Podcasts about aminobutyric

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.05.547662v1?rss=1 Authors: Zhao, X., Zhang, Y. E., Yang, L., Yang, Y. Abstract: The mammalian neocortex receives extensive cholinergic projections from the basal forebrain. Although it has been shown that acetylcholine (Ach) participates in learning-associated cortical plasticity, it's not clear whether Ach can directly modulate structural changes of cortical synapses. Using in vivo two-photon microscopy, we show that optogenetic and chemogenetic stimulation of cholinergic neurons in mouse basal forebrain leads to an increase in spine formation on apical dendrites of layer (L) 5 pyramidal neurons in auditory cortex and posterior parietal cortex, and these newly formed spines follow similar spatial rules as the spontaneously formed new spines. Selective blockage of Ach receptors (AchRs) revealed that nicotinic AchRs, but not muscarinic AchRs, are involved in the stimulation-triggered spine formation. Furthermore, {gamma}-Aminobutyric acid (GABA) transmission is required in this process, indicating that acetylcholine acts through GABAergic connections in promoting spine formation. Together, our findings demonstrate that acetylcholine can induce spine formation in both sensory and higher-order cortices, via activating nicotinic AchRs through GABAergic local circuitry. Our work established a direct link between Ach release and cortical spine formation in vivo, and shed light on synaptic mechanisms underlying Ach-associated cortical remapping and learning-induced plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.09.515792v1?rss=1 Authors: Altinok, A., Karabay, A., de Jong, J., Balta, G., Akyurek, E. G. Abstract: {gamma}-aminobutyric acid (GABA) is a primary inhibitory neurotransmitter that plays a significant role in the central nervous system. Studies on both animals and humans show it has the pharmacological potential for reducing the impact of cognitive disorders, as well as enhancing cognitive functions and mood. However, its specific effects on human attention and working memory have not yet been extensively studied. In this randomized, double-blind, placebo-controlled, and crossover trial, we tested whether the administration of 800 mg GABA, dissolved in a drink, acutely affected visual working memory maintenance, as well as temporal and spatial attention in healthy adults. The participants were 32 young adults (16 females and 16 males). Working memory recall precision, spatial attention and temporal attention were measured by a delayed match-to-sample task, a visual search task, and a speeded rapid serial visual presentation task, respectively. Participants completed two experimental sessions (GABA and Placebo) in randomized and counterbalanced order. In each session, forty-five minutes after administration of the drink, they completed the aforementioned cognitive tasks. Linear mixed model analysis results showed that GABA increased visual search time, compared to the placebo, but did not affect visual search accuracy, temporal attention, nor visual working memory precision. The results suggest that GABA increases visual search time but does not affect temporal attention and memory, and that previously reported effects on cognition might rely on other functions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Part 2 of how NUTRITION has a HUGE impact on your BRAIN! Everything in your brain is something you ate, something you made from something you ate, or, in a few cases, something your mother ate. Nutrition impacts your mental and emotional health, the function of your five senses, and your conscious and unconscious control over your body movements. Join me as I lead you in a safari through the textbook, “Neuroscience,” pointing out along the way all the interesting connections to nutrition. Listen in for part 2 on the NEUROTRANSMITTERS! 0:00:37     Cliff Notes 0:04:15     Overview of neurotransmitters 0:06:55     Glutamate is the primary excitatory neurotransmitter. 0:14:08      De novo glutamate in the central nervous system is overwhelmingly made from glucose. 0:16:55     Ketogenic diet for epilepsy 0:20:12    Glutamate metabolism 0:23:42    There are two classes of glutamate receptors: ionotropic and metabotropic. 0:24:45     There are three classes of metabotropic glutamate receptors, their actions are complex and variable, and they can be excitatory or inhibitory. 0:25:05     The ionotropic glutamate receptors include AMPA receptors, NMDA receptors, and kainite receptors, all of which have a depolarizing effect by allowing sodium and potassium to flow freely through them. 0:27:47     Four unique things about the NMDA receptor: magnesium is required to block its ion channel, it's important for coincidence detection, it allows calcium to come into the cell, and it has a glycine-binding site. 0:33:16     Long-term potentiation (LTP) and long-term depression (LTD) are important for forming memories, and glutamate receptors play an important role. 0:40:48     GABA and glycine are the two primary inhibitory neurotransmitters of the central nervous system. 0:44:04     GABA and presumably glycine can be stimulatory if there is more chloride on the inside of the neuron than the outside. 0:48:53     Evidence that GABA might cross the blood-brain barrier 0:51:44     GABA in foods 0:54:14     GABA metabolism in the nervous system 0:56:08     Glycine 1:02:02     Acetylcholine 1:07:50     The biogenic amines include histamine, serotonin, and the catecholamines (dopamine, norepinephrine, and epinephrine). 1:08:30     Synthesis of the catecholamines 1:10:46     Dopamine 1:14:08     Norepinephrine 1:16:32     Histamine 1:20:15     Serotonin 1:23:10     ATP and adenosine 1:26:38     Peptide neurotransmitters 1:27:00     Hypothalamic releasing hormones include thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), and gonadotropin-releasing hormone (GnRH). 1:29:15     Melanocyte-stimulating hormone (MSH) 1:29:32     Oxytocin 1:30:18     Vasopressin 1:30:57     Synthesis of the neuropeptides Substance P, MSH, oxytocin, and vasopressin requires glycine, zinc, copper, and vitamin C. 1:34:24     Endocannabinoids and the importance of arachidonic acid, EPA, and DHA Nutrition in Neuroscience Related Content Chris Masterjohn Lite: Could Oxaloacetate Supplements Help With Glutamate Sensitivity? Chris Masterjohn Lite: 5 Ways to Help With Glutamate Sensitivity and Glutamate Dominance Chris Masterjohn Lite: Does Glycine or GABA Wake You Up? Chris Masterjohn Lite: Carbs or Keto for Sleep? Chris Masterjohn Lite: How to Manage Your Magnesium Status Mastering Nutrition: Why You Need Glycine -- A Panel Discussion Balancing Methionine and Glycine in Foods: The Database  Chris Masterjohn Lite: Get Better Sleep With Glycine Start Here for Methylation has glycine and choline resources, and covers the methylation process used in the synthesis and degradation of biogenic amines. Mastering Nutrition: Methylate Your Way to Mental Health With Dopamine The Pursuit of Happiness: How Nutrient-Dense Animal Fats Promote Mental and Emotional Health, covers the endocannibinoids. Testing Nutritional Status: The Ultimate Cheat Sheet is a comprehensive guide for testing nutritional status for all the nutrients discussed in this episode, and more. Use the code MASTERINGNUTRITION for $5 OFF. Nutrition in Neuroscience Research The textbook, Neuroscience. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. on the use of GABA for fear of heights and to alter anxiety- and focus-related brain waves. γ-Aminobutyric acid (GABA) administration improves action selection processes: a randomised controlled trial on use of GABA to improve decision-making under pressure. Desarrollo de un pan de masa madre rico en GABA y péptidos IECA contains a table on the GABA content of foods on page 84 of the PDF. Acetylcholinesterase inhibitor from plants on the different plants containing natural acetylcholinesterase inhibitors. A Mass Spectrometry-Based Method to Screen for α-Amidated Peptides on the neuropeptides that require glycine, vitamin C, copper, and zinc for their biological activity. Effects of copper occupancy on the conformational landscape of peptidylglycine α-hydroxylating monooxygenase also on the neuropeptides that require glycine, vitamin C, copper, and zinc for their biological activity.

Just in time for spooky season we explore a treat of a fine spirit with a tricky past. Absinthe: what it is, how it behaves in the glass, the deal on wormwood, a brief history, and some thujone theory. Please absinthe responsibly, and apologies for the historical nugget on dog flatulence. Resources from this episode: Books: Absinthe: History in a Bottle, Conrad, B. (1988) The Drunken Botanist: The plants that create the world's great drinks. Stewart, A. (2013) The Greater Journey: Americans in Paris, McCullough, D. (2012) Society of Wine Educators: Certified Specialist of Spirits (CSS) Study Guide, Nickles, J. (2020) Academic Journals/Papers: Chemistry Central Journal (5:44): Determination of the biologically active flavour substances thujone and camphor in foods and medicines containing sage (Salvia officinalis L.), Walch, S. Kuballa T., Stühlinger, W., Lachenmeier, D., (21 July 2011) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155476/ Proceedings of the National Academy of Sciences of the United States of America (97(8)): α-Thujone (the active component of absinthe): γ-Aminobutyric acid type A receptor modulation and metabolic detoxification, Höld, K., Sirisoma, N., Ikeda, T., Narahashi, T., Casida, J., (11 April 2000), pp. 3826 - 3831, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18101/ Websites: Cocktail Safe: Wormwood and thujone safety information for cocktails https://www.cocktailsafe.org/wormwood-and-thujone.html The Spirits Business: The 10 most famous absinthe drinkers, Hopkins, A. (2014) https://www.thespiritsbusiness.com/2014/08/the-10-most-famous-absinthe-drinkers/ The Nachtkabarett: Mansinthe, Kushner, N. http://www.nachtkabarett.com/mansinthe Wormwood Society: Absinthe Original D- Don't believe the hype, Robinson, B., (24 November 2009) https://wormwoodsociety.org/index.php?option=com_content&view=article&id=665&catid=16&Itemid=233 Podcasts: Glass in Session® Winecast: S1E2: Aperitif Wines (2019) https://glassinsession.libsyn.com/s1e2-aperitif-wines Wine Two Five: Anise Spirits and a Nice (Wine!) Surprise (2018) https://podcasts.apple.com/us/podcast/anise-spirits-and-a-nice-wine-surprise/id986650051?i=1000415280141 Wine Two Five: Boos & Booze: Spooky Wine & Spirits Stories (2015) https://podcasts.apple.com/us/podcast/boos-booze-spooky-wine-spirits-stories/id986650051?i=1000355843969 Glass in Session® is a registered trademark of Vino With Val, LLC. Music: “Write Your Story” by Joystock (Jamendo.com cc_Standard License, Jamendo S.A.)

We live in a fast-paced world, with more everyday demands. And we know that we need good health to keep up. Nutrition, exercise, and mindfulness are often hailed as important pillars. However, there is something even more fundamental for better health—sleep. Sleep ensures we can actually perform. With better sleep, we'll be living better lives. But, how many of us actually prioritise sleep?     Dr Kirk Parsley joins us in this episode to explain how sleep affects our lives. Poor sleep can significantly change our bodies and performance. He also shares that we can achieve good sleep through lifestyle changes. A better life is not about taking more supplements or using gadgets and tools; it's about creating new and better habits.  If you want to know more about the science of sleep and how sleep affects our lives, then this episode is for you.    Here are three reasons why you should listen to the full episode: Learn how sleep affects our lives and why it is so fundamental to our health.  Understand that it's more important to change our behaviours and lifestyle rather than depending on supplements.  Discover the ways we can create the right conditions for better sleep.     Resources Get Dr Kirk's Sleep Remedy here!  Gain exclusive access and bonuses to Pushing the Limits Podcast by becoming a patron!  A new program, BoostCamp, is coming this September at Peak Wellness!  Listen to my other Pushing the Limits episodes:  Episode with Mark Divine Connect with Dr Kirk: Website I LinkedIn I Instagram I Facebook I Email  You can also get the free downloadable resource on decreasing stress before sleep here.   The Unbeatable Mind Podcast with Mark Divine Dr. Kirk Parsley - How to Supercharge Your Sleep Dr. Kirk Parsley on Sleep And Longevity Melatonin Supplementation with Dr John Lieurance in the Ben Greenfield Fitness podcast.     Melatonin: The Miracle Molecule by Dr John Lieurance Dr Harch's Hyperbaric Oxygen Therapy America's Frontline Doctors How to save the world, in three easy steps. from Bret Weinstein's DarkHorse Podcast   Get Customised Guidance for Your Genetic Make-Up For our epigenetics health programme, all about optimising your fitness, lifestyle, nutrition and mind performance to your particular genes, go to  https://www.lisatamati.com/page/epigenetics-and-health-coaching/.   Customised Online Coaching for Runners CUSTOMISED RUN COACHING PLANS — How to Run Faster, Be Stronger, Run Longer  Without Burnout & Injuries Have you struggled to fit in training in your busy life? Maybe you don't know where to start, or perhaps you have done a few races but keep having motivation or injury troubles? Do you want to beat last year's time or finish at the front of the pack? Want to run your first 5-km or run a 100-miler? ​​Do you want a holistic programme that is personalised & customised to your ability, goals, and lifestyle?  Go to www.runninghotcoaching.com for our online run training coaching.   Health Optimisation and Life Coaching If you are struggling with a health issue and need people who look outside the square and are connected to some of the greatest science and health minds in the world, then reach out to us at support@lisatamati.com, we can jump on a call to see if we are a good fit for you. If you have a big challenge ahead, are dealing with adversity, or want to take your performance to the next level and want to learn how to increase your mental toughness, emotional resilience, foundational health, and more, then contact us at support@lisatamati.com.   Order My Books My latest book Relentless chronicles the inspiring journey about how my mother and I defied the odds after an aneurysm left my mum Isobel with massive brain damage at age 74. The medical professionals told me there was absolutely no hope of any quality of life again, but I used every mindset tool, years of research and incredible tenacity to prove them wrong and bring my mother back to full health within three years. Get your copy here: https://shop.lisatamati.com/collections/books/products/relentless. For my other two best-selling books Running Hot and Running to Extremes, chronicling my ultrarunning adventures and expeditions all around the world, go to https://shop.lisatamati.com/collections/books.   Lisa's Anti-Ageing and Longevity Supplements  NMN: Nicotinamide Mononucleotide, an NAD+ precursor Feel Healthier and Younger* Researchers have found that Nicotinamide Adenine Dinucleotide or NAD+, a master regulator of metabolism and a molecule essential for the functionality of all human cells, is being dramatically decreased over time. What is NMN? NMN Bio offers a cutting edge Vitamin B3 derivative named NMN (beta Nicotinamide Mononucleotide) that can boost the levels of NAD+ in muscle tissue and liver. Take charge of your energy levels, focus, metabolism and overall health so you can live a happy, fulfilling life. Founded by scientists, NMN Bio offers supplements of the highest purity and rigorously tested by an independent, third party lab. Start your cellular rejuvenation journey today. Support Your Healthy Ageing We offer powerful, third party tested, NAD+ boosting supplements so you can start your healthy ageing journey today. Shop now: https://nmnbio.nz/collections/all NMN (beta Nicotinamide Mononucleotide) 250mg | 30 capsules NMN (beta Nicotinamide Mononucleotide) 500mg | 30 capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 250mg | 30 Capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 500mg | 30 Capsules Quality You Can Trust — NMN Our premium range of anti-ageing nutraceuticals (supplements that combine Mother Nature with cutting edge science) combats the effects of aging while designed to boost NAD+ levels. Manufactured in an ISO9001 certified facility Boost Your NAD+ Levels — Healthy Ageing: Redefined Cellular Health Energy & Focus Bone Density Skin Elasticity DNA Repair Cardiovascular Health Brain Health  Metabolic Health   My  ‘Fierce' Sports Jewellery Collection For my gorgeous and inspiring sports jewellery collection, 'Fierce', go to https://shop.lisatamati.com/collections/lisa-tamati-bespoke-jewellery-collection.   Episode Highlights [03:28] How Dr Kirk Started Working on Sleep Dr Kirk used to work for the SEALs. Later on, he enrolled in the military's medical school. After getting his degree, Dr Kirk became the manager of a sports medicine facility for the military. Here, he worked with other medical experts.  Those in the military will usually lie to healthcare providers so they won't get excluded from work, but they tend to be more honest with Dr Kirk because they have worked with him before.  After testing for vitamin deficiencies and adrenal fatigue, Dr Kirk realised that many of his patients were taking Ambien, a sleeping drug.  After learning more about sleep, Dr Kirk realised that every symptom his patients were presenting could be explained by poor sleeping.  [17:31] Sleep's Various Cycles With a sleep drug, you are just unconscious and not sleeping.  Proper sleep needs to go through a repetitive pattern of deep sleep at the beginning of the night and then REM sleep by morning.  The different cycles are important since they affect our bodies in different ways.  Sleep can help boost your immunity and memory! Learn more benefits in the full episode.  [20:12] How Sleep Affects Our Lives If you don't give yourself time to recover, sleep pressure can accumulate and have progressively worse effects.  If you go to bed with high stress hormones, this can worsen your sleep. Poor sleep then leads to higher stress levels, and the cycle gets worse.  People who get poor sleep age faster, not just in appearance but also in their physiology.  Poor sleep can lead to protein structure breakdown, decreased blood supply, aged tissues, and more.  As we age, we also face the problem of not repairing as fast. This is how sleep affects our lives.  [23:56] The Foundation For Better Health We are often taught the basics of health are sleep, nutrition, exercise, and stress management.  However, these pillars cannot function without sleep as their foundation, emphasising how sleep affects our lives.  For example, exercise becomes counterproductive when you're sleep deprived because you're not recovering.  Poor sleep can also change your insulin sensitivity and gut biome, which changes your nutrition levels. Because of how sleep affects our lives, it should be our priority. Sleep deprivation is the fastest way to break someone down, this is why it's used as an interrogation technique.    [28:35] How Do We Sleep? We need eight hours of sleep a night. Make your sleeping routine simple. The more complex it is, the more likely you will fail.  First, convince yourself that sleep is important.  We are all born to sleep, and we don't need to learn how.  Before electricity, people used to fall asleep three hours after sunset. Tune in to the full episode to learn more about the neurochemical process of sleep.   [35:36] Creating the Right Conditions for Sleep During sleep, our senses still work, but they don't pay as much attention to external stimuli.  For our ancestors, the sunset will lead to decreased blue light, decreased temperature, decreased stimuli, and increased melatonin.  Better sleep is just creating these conditions in our environment.  If we take melatonin, we should be careful to take only small amounts.  [39:20] Melatonin Supplementation Some have argued that melatonin supplementation does not downregulate our brain receptors, but there are no definitive studies on this yet.  In fact, measuring melatonin is difficult due to its quantity and concentration in each part of the brain.  It's okay to take melatonin supplements but not in physiologic amounts.  [45:15] Can We Reverse Aging? You need to understand your genetics and what ratios will work for you.  While good habits and supplements can improve your overall health, we don't know if it undoubtedly reverses age.  Our bodies are more complex than we think. Shorting yourself two hours of sleep can change over 700 different epigenetic markers.  We can only describe biology. We don't know how to manipulate it most of the time.  Dr Kirk also shares his experience with hyperbaric oxygen therapy in the full episode.  [1:03:36] Paradigm Shifts in the Medical Industry There is a lot of dishonesty in both the media and the medical industry.  Many doctors and medical experts have been silenced on potentially better cures, especially during this pandemic.  Western medicine is effective in treating the sick, but it doesn't keep people from getting severely sick in the first place. A lifestyle change is more important than taking supplements.  [1:12:22] The Importance Of Behaviour Change  People often don't want to work on their behaviour because taking medicine is easier.  We also need to be aware of how the food industry is tapping into our addictive mechanisms to keep us eating more.   Caffeine consumption can also ruin our sleep. More than 200 milligrams can give the opposite effect of staying awake and alert.  Learn exactly how sleep affects our lives, together with caffeine and sugar consumption, when you listen to the full episode. [1:19:40] Widespread Impressions on Sleep and How It Affects Our Lives People have grown to believe that sleep is for the weak and lazy.  This belief also impacts our children, especially since they are still developing.  Losing two hours of sleep can decrease testosterone and growth hormone by 30% and increase inflammation by 30%, among others.   Dr Kirk delved into researching how sleep affects kids after giving a lecture for American kids overseas to professionals in the school system. Kids' brains are still developing. The prefrontal cortex, the part of the brain that allows us to simulate things, experiences a shift during adolescence. [1:26:34] How Sleep Affects Our Lives as Kids Dr Kirk delved into researching how sleep affects kids after giving a lecture for American kids overseas to professionals in the school system. Kids' brains are still developing. The prefrontal cortex, the part of the brain that allows us to simulate things, is formed during adolescence. Furthermore, adolescents also require more sleep because of a shift in their circadian rhythm. Requiring kids to do more with less sleep interferes with their development. [1:31:40] How Sleep Affects Our Lives When We are Sick A new field in medicine called chronobiology is studying how sleep deprivation precedes any psychiatric disease or psychological flare-up. An Ivy League hospital managed to get their patients off medication by regulating their circadian rhythm and chronobiology. [1:34:34] It's More Than Switching Things On and Off Medications can be difficult to get off because they have too many side effects.  For example, most antidepressants are not just working on serotonin. Instead, they affect several neurotransmitters as well.  Physiological doses are artificial and can cause you more trouble.  Learn how sleep medication and affects GABA receptors that slow down the brain when you listen to the full episode. [1:41:17] Dr Kirk's Sleep Remedy Dr Kirk discusses how cavemen took around three hours after the sun went down to fall asleep. In the present day, what can people do in those three hours? To fall asleep, stress hormones need to come down due to lifestyle. Dr Kirk's Sleep Remedy involves getting the proper ratios of substances. His product comes in the form of tea, stick pouches, and capsules.  [1:46:27] Dr Kirk's Final Advice Change your environment by decreasing blue light and stimulation.  Learn to slow everything down.  Just like how you slow everything down to get a kid to sleep, so should you do the same for an adult.   7 Powerful Quotes ‘You aren't actually sleeping when you're on sleep drugs. You're just unconscious. Your brain is dissociated, but it's not sleep.' ‘Often, if you're sleep-deprived, more is worse for sure. You don't really need to do any exercises. You just stay active until you've recovered, and then you can exercise again.' ‘Insulin sensitivity is decreased by 30%, just by losing two hours of sleep. One night with two hours of sleep. So you go from sleeping eight hours of sleep to six. If you're pre-diabetic, you're waking up diabetic.' ‘Even though I'm known for sleep, the hardest thing for me to coach people to do is to sleep.' ‘The most sleep-deprived years are the most horrible years of the brain development.' ‘Get rid of the blue light. Decrease the stimulation. Lower your body temperature. That's sleep hygiene.' ‘Part of lowering stress is just slowing down your thinking. You can't work on your computer until 9:59 and get in bed in 10 and think you're gonna be asleep.'   About Dr Kirk Dr Kirk Parsley was a former Navy SEAL who went on to earn his medical degree from Uniformed Services University of Health Sciences (USUHS) in Bethesda in 2004. From 2009 to 2013, he served as an Undersea Medical Officer at the Naval Special Warfare Group One. He also served as the Naval Special Warfare's expert on sleep medicine.  Dr Kirk has been a member of the American Academy of Sleep Medicine since 2006 and consults for multiple corporations and professional athletes. He gives lectures worldwide on wellness, sleep, and hormonal optimisation. He believes that many diseases and disorders are unnecessary complications of poor sleeping habits. We can achieve the highest quality of life possible by changing this habit problem.  Interested in Dr Kirk's work? Check out his website. You can also reach him on LinkedIn, Instagram,  Facebook, and email.       Enjoyed This Podcast? If you did, be sure to subscribe and share it with your friends! Post a review and share it! If you enjoyed tuning in, then leave us a review. You can also share this with your family and friends so they can learn how sleep affects our lives and what we can do about it. Have any questions? You can contact me through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts. To pushing the limits, Lisa   Full Transcript of the Podcast Welcome to Pushing the Limits, the show that helps you reach your full potential with your host Lisa Tamati, brought to you by www.lisatamati.com. Lisa Tamati: Well, hey everyone! And welcome to Pushing The Limits. This week, I have another amazing guest for you. I managed to get some incredible people. I have Dr Kirk Parsley with me. He is an ex-Navy SEAL, and also a medical doctor. A little bit of an overachiever, this one. He spent many years in the SEALs, an incredible man. He also was involved with the first sports medicine rehabilitation centre that was working with the SEALs, an incredible expert on sleep. And that's what we do a deep dive into today. We also talk about hyperbaric oxygen therapy. We also go into areas about the current state of the medical system, one of my favourite topics. And I hope you enjoy this episode. It's really, the most important thing is around sleep.  Sleep is something that all of us, I think, are underestimating its importance. And that this is the biggest lever, not food, not exercise, not meditation, not mindfulness, not anything else. Number one of all leverage points is sleep. So how the heck do you get enough sleep? What is enough sleep, and how to get it is what this episode is about.  Before we head over, I just want to remind you we have Boost Camp coming up. This is our eight-week live online program. There, Neil Wagstaff and I, my business partner and longtime friend and coach are doing. And we're going to, if you want to come and hang out with us live every week and learn everything about upgrading your life, basically, your performance, how to optimise all areas of your life, then we would love you to check the information out, head over to peakwellnessco.nz/boostcamp.  On that point, if you're also interested, come and check out our flagship program, which is our epigenetics program, where we look at your genetics, and how to optimise those specifically, all the areas of your life: your food, your nutrition, your exercise, your mood, and behaviour, your hormones, all these important areas, specifically to your genetics. One-on-one time with us and help us to understand everything about your genetics. It's an incredible platform and amazing AI technology behind us. And we'd love you to check that out.  Go to peakwellnessco.nz/epigenetics. Or reach out to me if you didn't get that. We will also have the links down in the show notes, if you want to just click over to that. Or you can just head over to my website, www.lisatamati.com. And hit the work with us button for our programs listed on there as well. So without further ado, now over to Dr Kirk Parsley.  Well, hi, everybody! And welcome to Pushing the Limits. This week, I have a superstar, who is a good friend of Commander Mark Divine, you may have heard previous weeks on my podcast. We have Dr Kirk Parsley with us today. Welcome to the show.  Dr Kirk Parsley: Thank you. I feel very welcome and happy to be here. I'm still here. I'm happy to be sharing this airspace with you or whatever it is sharing.  Lisa: I'm really super excited. I've heard you a number of times on Mark's show and just thought how hefty you're on because you're such an expert. We're gonna dive into a little bit into your background, but you're an absolute sleep expert. So I'm really keen to help my audience with their sleep, and their sleep patterns, and all of that good stuff. But before we get into that, we were just chatting about genetics and endurance. So, give us a little background. You've been a Navy SEAL. You've been in the military, in the naval military. So give us a bit of background on yourself, personally. Dr Kirk: Yes. So ironically, I actually dropped out of high school. I was a terrible student my whole life, didn't have any interest in school. And after you don't do well for long enough, you just convince yourself that you can't do well. And so you're just, ‘I'm just done. I can't do it'. I was always very physical, very athletic. Just fortunately, genetic lottery, I won, just be an athletic and strong guy. And it came pretty easy to me. But I worked hard at it because I didn't do school work. So when I dropped out of high school, to join the military and do the hardest training in the world. And that was what the SEAL training was supposed to be, as the toughest training in the world like, ‘Well, I'm gonna go do that.' So I went to do that.  This was a way long time ago. This is 1988. So, it was long before anybody knew what SEALs were. They didn't have the notoriety they have now for sure. And when I would come home from the Navy and tell people as I was a Sealer, like, ‘What do you mean, you work for SeaWorld or something? What do you do?' Kinda. So, I went through SEAL training, I would say I made it through SEAL training, I became a SEAL. That was pre-9/11, obviously. So we didn't have the combat that the SEALs of this generation do. So it's not really comparable. We were still mainly working in Southeast Asia doing police work and training other militaries.  I did three deployments. It was really the same thing over, and over, and over again because there was no combat. So you just did the same training, and then you deployed, and then came home, and you did the same training. And of course, I was like, ‘Maybe, I'll go do something else.' And I thought I would be—I was dating a woman who would become my wife. She was getting a master's in physical therapy. And I was reading her textbooks on deployment to make myself a better athlete. And I thought, maybe I could be a physical therapist. And so I started working, I started volunteering in a physical therapy facility in San Diego, called San Diego Sports Medicine Center. And it had every kind of health care provider you could possibly imagine. And this building, it's just this healthcare Mecca. It's the most holistic thing I've ever seen to this day.  I decided pretty quickly, I didn't want to be a physical therapist, but I don't know what else I wanted to do. But I got to follow the podiatrist around, and acupuncturist, and massage therapists, and athletic trainers, and conditioning coaches, and the orthopedist, and the family practice, and the sportsmen. I just got to follow them around and see how everybody worked. And a group of young doctors there, who were probably only five or six years older than me, and they were saying, ‘Well, you should go to medical school.' And I was like, ‘Pump the brakes, kiddo. I didn't even graduate high school. I'm not getting into medical school.' And then the senior doctor overhears the conversation. He comes out of the office. And he says, ‘Kirk, the question isn't, “Can you get in?” The question is, “Would you go if you've got in?”' And I said, ‘Of course, I'd go.' So, well, there you have it. So, he sort of shamed me into it/  I studied hard and got really good grades. And then when it came time to apply for medical school, this was pre-Internet, so you had to go to the bookstore and get your book review and look and see what schools are competitive for. And when I was going through one of those books, I found out that the military had their medical school. The military was a closed chapter in my mind. I'd done that. That's something that I figured I'd always do in my life. But it was never meant to be my whole life. And so I had done that. I was, I figured I was done. But I was already married and had kids. And I was like, ‘Well, the military will pay me to go to medical school. Or I can pay someone else to go to medical school and my wife can work while we're in medical school.'  I made enough to support my family and go to medical school for free. And then to pay off in the military's, they'll train you to do anything. You have to give them years of service and your job. So once you finish your medical training, you have to be a doctor for the military for eight years. And so I figured, ‘I'll get back to the SEAL teams, I'll go pay something back to the community that helped me, was hugely formidable in who I became in my life.' And went back to the SEAL teams, really well-prepped to do sports medicine and orthopedics. And I knew quite a bit about nutrition, and performance, and strength and conditioning. I was pretty sure I had the exact pedigree. When I got there, they had just gotten the money to build a sports medicine facility, which was actually their vision was exactly what I told you that I worked in in college. That's exactly what they wanted to build. I'm like, ‘I got this.' So they put me in charge of building this out. And I was a significant part of us hiring everyone we hired. So we hired our first strength and conditioning coach, our first nutritionist, our first PT, our first everything.  We built our own sports medicine facility. And then orthopedics was coming through every week, and they had to do rounds there. And we'd have pain rounds, pain management rounds come through. We had an acupuncturist coming through. And we hired all these people from the Olympic Training Center, and professional sports teams, and the best colleges. And so, we had all these brilliant people who knew way more than I did about what they do.  Lisa: So you went from there to there.  Dr Kirk: Yeah. And so at that point, I was the dumbest person around, right? Because we had all these experts in every little niche that I knew this much about. We hired experts who knew that much about. And so in the military, when you're the dumbest guy, they put you in charge, right and say, ‘Well, you manage this,' right? And so, I'm managing all these people who know more than I do, however that works. But my office was in this facility that we built.  The SEALs are a lot like professional athletes in that you put them on a bench, so to speak, right? Because they're injured, they need some help. So they can't work. It's the worst thing. Worst thing. So when they see a health care provider, they just lie because they don't want to be— Lisa:  They don't wanna be taken out.  Dr Kirk Parsley: They will take money out of their pocket, and go into the city, and find a doctor to treat them so that the doctor at work doesn't know, so they don't get put on the sideline. But because I was a SEAL, and there were still a lot of SEALs at the SEAL team. It was close enough to my time. There are still a lot of SEALs at the team who I worked with, and I trained with, and deployed with. And so they knew me. And I had a good reputation. And so they trusted me, and they come in my office and they say, ‘Let me tell you what's going on with me.'  They reported this litany of symptoms that didn't have any pattern that I could recognise. And so they were saying that their motivation was low, that they're very moody, that they couldn't concentrate. They're super forgetful. Their energy was low. Their body composition was shifting. They felt slower, and dumber, and colder. None of them were sleeping very well. They're all taking sleep drugs. They had low sex drive. They had a lot of joint pain, a lot of inflammation. And I didn't have the slightest idea. I'm like, ‘And I know it sounds like you're obese and 65. But I'm looking at you and you're not. So I don't know what's going on.'  I just started testing everything I could possibly test. I tested literally 98 blood markers. They were giving 17 vials of blood. Now just shotgun approaches, test everything, and see what's abnormal. And I started seeing some patterns. And they had really low anabolic hormones, so the DBTA, and testosterone, and dihydrotestosterone, pregnenolone. All of that was low. They really have high inflammatory markers. They really had poor insulin sensitivity for how healthy I knew they were, and how well they ate, and how much they exercised. But it's still within the normal range. But it wasn't. Everything was in the normal range. But everything that should be really high was just like barely in the normal range. And everything that should be really low, it's just barely inside of that range. They didn't have a disease. And I was a medical doctor, so I had learned how to treat disease, then they didn't have disease. So I was like, ‘I don't know. What am I going to do?' So that led me to having to train with outside providers. And fortunately, at that time, the SEALs did have the reputation. They'd already done all these amazing things. This was in 2009. So, I think they'd already shot Bin Laden and at that point. So I could call anybody, right? I'd watch somebody's TED Talk, read their book, I'd see them lecture. And I'll just call them and say, ‘I'm a doctor for the West Coast SEAL team. Could I come train with you? Can I consult with you? Can I ask you some questions?' And everybody was generous and said, ‘Absolutely'. So I get to learn a lot really quickly. I take a lot of leave from work and just go sit in these guys' clinics for four or five days. And just pick their brain, go see patients with them, and take notes, and learn. And then I just call them every time I have a question. And I just got to learn really quickly. It's like this team of experts who knew everything about the alternative world.  I was trying to treat people for adrenal fatigue. And I was trying to treat people for vitamin and mineral deficiencies, which are obvious from what was going on. And I couldn't quite figure out what it was. And about 100 patients into it, and probably after 30 guys came in, I could have told everybody, they could just sit down. I'll tell you what you're going to tell me. I could have just just route it off; it's so similar. And about 100 guys into it, embarrassing that it took so long, but I remember this guy telling me that he took Ambien every night. What do you guys call it? Stilnox, I think, right?  I was married to an Aussie, so I know a lot. I mean, I know you're not an Aussie, but I know a little bit about your world, as in your language. And I remember putting a note in the margin, ‘Seems like a lot of guys take an Ambien.' Then I go back through everybody's records, 100% of the guys who had been in my office were taking Ambien. So I thought, ‘Well, maybe that's an issue, right?' So, let me go look at the side effects of Ambien. And it was a fairly new drug. And the pharmaceutical industry, they get to cherry-pick their data. So they were like, ‘Oh, it's the safest drug ever. There's nothing, no problems.' And I'm like, ‘I don't quite believe that.'  Unfortunately, like every other doctor in America, I didn't know anything about sleep. I never had a single class on sleep in medical school, didn't have the foggiest idea what should be happening. I knew what you called a mechanism of action on this drug, which means molecularly what does it do. Well, it binds GABA receptors and has an effect called GABA analog, and benzodiazepines are the same, things like Valium. And so that's about as much as I knew, Well, what is GABA doing? What is GABA supposed to do? And then you can't really understand that without understanding what's actually going on in sleep.  Then, I had to learn about sleep physiology. And what's supposed to happen during sleep? And what are the normal shifts and changes? And what does that do? And if that doesn't happen, what effects do you get? So after studying quite a bit, I figured out the general Occam's razor principle of the thing with the least assumptions is, literally, every single symptom that these men told me about, could be explained by poor sleep.  Now, I didn't think that it would be, right? I wasn't naive, but it could have, then, right? So if this was definitely the most powerful thing, because being a Western doctor I wanted to give them Cortef and raise their cortisol. I wanted to give them testosterone and raise their testosterone. I wanted to get like, I wanted to give them medication to improve their insulin sensitivity. I wanted to just go in there and do it. But I couldn't do that, right? Because you can't give SEALs medication that they're dependent upon. Because then, what if they go out on the field, and they don't have their medication, they can't do their job and it's a waste. So that puts people on the bench, that disqualifies people. So I couldn't do that.  I had to figure out, well, what else can I do? So like I said, sleep seemed like the unifying theory. So let me see about that. And this was right around the time that everybody was catching on to the important vitamin B3. And that was associated with poor sleep. So, I tested all my guys. Every one of them had low vitamin B3. So I'm like, ‘Yeah, I'm going to give them vitamin B3. I'm going to be a hero. Everyone is gonna love me. I'm the best doctor ever.' And it helped a little bit. But it wasn't everything.  Like I said, I had this epiphany with this sleep drug. And once I learned enough about the sleep drug, you aren't actually sleeping when you're on sleep drugs. You're just unconscious. Your brain is dissociated, but it's not sleep. Because sleep has to have, as one of its criteria, you have to have this predictable sleep architecture. You have to be going through these sleep cycles that take you through these different stages. And a particular pattern is repetitive, and it's primarily deep sleep in the beginning of the night, and almost exclusively REM sleep by morning, and you have to do that transition.  If you don't do that, then it's not sleep. It can be partially sleep, if you're just getting poor sleep. But I was having these guys do sleep studies. And they were coming back with 99.9% of their sleep study being stage 2 sleep, which is just the transition. It's what we call a transitional sleep phase. So it's not deep sleep or REM. So they weren't really getting any of the benefits of sleep. And of course, that's an oversimplification. They're obviously getting something, or they'd be dead. But we don't know what they're getting.  That's all we know is that healthy sleep does this, and when you go through these cycles, we know these things happen. Like when you're in deep sleep, we know that's when you're the most anabolic, and you're secreting your anabolic hormones like growth hormone, and testosterone, and DHEA is being ramped up, your immune system's being ramped up. We know this happens. And then we know in REM sleep, what's going on in the brain: the physiological changes, forming more durable neural tracks, that neurological memories, shifting things from working memory into long term memory, pruning off useless information, these little buttons that grow on the side of your nerves that are starting to bud new information. You're like, ‘I don't need that.' You clean up all that. You get rid of weak products and you get the brain working better.  The whole purpose of going to sleep tonight is to prepare myself for tomorrow, right? Whatever I do today, that's what my brain and body are gonna think it needs to do tomorrow. It's gonna use today as a template to try to make me better tomorrow at doing what I did today. And if I don't get enough sleep, if I don't get to restore, I still have to do tomorrow. And how do I do that? Well, I do it the same way you do anything. I'm stressed out. I use Marinol and a bunch of cortisol and DHEA. And I start robbing all my nutrients for my cells. My blood glucose is going up, I'm getting fuel sources that way, epinephrine and norepinephrine stimulate my brain and my tissues to be able to get energy where there's really no energy there. And then I'm going to bed with these really high stress hormones, which are supposed to be low when I sleep, and then I'm trying to sleep with high stress hormones. Then, I get worse sleep. Then, I need more stress hormones tomorrow. And that's what breaks people.  In fact, when you see somebody who doesn't sleep well for even six months, they look so much older. ‘Why does he look old? That doesn't make sense. Is it just because they're tired? Is it tired old?' But if you think about it, you're born into this contract. You're born into this contract; you can't get around. It's just like you're born knowing you're going to die, 100% certain you're going to die. There's also this other contract that certainly is your body ideally worked for about 16 hours, and it needs eight hours to recover. That's the way it works. That's what you're born into. There's small variations there. But obviously, you can't get around that.  If you don't get those 8 hours, you didn't recover from those 16 hours. And so if you think about it logically, obviously, when you're a kid, you need more sleep. So it's not a great example, when you're really young. Kids actually sleep a lot more than eight hours by and large, but you see them actually getting better every day, right? They're growing. They're getting smarter. They're getting more coordinated. You can see that every day. But if you think about, say, like, once you hit 25, and your brain's fully formed, and everything's static. If you could recover 100% every night, and wake up the next morning as good as you were that other morning, you wouldn't age, right? There would be no aging because you would have recovered 100%.  Lisa: It's very important, yep.  Dr Kirk: Everything that you're deficient in, if you're missing 10%, you're going to age that 10%. And if you're missing a little more, you're going to age faster. So when you see people who haven't been sleeping well for a year, they are literally older because they've been recovering less and less every night. So yeah, there's a breakdown in their protein structure. There's decrease in their blood supply, their peripheral vascularisation. Their tissues are aging. There's a buildup of waste products that aren't getting out, and that's toxic. And that's damaging the mitochondria and forming more senescent cells, and all these other things, they're building up. And every marker that we have, even genetic marker, when you look at your children and linked methylation on the genes. Every marker, they look older. And then when you look at them, they look older. That's why.  That's really what aging is. It's really just the absence of being able to recover 100% every night. And as we get older, we just don't repair as fast. And that's, unfortunately, when most people quit sleeping as much. And now that's double whammy there. You're getting twice the aging effects that way. And there's no reason to sleep less when you're old. It's typical, but it's not something you have to do. I've had 84-year-old women who haven't slept more than 4 or 5 hours in 20 years, and I get them to sleep eight hours a night.  Lisa: I've got one over there who's rustling around, walking around behind me. She's 80 years old, nearly. Hey, mum. And she's struggling with sleep in the early morning hours. And therefore, you know her memory and things. So I want to pick your brain on that. Can I just slow you down a little bit because we just covered a ton of ground here. Dr Kirk: You just asked me about myself, and I just couldn't stop. Lisa: No, but you were on an absolute roll. So I didn't want to interrupt you because there was so many things, but my brain's just going like, ‘There's so many questions!'  Dr Kirk: That was just meant to be an overview.  Lisa: That was an overview. Now can we dive deeper into some of the weeds because now I understand why you've become, classically, the sleep expert because obviously that was the biggest leverage. In other words, this is the biggest leverage point that you see. When we think of the SEALs, we think of the SEALs as being these gods of amazingness that can do everything. But what you're saying is like these guys are pushing their limits: endurance, and in fatigue, and all things like that. And so they're going to be the Canaries in the Gold Mines in a way because they're going to be coming up against the limits of everything.  For you to say, as an ultra marathon, so I've come up against the limits in certain ways, like with sleep deprivation. And I sort of understand some of the things now that you were talking about. So you've ended up finding out that this is probably the biggest leverage point in anybody's life, basically, for their health is their sleep. So people, take a bit of a grip on that one. It's not necessarily the food or nutrition, it's the sleep. Would you agree? Dr Kirk: When I first started lecturing, I used to say there were four pillars of health: sleep, nutrition, exercise. And then the fourth pillar is audience dependent. It could be mindfulness, stress medication, it could be community, whatever it is that controls your stress hormones, and your emotions, and your mood, and all that stuff. Then after a while, I shift to there's three pillars sitting on the foundation of sleep. Because if you take the sleep away, none of those are going to work. There's nothing you can do. In fact, if you exercise when you're sleep deprived, it's counterproductive because you're not recovering. And we all know that you don't actually get better when you exercise. You damage yourself when you exercise. Then when you sleep, you recover, and you come back stronger. When you deprive yourself of sleep, you change your entire gut biome, you change your insulin sensitivity. You change everything here. And now your nutritional status doesn't work anymore. And when you don't sleep well, as I said, you increase your stress hormones. So you can do the mindfulness training and all of that stuff, meditate and all that, but you're just going to bring yourself down maybe to where you would have been if you just slept well and didn't do any kind of training.  It's really the foundation for everything. And I say that all the time. It sounds hyperbolic, but I'm 100% convinced it's true. There's nothing that you can do that will, nothing that will break you faster than poor sleep, and poor and insufficient sleep. There's a reason we use it as an interrogation technique.  Lisa: Exactly. Yeah.  Dr Kirk: There's a reason we break people down, intentionally, this way because it depletes all your resources. It interferes with your brain function, your willpower, your problem solving, your speech, your ability to formulate plans, your motivation, your mood. Everything goes almost instantaneously with one night of lack of asleep. Never mind keeping somebody up for three or four days in a row. They're just a mess. They're just in input mode. They just want you to just, ‘Tell me whatever I have to do. I'd do it. Then I'll sleep. Anything I can do to get sleep, I'll do it.' You don't have to rip people's fingernails out of stuff. You just deprive them from sleep.  Conversely, there's nothing that will improve the quality of your life and your performance faster than sleeping. Well, if you're an inadequate sleeper, which most people are. They don't even know they are. Everybody has these 30-day challenges and 60-day challenges. I'm like, ‘I only need seven days.' Again, one week where sleep is your number one priority. And you do everything right, and you get eight hours of sleep, at least eight and a half hours in bed every night, and you're sleeping approximately eight hours a night. And give me that for a week. And then, if you're not convinced this the most powerful thing, go back to wherever you're going. But nobody's ever gone back.  Lisa: A lot of us, I can hear people saying, ‘Yeah, but I go to bed, and I can't sleep. And I wake up at 2 am. And my brain is racing and I've been told to do some meditation. And maybe it's my cortisol.' Let's look now because if we haven't got the message across now that sleep is the number one thing that you should be prioritising about everything that you do, we haven't done very well for the last half an hour.  How do we sleep? What foods do we need to eat before we go to bed or not eat? What supplements can we take? You've got your sleep remedy that we'll get into a little bit. What routine can I do to optimise? What light-dark cycles? All of these things that can be leveraged points for us in optimising our sleep. And how do we test that we're actually in that deep-sleep phase? What are one of the best tools that you've found to work that out? So that was a mouthful, but yeah. Dr Kirk: So the first thing we need to do is get away from that phonetic question right there, which is what everybody's going through in their heads up like, ‘What about this? What about that?' And so my job is to make this really simple. Because simple things we can do, and the more nuanced your plan is around sleep, the more likely it is to fail. And we're doing big, macro movements here. So the very first thing is, what you said, I think we've already covered. The very first thing is to convince yourself that sleep is the most important thing. And to make it your priority for at least one week to get everything going.  Now, when I say your priority, I mean the true meaning of that word. There's only one thing there's nothing else, that's the one, including raising your kids, and your dog, and your exercise routine, and everything else. The most important thing is to sleep. The most important thing for winning. If you aren't quite convinced yet go to PubMed, or go to Google Scholar, or something like this, then put in sleep and anything else you care about: being a parent, mood, dating, sex drive, athleticism, strength, endurance, concentration, memory, I don't care. Whatever it is you care about—strength and this, strength and business, strength and I don't care. Anything you want.  Read to your heart's content. It will convince you that the one good thing about sleep, in the sleep sciences, it's not actually controversial. There's no one out there saying, ‘Oh, you don't really need to sleep.' Everybody agrees. There's nuances and people are different. Everybody agrees you need about eight hours of sleep a night. And just convince yourself that is the most important thing. Once you're there, that's the most important thing.  After that, recognise, ‘Okay. I'm going to make this my number one priority.' Recognise that you're born to sleep. You don't need to learn; you need to unlearn some stuff, right? You're designed to do this. And this should feel good. You should enjoy sleeping. You should usually look forward to going to bed and waking up in the morning, like, ‘Man, I feel so much better. I'm ready to go do my day.' This should be as easy as selling sex but it's not. People resist this forever. I have no idea why. It's great. Why don't you like sleep? I've always liked sleep. So then you just think, ‘Okay, when did sleep go bad for humankind?' Probably in the last seventy years.  Lisa: Yeah, when we got electric light.  Dr Kirk: That's about it, right? It's only been, really since rural electrification, right? Since they got electricity out to everybody. That's really when it started. When you look back in America just 100 years ago, look at people's journals in the winter, they spent like 14 hours a day in bed. That's a certain thing they do. So if you think about it, and just say, ‘I know this is simple. I'm going to let myself fall into it.' And then I'll tell you, there's all the sleep hygiene. You can get on the Internet, and you can find, ‘Oh, do this. Drink a hot cup of tea. Drink milk. Do this. Make your room really cold. Make your room really dark. Make your bed really soft. Make your bed really hard. And get a white noise machine. Get rid of all the EMF.' A million people are going to tell you all sorts of different things to do. And I'll cut through all the BS, and then you can pick and choose. The real answer is all of that stuff works, to some extent. All of that's important to some extent. The way I work with clients is at least 95% of all the successes is from lifestyle. And then all these little gadgets, and your mitigation tools, and supplements, and all this stuff back, that's the other 5. It's 95% behavioural. So you just look back, how did we evolve to sleep? Nobody teaches people how to sleep, right? You're born as a baby; you sleep. So how did we sleep as adults in cultures 100 years ago? Well, when the sun went down, we fell asleep about three hours later, and we woke up around the time the sun came up. It was pretty much that easy.  Okay, so let's reverse engineer that a little bit. I think most people know that blue light is a stimulus for being awake. We don't truly have a sleeping program. If you think of it like software, we don't have any sleeping software. We just have lack of awakening software. So we have things that go on in our brain and body that make us still awake and make us interact with our environment. And then when you take those things away, we're in what we call sleep. The blue light, actually, has nothing to do with the vision. There's nerve cells in the back of your eyes. It senses blue light. That's all they do. And then they fire pathways back to the circadian pathway membrane, essentially. And then the pineal gland secretes melatonin. The melatonin is a hormone, the starter pistol. It initiates all these cascades. And then one of the cascades that it initiates is the production of this peptide called GABA, capital G-A-B-A, gamma-Aminobutyric acid. And what that does is it slows down the neocortex.  When you think of the human brain, the picture of the human brain, we all have that big, wrinkly, massive crescent shape. That's what we call the neocortex. And that is how we interact with the world, right? All of our senses get processed in that, and then all of our movement is processed from that, right? So when we're asleep, all that's really different with our sleep, about in a general sense, right? There's nuances in every neuron and every molecule. And then, in the neural sense, there's a barrier between us and our environment is how it's phrased. What it means is we aren't paying attention to our environment anymore. Our eyes obviously still work, right? You can turn the light and you can wake somebody up. Our ears still work, you can make your noise and wake somebody up. Our sense of touch still works. You can shake somebody. They can roll into something sharp, and their pain receptors will wake them up. Heat will wake them up. Cold will wake them. So we still work. Everything still works. We start processing it. We're not paying attention to it.  What helps us do that is GABA. So GABA involves neurons. A neuron has what's called a resting potential. So there's like an electrical current in here. And when you put in enough electrical current, it goes like this. And that neuron fires. And then, does whatever it does and forms pathways. Well, GABA lowers that. Now, it takes more energy to make that thing fire. And you can overcome this by just putting a lot of energy into the cells. So if you've ever been exhausted, woken up exhausted, didn't get enough sleep for whatever reason. Like, ‘I'm going to go to work. I'm gonna come home. I'm going straight to bed. I'm gonna sleep 12 hours a day.' And then your friends talk you into going out or you get a cup of a drink. You stay up ‘til midnight, ‘I feel fine.' And then you suffer again the next day, right? Because you just overcame that.  You can actually read about this because this still exists, believe it or not, they're still I think 35 or 45 pretty large communities around the globe that have never experienced electricity. And they just lived like hunters and gatherers. They go out. And the men go out and hunt. And the women pick, and nurture their kids, and weave. And just when you think of your caveman doing, they still live like that today. And we study these people. And we did actigraphy. So it's not true sleep, say. It's just movement to know when they're likely to be asleep. And what we find is, the sun goes down. Again, the blue light goes out of their eyes. It fires, the brain starts secreting melatonin that leads to a cascade of 365 billion other chemical changes in the brain, right? But that initiation has to happen. Once that initiation is going, one of the things it does is secrete GABA, increase GABA production in lots of regions of the brain that starts slowing the brain down.  The sun goes down. They don't have electricity, right? The best they have is a fire. So what else happens? Their body temperature goes down. So when the sun goes down and it is dark, we can't see well at night, we can't see very far. So there's way less stimulus, right? They don't have flashing lights. They don't have loud music. So there's not much to stimulate them. So they sit around a fire. Maybe if they're lucky, if not, they just stare around the dark, and they have some quiet, calm conversations, and then they drift off to sleep.  That's all sleep hygiene is. That's it. Those three things: decrease the blue light, decrease the stimulation to your brain, and drop your body temperature. You need a cool place to sleep. One of the things that you can do to speed these things up is to concentrate the right nutrients in your brain. If you are going to take melatonin and just take a very, very, very, very small amount. You just want to initiate. You don't want to put so much melatonin in your brain that your brain doesn't need to make melatonin because then you start running insensitivity to melatonin, and now when you take it away, you don't have, you're essentially melatonin deficient because you've downregulated the receptors, and your brain is not sensitive to melatonin anymore. Lisa: Can I just stop in the first, one second. Dr John Lieurance is his name and he was on the Ben Greenfield podcast, and he's written a book about melatonin. And he argued that melatonin, interesting work, doesn't downregulate when you take melatonin, and doesn't cause that downregulation. All the other hormones do. If we take testosterone, we're going to downregulate our own testosterone, if we take right whatever. He said that they didn't. And he was advocating in his book for actually, super-physiological doses of melatonin. Certainly when you're doing things like jetlag, or whatever you're trying to reset, but also for a raft of other ailments to help with many diseases. Have you heard of his work or? Dr Kirk: I'm familiar with him and his work.  Lisa: Yeah. What's your take on that? Because I was like, ‘I don't know.' Dr Kirk: So, I disagree, obviously.  Lisa: Yeah. That's what I want to know. Dr Kirk: But specifically, so what he's talking about, 90% of his work is about the antioxidant. Lisa: Yes. Is it an antioxidant? Yep.  Dr Kirk: The studies that he's quoting are saying that melatonin doesn't downregulate. We don't know for sure. It's like, maybe it does, maybe it doesn't. The only way we would know is if we could actually drop a catheter into somebody's brain and sample their fluid in their brain 24 hours a day and study this over months. And so we can't say for sure. We can do animal models. Again, it's hard to quantify because from the time the sun goes down, which is about three hours before you'll fall asleep, to the entire time you slept, until the sun comes up, you're looking at somewhere between 11 and 12 hours. That entire time your brain will only produce five to six micrograms of melatonin.  Lisa: Tiny amount. Dr Kirk: So how do we study, right? It's really hard to study, and you think of it in a mouse model, how much smaller the quantities are we're looking at that point. And the concentration of melatonin in each region of the brain is not the same, it depends on some cells in the brain can actually be stimulated by melatonin. It's somewhere. It's different. And same with GABA. GABA doesn't go to every region of the brain because it can stimulate regions of the brain. But what we do know, so first, I always go with, we don't know anything. We have research that makes us believe certain things are likely to be true based on the best science we have right now. So we don't know anything. And I believe that to be true about everything in science. Just wait a week, it might change. But what we do know is that every other hormone does this.  Lisa: Yes.  Dr Kirk: But if it doesn't do this, it's the only hormone in the body that doesn't. Pretty unlikely. But what we do know with 100% certainty is that it does downregulate melatonin receptors. Lisa: Right. Dr Kirk: It can take away melatonin receptors. If I normally have 10 melatonin receptors, and I go down to just having one, now even if I'm sprayed with melatonin, I only have one. And I have to have this supersaturation for this one receptor to do all this work. And if I go down to normal physiologic levels of melatonin and this one receptor, there's just getting an occasional melatonin coming by, I'm going to be, it's no different. It doesn't matter whether I'm not producing enough, or I don't have enough receptors, it's the same end result. You have to have melatonin binders stuffing pulled into the cell to have it function. Lisa: So can I ask one question there like, so for elderly, who, from what I understand, in my basic research on melatonin, is that their melatonin production goes down with age, and, therefore, they could benefit from melatonin supplementation. Is that a thing or? Dr Kirk: Yeah, I agree. And so what happens is that the pineal gland calcifies just like our arteries. And every vessel, everything in our body calcifies, right. That's sort of aging. Lisa: One of the majors.  Dr Kirk: And so it calcifies, and you do almost certainly secrete less melatonin, right? And again, the only way we would know is to drop a catheter into somebody's brain. But I'm not saying that you shouldn't take melatonin at all. I'm just saying you shouldn't take super physiologic. So his example of when you're speaking about the melatonin work earlier, right? His example is, well, this is a great antioxidant. Now, if I do these super physiologic amounts, there's all these benefits to it. Well, if I give you 10 times the amount of testosterone that your body ordinarily has, you're gonna feel fantastic. If I give you something that secretes a bunch of epinephrine and norepinephrine, like cocaine. And you have this huge rush of norepinephrine; you feel fantastic. And you're super productive, and your brain's really sharp. Does that make that a good idea? I don't think so. I don't deal with anything super physiologic.  Again, I'm the behaviourist, and 95% of all your health is going to come from re-approximating the way you revolt. This body takes hundreds of thousands of years to adapt to this planet. And now we're just like, ‘No, we're smarter. Like I'm a 35-year-old biohacker. I read a bunch of books. I know I can do it better than–” We know nothing about the body. Lisa: Can we all mean for people–we also know that people tend to die. If we wanted to extend our healthspan and their lifespan, but healthspan mainly, can we, with hormone replacement therapy, there's a raging argument: should you be on hormone replacement therapy, should you not? If you're wanting to optimise. Now, there's downsides. And you need to understand your genetics, and you need to understand all of those aspects.  There is benefits for us to taking testosterone or DHEA or all these things in the right physiological doses of, say, a 30-year-old, like, I'm 50 or 52, I want to be at the level that I was, say at 30–35. I understand my genetics, I know where my risk factors are. I can keep an eye on all of that sort of stuff. Can I all meet that so that I live and function longer? Because I think the core question here is how do we optimise? Yes, we've developed like cavemen but then they die at 70–80, as well. Can we extend that with the knowledge that we currently have? Dr Kirk: Well, so I don't ever promise anybody that I can make them live longer. I say, ‘You might live longer from this.' If you think about it, think about it this way: at first, we talk about what sleep does, right? And if we could catch up every night, we wouldn't age. So what are we doing when we're doing things like hormone-replacement therapy? We're doing metabolomics. And we're doing all sorts of supplementation around that, or we're doing artificial things like hyperbaric, and near-far IR sauna, and ice baths, and doing all these steps to stimulate the production of the thing.  Of course, now we have antibiotics, and we have all sorts of treatments to keep people from dying as young from certain diseases. So certainly, we should be able to either, probably add years to your life. But if not, definitely we can add life to your years, right? If you're going to die at 80 either way, one version of this, you could die hiking Mount Kilimanjaro, another one you're dying in a little chair in a nursing home. So I don't know.  The question is, even with the longevity work that people are doing, really smart guys like Sinclair and all these guys are doing all these things, and they're doing all these things with clearing senescent cells, we're doing all these things with peptides. And now I give my patients peptides for certain things. I don't know nearly as much about the longevity stuff as I'd like to. And we and we're reversing aging genetically, right? We're going in there and saying, ‘Actually, over the course of a year, with a lot of work, a lot of effort, a lot of tries, a lot of modalities, really focusing on your lifestyle and doing everything. Ideally, we can actually, probably, reverse your genetic age a little bit.' Are we actually reversing age? I don't know, we made your telomeres longer. The increased the methylation on your genes, and those are markers for age, does that reverse it? We don't really know, right?  Lisa: We haven't been around long enough to work it out.  Dr Kirk: Right. It's like with omega-3s. If your omega-3s are this, then we know that certain things go this way. Well, but if we supplement your omega-3s, is that the same as you having that nutritionally. Or vitamin B3? Is that the same? We don't know. We're thinking that it probably is. And we're thinking if we're reversing the markers we know for genetic aging that's making you genetically younger. But maybe there's some totally different information in there on aging that we don't know anything about yet. That's possible, too.  I think from what I know about you, you probably agree with me. I think epigenetics is more important than genetics, anyway. You have certain genetics and you change half a dozen things about your day, and your epigenetics are totally different. If you short yourself 2 hours of sleep, you change 735 different epigenetic markers from just 2 hours. All your pro-inflammatory ones are the ones turning on, and all of your anabolic ones are the ones turning off. And again–  Lisa: That's still the biggest leverage point, isn't it?  Dr Kirk: It's still a crazy complex to think that you can decipher what 735 changes in epigenetics mean. We have some ideas of what certain things, how does all that work in synchronicity, but even though we're the smartest animal on this planet, we still have a very feeble mind. Lisa: We're still dumb.  Dr Kirk: When it comes to understanding the complexity of our bodies, we can't understand the complexity of the planet, much less our bodies. And life is just this amazingly complex thing. We don't have systems in our body. We divide the body up in systems as a way to learn it so that we can systematically learn and we can test about the learning, but the body doesn't work in systems. Lisa: I have such an issue with it, too. It's nothing like the way that the medical model breaks us all down. Dr Kirk: The reductionist model doesn't work for life. And if you think about it, most of biology is purely descriptive. All of it is, we've come up with better and better ways to test things and look at things, and then we can describe what's going on. We don't know how to manipulate it most of the time. If we do, it's really clumsy. And it's causing 500 other changes because we wanted to flip this one switch this way. Then what are the downstream effects? We don't know. We'll find out in like 30 years after 100,000 people go through this. It's really clumsy.  I don't know if can I make somebody live longer. I'd never make that claim. But can I make people look, feel, and perform better? Absolutely. I can do it all the time. And me, personally, like you're saying, I just approximate use. Their arguments, there are people out there saying, ‘Well, these hormones will cause this or that.' I'm like, ‘Okay. If high estrogen levels cause breast cancer, why don't young women get breast cancer? Older women, they're the ones who are getting breast cancer, why?' That thing with men and prostate cancer, giving them testosterone is gonna cause prostate. No, it's not. If that were true, then a 20-year-old would have prostate cancer, and a 60-year-old wouldn't, right? It's a lack of this. And I think breast cancer is a lot like prostate cancer. What we know with prosta

GABA or Gamma Aminobutyric acid is one of my favorite supplements for anxiety, stress, nausea, insomnia and more. It works like gangbusters! Find out how and why in this next podcast episode. As always, sharing is caring. Please share with anyone you feel would benefit from this information.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.01.322008v1?rss=1 Authors: Weis, J., Persson, J., Frick, A., Ahs, F., Versluis, M., Alamidi, D. Abstract: {gamma}-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a variety of psychiatric and neurological disorders. The main purpose of this study was to propose a combination of PRESS and MEGA-PRESS acquisitions for absolute GABA quantification and to compare GABA estimations obtained using total choline (tCho), total creatine (tCr), and total N-acetyl aspartate (tNAA) as the internal concentration references with water referenced quantification. The second aim was to demonstrate the fitting approach of MEGA-PRESS spectra with QuasarX algorithm using a basis set of GABA, glutamate, glutamine, and NAA in vitro spectra. Thirteen volunteers were scanned with the MEGA-PRESS sequence at 3T. Interleaved water referencing was used for quantification, B 0 drift correction and to update the carrier frequency of RF pulses in real time. Reference metabolite concentrations were acquired using a PRESS sequence with short TE (30 ms) and long TR (5000 ms). Absolute concentration were corrected for cerebrospinal fluid, gray and white matter water fractions and relaxation effects. Water referenced GABA estimations were significantly higher compared to the values obtained by metabolite references. We conclude that QuasarX algorithm together with the basis set of in vitro spectra improves reliability of GABA+ fitting. The proposed GABA quantification method with PRESS and MEGA-PRESS acquisitions enables the utilization of tCho, tCr, and tNAA as internal concentration references. The use of different concentration references have a good potential to improve the reliability of GABA estimation. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.24.057331v1?rss=1 Authors: Sigurdsson, H. P., Molloy, K. J., Jackson, S. R. Abstract: Transcranial magnetic stimulation (TMS) can be used to probe for the location of cortical somatomotor representations in humans. These somatomotor representations are dynamic and are perturbed following motor training, systematic intervention, and in disease. Evidence suggests that these representations are maintained by the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA). In the current study, we quantified the location, outline, and variability of the first dorsal interosseous (FDI) hand muscle somatomotor representation using a novel rapid-acquisition TMS method in 14 healthy young volunteers. In addition, resting motor thresholds were measured using established protocols. TMS was also used to examine short-interval intracortical inhibition (SICI), which is thought to measure transiently activated cortical gamma-Aminobutyric acid (GABA) interneurons. Using stepwise regression, our results showed that the level of intracortical inhibition was a significant predictor of the FDI somatomotor representation suggesting that greater excitability of the hand area representation is possibly governed by greater activation of transient GABA interneurons. Copy rights belong to original authors. Visit the link for more info

Today we’re taking a deep dive into stress: what causes it, how it affects us, and the various ways we can treat it. As someone who has lived in a huge city for a long time and who travels frequently, stress has wrecked me in various ways — but I know I’m definitely not alone. Gallup reports that 55% of Americans are regularly stressed during the day, and things just seem to be getting worse, as stress-related mental health issues are notably more common in Gen-Z than previous generations. So, clearly, this is a big issue, especially within the United States — but the silver lining is that we do have the tools and knowledge necessary to reduce those statistics. That’s why I was keen to sit down with one of the foremost stress experts, Jim Poole, President and CEO of Solace Lifesciences. Solace Lifesciences is a neuroscience company focused on personalized evidence-based wellness and performance. They created NuCalm, the world's first and only patented technology clinically proven to lower stress and improve sleep quality — without drugs. And by managing the stress response, NuCalm also helps with muscle recovery, healing, focus, productivity, and emotional balance. I’ve tried hundreds of different biohacks and technologies, and I fall off of most of them after a few weeks. But when I find a modality or device that’s this effective, I just become obsessed with it (like happily making myself look like a crazy person on the plane obsessed). I’ve used NuCalm nearly every day since I got one, and it’s really like meditating on steroids.   Interesting in trying out the NuCalm yourself? You can save $500 using the code “luke500” at NuCalm.com.   10:07 — What are some of the most common causes of stress? Everything in modern life causes stress The biggest culprits are technology, the increasing pace of our world, and our food supply Stress is an even more insidious problem than many people think, as most of us aren’t aware of the long-term implications of constant stress on mankind and our planet There’s a cultural issue with work in the USA, with people wearing stress as a badge of honor, but this does seem to be moving in a positive direction The epidemic of overprescribing our children When you’re a teenager, your brain is developing — and adding drugs that suppress the central nervous system is really dangerous What we can learn about stress from Provo, Utah   17:58 — The experience of starting to use NuCalm NuCalm has a cumulative effect How learning the mechanism of action behind a biohacking device helps with compliance I’ve been meditating for a long time and I can do it just about anywhere, but it’s crazy how different I feel when I combine my practice with NuCalm   20:47 — How stress affects your brain and body Self-awareness isn’t always enough to stop a stress response, especially when related to trauma What you should know about your amygdala, cortisol, and adrenaline Reacting Vs. Responding How your brain changes when you have a fight or flight response A perceived threat is just as real as a real threat to your brain and body Why focusing on mindfulness is the best thing we can do to minimize our unnecessary stress responses The intimacy we have with our own stress (and that we never share) Negative thoughts have a greater impact on us than positive ones The difference between fear and anxiety Why does stress wreck our digestion? What the Dalai Lama said about meditation Why is meditation so difficult for some people?   47:00 — The neurotransmitters that calm us down + what’s happening in our brain when we do GABA (gamma-Aminobutyric acid) is responsible for anything anti-anxiety occurring in your brain chemistry We’d die without GABA — but, weirdly, most people have never heard of it How stress creates disease and kills us Most of us will die from stress There are plenty of things we can use to temporarily alleviate stress by stimulating our GABA receptors (alcohol, opiates, marijuana, etc), but these short-term solutions often have long-term negative side effects What about taking GABA as a supplement? Or Kratom instead of an opiate? What is the vagus nerve and how does it regulate our nervous system and mood?   59:23 — How the NuCalm has evolved over the past 10 years + why the most recent version involves putting a metallic sticker on your wrist NuCalm’s 10-year product evolution The chemical messaging of NuCalm How governments classify some things as a drug vs. a food (even when it doesn’t make sense) How the metallic sticker (it’s a little more complicated than that, but that’s what it looks like) leverages cellular communication through frequency What biohacks can you stack with NuCalm? What shouldn’t you stack? (Hint: don’t use it near anything putting off strong EMFs)   01:23:40 — The neuroacoustics of NuCalm How do binaural beats work and what’s the difference between those and these crazy NuCalm audio files? How these audio files induce specific brain states Composing music with mathematics Why they use scales that most people never hear in popular music How you can use frequencies to affect people both negatively and positively   01:55:10 — NuCalm inventor Dr. Blake Holloway create a mathematical platform that can be used to train your brainwaves in a wide variety of ways — and they are working with people like Tony Robbins to create products that achieve different outcomes Ignite, the neuroacoustic audio track that can hype you up instead of chilling you out NuCalm is designed to help every person on the planet, but Ignite is much more specific Why they don’t want someone using Ignite until they make NuCalm a habit What happens if you use NuCalm in addition to alcohol or marijuana The difference between NuCalm and other products out there using sound, like HUSO, Brain Tap, or Alpha-Stim   02:10:28 — Why is NuCalm so helpful for air travel and jetlag? I would freak out if I left home for a flight without my NuCalm today The case studies they’ve done with pilots The wonders of the 20-minute power nap   02:19:20 — The future of NuCalm The launch of Ignite is imminent They will be releasing their first new track for over a year Why do we feel like we can’t take 30 minutes out of our day to take care of ourselves? The more you train your brain with NuCalm, the more quickly you will experience its benefits when you use it Jim’s words of wisdom for the planet Try NuCalm in person in NYC: www.recover.nyc Try NuCalm in person in LA: www.drgalitzer.com   More about this episode. Watch it on YouTube.   Connect with Luke on social media to learn how to take your lifestyle to the next level, plus catch exclusive live interviews & events: INSTAGRAM - @lukestorey // https://www.instagram.com/lukestorey/ FACEBOOK - https://www.facebook.com/MrLukeStorey/ TWITTER - @MrLukeStorey // https://twitter.com/MRLUKESTOREY YOUTUBE - https://www.youtube.com/c/LukeStorey THIS SHOW IS BROUGHT TO YOU BY: BLUBLOX. BLUblox offers a complete range of evidence-backed blue light blocking glasses to suit every need (and, as a rad bonus, you won’t look like a tool while you’re wearing them). Plus, they even do prescription and reading glasses now, as well as an epic send your own frame service, both using the same world renowned blue light blocking lenses. I’ve also been digging their new REMedy Sleep Mask, which blocks out 100% of the light while you’re sleeping. And it’s not just great for better sleep — it can also be used for meditation, deep touch pressure therapy, air travel, and migraine relief! You can get all of this epicness and more by using the code LIFESTYLIST for 15% off at BLUblox.com.   AND...   CURED NUTRITION. Cured Nutrition makes some of the highest quality CBD-infused products on the market, all made from Colorado-grown organic hemp — and now they’re taking things to the next level with functional mushrooms and adaptogens combined with CBD! I also appreciate their dedication to transparency, which is a big problem in the supplement world. Each Cured product is third-party tested for potency, purity & the absence of harmful contaminants like microbials, pesticides and heavy metals. Fully aligned with complete transparency, they’ve even published the details directly on their website You can get 15% off by using code “lifestylist” at curednutrition.com.   AND…   SUPERFAT. There are certain fats that your body can’t make on its own so you have to get them from your diet. These are called “essential fatty acids.”  Almonds and macadamia nuts are two of the best places to get them, and that’s why the team at SuperFat have created a delicious line of on-the-go nut butter snacks based on these two healthy nuts. With only 3-5 net carbs per serving, SuperFat provides your body with a natural source of fuel — without the crash! Use code LUKE to get 15% off SuperFat nut butter snacks at SuperFat.com. HELP SUPPORT THIS SHOW! Love the Show? You’ll really love Luke’s Master Market Online Store!  It’s a win/win! Get direct links to all of Luke’s hand-picked biohacking and health products all in one place, get exclusive discounts, and support the show by making purchases through the web store >> SHOP NOW.   Other ways to support:  SUBSCRIBE >> Apple Podcasts + Stitcher + Google Podcasts + Spotify LEAVE APPLE PODCASTS REVIEW >> Simple step-by-step instructions SHARE >> Spread the word! Tell your family, friends, neighbors, and all your social pals Resources Use the code “luke500” to save $500 at www.nucalm.com Try NuCalm in person in NYC: www.recover.nyc Try NuCalm in person in LA: www.drgalitzer.com Facebook: www.facebook.com/NuCalm Twitter: twitter.com/NuCalm Liposomal GABA with L-Theanine Jimmy Paige: www.jimmypage.com Brother Craig Marshall: www.nucalm.com/brother-craig Dr. G. Blake Holloway: www.nucalm.com/g-blake-holloway-m-phil-nd Related Shows Episode 94: The Walking Dead And The Path Of Enlightenment Part One With Jeff Kober Episode 95: The Walking Dead And The Path Of Enlightenment Part Two With Jeff Kober

  Keto diets have been extremely popular lately, but how does being in ketosis impact our training and performance? The expert on these topics is Dr. Dominic D’Agostino. Dr. Dominic is a Professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida, and Research Scientist at the Institute for Human and Machine Cognition (IHMC). He is well-respected in the science world as well as the performance industry having been featured on Tim Ferriss' podcast as well as having his research supported by the Department of Defense, the Navy SEALs, etc. 35. Keto Diets, Training and Performance with Dr. Dominic D’Agostino In today's episode, we dig into Dr. D'Agostino's research plus his own personal experience and experimentation with keto diets and bodybuilding, including how he achieved his personal best deadlift while fasting! We also discuss what it means to be "fat adapted" and why our bodies can run on both ketones and glucose at the same time. Dr. D’Agostino says the idea is to adapt our bodies over time by training while we're fasting periodically; if we are training in a state of nutritional ketosis and occasionally consuming carbohydrates then our body recognizes carbs and as ketones both as fuel sources. One strategy to do this could be to eat a carbohydrate-based diet that is low enough to maintain optimal insulin sensitivity while including ketogenic nutrition, such as MCT oils or ketone supplements. But it's important to also do this without necessarily restricting carbohydrates to the point of entering ketosis. And we finish up with a chat about when it's beneficial to be on a keto diet as well as how often to follow a ketogenic protocol to get the full benefit. Dr. D'Agostino suggests we can achieve many of the metabolic benefits and anti-cancer benefits by going keto for just three to five days per month either through fasting or by going down to 500 calories per day. You’ll hear him explain the science behind these approaches plus much more on this fascinating and enriching conversation on today’s edition of the Awesome Health Podcast! Resources for this Episode Dr. Dominic's Website Dr. Dominic on Instagram Dr. Dominic on Facebook Read the Episode Transcript : Wade Lightheart: Good afternoon, good morning and good evening. It's Wade T Lightheart here today with co-founder Matt Gallant. And a super special guest, Dr Dominic D'Agostino. I have been, you know, hoping for this interview for a long time. For those who don't know who Dominic D'Agostino is, he is one of the preeminent experts on ketogenic diets and ketosis. He works with the Navy seals and in a variety of projects that he's done, they're heavily research oriented and the benefits that this potential dietary practice can have both in performance applications as well as physical health issues, you know, related to cancer, things like that. Cognitive function, a bunch of different things. Dom is a professor at the department of molecular pharmacology and physiology at the university of South Florida and a research scientist at the Institute for human and machine cognition. His laboratory develops and tests metabolically based strategies for neurological disorders, cancer and for enhancing the safety and resilience of military personnel in extreme environments. His research is supported by the office of Naval research, department of defense, private organizations and foundations. He just recently came back from a trip from Australia where he was speaking literally in what, five cities in 11 days. And he was gracious enough to take the time to join us on the Awesome Health Podcast. So delighted to have you here. Dom, welcome to the show. Dominic D'Agostino: Great to be here. Thanks for having me Matt and Wade. Matt Gallant: As much as Wade is excited, I'm, I'm even more excited. You know, I've been a fan of your work since. I think I first heard you probably I think on the Tim Ferriss podcast which, which was very enlightening and I've been a longtime keto user and dieter for over 26 years on and off nonstop now for four and a half. And a BiOptimizers, you know, we have these, this three sided triangle of, you know, aesthetics, how we look, the performance and the health side. And I think you're one of the top guys in the world to talk about the performance side and the health side of keto. Cause most people talk more about the aesthetics, the fat loss and that, that component. But today I really like to dive into maybe we could start with some of your background and what you've been doing research wise and then we can get really into all of their current stuff you're doing in a run performance and help. So maybe give us a little bit of background as far as what you've been up to the last five, 10 years. First Quito and kettle research. Dominic D'Agostino: Yeah. for 10 years, well, this quickly, going back to 25 years ago, I was always interested in nutrition and I majored actually in as an undergrad in nutrition scientists and dietetics. And as I navigated my, you know, college career, I realized that there wasn't a whole lot of jobs in nutrition. So I kind of moved to majoring in biology too. And then I did my PhD actually in neuroscience and, and when I finished my pHD I was funded by the office of Navy research for my fellowship, a postdoctoral fellowship. And that was really to understand oxygen toxicity seizures as it pertains to the Navy seal dieter that's using a closed circuit rebreather that they use or operational conditions. There's a stealth component to this equipment. There's no bubbles when you dive underwater. A disadvantage would be that you're breathing high oxygen 100%, actually with a certain type of breather and it just did the be the seawater. Dominic D'Agostino: You can have a seizure and within 10 minutes some people you know can have that and there's really no way to predict or prevent them. So the first area of my research was developing different technologies that would allow us to understand sort of how the brain is working under these conditions. And if you understand the problem, then you can come up with a solution. But we didn't fundamentally understand the problem. So we developed things like microscopes and electrophysiology equipment and telemetry equipment and we adapted that for use inside a hyperbaric chamber. And then over, you know, five or six years, I started to realize that targeting brain energy metabolism and the neuropharmacology of the brain are two strategies to protect the brain under these extreme conditions. And I was sort of interested in antioxidants, loading up animals with antioxidants really did not seem to work much, although in theory it should have. Dominic D’Agostino: But then I started moving towards like coaxing our own bodies to be more resilient. And there was some studies that we've done with fasting rats for 24 to 36 hours and that actually had a remarkable effect at preventing the seizures and it was actually greater neuroprotection than the antiseizure drugs. So I began sort of became interested in how fast and could mitigate and be a mitigation strategy or counter measure against these types of seizures. And then discovered the ketogenic diet, which I thought of, sort of thought I knew, but I really didn't know the whole history of the ketogenic diet, you know, growing up you hear about low carb diets, Atkins diets and you know, I had interested in the ozone diet at one point and a little carb a little bit and I did it kind of on and off for different years. Dominic D’Agostino: But when I delved into the history of the ketogenic diet and met with the practitioners at major universities, like especially Johns Hopkins group I realized that this could potentially be, I could incorporate nutrition back into my research program and do sort of like a nutritional neuroscience project. I would just have to convince my program officer at the department of defense or Navy that, you know, this was a good strategy and the science was actually there like on PubMed, you know, I mean it was good peer reviewed studies sharing that independent of the etiology independent of the cause of the seizures. The ketogenic diet seemed to help across the board. So, and oxygen toxicity seizures are powerful. Tonic clonic seizures we think are being generated in the hippocampus, which was an area that I was studying and published on. And also maybe influencing the neuro control of autonomic regulation and actually did my PhD on respiratory neurobiology brain set. Dominic D’Agostino: So I had a sort of an understanding of, of sort of what was happening and, and a new understanding and appreciation for nutrition as a metabolic therapy. And and I was never taught anything about the ketogenic diet through my four years of training and two, two semesters actually, the advanced nutrition and graduate nutrition. I never even heard about the ketogenic diet being used, and it was like the standard of care for drug refractory epilepsy. So long story short the dietary approach wasn't, it didn't really grab the attention of the program officers. They wanted to see a ketogenic diet sort of in a drug. So I went down the path personally from a research perspective of just studying ketones and different formulations or ketones. But I also started doing the ketogenic diet myself to understand it from the implementation perspective. And, and, and not people weren't doing the ketogenic diet, the clinical ketogenic diet back when I started and maybe 2008, seven or eight. Dominic D’Agostino: But as I followed it, I realized after I got through the initial adaptation, I felt really good. And I I, prior to this, my, my meal frequency was five or six meals a day and I transitioned actually to eating less often and to the point where I adapted to doing intermittent fasting occasionally, once in awhile. And, and then as we developed ketone various ketone technologies, including ketone esters and ketone electrolyte preparations mixed with a MCT and started studying it, we realized that these are very powerful neuroprotective compounds that have a wide range of applications, not just oxygen toxicity seizures, but different metabolic disorders are highly responsive to nutritional ketosis. Some are the standard of care are the ketogenic diet, I should say, is the standard of care for things like metabolic disorders, like glucose transporter deficiency, other deficiency complex. We studied Kabuki syndrome, which is a genetic disease. Dominic D’Agostino: And we look at the role of ketone bodies as an epigenetic regulator activating some genes and silencing others that can impart their therapeutic effects. So, and then cancer too is another area. I've had three PhD students graduate under me training under me that actually focused on looking at the ketogenic diet to impact the growth and proliferation of cancer, metastatic cancer. We we're looking at cancer parts, which is muscle wasting associated with cancer. We're also looking at drugs like Metformin and other metabolic drugs that sort of target different pathways that overlap with the ketogenic diet. So, so I started studying it for something that was relatively esoteric to most people. Oxygen toxicity seizures are now, we now are studying, I would say probably close to a dozen different things including glucose regulation, you know, everything from ALS to angelman syndrome to Alzheimer's disease, Kabuki syndrome, glucose transporter syndrome a number of other kind of even more rare things that you may not have heard of. Dominic D’Agostino: And, and we're also, you know, developing forms of ketogenic compounds, diets, and also supplements that would allow the war fighter and potentially even the astronaut to implement some form of ketogenic nutrition to enhance performance and resilience in extreme environments. You know, so going back to the, the Navy project, I've continued to be funded by them, you know, for like almost 12 to 13 years now. And I continue to have projects and we've developed the animal work and now we're actually doing studies in humans. And, and now we've actually moved on to working with NASA where we, eh, we do experiments where we live in an undersea environment for an extended period of time in what's called saturation. And when you're in saturation, it takes a long time to decompress and to come up. So your body is an extreme environment, not just pressure, but higher ATA of oxygen, higher partial pressure of carbon dioxide too, which has an effect. Dominic D’Agostino: So we have projects where I look at the gut microbiome, psychological testing, body composition. We look at a number of other factors, you know that are influenced, you know, in these extreme environments, a lot of like psychological, what we call team-building or cognitive team cognition. So how the group works together and that can be impacted by our energy state, our metabolism, and our pharmacology. So we're looking at a whole suite of parameters of people in these environments. So we figure out where the detriment is. And then once we understand that, then we develop a sort of a lifestyle, which is micro focuses, nutrition and supplementation to basically enhance, you know, resilience in that environment. And that would be physiological resilience and psychological resilience. So that's, we're putting a lot of time and effort into that project now. Wade Lightheart: That's pretty exciting stuff. Yeah, no I just wanted to comment on that. And one of the things I think from a practical standpoint that I think people can relate to. And I'm curious about this one because I think as listening to you on Tim Ferris, you had gone an extended period time of fasting and were able to like do a ridiculous deadlifts set. Do you want to talk about that just, just briefly, cause I'm just, this is a curiosity component of I heard about it. I want to be confirmed that I heard it correctly. So I'll let you speak from the hearts because what it seems that you've been able to do is something that almost no one would believe possible. Dominic D’Agostino: Well, I, I don't, I don't think fasting or being in it, and I don't think the ketogenic diet has, some people didn't accuse diet will dramatically impair your strength and performance and once you're adapted, and I don't see that as being necessarily a problem if you have protein a equate for protein and total calories. So fasting is sort of like another thing, but also kind of similar in a fasting state. It after about the second or third day it gets hard around that time, but once your body adapts you actually feel better. Your energy level starts to get a little bit low. Towards day five or day seven in me. I haven't went beyond a seven day fast. And I realized that, you know, I wouldn't want to do a high volume workout during that time, but I realized that my, my overall strength just by how I felt really was not impaired much in a, I just wanted to, you know, kind of feel how the weight spell on my body and actually my inflammation was gone. Dominic D’Agostino: Like, I mean, I felt good in so many ways that I just kept adding weight. One 35 to 25, three 15 four or five, four or five easier than I expected. So I was like, okay, let me try five plates. And I did five and I was thinking maybe I should stop there and my body's sort of in a low energy state and I just kept going. I normally can do more, but I, I felt that the 10, I don't even think I got sore the next day. But yesterday actually I just, I got back from traveling in Australia and I picked up a stomach bug on the last day as I really didn't eat for about two or three days. And yesterday I just posted it on Instagram, Facebook, I deadlifted five plates for 15. And my body weight was really low to one 98. Dominic D'Agostino That's extremely low for me. I'd be, haven't been that low since I was a teenager and I was kind of in a backseat state again. And again, I don't for exercises, like if for things pressing movements, if I lose weight, my, my strength goes way down. But for things like deadlift, I always kind of feel strong in a semi fasted state. And I think I've mentioned this to Tim's brand and Tim friend told Tim and then he unexpectedly added it to that podcast and it's like, I don't, I don't, don't, it's like, no, no, I think it's, you've got to start off. That's how you engage people. So I requested it not, you know, I mentioned that, but he mentioned it and it's like, then I had to live up to it, then I had to actually go and do it. Wade Lightheart: That's a fascinating, it's the next fascinating segue cause it's a pattern interrupt for most people who think three or four hours without eating, they're going to die. Especially bodybuilding six times a day probably. Yeah, exactly. So it's a point of interest. I think that kind of, you know, creates another level of curiosity for people to find out, well, well how is that possible? What is this guy doing? You know? And, and it, I think it just adds a a level of verification about the efficacy of what you're doing and what you're promoting and, and, and how you're going about doing it. It also opens a door, I think, which Matt's going to dive into here about asking some very specific questions because as is, he'll reveal he's, he's been deep down the ketogenic adventure for as long as anybody I know. Matt Gallant: So, so I want to get into I guess some nerdy stuff and you know, one of the things I believe in, I'm curious what your thoughts on this phone is that if we look at health as a spectrum on one side you got, you know, sickness and then your death and that in the middle what people call normal. Wade Lightheart: And then at the very end of the other side you have peak performance, peak health. So what I've seemed to notice is that all the things that might fix health issues, you know, for that get us from no sickness to normal will typically also get us from normal to a peak state. And you know, I want to get into the neuro cognitive enhancements that happened with the ketogenic side and you really want to understand what's happening exactly, again on a brain level and on a nervous system level that is producing enhancements. Like why, why is ketones enhancing the cognitive side? Dominic D'Agostino: Yeah, that's a subject of intense research and numerous labs right now. We have garnered sort of a lot of information over the years. Well personally doing it myself and actually measuring my neurotransmitters and, and other blood markers of metabolic health and inflammatory health and neuroinflammation. Matt Gallant: So can I ask you, like what have you seen on a neurotransmitter level? Wade Lightheart: Yeah. And what tests are you running. Dominic D'Agostino I Oh, have different kits here in my drawers. I was going to say that for neurotransmitters, it's not a great test, but one of them that I did, and I did a couple ZRT labs has a urine neurotransmitter test. And I think when I did it down inside the habitat for the NASA emo mission, a couple of them for some reason didn't come out. But the things that came out and made a lot of sense you know, I've, I've done repeated measurements and my GABA to glutamate ratio is very high. It's on the order of two to three times outside the range of normal. So I tend to, at least in a ketogenic state, you make the neurotransmitter gamma-Aminobutyric acid GABA you make, it's a brain stabilizing your transmitter. You actually make that from an excited Tori neurotransmitter called glutamate through the an enzyme called glutamic acid decarboxylase and being in a state of nutritional ketosis with the diet and now we know with supplementation activates the GAD enzyme to convert more glutamate to GABA. Dominic D’Agostino: So you go from a a state of the brain that's hyperactive in the context of what we study. There's excitotoxicity, glutamate, excitotoxicity and it, I think it's in part therapeutic because you are reducing in neurotransmitter that's causing a neuronal hyperexcitability and making GABA, which I don't want to get too down in the weeds, but it mediates, it does chloride mediated post-synaptic inhibition, which it opens up an ion channel that hyperpolarizes the membrane potential of the cell. And when a membrane potential is hyperpolarized, it doesn't fire action potentials as fast. It's more, it's very stabilized. And if there's lots of glutamate excitatory, that will deep polarize the membrane potential and it comes closer to its threshold for firing. So it starts firing action potentials very fast. And if all your neurons are doing that, then you're like dumping glutamate, you're dumping potassium, you're dumping calcium potentially. And this can create a scenario where you have excited toxicity. So in a nutshell, what being in nutritional ketosis does is it changes the neuropharmacology of your brain to prevent you from entering that hyperexcitable state. And so that's one of about a dozen things. And I could go down that sort of list of that on a dozen different things. Another thing that we can, Matt Gallant: No, but that's, that's, that's fascinating. Cause I've done some tests and I'm on the slightly deficient side of, of GABA. So it's probably one of the reasons why I love keto in general and, and why I respond well in that I did not know it what you just reveal. That's fascinating. Dominic D’Agostino: Yeah, we've published that too actually in well it's been published in Humans. But we, we did it in a model of Angelman syndrome and we actually have an Angelman syndrome clinical trial at Vanderbilt right now because of, you know, some of this, the work that we did in preclinical models. Matt Gallant: So a question. I mean when obviously common belief is that the brain runs on glucose, what's your answer to people that go with that? Dominic D’Agostino: Well, you know, that's what I was taught, that that was part of my training in nutrition. You know, you never go below a 60 grams of glucose because that's what the brain's obligate requirement. But then because I got interested in fasting, I was thinking, well, like what does happen when you fast? And I was thinking you know, well, how can people, how can people fast and not go hypoglycemic? And then I started reading a work of Dr. George F Cahill from Harvard medical school where he facet subjects for 40 days. You know, towards the end of that, he injected them with insulin to push their glucose down farther. And it revealed that they were asymptomatic for hypoglycemia because they're the fact that their bodies are adipose was releasing for energy to be used by skeletal muscle and the heart, the brain really doesn't use these large fat molecules for fuel because of the blood brain barrier. Dominic D’Agostino: So the liver converts them to small water-soluble fat molecules. We call ketone bodies or fat derived molecules. And then the ketone bodies can largely replace glucose as an energy source. Although we still our blood glucose levels, they're very powerful homeostatic mechanisms that maintain our blood glucose levels. So glucose really doesn't change all that much. It'll go down to like maybe three millimole or something like that at the glycerol backbone of triglycerides. We'll make continue to make glucose. And then you have gluconeogenic amino acids, especially Alanine that gets released from muscle tissues and that becomes can become glucose. But the primary fuel for brain energy metabolism can switch to from glucose to ketone bodies. And I say that I say primary fuel because more than 50% of brain energy metabolism, it's kind of universally agreed that after prolonged fasting that we are using primarily ketones. And the same thing can happen with a, a strict clinical ketogenic diet. You're primarily running the brain off a ketone bodies. Matt Gallant: So, just to recap, your body has a lot of different ways to internally produce glucose, which is kind of a fascinating cause I've noticed that too, that even when you know, zero carbs, carb or fasting, that, you know, my blood glucose might drop as, you know, high seventies, but it's, it's, it's hard for me to go lower than that even if I'm zero carb and fasting and what not. So, yeah. Have you noticed too that the longer, and I've seen some interesting research recently on this that if you're, it'd been on keto for a long time. That seems to be another level of adoptation where even while you're exercising, the glucose is staying in the muscle. Like the body's actually not even touching some of the glucose, cause I've noticed that even in the last like year or so that I, I just seem to be holding onto more glycogen in the muscle than I used to, even when I'm doing all the same things. Dominic D’Agostino: Yeah. That'll be dependent to some extent on calories. So if calories are if you're, you caloric and you're not at a calorie deficit actually, well I'll come to that later. But if you are, if you do become at a calorie deficit and you're carb dependent, you lose glycogen really fast. If you do become calorie deficit and you're adapted to a ketogenic diet, you, you, you lose glycogen much slower because you are using fat for energy or more fat. The ratio is higher than the ratio of glucose you're using. So, but yes, I think Jeff Bullock has published on these two and athletes is that skeletal muscle glycogen, not liver glycogen, but skeletal muscle glycogen does not change that much. And athletes that are extremely carbohydrate restrictive with their diets, which is difficult for some people to believe. But once you understand metabolic physiology and that we've had adapted the skeletal muscle, the primary engine, you know, that's, that's burning and a substrate to using fatty acids for fuel that actually has a glucose sparing effect and the glucose sparing effect because you're using more fats as opposed to glucose will preserve muscle glycogen. Dominic D'Agostino: Over time there becomes a tipping point. And I think everybody's a little bit different. But I think the point is that, you know, athletes that are, that are adapted to nutritional ketosis really do have a remarkable ability to retain also glycogen. Matt Gallant: So one of the big concerns that some people have and Wade has this concern as well is the loss in kind of, let's just call it the, the last 10% like that peak, especially if you're more of a power athlete. What's your opinion on that? Is that something that if you're fat adapted for long enough that you can regain? What have you seen as far as peak performance, again from a sprinting, weight lifting, those types of athletic endeavors? Dominic D’Agostino: Yeah, these are really good questions. You know, I do believe I've seen enough data to suggest that if you are on a very carbohydrate restricted ketogenic diet and you push an athlete to two dates, extreme short bursts of, of output, total power output may be compromised would likely be compromised to some degree. If someone's on a very restrictive ketogenic diet if you don't add carbohydrates in. So I think, you know, there, there's a lot of nuances here but, but I think that if you take the average athlete who's carbohydrate adapted and adapt them to a low carbohydrate diet forcing their body to sort of burn preferentially more fat for fuel, they can get 80 to 90% of the benefits of low carb without compromising their glycolytic capacity. And you can do this simply by titrating in the carbohydrates back into the diet. Dominic D’Agostino: A tip, you know, low glycemic index carbohydrates, small amounts of carbohydrates will keep glycolytic pathway sort of open various enzyme systems like every big dehydrogenase complex. So that enzyme, the people who favor high carb diets will say, well, your pre-rebate dehydrogenate complex will be suppressed. You won't make as much protein and that the enzyme itself won't be as active. I think one way to keep that, that energetic path open is to periodically add some carbohydrates in, maybe in around your training. And that could be beneficial too. And also if you are, if you are a low carb athlete, when you fuel up intro workout, the type of workouts I do, I don't, I don't really have a fuel up if I, I work my workouts are like 15, 20 minutes or something. But for athletes that work out for like hours at a time to then introduce a sort of a, you know, a carb and a bat sort of supplement at the same time like MCT oil or maybe even mixed with some long chain fats but also a slower burning carbohydrate source after a certain point because you do get carbohydrate, you know it does become a limiting substrate under some conditions and I think each person is a unique metabolic entity. Dominic D’Agostino: I need to experiment, but like the take home messages that if you go on a super strict diet, your low end maybe knocked down a little bit. But if you learn how to use carbohydrates as a performance enhancing substance and you use it sparingly, then I think you can get the best of both worlds. From, from my perspective. Matt Gallant: Yeah, I've seen, I know some guys that have tested their, their, their ketones by doing some cyclical carb re feeds, intro workout, and you know, they've gone as high as like 80 grams on a leg day and had no changes. So they've been able to just maintain ketosis. And because obviously in a squat day, you know, the big deadlift day, you're just going to be burning that glucose in real time. Dominic D’Agostino: The keto community may like cringe at this, but I, I really believe that carbohydrates are a powerful performance enhancing sort of substrate. If you strip strategically and if you deliver a certain types of carbs. I mean, it could be any kind of carb. I mean, when I experiment, I'll use chocolate. I mean, I'll, she's like stuff like that. So it doesn't really have to be a particular kind of carbohydrates, but if you add also lots of water and sodium too, while you're delivering the carbohydrates your blood volume will go up. I mean, you'll notice things in the gym, you know the energy that you feel may just be due to the hyperhydration you get and it doesn't take much. So that's the key. You don't have to throw in like three, 400 grams of carbs and it can be as little as 30 or 40 grams of carbs. If you're a really big guy doing a long workout. Yeah, you might want to titrate, you know, 80 grams of carbs over that duration and maybe a little bit with a refeed. But it certainly doesn't take a lot of carbs to when you're talking about someone who's fat adapted and the, I think 30 grams of carbs for the typical, you know, one, one and a half hour workout, however long people work out these days. Matt Gallant: So you really open up a topic that I had in mindful on time, which is the idea of dual fuel, right? So the idea that you can both run on glucose and ketones simultaneously. I mean, I've done it personally many times. Can you, first of all, can we start with the physiology? Like, how, how is that happening? How is the body burning both glucose and ketones at the same time? Dominic D’Agostino: Yeah, there doesn't seem to be like, it's a strange question for me, like someone who studies physiology because I mean it's just, that's what the body does. But I know there's two camps out there who just kind of believed that, you know, we fuel off carbohydrates or refuel off ketones and fat. But your body has in your brain. We now know, has amazing metabolic flexibility. So if we adapt our bodies over time, and the best way to adapt is to train under specific metabolic conditions. So training while you're fasting periodically, I mean, some people cringe at that, but I think doing it occasionally is a good idea. Training in a state of nutritional ketosis occasionally throwing carbohydrates in so your body recognizes that fuel and to do that periodically. So I mean, I'm coming at a, at a neuroscience perspective because I, I believe a lot of our digital output and our brains are wired to our muscles. Dominic D’Agostino: So if our central nervous system is energized and we have good fuel flow to it, it's going to buy our muscles and can attract more muscle fibers so we can actually get stronger contractions and maintain that over longer periods of time. If we give, our brain has metabolic flexibility and we'll use whatever fuel is available. So glucose and, and ketone bodies we know it can use lactate to a little bit amino acids, but usually, you know, glucose or ketones. So it will use whatever's available and whatever's in the blood. So one strategy could be to do a carbohydrate-based diet that you know, low enough that you maintain optimal insulin sensitivity and then throw in ketogenic nutrition, which could be MCT oils or on supplements without necessarily restricting carbohydrates to the point where you are in ketosis. A MCQ oils can achieve that. Dominic D’Agostino: And also ketone supplements on the market can also achieve that. This is a new idea. But we do know that independent of a carbohydrate restriction, if you administer a ketogenic agent, whether it's a ketone salts, even MCTs or ketone esters, the body will use what's available. So if you elevate that substrate, interestingly, if your ketones are elevated, it seems to facilitate a glucose disposal into the tissue to although it, it kind of appears that because your blood glucose goes down when you administer acutely a ketogenic agent, some individuals, some labs believe that that's an increase in insulin sensitivity that's facilitating glucose disposal that could be happening. But I think when you orally administer a ketogenic compound through counter-regulatory mechanisms, we don't quite understand. There's a decrease in hepatic gluconeogenesis and thereby a paddock glucose output is reduced. We have not done a liver metabolics to figure out what's going on, but it kind of makes sense that it delivers, you know, seeing a high concentration of ketone bodies, it's going to want to spare glucose. Dominic D’Agostino: The glucose you have in your blood now is not like it's the glucose that your liver regulates. So your liver is the master regulator of the glucose that your peripheral tissues seats. So the glucose that's in your blood now, it might be from a couple of days ago, the glycogen that's stored in the liver a couple of days ago. So your liver is like the master regulator. It's why it's important to keep the liver healthy. And when the literacy is ketones, I think that it's a decreasing glucose output. This is important therapeutically for like type two diabetes and also, but it's also kind of important too from a fuel, a dual fuel perspective, which was the question I think people will ask, well what will happen if you throw ketones on top of glucose? You know, then you're just, you're creating this artificial scenario, which could be dangerous. But I believe that, well, we now have experimental data to show that the liver does a pretty good job at recognizing it. Dominic D’Agostino: You know, the, the level of ketones that you have and, and utilizing those fuels and people maybe look at exogenous ketones as an artificial fuel, but it's really just another energy source. I mean you could say that it's creatine, right? I mean, we take or we make creatine, we store it a little bit and when we drink it, we're getting super physiological levels. And from the literature all we can tell it's doing positive things. And I think ketones are kind of like it's good to make them through our own physiology because that forces adaptations and adaptations are necessary for the ketogenic process, that ketone transporter process going across biological membranes. And also with cell C ketones, you're also up regulating keto lit enzymes which allow cells to derive energy and ATP from the ketone molecules. And I think that happens faster when you do it naturally with the ketogenic diet or fasting. And then if you throw ketone supplements on, you know, sparingly. I don't, I don't use em today. I don't use them every day, but I think you can kind of gain, you can kind of gain the system a little bit and gain an advantage. I mean, what our research shows. Wade Lightheart: I can, I would echo that from just a clinical conspiracy, my own stuff. Matt, of course, has been on the ketogenic diet. I'm a, I'm a plant based guy and, but I have an extraordinary blood insulin response, you know, whether it's genetics or whatever. I, you know, when I measure myself, I'm often in a ketogenic state almost when we do our typical fasting on a HomeAway or that sort of stuff. But when I've added ketones, exogenous ketones that Matt's provided for me I, I noticed an instant cognitive performance benefit. Like it's like, okay, I'm a little sharper, everything's a little, little, little crisper and the endurance factor seems amplified for sure. So I, I would echo that just, and that's not very scientific, but it's certainly experimental. And I, and I'm curious, do you kind of do these experiments on your own and then start doing the data and kind of like hitting your bio feedback and then go, I didn't, let's dive into this and see if this is true. I'm just projecting. Or is it you come up with a theory you do in the lab and then you go the other way? I'm kind of curious which way you like to go. Dominic D'Agostino: Well that's a good question. It goes both ways sometimes. And when I got interested in fasting and I read the Cahill studies, then I was like, okay, I gotta do this myself. You know, I gotta, you know, I'm not going to do 40 days, but I'll do a week and see what happens and do the blood work and things like that. And basically all my health markers improved, kind of as you guys would expect. And you know, and as we develop things in the lab, like synthetic ketogenic agents, you know, we'll use them experimentally and sometimes I, you know, take a little myself through the years and, and so some of the things that we use are not, you know, they are experimental compounds right now, but they are tracked towards a clinical use. And once you tinker with these things, then you start to realize some of their potential, right? Their therapeutic potential because some of them like you can actually feel you know, quite remarkably with a acute administration and it's not acting like stimulant. It's not, you know, you're not mixing with caffeine, you're just, you're just elevating the level of available fuel that your brain sees and that has, that has an effect. Matt Gallant: I have a question on that. Cause I usually a twice a year we, we go and do some really extensive hardcore difficult brain training. It's about six hours a day of pushing your brain to its absolute limit, be the equivalent of probably running a couple of marathons a day. And I D I did the first couple of times without ketones and then we started adding like, you know, 30 to 60 grams of esters a day and that allowed us to just continue training cause usually your brain crashing by day three, day four, you know, Wade and I've gone through that. But with the, with the, with the testers, there was no crash. Like day four, day five, day six. I mean you're, you're kind of getting tired, but that's more of a nervous system, you know, but at the same time we were able to continue the training, but the thing that really blew my mind, and I don't understand the, what's going on was the recovery. Like yeah, it gave me a little more energy, but what I really noticed was one, it seemed like I needed almost less sleep taking that many ketones and that I just felt relatively fresh the next day. Again, even despite pushing myself. So from a recovery standpoint, like why, what's going on there? Dominic D’Agostino: Yeah, that's a good, interesting observation too. If you collected data on that, it'd be good to put that together. I, I guess going back to the experience that I can draw off of where I've quantified things to as much as possible would be the NASA extreme environment, mission operations NEMO 22 where a lot of people think I use ketone supplements like every day because we kind of, we're kind of like the people who brought them to market. It mean like Patrick Arnold actually had and you know, years ago and, and different companies or some now. But you know, I don't use ketone supplements every day, but I did during that mission, especially doing the EDAs, the extra vehicular activities and things like that. And for morning multidose and Europe day and and I experimented with in the past. And what I do consistently notice getting back to recovery is that if I'm in a state of deep ketosis I do tend to sleep a little bit less. Dominic D’Agostino: Like lately I've been sleeping like eight hours, sometimes not, but I could sleep about six and a half. And then my amount of deep and REM are the same. So the restorative sleep that I'm getting when my body is in a state of nutritional ketosis seems to be better. So if you have ketones, if your brain has ketones available we now know that the carbon backbone of those ketones are part of the biosynthetic process of making neurotransmitters. Like alpha-ketoglutarate for example, is the precursor to glutamate is the precursor to GABA. And this is called an anaplerotic pathway. So the try-carboxylic acid cycle or the Krebs cycle and the cycle of the NSX make you make the Murray Mallee etc. All these, the, we have demonstrated through metabolomics that these become elevated and you are sort of driving the biosynthesis of neurotransmitters by virtue of increasing TCA cycle intermediates. Dominic D’Agostino: So I believe that this is accelerated a bit because you have the substrate available, you have more precursors can make neuro-transmitters when you sleep. Also, if you're in a state of ketosis, our astrocytes, so we have neurons and we have astrocytes and there's other cells like, like oligodendrocytes and other. But if we just talk about, you know, the two main cells, neurons and astrocytes, the astrocytes tend to store energy in the form of glycogen. When you're on, when you're in a state of ketosis, the ketones will spare just as it does sparing muscle glycogen. The ketones will spare that glycogen in the astrocytes. And part of the restorative process of sleep is to restore the glycogen levels in the astrocytes. So because you're using ketones, you don't have to kind of restore a glycogen levels. So I think that's something. And also there's something called the glymphatic system. Dominic D’Agostino: So your brain has a system that is activated. It's activated all the time, but more so when you sleep and there are things ketones can enhance brain blood flow by 30% with an acute when you acutely elevate ketones with like different ketogenic competence. So I believe that that increase in blood flow and other other factors that are associated with ketosis will increase the glymphatic system performance, if you will. And we'll get a, and this needs to be tested. It's just my, my speculation is that you're enhancing astrocyte glycogen neurotransmitters synthesis and also the glymphatic activity while we sleep. Makes sense. That's a multi-day thing that you're doing. So you're looking at it. So sleep is what would be really important. Matt Gallant: It's critical and we're running dual fuel during that time. So like I'll, I'll, I'll eat a little more carbs. So actually running dual-fuel seems to help. Your thing it seems to help too is like I'll, I'm not a big branch chain amino or amino guy, but adding aminos. So I'm taking 60 grams of ketones, taking like 20 grams of aminos. Plus I'm eating carbs and a lot of good fats as well. And it just seems to help on a lot on all levels. One question that I've had in a, and I haven't seen too much research on this, but experientially I've certainly noticed that. What have you seen in terms of the types of fats and their ketogenic response? Cause for an example, like if I eat animal saturated fats and I measure my ketones, especially like things like pig fat or that it definitely seems to produce more ketones then, you know, monounsaturated, you know, like just different fats seem to produce a different ketone response. What have you seen around that? And, and do you think that's important? Dominic D’Agostino: Yeah, so that's an ongoing question in a ketogenic diet. Well, it should have been ongoing for like 20 years, but only recently are they kind of recognizing that, you know, different fats have different effects. It's not just like macronutrient profiles. And I think it people will have, people have different food sensitivities. So some people who have a dairy a mild dairy allergy, if they take a dairy-based spat it the, the activation of the sympathetic nervous system or various immune factors may actually prevent ketone production. You know, so that's, I found that mildly in myself. But I kind of going back to your observation, I think a fat in the form of butter, you know, a meat fat like pork fat be fat and to some extent maybe chicken fat, these all contribute to very stable, predictable ketone production and meat. And when I tried to sort of mimic that with more of a plant based, I could get my ketones elevated, but it's a little bit less predictable. Dominic D’Agostino: But I think that's primarily because of sort of the plants that I'm getting the fat from. Like nuts, like macadamia nuts and almonds and avocados. You're delivering fiber with it too. So sometimes I can get my ketones elevated to the same extent. And sometimes I think because the natural fibers that are in plants are maybe preventing the release of the fat. And it's going through me. I know if I like a lot of raw homage or something like that, I'm definitely not absorbing all those fats, you know. So if I eat an equivalent amount of fat from raw almond as opposed to pig fat and I acutely do it, I eat the meal and then measure fat. There you're keeping on production will be like proportional to the amount of fat that the liver is seen, dietary fat. So it's kinda hard to quantify that. I guess you could use plant oils and things like that, but Matt Gallant: It seemed that though of course there's the neutrogenomic aspect, there are certain certain genes that obviously seem to indicate better saturated fat breakdown and so on and so forth. So there's probably a pretty strong genetic component to that question. Dominic D'Agostino: Absolutely. And you know, I sh I would like to know more about that and I try to keep up on that as much as possible. I have my own 23andme data and just looking at, you know, putting it on different platforms. I kind of know what works me just through experientially and I know some people have, you know, they have different snips that prevent them from, from metabolizing fatty acids as efficiently as possible. And it may not be an honor off kind of thing, but on a spectrum, right. And some people are just poor oxidizers or metabolizers of fat, so they will if they eat a high fat diet of animal fat, they feel sick, they don't feel good and their triglycerides go up and then does it come down over time. And I would tell that person don't do an animal based. Dominic D'Agostino: You know, and some people feel really good on a, on a plant based diet and all their health markers improve. And you know, I don't know if they give the ketogenic diet enough time, but cause your body does need to adapt to that over time. But I'm not one or the other. But actually I probably eat an enormous amount of plants and I have lots of and I do believe that they should sort of be in the raw form as much as possible. A lot of broccoli, asparagus, cauliflower, things like that and a big salad pretty much every day. And then I add a fatty beef, chicken or a lot of fish and eat a lot of fish in our house to that salad typically. And then maybe add oil on top of that in the form of avocado oil, macadamia nut oil, olive oil. And then I mix MCT oil with the salad dressings too. So I find that the optimal way to get my ketones as high as possible. Matt Gallant: I mean, Wade is the king of the big ass salad. He is, you know, we had introduced me to that know 20 years ago when we were both living in Vancouver and a half to say. And usually I'll try to do at least one big, a solid a week that just like another energy component that I feel from, I don't know if it's a phytonutrients or what's going on exactly. But you know, it, it kicks her, it just kicks something in. So wait, I mean maybe talk about your big ass salad strategy. Dominic D’Agostino: Yeah, I'd like to hear that. I mean, from a, I'll add this real quick if you, cause there's a lot of people are carnivore now and they do one or the other, but if you put your meat, if you eat it with a salad, the fiber from the salad will delay gastric absorption. And also it's aiding your gut microbiome, especially if you have a diverse array of things in the salad. And that's actually enhancing. It's decreasing your glucose and insulin response to the protein. But but I also think it's promoting, you know, healthy digestion, optimal gut microbiome. So I'm just kinda throwing it out there because I dunno, I just posted something recently and someone said, I'm killing myself by eating plants or something because plants are trying to kill you. So it's like, Wade Lightheart: Yeah, that's a pretty extreme position that something Wade Lightheart: We have adapted convenience land. Like wow, I didn't know my salad was so dangerous. Yeah. I've, I've been a big proponent of, you know, there's this certain, you know, when I go, I go to obviously whole foods and things like that to the salad bar, especially when I'm on the road. That's my first stop. And there's something I, there's two things that I think are anecdotally interesting. One is I noticed they're at different times I'll be attracted to different colors. Like I like and, and, and I always indicate to me that there's some sort of mechanism that's letting me know that I need to get more beets today or I need to get more cabbage or whatever it happens to be that. And so I always find it interesting about the colors. The second thing that I've noticed, it was without a doubt, and I'll be going to whole foods right after this call in variably I make these giant sounds like I get the big green bowls at the whole foods that they have them and it's piled up and it's 30 bucks or whatever for my salad. Wade Lightheart: And every single time somebody in the lineup or the cashier will comment that and say, that looks amazing. And I find that's a very interesting response that it's so across the board that there's seems to be some sort of internal recognition that that's good or that's healthy or that's something that I'd like to try. You know, cause it's obviously a ridiculous salad, but I think there was a good point you brought up was the fiber relation to insulin response or the use of fats. And it's, I believe it's one of the reasons why I have such a great insulin response to spite the fact I'm on a plant based diet. I eat a ton of carbs. Yet when you do my testing, it's like, it looks like I'm on a ketogenic diet from a, from an insulin response. Any other comments on your work? Dominic D’Agostino: It doesn't surprise me. I mean, you know, all those vegetables are carbohydrates, right? So as you would expect an increase in glucose, but if you have a steak and then you have that same steak with a big salad you will have a less of a glycaemic response and less of a rise in insulin too because it's the fiber is delaying gastric absorption to some extent and just delaying the breakdown and release of amino acids into the blood. And and I think it's even more pronounced if you add back to that salad. I actually think of in ketogenic diet formulation, the vegetables are a way are a fat delivery vehicle. So you could lightly steam vegetables, saute them, and then add a lot of fat to that or a salad. You can add a significant amount that to that you can add up condos and nuts and olive oil or a mixed oil dressing and then deliver in a relatively small salad, you can deliver 50 or 60 grams of fat. Dominic D’Agostino: So that, that's, that's important clinically. And this, these approaches are now being used and to keep the genic diets that are having better outcomes as far as seizure controls or metabolic management of particular disorders. And it kinda goes against what was traditionally that the carbohydrates need to be below a certain level. You're adding a lot more carbohydrates in the form of these essentially non glycemic fats, but the fiber and the phytonutrients and other factors are greatly helping to actually induce and sustain ketosis. And you're actually probably significantly enhancing the nutritional status of that patient too by not, you know, eliminating plants, which some ketogenic diets do, but actually being very liberal with your plants consumption, which I think as our nutrition evolves, we need to start incorporating more plants into ketogenic diets. Wade Lightheart: Sounds like there might be an actual unification between ketogenic and plant based diet. Yeah, I'm on that. I'm on that train because you know, we're just into optimal. What is the optimal diet for any given person in there, any, any given lifestyle and something they can sustain. So yeah, great, great to hear that you're on the bleeding edge of that. Matt Gallant: Speaking of optimal diets, I mean when one thing I'll share is I optimize my big ass salad using VIUM data. So the VIUM data is, it got tests and you can send them a school sample and it tells you which foods you should eat, a lot of which food you should eat less of. So I decided, you know what, I'm going to build like a super salad kind of just with the foods that it's saying or should eat a lot of. Matt Gallant: So for example, watercress, rucola those came up because I, I guess I have the gut biome that breaks those foods down. So what was really fascinating was despite eating like two pounds of, it almost sounds about two pounds. I would just incinerate it, like almost nothing would come out and like even my weight would go down. It almost like it almost defied science in the sense that it's like, okay, I'm meeting two pounds, almost nothing's coming out and my weight would drop. And, but if we look at it from a gut biome perspective where they're eating all, like I'm feeding all the bacteria that I have and they're just devouring that food, then it does make sense. So I just wanted to share that anecdotal story cause it kind of surprised me so significantly. You know, it is to shift gears here. You know, to talk about a subject that I think is, is near and dear to all of our hearts, which has cancer. I lost one of my best friends and recently an Matt Gallant::Aunt and an uncle and I like Wade to share his story about his experience with this. And then I love to get into what you've seen as far as ketosis, ketones and cancer. But Wade, why don't you share your story? Wade Lightheart: Yeah. So for those who don't know my sister died at the age of 22. She got sick with Hodgkin's disease of formula lymphatic cancer and progressed over four years. When I was young, it had a big impact, got me into kind of physiology and exercise and performance. And I've been graced now to actually serve as an advisor for the American Anti-Cancer Institute. And we help people who are either going through cancer or recovering from cancer to, to, to make better nutritional solo selections and to prevent it in the future or to optimize their diet. So it's something I'm really, really passionate about. And I'm curious what you have kind of revealed, cause I think one of the, one of the things you talk about was the death at cancer. The, the powerful effects of both the ketogenic diet and its relation to the pre cancer prevention or even as an augmentation. What, what, of, what's kind of fueled that and what have you learned and how can people who may be in one of those situations, where would they go and how would they start researching and for the self to kind of create the best survival situation for them? Dominic D’Agostino: Yeah, that's a, well, it's kind of a long story, but I'll make it as short as possible. Some of the, some of the technologies that we developed for the office of Navy research allowed us to look at a variety of cell lines. And one of them was a equal glioblastoma, a cancer cell line. And I made two observations. One was that high pressure oxygen killed the cancer cells faster than normal healthy cells. And that was because cancer cells had a dysregulation in their mitochondrial function. And if you hyper oxygenate them, they divert more molecular oxygen to super oxide anion, which is the precursor free radical that can go on to other radicals that can basically trigger apoptosis and cells. So we observed this acutely and I thought it was interesting and nobody had observed it before because they didn't have a confocal microscope inside a hyperbaric chamber. Dominic D’Agostino: So so this was like, I was curiously interested in that. And also when I grew cancer cells under different substrates, including low glucose or high glucose in particular high ketones, the ketones suppressed the growth and proliferation of the cancer cell lines I was looking at. So I made, I made two observations studying a military project, which is oxygen and how high oxygen high ketones are bad for cancer. So, so a, a PhD student came along and actually this became a PhD. She's now Dr Angela Pop. And throughout her PhD studies in the lab, we observed that a ketogenic diet with hyperbaric oxygen therapy given three times per week suppressed the growth of a cancer in a particularly aggressive form of metastatic cancer, a model of metastatic cancer that we had in the lab. And you know, so it, it kind of begs the question then, how does a high fat ketogenic diet, how does that contribute to suppressing cancer growth? Dominic D’Agostino: And proliferation and it does it through a number of different pathways. One is that we understand now we actually did back, you know, in the 1920s and thirties, that cancer growth is primarily fueled by glucose and cancer cells preferentially use a higher consumption glucose than normal. Healthy cells do. And we can, we can use a fluorodeoxyglucose pet scan oncologists use a pet scan to image the location and aggressiveness of cancer, but they don't really use that information to target the cancer. But we can, we can share through our best imaging techniques that, that there are consumption of glucose a hundred times higher in certain cancers relative to the healthy tissue that's surrounding it. So it's out competing the healthy tissue to get the glucose. So it keeps a genic diet restricts glucose availability to some extent, right? We know baseline glucose doesn't change all that much unless calories are restricted. Dominic D’Agostino: But when you eat a ketogenic diet, there is a very minimal increase in blood glucose and insulin. When you eat at carbohydrate-based diet, there's a relatively high spike in glucose and insulin. Those spikes in glucose and insulin are abolished if not significantly attenuated on a ketogenic diet. So I think that's important. And, and really what's important, it's a suppression of the hormone insulin. That's how actually we make ketones. The ketogenetic diet works by suppressing the hormone insulin, maybe slightly increase in glucagon and that accelerates fatty acid oxidation in the liver. And that continual suppression of the hormone insulin is absolutely necessary for us to stay in a state of ketosis. Cancer cells are there, growth is driven by insulin. IGF1, PI3-kinase, AKT/mTOR pathway and a few other, you know, things related to that. So what the key to dining diet does is suppress insulin and insulin signaling. Dominic D’Agostino: IGF1, PI3-kinase, AKT/mTOR pathway is acutely and continually suppressed if you follow a ketogenic diet. So what that does is it takes the foot off the gas pedal of cancer growth. Most cancers are driven in growth and proliferation by this particular pathway. And that's why pharmaceutical companies are scrambling to develop drugs that target enter PI three kinase IGF one, things like that. So that the ketogenic diet does that naturally as this fasting, but that that can't be sustained. So what you do is create a scenario where you slow down cancer growth. The ketogenic diet is not going to cure cancer. So that's really important. But what you do is you see in some people it has actually, so I should kind of stop and there's anecdotal or it's an even case board, but most importantly it will slow cancer growth and make cancer a more vulnerable target for other modalities. Dominic D’Agostino: And those modalities could be chemotherapy, it could be radiation. We know from clinical data that chemo and radiation can be a lifesaving for many people there are things like advanced brain cancer and metastatic cancer where these things do not offer much of an advantage. But in the context that I keep a general diet, you may sensitize the tumor in a way or make it more vulnerable to make the cancer or the tumor solid tumor more sensitive to these modalities. And also immune based therapies to may work better in the context of the ketogenic diet where you are limiting glucose availability. So essentially what's that's doing? It's suppressing the glycolytic pathway. That's how cancer cells are primarily making energy, glutamine and glucose. When cancer cells do that, it activates a particular pathway called the pentose phosphate pathway. And that pathway develops, it generates reduced glutathione, and that reduced glutathione makes that cell like a super cell. Dominic D’Agostino: It can protect it against a chemo and radiation because it's, it's an endogenous antioxidant. If you inhibit the glycolytic pathway, you could do it with a Cuban drank diet. There are now drugs that inhibit glycolytic pathways. You crippled the cancer cells ability to defend itself by virtue of suppressing reduced glutathione. And so now that cancer cell becomes more vulnerable target, especially to modalities that kill cancer cells through an oxidative stress mechanism. And that could be various chemo drugs and also radiation. So I'm trying to keep it as simple as possible, but I think that the thing is that the, the, the ketogenic diet works through many different ways. I just described a metabolic way, but it also functioned that suppressing inflammation, which is a major driver of cancer. And then the ketone bodies themselves are epigenetic regulators by acting as class one and class two histone deacetylase inhibitors. So that's an intense area of focus now in our lab and other labs as ketones functioning as signaling molecules, even hormones, if you like, in ways that have anticancer effects by activating tumor suppressors and actually turning off or turning down a oncogenic drivers. So that's an area of intense interest right now that ketones functioning independent of metabolism as influencing various anti-inflammatory pathways. NF-Κb, NALP3 inflammasome, but also through epigenetic regulation. Matt Gallant: I'm gonna steal a question from Tim Ferris and see if your answers is different today, which is if you or a loved one had cancer, what would you do? Dominic D’Agostino: Find out what all the options are given the type of cancer if it's an option where, or if it's a type of cancer where the options are very limited in regards to the standard of care not being very efficacious, and if it's minimally efficacious, you have to evaluate the patient, you know, with their doctor, whether it's worth doing that. Right. So I guess the simplest thing to do is to use a what's called a glucose ketone index. So we know if we can normal glucose being five millimolar, say if we could bring our glucose down to say three millimolar and elevate our ketones to three millimolar, that would give us a glucose ketone index of one. So if our glucose stays at four millimolar and we get our ketones only at two millimolar, that would give us a glucose ketone index of two. Dominic D’Agostino: If you could maintain a glucose ketone index of one to two, even one to four, normal American is like 25, right? So if we can bring that down from 25, which is a glucose dominant metabolism to a glucose ketone index between one and four, again, which is glucose over ketones in millimolar concentrations. And in America we use milligrams per deciliter for some reason, but in millimolar concentrations, so get a GKI of one to four and that will slow cancer growth. Right? I think that's incredibly important. Evaluate the potential for drugs like Metformin. Metformin is available. You could jump online and probably get it. Metformin is when we started studying Metformin, there was maybe two or three clinical trials. Now there's about 200 clinical trials looking at the drug, Metformin as a means to enhance other

I'm constantly playing and experimenting with new devices and so-called biohacks to enhance sleep and cognition. One of my favorites of late is a very handy device called the , which I've been using to simulate an entire 120 minute sleep cycle with just a 20 minute daily powernap. The NuCalm is a next-level cranial electrotherapy stimulation device that uses both a relaxation cream and mild stimulation to help your brain interrupt the adrenaline and cortisol release by mimicking what naturally occurs in your brain right before you sleep. It includes an app with “music” – which is actually neuroacoustic software that delivers frequencies to your brain which take you down to theta brain wavelength. This thing lets me get a 20-minute intense period of relaxation even when I can’t nap, and I’m now ducking away and using it nearly every day, particularly during travel and on airplanes. It’s spendy, but in my opinion, well worth it. You can  and save $500 with code: BEN500. My guest on this show is Jim Poole Chairman, President and CEO of Solace Lifesciences, Inc., the maker of NuCalm. J im is an accomplished business executive with extensive experience in the healthcare,. biotechnology, dental, market research, and IT industries. Mr. Poole manages the strategic direction and ongoing operations of Solace Lifesciences, Inc., a neuroscience company focused on personalized wellness and performance. In 2015, Solace Lifesciences, the maker of NuCalm, was granted the world’s sole patent for “Systems and Methods for Balancing and Maintaining the Health of the Human Autonomic Nervous System.” Mr. Poole has successfully launched global products, managed growth strategies, and effectively optimized business operations for large and small organizations alike. Prior to joining Solace Lifesciences, Jim co-founded Focused Evolution, a premier global management strategy-consulting firm. As a Managing Partner, he managed mergers and acquisitions, due diligence, and growth strategies for venture capital and private equity firms. Under Jim’s leadership, Focused Evolution grew into a multi-million dollar consulting firm, serving a global client portfolio of 49 companies, across a broad in a range of industries. Jim serves on the board of directors of several medical device firms around the world. He is a recognized business leader, public speaker, an accomplished author, and has published numerous articles in industry trade journals and lectures all over the world globally on topics including stress, recovery, performance, and business strategy. Jim has published over 30 articles in industry trade journals. A New York state native, Poole earned a BA in psychology from the University of Massachusetts at Amherst and an MBA in International Business & Marketing from Babson College. During our discussion, you'll discover: -What exactly is a NuCalm?...8:30 Cranial electrotherapy stimulation (CES) Designed to halt the stress response and raise the parasympathetic response Was developed over the course of 20 years by a neuroscientist/quantum physicist/naturopath, Dr. Holloway He's not myopic: you'll find biochemistry, electrical signaling Physiological benefit of living like a monk The is the core of the product Brain and body communicate in 2 ways: chemical and electrical messaging Cycles brain wave function into data Key is in controlling the adrenal glands It's FDA cleared to treat insomnia, anxiety, depression Amino acid GABA (gamma-Aminobutyric acid0); the antithesis of adrenal stimulation GABA is transmitted to the brain via the cream Shuts down the HPA axis (adrenals) The cream contains, in addition to GABA, taurine, glycine, casein tryptic hydrolysate (the protein found in mother's milk) If you didn't get all that, get this: The device relaxes the nervous system, which allows the GABA in the cream to reach the brain and work its magic -How the audio features in the NuCalm app enhance the user experience...22:20 Binaural beats: Discovered in 1839 The ear can't hear them; they bring the signal into the brain Binaural signal processing (512 hz into the left ear; 500 hz into the right ear) Reticular activating system: Stimulation filter to the brain Two functions: pattern recognition and find a shortcut One track on the NuCalm app is over 700 mb of data (compared to 5-6 mb on an iTunes track) Non-linear oscillating algorithm: Takes the brain from beta (awake) to alpha and theta Theta is when the cells cleanup and create energy source for themselves (healing zone) -The science behind going through an entire sleep cycle in a 20 minute power nap...28:00 NuCalm's claims attracted top scientists to validate them World's preeminent expert in HRV verified that the NuCalm truncates a 2 hours of sleep into 20 minutes Won "best of CES" at Consumer Electronics Show Dr. Hollowell was resistant to creating a 20 minute track mimicking an entire sleep cycle (was 40-50 minutes) Supply followed demand; after months of research the 20 minute track was a reality -How the NuCalm device measures heart-rate variability...37:40 Low frequency (LF) pertains sympathetic nervous system High frequency (HF) the parasympathetic Monk-like meditation level within one minute Took 5 years to secure a patent on the technology Worked with the most renowned experts on HRV Captured date from 2 groups: metastatic stage 4 cancer, professional athletes LF is lowered while raising the HF 100 patients with depression and anxiety were studied with astounding results after using the device We understand intuitively that stress causes disease, but don't understand why We can't understand the intangible Long-term time horizons make us apathetic in our youth High-stress/poor sleep lifestyle = not enough time in theta or the 2nd stage of sleep Cancer is the best way to articulate the breakdown We all have cancer in our bodies, however our immune system kills them when it's functioning properly Stress breaks down this function over time Physiological benefit: It activates the vagus nerve Slows breath down to one breath per 10 seconds Syncs heart with the lungs Fully oxygenated -How the NuCalm affects recovery...47:55 Elite military units use the device for expedited recovery without the use of drugs It takes the foot off the accelerator, in a manner of speaking Return on investment: 30 minutes yields 12-15 hours of highly focused work Autonomic system is key to managing stress, anxiety, fear, etc. The itty bitty shitty subcommittee in the back of your brain goes away Without proper sleep, we literally stress ourselves to death The offer is not to cure or heal anything; it's to alleviate stress and allow the body to heal itself, the immune system to fight disease Even monks love the device -The NuCalm's effect on the nervous system beyond HRV and the vagus nerve...56:30 24 page study  -How the NuCalm affects (or interrupts) your normal sleep schedule...1:01:05 Don't take the power nap close to normal bedtime 15 minute rule: use it as an aid to fall back asleep in the middle of the night Sweet spot: between 1-4 pm (normal time body wants to take a nap) Your body cannot compensate for sleep debt NuCalm is not a "hack" for getting less sleep If you live 100 years, you should sleep for 33 years You stay in theta during the NuCalm power nap (which is where the body heals itself); ordinarily you'll be in delta The body relies on GABA during sleep The body keeps the nutrients it needs; secretes what it doesn't The GABA in the cream during a mid-day power nap will still be there when you go to bed at night -Final rapid-fire questions...1:10:45  Whether there is any efficacy in increasing the cranial electrical stimulation using the device About the other settings on the device (relaxation and recovery) About the Ignite app [link] (sympathetic stimulation) Opposite effect of the NuCalm Can be used in tandem, but not independently of NuCalm -And much more... Resources from this episode: : The NuCalm is a next-level cranial electrotherapy stimulation device that uses both a cream and mild stimulation to help your brain interrupt the adrenaline and cortisol release by mimicking what naturally occurs in your brain right before you sleep. It includes an app with “music” – which is actually neuroacoustic software that delivers frequencies to your brain which take you down to theta brain wavelength. This thing lets me get a 20-minute intense period of relaxation even when I can’t nap, and I’m now ducking away and using it nearly every day, particularly during travel and on airplanes. It’s spendy, but in my opinion, well worth it. You can  and save $500 with code: BEN500. - The Fisher Wallace Circadia Ben mentions early in the interview -The other apps Ben mentions: Sleepstream Pzizz Brain.FM - - Episode sponsors: -: My personal playground for new supplement formulations. Ben Greenfield Fitness listeners receive a 10% discount off your entire order when you use discount code: BGF10. -: Now you can get all your healthy superfoods in one glass...with No Shopping, No Blending, No Juicing, and No Cleanup. Get a 20% discount on your entire order when you use discount code: BENG20 -: Achieve your health goals easier and faster with Pique Tea. My mental clarity is through the roof and energy levels have never been better since I've been drinking Pique Tea. Get 15% off your entire order when you use code: GREENFIELD -: Are you ready for upgraded digestion? Take your body to the ultimate edge of human potential and become biologically optimized with Gluten Guardian. Save an additional 10% off your entire order when you use discount code: GREENFIELD Do you have questions, thoughts or feedback for Jim or me? Leave your comments below and one of us will reply!

My guest this week is Trudy Scott, a certified nutritionist on a mission to educate and empower parents and children who suffer from anxiety. She is known for her expertise in the use of targeted individual amino acids, the social anxiety condition pyroluria and the harmful effects of benzodiazepines. Trudy is the author of The Antianxiety Food Solution: How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood and End Cravings. In this episode, Trudy and I discuss the incredible impact that targeted amino acids can have on both children and adults when approached with the right guidance. Trudy shares a few case studies demonstrating the use of amino acids such as Tryptophan, GABA, DPA and more. Connect with Trudy online via her blog, Facebook, and Twitter.   Where does anxiety come from? Trauma Psychological impact Biochemical imbalances   What Are Amino Acids? Amino acids help create and maintain good levels of brain chemicals and neurotransmitters This helps with nutritional deficiencies, such as malabsorption They are the building blocks of proteins i.e. When you consume fish, eggs, red meat - they are broken down into amino acids   Amino Acid Supplements Amino acids such as GABA and Tryptophan can be taken in supplemental form Tryptophan - used to help make Serotonin Serotonin is a calming amino acid that aids in low mood GABA - a neurotransmitter used to control GABA levels, has a calming effect   Assessing Anxiety Caused by Low Serotonin Anxiety symptoms often related to low Serotonin include: Incessant worry, constant re-processing thoughts, insomnia, afternoon/evening cravings, lack of confidence, fearful, phobias, anger issues Upon determining low Serotonin levels an Amino Acid supplement trial can be initiated Case Study example of an 11-year old girl using Tryptophan 5-HTP, also helps with low Serotonin Must be observed carefully within adults in children Often if an amino supplement works with the parents it also works well with the child   Amino Acid In-Office Trial   Chewable or sublingually is best Allows for quick results, 5-10 minutes Sometimes effects are subtle but commonly a noticeable change can be seen This is easier to detect in adults. It may be more difficult for children to express how they are feeling. Level of symptoms will be assessed before and after consuming the amino acid supplement to determine whether the dosage needs to be increased or maintained Visible changes can also be seen in non-verbal children   Anxiety Caused by GABA GABA (gamma-Aminobutyric acid) In children - i.e. poor sleep, holding stomach when anxious or stomach butterflies, tension in shoulders, use of sugary foods to self-medicate In adults - i.e  tension in shoulders, stomach butterflies, using carbs or alcohol to self-medicate tension at end of day Low GABA levels result in physical tension   In-Home Amino Acid Trial ‘GABA Calm' - sublingual supplement 125 mg low-dose, a good place to start if you are trying at home All types of Amino Acid supplements should not be consumed with meals Example of Mother-Daughter GABA trial Anxiety is often manifested as hyperactivity and can be mistaken for ADHD Trudy's book is a great guide to approach Aminos at home   Other Amino Acids to Consider Tryptophan - (use the chewable for better taste) Tyrosine - for attention issues DPA - can help to break carb addiction in children who will only eat carbs and dairy. It is an amino acid that raises endorphin levels so we have the feeling of comfort, reward, etc.   Where to Learn More About Trudy Scott Website & Blog Book The Anxiety Summit The Anxiety Nutrition Institute

I recently worked with a man who took LSD once in college and never stopped hallucinating. It’s been ten years now and it’s still going. We can control it with medication, but take the meds away and it starts right back up again. This is a real disease – hallucinogen persisting perception disorder. Most descriptions of the condition emphasize that it’s just some the visual effects and doesn’t involve distorted reality perception. I’m not sure I believe this – my patient has some weird thoughts sometimes, and 65% of HPPD patient have panic attacks related to their symptoms. Maybe if you can see the walls bubbling, you’re going to be having a bad time whether you believe it’s “really true” or not. Estimates of prevalence vary. It seems more common on LSD and synthetic cannabinoids, less common (maybe entirely absent) on psilocybin and peyote. Some people say about 1-4% of LSD users will get some form of this, which seems shockingly high to me – why don’t we hear about this more often? If I were a drug warrior or DARE instructor, I would never shut up about this. But if most people just get some mild visual issues – by all accounts the most common form of the condition – maybe they never tell anybody. Maybe 1-4% of people who have tried LSD are walking around with slightly distorted perception all the time. There’s a lot to say about this from an epidemiological or cultural perspective. But I want to talk about the pharmacology. How can this happen? Why should a drug with a half-life of a few hours have permanent effects on your psyche? It can’t be that the LSD sticks around. That doesn’t make metabolic sense. And a study discussed here using radio-labeled LSD definitively finds that although a few molecules might stay in the body up to a week or so, there’s no reason to think the drug can last longer than this. I like this study, both for its elegant design and because it implies that somewhere someone got a consent form saying “we’re going to give you radioactive LSD” and thought “sure, why not?” But then why does it have permanent effects? I know very few other situations where this happens, aside from obvious stuff like “it gives you a stroke and then you’re permanently minus one lobe of your brain”. The only other open-and-shut case 100% accepted by every textbook is a movement disorder called tardive dyskinesia. If you take too many antipsychotics for too long, you can get involuntary tremors and gyrations that never go away, even off the antipsychotic. Although traditionally associated with very-long-term antipsychotic use, in a few very rare cases you can get it from a single dose. On the other hand, most people can take antipsychotics for decades without developing any problems. Some other possibilities are controversial but plausible. The sexual side effects of SSRIs almost always stop within a few months of stopping the medication, but a few people have reported cases where they can last years or decades. Psychedelics may permanently increase openness and hypnotizability, though it’s unclear if this is biochemical or just that drug trips are a life-changing experience – see my discussion here for more. Also, for every drug that has a mild week-long withdrawal syndrome in the average population, you can find a handful of people who claim to have had a five-year protracted nightmare of withdrawal symptoms that never go away. So, again, how does this happen? Every discussion of HPPD etiology I’ve seen is speculative and admits it doesn’t know what it’s talking about. Also, most of them are in gated papers I can’t access. But a few papers seem to gesture at a theory where LSD kills an undetectably small number of very important neurons. Hermle et al talk about “the excitotoxic destruction of inhibitory interneurons that carry serotonergic and GABAergic receptors on their cell bodies and terminals, respectively”. Martinotti seems to be drawing from the same inaccessible source in mentioning “an LSD-generated intense current that may determine the destruction or dysfunction of cortical serotonergic inhibitory interneurons with gamma-Aminobutyric acid (GABAergic) outputs, implicated in sensory filtering mechanisms of unnecessary stimuli”. This would require some extra work to explain the coincidence of why the effects of HPPD are so similar to the effects of an LSD trip itself. In particular, if we’re talking excitotoxicity, shouldn’t the neurons be stimulated (ie more active) in the tripper, but dead (ie less active) in the HPPD patient? Maybe the tripper’s neurons are just so overwhelmed that they temporarily stop working? Or maybe you could interpret the comments above to be about LSD exciting some base population of neurons, the relevant inhibitory neurons having to work impossibly hard to inhibit them, and then the inhibitory neurons die of exhaustion/excitotoxicity. Against cell death based explanations, some people seem to recover from HPPD after a while. But this could just be the same kind of brain plasticity that eventually lets people recover from strokes that kill off whole brain regions. The body is usually pretty good at routing around damage if you give it long enough.

Today’s podcast is our “Feel Good” show where we will be joined by Adriene Mishler who is the co-founder of the website findwhatfeelsgood.com, she also leads a Yoga community of over a million people on YouTube with her weekly class called Yoga with Adriene.   When we talk about herbs and extracts on the show we often talk about how it makes us feel. It’s important to have a sense of connection with your body and this goes for anything you do, whether it’s things you put into it or things you do with it.  If you have questions regarding herbal nutrition or are looking for a natural solution to something that ales you, please give us a call at 512 853 9005 and we will try our best to answer your question. This show is sponsored by Dr. Vim's Herbal Nutrition. Dr. Vim's herbal formulas are designed for men and women to mental focus, physical energy, stress reduction and a healthy libido. They use only filler free high potency botanical extracts. ensuring that every batch delivers a full dose of the most powerful phytonutrients on the planet.     Herbs make you feel good! The modern lifestyle can be overwhelming stressful. We end up overworked We are overstressed We are over-critical We are restless and sleep deprived. The result: Improper Stress Response Cortisol is out of balance -constant release of cortisol and fight or flight hormones can have harmful results: weakened immune response problems with sleep over-stressed mind general fatigue harmful inflammation.   Adaptogens and Nervines help you feel good: Adaptogens help us to decrease stress and fatigue, while promoting healthy levels of energy and boost mood. Herbal nervines can help calm the nerves allowing us to relieve stress and tension by calming the nervous system. Some nervines even act as nervous system tonics, strengthening and restoring the nervous system over time. Adaptogens - Rare herbs that are safe, non-toxic and generally normalizing to various systems and organs in the body. The help the body adapt to stress weather is be emotional, physical, or environmental. Nervines - Herbs that are nutritive to or generally support the nervous system with varying effects. Sedatives - Herbs that relax the nervous system and promote restful sleep. Tonic - Herbs that strengthen or tonify an organ or system in the body. Ayurveda - The traditional Hindu system of health and medicine, based on maintaining balance among the five elements earth, air, fire, water, and ether.  The word Ayurveda is derived from the Sanskrit words “ayur,” meaning life, and "veda,” meaning knowledge. Holy Basil (Tulsi) - Referred to as "The Elixir of Life", Holy Basil is a Ayurvedic herb famous for its ability to promote positive mood and relaxation.  It's and adaptogen associated with adrenal health, respiratory tract function, and celebrated for its ability to help the body cope with stress and inflammation.  It has a clove like aroma and makes a tasty herbal infusion. It's one of our favorite sipping herbs at the Power Plant podcast. Vana - known for its aromatic fragrance, Vana Tulsi is a powerful plant with green leaves and stem and white flowers. It’s been used for centuries and can be found in the Himalayas as well as India, Asia and Africa. Rama- Know for is sweet aroma and great taste, Rama Tulsi has been used for centuries to promote a calm, alert mind, promote relaxation, and to support strength and stamina. Krishna - known to be the most "medicinal" of the Tulsi family, Krishna Tulsi has an aromatic, sweet, and clove-like flavor. It is named after the blue skinned God, Krishna, because is dark purple leaves resemble the color of the widely revered Hindu God.   Adaptogenic Herbs that help combat stress and boost energy: Ashwagandha - A key herb in Ayurveda, the traditional medical system of India, that is known as a Rasayana or herb that gives strength. It is one of the most popular adaptogens on Earth because of its ability to safely improve the bodies resistance to stress, restore youthful energy, combat inflammation, and balance the stress hormone, Cortisol. Ginseng (American, Chinese, Korean) - There are 3 popular types of Ginseng used around the world; Chinese, Korean, and American. Chinese Ginseng (Ren Shen) is considered the "king of herbs" in Traditional Chinese Medicine (TCM) and is celebrated as THE premier tonic herb. Ginseng's active compounds, referred to as ginsenosides, are known to restore qi (pronounced "chi") or energy levels and to support a calm, alert mind. Korean Ginseng has similar properties, of course the Koreans report that Korean Ginseng is more potent than Chinese Ginseng. American Ginseng, known as the ‘Yin Ginseng’, has similar ginsenosides to its Chinese and Korean counterparts, although is traditionally viewed as a gentler tonic better suited to people with excess metabolic heat, including but not specific to menopausal women.  It can also help promote a relaxed, calm attitude among those prone to stress and overwork. Rhodiola Rosea - A favorite among athletes and herbal practitioners, Rhodiola has a reputation as one of the world’s greatest mood and energy tonics. It's unique array of phytochemicals have been researched for their ability to regulate key neurotransmitters like dopamine and serotonin. Rhodiola Rosea is a versatile herb that can help you manage stress, boost your mood, restore your energy, and invigorate your workout. Tongkat Ali - Decoctions of Tongkat ali roots have been utilized for centuries in Malaysia and Southeast Asia to support energy levels and mood. In modern times body builders and athletes love it for its ability to promote lean muscle mass. Although commonly taken by men, Tongkat ali can also support women’s libido, mood, and energy.   Nervine Herbs that promote GABA:   GABA (gamma-Aminobutyric acid) - the main inhibitory or calming neurotransmitter in the brain, GABA influences our mood by reducing high levels of the hormones adrenalin, noradrenalin and dopamine. It also affects the neurotransmitter serotonin. Having sufficient GABA in our brain is linked to being relaxed and happy, while having too little GABA is associated with sleep problems, and feeling anxious, stressed, and depressed. Lemon Balm - a member of the mint family, this calming herb has been used in Europe, the Mediterranean, Northern Africa, and India for thousands of years because of its myriad benefits. The rosemarinic acids present in Lemon Balm are believed to boost levels of GABA, a calming neurotransmitter, in the brain. Chamomile - One of the most famous nervine herbs used to calm the nerves and to promote restful sleep. Passion Flower - A calming nervine that help relax the nervous system, relieving tension and restlessness and promoting restful sleep. It's also a common ingredient in herbal aphrodisiacs.  Magnolia - A calming nervine popular for keeping the stress hormone, cortisol, in check. In addition, Magnolia also promotes GABA making it a choice sleep aid as well. Valerian (Sedative) - Valerian is a potent nervine and a strong sedative. It is commonly used in herbal sleep remedies and formulas used to relieve tight muscles. There are some people that find Valerian to do just the opposite and act as a stimulant and cause paranoia. Passionflower – A nervine herb native to southeastern parts of the Americas, Passionflower is now grown throughout Europe and in the United States as well. It has been treasured historically for its' ability to allay anxiety, insomnia, seizures, and hysteria. It has also been used. It is believed that Passionflower works by increasing GABA levels. Other useful Nervine Herbs: Oatstraw – Although it is not a sedative, Oatstraw is a nervine tonic that is generally beneficial to the nervous system. It has also been used to gently restore vigor libido and acts as a restorative to the Adrenal glands. The amazing plant can get you through a stressful day or help you get a good night's rest. Lavender – A herb that's calming to the mind and uplifts the spirit. It's commonly used in Aromatherapy and is used in calming herbal infusions to relieve anxiety and promote restfulness. Some people refer to Lavender as "herbal valium".   Herbs that boost immune function and keep you feeling good in the long run: Astragalus Root – Adaptogenic herb made famous in TCM (Traditional Chinese Medicine) that helps boost white blood cell count and helps to normalize immune function. In TCM it is also celebrated as a powerful energy tonic.  Lemon Balm - a member of the mint family, Lemon Balm is native to Southern Europe and India. It is classically used to calm the nerves, relieve anxiety, and to boost immune function. It's also used to treat cold sores, herpes, and shingles. Medicinal Mushrooms (Ex. Reishi, Corcyceps, Agaricus, Turkey Tail, etc) - Powerful adaptogenic mushrooms that boost white blood cell count and help normalize immune function. Don't get these mushrooms confused with the common variety store bought mushrooms. Button mushrooms and other hybridized mushrooms do not have medicinal value and could be toxic in some cases if not prepared properly. Adaptogens - in regards to long run immune health, Adaptogens work by normalizing the immune system. If the immune system is underperforming it strengthens it, but if it's over performing it normalizes it.   Herbs that help you feel better when your sick:   Oregano Oil - herb used to remedy the common cold, flu, and bronchitis. It's a versatile plant also used for ear aches, intestinal parasites, allergies and sinus pain. We at Power Plant prefer Wild Mediterranean Oregano in most situations. Echinacea Purpurea and Echinacea Angustifolia - an herb native to areas east of the Rocky Mountains, different species of Echinacea are used to fight the common cold, the flu, and other upper respiratory infections. Andrographis - plant native to Southern Asian frequently used for preventing and treating the common cold and flu. Thieves Oil - Legend has it that during the times of the Bubonic Plague that thieves went from house to house to rob those who had died for Plague. A special blend of oils to protect themselves from getting this deadly disease. The powerful blend of oils they used is known as Thieves Oil and continues to be used in modern times to support immune function.   Holy Basil Oatstraw Infusion recipe: Makes 32 oz. of tea   Ingredients: 1 Oz dried Holy Basil (Krishna, Vana, and Rama Blend) 1 Oz Oatsraw Pinch of Damiana Pinch of Passionflower Pinch of ground Vanilla bean Pinch of clove buds to enhance flavor   Instructions: Separate the Damiana and Passionflower into a separate teabag. Combine the rest of the herbs together and place them and the Damiana, Passionflower teabag into a quart sized ball jar. Pour boiling water over the herbs, and tighten the lid. Steep for 20 minutes, then pull the Damiana, Passionflower teabag out. Tighten the lid back down and steep the Holy Basil, Oatstraw, Clove Buds, and Vanilla Bean for an additional 6 hours. This is done to extract the valuable minerals out of the Oatstraw and to maximize taste! Chill and Enjoy!

Welcome to the Power Plant Podcast! Know your enemy! In this episode we'll talk about Stress and ways to combat it through herbal nutrition. We discuss the physical effects of stress as well as the warning signs. We will discuss different ways to regulate the nervous system and recommend some powerful herbs and extracts to combat fatigue. In this episode we will be taking calls from John in New York, who has a high stress job and can't seem to turnoff the mental chatter after work hours. We'll also hear from Sharon in Washington DC, who also has a very demanding job and is looking for a natural way to combat stress. Last we will hear from Lucy in Portland who lost her job, has two kids and is looking for something to help with focus as well as combat stress.    This show is sponsored by Dr. Vim's Herbal Nutrition. Dr. Vim's herbal formulas are designed for men and women to  mental focus, physical energy, stress reduction and a healthy libido. They use only filler free high potency botanical extracts. ensuring that every batch delivers a full dose of the most powerful phytonutrients on the planet.    Podcast 2: Stress: 3 types of stress responses: Social Engagement Mobilization Immobilization   1. Social engagement - our most evolved strategy for keeping ourselves feeling calm and safe. Since the vagus nerve connects the brain to sensory receptors in the ear, eye, face and heart, socially interacting with another person can calm you down and deescalate a “fight-or-flight” type response. When using social engagement you can think clearly, and body functions such as digestion, the immune system, blood pressure, and heartbeat continue to work normally. 2. Mobilization -commonly referred to as "fight-or-flight" response. When social engagement is no longer an appropriate response and we need to either defend ourselves or run away from danger, the body prepares for mobilization. It releases hormones and neurotransmitters to provide the energy you need to protect yourself. When this happens, body functions such as digestive function and immune function, stop working. Under normal conditions, when the danger has passed your nervous system calms the body, the heart rate and blood pressure normalize, and the body goes back into balance. 3. Immobilization - the least evolved response to stress and used by the body only when social engagement and mobilization have failed. You may find yourself traumatized or frozen in an angry, panic-stricken or otherwise dysfunctional state. In extreme, life-threatening situations, you may even lose consciousness or find yourself enabled to survive high levels of physical pain. However, until you’re able to deescalate to a mobilization response, your nervous system may be unable to return to its pre-stress state of balance.   Inappropriate Stress Response!! While it’s not always possible to respond to stress using social engagement, many of us have become conditioned to responding to every minor stressor by immediately resorting to fight or flight. Since this response interrupts other body functions and clouds judgment and feeling, over time it can cause stress overload and have a detrimental effect on both your physical and mental health. Effects of stress overload The body’s autonomic nervous system often does a poor job of distinguishing between daily stressors and life-threatening events. For example: you have a mild, low level stress situation in life and have a stress response like you’re facing a life-or-death situation. When you repeatedly experience the fight or flight stress response in your daily life, it can raise blood pressure, suppress the immune system, increase the risk of heart attack and stroke, speed up the aging process and leave you vulnerable to a host of mental and emotional problems.   Health problems which are caused or exacerbated by stress include: Pain of any kind Heart disease Digestive problems Sleep problems Depression Weight problems Auto immune diseases Skin conditions, such as eczema   Common warning signs of chronic stress: Memory Problems Inability to concentrate Poor judgements Moodiness Sense of loneliness and isolation Depression or general unhappiness Aches and pains Digestive problems Nausea Chest pain or rapid heartbeat Loss of libido Weakened immune function Eating more or less Sleeping problems Substance abuse   Power Plants that promote a healthy stress response:   Energizing herbs for stress management 1. Ashwagandha - The flagship herb of Ayurveda supports healthy adrenal function, energy, and mental focus. Ashwagandha (KSM-66) has been clinically researched and is backed by several randomized, double-blind, placebo controlled human clinical trials to support a multitude of body function. Ashwagandha is one of the most versatile plants in existence and is a key herbal component in countless herbal stress formulas. 2. Rhodiola Rosea -A favorite among athletes and herbal practitioners, Rhodiola has a reputation as one of the world’s greatest mood and energy tonics.  It's unique array of phytochemicals have been researched for their ability to regulate critical neurotransmitters like dopamine and serotonin.  Rhodiola Rosea may help you manage stress, but it won't be sedating. 3. Ginseng (Chinese, Korean, and American) - There are 3 popular types of Ginseng used around the world; Chinese, Korean, and American.  Chinese Ginseng (Ren Shen) is considered the "king of herbs" in Traditional Chinese Medicine (TCM) and is celebrated as its' premier tonic herb.  It's active compounds, referred to as ginsenosides, are known to restore qi (pronounced "chi") or energy levels and to support a calm, alert mind. Korean Ginseng has similar properties. American Ginseng, known as the ‘Yin Ginseng’, has similar ginsenosides to its Chinese counterpart, although is traditionally viewed as a gentler tonic better suited to people with excess metabolic heat.  It can also help promote a relaxed, calm attitude among those prone to stress and overwork. 4. Holy Basil - one of the most celebrated plants in India, Holy Basil has been valued for centuries for benefiting the mind, body, and spirit.  This great tasting Ayurvedic has been researched for it's potential in the areas of stress relief and relaxation in recent times.  It's the perfect herb to help stay calm and cool in the fast-paced, modern era. 5. Eleuthero - Once thought to be a member of the Ginseng family and referred to as Siberian Ginseng, Eleuthero, is well known as one of the best adaptogenic agents ever used by man.  The epitome of an adaptogen, it supports decreased stress and fatigue while boosting energy and endurance.  Eleuthero is also used in formulas to support memory and concentration. 6. St. John's Wort- revered in Europe for it's ability to help cope with stress and support a positive outlook.  St. Johs's Wort is believed to promote serotonin, a key neurotransmitter thought to play a major role in the central nervous system and in maintaining mood balance.  7. Damiana - traditionally used as an aphrodisiac in Mexico, Damiana also has a reputation for relieving stress and anxiety. Damiana is relatively easy to find, makes a great herbal infusion, and blends well with other herbs.    Calming herbs for stress management 1. Lemon Balm - a member of the mint family, this calming herb has been used in Europe, the Mediterranean, Northern Africa, and India for thousands of years because of it's myriad benefits.  The rosemarinic acids present in Lemon Balm are believed to boost levels of GABA, a calming neurotransmitter, in the brain. Elevated GABA levels are thought to reduce the level of anxiety. 2. Lavender -one of the most common herbs or oils used for stress relief, Lavender has been used for centries for restlessness, sleep problems, nervousness, and mood balancing.  It has a fabulous aroma, tastes great, and blends well with other herbs like Lemon Balm and Chamomile. 3. Wild Milky Oats -rich in B vitamins, potassium, and magnesium Wild Milky Oats are thought to be soothing to the brain and nervous system, while at the same time being restorative to the adrenal glands and nerves.  It's the perfect herb to use to relax and calm the nerves and to tonify the endocrine system. 4. Skullcap Herb - an herb found in countless sleep and stress formulas, Skullcap Herb is believed to help combat mental chatter and relax the mind  and calm the nerves to provide a calm focus.  Some people use it before bedtime to mitigate feelings of agitation and nervous tension. 5. Chamomile - documentation of the herb for its therapeutic benefits goes back over 5000 years, and today it is still one of the most commonly consumed herbs on the planet. Chamomile tea and extracts of Chamomile are frequently used as a mild sedative to calm nerves and reduce anxiety, to help with nightmares and other sleep problems.  6. Peppermint - A common herb that you may even have in your garden, Peppermint has been steeped for hundreds of years to cool the body, calm the nerves, and help the body relax. Peppermint is the perfect herb to relax with during those hot summer evenings. 7. Magnolia -used in Chinese medicine for hundreds of years, Magnolia is believed to help manage stress by keeping the stress hormone, cortisol, in check.  It has also been shown to increase levels of GABA, a calming neurotransmitter, in mice.  It is commonly found in herbal sleep an stress formulas.  8. Passion Flower - Native to southeastern parts of the Americas, Passionflower is now grown throughout Europe and in the United States.  It has been used historically as a calming herb for anxiety, insomnia, seizures, and hysteria and is still used today to alleviate anxiety and insomnia. Scientists believe Passionflower works by increasing levels of GABA, a calming neurotransmitter, in the brain.  Although it can be used as a stand alone herb, it commonly found in herbal infusions with other herbs such as Valerian, Lemon Balm, and Chamomile to promote sleep or relaxation. 9. L - Theanine - not an herb per se, L - Theanine is an amino acid found in green and black teas. It's famous for it's ability to promote alphawave activity in the brain resulting in a feeling of relaxation and mental clarity.  L-Theanin is an excellent choice for stress support, focus, or calming down before bedtime. 10. Kava Kava -  a plant native to the western Pacific islands, Kava was consumed in ceremonies to promote relaxations.  Today, it is still commonly used to help calm anxiety, stress, and restlessness, and to treat sleeping problems. It is important to research Kava before using it, especially if you have a history of liver problems, because it has been associated with liver problems in the past.      Key Word Definitions:  Adaptogen - a nontoxic substance and usually a plant extract that is used to increase the body's ability to resist the damaging effects of stress and promote or restore homeostasis. Tonic -  A remedy believed to restore exhausted function and promote vigor and a sense of well-being. Tonics are categorized according to the organ or system on which they are presumed to act, as cardiac, kidney, adrenal, vascular etc. Neurotransmitter - a substance  that transmits nerve impulses across a synapse.  Some neurotransmitters are inhibitory (calming) such as GABA and some are exitotory (stimulating) like dopamine. Serotonin -  An important neurotransmitter that has many functions including the regulation of mood, appetite, and sleep. Serotonin also plays a role in cognitive functions, including memory and learning. The modulation of serotonin at synapses is believed to be a major factor in several classes of pharmacological antidepressants. GABA (gamma-Aminobutyric acid) - the main inhibitory or calming neurotransmitter in the brain, GABA influences our mood by reducing high levels of the hormones adrenalin, noradrenalin and dopamine. It also affects the neurotransmitter serotonin. Having sufficient GABA in our brain is linked to being relaxed and happy, while having too little GABA is associated with sleep problems, and feeling anxious, stressed, and depressed. Tryptophan - as a precursor to many neurotransmitters and neurochemicals, including serotonin and melatonin, L-tryptophan is an essential amino acid that helps improve sleep and reduce stress. Melatonin is known to help improve sleep, and serotonin is needed to improve mood and mental health. Cortisol - Cortisol is a steroid-based hormone and is synthesized from cholesterol and belongs to a group of hormones called glucocorticoids. Cortisol is made in the adrenal cortex of the adrenal gland, which is near the kidney. It is the primary stress hormone.  It's functions are to increase sugars (glucose) in the bloodstream, enhance your brain's use of glucose and to increases the availability of substances for tissue repair.  Cortisol also curbs functions that would be nonessential or detrimental in a fight-or-flight situation. It alters immune system responses and suppresses the digestive system, the reproductive system and growth processes. It alerts regions in your brain that control mood, motivation and fear. Stimulant - a substance that temporarily increases the physiologic activity of an organ, a system of organs, or that increases nervous excitability and alertness. Adrenal Gland - One of two small endocrine glands, located above each kidney. The outer part, or adrenal cortex, secretes steroid hormones (corticosteroids). The inner part, or adrenal medulla, secretes epinephrine and norepinephrine. Traditional Chinese Medicine (TCM) - The current name for an ancient system of health care from China. Traditional Chinese medicine (TCM) is based on a concept of balanced qi (pronounced "chi"), or vital energy, that is believed to flow throughout the body. Qi is proposed to regulate a person's spiritual, emotional, mental, and physical balance and to be influenced by the opposing forces of yin (negative energy) and yang (positive energy). Disease is proposed to result from the flow of qi being disrupted and yin and yang becoming imbalanced. Among the components of TCM are herbal and nutritional therapy, restorative physical exercises, meditation, acupuncture, and remedial massage. Ayurveda - The traditional Hindu system of health and medicine, based on maintaining balance among the five elements earth, air, fire, water, and  ether.  The word Ayurveda is derived from the Sanskrit words “ayur,” meaning life, and "veda,” meaning knowledge. Homeostasis - The tendency of biological systems to maintain relatively constant conditions in the internal environment while continuously interacting with and adjusting to changes originating within or outside the system.   Function Nutrition: B- vitamins (Folate, B-12, etc.) - a group of water-soluble vitamins that have varied metabolic functions and include coenzymes and growth factors. These essential nutrients allow us to convert our food into fuel, keeping us energized throughout the day. Vitamin B5 is very important for the adrenals and therefore helps with modulating stress. Folate and vitamin B12 are important for mood balance, and given the links between anxiety and depression, they may also be helpful for anxiety. B-6 - an important co-factor nutrient that may boost the production of GABA, a calming neurotransmitter.  GABA is  a key factor supporting the production of other neurotransmitters (chemical messengers) such as serotonin. When supplementing with B-6, the conenzyme or active form (pyridoxal 5'-phosphate) is superior to the isolated form (Pyridoxine), because some people can't activate pyridoxine. Folate - Folate has literally hundreds of function in the human body. It helps the body use Iron, Amino Acids, and Vitamin B-12, thus impacting energy on many levels.  It facilitates the synthesis of key neurotransmitters, such as dopamine, serotonin, and norepinephrine, that are involved in mood regulation and other important functions. Magnesium - Magnesium is needed for the production of ATP, which is the main energy-producing molecule in the body. When magnesium is deficient our cells produce less energy resulting in fatigue. Magnesium is also the fourth most abundant mineral in the human body, a necessary co-factor for hundreds of enzymes, and the most critical mineral of all for coping with stress. Lithium - Lithium is a mineral that is associated with brain function, mood, focus, and the neurotransmitters dopamine.  It has a wide range of other health benefits including immune health, bone health, and antioxidant support. Zinc - Supports the regulation of key energizing neurotransmitter, dopamine, that supports cognitive function and gives you your drive. It is also key in the metabolization of melatonin, which impacts our quality of sleep.  It's also essential for male and female reproductive health and fertility.  It also impacts strength and athletic performance by regulating the flow testosterone and inulin-like growth growth factor-1 (IGF-1). It's noteworthy that the highest concentrations of zinc found in the body is in our brain! It is a principal factor in modulating the brain and body’s response to stress and key to regulating mood.  Selenium - Support thyroid health and supports hormonal balance impacting energy on many levels. Omega 3's (Fish Oils and Algae) - Essential fatty acids that support a healthy inflammation response, combat depression and promote healthy mood and cognitive function.  Omega 3's also support adrenal function and provide hormone support.  Maintaining healthy a adrenal function is imperative for proper stress management. Lifestyle: Sleep, Diet, Personal Relationships, and Exercise all impact how we feel, how we cope with stress, and how much energy we have.  It's important to not overlook the obvious.  Sleep hygiene -  simple habits that promote quality sleep. Prioritize sleep.  Get what ever it is your body requires (7-9 hrs generally). Try to go to sleep around 10pm, when cortisol levels are at their lowest and melatonin levels are at their highest. Stop eating 2 hours before bedtime, and stop hydrating at least an hour before bedtime.  Create at dark environment to sleep in.  Avoid light before bedtime, including T.V., computers, and smart devices that emit light.  You can even dim the lights ahead of time when you're ready to unwind. Try not to hit that snooze button in the morning.  We don't want to interrupt our hormone and neurotransmitter cycles. Avoid the use stimulants, especially in the afternoon and evening.  Diet - No matter what herbs and supplements you take, you still have to support your body with healthy eating habits. Poor eating habits stress our bodies out and may even affect our mood. Eat lots of fresh fruits and especially vegetables.  Try to get the full color spectrum when selecting fruits and vegetables.  Complete nutrition is essential for stress, mood, and energy support.  We've already mentioned key vitamins, minerals, Omega 3's, etc.  Try to find foods rich in these valuable nutrients that support healthy energy levels and promote a healthy stress response.  You can reference the functional nutrition list above to narrow down your search. Exercise - Try and get a moderate amount of fresh air, sunlight, and exercise.  Don't over exercise! The goal is to promote health, and over training can deplete the adrenal and negatively impact your stress and energy levels negatively.  Do it, but don't over do it! Toxic Relationships - Social engagement is the most evolved way to cope with stress. That's why it is so important to surround yourself with people who do not normally add to your stress load.  If simply being around a particular person provokes a fight or flight response, chances are that's a Toxic Relationship!  Always look to build a strong supporting cast of good people to de-stress with.  

In dieser Folge: Das Video der aktuellen Folge direkt auf Youtube öffnen Kurze Zusammenfassung Im Altgriechischen steht die Vorsilbe “Noos” für den “Geist” und “trapein” für “verändern”. Ein Nootropikum (plural Nootropika) verändert also den Geist. Es soll die mentale und kognitive Leistungsfähigkeit des menschlichen Gehirns verbessern und steht für alle möglichen Arten von Substanzen und Supplements (Nahrungsergänzungsmitteln), die positiv auf den Geist wirken sollen, ohne dabei Nebenwirkungen hervorzurufen. Die Mehrheit der Nootropika sind für die kognitive Verbesserung. Sie haben Einfluss auf die Aufmerksamkeit, das Gedächtnis, die Konzentration und Lernfähigkeit, die Problemlösungsfähigkeit und sie Sinneswahrnehmungen und Stimmung. Andere Nootropika zielen auf den Abbau von psychischem Stress und Müdigkeit ab. Sie entspannen den Geist und Körper und verbessern die Stimmung für den ganzen Tag. Nicht zu verwechseln mit verschreibungspflichtigen Medikamenten Nootropika sind nicht mit verschreibungspflichtigen und oft schädlichen Medikamenten zu verwechseln wie Modafinil, mit zahlreichen schädlichen Nebenwirkungen. Wie der Gesundheitsreport der DAK von 2015 zeigt, ist „Doping“ am Arbeitsplatz leider keine Seltenheit mehr. ##Dosierung der Nootropika Die Dosierung sollte nicht zu hoch ausfallen, denn fast jedes Nootropikum weist eine Parabelkurve hinsichtlich seiner effektiven Wirkung auf. D. h., wenn bestimmte Schwellen überschritten werden, die je nach Substanz unterschiedlich sind, sinkt die Wirksamkeit des Nootropikums in vielen Fällen sehr stark ab. Wirkung Wirkung Ein Nootropikum wirkt meist über einen von 3 Hauptmechanismen oder einer Kombination: Stellt dem Gehirn mehr Sauerstoff zur Verfügung. Regt die neuronale Plastizität an. Stimuliert die Konzentration von Neurotransmittern. Acetylcholin Dopamin GABA (Gamma-Aminobuttersäure) Glutamat Noradrenalin Serotonin Mehr Fokus? Grüner Tee Extrakt, Koffein, Vitamin B, L-theanin SOLIDMIND FOCUS Kapseln Einfacher Stack für Anfänger Koffein – 150 mg & L-Theanin – 100 mg Optineuro - mit Guarana, L-Theanin, Cholin, L-Carnitin, Bacopa Extrakt, TMG, Alpha GPC, Tyrosin, Phosphatidylserin (PS), Coenzym Q10, B12 (Methylcobalamin) Fischöl (DHA) Jod – 1 mg Vitamin B12 – 5 mg Stimmungsaufheller GABA Die γ-Aminobuttersäure (GABA, aus dem englischen gamma-Aminobutyric acid) ist das biogene Amin der Glutaminsäure, ein Amin der Buttersäure und der wichtigste inhibitorische (hemmende) Neurotransmitter im Zentralnervensystem. Quelle: (Wikipedia)[https://de.wikipedia.org/wiki/%CE%93-Aminobutters%C3%A4ure] GABA ist ein weit verbreitetes Nootropikum zur Beruhigung des Nervensystems und der Linderung der Symptome von Angst. Es wird auch von Bodybuildern verwendet wegen seiner Fähigkeit, das menschliche Wachstumshormon freizusetzen. SOLIDMIND SLEEP Schlaf Optimierer | Weniger Schlafstörungen | Schneller besser einschlafen | 200g Pulver #Fazit Wenn Du bereits auf einem hohen Level bist, Deine Ernährung und Deinen Lebensstil angepasst hast und das letzte Fünkchen aus Dir herausholen willst, dann sind Nootropika eventuell für Dich geeignet. Vielleicht ergänzt Du sogar bereits mit Nootropika, denn selbst Fischöl fällt darunter oder auch Koffein und Nikotin. Weitere Folgen Evolution Radio Show #032: Der richtige Fokus zählt! Interview mit Biohacker und Unternehmer Lars Müller Webseiten JULIAS BLOG PAWELS BLOG

gamma-Aminobutyric acid (GABA) is an emerging signalling molecule in endocrine organs, since it is produced by endocrine cells and acts via GABA(A) receptors in a paracrine/autocrine fashion. Testicular Leydig cells are producers and targets for GABA. These cells express GABA(A) receptor subunits and in the murine Leydig cell line TM3 pharmacological activation leads to increased proliferation. The signalling pathway of GABA in these cells is not known in this study. We therefore attempted to elucidate details of GABA(A) signalling in TM3 and adult mouse Leydig cells using several experimental approaches. TM3 cells not only express GABA(A) receptor subunits, but also bind the GABA agonist {[}H-3] muscimol with a binding affinity in the range reported for other endocrine cells (K-d = 2.740 +/- 0.721 nM). However, they exhibit a low B-max value of 28.08 fmol/mg protein. Typical GABA(A) receptor-associated events, including Cl- currents, changes in resting membrane potential, intracellular Ca2+ or cAMP, were not measurable with the methods employed in TM3 cells, or, as studied in part, in primary mouse Leydig cells. GABA or GABA(A) agonist isoguvacine treatment resulted in increased or decreased levels of several mRNAs, including transcription factors (c-fos, hsf-1, egr-1) and cell cycle-associated genes (Cdk2, cyclin D1). In an attempt to verify the cDNA array results and because egr-1 was recently implied in Leydig cell development, we further studied this factor. RT-PCR and Western blotting confirmed a time-dependent regulation of egr-1 in TM3. In the postnatal testis egr-1 was seen in cytoplasmic and nuclear locations of developing Leydig cells, which bear GABA(A) receptors and correspond well to TM3 cells. Thus, GABA acts via an untypical novel signalling pathway in TM3 cells. Further details of this pathway remain to be elucidated. Copyright (c) 2005 S. Karger AG, Basel

Double-barrelled ion-sensitive micro-electrodes were used to measure the changes of the intracellular activities of Cl-, K+, and Na+ (aiCl, aiK, aiNa) in neurones of isolated rat sympathetic ganglia during the action of gamma-aminobutyric acid (GABA). The membrane potential of some of the neurones was manually 'voltage clamped' by passing current through the reference barrel of the ion-sensitive micro-electrode. This enabled us to convert the normal depolarizing action of GABA into a hyperpolarization. A GABA-induced membrane depolarization was accompanied by a decrease of aiCl, aiK and no change in aiNa, whereas a GABA-induced membrane hyperpolarization resulted in an increase of aiCl, aiK and also no change in aiNa. GABA did not change the free intracellular Ca2+ concentration, as measured with a Ca2+-sensitive micro-electrode, whereas such an effect was seen during the action of carbachol. pH-sensitive electrodes, on the other hand, revealed a small GABA-induced extracellular acidification. The inward pumping of Cl- following the normal, depolarizing action of GABA required the presence of extracellular K+ as well as Na+, whereas CO2/HCO3--free solutions did not influence the uptake process. Furosemide, but not DIDS, blocked the inward pumping of Cl-. In conclusion, our data show that only changes in intracellular activities of K+ and Cl- are associated with the action of GABA. Furthermore, they indicate that a K+/Cl- co-transport, and not a Cl-/HCO3- counter-transport, may be involved in the homoeostatic mechanism which operates to restore the normal transmembrane Cl- distribution after the action of GABA.

Carbachol and γ-aminobutyric acid depolarize mammalian sympathetic neurons and increase the free extracellular K+-concentration. We have used double-barrelled ion-sensitive microelectrodes to determine changes of the membrane potential and of the free intracellular Na+-, K+- and Cl−-concentrations ([Na+]i, [K+]iand [Cl−]i) during neurotransmitter application. Experiments were performed on isolated, desheathed superior cervical ganglia of the rat, maintained in Krebs solution at 30°C. Application of carbachol resulted in a membrane depolarization accompanied by an increase of [Na+]i, a decrease of [K+]i and no change in [Cl−]i. Application of γ-aminobutyric acid also induced a membrane depolarization which, however, was accompanied by a decrease of [K+]i and [Cl−]i, whereas [Na+]i remained constant. Blockade of the Na+/K+-pump by ouabain completely inhibited both the reuptake of K+ and the extrusion of Na+ after the action of carbachol, and also the post-carbachol undershoot of the free extracellular K+-concentration. On the other hand, in the presence of ouabain, no changes in the kinetics of the reuptake of K+ released during the action of γ-aminobutyric acid could be observed. Furosemide, a blocker of K+/Cl−-cotransport, inhibited the reuptake of Cl− and K+ after the action of γ-aminobutyric acid. In summary, the data reveal that rat sympathetic neurons possess, in addition to the Na+/K+-pump, another transport system to regulate free intracellular K+-concentration. This system is possibly a K+/Cl−-cotransport.

Responses to bath-applications of 4-aminopyridine (4-AP) and -aminobutyric acid (GABA) were recorded intracellularly from neurones in the rat isolated superior cervical ganglion. 4-aminopyridine (0.1–1.0 mmol/l) usually induced spontaneous action potentials and excitatory postsynaptic potentials (EPSPs), which were blocked by hexamethonium. Membrane potential was unchanged; spike duration was slightly increased. Vagus nerve B-and C-fibre potentials were prolonged. In 4-AP solution (0.1–0.3 mmol/l), GABA (0.1 mmol/l), 3-aminopropanesulphonic acid or muscimol evoked bursts of spikes and EPSPs in addition to a neuronal depolarization. These bursts, which were not elicited by glycine, glutamate, taurine or (±)-baclofen, were completely antagonised by hexamethonium, tetrodotoxin or bicuculline methochloride. It is concluded that: (a) 4-AP has a potent presynaptic action on sympathetic ganglia; (b) presynaptic actions of GABA can be recorded postsynaptically in the presence of 4-AP; and (c) the presynaptic GABA-receptors revealed in this condition are similar to those on the postsynaptic membrane.