Listen to this episode to hear Dr. Seheult's thoughts on:

• 00:06:20 - How MedCram Videos got started and the future of medical education from Dr. Seheult's standpoint.
• 00:09:37 - What to do when life is on the line and the usual hierarchy of evidence doesn't exist, as in early emergency COVID-19 treatment.
• 00:12:46 - The crucial differences in treating early vs. late-stage COVID-19 illness.
• 00:14:40 - How doctors would've treated COVID-19 one-hundred years ago.
• 00:18:13 - How increasing ventilation may powerfully impact COVID-19 disease transmission and why airplanes have surprisingly little disease transmission.
• 00:20:28 - How masks are virtually universally beneficial in the pandemic regardless of type.
• 00:21:32 - Vitamin D and COVID-19
• 00:22:22 - How the steroid chemical structure of vitamin D confers qualities on vitamin D that other vitamins ("vital amines") do not possess, such as membrane permeability that provides access to the nucleus and broad gene regulatory effects mediated by a specialized vitamin D receptor element.
• 00:23:24 - How calcium homeostasis, which was the early and exclusive focus for scientists and doctors that were trying to determine the ideal vitamin D levels, may have caused the RDA to be set too low since we now know vitamin D regulates around 5% of the protein-encoding genome and have much broader effects.
• 00:24:23 - How the hormonal role of vitamin D confers on it properties more similar to other hormones like testosterone and cortisol rather than those of ordinary vitamins.
• 00:26:21 - The surprising level of overlap between COVID-19 positivity and groups most affected by vitamin D deficiency and the surprise finding of how less than 50 ng/mL blood levels of vitamin D associated with greater likelihood of SARS-CoV-2 positivity in the hospital.
• 00:30:27 - How scientists are able to interrogate the effects of low vitamin D levels through genetic research, a type of study known as mendellian randomization.
• 00:34:20 - The gene regulatory effects of vitamin D and the implications for the scale of its biological impact.
• 00:35:49 - How Vitamin D's ACE2/renin-angiontensin-promoting effects may be mechanistically involved in the effects observed in vitamin D COVID-19 studies.
• 00:42:00 - Why ameliorating vitamin D deficiency in one large monthly bolus might be less effective than daily or weekly doses.
• 00:43:23 - How a prescription-only form of vitamin D known as Calcifediol might have an advantage in acute care for COVID-19.
• 00:47:06 - Why skin synthesis of vitamin D from UV B radiation can be extraordinarily unreliable when compared to supplementation.
• 00:53:43 - What the safest dose range for vitamin D is that should also address deficiency in most populations.
• 01:06:15 - The beneficial circadian effect of early morning sunlight.
• 01:07:38 - How sleep deprivation is meaningfully implicated in profound and immediate impairment of viral immunity.
• 01:12:08 - Dr. Seheult's suggestions for how to achieve the highest quality of sleep.
• 01:19:18 - How a century old sanitarium technique used during the Spanish flu era massively boosts interferon by up to ten-times using heat exposure.
• 01:22:38 - How genetic and antibody-induced failures of the interferon system underpin up to 14% of all severe cases of COVID-19 and why interferon is so vitally important for viral response.
• 01:26:43 - Why treating the symptoms of fever during the spanish flu turned out to not be a good idea, immunologically speaking.
• 01:31:58 - Dr. Seheult's on-going research into using hot hydrotherapy as a viral immunity booster.
• 01:47:00 - COVID-19 Vaccines

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In this special two-hour Q&A episode with Dr. Jed Fahey, a world-leading expert on the science of chemoprotection and, in particular, sulforaphane, we discuss many of the listener-submitted questions from the hundreds of live event participants.

Get the full timeline and show notes.

Listen to learn Dr. Fahey's thoughts on…

• 00:07:19 - The minimum daily dose of sulforaphane that elicits beneficial health effects
• 00:12:04 - Why gauging the amount of sulforaphane in foods presents challenges
• 00:17:37 - Workarounds to enhance the sulforaphane in cooked foods
• 00:23:38 - How often to consume broccoli sprouts and how long their effects last
• 00:39:28 - The effects of sulforaphane on glutathione production in the brain
• 00:43:12 - The effects of sulforaphane on cancer
• 01:17:26 - Alternatives to sprouts, such as supplements (and which ones Dr. Fahey recommends)
• 01:33:08 - Safety concerns regarding sulforaphane

In this episode, Dr. Fahey mentions the following companies, websites, and supplements:

• Brassica Protection Products
• Cullman Chemoprotection Center
• Crucera SGS® (Thorne)
• Oncoplex® (Xymogen)
• Avmacol®
• Vision Defense® (Swanson)
• MaxN-Fuze®
• MitoCORE® (Ortho Molecular Products)

Extra resources

Learn how to sprout at home safely by downloading the 15-page sprouting guide developed with Dr. Fahey.

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Giselle Petzinger, MD, an associate professor of Neurology at the University of Southern California and today’s guest, studies the extensive effects of how different types of exercise, in particular skill-based exercise, can affect the clinical outcome for people with Parkinson’s disease.

Dr. Petzinger's work focuses on understanding how to promote brain repair after injury, particularly in the context of Parkinson's disease. She is currently investigating ways to enhance neuroplasticity in a preclinical model of the disease. She has examined the role of exercise in Parkinson's disease, with emphasis on how different types of exercise affect distinct regions of the brain. Her work has implications for improving the quality of life of patients diagnosed with the neurological disorder — a condition for which there is no cure.

In this episode, we discuss...

• 00:06:57 - What is Parkinson’s disease?
• 00:11:57 - How symptoms of Parkinson’s disease generally only appear when ~50% of dopamine-secreting neurons in substantia nigra are lost. 1
• 00:14:57 - How other circuits in the brain can compensate for the loss of function of the substantia nigra.
• 00:18:37 - Prevalence and hereditary risk factors of Parkinson’s disease.
• 00:21:25 - How epidemiological studies have linked increased Parkinson’s disease risk with exposure to pesticides, herbicides, solvents, and certain heavy metals such as manganese. 1
• 00:26:57 - How exercise can lower the risk of developing Parkinson’s disease. 1 2 3
• 00:35:38 - How skill-based exercise, such as yoga, Tai chi, boxing, tango or skateboarding may play a special role in ameliorating some of the effects of the disease by driving circuit-specific effects, by creating top-down cognitive challenge for skills involved in a patient's movement through space.
• 00:47:49 - How serum BDNF significantly increases in Parkinson’s patients after 1 month of treadmill exercise and why this might mean better cognitive function. 1 2
• 00:58:33 - How treadmill exercise with heart rate 80-85% maximum for at least 3x per week slowed the progression of Parkinson’s disease symptoms. 1
• 01:01:31 - Why exercise may not fully replace the use of medications.
• 01:09:58 - How the omega-3 fatty acid DHA has some preclinical evidence suggesting it may reduce motor-symptoms and dyskinesia in Parkinson’s disease. 1 2 3 4
• 01:12:12 - How patients with Parkinson’s disease have higher levels of inflammatory biomarkers and how this might contribute to the disease. 1

Click here to get this episode's show notes and transcript

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Get a sample of our new premium member's content, known as Aliquots, by listening to this in-depth Q&A mashup on Fasting.

What's an aliquot, you may ask? Aliquots are special, curated segments prepared and distributed to premium members via the premium members podcast feed.

This collection of clips covers a range of topics related to fasting, including associated mechanisms of healthspan and longevity, purported health benefits, and when and how to break the fast.

Episode Highlights

• 00:01:36 - Fasting mimicking diet, the ketogenic diet and autoimmune diseases

• 00:13:42 - Spermidine is a fasting mimetic compound

• 00:16:51 - Aerobic exercises in a fasting state induces autophagy quicker than in a fed state.

• 00:25:15 - Intermittent fasting, prolonged fasting and healthspan.

• 00:28:02 - What we know about the minimal fasting time it takes to induce autophagy and apoptosis.

• 00:33:35 - Comparing and contrasting a ketogenic diet with prolonged fasting.

• 00:37:33 - Rhonda compares the rejuvenation effect of time-restricted eating vs prolonged fasting vs fasting mimicking diet.

• 00:41:16 - Rhonda's thoughts on coffee breaking a fast.

• 00:52:29 - Supplements and other medications outside of a time-restricted eating window.

• 01:01:28 - Differences between a fasting-mimicking diet vs a water-only fast.

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Get a sample of our new premium member's content, known as Aliquots, by listening to this in-depth Q&A mashup on Sauna use.

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This collection of clips covers some of the many health benefits associated with sauna use, including heat shock protein activation, cardiovascular health, muscle mass preservation, and more.

Episode Highlights

• 00:07:00 - What are the effects of sauna and hot baths on heat shock proteins and the immune system?

• 00:16:14 - What are your recommendations for infrared sauna temperature and time?

• 00:24:03 - At what temperature and how long do you need to stay in the sauna to activate heat shock proteins?

• 00:26:50 - Does sauna use promote excretion of heavy metals such as arsenic?

• 00:29:12 - Are there ways of mimicking sauna use without regular access to a sauna?

• 00:33:55 - If compounds such as metformin, resveratrol and vitamin E counteract exercise-induced hormesis, would this be true for other stressors such as the sauna, fasting, broccoli sprouts, polyphenols?

• 00:37:06 - How does fasting affect human growth hormone and IGF-1 in respect to muscle mass?

• 00:43:30 - Can saunas be used during fasting to preserve more muscle and increase fat burning?

• 00:45:50 - Can saunas be used to treat headaches?

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Get a sample of our new premium member's content, known as Aliquots, by listening to this in-depth Q&A mashup on pregnancy and child development.

What's an aliquot, you may ask? Aliquots are special, curated segments prepared and distributed to premium members via the premium members podcast feed.

This particular collection of segments covers every single major discussion of pregnancy and child development spanning years of members-only Q&As.

Just for a few examples, it covers...

• My pre-pregnancy regimen, including diet, exercise, vitamins and sleep
• Nutrition for babies and toddlers to maximize brain development and growth
• Extra precautions that I took during my pregnancy
• And much, much more!

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This episode aims to be the most comprehensive compendium on the biology of breast milk ever recorded. Looking at the converging clinical and animal evidence of the impact of breast milk paints a complex and beautiful mosaic of developmentally supportive effects that range from allowing the mother to act as a “compensatory” immune system to possibly supporting the development of entire organ systems through the integration of maternal stem cells found in breast milk.

Episode Highlights

• 00:07:11 - Breast milk composition and production
• 00:09:59 - Human milk oligosaccharides in breast milk establish the infant gut microbiome
• 00:15:48 - Omega-3 fatty acids and other components in breast milk boost brain development
• 00:18:14 - Vitamins and minerals in breast milk
• 00:22:05 - Breast milk stem cells and multi-organ microchimerism
• 00:22:54 - Harmful substances transferred to infant via breast milk
• 00:28:03 - The effects of breastfeeding on the infant's immune system
• 00:31:17 - Effects on intelligence
• 00:34:36 - Breastfeeding as a benefit to maternal health

Get our detailed summary, timeline, references and more on the FoundMyFitness episode page.

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Did you enjoy this episode? If you’re interested in learning more about this topic, check out a preview of our very first Aliquot episode: Aliquot #001: Pregnancy & Child Development. It features a compilation of pregnancy and child development-related topics taken from several Q&A episodes over the last couple of years.

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This is a continuation of the last episode where Dr. Patrick took questions from newsletter subscribers around the on-going pandemic and tried to add value by talking about some of the recent research, among other things.

Some of the topics that came up as a result of the questions submitted include:

• 00:04:03 - Data surrounding SARS-CoV-2 duration
• 00:06:37 - SARS-CoV-2 and potential immunity
• 00:11:35 - Some of the main factors known to play a role in immune variation
• 00:12:05 - What role genetics may play in immune function
• 00:14:27 - How previous viral exposure regulates immunity
• 00:15:05 - What cross immunity is and how it may be relevant for SARS-CoV-2
• 00:19:46 - Antibody-dependent enhancement and SARS-CoV-2 relevance
• 00:21:50 - How sleep is a key regulator of immune function
• 00:23:44 - Microbiome composition and immune function
• 00:28:31 - The differential effects of exercise intensity and duration on immune regulation
• 00:35:00 - How specific micronutrient inadequacies may promote immune dysregulation
• 00:47:20 - The effect of sex hormones on immune function
• 00:48:55 - How biological age age may play a role in immune regulation
• 00:49:46 - Controversy surrounding hypertension drugs such as ACE inhibitors and COVID-19
• 00:53:15 - ARDS and long-term lung damage

Get our detailed summary, timeline, references and more on the FoundMyFitness episode page.

This episode mentions a number of genetic polymorphisms that affect viral entry into the host cell, viral replication, host immune response ranging from cytokine production to viral-induced inflammation, SNPs that affect vitamin D levels and more. If you have used any consumer-based genetic testing services like 23andMe or Ancestry DNA we have a free viral report with these SNPs that you can check out.

• Learn more about this free report by clicking here.

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In this episode, Dr. Rhonda Patrick discuss all things vitamin C. This episode covers oral bioavailability, intravenous vitamin C bioavailability, immune cell function, common cold and other viral infections, lung function, sepsis, pneumonia, inflammation, intravenous vitamin C and cancer, role in exercise, safety concerns, and so, so much more!

Episode Timeline (abridged)

• 00:07:33 - Background on vitamin C
• 00:17:09 - Bioavailability of vitamin C [including dosing frequency]
• 00:22:53 - Vitamin C in the context of the common cold
• 00:28:09 - Vitamin C and lung function
• 00:35:54 - Vitamin C in the context of exercise [includes discussion of blunting of exercise adaptation]
• 00:45:51 - Vitamin C and fatty acid oxidation, including relevance in obesity
• 00:48:44 - Vitamin C and the brain
• 00:51:15 - Intravenous Vitamin C and its use for the treatment of certain kinds of infection
• 00:55:33 - Intravenous Vitamin C and cancer
• 00:57:40 - Effect of Vitamin C on fertility and reproduction
• 00:58:36 - Intravenous vitamin C and cardiovascular health
• 01:00:42 - Vitamin C and inflammation
• 01:02:38 - Vitamin C’s mechanisms of action
• 01:08:34 - Intravenous and Oral vitamin C safety
• 01:10:20 - Vitamin C intake and kidney stone risk
• 01:13:57 - Conclusions

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View our new 28-page vitamin C overview article with over 190 references by clicking here.

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This episode features Dr. Rhonda Patrick answering some of the most popular questions related to COVID-19. Look for another COVID-19-focused Q&A, coming soon.

Some of the questions we selected from the batch to cover in this episode include:

• 00:02:36 - Are children and infants susceptible to COVID-19? Are some more susceptible to a more severe form of the disease? Are they carriers of it and possibly spreading transmission?

• 00:11:00 - Can you explain a little about hydroxychloroquine as possibly treating COVID-19? How does it work? Does it have to do with it being a zinc ionophore?

• 00:17:58 - Can you talk about quercetin's role as a zinc ionophore?

• 00:20:51 - Is there any indication blood type influences COVID-19 risk?

• 00:24:52 - Would you shed light on the conversation regarding vitamin D upregulating ACE2 receptors and vitamin D's influence on susceptibility to COVID19 infection?

• 00:43:45 - Can you discuss whether sauna use might help prevent COVID19?

• 00:52:55 - Is it true that high dose intravenous vitamin C might help treat COVID-19?

• 01:04:35 - What are your thoughts on melatonin being a potential factor for impacting the severity of the virus via its effects on inflammation and oxidative stress?

To supplement this podcast Q&A, we’ve also made a video, summary, timeline, and references. You can view all of these on the episodes page on my website at foundmyfitness.com/episodes/covid-19-qa-1.

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This episode was originally recorded for The Kevin Rose Show. Given some of the unique discussions we had, I had no choice but to ask the great Kevin Rose if he would let me re-post it over here on the FoundMyFitness podcast feed. A request which he graciously obliged.

In this episode, we discuss...

• 00:08:00 - Omega-3
• 00:27:23 - Metformin
• 00:50:05 - Sulforaphane
• 01:06:57 - Magnesium L-Threonate
• 01:13:44 - Sauna
• 01:23:48 - New FMF Membership

Learn more about the new premium membership.

Learn more about sauna on our overview page.

Learn more about metformin on our overview page.

Learn more about Kevin Rose at his website or on his Twitter @kevinrose. You can also subscribe to either of his two podcasts:

• Kevin Rose Show
• Foundation by True Ventures

In this episode, Rhonda gives a summary of the science of resveratrol including its effects in animals and humans, mechanisms, and the bottom line on resveratrol supplementation and safety.

Learn more about resveratrol at our comprehensive overview

Relevant timepoints...

• 00:03:39 - Clinical effects of resveratrol in humans
• 00:04:10 - Effects on cardiovascular health biomarkers in humans
• 00:06:54 - Reduction of inflammatory biomarkers in humans
• 00:08:11 - Improved cognition and memory in clinical studies
• 00:11:23 - Healthspan improvements in animals
• 00:12:28 - Induction of longevity genes via xenohormesis
• 00:16:19 - Contradictory effects on exercise-associated benefits
• 00:20:34 - Various factors that affect resveratrol bioavailability
• 00:23:09 - Unintentional effects on drug metabolism

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• Learn more about NAD+
• Learn more about nicotinamide riboside
• Learn more about nicotinamide mononucleotide
• Learn more about sirtuins

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David A. Sinclair, PhD, is a professor in the Department of Genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for the Biological Mechanisms of Aging. He is the co-founder of the journal Aging, where he serves as co-chief editor.

Dr. Sinclair's work focuses on understanding the mechanisms that drive human aging and identifying ways to slow or reverse aging's effects. In particular, he has examined the role of sirtuins in disease and aging, with special emphasis on how sirtuin activity is modulated by compounds produced by the body as well as those consumed in the diet, such as resveratrol. His work has implications for human metabolism, mitochondrial and neurological health, and cancer.

In this episode, we discuss...

• 00:17:59 - How caloric restriction, fasting, and exercise increase levels of a molecule called NAD+ and how this activates sirtuins, a family of genes involved in longevity.
• 00:21:47 - How NAD+ levels and sirtuin activities decrease with age, and how animal studies suggest that raising cellular NAD+ levels can trick the body into thinking it is younger.
• 00:23:03 - How resveratrol enhances the binding of sirtuins to NAD+ thus making sirtuins more easily activated for a longer period.
• 00:27:36 - We also discuss Steve Horvath's epigenetic aging clock, which measures DNA methylation groups, and how they may play a role in widespread gene regulation, including sirtuin genes, and how NAD+ may participate in resetting the clock.
• 00:31:54 - How the signal that resets the epigenetic clock in mice involves the Yamanaka factors -- a group of four transcription factors that can reprogram an adult cell to become a pluripotent stem cell that can form any cell type.
• 00:46:48 - How resveratrol is a xenohormetic compound and is produced when grape plants are stressed either in response to fungus or lack of water.
• 00:55:35 - How a phase 2 clinical trial involving people with Alzheimer's disease showed resveratrol improved cognitive function, improved cerebrospinal fluid amyloid beta levels, lowered markers of activated microglia, and more.
• 00:58:03 - How both nicotinamide riboside and nicotinamide mononucleotide have been shown to improve cognitive function and brain pathology in mice that have been engineered to get a disease similar to Alzheimer's disease.
• 01:06:19 - How older mice that were given nicotinamide mononucleotide experienced delayed aging in the liver, muscle, immune cells, eyes, and bones, but those that took a lower dose had improved mitochondrial function and enhanced physical performance.
• 01:01:22 - How there may be challenges in translating animal studies on nicotinamide riboside and nicotinamide mononucleotide to humans particularly due to the need to determine the dose required to promote health benefits.
• And so much more!

Click here to get this episode's show notes and transcript

Watch this episode's highlights on the FMF Clips channel

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This podcast is the audio from a presentation Dr. Rhonda Patrick gave on how the sauna may be an exercise mimetic for heat health and healthspan. Sauna use has emerged as a means to increase lifespan and improve overall health, based on compelling data from observational, interventional, and mechanistic studies. Listen in to find out more.

Click here to get the episode show notes and video.

Watch the episode with cardiologist and sauna scientist Dr. Jari Laukkanen.

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In this short episode, Dr. Patrick discusses some of the compelling science including observational studies, randomized controlled trials, and human mechanistic studies that suggests exercise is a powerful tool for preventing or managing the symptoms of depression and mental illness. Moreover, she talks about the specific types of exercise and exercise parameters that evidence suggests might be the most helpful for depression.

This podcast started its life as a video, so make sure to check out the full video or the references and episode notes on the episode page.

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Click here to visit the in-depth depression topic page.

See the full interview with Dr. Charles Raison.

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Elissa Epel, PhD, is a Professor in the Department of Psychiatry at the University of California, San Francisco where she serves as the director of the Aging, Metabolism, and Emotions Center. Her research centers on the mechanisms of healthy aging and the associations between stress, telomere length, addiction, eating, and metabolic health.

In this episode, we dive deep into the world of telomeres, the length of which is one of the useful biomarkers scientists have for getting a sense of the differences between how individuals or groups of individuals age. Telomere shortening is both a cause and a symptom of aging and plays key roles in not only how long we live, but in how well. Lifestyle factors such as poor nutrition and smoking can accelerate telomere shortening by generating oxidative stress and inflammation.

Click here to get this episode's show notes and transcript.

Watch this episode's highlights on the FMF Clips channel.

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Matthew Walker, Ph.D., is a professor of neuroscience and psychology at the University of California, Berkeley, and serves as the Director of the Center for Human Sleep Science. Formerly, Dr. Walker served as a professor of psychiatry at the Harvard Medical School.

Walker's research examines the impact of sleep on human health and disease. One area of interest focuses on identifying "vulnerability windows" during a person's life that make them more susceptible to amyloid-beta deposition from loss of slow wave sleep and, subsequently, Alzheimer's disease later in life.

Dr. Walker earned his undergraduate degree in neuroscience from the University of Nottingham, UK, and his Ph.D. in neurophysiology from the Medical Research Council, London, UK. He is the author of the New York Times best-selling book Why We Sleep: Unlocking the Power of Sleep and Dreams.

Click here to get this episode's show notes and transcript.

Watch nearly twenty-seven episode highlights on the new FMF Clips channel.

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This episode features a Q&A session with Dr. Rhonda Patrick. The questions were sourced from social media followers of both FoundMyFitness and also Zero Fasting Tracker, a convenient mobile app used widely in the fasting community for logging.

In this 45-minute podcast, Dr. Patrick answers some of the most popular questions related to fasting, including:

• What effects coffee, supplements, and amino acids have on fasting
• Whether one method of fasting is more beneficial than others
• What effect the consumption of exogenous ketones have on fasting
• Whether it is good to exercise while fasting
• The ideal way to break a fast
• How fasting affects muscle mass
• How fasting plays a role in the growth-longevity tradeoff

... and more!

Watch the video of the conversion or get the timeline here.

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Dale E. Bredesen, M.D., is a professor of neurology at the Easton Laboratories for Neurodegenerative Disease Research at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA).

Dr. Bredesen's laboratory focuses on identifying and understanding basic mechanisms underlying the neurodegenerative process and the translation of this knowledge into effective treatments for Alzheimer's disease and other neurodegenerative conditions. He has collaborated on the publication of more than 220 academic research papers.

His work has culminated in the development of a protocol called ReCODE – reversal of cognitive decline – currently used by over 3,000 patients with the goal of not just preventing, but reversing Alzheimer's disease and mild cognitive impairment.

Click here to get the episode's show notes and transcript.

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This podcast is a spectacular round two podcast with Dr. Valter Longo. Dr. Longo is the current director of the longevity institute at the University of Southern California and also director of the Oncology and Longevity Program at the Institute of Molecular Oncology Foundation in Milan, Italy. Dr. Longo’s research focuses understanding the biological mechanisms that regulate the aging process, the role of fasting and diet in longevity and healthspan in humans as well as metabolic fasting therapies for the treatment of human diseases.

In this episode, we discuss...

• What two seminal studies on chronic caloric restriction in primates from the 80s teach us about caloric restriction as a preventer of age-related disease, and how the effects of caloric restriction may actually be stronger when the diet that is being restricted is an unhealthy one – similar, in some ways, to the typical western diet.
• How certain macronutrients influence the insulin/IGF-1/growth hormone axis interact to modulate aging in many cell types.
• How mice and humans who have growth hormone receptor deficiencies have low circulating IGF-1 – as little as 10% of normal levels – and have reduced risk of diseases like cancer, diabetes, and age-related cognitive decline, hinting at what future research might reveal about the beneficial effects of prolonged fasting and fasting-mimicking diets through the downstream effects of periodic deprival of growth-related factors.
• How the growth hormone / IGF-1 axis got a big boost early on in scientific interest when it was revealed that mice that have either deficiency in growth hormone itself or the growth hormone receptor live up to 40% longer and how this is accomplished through what is essentially a delaying of the decrepitudes of old age.
• The origins of what Dr. Longo calls the fasting-mimicking diet – a 5-day diet focused on recapitulating some of the benefits of prolonged fasting, like dramatic changes in metabolic biomarkers, but without some of the drawbacks like reduced compliance and other risks that can come with multiple days of grueling strict water fasting in large, heterogeneous populations.
• How periodic prolonged fasting or the fasting-mimicking diet may be able to render cancer cells more vulnerable while conferring stress resistance to healthy cells, a quality known as differential stress resistance. This can happen because of the way fasting interferes with what is known as oncogenic signaling.
• The mixed results associated with the use of the ketogenic diet in treatment of cancer and how some cancers seem to be hurt by the metabolic switch of utilizing ketone bodies, which creates oxidative stress from the use of mitochondria, while other cancers seem to be able to use ketones effectively as an energy source, potentially accelerating their growth.
• Some of the early but promising pre-trial clinical anecdata suggesting potential complementary roles for the ketogenic diet and the fasting-mimicking diet (FMD) used in conjunction with conventional treatments like chemotherapy or radiotherapy for certain cancers like gliomas.
• In the context of aging, how the fasting mimicking diet has been shown to “reset” metabolism, driving down biomarkers associated with poor metabolic health, inflammation, and cardiovascular health.
• How fasting, through the shrinking and then re-expansion of whole systems like the liver, kidneys, heart, and immune cells may represent a type of whole-system renewal that originated as a three-billion-year-old self-repair mode that was only activated during periods of famine or inconsistent food availability, but might now be dormant in people living in a modern world of regular food intake.
• How Dr. Longo’s group has shown that, in animal models of multiple sclerosis and pharmacologically-induced type 1 diabetes, several cycles of the fasting-mimicking diet is able to reverse disease and restore healthful function. This mechanism also may generalize to erasing other diseases of autoimmunity through the destruction of autoimmune immune cells that are essentially reset through fresh differentiation from progenitors untainted by autoimmunity. A very exciting area of continued inquiry!
• How shorter fasts may fail to approach some of the effects of periodic fasting and the fasting-mimicking diet by failing to achieve adequate glycogen depletion and ketogenesis.
• Dr. Longo’s “top picks” for assessing biological age – markers a person can ask their doctor to measure to gauge how well they’re aging.
• A sneak peek at what’s covered in Dr. Longo’s new book, The Longevity Diet.

… and so much more. Go to the timeline on the episode page to see a full breakdown.

Click here to visit the episode page and show notes now.

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Charles Raison, M.D. is a professor at the School of Human Ecology at the University of Wisconsin-Madison and Founding Director of the Center for Compassion Studies in the College of Social and Behavioral Sciences at the University of Arizona. Dr. Raison’s research focuses on inflammation and the development of depression in response to illness and stress. He also examines the physical and behavioral effects of compassion training on the brain, inflammatory processes, and behavior as well as the effect of heat stress as a potentially therapeutic intervention major depressive disorder.

In this nearly 2-hour episode, we discuss the extremely dynamic interaction that the immune system has with mood, behavior, and the brain, as well as the potential that whole-body hyperthermia, a research technique mostly indistinguishable from sauna use, may have for the treatment of clinical depression.

Additionally, we also talk about….

• How depression as a disease may be subdivided based on whether or not there is involvement of chronic inflammation and how this could influence how it should be treated.
• The changes in functional brain connectivity that are associated with the high inflammation subtype of depression.
• The physiological similarities a sauna, hot bath, steam shower, and hot yoga have with whole-body hyperthermia from the standpoint of potentially therapeutically boosting body temperature.
• Preliminary evidence that increased expression of a certain heat shock protein in the brain may influence behavior by protecting against stress-induced depression.

… and so much more. Go to the timeline on the episode page to see a full breakdown.

Click here to visit the episode page and show notes now.

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Eric M. Verdin, M.D. is the fifth president and chief executive officer of the Buck Institute for Research on Aging and is a professor of Medicine at UCSF. Dr. Verdin's laboratory focuses on the role of epigenetic regulators in the aging process, the role of metabolism and diet in aging and on the chronic diseases of aging, including Alzheimer’s, proteins that play a central role in linking caloric restriction to increased healthspan, and more recently a topic near and dear to many of you, ketogenesis. He's held faculty positions at the University of Brussels, the NIH and the Picower Institute for Medical Research.

In this episode, we discuss...

• The effects of a low protein, cyclic ketogenic diet beginning in midlife (12 months of age) in male mice. The result? Increased healthspan and improved memory. Dr. Verdin explains how the cyclic ketogenic diet decreased insulin, IGF-1, and mTOR signaling and decreased fatty acid synthesis, and increased PPAR-alpha (which promotes beta-oxidation and mitochondrial biogenesis in muscle).
• How this diet is somewhat qualitatively similar to fasting.
• Some of the possible reasons why the cyclic ketogenic diet created such a striking improvement in memory even when compared to younger mice.
• How beta-hydroxybutyrate, which is the major circulating ketone body during fasting and nutritional ketosis, may, in addition to being an energy source, regulate inflammation and gene expression by acting as a signaling molecule by inhibiting what are known as class 1 histone deacetylases (HDACs).
• How this inhibition of class 1 HDACs leads to the increased expression of notorious longevity gene Foxo3, which may help explain why mice given an exogenous beta-hydroxybutyrate ester had lower markers of inflammation and oxidative damage, which are physiological contributors to the aging process.
• The role of the nicotinamide adenine dinucleotide (NAD+) in the aging process and how replacing declining levels (or preventing them from declining in the first place) may prove to be an important anti-aging strategy.
• Some of the reasons why NAD+ might be declining with age, its role in DNA damage repair via an enzyme known as PARP, and what the literature says about the NAD+ precursor nicotinamide riboside.
• How a special class of enzymes called sirtuins, also known to be activated by caloric restriction and caloric restriction mimetic resveratrol, is tightly correlated with the level of NAD+ and how this "energetic currency" rises in response to fasting.
• The role of the sirtuin enzymes in regulating mitochondrial function, neuronal functions, stem cell rejuvenation and why they may be important in delaying the aging process.

Grab the full show notes, timeline & glossary from the episode page now.

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This is a nearly 2-hour round 2 episode with none other than Dr. Satchin Panda of the Salk Institute!

At nearly two hours of dialog, this episode touches on a lot of material but has a special focus on practical implementation of time-restricted eating. Put another way, I kept a list of a lot of questions that seem to keep coming up and present them directly to Satchin.

We talk about dealing with shift work, black coffee when fasting, and some of the distinctions between Satchin's approach to time-restricted eating which is influenced by his deep background in circadian biology and more conventional protocols like 16:8 that many people are familiar with.

In addition to these important and very practical how-to tidbits, we dive into lots of interesting new territory as well, including...

• How human anecdote and animal evidence suggests time-restricted feeding may be especially useful for gut-related issues, including inflammatory bowel disease and acid reflux.
• The fascinating way Dr. Panda is using human anecdote from his trial to ask new scientific questions he wouldn't think to ask and then going back to animal data to figure it out and how this unique approach forms a sort of closed loop pattern: animal → human feedback → back to animal for mechanism.
• How labs doing caloric restriction research may have actually been reaping the benefits of time-restricted without realizing it as an incidental to their experimental design.
• The revelation that 70% of FDA drugs are subject to circadian effects and are either less effective or more effective at certain times of the day.
• The effect melatonin has on the pancreatic production of insulin and the insight this lends to why we should probably stop eating 3-4 hours before we go to bed.
• The bizarre way circadian rhythms affects everything from susceptibility to UV damage to recovery from surgery to cancer risk.

Sign-up for Dr. Panda's mobile app study on time-restricted eating.

Grab the full show notes, timeline & glossary from the episode page now.

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Dr. Guido Kroemer is a professor at the University of Paris Descartes and an expert in immunology, cancer biology, aging, and autophagy. He is one of the most highly cited authors in the field of cell biology and was the most highly cited cell biologist for the period between 2007 and 2013. Especially notable among his contributions: he was the first to discover that the permeabilization of mitochondrial membranes is a concrete step towards apoptotic cell death.

This episode is decidedly focused on autophagy, an important cellular program that is inducible by dietary fasting and has broad implications for aging and cancer. Autophagy discussion includes:

• How the 3 main signals that activate autophagy all involve nutrient sensing (00:09:09).
• The role of different types of fasting and nutrient deprivation in autophagy (00:20:55).
• How different types of exercise can induce autophagy (00:24:35).
• How a specific type of autophagy called mitophagy keeps mitochondria healthy (00:36:29).
• How autophagy has been shown to slow cellular aging (00:33:07).
• How autophagy prevents neurodegenerative diseases by clearing away protein aggregates (00:39:38).
• The role of autophagy in cancer as a possible double-edged sword (00:48:29).
• How certain compounds known as caloric restriction mimetics (or fasting mimetics) including resveratrol, spermidine, hydroxycitrate can induce autophagy by tricking the cell through the modulation of one or more of the 3 main autophagy signaling pathways (00:54:52).

Visit Dr. Guido Kroemer's website.

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Watch the full video on YouTube.

This podcast features Jari Laukkanen, M.D., Ph.D., a cardiologist and scientist at the Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio. Dr. Laukkanen has been conducting long-term trials looking at the health effects of sauna use in a population of over 2,000 middle-aged men in Finland. The results? Massive reductions in mortality and memory disease in a dose-response fashion at 20-year follow-up.

In this almost 25-minute episode, we talk about...

• 00:00:37 - The association between sauna use and fatal cardiovascular outcomes.
• 00:00:37 - The inverse association between cardiovascular-related deaths and all-cause deaths.
• 00:02:00 - How men that used the sauna 2-3 times per week had a 27% lower cardiovascular-related mortality than men that used the sauna 1 time per week.
• 00:02:15 - How men that used the sauna 4-7 times per week had a 50% lower cardiovascular-related mortality than men that used the sauna one time per week.
• 00:02:50 - The confounding factors Dr. Laukkanen and his colleagues had to adjust for, such as physical exercise, cholesterol, obesity, smoking, alcohol consumption, socioeconomic status.
• 00:03:26 - The various types of cardiac-related deaths their reductions were shown in, including coronary artery disease, sudden cardiac death and more.
• 00:05:00 - How one of the major mechanisms by which sauna use improves heart health is by reducing blood pressure and incident hypertension.
• 00:05:40 - The mechanisms by which the sauna lowers blood pressure, which can occur via balancing of the autonomic nervous system, improvements in blood vessel function, decreases in arterial stiffness and compliance of arteries.
• 00:06:17 - The increases in heart rate seen with sauna use that make it similar to moderate aerobic exercise in some ways (up to 150 beats/min!).
• 00:06:56 - How time spent in the sauna was one of the more important factors for risk reduction with at least 20 minutes per session in a 174 F (79C) 4-7 times per week being a "sweet spot."
• 00:09:29 - The inverse, dose-response relationship between sauna use and all-cause mortality: 24% for 2-3 times per week, 40% for 4-7 times.
• 00:10:00 - His newest study that now shows a reduction in risk in a similar dose-response fashion for dementia and Alzheimer’s disease by around 65% for the most frequent sauna users.
• 00:10:18 - The way sauna use increases heat shock proteins which repair damaged proteins and prevent protein aggregates and how this could end up being at least one potential molecular mechanism at play.
• 00:13:03 - How sauna use increases growth hormone by 200-330%.
• 00:14:10 - The patterns of sauna use and especially whether to sauna before or after you weight train.
• 00:15:55 - The effect of sauna on mood which may be from improvements in cardiorespiratory fitness and possibly endorphins as well.
• 00:18:39 - How sauna improves heart rate variability.
• 00:20:04 - Cold-water immersion after sauna and a few cautionary words for extreme contrast therapy in people with a pre-existing heart condition that is currently unstable.

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Dr. Judith Campisi is a professor of biogerentology at the Buck Institute for Research on Aging and a co-editor in chief of the Aging Journal.

As an expert on cellular senescence, the discussion involves a lot of talk about aging and cancer, where senescence plays a very important fundamental role. What are some of the strategies we might use in the future to prevent senescent cells? What causes them in the first place?

In this 1-hour long conversation, we discuss a great number of very interesting things including:

• Why diseases of aging, despite occurring in vary diverse tissue types, all begin to crop up simultaneously after 50 or 60 years of life.
• What the fundamental molecular processes of aging are and what some of the on-going research and general thoughts are surrounding these processes.
• What senescence is and the evolutionary biology explanation for why we have the mechanism of cellular senescence in the first place.
• The infiltration of immune cells into our tissues that occurs as a function of aging and the role of damaged or senescent cells in attracting these immune cells.
• The changes in gut permeability that happens with age and how that may increase our susceptibility to chronic, low-level inflammation.
• The role of senescent cells in cancer metastasis and progression.
• The clearance of senescent cells as a valid life extension strategy.
• How mitochondrial dysfunction, even in the absence of DNA damage, can cause cells to undergo senescence.
• The interesting observation that senescence from damage versus energy crisis (failed mitochondria) demonstrates a different and unique phenotype of cellular senescence.
• The effects prolonged fasting may have on the clearance of senescent cells.
• How periodic prolonged fasts might mimic some of the effects associated with an mTOR dampening drug like rapamycin.
• How the secretions of senescent cells can affect the regenerative capacity of stem cells.
• The practicality of a consumer available clinical assays for DNA damage and the challenge of assessing tissue-specific senescence without the use of invasive biopsy.
• The effect of so-called fasting mimetic compounds (e.g. hydroxycitrate, resveratrol & spermidine) on senescent cells.
• And believe it or not much more!

Studies mentioned: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17

Learn more about Dr. Judy Campisi.

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Dr. Gordon Lithgow of the Buck Institute for Research on Aging tells us about worms! Well, more accurately, his lab does research on nematodes, particularly an animal known as C. elegans.

This unassuming scientific model has a lot of important advantages for science: they can be frozen and subsequently thawed and retain viability, they are extremely well understood down to the precise number of cells in their body and the wiring of their nervous system, known as the connectome. Additionally, they have a short lifespan and are cheap to work with. Why would that be advantageous, you may ask?

This is where Dr. Lithgow's work on the Caenorhabditis Intervention Testing Program comes in. Short-lived organisms give Dr. Lithgow and his colleagues the opportunity to see how their biology responds to compounds in different contexts and to do so cheaply and rapidly. Think a vitamin, pharmaceutical or one of any number of other compounds may have a broad effect on longevity? Try it on Caenorhabditis first! Taking this approach allows the broad screening of compounds that might not otherwise get its chance in the limelight if science were limited to only working with rodents, for example.

But what could nematodes possibly have in common with us? The answer to the question is... gene homology! In fact, around 35% of C. elegans genes have a corresponding human version.

In this over 40-minute long conversation with professor Dr. Gordon Lithgow, we talk about...

• Nematodes... especially C. elegans, of course!
• The synergistic way in which research in lower organisms (C. elegans in this case) works together with rodent research to better understand the biology of aging and identify potential therapeutics.
• The story behind the Caenorhabditis Intervention Testing Program, a multi-institutional effort using the advantages of C. elegans short lifespan to screen for potential compounds that may increase lifespan. We also discuss the more expensive-but-closer-to-humans version of this program known just the Intervention Testing Program.
• The various qualities of C. elegans, especially as related to science's deep knowledge of the organism, that make it a perfect fit for this type of research.
• Some of the early experiences that actually lead to my early interest in the aging field and how it actually holds a bit in common with Gordon's story today.
• The role of protein aggregation as a possible fundamental mechanism of aging... even beyond its more established role in neurodegenerative diseases.
• Some of the fascinating research surrounding mild heat stress as a means to increase lifespan in lower organisms.
• Some of Gordon's research into the effects of metal accumulation, particularly iron, on aging in lower organisms and how, in humans, it may be important to approach the intake of these minerals with care.
• The interplay between genes that influence iron-binding and the development of Alzheimer's disease.
• Some of Gordon's research into the (perhaps surprising) effect of vitamin D on aging in C. elegans and, particularly, on the solubility of proteins... the loss of which is a feature of aging of particular interest.
• The critical involvement of the Nrf2 stress-response pathway in conferring benefits of vitamin D in worms... a pathway many of you may know about from previous discussions of sulforaphane, a robust activator of Nrf2 in humans.
• Some of the challenges encountered with ensuring standardization of protocols across all of the participating labs in the Caenorhabditis Intervention Testing Program.
• The amazing genetic diversity represented in soil-dwelling nematodes and how this is also an advantage in longevity research.
• The interesting possibility that certain compounds may have a different overall effect on lifespan or healthspan that is dependent within certain contexts (e.g. environmentally stressed or not).

Learn more about Dr. Gordon Lithgow.

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Have you done a 23andMe genetic test?
You can learn more about whether you have some of the specific polymorphisms discussed in this podcast, including ones related to the hemochromatosis and transferrin genes, by clicking here.

If you're anything like me, having the facts straight can sometimes help you to push through the tough part of building new habits or breaking old bad ones. This podcast talks about the realities about what the science says surrounding the consumption of refined sugar.

Some of the facts may surprise you! We talk about the relationship of consumption of refined sugar with...

• mortality and aging
• brain function, memory, and neuroinflammation
• the development of cancer and expression of oncogenes
• sex hormones

... and, of special relevance, if you're hoping to cut out a soda habit, the real addictive properties of refined sugar consumption that mirror that of more well-known drugs of abuse.

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Studies mentioned in podcast:
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 10, 11, 14, 15, 16, 17, 18, 19

Today we try to answer or at least explore a big question in the world of health: does saturated fat cause heart disease?

This is not an unreasonable concern given the fact that there have been several associative studies that have found a link between saturated fat and heart disease, which is, no doubt, a fat that we find abundantly in the typical American diet since it is richly found in staples like fatty beef, pork, butter, cheese, and other dairy products.

And if you're in the United States and you're not at least a little concerned about heart disease, you may be asleep at the wheel since it's currently our leading cause of death.

Studies mentioned in this episode:

• Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis.
• Visceral adiposity and metabolic syndrome after very high–fat and low-fat isocaloric diets: a randomized controlled trial.
• Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial.
• Personalized Nutrition by Prediction of Glycemic Responses.
• Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease.
• Added sugar intake and cardiovascular diseases mortality among US adults.

Genetics resources:

• 23andme.com
• promethease.com
• foundmyfitness.com/genetics

Does meat consumption cause cancer? Or, put another way… does avoiding meat help prevent cancer?

If you aren't already savvy to the topic, this may sound more absurd than it should. Here's why: there have been many, many, many correlative studies that have found that higher meat consumption is associated with a significantly higher risk of cancer and cancer mortality.

To try to answer this question we end up going deep into discussing plausible mechanisms that might help explain this phenomenon and, indeed, discussing a little bit of cancer biology as well.

Some of the publications mentioned in this podcast:

• Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality
• Effect of aerobic exercise on insulin, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in overweight and obese postmenopausal women
• Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3
• Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control.
• Functionally significant insulin-like growth factor I receptor mutations in centenarians
• Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies
• Changes in plasma somatomedin-C in response to ingestion of diets with variable protein and energy content

The World Health Organization estimates that more than 350 million individuals of all ages have depression and approximately one-third of all patients with depression fail to respond to conventional antidepressant therapies like SSRI’s.

The good news is that today, perhaps more than ever, good science is starting to illuminate some of the underlying biological mechanisms surrounding the development of depression. This new understanding may soon help the clinical world develop new approaches to treatment that may be vastly more effective and for a greater number of people than the traditional approaches.

Publications mentioned:

• Antidepressants versus placebo in major depression: an overview

• Inflammation: Depression Fans the Flames and Feasts on the Heat

• Association of high-sensitivity C-reactive protein with de novo major depression.

• Sex Differences in Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex Differences in Depression

• Dopaminergic Mechanisms of Reduced Basal Ganglia Responses to Hedonic Reward During Interferon Alfa Administration

• Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.

• Structural and functional features of central nervous system lymphatic vessels

• Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans

• Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism

• Neurobiology: Rise of resilience

• First biological marker for major depression could enable better diagnosis, treatment

• Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial

• Sweetened-Beverages, Coffee, and Tea in Relation to Depression among Older US Adults (P05.122)

• Consuming highly refined carbohydrates increases risk of depression

Dr. Roland R. Griffiths is a clinical pharmacologist at Johns Hopkins and has been researching mood-altering compounds for over 40 years. As an unusually prolific scientist, having published over 360-times, he's also responsible for having started the psilocybin research program at Johns Hopkins nearly 2 decades ago.

In this 1-hour and 15-minute podcast, we discuss…

• 00:01:03 - the broader story of Dr. Griffiths 40 years of mood-altering drug research, including what got him started and how taking up a meditation practice ultimately influenced the eventual focuses of his research.
• 00:02:22 - the effect psilocybin has had in clinical trials in eliciting so-called mystical experiences that can act as a long-term catalyst for meaningful spiritual change and is amenable to being reproduced and clinically studied in a prospective manner.
• 00:03:45 - what distinguishes psilocybin from other drugs, particularly when reflecting backward on the experience months afterward.
• 00:05:11 - the process by which Dr. Griffiths and his team create an appropriate “setting” and facilitate feelings of safety for those participating in his trials.
• 00:06:42 - the elusive fundamental nature of a classical psychedelic experience whereby people often simultaneously describe the experience as ineffable (indescribable) but yet also often assign it a truth value that may even exceed that of everyday consensus reality.
• 00:07:36 - a description of the core features of a classical mystical experience that overlap with those found in a mystical experience induced by psilocybin.
• 00:08:58 - the qualities of the experience that Dr. Griffiths believes to most underlie the “reorganizational” potential it can have.
• 00:10:55 - the interesting potential areas for scientific exploration that the reproducibility of the psilocybin experience makes the substance amenable to.
• 00:11:25 - the promise psilocybin has shown as an effective therapeutic for anxiety and depression in patients with life-threatening cancer and also treatment-resistant depression in otherwise healthy patients (00:18:46).
• 00:13:04 - the lack of rigor in the very early trials on these compounds and the way in which cultural stigma surrounding psychedelic drugs ultimately played a role in impeding real, substantive clinical research for decades afterward.
• 00:16:31 - the long-term resilience of the antidepressant and anxiolytic effect, lasting six months and possibly even longer.
• 00:21:01 - the effect psilocybin has demonstrated in animal studies to increase hippocampal neurogenesis and enhance extinction of trace fear conditioning.
• 00:23:07 - the somewhat unintuitive neurobiological mechanism that may tie together some of the antidepressant properties of both psilocybin and ketamine, an anesthetic currently being studied as a rapid-onset antidepressant.
• 00:25:16 - whether or not the mystical subjective experiences are necessary for drugs like psilocybin to exert their antidepressant or anxiolytic effects.
• 00:26:43 - what the default mode network is and what its pattern of activity is in depression, long-term meditators, and after the acute use of psilocybin.
• 00:32:16 - the hard problem of consciousness.
• 00:37:26 - the challenge of finding the neurological correlates to match the phenomenology of individual’s subjective experiences.
• 00:38:16 - the promise psilocybin has shown in a small trial on smoking cessation where 60% of the treatment group were still abstinent a year afterward and plans Dr. Griffiths has to expand this area of research
• 00:41:10 - the possibility that the “reorganizational nature” of these experiences may open up new avenues as trials continue to try to embed the experience within different therapeutic contexts.
• 00:44:02 - the roadmap to FDA approval for use of psilocybin as a medication, particularly in the context of cancer-associated depression and anxiety.
• 00:45:05 - the risks inherent in taking psilocybin and the frequency of self-reported negative experiences in the general population.
• 00:47:22 - the criteria Dr. Griffiths and his colleagues use when screening for volunteers to participate in his studies involving psilocybin.
• 00:49:21 - the inability for clinicians to predict who is at risk of having challenging experiences defined by fear and anxiety (“bad trip”) and whether or not it is desirable, in terms of achieving a therapeutic outcome, to prevent these types of experiences altogether or not.
• 00:51:43 - the sort of dosages used in the trials.
• 00:54:45 - the clever ways devised by Dr. Griffiths to placebo control trials where expectation itself can affect outcome.
• 00:57:45 - some of the interesting anecdotes gleaned from Dr. Griffiths’ working with long-term meditators participating in the psilocybin trial.
• 01:05:13 - a brief discussion about some of the other psychedelics besides psilocybin, such as salvia divinorum and DMT (at 01:10:24).
• 01:12:08 - the historical indigenous use of psychedelics in various cultures spread throughout the world.

Watch this as a video on YouTube.

Dr. Jed Fahey is a multi-decade veteran of isothiocyanate research and is the director of the Cullman Chemoprotection Center at Johns Hopkins University.

Much of this conversation, as you might expect given Dr. Fahey's pedigree as a research scientist, is focused on isothiocyanates and, indeed, sulforaphane!

While we covered quite a lot on this very topic (isothiocyanates) via my solo podcast a few weeks ago, this covers everything that may have been overlooked.... and, indeed, so much more! Skip to the timeline below for a sampling.

Dr. Fahey and his colleagues have been, in a big way, at the absolute center of what is a staggering amount of research on these very powerful compounds.

There is hardly a topic which we can discuss in which he doesn't have an anecdote about a study he was involved in, or, in some cases, tribal knowledge that may not even be published but is nonetheless interesting and an important part of the story that is unique to his particular vantage point.

In this 2-hour and 30-minute interview, we discuss...

• 00:00:00 - the early history of sulforaphane research, including key initial discoveries.
• 00:00:37 - the serendipitous unfolding of events that lead to the converging of the research on the NRF2 stress response pathway with the sulforaphane-related research going on at the same institute Johns Hopkins.
• 00:05:06 - why cruciferous vegetables bother to create isothiocyanates in the first place.
• 00:07:26 - the involvement of the heat shock proteins, in addition to the increased activity of Nrf2, as an additional cellular response mechanism that's been observed in association with sulforaphane.
• 00:08:11 - how sulforaphane affects a diverse array of biochemical processes from glutathione synthesis to elimination of reactive oxygen species and detoxification of harmful compounds, including carcinogens.
• 00:15:01 - whether or not to cook your cruciferous vegetables.
• 00:15:34 - the epidemiological (associative) evidence that cruciferous vegetable consumption may help reduce the risk of cancer.
• 00:18:30 - the extremely unpredictable nature of endogenous conversion of glucorapahanin (the precursor) into sulforaphane between person to person.
• 00:22:14 - practical information surrounding supplementation of sulforaphane.
• 00:27:05 - the effect one particular french sulforaphane supplement had on the doubling rate of PSA, which is a marker for prostate cancer recurrence in prostate cancer patients.
• 00:28:17 - the role that the Cullman Chemoprotection Center at Johns Hopkins has played, in addition to fundamental research, in providing early, vital infrastructure enabling some of the efforts of the international research community in elucidating the effects of sulforaphane and related compounds and the underlying biological pathways.
• 00:28:26 - the incredible, almost geometric growth in new studies that has occurred since the advent of a few of the key discoveries about sulforaphane and its method of action.
• 00:32:48 - the practicality of probiotics as a way to improve endogenous myrosinase activity needed to convert the precursor to sulforaphane into the bioactive sulforaphane.
• 00:33:26 - the involvement of our gut bacteria in our ability to convert the precursor of sulforaphane into its active form.
• 00:37:13 - whether or not endogenous myrosinase activity improves as a function of repeated challenge with glucoraphanin (the precursor to sulforaphane).
• 00:39:30 - why probiotics may vary in their degree of efficacy.
• 00:43:00 - why consuming isothiocyanates to reduce the number of bacterial colonies of h. pylori, a risk factor for peptic ulcers and stomach cancer, may turn out to be a better intervention than complete eradication of the species with antibiotics.
• 00:47:21 - the bizarre relationship h. pylori has with childhood asthma, where it has been shown that having some h. pylori seems to reduce asthma incidence in childhood.
• 00:52:28 - the effect sulforaphane has on inflammation and why inflammation is often a great therapeutic target for many different diseases, including diseases of aging.
• 00:54:05 - the life extension properties broccoli has been shown to have in an insect model of aging.
• 00:59:27 - the underlying causes of Hutchinson-Gilford progeria and the promise sulforaphane may hold for this disease of rapid aging.
• 01:09:00 - the effects of sulforaphane or Nrf2 activation on diseases of the brain, such as autism (human evidence) and Alzheimer's (animal evidence), possibly through anti-oxidative or anti-inflammatory effects.
• 01:11:09 - the so-called autistic fever response whereby autistic patients report a sudden reversal of symptoms during brief periods of fever.
• 01:10:05 - the role heat shock proteins might play more broadly in the prevention of certain neurological diseases.
• 01:19:00 - the challenges inherent in clinical trials where scientists may be extremely optimistic about the effects that might be observed, but still have to exercise caution and choose trial conditions that may be conservative, for the good of the people whose lives and hopes hang in the balance.
• 01:27:01 - the role of inflammation and depression and what some studies on animals have demonstrated in terms of sulforaphane's potential as an antidepressant.
• 01:42:30 - a special isothiocyanate-containing plant known as Moringa or sometimes referred to as the drumstick tree or the horseradish tree.
• 01:46:32 - Dr. Fahey's inadvertent foray into the consumption of exotic meats during a visit to Africa.
• 01:51:15 - a compound commonly associated with broccoli: indole-3-carbinol and its downstream product diindolylmethane (DIIM).
• 01:57:00 - the practicality of using mustard seed powder as an extra source of myrosinase, possibly for your cooked cruciferous vegetables.
• 02:00:13 - whether or not it makes sense to freeze broccoli sprouts in order to extend their shelf life, and possibly even increase sulforaphane within certain contexts.
• 02:05:25 - Dr. Fahey's thoughts on where endogenous conversion of glucoraphanin occurs in the body, as well as how long it takes before sulforaphane metabolites hit the bloodstream after ingestion.
• 02:07:25 - Some general thoughts on frequency in terms of how often one might need to take sulforaphane to elicit its biological effects.
• 02:12:16 - why sulforaphane may one day be a component of sunscreen.
• 02:12:31 - what some of the upcoming trials involving sulforaphane are at the Cullman Chemoprotection Center.
• 02:17:07 - the incredible way in which a sulforaphane-rich broccoli sprout beverage was shown to dramatically enhance the detoxification of benzene through excretion: one study showed up to 61% starting immediately after supplementation.

You can find out more about Dr. Fahey and the Cullman Chemoprotection Center by visiting:

• The Cullman Chemoprotection Center Website (donation link)
• facebook.com/chemoprotectioncenter
• twitter.com/jedosan (Jed's twitter)
• jedfahey.com

This podcast is about one of the most important biological pathways you could possibly take the time to learn about: the NRF2 pathway.

The most potent naturally-occurring inducer of this pathway, a plant compound known as sulforaphane, may be one of the most potent health-enhancing compounds at our disposal and yet... no one is keeping it out of your hands! No $1,000 per pill markup is keeping it out of your hands -- it’s available to anyone willing to take the little bit of time it takes each week to produce broccoli sprouts.

In some respects, broccoli sprouts may even be a great equalizer in a way... while it’s true that healthy food can often be expensive, it’s even reasonably possible for a person to take $20 worth of seeds and feed their whole family some of the most healthful greens you could get your hands on. This video will tell you why.

Here are a few of the more salient points surrounding sulforaphane that are discussed in this podcast...

• Profound changes in lipid biomarkers, reducing heart disease risk by as much as 50% in humans.
• Massive reductions in cancer risk in humans and also highly effective as a cancer intervention, particularly prostate and breast but also many others.
• Steep reductions in inflammation in humans.
• Shown in mice to be as effective as prozac as an anti-depressant.
• Steep behavioral changes in humans with respect to certain neurological disorders, such as autism.
• Causes dramatic boosts in the excretion of air pollutants (up to 60%) in humans.

Key sections you may want to skip to:
00:03:35 - Cancer and mortality
00:21:56 - Aging
00:29:37 - Brain and behavior
00:41:33 - Final recap
00:44:18 - Dose

NOTE: If you enjoy this podcast, you'll enjoy the YouTube video more since it shows all of the figures and citations.

This episode of the FoundMyFitness podcast features Dr. Valter Longo, a professor of gerontology and biological sciences and director of the longevity institute at the University of Southern California. Dr. Longo has made huge contributions to the field of aging, including the role of fasting and diet in longevity and healthspan in humans as well as metabolic fasting therapies for the treatment of human diseases.

In this podcast, Valter and I discuss...

• The effects of prolonged fasting, which refers to 2-3 day fasting intervals in mice and 4-5 days in humans.
• Dr. Longo’s work on the fasting-mimicking diet, which is 5 day restricted diet that is meant to simulate some of the biological effects of prolonged fasting while still allowing some food.
• How clinical trials have demonstrated efficacy for this diet for type 2 diabetes, multiple sclerosis, and cancer patients.
• Fasting as an inducer of differential stre�ss resistance, where it can simultaneously make cancer cells more sensitive to death while also making healthy cells more resistant to these same death stimuli (such as chemotherapy) which might otherwise induce cell death amongst healthy cells as collateral damage.
• Fasting as a biological state which humans historically experienced with extreme regularity and we may ultimately need in order to mitigate various disease states.
• The effects of prolonged fasting on the immune system, namely, how it clears away damaged white blood cells via autophagy and how this causes hematopoietic stem cells to self renew and make more stem cells and also produce new blood cells to fully replenish the white blood cell population.
• How prolonged fasting causes a shift in the immune cell population towards one that is more representative of youth by normalizing the ratio of myeloid cells to lymphoid cells.
• The positive effects of prolonged fasting and the fasting-mimicking diet on markers of systemic inflammation, blood glucose levels and other aging biomarkers.
• The conclusions of Dr. Longo & Dr. Marcus Bock’s research comparing 1 week of the fasting-mimicking diet followed by 6 months of mediterranean diet to six months of a ketogenic diet in people with multiple sclerosis.
• The strange, somewhat paradoxical role of autophagy genes in cancer progression and some of the open questions surrounding the exact role that these genes are playing.
• Dr. Longo’s high level thoughts on metformin as an anti-aging drug.
• How the growth hormone/IGF-1 axis is one of the most important genetic pathways in aging from yeast to worms to mice to humans.

You can learn more about the fasting-mimicking diet by visiting prolonfmd.com and you can receive an email when Dr. Longo published his upcoming book (English version) by following his profile on Amazon.

Today's episode features Dr. Ruth Patterson, a professor in the UC San Diego Department of Family Medicine and Public Health as well as Associate Director of Population Sciences and leader of the Cancer Prevention program at Moores Cancer Center at UC San Diego Health. If you enjoyed my last episode with Dr. Satchin Panda, I have good news! This will also be a great episode for you, since we talk about some similar ideas, but focus more on the human side of things, especially when it comes to time-restricted eating, since Dr. Patterson does primarily clinical research.

In this 45-minute podcast, we talk about...

• The importance of time-restricted eating as a practical public health intervention, mostly for it's ease of implementation, that may have a widespread impact on disease risk.
• Why you should probably make sure your time-restricted eating window occurs earlier in the day, rather than later.
• How the first 5% drop in weight loss can have disproportionately large effects on the metabolic factors associated with breast cancer risk when compared with subsequent weight loss.
• The association of longer fasting durations beginning earlier in the evening and improved sleep in humans, as well as spontaneous physical activity in their day-to-day lives.
• The relationship between metabolism and breast cancer risk.
• The effect of lifestyle factors, such as obesity, physical activity, what and even when you eat, whether or not you smoke tobacco... and how even modest changes, such as consuming food earlier in the day and only during an 11-hour window, can decrease breast cancer risk and recurrence by as much as 36%.
• The importance of starting your fast earlier in the evening, and how an earlier eating window has been shown to correlate to reductions in inflammatory markers.
• The association of higher circulating insulin levels with breast cancer risk, and how insulin itself has an important relationship with estrogen by affecting the levels of sex-hormone binding globulin.
• The dangers of having a cellular environment that is inflamed, as the case is with the obese, and simultaneously having elevated cellular growth signals, which is also characteristic of the hormonal milieu of the obese.
• The surprisingly small role heredity plays in determining overall risk of breast cancer when compared to lifestyle factors.
• How healthful lifestyle habits, like choosing to eat during the right window, ultimately helps us trend our risk for many of the diseases of old age in the correct direction instead of influencing only one or another.

If the concept of time-restricted eating especially piques your interest, make sure to...

1. Check out the podcast released just prior to this one: Dr. Satchin Panda on Time-Restricted Feeding and Its Effects on Obesity, Muscle Mass & Heart Health.
2. Make sure your data points go to good use! Visit myCircadianClock.org to learn how you can, by committing to a minimum of a 14 week "intervention" and submitting pictures of your food from your iPhone or Android phone, move human research on time-restricted eating forward.

Huge special thanks to Dr. Ruth Patterson for coming on. Enjoy the podcast!

Dr. Rhonda Patrick speaks with Dr. Satchin Panda, a professor at the Salk Institute for Biological Studies in La Jolla California. Satchin's work deals specifically with the timing of food and it's relationship with our biological clocks governed by circadian rhythm and also the circadian rhythm in general.

In this video we discuss...

• The fascinating history of experimentation that ultimately elucidated the location for the region of the brain necessary for a properly timed sleep-wake cycles.
• The relationship between our body's "master clock" and it's many peripheral clocks.
• Why infants sleep so intermittently, instead of resting for a longer, sustained duration like healthy young adults... and why this sustained rest also goes haywire in the elderly.
• The fascinating work Dr. Panda took part in that lead to the discovery of a specialized light receptor in the eye that sets circadian rhythms and is known as melanopsin.
• The important relationship between the relatively light insensitive melanopsin, which requires around 1,000 lux of light to be fully activated, and its control of the circadian clock by means of activation of the suprachiasmatic nucleus and suppression of melatonin.
• The effects light exposure seems to have on next-day cortisol, a glucocorticoid hormone that regulates around 10-20% of the human protein-encoding genome.
• The clever experimental design by which Dr. Panda and his colleagues discovered that certain circadian rhythms, especially of the liver, are entrained by when we eat, instead of how much light we get. This underlines the fact that, when managing are circadian rhythm, both elements are important!
• One of the more surprising effects of time-restricted feeding in mice eating a so-called healthy diet: increases in muscle mass and even endurance in some cases.

Interested in trying out time-restricted feeding? Don't let your data points go to waste! You can try out time-restricted feeding and have a real impact on human research! Commit to 14 weeks and download Dr. Panda's mobile app to get started. Learn more at: mycircadianclock.org/participant

Dr. Rhonda Patrick speaks with Ray Cronise, a former NASA material scientist and cofounder of zero gravity, a company that offers weightless parabolic flights to consumers and researchers. In this episode, coming at the tail end of a rather extreme 23-day water fast for Ray, we discuss, perhaps unsurprisingly, some of the benefits that are associated with fasting! Ray talks about shifting one's perspective from looking at nutrition only through the lens of meeting day-to-day nutritional needs, and instead, also considering optimizing metabolism for longer-term effects as well, the importance of thinking about longevity in the context of functional healthspan, some of the similarities between the body’s physiological response to heat stress, cold stress, and exercise and so much more.

Learn more about Ray Cronise by visiting his website at hypothermics.com (raycronise.com) or by saying hello on twitter: twitter.com/raycronise.

Finally, Ray also has a book available for pre-order called "Our Broken Plate."