In this eye-opening episode of the Better Than Before Breast Cancer Podcast, host Laura Lummer dives into the powerful connection between your body's natural rhythms and the timing of your meals. Have you ever noticed how aligned you feel when you live in sync with nature's cycles? Drawing from Ayurveda—an ancient system of medicine from India—and contemporary scientific research, Laura reveals how understanding your body's internal clock, or circadian rhythm, can significantly enhance your health, especially after breast cancer.   What You'll Discover in This Episode: A gentle introduction to Ayurveda and how this 5,000-year-old wisdom emphasizes living in harmony with Earth's natural cycles. Clear, practical explanations of circadian rhythm, metabolism, hormonal balance, and their critical roles in breast cancer recovery. How Ayurvedic principles align surprisingly well with modern Western nutritional science. The profound health benefits of aligning meal timing with daylight hours, including improved sleep, reduced inflammation, and optimized metabolism. Easy strategies to shift your eating patterns gently, starting with simple steps like adjusting dinner times.   Key Studies Referenced: JAMA Oncology Study:Catherine R. Marinac, Dorothy D. Sears, Lok-Hei Lam, Shirley W. Flatt, Loki Natarajan, Ruth E. Patterson; "Prolonged Nightly Fasting and Breast Cancer Prognosis." JAMA Oncology, 2016; Read the full study here.   Cell Metabolism Study: Emily N.C. Manoogian, Satchidananda Panda et al.; "Time-restricted eating improves cardiometabolic health in overweight individuals." Cell Metabolism, 2019; Explore the study here.   Listen in to explore: How simple shifts in meal timing can powerfully support your body's natural detoxification pathways and hormonal balance. The Ayurvedic recommendations for ideal meal times and how they beautifully complement modern scientific guidelines. Ways to incorporate a loving, compassionate mindset toward food, meal timing, and your body's natural rhythm.   This episode encourages you to foster a nurturing, compassionate relationship with your body by syncing your daily habits with the earth's rhythms, creating lasting health and harmony after breast cancer.   Connect with Laura: Visit The Breast Cancer Recovery Coach for personalized metabolic health coaching, mindset transformation, and guidance specifically tailored for breast cancer survivors. Enjoyed the episode?  Subscribe, leave a review, and share with friends who could benefit from this healing wisdom!  

NADs have been a hot topic lately when it comes to conversations regarding longevity and anti-aging. Today, Courtney Van Bussem, Biomedical Engineer and COO at Longevity Launch Labs, joins us to talk about cellular health, longevity pathways, and precursors to NADs.  Courtney Van Bussem: https://www.linkedin.com/in/courtneyvanbussum Longevity Launch Labs: https://longevitylaunch.com/ Where to find 1MNA: https://www.1mna.com/

Are Brean deler siste nytt fra andre vitenskapelige tidsskrifter. Bakteriell vaginose rammer omtrent 1/3 av alle kvinner i reproduktiv alder – hjelper det om man også behandler deres mannlige partnere (1, 2)? Har det noe å si for utfallet om man opereres før eller etter helga (3)? Er det forskjell i mortalitet hos folk som inntar mye smør versus de som heller inntar mer plantebaserte oljer (4, 5)? Gir multivitamininntak helsemessige fordeler hos pasienter med diabetes (6)? En dyrestudie publisert i Cell Metabolism antyder at forstyrrelser i mors døgnrytme kan predisponere avkommet for metabolsk stress og vektøkning senere i livet (7). Akkumulering av beta-amyloid i hjernen er et tidlig kjennetegn ved Alzheimers sykdom – men kan det også være direkte knyttet til de første kognitive endringene (8, 9)? Det foregår for tiden et større utbrudd av Guillain-Barré-sykdom i India (10). Og hvor vanlig er det egentlig at barnets biologiske far er noen andre enn den registrerte faren (11, 12)? Se hele litteraturlista her: https://tidsskriftet.no/2025/03/podkast/redaktorens-hjorne-82-bakteriell-vaginose-epigenetikk-og-dognrytme-registrert-vs-biologisk-far Tilbakemeldinger kan sendes til stetoskopet@tidsskriftet.no.  Stetoskopet produseres av Caroline Ulvin Johansson, Are Brean, Ragnhild Ørstavik og Julie Didriksen ved Tidsskrift for Den norske legeforening. Ansvarlig redaktør er Are Brean.  Jingle og lydteknikk: Håkon Braaten / Moderne media  Coverillustrasjon: Stephen Lee  See omnystudio.com/listener for privacy information.

¿Por qué siempre tienes hambre? Si sientes que comes y al poco rato vuelves a tener hambre, no es tu culpa. Hay razones científicas que explican por qué sucede esto y, más importante aún, cómo puedes solucionarlo.En este video te explico:✅ Por qué sientes hambre todo el tiempo y cómo engañan a tu cerebro para que comas más.✅ Los alimentos ultraprocesados que hackean tu organismo y te hacen comer sin control.✅ El truco definitivo para controlar tu apetito sin hacer dietas extremas ni pasar hambre.✅ 10 estrategias efectivas para reducir el hambre de forma natural y mejorar tu salud.

Die Themen in den Wissensnachrichten:+++ Mäuse leisten erste Hilfe +++ Süßstoff Aspartam verengt Blutgefäße +++ Google will Forschung mit KI voranbringen +++ **********Weiterführende Quellen zu dieser Folge:Hörtipp: Update Erde - deine News zu Klima, Mensch und NaturReviving-like prosocial behavior in response to unconscious or dead conspecifics in rodents, Science, 20.2.25A neural basis for prosocial behavior toward unresponsive individuals, Science 20.2.2025Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation, Cell Metabolism, 19.2.25Accelerating scientific breakthroughs with an AI co-scientist, Google Research, 19.2.25Alle Quellen findet ihr hier.**********Ihr könnt uns auch auf diesen Kanälen folgen: TikTok auf&ab , TikTok wie_geht und Instagram .

There are so many weightloss myths out there that it is so easy to become distracted and disillusioned. In this episode, I draw on the advice of many of the scientists and doctors I have interviewed on this channel about nutrition, metabolism and weightloss, and I detail 9 commonly held misconceptions about weightloss which is hampering peoples' weight loss goals .For example, I examine if skipping breakfast really helps you lose weight and I analyse if consuming fat can actually help you lose weight. Throughout this video I use science and research to flesh out each argument.You'll find all the references to the research papers I mention below :Westerterp, K. R. (2004). “Diet-induced thermogenesis.” Journal of Nutrition.Stote, K. S., et al. (2007). “Meal frequency and energy balance.” British Journal of Nutrition.Mozaffarian, D., et al. (2006). “Trans fatty acids and cardiovascular disease.”Circulation. Bazzano, L. A., et al. (2010). “Comparison of low-fat and low-carbohydrate diets for weight loss.”Annals of Internal Medicine. Estruch, R., et al. (2018). “Mediterranean diet and cardiovascular health.” New England Journal of Medicine.Sutton, E. F., et al. (2018). “Meal timing, circadian rhythms, and metabolic health.” Cell Metabolism.Almoosawi, S., et al. (2013). “Late-night eating and its metabolic consequences.”Obesity Reviews. Garaulet, M., et al. (2013). “Timing of food intake and obesity: A review.” International Journal of Obesity.Betts, J. A., et al. (2014). “Impact of breakfast on daily energy intake and weight regulation.” British Journal of Nutrition. Jakubowicz, D., et al. (2013). “The effect of breakfast on weight regulation.” Obesity. Farshchi, H. R., et al. (2005). “Regular meal patterns are associated with better food choices.” American Journal of Clinical Nutrition. Ludwig, D. S. (2002).“The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease.” New England Journal of Medicine. Hall, K. D., et al. (2015). “Energy balance and weight loss: The role of diet composition.” American Journal of Clinical Nutrition. Pereira, M. A., et al. (2002).“Effect of fat intake on satiety and energy balance.” American Journal of Clinical Nutrition. Slavin, J., & Lloyd, B. (2012). “Health benefits of fruits and vegetables.”Nutrition Journal. He, F. J., et al. (2007). “Fruit and vegetable intake and risk of cardiovascular disease.” British Journal of Nutrition. Astrup, A., et al.(2011). “The role of diet in weight loss and maintenance.” Obesity Reviews. Mann, T., et al. (2007). “Medically supervised weight loss: A review of crash diets.” The New England Journal of Medicine. Heymsfield, S. B., et al. (2014). “Mechanisms of weight regain after rapid weight loss.” Obesity Reviews. Hill, J. O., et al.(2012). “Sustainable weight loss: Lessons from the long term.” Journal of the American Dietetic Association. Longo, V. D., & Panda, S. (2016).“Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan.” Cell Metabolism. Tinsley, G. M., & La Bounty, P. M. (2015). The dangers of high carbohyrate foods : https://www.youtube.com/playlist?list=PLSKlhyEANfi8hZFoFoJun_lLhULcYg5JWWeightloss series : https://www.youtube.com/playlist?list=PLSKlhyEANfi-pO3W2hejnDUsgMQ9GPvpZThe health benefits fo exercise : https://www.youtube.com/playlist?list=PLSKlhyEANfi_vM1nbpcV-PlvWjSZ872ECListen to all previous podcast episodes of the Happy Habit Podcast via these podcast platforms :Apple Podcasts https://podcasts.apple.com/ie/podcast/happy-habit-podcastAmazon https://www.amazon.com/Happy-Habit-Podcast/dp/B08K5887J8Amazon music : https://music.amazon.com/podcasts/670836c2-ea4c-4a23-a67d-a54dd804ef61/happy-habit-podcastSpotify https://https://open.spotify.com/show/2VKIhQK6mYTzLCO8haUoRdFollow the Happy Habit Podcast Website: https://happyhabitpodcast.wordpress.com/Music used is Purple planet Music crediit goes to them

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Introducing Blood sugar hacks to give you more energy | Glucose Goddess Jessie Inchauspé and Prof. Tim Spector from ZOE Science & Nutrition.Follow the show: ZOE Science & Nutrition Why do some people feel fine eating lots of carbs when others feel energy slumps? Is blood sugar to blame?In this episode, we learn why blood sugar varies so much between people, and the tools to manage these levels. Tim Spector and Jessie Inchauspé (aka the Glucose Goddess) will discuss the latest science around glucose control, what the cool new device on the block – the CGM – can tell us and why blood sugar levels are only one part of the picture of our health.Jessie is a bestselling author and science communicator with a community of over 5 million followers. Tim is a professor of epidemiology at King's College London and ZOE's scientific co-founder.

The Chief Scientific Advisor at Novo Nordisk, Lotte Bjerre Knudsen, was the key force who pushed hard to develop GLP-1 drugs for treating obesity and subsequently for Alzheimer's. She was recently recognized by the 2024 Lasker Medical Research Award, and the 2024 AAAS Bhaumik Breakthrough of the Year Award. That recognition is richly deserved, since it is unclear if the GLP-1 drug path to obesity treatment, and all of the associated benefits, would have been seen at this time without her influence. That's especially true given the mystery for why people with Type 2 diabetes (for which these drugs were used for many years) did not exhibit much in the way of weight loss. We discussed that and the future of these drugs, including their potential to prevent neurodegenerative diseases. And about dressing up in pink!The Ground Truths podcasts are also available on Apple and Spotify.Our entire conversation can also be seen by video at YouTube along with all of the Ground Truths podcasts. If you like the video format, please subscribe to this channel. Even if you prefer video, please take a look at the transcript with graphics and useful links to citations.A Video Clip below on the barriers of a woman scientist to push Novo Nordisk to develop GLP-1 for obesity. “I was always just been a nerdy little scientist who kind of found home here in this company for 35 years.”—Lotte Bjerre Knudsen, 60 MinutesTranscript with Links to audio and external referencesEric Topol (00:06):Well, hello, it's Eric Topol with Ground Truths, and I have with me a special guest. She's the Chief Science Officer of Novo Nordisk and it's Lotte Bjerre Knudsen, and we're delighted to have her. She's a recent recipient of the Lasker Award, which I think is considered like the pre-Nobel Award here in the United States. And I was involved with her in terms of researching who was the principal person who brought the GLP-1 drugs to the forefront for obesity, and it turned out to be Lotte. So welcome, Lotte.Lotte Bjerre Knudsen (00:48):Thank you very much. And also very, very happy to be here. I'm not the Chief Science Officer for Novo Nordisk, I'm the Chief Scientific Advisor of working for the Chief Science Officer of Novo Nordisk, but maybe too many people, not so different, right?From Laundry Detergents to GLP-1 DrugsEric Topol (01:06):Yes. Thank you, I actually meant to say advisor, but yes, I'm glad you cleared that up. I know from speaking to some of your colleagues, I actually spoke to Robin yesterday that you are looked to very highly, the most highly regarded person in science there, so not surprisingly. What I want to do is first talk about the glucagon-like peptide-1 (GLP-1) that got its legs back in, I guess 1984. So we're going way back. And what's also interesting is that you go way back at Novo Nordisk to 35 years in 1989. And so, there had been this work with this extraordinary hormone and neurotransmitter with a very short half-life that you knew about. But when you first started in Novo Nordisk, you weren't working on this. As I understand it, you're working on laundry detergent enzymes. How did you make this pivot from the laundry enzymes to getting into the GLP-1 world?Lotte Bjerre Knudsen (02:16):Yeah, thank you for that question. I'm from the technical University of Denmark, so I'm trained in biotechnology, and we're a small country, so not that many companies to work for. And I always had my mind set on, I wanted to work for Novo as it was called back then, and it just happened to be in the industrial enzyme part that I got my foot in first. And then I had a very interesting boss at the time. Unfortunately, he's not alive anymore, but he was both a medical doctor as well as a chemist. So he was actually put in charge of actually, let's see if we can do something new in diabetes. And then since he hired me and I had not been there that long, I simply tagged along as the youngest scientist on the team, and then suddenly I became a diabetes researcher. Around the same time, I think you remember that all of pharma was interested in obesity in the early 90s, everyone wanted to do diabetes as well as obesity, but they were separate teams and they all wanted to do small molecules, but it just happens to be so that the best idea we could find at that time was actually GLP-1, because we actually had clinical data relatively early that GLP-1 was a really good candidate as a treatment for diabetes because of the glucose sensitivity of the actions.(03:43):So you'd have efficient lowering of glucose through a dual mechanism with increasing insulin, lowering glucagon, and then it was safe because there wasn't this hypoglycemia you get from insulin. But then I had other colleagues who were working on obesity, and I was just kind of listening, right, what's going on there? And then also a colleague that I had, we had, I don't know if you remember the old Hagedorn Research Institute, but Novo actually had kind of like an academic research institute that was affiliated with us. And there was this group that were working on this glucagon tumor model that produced high levels of glucagon, GLP-1 and PYY. And these rats, they starved themselves to death. And I knew about that from 1994. So that actually inspired my thinking. So when Stephen Bloom's paper came out in January of 1996, and he was the first one to call GLP-1 a neurotransmitter, I think, but I was already way into actually screening these kind of molecules that later then became liraglutide.No One Else Thought About This [Obesity](04:54):And then I thought, why on earth should we not actually do both things at the same time? If we have an idea that can both work in diabetes in a much safer way than in insulin, and then also at the same time work in obesity. But the reality is that no one else thought about this, or if they thought about it, they didn't really think that it would a good idea. But I think I had the luxury of being in a biotech company, so everyone was working with peptides and proteins. So I don't think I got the same challenge that the other people in the other pharma's got when they all wanted small molecules.Eric Topol (05:36):Well, also just to set the foundation here, which you alluded to, there had been so many attempts to come up with a drug that would work, not just of course in diabetes where there are many classes of drugs, but moreover, to treat the condition of obesity. Actually, I was involved with one of them, Rimonabant and did the large trial, which as you know, led to having to stop the drug, discontinue it because it was associated with suicidal ideation and actual some suicide. So there had been such a long history of checkered inability to come up with a drug. But what was striking is the challenge, and this is one of the first important questions about, when you had the extended half-life of the first GLP-1 drug, that instead of having to take multiple times a day, you could actually, with liraglutide get to a point where you were starting to get to an extended half-life. This is now going back to 1997 with approval in 2010, still 14 years ago. But when you came up with this drug, because this was certainly one of your great contributions, this drug was just a step along the way in this kind of iterative process, wouldn't you say? It wasn't the long half-life and the potency that eventually got us to where we are today. Is that true?Lotte Bjerre Knudsen (07:15):Yeah, it was a stepwise process. And what's super interesting about this class of medicines is that they're actually so different. If you talk about a class of medicine where small molecules, they can be different, but they're usually more alike than they're different. And when it comes to this class with these medium-sized peptides, people tried a whole bunch of different things. So they're actually really, really different. Some are simple peptides. So the idea that I came up with was to use this fatty acid isolation principle, and that's then a subclass in the class. And then the first, once weekly, for example, was an antibody-based molecule liraglutide. So they're much, much, much larger molecule compared to the small peptides. So they're very different. And neither the simple peptides nor the really big antibody derived molecules, they don't give a lot of weight loss. So we actually get more weight loss with these kinds of molecules, which is also why you can now see that it has actually kind of inspired a whole industry to kind of try and go and make similar kinds of molecules.Eric Topol (08:27):Well, inspired a whole industry is an understatement. It's become the most extraordinary class of drugs, I think in medical history, having been a student of various, I mean obviously statins have been a major contribution, but this seems to have transcended that already. We're going to talk about more about where things are headed, but this fatty acid acetylation was a major step forward in extending the half-life of the drug, whereby today you can give semaglutide once a week. And this, I think, of course, there are many ways that you might've been able to extend the half-life, but you were starting with a hormone, a natural hormone neurotransmitter that had such an exquisitely short half-life of basically second or minutes rather than that you could give for a week. So I know there were many different ways you could have protected or extended the half-life one way or another, but this seemed to be a breakthrough of many along the chain of breakthroughs. But the question I have is when you were giving this to the diabetics, which was the precedent, that was really what these drugs were first intended, they didn't lose that much weight, and they never, still today when it's looked at for obese non-diabetics versus diabetics, there's a gap in weight loss. Why is that at the exact same dose, with the exact same peptide that the weight loss differs for people with type 2 diabetes as compared to those who have pure obesity?The Mystery of Why People With Type 2 Diabetes Don't Lose Weight Like Those With Obesity Lotte Bjerre Knudsen (10:09):Yeah, I can't give you a molecular answer to that, right. But I think the notion, I think it's the same for example with metformin, even though it gives less weight loss because that has also been tried in both people with diabetes and people without diabetes. So I think it's just for somehow people with diabetes are more resistant to weight loss. I think it's a really good question that I'm hoping maybe we could get through, for example, with proteomics and actually comparing people with diabetes and people without diabetes and looking at people who have the similar kind of weight loss. That could be really interesting. But I really don't have a good molecular answer for you, but it's just a really, really strong fact. But it also leads me to wanting to say it's interesting, because if that had been our motivation to actually say, oh, there's weight loss in diabetes, let's pursue it in people with obesity, I don't think we would've done that because the weight loss in people with diabetes wasn't that impressive. So it was very important for our chain of thought and decision early on that we actually knew that GLP-1 had these separate effects and that they could work in the brain and have a separate effect on well-known pathways in the brain. And that was more our motivation to actually continue to invest in obesity.Eric Topol (11:42):Yeah, no, I think this is when we did the research on the committee for the American Association for Advancement of Science (AAAS) award, the Mani L. Bhaumik Award, that you were recognized for the breakthrough of the year, this year. We tried to scour all the work and we actually had to hit Danish translations and all sorts of other papers they reviewed. And we learned through that process working on this committee that you were the one to be the champion of pushing this towards obesity, and it would've easily been missed because as we've been discussing, the weight loss in people with diabetes was small, but you push for it. And this was an extraordinarily important push because what it has resulted in, of course, has been spectacular. And obviously as we're going to get into much more than just obesity and obesity related conditions. But before we get to those other conditions, and as you've been known in the medical community as “the mother of GLP-1”, you were dubbed that term. The GLP-1 receptor is expressed in many parts of the body. Maybe you could just tell us about the distribution because this, I think is tied into these central nervous system effects that are not just related to the gut hormone type of axis.GLP-1 Receptors and the BrainLotte Bjerre Knudsen (13:17):So I spent a lot of time on that together with my amazing colleague, Charles Pyke, who's an histology expert because it turned out to be so very important. In general, when you're trying to make new medicines, understanding the mechanism, sometimes people say, yeah, who cares? But actually, it should matter, I think because where it becomes really important can be an understanding what they do not do. We've had to do a lot of proving the negatives for GLP-1. We went through these issues with thyroid cancer, pancreatitis, pancreas cancer. In all of that work, it was actually really important that we could show where the GLP-1 receptor was not expressed. So in the pancreas, we know that it's primarily on the insulin producing cells, and then we also have them in the intestine where they're probably involved in regulating inflammation and really creating a much healthier gut.(14:15):And then we have a lot of receptors in the brain. They're typically expressed on neurons, but they're also on astrocytes, they're also on smooth muscle cells. We have them on the heart and the sinus node. That's why there's a small increase in heart rate. We have them in the kidney, on again some smooth muscle cells that are renin positive. So there we can start thinking blood pressure and other things. So it turns out that you can go around the body and there are all of these specific GLP-1 receptor population, that you can see how they tie into the pharmacology. But obviously in physiology, they're not as important as they have turned out to be in pharmacology when we suddenly come with 24 hours a day exposure for a day or a week or for as long as the administration interval is. So, but specifically for obesity, I think it's in the vein, it's hard to, you should always be careful.(15:18):That's something I've learned to never say never. Of course, there could be a contribution from the peripheral nervous system as well to the effects in obesity. But I do think there are so many important and well described neuronal populations that have the GLP-1 receptor and which are accessible from the periphery. So just to mention, maybe one of the most, well-known is a POMC/CART neuron in the hypothalamus. They have the GLP-1 receptor, they're activated, but there also is an inhibitory tone on the AgRP and NPY neurons, and it fits very well with that. We know that people report that they feel more sated, they feel less hungry. But then there are also effects in the hindbrain and in some of the reward centers also have GLP-1 receptors. And we know that also now, we have really good actually clinical studies that show that there is a change in food choice and people can control their food intake better. So I think that fits very well with effects on the reward system. So it's a whole myriad, or maybe you could say that GLP-1 orchestrates a number of different neuronal populations to have these overall effects that reduce energy intake.Eric Topol (16:42):Yeah, it's pretty striking. It's almost like we're all walking around with GLP-1 deficiency, that if we had this present at higher levels around the clock, and of course eventually we'll see things that are well beyond obesity, how well this has an impact. Now, there was an extraordinary review in Cell Metabolism on the brain and GLP-1, and not just the brain, but the essential nervous system, the neurovascular, it's called the “GLP-1 programs and neurovascular landscape.”(17:20):And in this review, it got into the brain effects that were well beyond, I think what are generally appreciated. Not only the protection of the integrity of the blood-brain barrier, this whole neuroglial vascular unit, the myelin sheath protection, reducing inflammation within the brain, improving the glymphatic flow, which is of course critical for clearing waste and promoting cerebral vascular remodeling and more, so the brain effects here is what it seems to be. You mentioned the reward circuit, of course, but the brain effects here seem to be diverse, quite a bit of breath and extraordinary. And as we've seen in the clinic now with the work that's been done, we're seeing things about addiction, even gambling, alcohol, drugs, I mean neuropsychiatric impact, it's pretty profound. Maybe you could comment about that.On to Alzheimer's and Parkinson's DiseasesLotte Bjerre Knudsen (18:23):Yeah. I haven't read that paper yet, but I just saw it earlier. And I have been following this for about actually more than 10 years because when I was kind of over the big work of actually getting the approval for diabetes and obesity. I thought I had a little bit of capacity to actually look at Alzheimer's and Parkinson's disease because I just thought there's such an insane unmet need and what if GLP-1 could actually make a difference? And the first big paper that talked about this was actually in Nature Medicine in 2003, and it was originally, I think I should credit Nigel Greig. Greig, he's from NIH or from NIA, I can't remember, right. But he was actually the first one, I think to say if GLP-1 has all of these important effects in the pancreas and to protect cells, and there are all these GLP-1 receptors in the brain, maybe it also protects neurons.(19:25):So that was the first hypothesis. And the paper on Nature Medicine in 2003 describes how the GLP-1 receptor in the hippocampus is involved in cognition. And then we did a couple of studies in different animal models, and I was, to be honest, really confused. But then there was a new paper in Nature Medicine in 2018 that started to focus in on neuroinflammation. And by that time, I knew much more about inflammation and knew GLP-1 actually lower CRP by about 50% in the different trials. So I was really tuned into the potential importance of that in cardiovascular and kidney disease. But I was like, oh, what if that's also something that is important in the brain? Then it made more sense to me to try and build some evidence for that. So that was how we actually started looking at a hypothesis for Alzheimer's and Parkinson's.(20:21):And we now have a really large phase three study ongoing, but of course, it's a hypothesis, right? And no one has yet, I think, proven that GLP-1 has really important effects on these indications, but we are testing it in 4,000 people with Alzheimer's disease. So our hypothesis is around neuroinflammation, but defined in a way where you could say it's both peripheral inflammation and the effect it has on the vasculature, it's the effect on the blood-brain barrier. It's the astrocytes and the microglia, and there are probably also some T cells that have the GLP-1 receptor that could be important. And then couple that up also with some of the new information from neurons, because there are two papers to think in the last year that has highlighted neurons either in the hindbrain or a little bit further on. Both of them are probably hindbrain populations that actually seem to be really important in regulating both peripheral as well as central information.(21:27):So what if neurons are actually also an overlooked mechanism here, and both of these neuronal populations have the GLP-1 receptor and are accessible from the periphery, even though the child super paper in Nature doesn't mention that, but they do have the GLP-1 receptor. So there are all these different mechanisms that GLP-1 can have an impact on the broad definition maybe of neuroinflammation. And maybe the way one should start thinking about it is to say it's not an anti-inflammatory agent, but maybe it induces homeostasis in these systems. I think that could maybe be a good way to think about it, because I think saying that GLP-1 is anti-inflammatory, I think that that's wrong because that's more for agents that have a really strong effect on one particular inflammatory pathway.Eric Topol (22:22):That's a very important point you're making because I think we conceive of these drugs as anti-inflammatory agents from these more diverse actions that we've just been reviewing. But I like this restoring homeostasis. It's an interesting way to put it. This brings us, you mentioned about the Parkinson's, and when I reviewed the three randomized Parkinson's trials, they're all small, but it appears to be the first disease modifying drug ever in Parkinson's. Of course, these were done with different drugs that were older drugs. We haven't seen the ones that yet to be with semaglutide or other agents. And I wondered if you pushed, just like you did for obesity within Novo Nordisk, you pushed to go into obesity. Did you also force to push for Alzheimer's?Lotte Bjerre Knudsen (23:19):Yes. So that is also me who had to argue for that. I'm happy to do these things. I was born brave. I am happy to do these things.Eric Topol (23:31):That's wonderful. Without you, we would be way behind, and it took decades to get to this point. But look where we are now, especially with all the rigorous trials, the large clinical trials. You're into one right now of some 20,000 participants to see whether not just people with prior heart disease, but people without known heart disease to see whether or not this will have an effect. And there's so much data now, of course, already a completed trial with reduction of heart attacks and strokes. But now to extend this to people who are not such high risk, but these large trials, we keep learning more. Like for example, the reduction of inflammatory markers is occurring even before the weight loss that starts to manifest. So we learned a lot from the trials that are just even beyond some of the major primary outcomes. Would you agree about that?Lotte Bjerre Knudsen (24:34):So I'm not sure we can say that it comes before the weight loss because the energy intake reduction happens instantly. The glycemic response happens instantly. And all of these improvements will of course also have an effect to dampen inflammation. We do not have data that supports that it comes before because we haven't sampled that much in the beginning.Eric Topol (25:04):Okay.Lotte Bjerre Knudsen (25:05):I wouldn't be able to say that, and I don't think there are any, well, it's hard to keep up that the entire literature on GLP-1 these days, but I don't think anyone has actually shown that there is a separation because it's super hard to separate when things are occurring at the same time.Eric Topol (25:24):Yeah, I'm just citing the heart disease trial where in the New England Journal that point was made. But I think your point also that there was already a change in energy intake immediately is apropos for sure. Now, when we get into this new paper of yours, the proteomics, can you tell us about that because that's really exciting. We're in a high throughput proteomics era right now that we can analyze thousands of plasma proteins in any given individual. What are you learning about proteomics with the GLP-1 drug?The GLP-1 Drug Impact on ProteomicsLotte Bjerre Knudsen (26:07):Yeah, yeah. So I'm also the super excited about omics, right? Because I have worked in a wonderful organization of people who can do these large scale clinical trials, and we used to not collect a lot of samples for future use, but we've done that for some years now. So now we have this amazing collection of samples we can learn from and actually both inform the patients and the physicians, but also inform future research. So we have been doing that in our semaglutide trials, and we've just published the proteomics data from the step one and step two trials. So the phase 3a trials that supported the approval of semaglutide for the treatment of obesity. So one of them in people with obesity and one in people with obesity and diabetes, and those data are now published in Nature Medicine. [3 January 2025]. And we were learning a lot of things because you can compare the proteome effects to what has been done in the decode cohort.(27:11):So they have all these disease signature. So that's one thing that you can for sure see, and you can see a lot of things there with hints towards addiction. And then also you can take more predefined signatures also to look into what actually might be driving the cardiovascular risk. So I think there are so many things that you can learn from this, and of course it can also inform when you look at what's actually mediating the effect and probably something around inflammation is important. We have already also shown a more standard mediation analysis that shows that actually the most explainable factor for the effect on MACE [major adverse cardiovascular events] in the select trial is inflammation. It doesn't explain everything, but it actually looks like it's more important than BMI and weight loss. So that's really interesting how much we can learn from there. We're making the data are available at the summary statistic level so people can go and play with them ourselves.(28:23):And I think as we have more different kinds of medicines available in obesity, it's also a way to kind of compare how these different medicines work. And as we get more and more better at maybe also characterizing people with obesity, because I think that's a great thing that's going to happen now is there's going to be more funding for obesity research. Because I think that's what the attention that we are seeing right now is also giving. Then we can better start to understand. We always, we've been saying that people probably have different kinds of obesity, but we don't really know. So now we can actually start to understand that much better and maybe also understand how these different classes of medicines will work if we have the proteome data from different trials.Eric Topol (29:10):No, I'm absolutely fascinated about the proteomics. I call it a quiet revolution because many people don't know about it. [My recent post on this topic here.](29:18):The ability to assess thousands of proteins in each individual, and it's giving us new insights about cause and effect as you alluded to, the relationship with as you said, MACE (major adverse cardiovascular events) and the actions of this drug class. I mean, there's just so much we can learn here from the proteomics. Another thing that's fascinating about the GLP-1 is its effect on epigenetic clocks. And recently at one of the meetings it was presented, this is Steven Horvath that we had on Ground Truths not long ago. He talked about at this talk that for the first time to see that you could basically slow the epigenetic clock with a GLP-1. Is there any further information about that?Lotte Bjerre Knudsen (30:16):Yeah, no. We've never had enough of a sample size to actually be able to look at it, so unfortunately, no. But there is something else, right, because there is this group at the Stanford, Tony Wyss-Coray or something.Eric Topol (30:33):Yes, Tony Wyss-Coray.Lotte Bjerre Knudsen (30:35):Now he published a paper, is it two years ago? Where he did it using proteomics. He defined an anti-aging signature for various different organs.Lotte Bjerre Knudsen (30:46):We are in the process of trying to see if we could take those signatures and apply them on to our data.Eric Topol (30:55):Well, what's interesting is we're pretty close friends, and he, not only that paper you mentioned on organ clocks, which is a phenomenal contribution, but he has a paper coming out soon in Nature Medicine, the preprint is up, and what he showed was that the brain and the immune system was the main organ clocks that were associated with longevity. And so, it takes another step further and it's looking at 11,000 plasma proteins. So it's really interesting how this field is evolving because the omics, as you put it, whether it's proteomics, and now we're learning also about the epigenome and what brings us to the potential that this class of drugs would have an impact on health span in all people, not just those who are obese. Would you project that's going to be possible in the years ahead?Lotte Bjerre Knudsen (32:02):I don't know about health span, but because certainly there's been so many studies with metformin and there's been a lot of wonderful data showing an effect on the epigenetic clocks, but not really an effect on lifespan because that metformin is so widely used. If that was the case, it would be easy to dig those data out of different registries. But certainly a healthier aging is the most obvious one because when you have one class of medicine that actually has so many different effects. Right now we are looking at them at a one by one case, but we really should be looking at them so you are getting the benefits on the heart and the vasculature on the brain and the kidneys and the diabetes and the knees. You're getting all of that at the same time, and that certainly should lead to much, much healthier lives. And then of course, we just need to get people to eat healthier. Also, maybe we should talk a little bit about the food industry. I heard you did that in some of your podcast, right?Eric Topol (33:17):Yes. That is the big food, if you will. It's a big problem, a very big problem, and the ultra-processed foods. And so, lifestyle is not good and trying to compensate for that with a drug intervention strategy is like chasing your tail. So you're absolutely right about that. I mean, I guess what I'm getting into here is that whereas today we keep seeing the effects, whether it's the liver, the kidney, the heart, obesity, and people with diabetes. But for example, in the Alzheimer's trial, do you have to be obese to be enrolled in the Alzheimer's trial, or is it just people who are at risk for developingAlzheimer's?Lotte Bjerre Knudsen (34:01):Yeah, no, you do not have to be obese. It's a standard Alzheimer's trial.GLP-1 PillsEric Topol (34:07):So this will be one of the really important trials to get a readout in people who are not having an obesity background. Now, the future, of course, gets us to oral GLP-1 drugs, which obviously you have there at Novo Nordisk. And it seems to me once that happens, if it can simulate the effects we see with the injectables, that would be another big step forward. What do you think about that?Lotte Bjerre Knudsen (34:39):Yeah. Isn't it interesting, what we've learned is that people actually don't mind the injections, right? Also, because I think it's simple, once a week injection and the needles are so small, obviously there are people who really have needle phobia, but take those aside, it's relatively few. I would argue if you close your eyes and somebody else used this needle on you, you would not be able to feel where it was inserted, right? They're so small. So it becomes maybe a personal preference. Would you like to have once a day or maybe twice a day tablets, or are you fine with once a week injection? And I think there probably will be quite a few once they've tried it. And now so many have tried it and they actually, maybe it gives us a simple lifestyle. You don't have to do it every day, right? You can just have a weekly reminder.Eric Topol (35:46):Yeah, no, I think that's really interesting what you're bringing up. I never thought we would evolve to a point where injectables were becoming some common, and I even have some physician colleagues that are taking three different injectable drugs.Lotte Bjerre Knudsen (36:00):That's also just mentioned Richard DiMarchi, who I shared the Breakthrough Prize with, and also Svetlana Mojsov, who I was one of the other two recipients for the Lasker prize because they both been at Rockefeller, and they both have worked a lot with peptides, and they both say the same thing. They were told so many times, this is not medicines, these kinds of molecules just they're not medicines. Forget about it. It turns out people were wrong. And peptides can be medicines, and they can even be produced also in a sustainable manner with fermentation, which is not a bad way of producing medicines. And people actually don't mind. Maybe some people actually even like it because it's once a week and then it's done.Confronting BarriersEric Topol (36:58):Yeah, no, that's a very important point. And the quest for the oral, which have more issues with bioavailability versus the peptides that are having such pronounced impact is really interesting to ponder. Well, before we wrap up, it's very clear the impact you've had has been profound, not just obviously at Novo Nordisk, but for the world of advancing health and medicine. And you've mentioned some of the key other people who have made seminal contributions, but I think you stand out because when we went deep into who took this field forward into obesity and who might also wind up being credited for Alzheimer's, it was you. And as a woman in science, especially in an era that you've been at Novo now for three and a half decades, there weren't many women in science leaders. And for one to be, as you said, you're brave for the good old boys to listen to the woman in science. Tell us about that challenge. Was this ever an issue in your career? Because obviously we want to have this whole landscape change. It is in the midst of change, but it's certainly still a ways to go. So maybe you can give us insight about that.Lotte Bjerre Knudsen (38:27):Yeah. Well, it for sure was a thing. It was a very male dominated world, and in a way, it might have prevented other people from doing it. But then, as I said, I was born brave for some reason. I'm not really sure why. It actually motivated me to kind of like, yeah, I'm going to show them. I'm going to show them. So it never really got to me that people, not everyone was nice to say. There was the first 10 years of my career, I think they were quite lonely, but then I was really inspired. I was so happy to be allowed to work on this. I thought it was super fun. And I did find people who wanted to play with me. And I also have to say that the CSO back then, Mads Krogsgaard Thomsen, he always supported me. So maybe I didn't get everything I wanted, but I always got what I needed in order to progress.(39:29):So on the women's side, and I think that yes, and there's still a change to be made, and I'm actually a little bit on behalf of my generation, maybe not too proud of the change we made because we didn't do a lot of change. It was all the women coming from the arts and the culture. They were the ones who actually make the big change here like 5 or 10 years ago. So I've also started to be more open about sharing my journey and advocating for women in science. So that's why I show up in pink to some of these award sessions just to be a little bit different and to maybe also just show that you don't have to be a certain type in order to fit into a certain job. But there is still a change to be made where people should be better at listening to what a person say and what ideas they say.(40:28):And they should be mindful about not always labeling women as passionate. When people call me passionate, I say like, no, thank you. I'm actually not too happy about the mother of either, because men always are being told. They're being told that they're brave and ambitious and courageous and strategic, whereas we we're, oh, you're so passionate. No, thank you. I'm also brave and strategic and ambitious and all of that. So we simply put different vocabulary on. I don't think people don't do it on purpose. I think we need to be better at actually giving people at work the same kind of vocabulary for their contributions. And I think that would mean that we get listened to in the same way. And that would be important. And then I also have to say that science, whether it comes from men or women, doesn't really matter.(41:32):Successful science is always the work of many. And I hope that some of you will actually listen to my last speech because that's what I speak about, how it's always the work of the many. And also, how if you want to do something novel, then you actually have to do it at a time when no one else is doing it, and you should believe in your ideas. So believe in it, listen to the critique, but believe in it, and then come back with new arguments or give up if you can't come up with any new arguments, right?Eric Topol (42:05):Well, we'll definitely put a link to the Lasker Awards speech that you gave. And I just want to say that the parallels here, for example, with Kati Karikó , my friend who had the Nobel Award for mRNA, she spent three decades trying to get people to listen to her and never got a grant from the NIH or other places [our conversation here]. And it was a really tough battle. And as you already touched on Svetlana Mojsov, who did some of the seminal work at Rockefeller to isolate the portion of GLP-1, that really was the key part peptide, and it was overlooked for years. And so, it's a tough fight, but you're paving the way here. And I think the contributions you've made are just so extraordinary. And I hope that over the years we will continue to see this momentum because people like what you've done, deserve this extraordinary recognition. I'm glad to see. And the Lasker Award is really capping off some of that great recognition that is so well deserved. We've covered a lot of ground today, and I want to make sure if I missed anything that you wanted to get into before we wrap up.Lotte Bjerre Knudsen (43:30):I think we've been around all the exciting biology of GLP-1, both in diabetes, obesity, cardiovascular, kidney, potential in Alzheimer's and addiction. We'll see, we need the clinical data and we've put out a message to inspire people to do new science. There's still a lot of unmet need out there. There's a lot of diseases that don't have good treatments. Even in the diseases we've talked about there's a lot of money for diabetes. There are no disease modifying therapies for diabetes. It's not really changing the course of the disease. So there's a lot of things that needs great scientists.Eric Topol (44:17):And I guess just in finishing the discovery of this class of drugs and what it's led to, tells us something about that, there's so much more to learn that is, this has taken on perhaps the greatest obstacle in medicine, which was could you safely treat obesity and have a marked effect. Which decades, many decades were devoted to that and gotten nowhere. It's like a breakthrough in another way is that here you have an ability to triumph over such a frustrating target, just like we've seen with Alzheimer's, of course, which may actually intersect with Alzheimer's, with a graveyard of failed drugs. And the ones that it were approved so far in certain countries, like the US are so questionable as to the safety and efficacy. But it gives us an inspiration about what is natural that can be built on the basic science that can lead to with people like you who push within the right direction, give the right nudges and get the support you need, who knows what else is out there that we're going to be discovering in the years ahead. It's a broad type of lesson for us.Lotte Bjerre Knudsen (45:38):Yeah, there is another hormone that's also in phase three clinical development, right? The amylin hormone. We've had pramlintide on the market for years, but we have this long-acting version that is in phase three clinical development. That could be the same kind of story because there's also additional biology on that one.Eric Topol (45:58):Yeah, this is what grabs me Lotte, because these gut hormone, we've known about them, and there's several more out there, of course. And look what they're having. They're not just gut hormones, like you said, they're neurotransmitters and they're body-wide receptors waiting to be activated, so it's wild. It's just wild. And I'm so glad to have had this conversation with you. Now, congratulations on all that you've done, and I know the Nature Medicine paper that just came out is going to be just one of many more to come in your career. So what a joy to have the chance to visit with you, and we'll be following the work that you and your colleagues are doing with great interest.Lotte Bjerre Knudsen (46:45):And thank you very much, and thank you for your wonderful podcast. They're really great to listen to on the go. 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Send us a textIn this episode, we explore the fascinating world of circadian rhythms—your body's internal clock that impacts sleep, energy, hormones, and more. Learn what circadian rhythms are, how they function, and why they're crucial for your health. We'll dive into research-backed benefits of optimizing your sleep cycle and the adverse effects of ignoring it. Discover surprising insights about morning and evening types (chronotypes) and how light exposure, meal timing, and even exercise influence your internal clock. Plus, get a practical tip to improve your sleep tonight and download a free, customizable sleep calendar to align your schedule with your circadian rhythm. Cited Resources:•“The Circadian Code” by Dr. Satchin Panda•Study on circadian rhythms and metabolic health (Cell Metabolism, 2018)•Harvard Health on blue light and sleep disruption•Research on chronotypes and performance (Journal of Biological Rhythms, 2015)Hey Hormone Hotties:If you want to learn more about how you can work with me or what services I offer including those below- https://linktr.ee/Faithhealthfitness Interested in being a guest expert (even if you are not in business but a woman who has a story to share) fill out the application and book an appointment. Affiliated Partner for awesome products in wellness and more including the "Body balancing" slenderize for a discount using my code HAPPY24 Join me in Happy Hormones Circle. This and my email list is where I will be focusing my time and content Disclaimer: The content shared in ‘The Happy Hormones Coach' podcast (including affiliate and non affiliate products) is for informational purposes only and is not intended as medical advice, diagnosis, or treatment. Please consult with a qualified healthcare provider before making any changes to your diet, exercise, or health routine. The opinions expressed in this podcast are those of the host and guests and do not necessarily reflect the views of any healthcare organizations. The statements made regarding any of the products that I mention have not been evaluated by the Food and Drug Administration (FDA). Individual results may vary.

A leader for conducting rigorous randomized trials of humans along with animal models for understanding nutrition and metabolism, Dr. Kevin Hall is a Senior Investigator at the National Institutes of Health, and Section Chief of the Integrative Physiology Section, NIDDK. In this podcast, we reviewed his prolific body of research a recent publications. The timing of optimizing our diet and nutrition seems apropos, now that we're in in the midst of the holiday season!Below is a video snippet of our conversation on his ultra-processed food randomized trial.Full videos of all Ground Truths podcasts can be seen on YouTube here. The current one is here. If you like the YouTube format, please subscribe! The audios are also available on Apple and Spotify.Note: I'll be doing a Ground Truths Live Chat on December 11th at 12 N EST, 9 AM PST, so please mark your calendar and join!Transcript with links to publications and audioEric Topol (00:05):Well, hello. This is Eric Topol with Ground Truths, and I'm really delighted to have with me today, Dr. Kevin Hall from the NIH. I think everybody knows that nutrition is so important and Kevin is a leader in doing rigorous randomized trials, which is not like what we usually see with large epidemiologic studies of nutrition that rely on food diaries and the memory of participants. So Kevin, it's really terrific to have you here.Kevin Hall (00:34):Thanks so much for the invitation.Ultra-Processed FoodsEric Topol (00:36):Yeah. Well, you've been prolific and certainly one of the leaders in nutrition science who I look to. And what I thought we could do is go through some of your seminal papers. There are many, but I picked a few and I thought we'd first go back to the one that you published in Cell Metabolism. This is ultra-processed diets cause excessive caloric intake and weight gain. (Main results in graph below.) So maybe you can take us through the principle findings from that trial.Kevin Hall (01:10):Yeah, sure. So that was a really interesting study because it's the first randomized control trial that's investigated the role of ultra-processed foods in potentially causing obesity. So we've got, as you mentioned, lots and lots of epidemiological data that have made these associations between people who consume diets that are very high in ultra-processed foods as having greater risk for obesity. But those trials are not demonstrating causation. I mean, they suggest a strong link. And in fact, the idea of ultra-processed foods is kind of a new idea. It's really sort of appeared on the nutrition science stage probably most prominently in the past 10 years or so. And I first learned about this idea of ultra-processed foods, which is really kind of antithetical to the way most nutrition scientists think about foods. We often think about foods as nutrient delivery vehicles, and we kind of view foods as being the fraction of carbohydrates versus fats in them or how much sodium or fiber is in the foods.Kevin Hall (02:17):And along came this group in Brazil who introduced this new way of classifying foods that completely ignores the nutrient composition and says what we should be doing is classifying foods based on the extent and purpose of processing of foods. And so, they categorize these four different categories. And in the fourth category of this so-called NOVA classification scheme (see graphic below) , they identified something called ultra-processed foods. There's a long formal definition and it's evolved a little bit over the years and continues to evolve. But the basic ideas that these are foods that are manufactured by industries that contain a lot of purified ingredients made from relatively cheap agricultural commodity products that basically undergo a variety of processes and include additives and ingredients that are not typically found in home kitchens, but are typically exclusively in manufactured products to create the wide variety of mostly packaged goods that we see in our supermarkets.Kevin Hall (03:22):And so, I was really skeptical that there was much more about the effects of these foods. Other than that they typically have high amounts of sugar and saturated fat and salt, and they're pretty low in fiber. And so, the purpose of this study was to say, okay, well if there's something more about the foods themselves that is causing people to overconsume calories and gain weight and eventually get obesity, then we should do a study that's trying to test for two diets that are matched for these various nutrients of concern. So they should be matched for the macronutrients, they should be matched for the sugar content, the fat, the sodium, the fiber, and people should just be allowed to eat whatever they want and they shouldn't be trying to change their weight in any way. And so, the way that we did this was, as you mentioned, we can't just ask people to report what they're eating.Kevin Hall (04:19):So what we did was we admitted these folks to the NIH Clinical Center and to our metabolic ward, and it's a very artificial environment, but it's an environment that we can control very carefully. And so, what we basically did is take control over their food environment and we gave them three meals a day and snacks, and basically for a two-week period, they had access to meals that were more than 80% of calories coming from ultra-processed foods. And then in random order, they either received that diet first and give them simple instructions, eat as much as little as you want. We're going to measure lots of stuff. You shouldn't be trying to change your weight or weight that gave them a diet that had no calories from ultra-processed foods. In fact, 80% from minimally processed foods. But again, both of these two sort of food environments were matched for these nutrients that we typically think of as playing a major role in how many calories people choose to eat.Kevin Hall (05:13):And so, the basic idea was, okay, well let's measure what these folks eat. We gave them more than double the calories that they would require to maintain their weight, and what they didn't know was that in the basement of the clinical center where the metabolic kitchen is, we had all of our really talented nutrition staff measuring the leftovers to see what it was that they didn't eat. So we knew exactly what we provided to them and all the foods had to be in our nutrition database and when we compute what they actually ate by difference, so we have a very precise estimate about not only what foods they chose to ate, but also how many calories they chose to eat, as well as the nutrient composition.And the main upshot of all that was that when these folks were exposed to this highly ultra-processed food environment, they spontaneously chose to eat about 500 calories per day more over the two-week period they were in that environment then when the same folks were in the environment that had no ultra-processed foods, but just minimally processed foods. They not surprisingly gained weight during the ultra-processed food environment and lost weight and lost body fat during the minimally processed food environment. And because those diets were overall matched for these different nutrients, it didn't seem to be that those were the things that were driving this big effect. So I think there's a couple of big take homes here. One is that the food environment really does have a profound effect on just the biology of how our food intake is controlled at least over relatively short periods of time, like the two-week periods that we were looking at. And secondly, that there's something about ultra-processed foods that seem to be driving this excess calorie intake that we now know has been linked with increased risk of obesity, and now we're starting to put some of the causal pieces together that really there might be something in this ultra-processed food environment that's driving the increased rates of obesity that we've seen over the past many decades.Eric Topol (07:18):Yeah, I mean I think the epidemiologic studies that make the link between ultra-processed foods and higher risk of cancer, cardiovascular disease, type 2 diabetes, neurodegenerative disease. They're pretty darn strong and they're backed up by this very rigorous study. Now you mentioned it short term, do you have any reason to think that adding 500 calories a day by eating these bad foods, which by the way in the American diet is about 60% or more of the average American diet, do you have any inkling that it would change after a few weeks?Kevin Hall (07:54):Well, I don't know about after a few weeks, but I think that one of the things that we do know about body weight regulation and how it changes in body weight impact both metabolism, how many calories were burning as well as our appetite. We would expect some degree of moderation of that effect eventually settling in at a new steady state, that's probably going to take months and years to achieve. And so the question is, I certainly don't believe that it would be a 500 calorie a day difference indefinitely. The question is when would that difference converge and how much weight would've been gained or lost when people eventually reached that new plateau? And so, that's I think a really interesting question. Some folks have suggested that maybe if you extrapolated the lines a little bit, you could predict when those two curves might eventually converge. That's an interesting thought experiment, but I think we do need some longer studies to investigate how persistent are these effects. Can that fully explain the rise in average body weight and obesity rates that have occurred over the past several decades? Those are open questions.Eric Topol (09:03):Yeah. Well, I mean, I had the chance to interview Chris van Tulleken who wrote the book, Ultra-Processed People and I think you might remember in the book he talked about how he went on an ultra-processed diet and gained some 20, 30 pounds in a short time in a month. And his brother, his identical twin brother gained 50, 60 pounds, and so it doesn't look good. Do you look at all the labels and avoid all this junk and ultra-processed food now or are you still thinking that maybe it's not as bad as it looks?Kevin Hall (09:38):Well, I mean I think that I certainly learned a lot from our studies, and we are continuing to follow this up to try to figure out what are the mechanisms by which this happen. But at the same time, I don't think we can throw out everything else we know about nutrition science. So just because we match these various nutrients in this particular study, I think one of the dangers here is that as you mentioned, there's 60% of the food environment in the US and Great Britain and other places consist of these foods, and so they're unavoidable to some extent, right? Unless you're one of these privileged folks who have your backyard garden and your personal chef who can make all of your foods, I'm certainly not one of those people, but for the vast majority of us, we're going to have to incorporate some degree of ultra-processed foods in our day-to-day diet.Kevin Hall (10:24):The way I sort of view it is, we really need to understand the mechanisms and before we understand the mechanisms, we have to make good choices based on what we already know about nutrition science, that we should avoid the foods that have a lot of sugar in them. We should avoid foods that have a lot of saturated fat and sodium. We should try to choose products that contain lots of whole grains and legumes and fruits and vegetables and things like that. And there's some of those, even in the ultra-processed food category. I pretty regularly consume a microwavable ready meal for lunch. It tends to be pretty high in whole grains and legumes and low in saturated fat and sugar and things like that. But to engineer a food that can heat up properly in a microwave in four minutes has some ultra-processing technology involved there. I would be pretty skeptical that that's going to cause me to have really poor health consequences as compared to if I had the means to eat homemade French fries every day in tallow. But that's the kind of comparison that we have to think about.Eric Topol (11:36):But I think what you're touching on and maybe inadvertently is in that NOVA class four, the bad ultra-processed foods, there's a long, long list of course, and some of those may be worse than others, and we haven't seen an individual ranking of these constituents. So as you're alluding to what's in that microwave lunch probably could be much less concerning than what's in these packaged snacks that are eaten widely. But I would certainly agree that we don't know everything about this, but your study is one of the most quoted studies ever in the ultra-processed food world. Now, let me move on to another trial that was really important. This was published in Nature Medicine and it's about a plant-based diet, which is of course a very interesting diet, low-fat versus an animal-based ketogenic diet. Also looking at energy intake. Can you take us through that trial?Plant-Based, Low Fat Diet vs Animal-Based, Low Carbohydrate Ketogenic DietKevin Hall (12:33):Sure. So it's actually interesting to consider that trial in the context of the trial we just talked about because both of these diets that we tested in this trial were relatively low in ultra-processed foods, and so both of them contained more than a kilogram of non-starchy vegetables as a base for designing these, again, two different food environments. Very similar overall study design where people again were exposed to either diets that were vegan plant-based diet that was really high in starches and was designed to kind of cause big insulin increases in the blood after eating the meals. And the other diet had very, very few carbohydrates of less than 10% in total, and we built on that kind of non-starchy vegetable base, a lot of animal-based products to kind of get a pretty high amount of fat and having very low carbohydrates. Both diets in this case, like I mentioned, were pretty low in ultra-processed foods, but what we were really interested in here was testing this idea that has come to prominence recently, that high carbohydrate diets that lead to really large glucose excursions after meals that cause very high insulin levels after meals are particularly obesogenic and should cause you to be hungrier than compared to a diet that doesn't lead to those large swings in glucose and insulin and the prototypical case being one that's very low in carbohydrate and might increase the level of ketones that are floating around in your blood, which are hypothesized to be an appetite suppressant. Same sort of design, these minimally processed diets that one was very high in carbs and causes large swings in insulin and the other that's very low in carbs and causes increases in ketones.Kevin Hall (14:22):We ask people, again, while you're in one food environment or the other, don't be trying to gain weight or lose weight, eat as much or as little as you'd like, and we're going to basically measure a lot of things. They again, don't know what the primary outcome of the study is. We're measuring their leftovers afterwards. And so, the surprise in this particular case was that the diet that caused the big swings in glucose and insulin did not lead to more calorie consumption. In fact, it led to about 700 calories per day less than when the same people were exposed to the ketogenic diet. Interestingly, both food environments caused people to lose weight, so it wasn't that we didn't see the effect of people over consuming calories on either diet, so they were reading fewer calories in general than they were when they came in, right. They're probably eating a pretty ultra-processed food diet when they came in. We put them on these two diets that varied very much in terms of the macronutrients that they were eating, but both were pretty minimally processed. They lost weight. They ended up losing more body fat on the very low-fat high carb diet than the ketogenic diet, but actually more weight on the ketogenic diet than the low-fat diet. So there's a little bit of a dissociation between body fat loss and weight loss in this study, which was kind of interesting.Eric Topol (15:49):Interesting. Yeah, I thought that was a fascinating trial because plant-based diet, they both have their kind of camps, you know.Kevin Hall (15:57):Right. No, exactly.Immune System Signatures for Vegan vs Ketogenic DietsEric Topol (15:58):There are people who aren't giving up on ketogenic diet. Of course, there's some risks and some benefits and there's a lot of interest of course with the plant-based diet. So it was really interesting and potentially the additive effects of plant-based with avoidance or lowering of ultra-processed food. Now, the more recent trial that you did also was very interesting, and of course I'm only selecting ones that I think are particularly, there are a lot of trials you've done, but this one is more recent in this year where you looked at vegan versus ketogenic diets for the immune signature, immune response, which is really important. It's underplayed as its effect, and so maybe you can take us through that one.[Link to a recent Nature feature on this topic, citing Dr. Hall's work]Kevin Hall (16:43):Yeah, so just to be clear, it's actually the same study, the one that we just talked about. This is a secondary sort of analysis from a collaboration we had with some folks at NIAID here at the NIH to try to evaluate immune systems signatures in these same folks who wonder what these two changes in their food environment. One is vegan, high carbohydrate low-fat diet and the other, the animal-based ketogenic diet. And again, it was pretty interesting to me that we were able to see really substantial changes in how the immune system was responding. First of all, both diets again seem to have improved immune function, both adaptive and innate immune function as compared to their baseline measurements when they came into the study. So when they're reading their habitual diet, whatever that is typically high in ultra-processed foods, they switched to both of these diets.Kevin Hall (17:39):We saw market changes in their immune system even compared to baseline. But when we then went and compared the two diets, they were actually divergent also, in other words, the vegan diet seemed to stimulate the innate immune system and the ketogenic diet seemed to stimulate the adaptive immune system. So these are the innate immune system can be thought of. Again, I'm not an immunologist. My understanding is that this is the first line defense against pathogens. It happens very quickly and then obviously the adaptive immune system then adapts to a specific pathogen over time. And so, this ability of our diet to change the immune system is intriguing and how much of that has to do with influencing the gut microbiota, which obviously the gut plays a huge role in steering our immune system in one direction versus another. I think those are some really intriguing mechanistic questions that are really good fodder for future research.Eric Topol (18:42):Yeah, I think it may have implications for treatment of autoimmune diseases. You may want to comment about that.Kevin Hall (18:51):Yeah, it's fascinating to think about that the idea that you could change your diet and manipulate your microbiota and manipulate your gut function in a way to influence your immune system to steer you away from a response that may actually be causing your body damage in your typical diet. It's a fascinating area of science and we're really interested to follow that up. I mean, it kind of supports these more anecdotal reports of people with lupus, for example, who've reported that when they try to clean up their diet for a period of time and eliminate certain foods and eliminate perhaps even ultra-processed food products, that they feel so much better that their symptoms alleviate at least for some period of time. Obviously, it doesn't take the place of the therapeutics that they need to take, but yeah, we're really interested in following this up to see what this interaction might be.Eric Topol (19:46):Yeah, it's fascinating. It also gets to the fact that certain people have interesting responses. For example, those with epilepsy can respond very well to a ketogenic diet. There's also been diet proposed for cancer. In fact, I think there's some even ongoing trials for cancer of specific diets. Any comments about that?Kevin Hall (20:10):Yeah, again, it's a really fascinating area. I mean, I think we kind of underappreciate and view diet in this lens of weight loss, which is not surprising because that's kind of where it's been popularized. But I think the role of nutrition and how you can manipulate your diet and still you can have a very healthy version of a ketogenic diet. You can have a very healthy version of a low-fat, high carb diet and how they can be used in individual cases to kind of manipulate factors that might be of concern. So for example, if you're concerned about blood glucose levels, clearly a ketogenic diet is moderating those glucose levels over time, reducing insulin levels, and that might have some positive downstream consequences and there's some potential downsides. Your apoB levels might go up. So, you have to kind of tune these things to the problems and the situations that individuals may face. And similarly, if you have issues with blood glucose control, maybe a high carbohydrate diet might not be for you, but if that's not an issue and you want to reduce apoB levels, it seems like that is a relatively effective way to do that, although it does tend to increase fasting triglyceride levels.Kevin Hall (21:27):So again, there's all of these things to consider, and then when you open the door beyond traditional metabolic health markers to things like inflammation and autoimmune disease as well as some of these other things like moderating how cancer therapeutics might work inside the body. I think it's a really fascinating and interesting area to pursue.Eric Topol (21:55):No question about it. And that also brings in the dimension of the gut microbiome, which obviously your diet has a big influence, and it has an influence on your brain, brain-gut axis, and the immune system. It's all very intricate, a lot of feedback loops and interactions that are not so easy to dissect, right?Kevin Hall (22:16):Absolutely. Yeah, especially in humans. That's why we rely on our basic science colleagues to kind of figure out these individual steps in these chains. And of course, we do need human experiments and carefully controlled experiments to see how much of that really translates to humans, so we need this close sort of translational partnership.On the Pathogenesis of Obesity, Calories In and Calories OutEric Topol (22:35):Yeah. Now, you've also written with colleagues, other experts in the field about understanding the mechanisms of pathogenesis of obesity and papers that we'll link to. We're going to link to everything for what we've been discussing about calories in, calories out, and that's been the longstanding adage about this. Can you enlighten us, what is really driving obesity and calories story?Kevin Hall (23:05):Well, I co-organized a meeting for the Royal Society, I guess about a year and a half ago, and we got together all these experts from around the world, and the basic message is that we have lots of competing theories about what is driving obesity. There's a few things that we all agree on. One is that there is a genetic component. That adiposity in a given environment is somewhere between 40% to 70% heritable, so our genes play a huge role. It seems like there's certain genes that can play a major role. Like if you have a mutation in leptin, for example, or the leptin receptor, then this can have a monogenic cause of obesity, but that's very, very rare. What seems to be the case is that it's a highly polygenic disease with individual gene variants contributing a very, very small amount to increased adiposity. But our genes have not changed that much as obesity prevalence has increased over the past 50 years. And so, something in the environment has been driving that, and that's where the real debates sort of starts, right?Kevin Hall (24:14):I happen to be in the camp that thinks that the food environment is probably one of the major drivers and our food have changed substantially, and we're trying to better understand, for example, how ultra-processed foods which have risen kind of in parallel with the increased prevalence of obesity. What is it about ultra-processed foods that tend to drive us to overconsume calories? Other folks focus maybe more on what signals from the body have been altered by the foods that we're eating. They might say that the adipose tissue because of excess insulin secretion for example, is basically driven into a storage mode and that sends downstream signals that are eventually sensed by the brain to change our appetite and things like that. There's a lot of debate about that, but again, I think that these are complementary hypotheses that are important to sort out for sure and important to design experiments to try to figure out what is more likely. But there is a lot of agreement on the idea that there's something in our environment has changed.Kevin Hall (25:17):I think there's even maybe a little bit less agreement of exactly what that is. I think that there's probably a little bit more emphasis on the food environment as opposed to there are other folks who think increased pollution might be driving some of this, especially endocrine disrupting chemicals that have increased in prevalence. I think that's a viable hypothesis. I think we have to try to rank order what we think are the most likely and largest contributors. They could all be contributing to some extent and maybe more so in some people rather than others, but our goal is to try to, maybe that's a little simple minded, but let's take the what I think is the most important thing and let's figure out the mechanisms of that most important thing and we'll, number one, determine if it is the most important thing. In my case, I think something about ultra-processed foods that are driving much of what we're seeing. If we could better understand that, then we could both advise consumers to avoid certain kinds of foods because of certain mechanisms and still be able to consume some degree of ultra-processed foods. They are convenient and tasty and relatively inexpensive and don't require a lot of skill and equipment to prepare. But then if we focus on the true bad guys in that category because we really understand the mechanisms, then I think that would be a major step forward. But that's just my hypothesis.Eric Topol (26:43):Well, I'm with you actually. Everything I've read, everything I've reviewed on ultra-processed food is highly incriminating, and I also get frustrated that nothing is getting done about it, at least in this country. But on the other hand, it doesn't have to be either or, right? It could be both these, the glycemic index story also playing a role. Now, when you think about this and you're trying to sort out calories in and calories out, and let's say it's one of your classic experiments where you have isocaloric proteins and fat and carbohydrate exactly nailed in the different diets you're examining. Is it really about calories or is it really about what is comprising the calorie?Kevin Hall (27:29):Yeah, so I think this is the amazing thing, even in our ultra-processed food study, if we asked the question across those people, did the people who ate more calories even in the ultra-processed diet, did they gain more weight? The answer is yes.Kevin Hall (27:44):There's a very strong linear correlation between calorie intake and weight change. I tend to think that I started my career in this space focusing more on the metabolism side of the equation, how the body's using the calories and how much does energy expenditure change when you vary the proportion of carbs versus fat, for example. The effect size is there, they might be there, but they're really tiny of the order of a hundred calories per day. What really struck me is that when we just kind of changed people's food environments, the magnitude of the effects are like we mentioned, 500 to 700 calories per day differences. So I think that the real trick is to figure out how is it that the brain is regulating our body weight in some way that we are beginning to understand from a molecular perspective? What I think is less well understood is, how is that food intake control system altered by the food environment that we find ourselves in?The Brain and GLP-1 DrugsKevin Hall (28:42):There are a few studies now in mice that are beginning to look at how pathways in the brain that have been believed to be related to reward and not necessarily homeostatic control of food intake. They talk to the regions of the brain that are related to homeostatic control of food intake, and it's a reciprocal sort of feedback loop there, and we're beginning to understand that. And I think if we get more details about what it is in our foods that are modulating that system, then we'll have a better understanding of what's really driving obesity and is it different in different people? Are there subcategories of obesity where certain aspects of the food environment are more important than others, and that might be completely flipped in another person. I don't know the answer to that question yet, but it seems like there are certain common factors that might be driving overall changes in obesity prevalence and how they impact this reward versus homeostatic control systems in the brain, I think are really fascinating questions.Eric Topol (29:43):And I think we're getting much more insight about this circuit of the reward in the brain with the food intake, things like optogenetics, many ways that we're getting at this. And so, it's fascinating. Now, that gets me to the miracle drug class GLP-1, which obviously has a big interaction with obesity, but of course much more than that. And you've written about this as well regarding this topic of sarcopenic obesity whereby you lose a lot of weight, but do you lose muscle mass or as you referred to earlier, you lose body fat and maybe not so much muscle mass. Can you comment about your views about the GLP-1 family of drugs and also about this concern of muscle mass loss?Kevin Hall (30:34):Yeah, so I think it's a really fascinating question, and we've been trying to develop mathematical models about how our body composition changes with weight gain and weight loss for decades now. And this has been a long topic, one of the things that many people may not realize is that people with obesity don't just have elevated adiposity, they also have elevated muscle mass and lean tissue mass overall. So when folks with obesity lose weight, and this was initially a pretty big concern with bariatric surgery, which has been the grandfather of ways that people have lost a lot of weight. The question has been is there a real concern about people losing too much weight and thereby becoming what you call sarcopenic? They have too little muscle mass and then they have difficulties moving around. And of course, there are probably some people like that, but I think what people need to realize is that folks with obesity tend to start with much higher amounts of lean tissue mass as well as adiposity, and they start off with about 50% of your fat-free mass, and the non-fat component of your body is skeletal muscle.Kevin Hall (31:45):So you're already starting off with quite a lot. And so, the question then is when you lose a lot of weight with the GLP-1 receptor agonist or with bariatric surgery, how much of that weight loss is coming from fat-free mass and skeletal muscle versus fat mass? And so, we've been trying to simulate that using what we've known about bariatric surgery and what we've known about just intentional weight loss or weight gain over the years. And one of the things that we found was that our sort of expectations for what's expected for the loss of fat-free mass with these different drugs as well as bariatric surgery, for the most part, they match our expectations. In other words, the expected amount of fat loss and fat free mass loss. The one outlier interestingly, was the semaglutide study, and in that case, they lost more fat-free mass than would be expected.Kevin Hall (32:44):Now, again, that's just raising a little bit of a flag that for whatever reason, from a body composition perspective, it's about a hundred people underwent these repeated DEXA scans in that study sponsored by Novo Nordisk. So it's not a huge number of people, but it's enough to really get a good estimate about the proportion of weight loss. Whether or not that has functional consequences, I think is the open question. There's not a lot of reports of people losing weight with semaglutide saying, you know what? I'm really having trouble actually physically moving around. I feel like I've lost a lot of strength. In fact, it seems to be the opposite, right, that the quality of the muscle there seems to be improved. They seem to have more physical mobility because they've lost so much more weight, that weight had been inhibiting their physical movement in the past.Kevin Hall (33:38):So it's something to keep an eye on. It's an open question whether or not we need additional therapies in certain categories of patients, whether that be pharmacological, there are drugs that are interesting that tend to increase muscle mass. There's also other things that we know increase muscle mass, right? Resistance exercise training, increase this muscle mass. And so, if you're really concerned about this, I certainly, I'm not a physician, but I think it's something to consider that if you go on one of these drugs, you might want to think about increasing your resistance exercise training, maybe increasing the protein content of your diet, which then can support that muscle building. But I think it's a really interesting open question about what the consequences of this might be in certain patient populations, especially over longer periods of time.Dietary Protein, Resistance Exercise, DEXA ScansEric Topol (34:30):Yeah, you've just emphasized some really key points here. Firstly, that resistance exercise is good for you anyway. And get on one of these drugs, why don't you amp it up or get it going? The second is about the protein diet, which it'd be interesting to get your thoughts on that, but we generally have too low of a protein diet, but then there are some who are advocating very high protein diets like one gram per pound, not just one gram per kilogram. And there have been studies to suggest that that very high protein diet could be harmful, but amping up the protein diet, that would be a countering thing. But the other thing you mentioned is a DEXA scan, which can be obtained very inexpensively, and because there's a variability in this muscle mass loss if it's occurring, I wonder if that's a prudent thing or if you just empirically would just do the things that you mentioned. Do you have any thoughts about that?Kevin Hall (35:32):Yeah, that's really a clinical question that I don't deal with on a day-to-day basis. And yeah, I think there's probably better people suited to that. DEXA scans, they're relatively inexpensive, but they're not readily accessible to everyone. I certainly wouldn't want to scare people away from using drugs that are now known to be very effective for weight loss and pretty darn safe as far as we can tell, just because they don't have access to a DEXA scanner or something like that.Eric Topol (36:00):Sure. No, that makes a lot of sense. I mean, the only reason I thought it might be useful is if you're concerned about this and you want to track, for example, how much is that resistant training doing?Kevin Hall (36:13):But I think for people who have the means to do that, sure. I can't see any harm in it for sure.Continuous Glucose Sensors?Eric Topol (36:19):Yeah. That gets me to another metric that you've written about, which is continuous glucose tracking. As you know, this is getting used, I think much more routinely in type one insulin diabetics and people with type 2 that are taking insulin or difficult to manage. And now in recent months there have been consumer approved that is no prescription needed, just go to the drugstore and pick up your continuous glucose sensor. And you've written about that as well. Can you summarize your thoughts on it?Kevin Hall (36:57):Yeah, sure. I mean, yeah, first of all, these tools have been amazing for people with diabetes and who obviously are diagnosed as having a relative inability to regulate their glucose levels. And so, these are critical tools for people in that population. I think the question is are they useful for people who don't have diabetes and is having this one metric and where you target all this energy into this one thing that you can now measure, is that really a viable way to kind of modulate your lifestyle and your diet? And how reliable are these CGM measurements anyway? In other words, do they give the same response to the same meal on repeated occasions? Does one monitor give the same response as another monitor? And those are the kinds of experiments that we've done. Again, secondary analysis, these trials that we talked about before, we have people wearing continuous glucose monitors all the time and we know exactly what they ate.Kevin Hall (37:59):And so, in a previous publication several years ago, we basically had two different monitors. One basically is on the arm, which is the manufacturer's recommendation, the other is on the abdomen, which is the manufacturer's recommendation. They're wearing them simultaneously. And we decided just to compare what were the responses to the same meals in simultaneous measurements. And they were correlated with each other thankfully, but they weren't as well predictive as you might expect. In other words, one device might give a very high glucose reading to consuming one meal and the other might barely budge, whereas the reverse might happen for a different meal. And so, we asked the question, if we were to rank the glucose spikes by one meal, so we have all these meals, let's rank them according to the glucose spikes of one device. Let's do the simultaneous measurements with the other device.Kevin Hall (38:53):Do we get a different set of rankings? And again, they're related to each other, but they're not overlapping. They're somewhat discordant. And so, then the question becomes, okay, well if I was basically using this one metric to kind of make my food decisions by one device, I actually start making different decisions compared to if I happen to have been wearing a different device. So what does this really mean? And I think this sort of foundational research on how much of a difference you would need to make a meaningful assessment about, yeah, this is actionable from a lifestyle perspective, even if that is the one metric that you're interested in. That sort of foundational research I don't think has really been done yet. More recently, we asked the question, okay, let's ignore the two different devices. Let's stick to the one where we put it on our arm, and let's ask the question.Kevin Hall (39:43):We've got repeated meals and we've got them in this very highly regimented and controlled environment, so we know exactly what people ate previously. We know the timing of the meals, we know when they did their exercise, we know how much they were moving around, how well they slept the night before. All of these factors we could kind of control. And the question that we asked in that study was, do people respond similarly to the same meal on repeated occasions? Is that better than when you actually give them very different meals? But they match overall for macronutrient content, for example. And the answer to that was surprisingly no. We had as much variability in the glucose response to the same person consuming the same meal on two occasions as a whole bunch of different meals. Which suggests again, that there's enough variability that it makes it difficult to then recommend on for just two repeats of a meal that this is going to be a meal that's going to cause your blood glucose to be moderate or blood glucose to be very high. You're going to have to potentially do this on many, many different occasions to kind of figure out what's the reliable response of these measurements. And again, that foundational research is typically not done. And I think if we're really going to use this metric as something that is going to change our lifestyles and make us choose some meals other than others, then I think we need that foundational research. And all we know now is that two repeats of the same meal is not going to do it.Eric Topol (41:21):Well, were you using the current biosensors of 2024 or were you using ones from years ago on that?Kevin Hall (41:27):No, we were using ones from several years ago when these studies were completed. But interestingly, the variability in the venous measurements to meal tests is also very, very different. So it's probably not the devices per se that are highly variable. It's that we don't really know on average how to predict these glucose responses unless there's huge differences in the glycemic load. So glycemic load is a very old concept that when you have very big differences in glycemic load, yeah, you can on average predict that one kind of meal is going to give rise to a much larger glucose excursion than another. But typically these kind of comparisons are now being made within a particular person. And we're comparing meals that might have quite similar glycemic loads with the claim that there's something specific about that person that causes them to have a much bigger glucose spike than another person. And that we can assess that with a couple different meals.Eric Topol (42:31):But also, we know that the spikes or the glucose regulation, it's very much affected by so many things like stress, like sleep, like exercise. And so, it wouldn't be at all surprising that if you had the exact same food, but all these other factors were modulated that it might not have the same response. But the other thing, just to get your comment on. Multiple groups, particularly starting in Israel, the Weizmann Institute, Eran Segal and his colleagues, and many subsequent have shown that if you give the exact same amount of that food, the exact same time to a person, they eat the exact same amount. Their glucose response is highly heterogeneous and variable between people. Do you think that that's true? That in fact that our metabolism varies considerably and that the glucose in some will spike with certain food and some won't.Kevin Hall (43:29):Well, of course that's been known for a long time that there's varying degrees of glucose tolerance. Just oral glucose tolerance tests that we've been doing for decades and decades we know is actually diagnostic, that we use variability in that response as diagnostic of type 2 diabetes.Eric Topol (43:49):I'm talking about within healthy people.Kevin Hall (43:53):But again, it's not too surprising that varying people. I mean, first of all, we have a huge increase in pre-diabetes, right? So there's various degrees of glucose tolerance that are being observed. But yeah, that is important physiology. I think the question then is within a given person, what kind of advice do we give to somebody about their lifestyle that is going to modulate those glucose responses? And if that's the only thing that you look at, then it seems like what ends up happening, even in the trials that use continuous glucose monitors, well big surprise, they end up recommending low carbohydrate diets, right? So that's the precision sort of nutrition advice because if that's the main metric that's being used, then of course we've all known for a very long time that lower carbohydrate diets lead to a moderated glucose response compared to higher carbohydrate diets. I think the real question is when you kind of ask the issue of if you normalize for glycemic load of these different diets, and there are some people that respond very differently to the same glycemic load meal compared to another person, is that consistent number one within that person?Kevin Hall (45:05):And our data suggests that you're going to have to repeat that same test multiple times to kind of get a consistent response and be able to make a sensible recommendation about that person should eat that meal in the future or not eat that meal in the future. And then second, what are you missing when that becomes your only metric, right? If you're very narrowly focused on that, then you're going to drive everybody to consume a very low carbohydrate diet. And as we know, that might be great for a huge number of people, but there are those that actually have some deleterious effects of that kind of diet. And if you're not measuring those other things or not considering those other things and put so much emphasis on the glucose side of the equation, I worry that there could be people that are being negatively impacted. Not to mention what if that one occasion, they ate their favorite food and they happen to get this huge glucose spike and they never eat it again, their life is worse. It might've been a complete aberration.Eric Topol (46:05):I think your practical impact point, it's excellent. And I think one of the, I don't know if you agree, Kevin, but one of the missing links here is we see these glucose spikes in healthy people, not just pre-diabetic, but people with no evidence of glucose dysregulation. And we don't know, they could be up to 180, 200, they could be prolonged. We don't know if the health significance of that, and I guess someday we'll learn about it. Right?Kevin Hall (46:36):Well, I mean that's the one nice thing is that now that we have these devices to measure these things, we can start to make these correlations. We can start to do real science to say, what a lot of people now presume is the case that these spikes can't be good for you. They must lead to increased risk of diabetes. It's certainly a plausible hypothesis, but that's what it is. We actually need good data to actually analyze that. And at least that's now on the table.Eric Topol (47:04):I think you're absolutely right on that. Well, Kevin, this has been a fun discussion. You've been just a great leader in nutrition science. I hope you'll keep up your momentum because it's pretty profound and I think we touched on a lot of the uncertainties. Is there anything that I didn't ask you that you wish I did?Kevin Hall (47:23):I mean, we could go on for hours, I'm sure, Eric, but this has been a fascinating conversation. I really appreciate your interest. Thank you.Eric Topol (47:30):Alright, well keep up the great stuff. We'll be following all your work in the years ahead, and thanks for joining us on Ground Truths today.**************************************Footnote, Stay Tuned: Julia Belluz and Kevin Hall have a book coming out next September titled “WHY WE EAT? Thank you for reading, listening and subscribing to Ground Truths.If you found this fun and informative please share it!All content on Ground Truths—its newsletters, analyses, and podcasts, are free, open-access.Paid subscriptions are voluntary. All proceeds from them go to support Scripps Research. Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. I welcome all comments from paid subscribers and will do my best to respond to them and any questions.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio and video support at Scripps Research.Note on Mass Exodus from X/twitter:Many of you have abandoned the X platform for reasons that I fully understand. While I intend to continue to post there because of its reach to the biomedical community, I will post anything material here in the Notes section of Ground Truths on a daily basis and cover important topics in the newsletter/analyses. You can also find my posts at Bluesky: @erictopol.bsky.social, which is emerging as an outstanding platform for sharing life science. Get full access to Ground Truths at erictopol.substack.com/subscribe

¿El ayuno intermitente es realmente seguro o puede ser un peligro oculto para tu salud? Este video te revela toda la verdad: los riesgos que nadie menciona, los errores más comunes y cómo implementar el ayuno intermitente de forma saludable y sostenible. Aprende a evitar los problemas metabólicos, hormonales y nutricionales para aprovechar los increíbles beneficios de esta práctica ancestral. ¿Qué aprenderás en este video? - ¿Qué es el ayuno intermitente y por qué ha sido tan popular? - Los principales errores al practicarlo y cómo evitarlos. - Los beneficios metabólicos, hormonales y mentales del ayuno intermitente. - Cómo empezar el ayuno intermitente de manera correcta, sin apps ni temporizadores. - La verdad sobre cómo afecta a tu salud y cómo aprovecharlo para tu bienestar. El ayuno intermitente no es solo una herramienta para perder peso, también puede transformar tu salud metabólica y mental, pero solo si lo haces correctamente. No te dejes llevar por mitos o prácticas incorrectas que puedan dañar tu cuerpo. ¿Qué te vas a llevar de este video? - Cómo preparar tu cuerpo antes de empezar un ayuno. - Por qué espaciar tus comidas poco a poco es clave para el éxito. - La importancia de escuchar a tu cuerpo en lugar de seguir horarios rígidos. - Cómo mejorar tu claridad mental y enfoque con esta práctica.

Welcome to the Olink® Proteomics in Proximity podcast! Below are some useful resources mentioned in this episode:  Olink tools and softwareOlink® Explore 3072, the platform utilized by the UK Biobank to measure ~3000 proteins in plasma: https://olink.com/products-services/explore/Olink® Explore HT, Olink's most advanced solution for high-throughput biomarker discovery, measuring 5400+ proteins simultaneously with a streamlined workflow and industry-leading specificity: https://olink.com/products-services/exploreht/  UK Biobank Pharma Proteomics Project (UKB-PPP), one of the world's largest scientific studies of blood protein biomarkers conducted to date, https://www.ukbiobank.ac.uk/learn-more-about-uk-biobank/news/uk-biobank-launches-one-of-the-largest-scientific-studies  Research articlesThe support of human genetic evidence for approved drug indicationsMatthew R Nelson et al,  Nature Genetics 2015https://www.nature.com/articles/ng.3314 Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populationsM. Austin Argentieri et al,  Nature Medicine 2024https://www.nature.com/articles/s41591-024-03164-7 Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systemsLudger J.E. Goeminne et al, Cell Metabolism 2024, in presshttps://www.sciencedirect.com/science/article/abs/pii/S1550413124004017?via%3Dihub Plasma proteomic associations with genetics and health in the UK BiobankBenjamin B. Sun et, Nature 2023https://www.nature.com/articles/s41586-023-06592-6 Rare variant associations with plasma protein levels in the UK BiobankRyan S. Dhindsa; Nature 2023https://www.nature.com/articles/s41586-023-06547-x Disease prediction with multi-omics and biomarkers empowers case–control genetic discoveries in the UK BiobankManik Garg, Nature Genetics, 2024https://www.nature.com/articles/s41588-024-01898-1 China Kadoorie Biobank: https://www.ckbiobank.org/publicationsPublications: https://www.ckbiobank.org/publications Subscribe to the podcast on your favorite player or app:Apple Podcasts: https://apple.co/3T0YbSm  Spotify Podcasts: https://open.spotify.com/show/2sZ2wxO...  Google Podcasts: https://podcasts.google.com/feed/aHR0...   Amazon Music: https://music.amazon.com/podcasts/d97...   Podcast Addict:

Episode 179: Impact of intermittent fasting Impact on T2DMFuture Dr. Carlisle explains the physiology of fasting and how it can help revert type 2 diabetes. Dr. Arreaza adds details on how to do intermittent fasting. Written by Cameron Carlisle, MSIV, Ross University School of Medicine. Comments and edits by Hector Arreaza, MD, FAAFP.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.What is type 2 Diabetes Mellitus (T2DM)?-Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and impaired glucose regulation. -This impaired regulation can lead to hyperglycemia, contributing to complications in a myriad of organs: heart, kidneys, eyes, nerves, etc. (target organs). According to the CDC, more than 38 million Americans have T2DM (about 1/10 people). -Multiple mechanisms are believed to contribute to insulin resistance in obese patients with T2DM, such as increased lipid deposition throughout the body and systemic inflammation.What is Intermittent Fasting (IF)? Intermittent fasting (IF) has recently gained popularity as a dietary approach for health benefits, but it has been around for thousands of years. IF is an eating pattern that alternates between eating and fasting (no calories consumed) over a specific period of time. When you are fasting, you are allowed and encouraged to keep drinking water and non-caloric drinks, like coffee, tea, and even homemade bone broth.-According to the International Food Information Council Foundation (IFIC), 10% of Americans engage in IF daily. -According to Mark Mattson, a neuroscientist and IF expert for over 25 years, a mechanism called “metabolic switching” is seen with IF. This is when your body runs out of glucose and starts burning fat (i.e., fatty oxidation). These metabolic changes can help protect your organs and reduce the risk of chronic conditions, like T2DM. Common IF methods: Time-restricted eating: Most common method, involves eating within a specific time frame (e.g., the 16:8, 18:6, 12:12 method is also common.  [16:8 means you have 16 hours of fasting and 8 hours of eating.]Alternate-day fasting: Alternating between fasting days and normal eating days.  [Find more info in The Complete Guide to Fasting, by Jason Fung, who is a nephrologist, he explains that alternate-day is basically eating every other day, which would give 36 hours of fasting, but if you are a beginner you can try a 24 hours fasting, in short, not eating breakfast any day of the week and having lunch 4 days a week, and dinner every night.]5:2 diet (aka periodic fasting): Maintaining a normal diet for 5 days, with 2 days (usually non-consecutive) of caloric restriction (25% of normal caloric intake; e.g., 500 calorie meal). IF is strongly believed to improve metabolic health in individuals with T2DM by reducing insulin resistance via increasing insulin sensitivity, promoting weight loss (patients with obesity and DM… AKA patients with diabesity), and enhancing lipolysis via fat oxidation.While fasting, the body goes through several phases that affect how energy is metabolized. Between 0 and 4 hours after eating, the body enters a feeding state, using glucose as its main energy source. After fasting for 12-16 hours, the body enters ketosis and starts to use fat for energy. Within 24-36 hours, autophagy begins, a process that recycles damaged cells and allows for cellular repair. This process can have great benefits for people with T2DM, such as improved insulin sensitivity and glucose regulation. Pathophysiology of Implementing IF in T2DM. -IF is thought to increase insulin sensitivity by decreasing fatty tissue in the body (i.e., visceral adipose tissue), which is correlated to insulin resistance. Insulin resistance is defined as higher than normal circulating insulin levels needed for a glucose lower response, which is thought to be the culprit for the generation of T2DM. It means you need high levels of insulin to keep glucose normal. -Obesity is an important risk factor for T2DM. Visceral adipose tissue functions as an organ via the secretion of adipokines (cytokines or cellular messengers produced by adipose tissue): leptin and adiponectin. Leptin: proinflammatory, leading to chronic inflammation. Patients with higher BMI levels and increased insulin resistance were found to have increased leptin levels.[Leptin is a good hormone at normal levels, but there is leptin resistance] Adiponectin: anti-inflammatory and antidiabetic effects. Higher adiponectin levels result in decreased hepatic gluconeogenesis, enhanced glucose absorption, and enhanced skeletal muscle and hepatic fatty acid oxidation. Levels drop as visceral fat increases. -Dr. López-Jaramillo, a Colombian endocrinologist and researcher, and colleagues published a review in 2014 examining the imbalance in the levels of leptin and adiponectin in individuals with metabolic syndrome. This imbalance (increase in leptin and decrease in adiponectin) is linked to obesity and insulin resistance, which has been shown to increase the risk of T2DM. It has been shown that IF has resulted in the reduction of leptin levels and increased levels of adiponectin, which leads to decreased insulin resistance and increased insulin sensitivity. -IF allows pancreatic beta-cells to rest by not having to secrete insulin constantly. This allows the beta-cells of the pancreas to improve in function over time. In addition, IF has been shown to lead to noticeable weight loss and loss in body fat, both of which play an important contribution in managing T2DM. Research demonstrates that this weight loss increases insulin sensitivity and decreases the need for insulin therapy, making IF a powerful approach for improving metabolic health. AMP-Activated Protein Kinase (AMPK) and Its Role in IF and T2DM Recent research has highlighted an important enzyme seen in IF, AMP-activated protein kinase (AMPK), which plays a vital role as an important energy sensor in cells. It is activated when cellular energy levels are low, such as during IF. A 2020 research study in Nature Reviews Endocrinology explains that activation of AMPK aids in suppressing gluconeogenesis and stimulates fatty acid oxidation, leading to optimal energy balance and reduction of visceral adipose tissue accumulation, a major contributor to insulin resistance and T2DM progression. AMPK is upregulated during fasting, which enhances glucose metabolism and reduces insulin resistance. This is imperative in managing T2DM, as it counters the effects of insulin resistance associated with T2DM.Exercise, which also promotes AMPK activation, complements IF and can promote a synergistic effect in improving insulin sensitivity and promoting fat burning, New Research Findings on IF and T2DM -The EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study is a randomized clinical trial published in JAMA Network Open (2024). Findings In this randomized clinical trial study found that a time-restricted eating window significantly improved fasting glucose levels and HbA1c levels in individuals with T2DM. The study examined the effect of a 16-week 5:2 meal replacement (5:2 MR) fasting plan that consisted of five days of normal eating and 2 days, nonconsecutive of restricted diet (500-600 calories). This group was examined alongside a group of patients who took metformin 0.5 g BID and empagliflozin 10 mg QD. The study wanted to investigate the changes in HbA1c in Chinese adults with early T2DM.-The study was a randomized clinical trial of 405 adults, and a study showed that the 5:2 MR approach led to better glycemic control at 16 weeks compared to the counter treatments with metformin and empagliflozin. The 5:2 MR group had the greatest reduction in HbA1c (-1.9%), followed by metformin (-1.6%), and empagliflozin (-1.5%). The 5:2 MR plan also revealed the greatest weight loss (-9.7 kg), followed by empagliflozin (-5.8 kg), and metformin (-5.5 kg). -This research suggests IF, such as 5:2 MR, can be a powerful tool in the management of T2DM and improving metabolic health. This study can potentially open doors for healthcare providers to provide the 5:2 MR approach for individuals as an effective initial lifestyle intervention. However, follow-up studies are needed to assess the effectiveness and durability of the 5:2 MR.Safety and Risks of IF in T2DM. -IF when combined with glucose-lowering medications (e.g., insulin, sulfonylureas, GLP-1 agonists) can increase the risk of hypoglycemia. Also, prolonged fasting can lead to nutrient deficiencies if not planned carefully. Patients should be counseled on maintaining a balanced, nutritious diet during non-fasting days. -IF is not suitable for everyone. Children under the age of 18 should not try IF due to needing proper calories for adequate development and proper growth. Also, it is recommended that pregnant or breastfeeding women do not undergo IF. It is advised that people with eating disorders should not try IF. -Individuals with certain medical conditions, such as kidney stones or gastroesophageal disease should speak with their doctor before trying IF. Also, patients on insulin or other glucose-lowering medications should adjust their dose and talk with their healthcare providers to prevent hypoglycemia during fasting. It is recommended that each person speak with their doctor to discuss the safety and risks of IF and see if it would benefit the individual before starting IF. -Many studies have explored the benefits of IF at the micro level revealing its cellular benefits and on a macro level of the body as a whole. However, more research is needed to confirm the long-term effects of IF on glycemic control and its sustainability as a therapeutic approach for T2DM. Conclusion:-IF shows potential for improving glycemic control, promoting weight loss, and enhancing metabolic health in individuals with T2DM. Despite its benefits, IF may present with risks, such as hypoglycemia, nutrition deficiencies, or dehydration in certain patients. Therefore, it may not be suitable for all individuals. It's important to monitor patients who engage in IF, especially for patients with T2DM. Patients should follow up with their doctor for individualized IF plans in patients with T2DM. ______________This week we thank Hector Arreaza and Cameron Carlisle. Audio editing by Adrianne Silva.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________References:Albosta, Michael, and Jesse Bakke. “Intermittent Fasting: Is There a Role in the Treatment of Diabetes? A Review of the Literature and Guide for Primary Care Physicians - Clinical Diabetes and Endocrinology.” BioMed Central, BioMed Central, 3 Feb. 2021, doi.org/10.1186/s40842-020-00116-1.Blumberg, Jack, et al. “Intermittent Fasting: Consider the Risks of Disordered Eating for Your Patient - Clinical Diabetes and Endocrinology.” BioMed Central, BioMed Central, 21 Oct. 2023, https://clindiabetesendo.biomedcentral.com/articles/10.1186/s40842-023-00152-7.De Cabo, Rafael, and Mark P. Mattson. “Effects of intermittent fasting on health, aging, and disease.” New England Journal of Medicine, vol. 381, no. 26, 26 Dec. 2019, pp. 2541–2551, https://doi.org/10.1056/nejmra1905136.Guo, Lixin, et al. “A 5:2 intermittent fasting meal replacement diet and glycemic control for adults with diabetes.” JAMA Network Open, vol. 7, no. 6, 21 June 2024, https://doi.org/10.1001/jamanetworkopen.2024.16786.Herz, Daniel, et al. “Efficacy of Fasting in Type 1 and Type 2 Diabetes Mellitus: A Narrative Review.” Nutrients, U.S. National Library of Medicine, 10 Aug. 2023, www.ncbi.nlm.nih.gov/pmc/articles/PMC10459496/. Herzig, S., & Shaw, R. J. (2018). AMPK: Guardian of metabolism and mitochondrial homeostasis. Nature Reviews Molecular Cell Biology, 19(2), 121-135.Longo, V. D., & Mattson, M. P. (2014). Fasting: Molecular mechanisms and clinical applications. Cell Metabolism, 19(2), 181-192. https://doi.org/10.1016/j.cmet.2013.12.008López-Jaramillo P, Gómez-Arbeláez D, López-López J, et al. The role of leptin/adiponectin ratio in metabolic syndrome and diabetes. Hormone Molecular Biology and Clinical Investigation. 2014;18(1):37–45.Mattson, Mark P., et al. “Impact of intermittent fasting on health and disease processes.” Ageing Research Reviews, vol. 39, Oct. 2017, pp. 46–58, https://doi.org/10.1016/j.arr.2016.10.005. Patikorn, Chanthawat, et al. “Intermittent fasting and obesity-related health outcomes.” JAMA Network Open, vol. 4, no. 12, 17 Dec. 2021, https://doi.org/10.1001/jamanetworkopen.2021.39558.Sharma, Suresh K, et al. “Effect of Intermittent Fasting on Glycaemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” TouchREVIEWS in Endocrinology, U.S. National Library of Medicine, May 2023, www.ncbi.nlm.nih.gov/pmc/articles/PMC10258621/#:~:text=In%20IF%2C%20eating%20habits%20are,the%20risk%20of%20developing%20T2DM.Xiaoyu, Wen, et al. “The effects of different intermittent fasting regimens in people with type 2 diabetes: A network meta-analysis.” Frontiers in Nutrition, vol. 11, 25 Jan. 2024, https://doi.org/10.3389/fnut.2024.1325894. Theme song, Works All The Time by Dominik Schwarzer, YouTube ID: CUBDNERZU8HXUHBS, purchased from https://www.premiumbeat.com/.

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Why do some people feel fine eating lots of carbs when others feel energy slumps? Is blood sugar to blame? In this episode, we learn why blood sugar varies so much between people, and the tools to manage these levels.  Tim Spector and Jessie Inchauspé (aka the Glucose Goddess) will discuss the latest science around glucose control, what the cool new device on the block – the CGM – can tell us and why blood sugar levels are only one part of the picture of our health. Jessie is a bestselling author and science communicator with a community of over 5 million followers. Tim is a professor of epidemiology at King's College London and ZOE's scientific co-founder.

References Cells 2020, 9(1), 228 Front. Immunol. 2020. vol 11. 29 November. FEBS 2013. Volume280, Issue15 August:3530-3541 Cell Metabolism 2016. 23, 1127–1139 Beethoven. LV . 1800. Septett Es-Dur op. 20 https://youtu.be/pXsj43qCcUA?si=r5vW4PpfzvywF9b3  Jacques Revaux  Gilles Thibaut and Claude François 1967. "My Way". Sinatra https://youtu.be/qQzdAsjWGPg?si=YWKurvGp9Xt0TYK1 --- Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Researchers at the University of Galway have created digital babies to better understand infants' health in their critical first 180 days of life. The team created 360 advanced computer models that simulate the unique metabolic processes of each baby. The digital babies are the first sex-specific computational whole-body models representing newborn and infant metabolism with 26 organs, six cell types, and more than 80,000 metabolic reactions. Real-life data from 10,000 newborns, including sex, birth weight and metabolite concentrations, enabled the creation and validation of the models, which can be personalised - enabling scientists to investigate an individual infant's metabolism for precision medicine applications. The work was conducted by a team of scientists at University of Galway's Digital Metabolic Twin Centre and Heidelberg University, led by APC Microbiome Ireland principal investigator Professor Ines Thiele. The team's research aims to advance precision medicine using computational modelling. They describe the computational modelling of babies as seminal, as it enhances understanding of infant metabolism and creates opportunities to improve the diagnosis and treatment of medical conditions during the early days of a baby's life, such as inherited metabolic diseases. Lead author Elaine Zaunseder, Heidelberg University, said: "Babies are not just small adults - they have unique metabolic features that allow them to develop and grow up healthy. For instance, babies need more energy for regulating body temperature due to, for example, their high surface-area-to-mass ratio, but they cannot shiver in the first six months of life, so metabolic processes must ensure the infant keeps warm. "Therefore, an essential part of this research work was to identify these metabolic processes and translate them into mathematical concepts that could be applied in the computational model. We captured metabolism in an organ-specific manner, which offers the unique opportunity to model organ-specific energy demands that are very different in infants compared to adults. "As nutrition is the fuel for metabolism, we can use breast milk data from real newborns in our models to simulate the associated metabolism throughout the baby's entire body, including various organs. Based on their nutrition, we simulated the development of digital babies over six months and showed that they will grow at the same rate as real-world infants." Professor Ines Thiele, study lead on the project, said: "New-born screening programmes are crucial for detecting metabolic diseases early on, enhancing infant survival rates and health outcomes. However, the variability observed in how these diseases manifest in babies underscores the urgent need for personalised approaches to disease management. "Our models allow researchers to investigate the metabolism of healthy infants as well as infants suffering from inherited metabolic diseases, including those investigated in newborn screening. When simulating the metabolism of infants with a disease, the models showed we can predict known biomarkers for these diseases. Furthermore, the models accurately predicted metabolic responses to various treatment strategies, showcasing their potential in clinical settings." Elaine Zaunseder added: "This work is a first step towards establishing digital metabolic twins for infants, providing a detailed view of their metabolic processes. Such digital twins have the potential to revolutionise paediatric healthcare by enabling tailored disease management for each infant's unique metabolic needs." The research was published this week in Cell Metabolism. This work was led by University of Galway and completed as part of a collaboration with Heidelberg University, Heidelberg Institute for Theoretical Studies and Heidelberg University Hospital, Germany.

A recent study from the Bass Lab has revealed how transcription factors within individual cells influence the identity and function of insulin-producing beta cells in the pancreas, according to findings published in Cell Metabolism.

I talk a lot about the fact that the world has changed. Immune systems, stress responses, metabolic health. We should be questioning our approaches to all of it.  One big change, that we are still gathering data on at Advanced Women's Health, is a liver clearance and bile acid challenge that has become much more prevalent. Although I am still not ready to teach on my protocols to the above-mentioned problems, because I don't teach until we have at least an 70-80% success and reliability rate, I do want to chat about how it's showing up and some factors that may be in play for you to watch for in your practice.Research DiscussedLelou E, Corlu A, Nesseler N, Rauch C, Mallédant Y, Seguin P, Aninat C. The Role of Catecholamines in Pathophysiological Liver Processes. Cells. 2022 Mar 17;11(6):1021. doi: 10.3390/cells11061021. PMID: 35326472; PMCID: PMC8947265.Adam J. Rose, Mauricio Berriel Díaz, Anja Reimann, Johanna Klement, Tessa Walcher, Anja Krones-Herzig, Oliver Strobel, Jens Werner, Achim Peters, Anna Kleyman, Jan P. Tuckermann, Alexandros Vegiopoulos, Stephan Herzig. Molecular Control of Systemic Bile Acid Homeostasis by the Liver Glucocorticoid Receptor. Cell Metabolism, 2011; 14 (1): 123 DOI: 10.1016/j.cmet.2011.04.010Join our Programs! The Holistic Practitioner Growth System April 2024 Click HereTransform Your Practice with the Revolutionary Fasting Mimicking Diet Program Click HereCertified Women's Health Practitioner 2024! Click HereEndometriosis Intensive: Click HereUse code: "endosuperhero" to save $50!The Insulin Intensive: Click Here Stay in touch! NCM Learning Platform | https://learning.naturopathicmentorship.com Advanced Women's Health Website | https://www.advancedwomenshealth.ca/Finally Lose It Book | https://sarahwilsonnd.com/finallyloseitInstagram | https://www.instagram.com/drsarah_nd/ ...

Note: This podcast is a companion to the Ground Truths newsletter “A Big Week for GLP-1 Drugs”Eric Topol (00:06):It is Eric Topol with Ground Truths, and with me today is Dr. Daniel Drucker from the University of Toronto, who is one of the leading endocrinologists in the world, and he along with Joel Habener and Jens Juul Holst from the University of Copenhagen and Denmark, have been credited with numerous prizes of their discovery work of glucagon-like peptide-1 (GLP-1) as we get to know these family of drugs and he's a true pioneer. He's been working on this for decades. So welcome, Daniel.Daniel Drucker (00:43):Thank you.Eric Topol (00:45):Yeah, it's great to have you and to get the perspective, one of the true pioneers in this field, because to say it's blossom would be an understatement, don't you think?Daniel Drucker (00:57):Yeah, it's been a bit of a hectic three years. We had a good quiet 30 plus years of solid science and then it's just exploded over the last few years.Eric Topol (01:06):Yeah, back in 30 years ago, did you have any sense that this was coming?Daniel Drucker (01:14):Not what we're experiencing today, I think there was a vision for the diabetes story. The first experiments were demonstrating insulin secretion and patents were followed around the use for the treatment of GLP-1 for diabetes. The food intake story was much more gradual and the weight loss story was quite slow. And in fact, as you know, we've had a GLP-1 drug approved for people with obesity since 2014, so it's 10 years since liraglutide was approved, but it didn't really catch the public's attention. The weight loss was good, but it wasn't as spectacular as what we're seeing today. So this really has taken off just over the last three, four years.Eric Topol (01:58):Yeah, no, it's actually, I've never seen a drug class like this in my life, Daniel. I mean, I've obviously witnessed the statins, but this one in terms of pleiotropy of having diverse effects, and I want to get to the brain here in just a minute because that seems to be quite a big factor. But one thing just before we get too deep into this, I think you have been great to recognize one of your colleagues who you work with at Harvard, Svetlana Mojsov. And the question I guess is over the years, as you said, there was a real kind of incremental path and I guess was in 1996 when you said, well, this drug likely will inhibit food intake, but then there were gaps of many years since then, as you mentioned about getting into the obesity side. Was that because there wasn't much weight loss in the people with diabetes or was it related to the dose of the drugs that were being tested?Why Did It Take So Long to Get to Obesity?Daniel Drucker (03:11):Well, really both. So the initial doses we tested for type 2 diabetes did not produce a lot of weight loss, maybe 2-3%. And then when we got semaglutide for type 2 diabetes, maybe we were getting 4-5% mean weight loss. And so that was really good and that was much better than we achieved before with any glucose lowering drug. But a lot of credit goes to Novo Nordisk because they looked at the dose for liraglutide and diabetes, which was 1.8 milligrams once daily for people with type 2 diabetes. And they asked a simple question, what if we increase the dose for weight loss? And the answer was, we get better weight loss with 3 milligrams once a day. So they learn that. And when they introduced semaglutide for type 2 diabetes, the doses were 0.5 and 1 milligrams. But in the back of their minds was the same question, what if we increased the dose and they landed on 2.4 milligrams once a week. And that's when we really started to see that the unexpected spectacular weight loss that we're now quite familiar with.Eric Topol (04:16):Was there also something too that diabetics don't lose as much weight if you were to have match dose?Daniel Drucker (04:22):Yeah, that's a general phenomenon. If one goes from either diet to bariatric surgery, and certainly with weight loss medicines, we tend to see maybe two thirds to three quarters of the amount of weight loss in people with type 2 diabetes. We don't really understand it. The brain pathways are probably resistant to some of the pathways that are activated that lead to weight loss, and it's really an interesting observation that needs further study.The Brain EffectEric Topol (04:50):Yeah, it's fascinating really. And it might've at least in part, held up this progress that has been truly remarkable. Now, recently you published a paper among many, you're a very prolific scientist, of course, physician scientist, but back in December in Cell Metabolism was a very important paper that explored the brain gut axis, the ability to inhibit inflammation and the mechanism through Toll-like receptors that you were seeing that. So maybe you could summarize the fact that you saw this, you were quoted in this Atlantic piece by Sarah Zhang, the science behind Ozempic was wrong. The weight loss effects of GLP-1 drugs have little to do with the gut and basically claiming that it's related to the effects on the brain, which of course could be reduced inflammation, reduced or inhibiting centers of addiction craving, that sort of thing. So how do you interpret your recent results and ongoing studies regarding GLP-1's effect on the brain?Daniel Drucker (06:02):Sure, so to be clear, I don't think that was a quote. I never would've said the science behind Ozempic was wrong. I think that was a headline writer doing what they do best, which is catching people's attention. I think what I was trying to say is that where this field started with insulin secretion first and then weight loss second, those are clearly very important pharmacological attributes of GLP-1. But physiologically, if we take GLP-1 away or we take the receptor away, you don't really develop diabetes without GLP-1. You don't really gain a lot of weight without GLP-1. So physiologically it's not that important. Why do we have GLP-1 in the distal gut? I think physiologically it's there to defend against infection and reduce gut inflammation. But we noticed that GLP-1 reduces inflammation in many different places in the heart and blood vessels and in the liver and many organs where you don't see a lot of GLP-1 receptors and you don't see a lot of GLP-1 receptors on immune cells.Daniel Drucker (07:04):So that really led us to the question, well, how does it work and affect all these organs where we don't see a lot of the receptors? And that's where we landed on the brain. Obviously the nervous system can communicate with many different cell types in almost every organ. And we identified neurons that expressed the GLP-1 receptor, which when blocked abrogated or completely eliminated the ability of GLP-1 to reduce inflammation in the periphery in white cells or in lungs. So it's been known for some time that the brain can control the immune system. So this is just the latest piece in the puzzle of how GLP-1 might reduce inflammation.Eric Topol (07:49):And just to be clear, I was quoting the Atlantic headline, not you that you were quoted within that article, but this is something that's really interesting because obviously GLP-1 is made in the brain in certain parts of the brain, it's transient in terms of its half-life made from the gut. But when we give these drugs, these agonists, how does it get in the brain? Because isn't there a problem with the blood brain barrier?Daniel Drucker (08:22):So I don't think the drugs get into the brain very well. We have a lot of data on this, so people have done the classic experiments, they either make radioactive ligands or fluorescent ligands, and they look how much gets in it and not very much gets in beyond the blood-brain barrier. And we also have big drugs that are immunoglobulin based and they work really well, so they don't get into the brain very much at all. And so, the way I describe this is that GLP-1 talks to the brain, but it doesn't directly get into the brain to meaningful extent, it does communicate somewhat there are areas obviously that are accessible in the area of the stream and circumventricular organs, but most of the time we have this communication that's not well understood that results in the magic that we see. And there are some discussions around for the neurodegenerative disease story where GLP-1 is being looked at in Parkinson's disease and in people with Alzheimer's disease. Would you be able to get more benefit if you could get the drugs into the brain to a greater extent, or would you simply increase the adverse event profile and the adverse response? So really important area for study as we begin to go beyond diabetes and obesity.Eric Topol (09:41):Yeah, I mean as you're pointing out, there's two ongoing trials, pretty large trials in Alzheimer's, early Alzheimer's, which may be a little bit too late, but at any rate, testing GLP-1 to see whether or not it could help prevent progression of the disease. And as you also mentioned, diseases and Parkinson's. But I guess, so the magic as you referred to it, the gut -brain axis so that when you give the GLP-1 family of drugs, we'll talk more about the double and triple receptor in a moment, but when you give these drugs, how does the message you get from the gut to the brain would you say?Daniel Drucker (10:27):So pharmacologically, we can give someone or an animal the drug, it does reach some of the accessible neurons that have GLP-1 receptors, and they probably transmit signals deeper into the brain and then activate signal transduction. So one way to look at it, if you use c-fos, the protein, which is an immediate early gene, which is increased when we activate neurons, we see rapid activation of c-fos in many regions that are deep within the brain within minutes. And we know that GLP-1 is not getting directly to those neurons, but it's activating pathways that turn on those neurons. And so, there's probably a very intricate set of pathways that sense the GLP-1 and the accessible neurons and then transmit those signals deeper into the brain.Double and Triple Receptor AgonistsEric Topol (11:18):Okay, well that makes sense. Now, as this has been moving along in obesity from semaglutide to tirzepatide and beyond, we're seeing even more potency it appears, and we have now double and triple receptors adding into glucagon itself and the gastric inhibitory polypeptide, and there's mixed data. So for example, the Amgen drug has the opposite effect on GIP as does the dual receptor, but comes out with the same weight loss I guess. How do we understand, I mean you know these gut hormones inside and out, how do we get such disparate results when you're either blocking or revving up a peptide effect?Daniel Drucker (12:13):Yeah, it's a mystery. I always sort of joke that you've invited the wrong person because I don't fully understand how to reconcile this honestly. There are some theories you could say that tirzepatide may possibly desensitize the GIP receptor, and that would align with what the GIP receptor blocking component is. And so, I think we need a lot of research, we may actually never know in humans how to reconcile these observations. I think we can do the experiments in animals, we're doing them, other people are doing them to look at the gain and loss of function and use best genetics. But in humans, you'd have to block or activate these receptors in very specific populations for a long period of time with tools that we probably don't have. So we may not reconstruct. We may end up with Maritide from Amgen that's producing 15-20% plus weight loss and tirzepatide from Lilly, that's spectacular, that's producing more than 20% weight loss. And yet as you mentioned at the GIP level, they have opposite effect. So I don't think we fully understand. Maybe your next guest will explain it to you and invite me on. I'd be happy to listen.Eric Topol (13:27):Well, I don't know. I don't think anybody can explain it. You've done it as well as I think as possible right now. But then we have the triple receptor, which it seems like if you take that drug, you could just go kind of skeletal. It seems like there's no plateau and its effect, that is I guess is it retatrutide, is that the name of it?Daniel Drucker (13:47):Retatrutide, yeah.Eric Topol (13:48):Retatrutide, okay. And then of course we're going on with potentially oral drugs or drugs that last for a year. And where do you see all that headed?Daniel Drucker (14:00):So I think the way I describe innovation in this field is there are two buckets that we've talked about today. So one bucket is the new molecule, so we're going to have all kinds of different combinations that will be peptides, that will be small molecule orals, the NIH is funding innovative programs to see if we can develop cell-based factories that produce GLP-1. There are gene editing and gene therapy approaches. So there are going to be multiple different molecular approaches to delivering molecules that are better and hopefully easier to take maybe once monthly, maybe every six months. So that's really exciting. And the other obvious bucket is the disease that we're targeting, so we started off with type 2 diabetes. We're now firmly established in the obesity field. In your field, we've seen consistently positive cardiovascular outcome trials. We had a press release a few months ago in October - November saying that semaglutide reduces chronic kidney disease. We have trials underway with peripheral artery disease with Parkinson's disease, with Alzheimer's and a number of neuropsychiatric conditions. So I think we're going to see both innovation on the molecule side as well as expanding if the trials are positive, expanding clinical indication. So it's going to be a pretty exciting next couple of years.Eric Topol (15:21):Right, no question. And as you well know, just in the past week, the FDA gave the green light for using these drugs for heart failure with preserved ejection fraction, which was an important randomized trial that showed that. Now there's got to be some downsides of course there's no drug that's perfect. And I wanted to get your comments about muscle loss, potentially bone density reduction. What are the downsides that we should be thinking about with these drugs?Side EffectsDaniel Drucker (15:54):Sure, so the known side effects are predominantly gastrointestinal. So we have nausea, diarrhea, constipation and vomiting. And very importantly, if those side effects are severe enough that someone can't eat and drink for 24 hours, we need to tell them you have to seek medical attention because some people will get dehydrated and rarely get acute kidney injury. This is rare, but it's described in many of the outcome trials, and we definitely want to avoid that. Gallbladder events are probably one in several hundred to one in a thousand, and that can be anywhere from gallbladder inflammation to gallbladder stones to biliary obstruction. Don't fully understand that although GLP-1 does reduce gallbladder motility, so that may contribute. And then very rarely we're seeing reports of small bowel obstruction in some people difficult to sort out. We don't really see that in the large clinical trials, but we have to take people at there were, we haven't seen an imbalance in pancreatitis, we haven't seen an imbalance of cancer.Daniel Drucker (17:01):There is no evidence for clinically significant bone disease either at the level of reduced bone densities or more importantly at the level of fractures. And we have a lot of real world data that's looked at that. Now muscle losses is really interesting. So when the initial drugs were approved, they didn't produce much weight loss. We didn't think about it. Now that we're getting the 15 20% plus, the question is, will we see clinically significant sarcopenia? And I use the word clinically significant carefully. So we definitely see muscle lean mass loss on a DEXA scan, for example. But what we're not seeing so far are people who are saying, you know what my grip strength is weak. I can't get up off the chair. I have trouble reaching up into the cupboard. My exercise or walking capacity is limited. We're not seeing that. In fact, we're seeing the opposite.Daniel Drucker (17:53):As you might expect, people are losing weight, they're less achy, they can move more, they can exercise more. So the question is buried within that data, are there some individuals with real clinical sarcopenia? And as we get to 25% weight loss, it's very reasonable to expect that maybe we will see some individuals with clinical sarcopenia. So you're very familiar. There are half a dozen companies developing medicines to promote fat mass loss and spare muscle with or without semaglutide or tirzepatide. And this is a really interesting area to follow, and I don't know how it's going to turn out. We really have to see if we are going to see enough clinically significant muscle loss and sarcopenia to merit a new drug category emerge, so fascinating to follow us.Eric Topol (18:46):No, I'm so glad you reviewed that because the muscle loss, it could be heterogeneous and there could be some people that really have some substantial sarcopenia. We'll learn more about that. Now that gets me to what do we do with lifelong therapy here, Daniel, where are we going? Because it seems as though when you stop these drugs, much of the benefit can be not potentially all, but a substantial amount could be lost over time. Is this something that you would view as an insulin and other hormonal treatments or how do you see it?The Question of ReboundDaniel Drucker (19:26):Yeah, so it's fascinating. I think that traditional view is the one that you just espoused. That is you stop the drug, you regain the weight, and people are concerned about the rebound weight and maybe gaining more fat and having less favorable body composition. But if you look at the data, and it's coming very fast and furious. A few months ago, we saw data for a tirzepatide trial, one of the surmount obesity trials, the first author was Louis Aronne in New York and they gave people tirzepatide or placebo for 38 weeks. And then they either continue the tirzepatide or stop the tirzepatide. One year later, so no tirzepatide for one year, more than 40% of the people still managed to keep at least 10% of their weight off, which is more than enough in many people to bestow considerable metabolic health. So I think there are going to be people that don't need to take the medicines all the time for weight loss, but we must remember that when we're excited about heart attacks and strokes and chronic kidney disease, there's no evidence that you can stop the medicines and still get the benefits to reduce those chronic complications.Daniel Drucker (20:46):So we're going to have to get much more sophisticated in terms of a personalized and precision medicine approach and ask what are the goals? And if the goals are to reduce heart attack strokes and death, you probably need to stay on the medicine if the goals are to achieve weight loss so that you can be metabolically healthy, there may be a lot of people who can come off the medicine for considerable amounts of time. So we're just learning about this. It's very new and it's really exciting.Suppressing Inflammation as the Common ThreadEric Topol (21:11):Yeah, no question. And just going back to the inflammation story in heart disease, it was notable that there were biomarkers of reduced inflammation in the intervention trial before there was any evidence of weight loss. So the anti-inflammatory effects here seem to be quite important, especially with various end organ benefits. Would you say that's true?Daniel Drucker (21:35):Yeah, I think that's one of my favorite sort of unifying theories. If we step back for a minute and we come into this and we say, well, here's a drug that improves heart disease and improves liver inflammation and reduces chronic kidney disease and may have some effect on atherosclerosis and is being studied with promising results and neurodegenerative disease, how do we unify all that? And one way is to say all of these chronic disorders are characterized by a component of chronic inflammation. And Eric, it's fascinating. I get reports from random strangers, people who've been on tirzepatide or people who have been on semaglutide, and they tell me, and you'll be fascinated with this, they tell me, my post Covid brain fog is better since I started the drug. They send me pictures of their hands. These are people with chronic arthritis. And they say, my hands have never looked better since I started the drug. And they tell me they've had ulcerative colitis for years on biologics and all of a sudden it's in remission on these drugs. So these are case reports, they're anecdotes, but they're fascinating and quite consistent with the fact that some people may be experiencing an anti-inflammatory effect of these medicines.Eric Topol (22:55):And I think it's notable that this is a much more potent anti-inflammatory effect than we saw from statins. I mean, as you know, well they have an effect, but it's not in the same league, I don't think. And also the point you made regarding this is a very good candidate drug class for Long Covid and for a variety of conditions characterized by chronic inflammation. In fact, so many of our chronic diseases fit into that category. Well, this is fascinating, and by the way, I don't know if you know this, but we were both at Johns Hopkins at the same time when you were there in the early eighties. I was there as a cardiology fellow, but we never had a chance to meet back then.Daniel Drucker (23:41):So were you just ahead of Cricket Seidman and the whole team there, or what year was that?Eric Topol (23:46):Just before them, that's right. You were there doing, was it your internship?Daniel Drucker (23:50):I was doing an Osler internship. I think Victor McKusick loved to have a Canadian every year to recognize Osler, one of the great Canadians, and I was just lucky to get the slot that year.Eric Topol (24:04):Yeah, it's wild to have watched your efforts, your career and your colleagues and how much of a profound impact. If you were to look back though, and you were to put this into perspective because there were obviously many other hormones along the way, like leptin and so many others that were candidates to achieve what this has. Do you think there's serendipity that play out here or how do you kind of factor it all together?Daniel Drucker (24:38):Well, there there's always serendipity. I mean, for decades when people would write review articles on the neuropeptides that were important for control of hunger and satiety and appetite circuits, I would open the article, read it, and I'd say, darn, there's no GLP-1 on the figure. There's no GLP-1 or receptor on the figure, but there's leptin and agouti and the POMC peptides and all the melanocortin and so on and so forth, because physiologically, these systems are not important. As I mentioned, you don't see childhood obesity or genetic forms of obesity in people with loss of function mutations in the GLP-1 sequence or in the GLP-1 receptor. You just don't see a physiologically important effect for having low GLP-1 or having no GLP-1. And that's of course not the case for mutations in NPY or the melanocortin or leptin, et cetera.Other EffectsDaniel Drucker (25:36):But pharmacologically, it's been extraordinarily difficult to make drugs out of these other peptides and pathways that we talked about. But fortuitously or serendipitously, as you point out, these drugs seem to work and amazingly GPCRs are notoriously prone to desensitization. We use that in clinical medicine to turn off entire circuits. And thankfully what goes away with GLP-1 are the adverse effects. So nausea, vomiting, diarrhea, constipation, we see those during the first few weeks and then there's tachyphylaxis, and they generally go away in most people, but what doesn't go away through good fortune are the ability of GLP-1 to talk to those brain circuits and say, you know what? You're not hungry. You don't need to eat. You don't need to think about food. And that's just good luck. Obviously pharmacologically that's benefited all of us working in this area.Eric Topol (26:31):It's extraordinary to be able to get desensitized on the adverse effects and not lose the power of the benefit. What about addiction that is, whether it's alcohol, cigarettes, gambling, addictive behavior, do you see that that's ultimately going to be one of the principal uses of these drugs over time?Daniel Drucker (26:55):The liver docs, when I give a talk at a metabolic liver disease meeting, they say we love GLP-1 because not only might it take care of liver disease, but there are still some people that we see that are having problems with alcohol use disorders and it might also reduce that. And obviously there are tons of anecdotes that we see. If you go on social media, and you'll see lots of discussion about this, and there's a hundred or so animal paper showing that addiction related dependence behaviors are improved in the context of these medicines. But we don't have the clinical data. So we have a couple of randomized clinical trials, small ones in people with alcohol use disorder, very unimpressive data. We had a trial in people with smoking, didn't really see much, although interestingly, they noted that people drank less alcohol than they did the smoking trial. So there are dozens and dozens of trials underway now, many investigator initiated trials looking at whether it's nicotine or cocaine or cannabinoids or all kinds of compulsive behaviors. I think in the next 12 to 24 months, we're going to start to learn are these real bonafide effects that are seen in large numbers of people or are these just the anecdotes that we won't get a very good complete response. So it's really exciting neuroscience and we're going to learn a lot over the next couple of years.Eric Topol (28:20):Yeah, no, it's a fascinating area which just extends the things that we've been discussing. Now, let's say over time, over the years ahead that these drugs become because of the competition and various factors, perhaps in pill form or infrequent dosing, they become very inexpensive, not like they are today.Daniel Drucker (28:44):That'd be great speaking as a non-pharmaceutical physician.Eric Topol (28:48):Yeah, yeah, no, these companies, which of course as you well know, it accounts for the number one economy in Denmark and is having a big impact in Europe. And obviously Eli Lilly is now the most valued biopharma company in the world from all these effects are coming from this drug class, but let's just say eventually it's not expensive and the drug companies are not gouging and pleasing their investors, and we're in a different world. With all these things that we've been discussing, do you foresee a future where most people will be taking one form or another of this family of drugs to prevent all these chronic conditions that we've just been discussing independent of obesity, type 2 diabetes, the initial frontier? Do you think that's possible?Daniel Drucker (29:42):Yeah, I'm a very conservative data-driven person. So today we don't have the data. So if I was in charge of the drinking water supply in your neighborhood and I had unlimited free cheap GLP-1, I wouldn't dump it in there just yet. I don't think we have the data, but we have trials underway, as you noted for Alzheimer's disease, a challenging condition for our society with a huge unmet need if like fingers crossed, if semaglutide does show a benefit for people living with early Alzheimer's disease, if it helps for Parkinson's, if it helps for metabolic liver disease, there are also studies looking at aging, et cetera. So it's possible one day if we have a lot more data that we will begin to think, okay, maybe this is actually a useful medicine that should deserve much more exposure, but today we just don't have the data.Eric Topol (30:38):Absolutely. I couldn't agree more, but just wanted to get you kind of speculate on that a bit off script if you will, but what your thoughts were, because this will take a long time, get to that point, but you just kind of wonder when you have an absence of chronic significant side effects overall with these diverse and relatively potent benefits that cut across many organ systems and as you just mentioned, might even influence the aging process, the biologic process.Worsening InequitiesDaniel Drucker (31:10):There's another related sort of angle to this, which is that the accessibility of these medicines is very challenging even in well-developed countries, the United States, Europe, et cetera, and we have hundreds of millions of people in the global south and less well-developed economies that are also challenged by heart disease and diabetes and obesity and chronic kidney disease and liver disease. And I think we need to start having conversations and I think they are happening just like we did for HIV and just like we did for hepatitis and certainly we did very quickly for the Covid vaccines. We need to think out of the box and say we need to help people in other parts of the world who may not have access to the medicines in their current form and at their current pricing. And I think these are really important moral and ethical discussions that need to be happening now because soon we will have small molecules and the price will come down and we need to make sure it's not just people in well-developed countries that can afford access to these medicines. I think this is a great opportunity for pharmaceutical companies and the World Health Organization and other foundations to really think broadly about how we can benefit many more people.Eric Topol (32:29):I couldn't agree with you more and I'm so glad you emphasize that because we can't wait for these prices to come down and we need creative ways to bridge, to reduce inequities in a vital drug class that's emerged to have far more applicability and benefit than it was initially envisioned, certainly even 5, 10 years ago, no less 30 years ago when you got on it. So Daniel, I can't thank you enough for this discussion. Really a candid discussion reviewing a lot of the things we do know, don't know will know someday perhaps. I just want to note, I know so many people are cheering for you and your colleagues to get recognized further like by the Nobel folks in the years ahead. I think it's pretty darn likely and hopefully when we get a chance to visit again in the years ahead, we'll unravel some of the things that we discussed today that we didn't know the answers and that you as a really an authority and pioneer in the field. Also, I could admit that there's a ways to go to really understand the boundaries if there are boundaries here for how these drugs are going to be used in the years ahead.Daniel Drucker (33:51):Yeah, it's another great story for basic science and bench to bedside, and it's just another story where none of us could have predicted the outcomes that we're talking about today to their full extent. And so to the extent that we can convince our governments and our funding agencies to really fund discovery science, the benefits are never apparent immediately. But boy, do they ever come in spades later on in an unpredictable manner. And this is just a great example.Eric Topol (34:20):Yeah, I also would say that this work cracking the case of obesity, which has been a stumbling block, I ran a big trial with Rimonabant, which was a failure with the neuropsychiatric side effects and suicidal ideation that had to get dropped. And there's many others like that as you know, very well Fen-Phen, and a long list. And the fact that this could do what it's doing and well beyond just obesity is just spectacular. And what I think it does, what you just mentioned, Daniel, is the basic science work that led to this is I think an exemplar of why we should put in these efforts and not expect immediate benefits, dividends of those efforts. Because look what's happened here. If you can break through with obesity, imagine what lies ahead. So thanks so much for joining and we'll look forward to continuing to follow your work. I know you're publishing the same pace, exceptional prolific pace over many, many years, and I'm sure that's going to continue.Daniel Drucker (35:34):Well, I have a great team and so it's a pleasure me to go into work and talk to them every day.********************Thanks for listening to/reading Ground Truths.Please share if your found this podcast informative Get full access to Ground Truths at erictopol.substack.com/subscribe

Effects of 4- and 6-h time-restricted feeding in adults with obesity. BIO: Dr Cienfuegos is a Clinical Assistant Professor in Kinesiology and Nutrition at the University of Illinois at Chicago. Dr. Cienfuegos has a Ph.D. in human nutrition and has been studying intermittent fasting for the last seven years. Dr. Cienfuegos is an emerging expert in this field, with more than 30 publications in the most prestigious journals, such as Cell, Annual Reviews, and Nature. She has participated in several national and international scientific conferences and trained other professionals worldwide. Dr. Cienfuegos is the Co-I on two R01s (R01DK119783 and R01DK128180), examining the health benefits of fasting.  Description of talk: Data from her Ph.D. work examining the weight loss efficacy of shorter TRE windows (4-h and 6-h TRE) was published in Cell Metabolism and received substantial media attention. She has extensive hands-on experience designing and coordinating R01-funded clinical trials and leading large research teams during recruitment, counseling, and data analysis. This seminar will focus on these original investigations.

Is your dog fat? If it's a Labrador, then science now provides an excuse.All dog owners know the challenge of resisting your pet's big, sad eyes as they beg for one more treat, but there is one dog breed that pushes its owners by begging more than others according to new research published this week in the journal Cell Metabolism. That dog breed is the Labrador Retriever, which was found in the study to be more likely to engage in behaviour that related to getting extra food - including begging. The scientists genetically tested 33 Labradors, of which 18 were fit and healthy, and 15 were obese. They found that the obese dogs were more likely to be carrying a variation in the gene called POMC. The variation in this gene turned off hunger cues in the dog meaning the dogs were much more food motivated and more likely to overeat. They then expanded the genetic study to include 700 more Labradors and found that the gene variation was in 23 percent or 1 in 4 of the Labs. All of the dogs that had the gene variant were also obese- and according to their owners, renowned for scavenging food and begging. To see if it was just Labradors, the researchers then studied 38 other dog breeds. They found this gene variation occurred in only one other breed - flat-coated retrievers, which are related to Labradors. The conclusion of the study was - if you own a lab and it constantly pesters you for extra treats - you as the human owner are going to need more will power to deny them if your dog is going to remain fit and healthy. LISTEN ABOVESee omnystudio.com/listener for privacy information.

Unlock the secrets of the ketogenic diet with Dr. Dominic D'Agostino as we navigate the nuances of ketogenic protocols, from their clinical roots in epilepsy treatment to their modern-day applications in enhancing athletic prowess and brain health. Whether you're a seasoned keto aficionado or simply curious about this high-fat lifestyle, you're in for a wealth of knowledge that could reshape your understanding of nutrition.Timeline (Episode 64)1:50 Dr. Dom has cows and gators in his backyard! His dogs have fought with gators. The mammals win! 3:45 Definition of Ketogenic Diet (KD)8:18 There are over 100 years of clinical use of the KD9:04 Fasting was a “cure” for seizures11:00 Effects on the brain – how does the KD affect normal healthy subjects15:10 Dom has been a KD for 15 years18:34 Dom used the old MET-Rx brand way back when!21:00 Exogenous ketone ester supplementation studies – where do we stand on this?21:58 Consume MCT oil (the poor man's ketone ester)26:30 Higher ketone levels is not better27:00 Ketone esters > Ketone salts in extreme environments28:00 Dosing of Ketone esters (higher is not better)29:22 Don't exceed 10 grams of Beta-hydroxybutyrate34:07 Advantage of being in ketosis vis a vis performance – under conditions of glycogen depletion esp. in the cognitive domain41:57 A good supplement to start with are MCT oils (since it will elevate your ketones)45:20 Perhaps use these esters as a training aid; given acute may enhance PVT49:30 Debunking the myth that high fat diets are always “bad.”About our guest: Dominic D'AgostinoPh.D., Physiology, Neuroscience, University of Medicine and Dentistry of New Jersey, 2004B.S., Biological Sciences, Nutrition Science, Rutgers University, 1998A researcher and professor with a diverse background in neuroscience, molecular pharmacology, nutrition, and physiology, Dominic D'Agostino, Ph.D., is a tenured Associate Professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida (USF) Morsani College of Medicine. He is also a Research Scientist at the Institute for Human and Machine Cognition (IHMC). Dr. D'Agostino earned his Ph.D. in 2004 and subsequently entered into a postdoctoral fellowship in neuroscience at the Boonshoft School of Medicine at Wright State University in Ohio.He has been awarded numerous grants that have resulted in national and international research collaborations and publications in such peer-reviewed journals as the Journal of Applied Physiology, Cell Metabolism, Neuroscience, Carcinogenesis, Nature Medicine, Journal of Neurophysiology, and the Journal of Microscopy.About the ShowWe cover all things related to sports science, nutrition, and performance. The Sports Science Dudes represent the opinions of the hosts and guests and are not the official opinions of the International Society of Sports Nutrition (ISSN), the Society for Sports Neuroscience, or Nova Southeastern University. The advice provided on this show should not be construed as medical advice and is purely an educational forum.Hosted by Jose Antonio, PhDDr. Antonio is the co-founder and CEO of the International Society of Sports Nutrition and the co-founder of the Society for Sports Neuroscience, www.issn.net. Dr. Antonio has over 120 peer-reviewed publications and 16 books. He is a Professor at Nova Southeastern University, Davie, Florida in the Department of Health and Human Performance.Twitter: @JoseAntonioPhDInstagram: the_issn and supphdCo-host Anthony Ricci EdDDr Ricci is an expert on Fight Sports and is currently an Assistant Professor at Nova Southeastern University in Davie Florida in the Department of Health and Human Performance.Instagram: sportpsy_sci_d

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References Cream 1968 Wheels of Fire J Neuroinflammation. 2019; 16: 34. Front Immunol. 2019; 10: 345. Cell Metabolism 2023. Volume 35 Issue 4. 601-619.e10 Sci Signal. 2017 Jan 31; 10(464):eaaf7478 --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

(AURN News) — Scientists at City of Hope, a cancer research and treatment institution in California, have made a breakthrough in identifying a crucial cell metabolism process shared by men grappling with diabetes and metastatic prostate cancer.  According to a press release, City of Hope says this discovery holds potential for enhanced diagnostic methods and treatments tailored to Black men, who face disproportionately high mortality rates from these conditions.  Prostate cancer is the second most prevalent cancer in men, and troublingly, Black men exhibit a 70% higher likelihood of diagnosis compared to white men, with a mortality rate two to four times greater than other racial groups, as per the American Cancer Society's latest data.  City of Hope's clinical trial, focusing on men of West African heritage, pinpointed four metabolism-related biomarkers connected to an elevated risk of metastatic prostate cancer, providing an essential stride toward more inclusive and effective medical solutions. Learn more about your ad choices. Visit megaphone.fm/adchoices

We all know exercise has all sorts of benefits beyond just making us stronger and fitter. It lowers and inflammation. It buffers stress and anxiety. It clarifies our thinking. In fact, regular exercise is one of the few things we know with reasonable confidence can help extend our healthy lifespan. But for all the evidence of the benefits of exercise, it's a bit surprising that we don't know more about how exercise does all these great things for our bodies and our brains.Today's guest, Jonathan Long, recently discovered a new molecule produced when we exercise a compound called Lac-Phe. Lac-Phe appears to be linked to a number of health benefits from regulating appetite to boosting learning and memory. Long is a chemist by training — and an institute scholar of Sarafan ChEM-H, the Institute for Chemistry Engineering and Medicine for Human Health, our sister institute here at Stanford. So I started our conversation by asking him how his background as a chemist informs how he thinks about studying exercise and human health.NOTE: Thanks to everyone who's tuned in to our first season! We're going to take a break for the summer to get ready for next season, but we'll have more tales from the frontiers of brain science for you in the fall. Learn MoreOrganism-wide, cell-type-specific secretome mapping of exercise training in mice (Cell Metabolism, 2023)Understanding how different cell types respond to exercise could be key step toward exercise as medicine  (Wu Tsai Human performance Alliance, 2023)An exercise-inducible metabolite that suppresses feeding and obesity (Nature, 2022)‘Anti-hunger' molecule forms after exercise, scientists discover (Stanford Medicine)Why Does a Hard Workout Make You Less Hungry? (New York Times)An exercise molecule? (American Society for Biochemistry and Molecular Biology blog)Mechanistic dissection and therapeutic capture of an exercise-inducible metabolite signaling pathway for brain resilience (Innovation Award from the Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute)Episode CreditsThis episode was produced by Michael Osborne, with production assistance by Morgan Honaker, and hosted by Nicholas Weiler. Art by Aimee Garza.Thanks for listening! Learn more about the Wu Tsai Neurosciences Institute at Stanford and follow us on Twitter, Facebook, and LinkedIn.

In this podcast episode, we hear from ISSA's own team members and bootcamp co-hosts Jenny Scott and John Bauer for our first edition of Lighting Fitness Facts and Trainer REAL talk. In this episode Jenny and John shed light on the latest scientific research and evidence-based information in the world of health and fitness, exploring fascinating studies and discoveries that can revolutionize the way we approach our well-being.In our first round of questions, Jenny and John dive into intriguing findings that uncover the mysteries behind our appetite, exercise motivation, cell metabolism, resistance training, and more. They then move into the Training Real Talk segment where they discuss strategies for making health cool and promoting scientific literacy in the fitness world. Discover how to prioritize your health, access reliable sources of information, understand basic science concepts, and seek guidance from experts!References from this episode: References for show notes:Yue Qi, Nicola J. Lee, Chi Kin Ip, Ronaldo Enriquez, Ramon Tasan, Lei Zhang, Herbert Herzog. Agrp-negative arcuate NPY neurons drive feeding under positive energy balance via altering leptin responsiveness in POMC neurons. Cell Metabolism, 2023; DOI: 10.1016/j.cmet.2023.04.020Leandro Garcia, Matthew Pearce, Ali Abbas, Alexander Mok, Tessa Strain, Sara Ali, Alessio Crippa, Paddy C Dempsey, Rajna Golubic, Paul Kelly, Yvonne Laird, Eoin McNamara, Samuel Moore, Thiago Herick de Sa, Andrea D Smith, Katrien Wijndaele, James Woodcock, Soren Brage. Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose–response meta-analysis of large prospective studies. British Journal of Sports Medicine, 2023; bjsports-2022-105669 DOI: 10.1136/bjsports-2022-105669Dohnalová, L., Lundgren, P., Carty, J.R.E. et al. A microbiome-dependent gut–brain pathway regulates motivation for exercise. Nature, 2022 DOI: 10.1038/s41586-022-05525-zWeakley, J., Schoenfeld, B.J., Ljungberg, J. et al. Physiological Responses and Adaptations to Lower Load Resistance Training: Implications for Health and Performance. Sports Med - Open 9, 28 (2023). https://doi.org/10.1186/s40798-023-00578-4

In episode 148, I go through the details of two recent studies investigating the impact of fasting on hunger and craving circuits within the brain. After one bout of fasting, persistent amplification of excitatory activity was noted onto agouti-related protein neurons of the arcuate nucleus of the hypothalamus. I believe these studies provide an understanding as to why we may binge and re-gain weight after weight loss. Can we use this information to our advantage? Yes. I give some neuroscience based strategies to help us prevent weight re-gain. Tune in for details. References: Grzelka et al., 2023, Cell Metabolism 35, 1–16Kerem et al., 2020, Physiological Reports 28(4).e14369.Want to buy me a coffee to say thanks for the episode? You can do so via Venmo or Patreon below.Venmo ID: Steph-CalPatreon: https://www.patreon.com/join/DrSCaligiurihttps://www.buymeacoffee.com/drscaligiuriFollow me on social media to see the papers I cite in this week's episode:IG: Dr.SCaligiuriFB: ThePeoplesScientistTwitter: DrSCaligiuriLinkedin: Stephanie CaligiuriTikTok: Dr.SCaligiuri Hosted on Acast. See acast.com/privacy for more information.

Intermittent fasting has recently gained popularity as a dietary approach for promoting health and longevity. Let's explore the latest research on time-restricted eating and how it impacts gene expression throughout the body, leading to increased life spans.Reference:Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals” by Shaunak Deota, Terry Lin, Amandine Chaix, April Williams, Hiep Le, Hugo Calligaro, Ramesh Ramasamy, Ling Huang and Satchidananda Panda, 3 January 2023, Cell Metabolism. DOI: 10.1016/j.cmet.2022.12.006VISIT OUR STOREStore: https://www.selfelements.comFOLLOW USwww.selfprinciple.orgwww. youtube.com/selfprinciplewww.youtube.com/plantbasedkidneyhealthwww.instagram.com/seanhashmimd

This week, please join author Vincent Aengevaeren and Associate Editor Jarett Berry as they discuss the article "Exercise Volume Versus Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes: Findings From the MARC-2 Study." Dr. Gregory Hundley: Welcome listeners to this March 28th issue, and I am one of your co-hosts, Dr. Gregory Hundley, Associate Editor and Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Peder Myhre: And I'm Dr. Peder Myhre, Social Media Editor from Akershus University Hospital and University of Oslo in Norway. And today, Greg, we have such an interesting feature paper. It comes to us from Professor Aengevaeren and it discusses the progression of coronary atherosclerosis in middle-aged and older athletes. They're looking at exercise volume versus intensity in the MARC-2 study. So Greg, this is really something us master athletes are interested in, and I'm really excited to hear this discussion. Dr. Gregory Hundley: Very nice. Well, how about we jump into some of the other articles first, Peder? And I could go first. So Peder, my first article involves pregnancy related complications. And as you know, these pregnancy complications are associated with increased risk of developing cardiometabolic diseases and an earlier mortality. However, much of the prior research has been limited to individuals of White race. So these investigators led by Professor Cuilin Zhang from the National Institutes of Health aimed to investigate pregnancy complications in association with total and cause specific mortality in a racially diverse cohort, and then evaluate whether associations differ between Black and White individuals. And they performed their work using the Collaborative Perinatal Project, which was a prospective cohort study of 48,197 pregnant women across 12 US clinical centers from the period of time of 1959 through 1966. Dr. Peder Myhre: Oh wow, Greg. Almost 50,000 pregnant women. Very huge initiative. So what did they find? Dr. Gregory Hundley: Right, Peder. So overall, 15% of participants had preterm delivery, 5% had hypertensive disorders of pregnancy, and 1% had gestational diabetes or impaired fasting glucose. Now, the preterm delivery was higher in individuals of Black race at 20% relative to those of White race, which were 10%. Now, in relation to all-cause mortality, the following were associated with increase adjusted hazard ratios. One, spontaneous labor; two, induced labor; three, pre-labor cesarean delivery. And all of those, those adjusted hazard ratios in comparison with a full term delivery. Next, in the world of blood pressure, preeclampsia and eclampsia as well as superimposed preeclampsia and eclampsia were all associated with adjusted hazard ratios that were elevated compared to individuals with normal blood pressure. And then finally, in those individuals with gestational diabetes or impaired fasting glucose, their adjusted hazard ratio, again for all-cause mortality, was elevated relative to those with normal glycemia. Now interestingly, in comparing the two racial groups, preterm induced labor was associated with greater mortality risk among those of Black race relative to those of White race. However, or while, preterm pre-labor cesarean delivery interestingly and conversely was associated with a higher adjusted hazard ratio for those of White race as compared to individuals of Black race. So Peder, in summary, within this large diverse US cohort, pregnancy complications were associated with higher mortality almost 50 years later. And the higher incidents of some complications occurred in individuals of Black race. And differential associations with mortality risk indicate that because of these racial differences, there could really be disparities in pregnancy related health. And finally, that these disparities and their relationship with overall health really could have long life implications for earlier mortality in these patients. Dr. Peder Myhre: Well, that is really interesting, Greg. Are you ready for the next paper? Dr. Gregory Hundley: Absolutely. Dr. Peder Myhre: So this paper is about the glucagon-like peptide-1 receptor agonist and large CV outcome trials clearly show that several GLP-1 agonists reduce CV outcomes in patients with Type 2 diabetes. Whether their cardioprotective effects are related to drug dose or potency remains uncertain however, but important due to recent introduction of high dose and high potency agents for diabetes and for weight loss indications. And therefore, Greg, in this paper, the investigators from the AMPLITUDE-O trial led by corresponding author Hertzel Gerstein from McMaster University Hamilton Health Sciences analyzed the effect of the different doses of the GLP-1 agonist efpeglenatide that is four milligram, six milligram compared to placebo. And the effect was assessed on major adverse cardiovascular events. Dr. Gregory Hundley: Interesting, Peder. So what did they find? Dr. Peder Myhre: So Greg, during a median follow-up of 1.8 years, MACE occurred in 9.2 participants assigned to placebo, 7.7 in participants assigned to efpeglenatide four milligrams, and 6.2% in participants assigned to efpeglenatide six milligrams. And participants receiving high dose of this GLP-1 agonist also experienced fewer secondary outcomes, including the composite of MACE coronary revascularizations or hospitalizations for unstable angina, a kidney composite outcome comprising sustained new microalbuminuria, decline in eGFR more than 40%, or renal failure. And there was also a clear dose response relationship noted for all primary and secondary outcomes with a P4 trend that was significant. So Greg, the authors conclude that the graded relationship between efpeglenatide dose and CV outcomes suggests that titrating this drug and potentially other GLP-1 agonists to high doses may maximize their cardiovascular and kidney benefits. Dr. Gregory Hundley: Very nice, Peder. Well, my next paper comes to us and involves the world of bleeding associated with Factor Xa inhibitors. So Peder, andexanet alfa is a modified recombinant inactive Factor Xa designed to reverse Factor Xa inhibitors. ANNEXA-4 is a multicenter prospective phase 3B single group cohort study that evaluated andexanet alfa in patients with acute major bleeding. And the study is led by Dr. Truman Milling of Seton Dell Medical School Stroke Institute and colleagues, and they present the results of their final analyses. Dr. Peder Myhre: Oh, this is really interesting, Greg. So what did they find? Dr. Gregory Hundley: Right, Peder. So first, 479 patients were enrolled. And their average age was 78 years. 54% were men, 86% were White. 81% of the individuals enrolled were anticoagulated for atrial fibrillation. And they had received this drug 11 hours median time since the last dose. 51% of the individuals were on a apixaban, 37% were on rivaroxaban, and 8% were on edoxaban, and then finally 5% were on enoxaparin. Now bleeding, Peder, was predominantly intracranial in 69%, it was GI in 23%. In evaluable apixaban patients, median anti Factor Xa activity decreased from 146.9 to 10 nanograms per milliliter. That's a 93% reduction. In rivaroxaban patients, it decreased from 214 to 10.8 nanograms per milliliter. That's a 94% reduction. In edoxaban patients, it decreased from 121 to 24 nanograms per milliliter; a 71% reduction. And in enoxaparin, it decreased from 0.48 to 0.11 international units per milliliter or a 75% reduction. So Peder, excellent or good hemostasis occurred in 274 of the 342 evaluable patients. So in 80%. In the safety population, thrombotic events occurred in about 10% of patients. And in 16 patients, this occurred during treatment with prophylactic anticoagulation that began after the bleeding event. So no thrombotic episodes occurred after oral anticoagulation restart. So Peder, in conclusion, in patients with major bleeding associated with the use of Factor Xa inhibitors, treatment with enoxaparin and andexanet alfa reduced anti Factor Xa activity and was associated with good or excellent hemostatic efficacy in 80% of patients. Dr. Peder Myhre: Oh wow. That was really impressive. Dr. Gregory Hundley: Yeah, what a very practical study. Well, Peder, we have some other articles in the issue. How about I go first? So first, there's a Research Letter from Professor Eleanor entitled “A Mouse Model of Atrial Fibrillation in Sepsis.” And then from Tracy Hampton we have some Cardiology News. First from Professor Shane et al, a paper on the impact of coffee subtypes on incident cardiovascular disease, arrhythmias, and mortality, long-term outcomes from the UK Biobank study, which is published in the European Journal of Preventive Cardiology. Next from Professor Morashige, there is a paper entitled “Extra Cardiac BCAA Metabolism Lowers Blood Pressure and Protects From Heart Failure.” And that's published in Cell Metabolism. And then finally from Professor Kessler and associates, the paper is entitled “Common and Rare Variant Associations with Colonial Haematopoiesis Phenotypes.” And that particular paper is published in Nature. Dr. Peder Myhre: That's great, Greg. And we also have an exchange of letters by Dr. Ding and Dr. Kirshenbaum regarding the article “Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy.” And finally we have On My Mind by Bertram Pitt entitled “Early Implementation of aldosterone Targeted Therapy in Patients with Hypertension.” Now Greg, let's go to the feature paper to discuss the progression of coronary atherosclerosis in middle-aged and older athletes. Dr. Gregory Hundley: Very good. Let's go. Welcome listeners to this feature discussion on March 28th. And we have with us today Dr. Vincent Aengevaeren from Radboud University Medical Center in Nijmegen in the Netherlands. And also with us one of our associated editors, Dr. Jarett Berry from University of Texas Southwestern Medical Center in Dallas, Texas. Welcome gentlemen. Well, Vince, we'll start with you. Can you describe for us some of the background information that went into the preparation of your study and what was the hypothesis that you wanted to address? Dr. Vincent Aengevaeren: So this specific study is actually a follow-up study of a previous study that we did on the relationship between exercise and coronary atherosclerosis. The original study was published also in circulation in 2017 and it really looked at the association of relationship between exercise volume, lifelong exercise volume and coronary atherosclerosis. And at that time we found that there was actually a sort of paradoxical association between lifelong exercise volume and coronary atherosclerosis that with higher lifelong exercise volumes, there was a dose upon dependent association with the prevalence of coronary atherosclerosis. And there was actually in the same issue, there was another paper in 2017 from a London group shown similar findings. And actually, yesterday on the ACC, there was another paper also showing increased coronary atherosclerosis in athletes. And this study of course there was also some critic like is this caused by confounding, these were observational perceptional studies, could there be other factors playing, but also none of the studies looked at the differentiation between exercise volume and exercise intensity. So the composition of the exercise. So that was the main question actually for this study. We want to do a follow-up study after at least five years do another CT scan, again, get everyone back the questionnaire, exercise habits, and then also specifically look at exercise volume versus exercise and density. Dr. Gregory Hundley: Very nice. So it sounds like in this study you have a cohort that you're following over time. So maybe describe for us a little bit more the specific study design and who is included. Who is your study population here? Dr. Vincent Aengevaeren: The study population is called the MARC study, Measuring Athletes Risk of Cardiac events. And the study was originally designed mainly based on the fact that healthy athletes, mainly male athletes, sometimes suddenly die of coronary atherosclerosis, which is not really recognized beforehand. So the main study idea was to look at healthy male athletes who didn't experience any symptoms and who underwent the screening, including an exercise test with EKG with normal findings and who then subsequently underwent a coronary CT scan. So blank CT scan for corona calcification score, but also contrast enhanced CT scan to look at the degree of coronary atherosclerosis to those of [inaudible 00:15:18] characteristics. So that's how the original study was designed and it included 318 male individuals over the age of 45 with a very heterogeneous exercise exposure. So they all had to do some type of sports, but there was no minimal dose. So it really depended. So we have some very high level athletes, but also some more of the regular people who exercise a lot less. So very heterogeneous exposure. And for this study, so in the follow-up study, we actually included 291 of those 318 individuals after six years, which I was pretty happy with. And for this specific analysis we excluded two individuals due to their PCI in between. So that's pretty much the cohort that we're looking at. And during this follow-up period of six years, they did the equivalent of about 40 MET hours per week, which equates to about five hours of the exercise. Dr. Gregory Hundley: Very nice. And Vince, you said you had a very diverse group. I mean, a lot of times I'll think about the extremes here. Folks that do a lot of aerobic exercise, those that I think about the power weightlifter. What kind of distribution of athlete, maybe just some practical identifiers for our listeners here. Dr. Vincent Aengevaeren: So it's a very important point. So the main type of athletes in this group who are endurance athletes, so mainly runners and cyclists. Of course also some other type athletes and some athletes do multiple type of sports, but mainly runners and cyclists and definitely large proportion of [inaudible 00:16:53] athletes. Dr. Gregory Hundley: Very nice. So Vince, describe for us your study results. Dr. Vincent Aengevaeren: During this follow-up period, and it's important to state that for this follow-up study we used the exercise characteristics during the follow-up period, we found that exercise volume during follow-up was not associated with progression of coronary atherosclerosis, but exercise intensity was. So we defined exercise intensity based on the MET score, the metabolic equipment of task score, which is derived from previous studies. And there's a compendium explaining MET scores for all the different sports and we used that to categorize the different sports. And we've found that vigorous intensity exercise, for example cycling, was associated with less progression of coronary calcification, but very vigorous intensity exercise, for example running was associated with more progression or coronary calcification. And if you then also look at plaque types, we also saw that those who did the most very vigorous exercise also had a bit more calcified plaque progression. So that was the main findings. Dr. Gregory Hundley: And Vince, describe for our listeners, many whom are cardiologists or others fellows, et cetera. Can you give me a specific example of vigorous exercise versus very vigorous exercise? Like, if I'm doing something during the week, describe for me those two categories, examples. Dr. Vincent Aengevaeren: So typically, and of course this is a very typical vigorous exercise was cycling and very vigorous exercise was running. But of course as you do cycling at a higher intensity, for example spinning on a spinning bike, it's traditionally at a higher exercise intensity. So that was counted as a very vigorous intensity exercise. And I have to say this was based on questionnaire data, so I did not have six-year or lifelong heart rate data. So it is based on questionnaire data, the categorization of exercise intensity. That's a good example. Other things of [inaudible 00:19:03] intensives, for example, soccer, hockey, I don't know how popular those sports are in America, but those are pretty popular in Netherlands as well. Dr. Gregory Hundley: When you mean very vigorous for some of our runners out there, I mean for the casual runner that might run two or three miles a day, is that very vigorous or are you talking about someone that's training periodically for marathons and running three or four marathons a year? Dr. Vincent Aengevaeren: That is really more, I guess, about volume. So if people do a lot of marathons, that can actually be at a lower intensity. Like, with intensity, we really, really mean the heart rate intensity and not the intensity of the volume. So I have to specify that. It's really exercise intensity such as for oxygen consumption or heart rate and not the volume in the hours per week. So typically the runners that we had were mostly very vigorous runners. So couple hours per week traditionally they did like trainings of one and a half hour, which is usually at a higher intensity. Dr. Gregory Hundley: Very nice. Well listeners, now we're going to turn to one of our associate editors, Dr. Jarett Berry, who really has some expertise in this area. And Jarett, you see many papers in circulation. What do you find is unique about this particular study and then how do you put its results really in the context of other studies that have focused on exercise both in duration as well as intensity? Dr. Jarett Berry: Yeah, thanks Greg. And Vince, a fantastic paper, such a privilege to be able to visit with both of you today about this important paper. I think if you take a step back here, challenges I think we all have as physicians is dealing with these uncertain questions that arise clinically where you encounter patients who are exercising at these extreme levels. And although it's not super common, we do encounter these scenarios clinically. And what we need in context like this is we need some data and understanding of what's happening clinically to be able to provide guidance. And so we're really in a context like this in a scenario where we have the common clinical problem of incomplete information. And I think it's studies like this that really help us move the needle to help us understand how to think about those patients of ours that exercise at very high levels. I do think it's important to put it into context, about 10% of the participants in this study exercised below 1,000 minutes per week. And so for those of you taking notes at home, that's the guidelines in 500 and 1,000 minutes per week would be, I mean you'd be hitting the guidelines. And two-thirds of these individuals were exercising at 2,000 minutes per week. So I think it's important to put it into context when we think about applying and understanding the question about toxicity of exercise, putting that into context that most of the patients that we encounter are not exercising at these high levels. However, as I mentioned, we do encounter this and we have to know what to do with it. The key here I think is... The other context is with a point that's been raised already in some of the questions and discussion is the heterogeneity that we see in individuals who exercise at these high levels. When you're trying to think about dose of exercise, we have to think about not just intensity but volume. And I think what the study's done here has done a really nice job of trying to parse that out because we can achieve the dose of exercise that's recommended or the dose of exercise that we want to achieve for personal reasons, but we can get there through different ways. We can get there through more hours or we can get there through a higher intensity. And then of course, obviously combinations of the two. And I think this study here does two things for us. Number one, it gives us a delta question. We've seen this before with just looking cross-sectionally and we have all the challenges that come with that with regard to recall of exercise. Here we have a prospective cohort that we're following or that events followed. And secondly, the ability to parse out both volume and intensity over time. And I think that for me, the finding that really sticks out is that in addition to all the complexities that are right here, we see that the story with regard the components of the dose may not be uniform. That intensity or exercising at very high intensity may be a different part of the equation beyond just volume. And I think that as we think about counseling our patients as they are engaging in this type of high level of exercise, I think it's one additional component of our way of interpreting this and providing counsel to these patients about how to think about volume and intensity. And maybe these data suggests the hypothesis that the volume part of the dose equation may be safer or maybe something that's more palatable for the heart perhaps over time than the intensity. I think the big elephant in the room, of course, is the fundamental question is that we're dealing with an intermediate phenotype and we know lots of observational data showing that more atheros bad. We all recognize that, but you can get to athero through different mechanisms here. And I think that these data and others suggest that exercise is one mechanism perhaps that though you can get athero, the question is what is the true clinical significance from a [inaudible 00:24:32] standpoint down the road as we try to extrapolate the intermediate phenotype into the future. And I think there's controversy, I think agreement about what the intermediate phenotype means in these high volume exercisers. And I think that question remains unknown, I think. But in the interim, as I said in the beginning, that as we think about putting all this into context, we don't have perfect information and we do have to take the information that we do have to provide the counsel that we need to provide if these patients. And I think I take away from this that when providing counsel, maybe I lean more towards volume and less towards this really high volume, sorry, this really high intensity for those individuals whose coronary calcium or their athero burden is particularly high. But a fantastic study. Another step in the road and it's really trying to understand an incredibly complex story and one that will continue to unfold. Dr. Gregory Hundley: Very nice, Jarett. And listeners, we're going to turn back to both Vince and Jarett here each in 30 seconds. Vince, what do you see as the next study that your group or others might want to be considering in this sphere of research? Dr. Vincent Aengevaeren: For me personally, the next big thing that we should do is really cardiovascular risk. So what's the clinical relevance of this finding? So coronary calcification is strongly associated with cardiovascular risk, but how that is in these athletes in which we see increased coronary calcification, that's still pretty much the question. I mean, any plaque is worse than no plaque, but how is this for the very vigorous exercisers who may show some more calcification and whether that risk is different. I mean, that's the question that all the athletes that email me after this type of publication have the question. And also the mechanisms. Like, what are the underlying mechanisms? That's also a next lead study for me. Dr. Gregory Hundley: Very nice. And Jarett? Dr. Jarett Berry: Yeah, I think the ultimate question is, I completely agree, is what is the clinical significance. I think that's going to be... That's a challenging question to answer just because of the on average these individuals are more rare. And so following these individuals over time to really tease out the clinical significance of this type of athero in these athletes, I think, is a challenge. I think for me the next step would be more studies like this where we can get more granular with regard to measured exercise intensity. I think wearable devices, things that Vince alluded to with regard to heart rate, really trying to get more quantitative to try to parse out the contribution of more objectively measured exercise intensities, I think would probably, for me, represents kind of probably the next step, is digging a little deeper into the phenotype and being a little bit more precise perhaps with studies like this to help us begin to understand the significance of these findings. Dr. Gregory Hundley: Very nice. Well, listeners, we want to thank Dr. Vincent Aengevaeren from Radboud University Medical Center in Nijmegen in the Netherlands, and our own associated editor, Dr. Jarett Berry from University of Texas Southwestern Medical Center in Dallas, Texas for bringing us this study highlighting that exercise intensity but not volume was associated with progression of coronary atherosclerosis during a six-year follow-up of this cohort of really trained athletes and intriguingly the very vigorous. So we want to distinguish that. The very vigorous intensity exercise was associated with greater coronary artery calcium calcified plaque progression, whereas simply just vigorous intensity exercise, casual riding of the bike, casual running, et cetera, was associated with less coronary artery calcium progression. Well, on behalf of Peder and Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. This program is copyright of the American Heart Association 2023. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Over the years, I've noticed that people veer away from supplements with complicated-sounding names like nicotinamide riboside (NR). That could be what's kept people in the dark so much about this specific form of vitamin B3. I have to admit that I ignored it for a while, when research papers began emerging several years ago, as well. But the health and fitness benefits are too good to ignore, which is why I decided it was time to write a guide covering what it is, how you might benefit from using it, how much to use, and a few other details about NR. You'll quickly see how it could be helpful for you or someone you know. What is Nicotinamide Riboside (NR)? Nicotinamide Riboside (NR) is a naturally occurring form of vitamin B3. As a precursor to nicotinamide adenine dinucleotide (NAD+), a critical coenzyme found in all living cells, NR maintains cellular energy and supports various biological processes.Canto, C., Menzies, K. J., & Auwerx, J. (2015). NAD+ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell metabolism, 22(1), 31-53. https://doi.org/10.1016/j.cmet.2015.05.023 NAD+ is essential for cellular metabolism, DNA repair, and proper functioning of the mitochondria, the "powerhouses of the cell." As we age, our NAD+ levels naturally decline, contributing to various age-related health issues.Verdin, E. (2015). NAD+ in aging, metabolism, and neurodegeneration. Science, 350(6265), 1208-1213. https://doi.org/10.1126/science.aac4854 Research suggests that supplementation with NR may help boost NAD+ levels and combat these effects, improving overall health and well-being.Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell metabolism, 27(3), 529-547. https://doi.org/10.1016/j.cmet.2018.02.011 You get trace levels of NR from dietary sources, such as milk, yeast, and some vegetables, but to consume NR at therapeutic levels, you need to supplement with it. Unlike other forms of vitamin B3, such as niacin and nicotinamide, NR maintains a better safety profile and produces fewer side effects.Conze, D., Brenner, C., & Kruger, C. L. (2019). Safety and metabolism of long-term administration of NIAGEN (nicotinamide riboside chloride) in a randomized, double-blind, placebo-controlled clinical trial of healthy overweight adults. Scientific Reports, 9(1), 9772. https://doi.org/10.1038/s41598-019-46120-z Fitness and Performance Benefits NR supplementation can improve muscle function, increase endurance, and enhance cellular energy production, making it a valuable supplement, especially for aging athletes. Improved Muscle Function One of the key benefits of NR supplementation is its positive impact on muscle function. An animal study found that NR supplementation increased muscle strength and improved exercise capacity. This is believed to result from NR's role in boosting nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme involved in various cellular processes, including energy metabolism and mitochondrial function.Trammell SA, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7:12948. doi: 10.1038/ncomms12948 By enhancing NAD+ levels, NR supplementation may help promote muscle health and function, making it a valuable addition to any fitness regimen. Increased Endurance NR supplementation increases endurance performance, too. Another animal study demonstrated that supplementation with NR increased endurance due to the activation of sirtuin 1 (SIRT1), a protein critical in regulating energy metabolism and mitochondrial biogenesis.Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., ... & Sauve, A. A. (2012). The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metabolism, 15(6), 838-847.

A new study by Harvard Medical School investigators at Brigham and Women's Hospital found that when we eat significantly impacts our energy expenditure, appetite, and molecular pathways in adipose tissue. Their results are published in Cell Metabolism. Frank Scheer, HMS professor of medicine, wanted to understand if the time people eat at matters everything else is kept consistent. Each participant they looked at completed two laboratory protocols: one with a strictly scheduled early meal schedule, and the other with the same meals, each scheduled about four hours later in the day. They found that eating four hours later makes a significant difference in hunger levels, the way people burn calories and the way we store fat, had profound effects on hunger and the appetite-regulating hormones leptin and ghrelin, which influence our drive to eat. So if you tend to be a late night eater and are struggling to slim down – see if you can eat your last meal or snack one hour earlier this entire week and see if you see any positive shifts in your weight. If not, stop eating a half-hour to one hour earlier next and assess. Slowly shift your window earlier until you find the zone in which you notice your body losing weight. PLUS, as a member of ThinWithinLife.com, this April I am leading members through a 30-Day stop late night eating challenge; just one of the many benefits of becoming a member. If that sounds JUST like what you need, come join us at ThinWithinLife.com #thinwithinlife, #timedeating, #harvardweightloss, #harvard, #Harvardstudy, #cellmetabolism, #newthinkingtoloseweight, #mentalweightloss, #newmindsettoolsweight, #mentalweightlosspodcast, #2023weightlossgoals, #weightlossplan, #overeatinghelp, #spiralingoutofcontrol, #helpmeloseweight, #helpmeloseweightpodcast, #bestweightlosspodcast, #mentalweightlosspodcast, #weightlosshabits, #weightlosstools, #bodylovepodcast, #howtoloseweightpodcast, #newhealthyhabits, #goalsettingpodcaast, #weightlosshabits, #weightllosstools, #bettereatinghabits, #bestweightlosspodcast, #over40weightloss, #over50weightloss, #over60weightloss, #popularweightlosspodcast, #weightlosstips, #stopyoyoieting, #emotionalhunger, #eatingmyfeelings, #theweightlosspodcast, #bestweightlosspodcasts, #weightlosspodcastspotify, #popularweightlosspodcast, #diets, #nodietpodcast, #nomoredieting, #sickofdieting, #intuitiveeating, #naturalhealth, #naturalweightloss, #tipstostopemotionaleating, #managingemotionaleating, #tipstoavoidgainingweight, #lose50poundspodcast, #lose30pounds, #lose100pounds, #intuitiveeatingpodcast, #mentalweightloss, #mindbasedweightloss, #marnathall, #thinwithin, #thinwithinonline, #thinwithinpodcast, #overeatingtips, #overeatingpodcast, #stopdietingpodcast, #readytoloseweight, #helpmeloseweightpodcast, #8poundsdown, #loseweightnnow, #popularweightlosspodcast, #weightloss

It's In the News.. a roundup of the top diabetes stories and headlines of the past seven days. This week: the first AID system to use Libre 3 is released, we learn more about Teplizumab, now brand name Tzield, to prevent T1D and how much it may cost. Couple of new research projects about what triggers type 1, a personal story about retinopathy and a player with T1D takes the stage at the World Cup. Check out Stacey's book: The World's Worst Diabetes Mom! Join the Diabetes Connections Facebook Group! Sign up for our newsletter here Episode Transcription Below (or coming soon!) Please visit our Sponsors & Partners - they help make the show possible! *Click here to learn more about OMNIPOD* *Click here to learn more about AFREZZA* *Click here to learn more about DEXCOM* Hello and welcome to Diabetes Connections In the News! I'm Stacey Simms and these are the top diabetes stories and headlines of the past seven days. XX In the news is brought to you by T1D Exchange! T1D Exchange is a nonprofit organization dedicated to improving outcomes for the entire T1D population. https://t1dexchange.org/stacey/ XX And by my new book “Still The World's Worst Diabetes Mom: More Real Life Stories of Parenting a Child With Type 1 Diabetes” available on Amazon in paperback and for kindle. XX XX The first automated insulin delivery system using the FreeStyle Libre 3 is now authorized in Germany. The mylife YpsoPump and the FreeStyle Libre 3, combined with the mylife CamAPS FX algorithm from CamDiab Ypsomed already launched mylife Loop in partnership with CamDiab in early summer 2022 in several countries. That was with the Dexcom G6. The company now says By enabling the FreeStyle Libre 3 sensor to work with mylife Loop, people with diabetes now have the option of choosing between two sensors, the Dexcom G6 and the FreeStyle Libre 3, and of customising their loop. with other European countries to follow in 2023. The mylife Loop offering is currently available for Android, iOS will follow in the second half of 2023. I spoke with Ypsomed last year, they are partnering with Lilly and plan to bring their pump the US. Right now oly the Dexcom G6 is approved for AID use, so we'll see if we get the same kind of flexibility. https://www.drugdeliverybusiness.com/ypsomed-camdiab-insulin-dosing-abbott-freestyle-libre-3/ XX Really interesting but very early work on protein known as Befa. It's produced by gut bacteria and triggers the division of cells that make insulin. Reserachers at Univesrty of Utah are working on understanding more about how Befa works.. hoping it could help them figure out a way to stimulate beta cell prdocution. The researchers' findings were recently published in the journal Cell Metabolism. The finding suggests that bacterial warfare in the gut can have collateral beneficial effects on the body, boosting the population of cells that can make insulin throughout the lifespan. In the future, Guillemin's team imagines possible therapeutic applications for the finding. For example, proactively fortifying the microbiomes of high-risk infants with BefA-producing bacteria could prevent them from later developing type 1 diabetes. https://scitechdaily.com/profound-implications-new-research-details-the-microbial-origins-of-type-1-diabetes/ XX A new serological test may be pivotal in the search for viral triggers of diseases like diabetes and celiac disease. PepSeq is a technology that allows scientists to test antibody binding against hundreds of thousands of protein targets at one time, instead of testing one at a time. This protocol is laid out in detail in an article published earlier in November in Nature Protocols. It's said to be an important step forward as concerns about bioterrorism, zoonotic diseases and the next pandemic are never far away. Understanding these pathogens will help scientists develop vaccines and track their movement and evolution. "This can help us to better understand the epidemiology of infectious diseases, and it is also empowering us in our search for potential viral triggers for non-infectious diseases like diabetes and celiac disease," Ladner said. https://medicalxpress.com/news/2022-11-serological-viral-triggers-diseases-diabetes.html XX The recent approval of teplizumab – brand name is now Tzield, for the delay of type 1 diabetes by the US Food and Drug Administration is expected to advance efforts to increase screening to cost-effectively identify those at risk for the condition who would be eligible to receive the new treatment. The anti-CD3 monoclonal antibody was approved November 17. In a clinical trial, teplizumab delayed the onset of clinical (stage 3) type 1 diabetes by approximately 2 years, and longer in some cases.. more than 4 years. It is administered by intravenous infusion once daily for 14 consecutive days and is expected to cost in the region of $200,000 for the course of treatment. During an investor call on November 18, Provention Bio chief commercial officer Jason Hoitt said that among the company's "strategic initiatives" were "advancing awareness and screening for autoantibodies in at-risk individuals, and ultimately, routine screening during pediatric well visits for the general population," as well as "[healthcare provider] belief in teplizumab and desire to prescribe it for their patients." Without broad population-based screening, first-degree relatives of people with type 1 diabetes are likely to be the first to be screened and those with stage 2 identified for receipt of teplizumab. Today, that population is estimated at about 30,000 in the United States, Hoitt said, adding, "with this approval we hope that more stage 2 patients can be readily identified so the course of the disease can be changed." https://www.medscape.com/viewarticle/984748 XX A new way to test for pancreatic cancer is being considered a breakthrough. Pancreatic cancer is commonly considered the deadliest of all cancers in part because with few symptoms and invasive testing, it's so difficult to detect. Bluestar Genomics, which has developed a new non-invasive “liquid biopsy” test that uses a blood test. Pancreatic cancer is eight times as common in patients over the age of 50 with a recent diagnosis of type 2 diabetes. Sometimes, new cases of type 2 diabetes may actually be a consequence of early, undetected pancreatic cancer. Bluestar has breakthrough designation from the FDA. It's too soon for doctors to recommend this for everyone with type 2 but those recently diagnosed should ask their doctors. https://www.diabetesdaily.com/blog/theres-a-new-test-for-pancreatic-cancer-heres-why-it-matters-for-type-2-diabetes-706202/ XX Not really news but a lot of social media chatter about a lame diabetes joke this time during Wednesday, the reboot of the Adams Family. Hearing great things about the show but not the diabetes joke. Good time to mention Diatribes d-stigamtize campaign . I'll link up the website, it's an effort to collect stories and to come up with action to fight diabetes stigma. https://www.dstigmatize.org/ XX Back to the news in a moment but first.. The T1D Exchange Registry is a research study conducted online over time, designed to foster innovation and improve the lives of people with T1D. The platform is open to both adults and children with T1D living in the U.S. Personal information remains confidential and participation is fully voluntary. Once enrolled, participants will complete annual surveys and have the opportunity to sign up for other studies on specific topics related to T1D. The registry aims to improve knowledge of T1D, accelerate the discovery and development of new treatments and technologies, and generate evidence to support policy or insurance changes that help the T1D community. By sharing opinions, experiences and data, patients can help advance meaningful T1D treatment, care and policy. The registry is now available on the T1D Exchange website and is simple to navigate, mobile and user-friendly. For more information or to register, go to www.t1dregistry.org/stacey XX Big shout out to friend of the show – and friend of mine – Mike Hoskins. Mike wrote for diabetesmine for many years and still works at the parent company, Healthline. He recently shared a lot of information and feeling about his diabetic retinopathy diagnosis. He goes into detail of what the treatment has been lie, saying that others sharing that with him has helped make it all a bit easier. Its'a wonderful article and I'll link it up in the show notes. https://www.healthline.com/health/my-diabetic-retinopathy-diagnosisXX XX Many of you have probably been following Jodan Morris for many years, but just in case.. the 28-year old professional soccer player was diagnosed at age 9. He's now part of the U.S. Men's National Team that beat Iran this week and moves ahead to the World Cup knock out rounds this weekend. He plays out of Seattle and has started a foundation, Jordan Morris Foundation, to support kids living with Type 1 Diabetes. XX On the podcast next week.. One Drop is making a CGM? We'll talk to CEO Jeff Dachis about that. Last week's show was with therapist JoAnne Robb. Listen wherever you get your podcasts That's In the News for this week.. if you like it, please share it! Thanks for joining me! See you back here soon.

In this episode, I chat with Professor John Hawley about the new research supporting the health benefits of time restricted eating and high intensity interval training (HIIT).   Professor Hawley is currently Head of the Exercise & Nutrition Research Program, and Director of the Mary MacKillop Institute for Health Research, at the Australian Catholic University in Melbourne.  John's research program primarily focuses on the interaction of exercise training and diet on human health outcomes, with a specific emphasis on lifestyle interventions to combat obesity, insulin resistance, type 2 diabetes and cancer. John is internationally recognised in his field of expertise, having published 300 articles in prestigious journal such as Cell, Science and Cell Metabolism. In this episode John and I discuss the latest emerging research relating to the effects of time restricted eating and HIIT on health outcomes and obesity in women.  Garmin Sq 2 Plus  This episode is brought to you by Venu Sq 2 – Garmin's GPS smartwatch with advanced health and fitness features to help you better understand your body. It will spend more time on your wrist and less time charging with up to 11 days of use on a single charge! Use code LEANNE10 at www.garmin.com.au to receive 10% off your very own Venu Sq 2 and start living better with Garmin today. Please subscribe and leave me a review   If you enjoyed this podcast, please tag me and share it in your Instagram stories and leave me a positive rating or review in the purple Apple Podcast app (in the rating & reviews section underneath the episode lists). This really helps my podcast get prioritised by Apple and helps me disseminate evidence based information to the people that need it the most! Don't forget to subscribe to my podcast so you never miss an episode!  

VIDEOS: EXCLUSIVE: UNDERTAKER EXPLAINS “MYSTERIOUS” CLOTTING PHENOMENON! | Louder with Crowder (part 2) Society is going to COLLAPSE -Neil Oliver ( 5:24) Fear Psychosis and the Cult of Safety – Why are People so Afraid?  – Academy of Ideas (13:25)   Dietary supplement found to improve concentration levels University of Granada, November 3, 2022 The research group from the University of Granada (UGR) has tested the effects of a multi-ingredient dietary nootropic on concentration levels and cognitive performance. Nootropics are cognitive enhancers that have traditionally been used in the treatment of cognitive pathologies. Leading this study was Lucas Jurado Fasoli—a researcher from the Scientific Unit of Excellence in Exercise, Nutrition and Health (UCEENS) at the Sport and Health Joint University Institute (iMUDS). He explains that, traditionally, nootropics have been drugs, with their corresponding side-effects. “To address the issue of potential side-effects, different dietary nootropics have emerged as an alternative way to enhance cognitive performance. And these, as is the case in this study, are used by healthy individuals in activities such as preparing for competitive exams or video-game competitions,” explains Jurado Fasoli. The results of the study showed that the acute intake of this multi-ingredient nootropic decreases the response time across different cognitive tests: in processing speed, inhibitory control, working memory, and cognitive flexibility. It also increases accuracy in tests involving processing speed, inhibitory control, and cognitive flexibility. The supplement contains L-tyrosine, acetyl L-carnitine, sodium citicoline, alpha-GPC, taurine, caffeine, mango leaf extract and huperzia serrata leaf. These results were accompanied by an increase in positive emotions and a decrease in negative emotions and depression. And, importantly, the favorable effects of this nootropic did not appear to have any effect on the heart-rate of participants. Previous studies have shown that supplementation with the combination of caffeine and taurine, L-theanine, tyrosine, and mango leaves extract can improve the RT in different cognitive and computerized tests. In this study, we showed that a dietary multi-ingredient nootropic improves the processing speed of information in young healthy adults. This effect could be due to the synergic effects of different dietary ingredients included in the nootropic. Also, it could be partially explained by the central nervous system activation and alertness enhancement effect of caffeine, which could increase the processing speed and decrease the RT. The inclusion of L-theanine as a dietary ingredient in the nootropic counteracts the potential effects derived from a high dose of caffeine on anxiety, psychological stress, blood pressure, and HR, which completely agrees with our results. A sample comprising 26 young adults (50:50 male/female, with an average age of 25) participated in the study. They were required to undertake various cognitive tests twice, separated by 48 hours, having ingested either the multi-ingredient dietary nootropic or a placebo (randomized and triple-blinded across the sample). Thirty minutes after ingestion, measurements were taken of processing speed, inhibitory control, working memory, cognitive flexibility, creativity, and verbal fluency. Different emotions were also evaluated and the participants' heart-rate was recorded while they undertook the tests. Consuming more magnesium associated with lower risk of mortality during years following heart attack Wageningen University and Research (Netherlands), October 31, 2022 A study of people with a history of heart attack found that those who consumed more magnesium lived longer than those whose intake was low. Having a high magnesium intake, defined as greater than 320 milligrams (mg) per day, was associated with a 28% lower risk of dying from cardiovascular disease and a 22% lower risk of death from any cause compared to a low intake, defined as less than 283 mg per day. The protective effect of magnesium was even stronger in patients who were being treated with diuretic drugs. In this group, the risk of mortality from cardiovascular disease was 45% lower among those with high magnesium compared to those with low magnesium. “Little is known about magnesium intake and long-term mortality risk in cardiovascular disease patients,” authors Ilse Evers and colleagues noted. “Magnesium requirements may be different in cardiovascular disease patients because of alterations in the cardiovascular system, comorbidities and/or medication use.” The study included 4,365 participants in the Alpha Omega Cohort, an ongoing follow-up of participants in the earlier 40-month Alpha Omega Trial. The Alpha Omega Trial included men and women between the ages of 60 and 80 years who had experienced a heart attack within 10 years prior to enrolling between 2002 and 2006. Dietary questionnaire responses obtained at enrollment provided information concerning magnesium intake from food and non-food sources. Mortality was ascertained through 2018. The findings were published in Frontiers in Cardiovascular Medicine. Calorie restriction promotes longevity through effects on mitochondrial network Harvard School of Public Health, October 27 2022. Research reported in Cell Metabolism helps explain the effects of calorie restriction and activation of AMP-activated protein kinase (AMPK, an energy-sensing protein) on longevity. Harvard researchers have determined that AMPK and calorie restriction promote homeostasis and plasticity of networks formed by the cells' power plants known as mitochondria. Mitochondria networks change shape according to energy demand, however, this ability declines with age. “Dynamic remodeling of mitochondrial networks by fusion and fission promotes maintenance of cellular homeostasis,” explain Heather J. Weir and colleagues at the Harvard T. H. Chan School of Public Health. “Dysregulation of mitochondrial dynamics and aberrant mitochondrial morphology are hallmarks of aging and are thought to contribute to the pathology of numerous age-related pathologies including Alzheimer's and Parkinson's disease.” By restricting calories in the diet of roundworms or using a strain of roundworm in which an AMPK subunit is activated, the researchers found that the roundworms maintained a youthful fused mitochondrial network shape with age. The youthful networks lengthen life by communicating with peroxisomes within the cells to alter fat metabolism. “Low-energy conditions such as dietary restriction and intermittent fasting have previously been shown to promote healthy aging,” Dr Weir commented. “Our work shows how crucial the plasticity of mitochondria networks is for the benefits of fasting. If we lock mitochondria in one state, we completely block the effects of fasting or dietary restriction on longevity.” Electroacupuncture found to ease nausea and vomiting in ICU patients recovering from chemotherapy Narbonne Hospital (France), October 28, 2022 Refractory vomiting is just one of many complications endured by patients confined to intensive care units (ICU) due to chemotherapy and other major medical treatments. But relief may be coming in the form of transcutaneous electroacupuncture (TEA) therapy that can alleviate the worst symptoms of persistent vomiting. Earlier studies have shown that TEA can reduce episodes of nausea and vomiting attributed to chemotherapy treatments, recently concluded medical operations, and pregnancy. It is growing popular as an alternative to anti-emetic medication. The TEA treatment consisted of two electrodes attached on either side of the Neiguan (PC 6) pressure point, also known as the pericardium meridian. The researchers employed a standard neuromuscular transmission monitor to stimulate the acupuncture point for 30 minutes. The overall incidence of nausea or vomiting within the first 24 hours after TEA was 50 percent. After the 24-hour mark, 30 percent of the patients perceived nausea, and 20 percent experienced vomiting. Ninety percent of patients reported suppression of nausea/vomiting immediately after undergoing TEA. During a six-hour period after TEA, 60 percent of patients did not sense nausea or experience vomiting. Between six to 24 hours after TEA, 60 percent of patients remained free from nausea or vomiting episodes. Two patients who experienced nausea were given a second TEA session that remedied all symptoms.TEA itself was free from any complication and side effects. The Mindfulness Skill That Is Crucial for Stress A new study suggests that practicing acceptance helps reduce our stress more than simple mindful awareness. Carnegie Mellon University, October 28, 2022 In this study, researchers randomly assigned 137 stressed adults of various ages and ethnicities to one of three programs: an eight-week Mindfulness-Based Stress Reduction (MBSR) course, where they learned to mindfully pay attention to their present-moment experiences in an accepting, nonjudgmental way; an MBSR course without instructions on acceptance; or no course. The courses included many lessons—for example, how to pay attention to your breath and your body sensations, and how to eat food or take a walk mindfully—as well as practice time outside of class. Before, during, and afterwards, participants reported five times daily about how stressed they felt in the moment and whether they'd experienced a stressful event since their last report.In response to stress, many people today are turning to meditation or mindfulness apps (myself included). But not all mindfulness practice is equally effective for combating stress, a new study suggests. It's possible that some of our practices may be missing a vital ingredient: acceptance. Though all of the groups experienced less stress and fewer incidents of feeling stressed over time, the people who took the full MBSR course had a significantly steeper improvement than the other two groups. “Learning how to accept your present-moment experience is really important for reducing stress,” says Emily Lindsay, one of the study's coauthors. “It seems to be a key element of mindfulness training.” Mindfulness practices that specifically emphasize acceptance teach us a nonjudgmental attitude toward our experiences—meaning, learning not to label our thoughts, feelings, or experiences as good or bad, and trying not to change or resist them in any way. While many mindfulness courses include instructions in acceptance as par for the course, those that don't may not be as effective. People who learn to accept and not just notice their experiences become less prone to mind-wandering, which has been tied to well-being, and less reactive to stress—meaning, they show reductions in systolic blood pressure, the stress hormone cortisol, and feelings of stress in a stressful situation. Her recent study adds to these results by monitoring participants daily, helping to show that acceptance makes a difference in everyday life situations and not just in the laboratory. Accepting stress helps people to stop focusing only on what's wrong and to notice other feelings, sensations, and thoughts occurring at the same time, enabling them to see the “bigger picture.” Acceptance is not about acquiescing to your fate, though —like getting a diagnosis of a terminal illness and just accepting that you're going to die. That kind of “acceptance” leads to worse outcomes. Nor is it about accepting poor treatment from other people. It's more about accepting your internal experience—your thoughts and feelings—which informs you about how to respond to your external circumstances in a wiser way. For example, if you feel angry and accept your anger in the moment, it may prevent you from lashing out at someone and help you see that your feelings aren't their fault Eat more trifoliate oranges to keep your prostate healthy Korean Institute of Oriental Medicine, October 26, 2022 Compared to younger individuals, older men are at a higher risk of developing benign prostatic hyperplasia (BPH) or an enlarged prostate. A study published in the journal BMC Complementary and Alternative Medicine reveals a compelling reason for men to eat trifoliate oranges, as extracts from the fruit were proven effective in preventing the onset of BPH and cease its progression. The trifoliate orange (Poncirus trifoliata), also known as the hardy orange, is a citrus fruit native to China. It is grown in parts of the US and Europe for use in jellies, marmalades, and jams despite its notoriously bitter taste. It has been used as an ingredient in Traditional Chinese Medicine since ancient times, and current studies have shown its importance in maintaining prostate health. As the word “benign” in its name implies, BPH is relatively harmless. In fact, some consider it a normal part of the aging process among males. It can, however, be extremely inconvenient as its symptoms can make the vital act of urinating difficult. It can also cause a constant feeling of needing to pee even at night; in most cases, sufferers may find themselves unable to sleep properly because of this particular symptom. The researchers in the aforementioned looked at the trifoliate orange as a possible treatment for BPH. In particular, the study investigated the extract from Ponciri Fructus (PFE), the young fruit of the trifoliate orange, and its protective effects on the development of the BPH. In the study, the researchers induced BPH in a rat model by injecting testosterone propionate (TP) and corn oil every day for four weeks. PFE was administered via oral gavage at a dose level of 200 mg/kg, one hour before these injections over the same duration. At the end of the study, the rats were sacrificed and examined for markers of BPH. Specifically, the researchers took note of relative prostate weight, the levels of testosterone and dihydrotestosterone (DHT), common factors influencing the development of BPH. At the end of the study, the researchers noticed reductions in relative prostate weight, the level of testosterone and DHT in serum and prostatic tissue, prostatic hyperplasia, and the expression of PCNA. They also noted higher levels of antioxidant enzymes.

This week we explore a brand new study published by Harvard researchers in The Journal of Cell Metabolism which compared early eating patterns to late eating patterns on markers contributing to hunger and weight gain. In this episode we'll give you a synopsis of the study and it's potential implications, as well as giving you some context as to whether this information applies to you and how to use it. Follow us on IG @eatritenutrition

This Week In Wellness a study published in Cell Metabolism has shown that eating late causes decreased energy expenditure, increased hunger, and changes in fat tissue that may increase the risk of obesity. https://www.sciencedaily.com/releases/2022/10/221004121928.htm https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00397-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2f Retrieve%2fapi%2FS1550413122003977%3Fshowall%3Dtrue The post TWIW 172: Eating late bad for metabolism, hunger and obesity risk appeared first on The Wellness Couch.

VIDEOS: Hang on, the WEF is now doing THIS to our internet? | Redacted with Clayton Morris – 7:00 This intense AI anger is exactly what experts warned of, w Elon Musk. – 15:01 New Brain Implant Begins Human Trials – Neuralink Update! – 14:00  Get the latest information from the CDC about COVID-19. Professor Sucharit Bhakdi, M.D – 10:00  Study links omega-3s to improved brain structure, cognition at midlife University of Texas Health Science Center, October 5, 2022 Eating cold-water fish and other sources of omega-3 fatty acids may preserve brain health and enhance cognition in middle age, new evidence indicates. Having at least some omega-3s in red blood cells was associated with better brain structure and cognitive function among healthy study volunteers in their 40s and 50s, according to research published in Neurology®, the medical journal of the American Academy of Neurology. “Studies have looked at this association in older populations. The new contribution here is that, even at younger ages, if you have a diet that includes some omega-3 fatty acids, you are already protecting your brain for most of the indicators of brain aging that we see at middle age,” said Claudia Satizabal, PhD the lead author of the study. Volunteers' average age was 46. The team looked at the relation of red blood cell omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging. Researchers also studied the effect of omega-3 red blood cell concentrations in volunteers who carried APOE4, a genetic variation linked to higher risk of Alzheimer's disease. The study of 2,183 dementia- and stroke-free participants found that: Higher omega-3 index was associated with larger hippocampal volumes. The hippocampus, a structure in the brain, plays a major role in learning and memory. Consuming more omega-3s was associated with better abstract reasoning, or the ability to understand complex concepts using logical thinking. APOE4 carriers with a higher omega-3 index had less small-vessel disease. The APOE4 gene is associated with cardiovascular disease and vascular dementia. “Omega-3 fatty acids such as EPA and DHA are key micronutrients that enhance and protect the brain,” said study coauthor Debora Melo van Lent, PhD, postdoctoral research fellow at the Biggs Institute. “Our study is one of the first to observe this effect in a younger population. More studies in this age group are needed.” Multiple health benefits of b-type procyanidin-rich foods like chocolate and apples consumed in right amounts Shibaura Institute of Technology (Japan), October 5, 2022 B-type procyanidins, made of catechin oligomers, are a class of polyphenols found abundantly in foods like cocoa, apples, grape seeds, and red wine. Several studies have established the benefits of these micronutrients in reducing the risk of cardiovascular diseases and strokes. B-type procyanidins are also successful in controlling hypertension, dyslipidemia, and glucose intolerance. Studies attest to the physiological benefits of their intake on the central nervous system (CNS), namely an improvement in cognitive functions. These physiological changes follow a pattern of hormesis—a phenomenon in which peak benefits of a substance are achieved at mid-range doses, becoming progressively lesser at lower and higher doses. Researchers from Shibaura Institute of Technology (SIT), Japan, led by Professor Naomi Osakabe, reviewed the data from intervention trials supporting hormetic responses of B-type procyanidin ingestion. The team conducted in vivo experiments to understand possible connections between B-type procyanidin hormetic responses and CNS neurotransmitter receptor activation. Their article has been published in Frontiers of Nutrition . The researchers noted that a single oral administration of an optimal dose of cocoa flavanol temporarily increased the blood pressure and heart rate in rats. But the hemodynamics did not change when the dose was increased or decreased. Administration of B-type procyanidin monomer and various oligomers produced similar results. According to Professor Osakabe, “These results are consistent with those of intervention studies following a single intake of food rich in B-type procyanidin, and support the U-shaped dose-response theory, or hormesis, of polyphenols.” To observe whether the sympathetic nervous system (SNS) is involved in the hemodynamic changes induced by B-type procyanidins, the team administered adrenaline blockers in test rats. This successfully decreased the temporary increase in heart rate induced by the optimal dose of cocoa flavanol. A different kind of blocker—a1 blocker—inhibited the transient rise in blood pressure. This suggested that the SNS, which controls the action of adrenaline blockers, is responsible for the hemodynamic and metabolic changes induced by a single oral dose of B-type procyanidin. The researchers next ascertained why optimal doses, and not high doses, are responsible for the thermogenic and metabolic responses. They co-administered a high dose of cocoa flavanol and yohimbine (an α2 blocker) and noted a temporary but distinct increase in blood pressure in test animals. Similar observations were made with the use of B-type procyanidin oligomer and yohimbine. Professor Osakabe surmises, “Since α2 blockers are associated with the down-regulation of the SNS, the reduced metabolic and thermogenic outputs at a high dose of B-type procyanidins seen in our study may have induced α2 auto-receptor activation. Thus, SNS deactivation may be induced by a high dose of B-type procyanidins.” Meditation keeps emotional brain in check Michigan State University, September 29, 2022 Meditation can help tame your emotions even if you're not a mindful person, suggests a new study from Michigan State University. Reporting in the journal Frontiers in Human Neuroscience, psychology researchers recorded the brain activity of people looking at disturbing pictures immediately after meditating for the first time. These participants were able to tame their negative emotions just as well as participants who were naturally mindful. “Our findings not only demonstrate that meditation improves emotional health, but that people can acquire these benefits regardless of their ‘natural' ability to be mindful,” said Yanli Lin, an MSU graduate student and lead investigator of the study. “It just takes some practice.” Researchers assessed 68 participants for mindfulness using a scientifically validated survey. The participants were then randomly assigned to engage in an 18-minute audio guided meditation or listen to a control presentation of how to learn a new language, before viewing negative pictures (such as a bloody corpse) while their brain activity was recorded. The participants who meditated – they had varying levels of natural mindfulness – showed similar levels of “emotion regulatory” brain activity as people with high levels of natural mindfulness. In other words their emotional brains recovered quickly after viewing the troubling photos, essentially keeping their negative emotions in check. In addition, some of the participants were instructed to look at the gruesome photos “mindfully” (be in a mindful state of mind) while others received no such instruction. Interestingly, the people who viewed the photos “mindfully” showed no better ability to keep their negative emotions in check. This suggests that for non-meditators, the emotional benefits of mindfulness might be better achieved through meditation, rather than “forcing it” as a state of mind, said Moser, MSU associate professor of clinical psychology and co-author of the study. A mother's ultra-processed food intake may be linked to obesity risk in her children Massachusetts General Hospital and Harvard Medical School, October 5, 2022 A mother's consumption of ultra-processed foods appears to be linked to an increased risk of overweight or obesity in her offspring, irrespective of other lifestyle risk factors, suggests a U.S. study published by The BMJ today. The researchers that mothers might benefit from limiting their intake of ultra-processed foods, that dietary guidelines should be refined, and financial and social barriers removed to improve nutrition for women of childbearing age and reduce childhood obesity. Researchers drew on data for 19,958 children born to 14,553 mothers (45% boys, aged 7-17 years at study enrollment) from the Nurses' Health Study II (NHS II) and the Growing Up Today Study (GUTS I and II) in the United States. The results show that a mother's ultra-processed food consumption was associated with an increased risk of overweight or obesity in her offspring. For example, a 26% higher risk was seen in the group with the highest maternal ultra-processed food consumption (12.1 servings/day) versus the lowest consumption group (3.4 servings/day). Reishi Mushrooms Proven For Fibromyalgia Pain Relief In Human Study University of Extremadura (Spain), September 29, 2022 A promising double-blind, randomized human clinical study of ganoderma lucidum, also known as reishi mushroom, has been shown to be effective in treating fibromyalgia chronic pain. To begin, science knows that the reishi mushroom is the most studied nutraceutical and that it has been used safely and effectively for thousands of years. It is often called the mushroom of longevity and immortality. Reishi has several biologically-active compounds in it, including triterpenes, which have been shown to increase the production of Nerve Growth Factor. NGF is a protein that helps to create new neurons and repair damaged neurons. This also enhances the communication between cells and reduces inflammation. In the fibromyalgia chronic pain study, one group consumed 6 grams of reishi mushroom powder per day and another group consumed 6 grams of carob powder per day. Each group participated for 6 weeks and continued to self-report their experiences for 72 days after the treatment. The reishi mushroom group experienced pain reduction by up to 30%, which is significant. They also reported getting better sleep, were happier and gained aerobic endurance and body flexibility. Time-restricted eating improves health of firefighters Salk Institute, October 3, 2022 In collaboration with the San Diego Fire-Rescue Department, scientists from the Salk Institute and UC San Diego Health conducted a clinical trial and found that time-restricted eating improved measures of health and well-being in firefighters. The lifestyle intervention only required the firefighters to eat during a 10-hour window and did not involve skipping meals. The new findings, published in Cell Metabolism may also have implications for shift workers, such as military personnel; health care, food service, and transportation professionals; telecommunications staff; and new parents, whose schedules often mimic shift work when caring for a new baby. “Doctors and researchers are always thinking about the magic pill that can cure or reduce disease. Our study showed that shift workers with high blood pressure, blood sugar, or cholesterol can benefit from a simple lifestyle intervention called time-restricted eating,” says Salk Professor Satchidananda Panda, co-corresponding author of the study and holder of the Rita and Richard Atkinson Chair. Almost every cell in the body has a 24-hour biological clock that produces circadian (daily) rhythms. These rhythms regulate behavior (e.g., when to be active and when to rest) and physiology (e.g., blood pressure, blood sugar, muscle function). Circadian rhythms coordinate with the environment in part by regular, timed cycles of light and dark and eating and fasting. Disruptions to these cycles, which can occur with shift work, can impact health, leading to obesity, heart disease, diabetes, and cancer. In this clinical trial, 150 firefighters from the San Diego Fire-Rescue Department used the myCircadianClock app on their phones to track their eating for three months. Half the group ate within a 10-hour window, while the other half (the control group) changed nothing and ate within a 14-hour window. Both groups were encouraged to follow a Mediterranean diet, which is known to have health benefits. The study included both individuals who were healthy and those who were overweight or who had health conditions such as high blood pressure, cholesterol, and/or blood glucose. The researchers found that time-restricted eating within a 10-hour eating window was feasible without adverse effects and helped the firefighters significantly decrease their VLDL (“bad”) cholesterol size by 1.34 nanometers (small VLDL is less likely to block arteries), improve their mental health, and reduce their alcohol intake by roughly three drinks per week. Time-restricted eating also significantly improved blood sugar and blood pressure in firefighters who had elevated levels at the start of the study. The researchers concluded that time-restricted eating may provide even greater benefit for those at risk for cardiometabolic disease and other chronic diseases.

VIDEOS: Unpayable Debt & Deadly Vax Causing Hell on Earth – Ed Dowd – start 6:30 -20:00 What Greta Thunberg does not understand about climate change | Jordan Peterson – 7:09 Gary Null – Speaks to U.N. on Earth Day (Part 2 of 2) – 9:30 Neil Oliver: ‘By taking back control of the money we can begin regaining control of our world'  Breast health linked to eating peanut butter and nuts Washington University School of Medicine, September 27, 2022 By eating more peanut butter during their high school years, girls could be improving their breast health in adulthood, according to a US study published recently in the journal Breast Cancer Research and Treatment. Dr. Graham Colditz, of Washington University School of Medicine in St. Louis, and colleagues found that girls aged 9 to 15 who ate peanut butter and nuts twice a week were 39% less likely to develop benign breast disease by the age of 30 than girls who did not. Benign breast disease includes lumps or tender spots that turn out to be fibrous tissue and/or cysts, as well as other conditions like hyperplasia, an overgrowth of the cells that line the ducts in the glandular breast tissue. Although benign breast disease is not cancerous, it can raise the risk of developing breast cancer later in life. For their study, he and his colleagues looked at health data on over 9,000 American schoolgirls recruited to The Growing Up Today Study.  The data also included reports from the girls between when they were 18 to 30 years old, that indicated whether they had ever been diagnosed with biopsy-confirmed benign breast disease. When they compared the two sets of data, the researchers found that participants who had eaten peanut butter or nuts twice a week were 39% less likely than peers who never ate those foods to receive a diagnosis for benign breast disease. The data suggest pulse foods – soy and other beans and lentils – and corn may also be linked to reduced risk of benign breast disease, but because they did not feature as much in the diets of these girls, the evidence was not so strong.And they concluded that “consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD [benign breast disease] as young women.” Pine bark extracts may help curb age-related muscle loss; Study D'Annunzio University (Italy), September 28, 2022 Supplements containing the French maritime pine bark extract Pycnogenol may help stabilize muscle loss, support muscular function, and boosts daily muscle endurance, says a new study. Data from a study with 64 healthy seniors aged 70-78 indicated that 150 mg per day of Pycnogenol may improve muscle function and endurance in a range of everyday activities, from carrying items to climbing stairs and walking. Results published in Minerva Ortopedica e Traumatologica also indicated that supplementation with the pine bark was associated with a reduction in oxidative stress of 14%. Oxidative stress is reportedly a common measurement of sarcopenia which prevents the body from normal detoxifying and repair. “Supplementation with Pycnogenol – suppressing the excess in oxidative stress and controlling muscular pain and fatigue – possibly in association with some specific protein and vitamins supplementation, may produce faster muscular replacement and muscular remodeling improving physical functions and fitness. In this study, muscle loss appeared to be controlled and reduced,” wrote the authors from Irvine3 Labs and D'Annunzio University in Italy. Sarcopenia Muscle loss is a natural part of aging, and researchers have estimated that, after the age of 50, we lose 1-2% of our muscles each year. Strength declines as well, at a rate of 1.5% per year beginning at 50 years and accelerating to 3% after the age of 60. Results showed that the pine bark group experienced greater muscular function and endurance in daily tasks such as carrying items (4-5 lbs) (71% improvement versus 23% in the control group), climbing stairs (52 % improvement versus 20% in the control ground) and distance walked (38% improvement versus 17% in the control group). Supplementation with Pycnogenol was also associated with reduced proteinuria – the presence of protein in urine which, with normal kidney function, can indicate waste from muscle erosion – by 40%. In addition, individuals who took the pine bark extract supplements demonstrated improved general fitness scores by more than 46% in comparison with the control group. Study links prenatal phthalate exposure to reduced childhood lung function Barcelona Institute for Global Health, October 3, 2022 A study led by the Barcelona Institute for Global Health (ISGlobal) has found that exposure to phthalates in the womb is associated with reduced lung function during childhood. The findings of the study, published in Environmental Pollution, support the European Union's current restrictions on the use of these substances Phthalates are chemical compounds that are widely used as plasticizers, as well as in lacquers and varnishes. They are found in a wide variety of consumer products, ranging from toys to food packaging, clothing, detergents, cosmetics, solvents, etc. Over time, phthalates in these products leach into the surrounding environment—for example, into the air, dust and food—making them virtually ubiquitous. Moreover, human exposure to phthalates starts as early as in utero, given that these compounds are able to cross the placental barrier. Phthalates act as endocrine disruptors and have been associated with numerous developmental and reproductive health problems. “Research has consistently found that gestational phthalate exposure is associated with increased risk of childhood asthma, but the evidence on its possible association with lung function is scarce and unclear,” explained ISGlobal researcher Magda Bosch de Basea, lead author of the study. The study included 641 mother-child pairs from the INMA Project birth cohorts in Sabadell and Gipuzkoa. Gestational phthalate exposure was analyzed using urine samples collected from the mothers during pregnancy. The children's lung function was assessed by spirometry at various stages of development between the ages of four and eleven years. As an indication of the ubiquity of these compounds, laboratory analyses detected all nine of the studied phthalate metabolites—i.e., substances into which phthalates are transformed once metabolized by the human body—in nearly 100% of the urine samples examined. At all stages of development, the studied metabolites were associated with decreases in two lung function parameters: forced vital capacity (FVC), which measures the maximum volume of air a person is able to exhale, and forced expiratory volume in 1 second (FEV1), which measures the maximum exhaled volume in the first second of exhalation. T The researchers found that the associations between certain metabolites (e.g. MiBP and MBzP) and decreased lung function were generally statistically significant at younger ages, but not in spirometries performed in later years. This pattern is consistent with the findings of studies in animal models suggesting that the possible effects of these compounds on lung function revert over time. Eating late increases hunger, decreases calories burned, and changes fat tissue Brigham and Women's Hospital, October 4, 2022 A new study by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, found that when we eat significantly impacts our energy expenditure, appetite, and molecular pathways in adipose tissue. Their results are published in Cell Metabolism. “In this study, we asked, ‘Does the time that we eat matter when everything else is kept consistent?'” said first author Nina Vujović, Ph.D. “And we found that eating four hours later makes a significant difference for our hunger levels, the way we burn calories after we eat, and the way we store fat.” Vujović, Scheer and their team studied 16 patients with a body mass index (BMI) in the overweight or obese range. Each participant completed two laboratory protocols: one with a strictly scheduled early meal schedule, and the other with the exact same meals, each scheduled about four hours later in the day. In the last two to three weeks before starting each of the in-laboratory protocols, participants maintained fixed sleep and wake schedules, and in the final three days before entering the laboratory, they strictly followed identical diets and meal schedules at home. In the lab, participants regularly documented their hunger and appetite, provided frequent small blood samples throughout the day, and had their body temperature and energy expenditure measured. To measure how eating time affected molecular pathways involved in adipogenesis, or how the body stores fat, investigators collected biopsies of adipose tissue from a subset of participants during laboratory testing in both the early and late eating protocols, to enable comparison of gene expression patterns/levels between these two eating conditions. Results revealed that eating later had profound effects on hunger and appetite-regulating hormones leptin and ghrelin, which influence our drive to eat. Specifically, levels of the hormone leptin, which signals satiety, were decreased across the 24 hours in the late eating condition compared to the early eating conditions. When participants ate later, they also burned calories at a slower rate and exhibited adipose tissue gene expression towards increased adipogenesis and decreased lipolysis, which promote fat growth. Notably, these findings convey converging physiological and molecular mechanisms underlying the correlation between late eating and increased obesity risk. “This study shows the impact of late versus early eating. Here, we isolated these effects by controlling for confounding variables like caloric intake, physical activity, sleep, and light exposure, but in real life, many of these factors may themselves be influenced by meal timing,” said Scheer.  The immune system benefits from life in the countrysideAarhus University (Denmark), September 30, 2022Research from Aarhus University has demonstrated that exposure to a farming environment may prevent or dampen hypersensitivities and allergies — even in adultsAdults who move to farming areas where they experience a wider range of environmental exposures than in cities may reduce the symptoms of their hypersensitivities and allergies considerably. This is the result of new research from Aarhus University.This pioneering result was published online in the esteemed periodical, The Journal of Allergy and Clinical ImmunologyThe immune systems of people who work in farming are frequently exposed to a wide range of bacteria, fungi, pollen and other irritants which may trigger a response that protects them against hypersensitivity. Working in a farming environment may therefore serve to prevent or dampen hypersensitivity to the most widespread plant allergens: grass and birch pollen.Surprisingly, the positive effect on the immune system is seen both in people who have lived in urban environments and in adults who were born and raised in farming areas. But the real surprise is that the effect is not only seen in children:”Previously, the assumption was that only persons who had lived in farming areas while growing up would benefit from the environment's protective effect on the immune system. But now we can demonstrate that it's not too late simply because you are an adult,” says postdoc Grethe Elholm.It is, in other words, possible to affect the immune system and thereby the hypersensitivity which may cause allergy and allergic asthma − and what is more, this can be done at a much later point in life than previously assumed. High Blood Pressure Linked To Faster Cognitive Decline, Dementia Risk   University of Michigan, October 1, 2022 High blood pressure, or hypertension, often causes people to feel perpetually stressed out or angry. Now, researchers from the University of Michigan say people with hypertension may also experience a faster deterioration in their cognitive abilities (thinking skills, decision making, memory) in comparison to those with normal blood pressure. The team performed a “study of studies” focusing on high blood pressure's association with declining brain function over a period of several years. They gathered and analyzed datasets collected for six large prior studies. Originally, researchers set out to determine if fluctuations in long-term blood pressure control may somewhat explain why Hispanic Americans experience a 50-percent higher risk of developing dementia by the end of their lives in comparison to non-Hispanic white people living in the United States. Somewhat surprisingly, that study failed to produce a clear answer, as blood pressure-related cognitive decline appears to occur at about the same pace among Hispanics and Caucasians. Study authors conclude their work suggests other factors are at play regarding why Hispanics are generally more at risk of dementia. Still, these findings make a strong case that blood pressure has a connection to cognitive outcomes later in life. Maintaining a healthy blood pressure level looks to protect thinking skills, study authors say. “Our findings suggest that high blood pressure causes faster cognitive decline, and that taking hypertension medication slows the pace of that decline,” says lead study author Deborah Levine, M.D., M.P.H., director of the University of Michigan's Cognitive Health Services Research Program and a professor of internal medicine at the U-M's academic medical center, in a media release. Researchers examined changes in the thinking and memory abilities among a group of adults (18+) who took part in six long-term studies conducted over the past five decades. Study authors enjoyed access to an average of eight years' worth of data for each participant, including systolic blood pressure (the top number in any blood pressure reading). The  data encompassed 22,095 non-Hispanic white adults and 2,475 Hispanic adults. None of the participants had any documented history of stroke or dementia at the time of enrollment. To start, average systolic blood pressure was lower among Hispanic adults in comparison to non-Hispanic white adults (132.5 mmHg compared with 134 mmHg). This is especially notable considering Hispanic adults in the study displayed an older average age than non-Hispanic adults (62 versus 54 years-old). Blood pressure readings tend to increase with age. Among both Hispanics and non-Hispanics, the team observed the same pace of deteriorating thinking skills and memory linked to high blood pressure. However, when researchers focused solely on the two studies that had deliberately recruited Hispanics, they noted an undeniably faster decline in overall cognitive performance among Hispanics in comparison to the non-Hispanic white group. Importantly, though, blood pressure differences between those two groups didn't appear to explain this cognitive decline difference. This may be due to Hispanic participants having lower blood pressure than non-Hispanic whites in these studies, researchers speculate.The study is published in the Journal of Alzheimer s Disease.

Videos : New Rule: Let the Population Collapse | Real Time with Bill Maher (HBO) – 8:29 The De-Population Bomb – hoover institution (0:43 – 8:15) THE GREAT AWAKENING: PLANDEMIC 3 PRELAUNCH PARTY – (21:00 – 30:20) Gary Null Speaking Out at the NYS Assembly Hearing  (25:00)   Meta-analysis finds less fatigue with CoQ10 supplementation National Yang Ming Chiao Tung University (Taiwan), September 16 2022. The results of a systematic review and meta-analysis of clinical trials, published in Frontiers in Pharmacology, support an anti-fatigue effect among individuals who supplemented with coenzyme Q10. “Coenzyme Q10 (CoQ10) is a popular nutritional supplement and a lipid-soluble antioxidant that is endogenously produced by the human body,” authors I-Chen Tsai of National Yang Ming Chiao Tung University and associates observed. “CoQ10 supplementation has been successfully applied for reducing fatigue in patients with various conditions, including chronic fatigue and fibromyalgia, as well as in healthy subjects.” For their analysis, Tsai colleagues identified 13 randomized, controlled trials that compared fatigue scores of participants who received CoQ10 or a placebo. The trials included a total of 1,126 participants. Analysis of the 13 trials showed a consistent significant effect for CoQ10 in reducing fatigue. When trials that included healthy participants were analyzed separately from trials that included patients with fatigue-associated diseases, both supplemented populations showed decreases in fatigue, however the effects were significant among the unhealthy participants, who may have more severe CoQ10 depletion. Higher CoQ10 doses and longer duration of supplementation were correlated with increased fatigue reduction. The anti-fatigue effect of CoQ10 is unsurprising, given its role in energy production. Chronic fatigue syndrome patients have lower plasma levels of CoQ10 in comparison with healthy subjects. While the body makes some CoQ10, the authors remarked that studies have provided evidence that supplementing with CoQ10 does not affect the body's synthesis of the coenzyme. Researchers identify a potential new approach with a dietary supplement to treat HER2 positive breast cancer Mayo Clinic, September 9, 2022 Researchers at Mayo Clinic have identified an important new pathway by which HER2 positive breast cancers grow and have discovered that a dietary supplement called cyclocreatine may block the growth of HER2 positive breast cancer. Their findings were published in Cell Metabolism. “The HER2 receptor tyrosine kinase, which functions as an ‘on' or ‘off' switch in cellular functions, is a key driver of breast cancer, and is overexpressed in about a quarter of all breast cancers,” says Taro Hitosugi, Ph.D., a pharmacologist at Mayo Clinic and corresponding author of the paper. Dr. Hitosugi and his colleagues decided to explore ways to resolve an unmet clinical need. Their strategy was to develop a treatment to target tumor mitochondrial energy metabolism, which is the process cancer cells use to manipulate energy during cell metabolism in order to grow. Dr. Hitosugi and his colleagues discovered that cyclocreatine, a dietary supplement used in sports drinks, effectively targets mitochondrial creatine kinase 1 enzyme and reduces cancer growth without toxicity. This finding was confirmed in mice models where a patient-derived, trastuzumab-resistant HER2 positive tumors were administered to the mice. “Mitochondrial creatine kinase 1 may be a new drug target for the treatment of HER2 positive breast cancer,” says Matthew Goetz, M.D., director of the Mayo Clinic Breast Cancer research program. “Future clinical trials will be necessary to determine the effectiveness of this drug for HER2 positive breast cancer resistant to standard therapies.” Excessive smartphone screen time linked to earlier puberty onset Gazi University (Turkey), September 16, 2022 Exposure to blue light, via regular use of tablets and smartphones, may alter hormone levels and increase the risk of earlier puberty, according to data from a rat study presented at the Annual European Society for Paediatric Endocrinology Meeting. Longer duration of blue light exposure was associated with earlier puberty onset in the female rats, which also showed reduced levels of melatonin, increased levels of some reproductive hormones and physical changes in their ovaries. Use of blue light-emitting mobile devices has previously been linked to disrupted sleeping patterns in children but these findings suggest there could be additional risks for childhood development and future fertility. The escalating use of blue light-emitting devices, such as tablets and smartphones, has previously been implicated in reducing sleep quality in both children and adults. This is thought to be through disruption of our body clock as blue light inhibits the evening rise in levels of the hormone, melatonin, which prepares our bodies for rest and sleep. Melatonin levels are overall higher during pre-puberty than in puberty, which is believed to play a role in delaying the start of puberty. Puberty is a complex process that involves co-ordination of several body systems and hormones. In recent years, several studies have reported increases in early puberty onset for girls, particularly during the COVID-19 pandemic. The link between blue light exposure and reduced melatonin levels suggests that increased screen time, such as during the pandemic restrictions, may be playing a role in this reported increase. However, it is very difficult to assess this in children. In this study, Dr. Aylin Kilinç Uğurlu and colleagues in Ankara, Turkey, used a rat model to investigate the effects of blue light exposure on reproductive hormone levels and the time of puberty onset. Female rats were divided into three groups of six and exposed to either a normal light cycle, 6 hours or 12 hours of blue light. The first signs of puberty occurred significantly earlier in both groups exposed to blue light, and the longer the duration of exposure, the earlier the onset of puberty. Rats exposed to blue light also had reduced melatonin levels and elevated levels of specific reproductive hormones (estradiol and luteinizing hormone), as well as physical changes in their ovarian tissue, all consistent with puberty onset. At the 12-hour exposure, rats also showed some signs of cell damage and inflammation in their ovaries. Dr. Aylin Kilinç Uğurlu comments, “We have found that blue light exposure, sufficient to alter melatonin levels, is also able to alter reproductive hormone levels and cause earlier puberty onset in our rat model. In addition, the longer the exposure, the earlier the onset.” Fitness trackers reveal links among exercise, memory, and mental health Dartmouth College, September 15, 2022 Exercise can improve your cognitive and mental health—but not all forms and intensities of exercise affect the brain equally. The effects of exercise are much more nuanced, as specific intensities of exercise over a long period of time are associated with different aspects of memory and mental health, according to a new Dartmouth study. The findings are published in Scientific Reports and provide insight into how exercise could be optimized. “Mental health and memory are central to nearly everything we do in our everyday lives,” says lead author Jeremy Manning, an assistant professor of psychological and brain sciences at Dartmouth. “Our study is trying to build a foundation for understanding how different intensities of physical exercise affect different aspects of mental and cognitive health.” The researchers asked 113 Fitbit users to perform a series of memory tests, answer some questions about their mental health, and share their fitness data from the previous year. They expected that more active individuals would have better memory performance and mental health, but the results were more nuanced. People who tended to exercise at low intensities performed better at some memory tasks while those who exercised at a high intensities did better on other memory tasks. Participants who were more intensely active also reported higher stress levels, whereas people who regularly exercised at lower intensities showed lower rates of anxiety and depression. Participants who had been more active over the prior year tended to show better memory performance overall, but the specific areas of improvement depended on which types of activity people did. The researchers found that participants who often exercised at moderate intensities tended to perform better on the episodic memory tasks while participants who often exercised at high intensities did better on the spatial memory tasks. Sedentary participants who seldom exercised tended to perform worse on the spatial memory tasks. The researchers also identified connections between participants' mental health and their memory performance. Participants with self-reported anxiety or depression tended to perform better on the spatial and associative memory tasks, while those with self-reported bipolar disorder tended to perform better on the episodic memorytasks. Participants who reported higher levels of stress tended to perform worse on the associative memory tasks. Positive psychological well-being can improve overall heart health Northwestern University, September 10, 2022 Maintaining positive thoughts and feelings through intervention programs can help patients achieve better overall outcomes when it comes to their cardiovascular health, according to a review paper published in the Journal of the American College of Cardiology. “We addressed how social environment, psychological well-being and the effectiveness of intervention strategies can help strengthen a patient's outlook,” said Darwin R. Labarthe, MD, MPH, Ph.D., professor of Preventive Medicine at Northwestern University Feinberg School of Medicine and the review's lead author. “We focused on whether psychological well-being can be consistently related with a reduced risk of heart disease.” In this review, the authors looked at a growing body of research to examine whether psychological well-being might lead to reduced risk of heart disease. Prospective studies have shown a positive relationship between optimism (one facet of psychological well-being) and heart disease, including a study showing older women in the highest quartile of optimism had a 38 percent reduced risk of heart disease mortality. Additional studies since 2012 have associated a perceived higher purpose in life with lower odds of having a stroke. Optimistic patients sustained healthier diets by consuming more fruits and vegetables, and less processed meats and sweets, leading patients to maintain a healthy BMI. The review authors found that psychological well-being influenced heart health through biological processes, health behaviors and psychosocial resources. Having a strong network of social support also gives patients confidence about their future health and helps them act readily on medical advice, engage in problem solving and take active preventive measures. A likely link is that favorable social environment, known to influence heart disease risk, has also been shown to predict psychological well-being. Milk thistle protects against COPD caused by secondhand smoke Sichuan University, (China), September 11, 2022 According to the U.S. Centers for Disease Control and Prevention (CDC), 15.7 million people suffer from chronic obstructive pulmonary disease (COPD) – a serious respiratory condition which can cause scarring of the lungs, narrowing of the airway and extreme difficulty breathing. Taking enough milk thistle – on a regular basis – can help protect you from harm. Exposure to tobacco smoke – whether through actively smoking or simply inhaling the smoke from another's cigarette – is the primary cause of COPD. Although Western medicine currently offers no cure for COPD, recent studies generate a ray of hope. Groundbreaking new research suggests that milk thistle extracts may not only prevent COPD but, help to treat it. In a study published in the journal Inflammation, researchers exposed mice to the equivalent of 1.5 packs of cigarettes a day for four weeks, creating drastic increases in peribronchial inflammation, thickening of airway walls and airway obstruction. The team found that pretreating the mice with silymarin – the active component of milk thistle – an hour before exposure dramatically decreased inflammatory changes, and cut production of pro-inflammatory chemicals such as TNF-alpha and interleukin. Encouragingly, silymarin also helped safeguard levels of superoxide dismutase, an important disease-fighting antioxidant produced in the body. A year later, the same team of researchers took another, closer look at the workings of milk thistle. And what they found was encouraging. In a study of human bronchial cells published in Scientific Report, the team explored the molecular and cellular mechanisms of silymarin – and found once again that the flavonoid attenuated cigarette smoke-induced upregulation of pro-inflammatory chemicals. And, researchers discovered for the first time that silymarin modulated a certain pathway – known as MAPK – that governs inflammation. The takeaway? The team concluded that silymarin might be “an ideal agent for treating inflammatory pulmonary diseases.” In a third study, recently published in Food and Chemical Toxicology, researchers treated mice with silibinin (a constituent of silymarin) one hour before exposure to cigarette smoke. The team found that the silibinin caused the mice to not only experience the sharp reductions in inflammatory changes seen in earlier studies – but discovered that it also suppressed the scarring and fibrosis that are typical of COPD in humans. This means that silibinin may not only help prevent COPD – but, reverse it! Intriguingly, the silibinin directly affected the expression of a certain pro-inflammatory protein – transforming growth factor beta-1 – that is activated and spurred on by exposure to smoke, making it appear that this compound is custom-designed to protect against secondhand smoke. Milk thistle extracts are available in the form of pills, powders, extracts, liposomes and teas. Look for a high-quality preparation that is standardized to contain 70 to 80 percent silymarin.

Society has come up with every diet imaginable in our journey toward living healthy, but rates of obesity continue to rise. Food journalist Mark Schatzker argues that tampering with the food we eat has harmed our ability to properly feed ourselves. MARK SCHATZKER is the author of The End of Craving, The Dorito Effect and Steak. He is a writer in residence at the Modern Diet and Physiology Research Center, which is affiliated with Yale University. His writing has appeared in the New York Times, the Wall Street Journal, Best American Travel Writing and Annual Review of Psychology. He lives in Toronto. LINKS Check out Mark Schatzker on Twitter, Instagram, and LinkedIn. See his website https://www.markschatzker.com for links to purchase his books. See some scientific studies mentioned in the interview and Schatzker's book:  • This 2020 in Cell Metabolism shows how artificial sweeteners can reduce insulin sensitivity and blunt brain response to sucrose https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30057-7 • This 2017 study in Current Biology suggests how artificial sweeteners disrupt normal physiological responses to carbohydrate ingestion https://www.cell.com/current-biology/fulltext/S0960-9822(17)30876-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS096098221730876X%3Fshowall%3Dtrue Learn more about Canada's permitted food additives and how they are regulated here.  https://www.canada.ca/en/health-canada/services/food-nutrition/food-safety/food-additives.html INSIGHTS 1. The stigma against people with obesity is that they are overindulgent or weak. “This is absolutely wrong,” says Schatzker. Instead, the brains of obese people respond to food differently. For example, at the sight of food, research has shown that obese people experience a spike in dopamine levels in their brains' reward centres. “The difference,” says Schatzker, “is one of craving.” 2. “We always thought that sweetness is this indulgent, enjoyable sensation,” says Schatzker. “It's actually like an instruction manual… for how much energy we're getting.” When our food contains additives like artificial sweeteners or fat replacers, it tastes like it should contain more sugar or fat than it actually does. “When there's this mismatch… the brain doesn't know what to do,” Schatzker says. “It kind of throws up its hands.” The uncertainty of how much energy we're getting leads the body to want to eat more, just to cover its bases. Which explains the obesity crisis in North America, where so much of the diet is processed (a.k.a. mismatched) food.  3. “We tend to think that our appetite is primitive and unhinged, and that there's something wrong with food,” says Schatzker. As a result, we've been adding things to our food to change its taste, texture, shelf-life or caloric content, and these additives have been directly altering our brains and the amount of food that we're driven to eat. To make matters worse, these additives are difficult to spot on ingredient labels. They're often called things that sound healthy and natural, like citrus fibre or milk protein (both fat replacers). 4. “If delicious food is a guilty pleasure, you would expect that Italians would be the heaviest people in the world,” says Schatzker. In fact Italy has one of the world's lowest obesity rates, and he credits that to Italy's cultural attitude toward mealtime, home cooking and savouring. “Eating is meant to be deeply pleasurable, so don't be afraid to enjoy real food. That's the way it's meant to be eaten,” he says. The content of our show is educational only. It does not supplement or supersede the professional relationship and direction of your healthcare provider. Always seek the advice of your physician or other qualified mental health providers with any questions you may have regarding a medical condition, substance use disorder, or mental health concern.