Timothy Ferriss's Blog

Welcome back to another in-between-isode, with one of my favorite formats: the good old-fashioned Q&A.

I answer questions submitted by the small-but-elite group of test readers of my upcoming THE NO BOOK. The community is closed for new members, as we have the right number of people now, but I hope to potentially expand it, once the book comes out. 

See below for show notes, links to everything discussed, and more!

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform.

This episode is brought to you by:

Monarch Money  track, budget, plan, and do more with your money Eight Sleep Pod Cover 5  sleeping solution for dynamic cooling and heating Shopify  global commerce platform, providing tools to start, grow, market, and manage a retail businessListen onApple Podcasts[image error]Listen onSpotify[image error]Listen onOvercastQ&A with Tim — Supplements I’m Taking, Austin vs. SF, Training for Mental Performance, Current Go-To AI Tools, Recovering from Surgery, Intermittent Fasting, and More

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SELECTED LINKS FROM THE EPISODEBooks & MediaThe 4-Hour Body: An Uncommon Guide to Rapid Fat-Loss, Incredible Sex, and Becoming Superhuman by Timothy Ferriss: My book on health and the human body, which I reference when discussing the PAGG supplement protocol.The 4-Hour Chef: The Simple Path to Cooking Like a Pro, Learning Anything, and Living the Good Life by Timothy Ferriss: My book about accelerated learning. I mention it in the context of sequencing and as a key resource for adapting in the AI era.The 4-Hour Workweek: Escape 9-5, Live Anywhere, and Join the New Rich by Timothy Ferriss: My first book on lifestyle design, mentioned in the context of needing a phase of openness in your career.How to Stop Worrying and Start Living by Dale Carnegie: A book I reference for its advice on gathering more information to address fears and challenges.Sin City (Collector’s Edition) by Frank Miller: A coffee table book that I use for creative inspiration, noting how it shows the artist’s process. Hyde : An upcoming gothic horror graphic novel series starring Johnny Depp and created in collaboration with Ridley Scott, reimagining the classic Dr. Jekyll and Mr. Hyde story as a sequel where Hyde has triumphed over his alter ego.Charlie and the Chocolate Factory by Roald Dahl: A book I recently finished listening to. The Wonderful Story of Henry Sugar : A Wes Anderson short film on Netflix, adapted from a Roald Dahl story that was recommended to me.Fast Like a Girl: A Woman’s Guide to Using the Healing Power of Fasting to Burn Fat, Boost Energy, and Balance Hormones by Dr. Mindy Pelz: A book recommended by a listener for its focus on fasting for women.Eat Like a Girl: 100+ Delicious Recipes to Balance Hormones, Boost Energy, and Burn Fat by Dr. Mindy Pelz: Another book recommended by a listener for its focus on nutrition for women. The Resetter Podcast : Dr. Mindy Pelz’s podcast, also recommended by a listener. Fall of Civilizations Podcast : A podcast I mention to illustrate that most legacies, even of great empires, fade over time.“The Art of Letting Bad Things Happen (And Weapons of Mass Distraction)”: One of my older blog posts that I say is very relevant to how I live my life.“The Karmic Capitalist: Should I Wait Until I’m Rich to Give Back?”: Another of my older blog posts, which I reference when discussing my philosophy on philanthropy.Batman: Year One by Frank Miller and David Mazzucchelli: Originally released in 1988 in four parts, these stories give us more insight into Batman’s origin. The Four Seasons : A modern, eight-part series adapted from the 1981 Alan Alda film The Four Seasons . Dirty Dancing : A 1987 romantic drama film starring Patrick Swayze and Jennifer Grey about a young woman who falls in love with a dance instructor during a family vacation.Health & Wellness SupplementsAGG Stack (PAGG minus the P): A supplement combination consisting of:Alpha-Lipoic Acid (ALA)Green Tea ExtractGarlic Allicin ExtractBPC-157: A peptide used to aid in elbow surgery recovery.Collagen & Vitamin C: Taken together prior to physical therapy or stretching to support tissue repair.N-acetylcysteine (NAC): A supplement taken for liver health, often between meals.Fish Oil (Pure Encapsulations ONE): Tested for purity by Kevin Rose and Dr. Rhonda Patrick.Magnesium L-threonate: A form of magnesium for cognitive support.Maca Root Extract: Taken for potential androgenic and reproductive health benefits.AREDS 2: A Bausch & Lomb supplement for ocular health being used experimentally for presbyopia.THC & CBN: A combination used at night for pain management post-surgery.Whey Protein: Used to supplement protein intake, especially within intermittent fasting windows.MCT Oil: A budget-friendly alternative to exogenous ketones for cognitive benefits.Ketone Ester (Monoester)/Keto Start (Ketone Salts): Expensive ketone monoesters vs. the more affordable Keto Start (a ketone salt product from Dominic D’Agostino).Prescription & Over-the-Counter Drugs

(Disclaimer: I emphasize multiple times not to copy my protocol and to consult a doctor.)

Uloric (Febuxostat): A prescription for managing uric acid to prevent future gout.Nexlizet (Ezetimibe and Bempedoic Acid): A prescription for managing my lipid profile.Famotidine (Pepcid): An over-the-counter medication I’m taking for its potential anti-COVID applications and as a mild vagal tone improver.DORA Class Sleep Medications: A class of prescription sleep medication I am researching for its potential to help clear amyloid plaque associated with Alzheimer’s.Diets & Training MethodsIntermittent Fasting: I have changed my mind on this and now practice it regularly, typically in a 16/8 format (eating within an eight-hour window).Ketogenic Diet: A diet I used to kickstart my intermittent fasting journey, which resulted in my best blood work in over a decade.Blood Flow Restriction (BFR) Training: A technique recommended by Kelly Starrett that I’m using to maintain muscle mass and flush tissue during rehab.Marc Pro Device: An electrical stimulation device used for decongestion and lymphatic drainage to aid healing.Apps, Tools, & TechnologyConsensus.app: An AI-powered search engine specifically designed to find and summarize findings from peer-reviewed scientific papers.ChatGPT, Claude, Perplexity: General large language models (LLMs) I use for initial research, which I then cross-reference.Zero: Kevin Rose’s app for tracking fasting periods.Discord: I mention using a Discord server to gather feedback from fans of Exploding Kittens games.Reddit: I note that subreddits can be a great place to cross-reference information and find very smart people (with the caveat that it is not medical advice).Ancestry.com: Mentioned as a tool for tracing family lineage for a potential family trip.Games & EntertainmentCoyote: The card game I created with Exploding Kittens, which is a central topic of discussion.Monopoly Deal: A fast-paced card game mentioned by a listener as a family favorite alongside Coyote.Dungeons & Dragons: I mention I still have all my old hardcover books, modules, and dice from when I was a kid.CØCKPUNCH/Legends of Varlata: My foray into fantasy fiction.Companies, Organizations, & BrandsExploding Kittens: The game company that published Coyote.Saisei Foundation: My own foundation, which funds research into mental health therapeutics.Maui Nui Venison: A company I am a large investor in, which I describe as providing highly nutritious red meat.PeopleRoald Dahl: Author of Charlie and the Chocolate Factory and The Wonderful Story of Henry Sugar and Six More .Wes Anderson: American filmmaker who directed the short-film adaptation of The Wonderful Story of Henry Sugar .Dale Carnegie: Author of How to Stop Worrying and Start Living .Pablos Holman: Hacker and inventor known for talks on proper problem sequencing.Keith Baar: UC Davis researcher whose work informs collagen and vitamin C usage.Kelly Starrett: Performance coach and PT who recommended BFR training.Kevin Rose & Rhonda Patrick: Friends who have discussed testing the purity of fish oil supplements.Kevin Tracey: Neurosurgeon known for research on vagus nerve stimulation.Seth Godin: Author and entrepreneur quoted on the idea that “money is a story.”Naval Ravikant: Investor and thinker referenced with the question, “How many Sumerians do you know?”Charles Babbage: English mathematician, philosopher, inventor and mechanical engineer considered by many to be the “father of the computer.”Valter Longo: Director of the USC Longevity Institute and biogerontologist known for his research on fasting-mimicking diets, cellular protection, aging, and longevity mechanisms across species.Dominic D’Agostino: Researcher focused on ketogenic diets, metabolic therapies, and nutritional strategies for neurological disorders and human performance optimization.Henry Shukman: Zen teacher at Mountain Cloud Zen Center.Frank Miller: Legendary comics creator of Sin City: The Hard Goodbye  and 300 .Elan Lee: Game designer and co-creator of Exploding Kittens; partner on the Coyote project.Johnny Depp: American actor and producer known for transformative film roles.Ridley Scott: British filmmaker behind Alien , Blade Runner , and Gladiator .Tom Hardy: British actor known for The Dark Knight Rises and Mad Max: Fury Road .Timothée Chalamet: American actor known for Call Me by Your Name and Dune (2021).Josh Waitzkin: Chess prodigy and author of The Art of Learning .Andrew Huberman & Peter Attia: Neuroscientist and physician who have discussed nicotine and health tradeoffs.Albert Hofmann: Swiss chemist best known for first synthesizing LSD.Javier Milei: President of Argentina since 2023, known for his libertarian economic policies and efforts to combat hyperinflation through drastic austerity measures and deregulation.Michael Phelps: Widely regarded as one of the greatest athletes of all time, he captured 28 Olympic medals and set 39 world records over the course of his swimming career.Mindy Pelz: Author and podcaster focused on fasting, particularly for women.Robert Rodriguez: American filmmaker known for El Mariachi , Desperado , and Sin City .Key Concepts & IdeasSequencing: The crucial importance of breaking a problem down and solving its pieces in the right order.80/20 Analysis: The principle of identifying the 20 percent of inputs that will yield 80 percent of the results.Saying “No”: The theme of turning down good opportunities to make space for “Hell, yes” moments.Vagus Nerve Stimulation: A topic I’m very interested in and would add a chapter about to The 4-Hour Body if I were to revisit it.Treating Philanthropy Like For-Profit Investing: My approach of applying rigorous, impact-driven analysis to my non-profit work.Extended Human Fasting: A neglected area of scientific research that I believe holds immense potential as a therapeutic tool.Fun as Recovery: The idea that delight, play, and laughter are not distractions but essential forms of recovery needed for high performance.PlacesAustin, Texas: Capital city of Texas and the “Live Music Capital of the World,” known for its vibrant music scene, breakfast tacos, technology industry, and the slogan “Keep Austin Weird.”Silicon Valley, California: California’s tech-centric region stretching from Belmont to San Jose around the south end of San Francisco Bay, home to major technology corporations like Google, Apple, Meta, and Stanford University.Glacier National Park: Montana national park showcasing melting glaciers, alpine meadows, carved valleys, and spectacular lakes with over 700 miles of trails, featuring the famous Going-to-the-Sun Road and historic lodges.Mountain Cloud Zen Center: A Zen meditation retreat in Santa Fe, New Mexico, run by Henry Shukman, which I describe as a magical experience.Taiwan: Island nation situated in the West Pacific between Japan and the Philippines, renowned for its democratic government, advanced technology sector, and semiconductor industry.Estonia: Baltic state and EU member known as one of the world’s most digitally advanced countries, offering innovative e-governance services, e-residency programs, and serving as the birthplace of technologies like Skype.Lithuania: Baltic state and EU/NATO member in Northern Europe, known for its medieval capital Vilnius, strong digital innovation sector, commitment to regional security and defense cooperation, and fascinating basketball-Grateful Dead connection.Mohonk Mountain House: A resort in Upstate New York I recommend for large, extended family outings.SHOW NOTES[00:00:00] Start[00:06:00] Coyote retail distribution challenges and data gathering.[00:09:12] Elbow surgery recovery: sequencing, decongestion, Marc Pro device, peptides, BFR training.[00:16:14] California vs. Austin for builders, mechanical engineers, and tech startups.[00:19:06] Using AI for medical advice workflow (and cross-referencing with professionals).[00:23:51] Current supplement regimen and PAGG/AGG status.[00:31:54] California vs. Texas considerations for aspiring parents.[00:32:48] Saying “No” to good things for “Hell, yes” moments.[00:34:34] Philanthropy lessons learned since starting Saisei Foundation.[00:37:45] Something I’ve changed my mind about recently: intermittent fasting.[00:42:44] Precious items from childhood I still keep: D&D relics and marine biology books.[00:43:03] Bucket list hike: Glacier National Park.[00:43:42] How the catalytic chaos of publishing The 4-Hour Chef led to launching this podcast.[00:45:52] Bringing delight vs. sixth-gear, high-performance focus.[00:49:05] Thoughts on extended human fasting research from the Soviet era.[00:52:58] Most magical New Mexico experience: Mountain Cloud Zen Center meditation retreat.[00:53:22] Meta skills for the AI era: Hyper-adaptability and world-class learning.[00:54:01] The (real and ideal) future of CØCKPUNCH/Legends of Varlata.[00:59:47] Competitive chess training enhancement: glucose management, intermittent fasting, MCT oil.[01:06:31] Behind-the-scenes projects: Fusion, algae feed additives, meat alternatives.[01:08:32] Countries I wish I had visited earlier, and places I’d still like to see.[01:11:06] “Not yet” vs. “No” in early growth phases.[01:14:14] Post Coyote, do I have any future games in the works?[01:14:46] Over-ear vs. in-ear headphones for podcasting.[01:15:16] What’s the uncrowded channel right now?[01:16:17] Recommendations for Dr. Mindy Pelz.[01:16:58] Robert Rodriguez and project juggling.[01:17:24] Fast neutron reactors and the Bugatti of ketones.[01:19:05] Extended family outings and Mahonk Mountain House.[01:20:31] NO BOOK meetup plans?[01:20:54] Parting thoughts.

Want to hear another episode where I answer questions directly from listeners? Have a gander at my recent Q&A session in which I discussed changing my mind about parenthood, identity diversification, how to find joy and live with urgency, career reinvention in the age of AI, avoiding complacency, getting unstuck, and much more.

The post Q&A with Tim — Supplements I’m Taking, Austin vs. SF, Training for Mental Performance, Current Go-To AI Tools, Recovering from Surgery, Intermittent Fasting, and More (#826) appeared first on The Blog of Author Tim Ferriss.

Dr. Dominic D’Agostino (@DominicDAgosti2) is a tenured associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine and a Visiting Senior Research Scientist at the Institute for Human and Machine Cognition.

He teaches medical neuroscience, physiology, nutrition, and neuropharmacology, and his research focuses on the development and testing of nutritional strategies and metabolic-based therapies for neurological disorders, cancer, and human performance optimization. His work spans both basic science and human clinical trials.

He has a strong personal interest in environmental medicine and enhancing the safety and resilience of military personnel and astronauts. In this capacity, he served as a research investigator and crew member on NASA’s Extreme Environment Mission Operations. His research has been supported by the Office of Naval Research, the Department of Defense, the National Institutes of Health, private organizations, and nonprofit foundations.

He earned his B.S. in Nutritional Science and Biological Sciences from Rutgers University in 1998, followed by a predoctoral fellowship in Neuroscience and Physiology at Rutgers and the University of Medicine and Dentistry of New Jersey. He then completed postdoctoral training in Neuroscience at Wright State University’s Boonshoft School of Medicine in 2004 and at University of South Florida Morsani College of Medicine in 2006.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube.

This episode is brought to you by:

AG1  all-in-one nutritional supplement Helix Sleep  premium mattresses Momentous  high-quality creatineListen onApple Podcasts[image error]Listen onSpotify[image error]Listen onOvercastDr. Dominic D’Agostino — All Things Ketones, How to Protect the Brain and Boost Cognition, Sardine Fasting, Diet Rules, Revisiting Metformin and Melatonin, and More

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SELECTED LINKS FROM THE EPISODEConnect with Dr. Dominic D’Agostino:

KetoNutrition.org | Facebook | Twitter | University of South Florida

Dr. Dominic D’Agostino’s Past AppearancesDom D’Agostino on Fasting, Ketosis, and the End of Cancer | The Tim Ferriss Show #117Dom D’Agostino — The Power of the Ketogenic Diet | The Tim Ferriss Show #172Dom D’Agostino on Disease Prevention, Cancer, and Living Longer | The Tim Ferriss Show #188Concepts & IdeasAPOE3/4 Genotype: A genetic variant where individuals carry one copy each of the APOE3 and APOE4 alleles, associated with moderately increased risk of Alzheimer’s disease compared to APOE3/3 but lower risk than APOE4/4.Type 3 Diabetes: A term used to describe Alzheimer’s disease as a form of insulin resistance and insulin deficiency that occurs specifically in the brain, characterized by impaired neuronal glucose metabolism.The Four Horsemen of Chronic Disease: The four pillars of chronic disease, according to Dr. Peter Attia.Glucose Hypometabolism: A state where the brain’s ability to use glucose for energy is impaired, often occurring more than 10 years before the onset of Alzheimer’s disease symptoms and considered a key feature of neurodegeneration.Neuroinflammation: Inflammation of nervous tissue involving activation of microglia and astrocytes, considered a major driver of neurodegenerative diseases including Alzheimer’s, Parkinson’s, and multiple sclerosis.Ketogenic Diet: A very low-carbohydrate (typically under 50g per day), high-fat diet originally developed at Mayo Clinic in the 1920s to treat epilepsy, which forces the body to produce ketones for fuel instead of using glucose.Mediterranean-Style Low-Carb Diet: A modified version of the traditional Mediterranean diet that reduces carbohydrate intake while emphasizing vegetables, fish, olive oil, nuts, and healthy fats to support weight loss and blood sugar control.Exogenous Ketones: Ketone bodies (primarily beta-hydroxybutyrate) that are consumed through nutritional supplements in the form of ketone salts, esters, or precursor compounds, allowing for rapid elevation of blood ketones without dietary restriction.Ketone Monoester vs. Diester vs. Salts: Different forms of exogenous ketone supplements where monoesters provide the most efficient ketone elevation, diesters are bonds between two ketone molecules, and salts combine ketones with minerals like sodium or potassium.Glucose Ketone Index (GKI): A ratio calculated by dividing blood glucose levels by ketone levels, used as a biomarker for metabolic health and the depth of ketosis, with lower values indicating better metabolic flexibility.Fasting and “Sardine Fasting”: Abstaining from food for therapeutic benefits, with “sardine fasting” referring to a modified fasting approach where only sardines are consumed, providing protein while maintaining some benefits of fasting.Autophagy: The body’s cellular recycling process of cleaning out damaged organelles and proteins to regenerate newer, healthier cellular components, enhanced during periods of fasting and ketosis.Cancer Cachexia: A complex metabolic syndrome characterized by severe loss of muscle mass and body weight, often accompanied by anemia, weakness, and loss of appetite in cancer patients.Metabolic Psychiatry: An emerging field that uses metabolic interventions, particularly ketogenic diets and exogenous ketones, to treat mental health conditions by addressing underlying metabolic dysfunction in the brain.NLRP3 Inflammasome: A multiprotein complex in immune cells that acts as a cellular sensor and triggers inflammatory responses, playing a crucial role in innate immunity and implicated in various neurodegenerative diseases.Metabolic Control of Epigenetic Regulation: The concept that metabolites like beta-hydroxybutyrate can directly influence gene expression by acting as signaling molecules and histone deacetylase inhibitors, affecting cellular function and health.Redox Stress: An imbalance in the cellular ratio of NAD+ to NADH that can impair mitochondrial function and energy production, often associated with aging and metabolic dysfunction.Hyperbaric Oxygen Therapy (HBOT): A medical treatment involving breathing pure oxygen in a pressurized chamber at 1.5 to 3 times normal atmospheric pressure, used to enhance healing and treat various conditions including wound healing and carbon monoxide poisoning.Lipid Energy Model: A metabolic model explaining how LDL cholesterol and ApoB particles can be elevated on low-carbohydrate diets as they function as transport vehicles for mobilized fatty acids used for energy production.SARM (Selective Androgen Receptor Modulator): A class of therapeutic compounds designed to selectively bind to androgen receptors in specific tissues, potentially offering the muscle-building benefits of anabolic steroids with reduced androgenic side effects.Substances & DrugsBeta-Hydroxybutyrate (BHB): The primary ketone body produced during fat metabolism and ketosis, used as an alternative energy source for the brain and body.1,3-Butanediol: A ketone precursor and alcohol compound that is metabolized into beta-hydroxybutyrate (BHB) in the liver.MCT Oil (Medium-Chain Triglyceride): A type of saturated fat that is readily absorbed and converted into ketones, commonly used in ketogenic diets.Creatine Monohydrate: A supplement that helps regenerate ATP in muscles, known for improving exercise performance, strength, and potentially cognitive function.Lipopolysaccharide (LPS): A component of gram-negative bacterial cell walls used in research to induce systemic inflammation and study immune responses.Ezetimibe (Zetia): A prescription medication that lowers cholesterol by inhibiting its absorption in the small intestine.Rapamycin: An immunosuppressive drug originally used to prevent organ rejection that has gained attention for potential anti-aging and longevity effects.Metformin: A first-line medication for type 2 diabetes that lowers blood glucose levels and has potential benefits for longevity and metabolic health.Berberine/Dihydroberberine: Plant-derived alkaloid compounds with glucose-lowering effects similar to metformin, used for metabolic health support.GLP-1 Agonists: A class of diabetes medications that mimic incretin hormones to regulate blood sugar and promote weight loss, including drugs like semaglutide and tirzepatide.SGLT-2 Inhibitors: A class of diabetes medications that lower blood sugar by preventing glucose reabsorption in the kidneys, causing excess glucose to be excreted in urine.NAD Supplements: Supplements like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) designed to boost cellular NAD+ levels for potential anti-aging benefits.Idebenone / CoQ10 / Ubiquinol: Antioxidant compounds that support mitochondrial energy production and cellular health, with CoQ10 being essential for ATP synthesis.GABA / Phenibut: Gamma-aminobutyric acid and related compounds that have calming, inhibitory effects on the central nervous system.Diphenhydramine (Benadryl): An over-the-counter antihistamine commonly used for allergies that causes drowsiness and is sometimes used as a sleep aid.Melatonin: A hormone naturally produced by the pineal gland that regulates the sleep-wake cycle and is commonly used as a sleep supplement.Ostarine: A selective androgen receptor modulator (SARM) that selectively targets muscle and bone tissue, mentioned for veterinary use in research contexts.Alpha GPC / Theanine: Nootropic compounds where Alpha-GPC supports acetylcholine production for cognitive function and L-theanine promotes relaxation without sedation.Products & BrandsKetoStart (Audacious Nutrition): A ketone electrolyte supplement company founded by Dr. Dominic D’Agostino’s wife, specializing in exogenous ketone products.Qitone: A brand that produces ketone diester powder supplements for enhancing ketosis and metabolic performance.Keto-Mojo: A company that manufactures portable blood glucose and ketone testing devices popular among those following ketogenic diets.Abbott Precision Xtra: A dual-purpose blood glucose and ketone monitoring system manufactured by Abbott for diabetes management and ketosis tracking.LMNT: An electrolyte supplement brand that provides sugar-free, keto-friendly hydration products with optimal sodium, potassium, and magnesium ratios.Levels: A metabolic health company that provides continuous glucose monitors (CGMs) paired with an app to help users optimize their blood sugar responses.Stelo: An over-the-counter continuous glucose monitor developed by Dexcom for people without diabetes to track their glucose patterns.GB HealthWatch: A genetic testing company that provides personalized reports for dyslipidemia and cardiovascular risk assessment based on DNA analysis.Dry Farm Wines: A wine company specializing in natural, low-sugar, additive-free wines that are lab-tested for purity and lower alcohol content.French Women Don’t Get Fat: The Secret of Eating for Pleasure by Mireille Guiliano: A bestselling lifestyle guide that reveals the “French paradox” of how French women stay slim while enjoying bread, wine, and three-course meals through principles of balance, quality over quantity, and eating for pleasure rather than restriction.Keto Brainz: A supplement brand that produces MCT powder enhanced with nootropic compounds to support both ketosis and cognitive function.Nutricost / Quest: Popular supplement brands that offer MCT powder products among their extensive product lines.Nordic Naturals: A premium omega-3 supplement brand known for high-quality fish oil products with third-party purity testing and sustainable sourcing.OmegaQuant: A testing company that measures omega-3 fatty acid levels in blood to help individuals optimize their omega-3 status and cardiovascular health.Metabolic Mind: An educational platform from the Baszucki Group that focuses on metabolic approaches to mental health and psychiatric conditions.MetPsy: An app currently in development designed to provide metabolic therapy coaching and support for mental health applications.InstitutionsNIH (National Institutes of Health): The primary agency of the United States government responsible for biomedical and public health research.USF (University of South Florida): Public research university in Tampa where Dr. D’Agostino is a professor.Byrd Alzheimer’s Center: Research institute at USF Health dedicated to Alzheimer’s disease prevention, treatment and cure where Dr. D’Agostino’s wife worked.Buck Institute for Research on Aging: Independent biomedical research institute in California focused on extending healthy years of life.Harvard University: Private Ivy League research university in Cambridge, Massachusetts where Chris Palmer and Georgia Ede are affiliated.Moffitt Cancer Center: National Cancer Institute-designated comprehensive cancer center in Tampa collaborating with Dr. D’Agostino.Stanford University: Private research university in California where Shebani Sethi is affiliated.Oxford University: Prestigious collegiate research university in England where Dr. Ally Houston is affiliated.Northwestern University: Private research university in Illinois where Dr. Nav Chandel conducts research.University of Edinburgh: Public research university in Scotland where Dr. Iain Campbell conducts research.Yale University: Private Ivy League research university in Connecticut where Dr. Deep Dixit is a researcher.Genentech: American biotechnology corporation and subsidiary of Roche, pioneering in recombinant DNA technology.Metro International Biotech: Clinical-stage pharmaceutical company developing NAD+ precursors and therapeutics like MIB-626.Relevant Resources & ResearchMeet Dr. Mary T. Newport — Neonatologist and Advocate for Treating Alzheimer’s with Ketones | Keto-MojoHyperbaric Oxygen Therapy Improves Post-Concussion Symptoms in Adults with Childhood Traumatic Brain Injury: A Retrospective Cohort Study | Frontiers in NeurologyEnantiomer-Specific Cardiovascular Effects of the Ketone Body 3-Hydroxybutyrate | Journal of the American Heart AssociationThe Many Faces of Beta-Hydroxybutyrate (BHB) | KetoNutritionWhy Do We Need Both D-BHB and L-BHB? | KetoNutritionStudy of the Ketogenic Agent AC-1202 in Mild to Moderate Alzheimer’s Disease | Nutrition & MetabolismA New Way to Produce Hyperketonemia: Use of Ketone Ester in a Case of Alzheimer’s Disease | Alzheimer’s & Dementia JournalThe Ketone Metabolite Beta-Hydroxybutyrate Blocks NLRP3 Inflammasome-Mediated Inflammatory Disease | Nature MedicineExogenous Ketone Supplements Reduce Anxiety-Related Behavior in Two Rodent Models | Scientific ReportsElevated Plus Maze Test Combined with Video Tracking to Investigate the Anxiolytic Effect of Exogenous Ketogenic Supplements | JoVEToxicological Evaluation of the Ketogenic Ester Bis-Hexanoyl (R)-1,3-Butanediol: Subchronic Toxicity in Sprague-Dawley Rats | ToxicologyA Dietary Ketone Ester Mitigates Histological Outcomes of Nafld and Markers of Fibrosis in High-Fat Diet Fed Mice | American Journal of Gastrointestinal and Liver PhysiologyTherapeutic Use of the Ketogenic Diet in Refractory Epilepsy: What We Know and What Still Needs to Be Learned | NutrientsMetabolic Therapy with Deanna Protocol Supplementation Delays Disease Progression and Extends Survival in Amyotrophic Lateral Sclerosis (ALS) Mouse Model | PLOS ONEPeopleMary Newport: Physician and author who pioneered the use of MCT oil for Alzheimer’s disease, founding medical director of newborn intensive care units in Florida.Steve Newport: Husband of Dr. Mary Newport, subject of a case report on using a ketone monoester for Alzheimer’s disease who experienced significant improvements.Sam Corcos: Co-founder and CEO of Levels, a health technology startup that uses continuous glucose monitors to help people understand how food affects their metabolic health.Richard Veech: NIH researcher who developed the beta-hydroxybutyrate monoester and studied ketones for cognitive decline and neurological disorders.Peter Attia: Physician and longevity expert, known for the “Four Horsemen” concept, host of The Drive podcast and author of the #1 New York Times bestseller Outlive .George F. Cahill Jr.: Scientist known for his historic fasting studies and research on metabolic physiology at Harvard Medical School.Thomas Seyfried: Professor and cancer researcher at Boston College, colleague of Dr. D’Agostino who studies metabolic approaches to cancer treatment.Fred Hatfield (“Dr. Squat”): Powerlifter and mentor to Dr. D’Agostino who used a ketogenic diet for metastatic prostate cancer treatment.Valter Longo: Researcher known for the Fasting Mimicking Diet and director of the USC Longevity Institute studying aging and disease prevention.Mike Dancer: Man whose experience with epilepsy and the ketogenic diet influenced Dr. D’Agostino’s research direction.Sam Henderson: Researcher who published early research on AC-1202 (MCT oil) for Alzheimer’s disease treatment.Jong Rho: Researcher who highlighted the importance of acetoacetate and acetone in seizure control mechanisms.Spencer Nadolsky: Physician who suggested Dr. D’Agostino might be a hyperabsorber of cholesterol based on his lipid profiles.Matt Kaeberlein: Aging researcher and professor at the University of Washington studying longevity and healthspan extension.Csilla Ari D’Agostino: Neuroscientist, Dom’s wife, and founder of Audacious Nutrition.Charles Poliquin: Late strength coach known for his innovative training methods and work with elite athletes worldwide.Dale Bredesen: Physician and researcher focused on Alzheimer’s disease treatment and prevention through the ReCODE protocol.Navdeep Chandel: Researcher at Northwestern University studying cellular metabolism and its role in health and disease.Andrew Huberman: Neuroscientist and professor at Stanford University, host of the popular Huberman Lab podcast on health and performance.Rhonda Patrick: Scientist and host of FoundMyFitness, specializing in nutrition, aging, and disease prevention through lifestyle interventions.Eric Verdin: President and CEO of the Buck Institute for Research on Aging, studying metabolism and aging processes.Vishwa Deep Dixit: Researcher at Yale University who studied the NLRP3 inflammasome and its role in metabolic health.Chris Palmer: Harvard psychiatrist and author of Brain Energy , advocate for metabolic psychiatry approaches to mental health treatment.Matt Baszucki: Son of David Baszucki, whose experience with bipolar disorder was treated with a ketogenic diet approach.Jan and David Baszucki: Founders of Roblox, philanthropists funding metabolic psychiatry research through the Baszucki Brain Research Fund.Shebani Sethi: Psychiatrist at Stanford University researching metabolic approaches to mental health treatment.Ally Houston: Researcher at Oxford University studying metabolism and brain function.Georgia Ede: Harvard-trained psychiatrist and author of Change Your Diet, Change Your Mind , specializing in nutritional psychiatry.Iain Campbell: Researcher at the University of Edinburgh studying bipolar disorder and metabolic interventions.Deanna Tedone: Individual with ALS who stabilized her condition using the “Deanna Protocol” nutritional approach.Angela Poff and Victoria Field: Colleagues of Dr. D’Agostino who run the Metabolic Health Initiative at the University of South Florida.SHOW NOTES[00:00:00] Start.[00:14:43] Why I’m interested in ketogenic strategies for neurodegenerative prevention.[00:16:18] Mary and Steve Newport’s ketone-linked temporary cognitive improvements.[00:18:18] A mechanisms overview for Alzheimer’s/dementia.[00:21:25] The immune system as longevity’s “fifth horseman” — and why metabolic control is key.[00:22:04] How to measure ketones and GKI.[00:23:00] Fasting vs. ketogenic diet.[00:24:18] There’s nothing fishy about sardine fasting.[00:28:32] My hiatal hernia discovery and increased cancer risk concerns.[00:30:04] HSCRP as a superior biomarker to LDL for cardiovascular risk.[00:31:57] Glucose tolerance testing revelations and CGM importance.[00:31:57] Upgrading the metabolic machinery through keto without getting bored.[00:42:07] What do do if you, like Dom and me, are among the 30% who suffer from cholesterol hyperabsorption.[00:43:42] Dom’s day-to-day diet regimen.[00:45:56] How Dom optimizes his aging dogs with ketones, SARMs, and supplements.[00:51:30] Supplementing for sleep disruption while fasting.[00:55:41] Why Dom doesn’t have misgivings about melatonin.[00:59:15] Shingles prevention through fasting protocols.[01:00:15] Immune system modulation: Innate vs. adaptive, vegan vs. ketogenic.[01:03:54] Dom at 50-something: Current meal timing and composition.[01:05:57] Blue zone observations: Greek and Sardinian longevity habits.[01:08:16] Ketogenic diet initiation tips: MCT, electrolytes, and fasted cardio.[01:15:18] Ketone metabolic therapy for cancer.[01:18:15] The metabolic psychiatry revolution.[01:22:10] The soothing effects of hyperbaric oxygen and ketosis on seizure sufferers.[01:28:27] Metformin vs. berberine.[01:31:43] The low-dose neuroprotective potential of GLP-1 drugs.[01:34:58] NAD research: MIB-626 and stabilized forms for mitochondrial health.[01:39:48] Idebenone, CoQ10, and the Deanna protocol for ALS.[01:42:05] Dom’s supplement short list: CoQ10, creatine, ketones, vitamin D, melatonin.[01:44:43] KetoNutrition.org, Metabolic Health Summit, Audacious Nutrition, veteran-focused research protocols, and other parting thoughts.DR. DOMINIC D’AGOSTINO QUOTES FROM THE INTERVIEW

“I think the beauty of ketogenic [therapy] is that it’s pleiotropic, right? Which means it’s many mechanisms working in synergy.”

— Dr. Dominic D’Agostino

“I think the best way to measure to suggest you’re in autophagy is a glucose ketone index after a period of fasting.”

— Dr. Dominic D’Agostino

“About 30 percent of the population hyperabsorbs cholesterol.”

— Dr. Dominic D’Agostino

“HSCRP is a better indicator of cardiovascular disease than LDL cholesterol. We know that now. [No one would believe it] If someone said that 10 years ago.”

— Dr. Dominic D’Agostino

“I wouldn’t go above three, probably 1.5 to 2 millimolar range. That seems to be a level of ketones that safely does not produce a metabolic acidosis.”

— Dr. Dominic D’Agostino

“When we published the NLRP3, I got requests from Genentech and various pharmaceutical companies to go there and give a talk on the mechanism so they could drugify. And I would throw up a big flow chart of all these mechanisms, and I think they would get frustrated. And it was like, ‘Well, tell us the mechanism so we can make a drug out of this.'”

— Dr. Dominic D’Agostino

“I went on a vacation where I forgot melatonin and I slept like a baby probably because I was up every morning. The sun is the ultimate circadian synchronizer. I got off of melatonin to check my endogenous melatonin, and there was no suppression.”

— Dr. Dominic D’Agostino

“So we went to these blue zones and they just, at night after their dinner, the males will do a shot of alcohol, usually wine, but sometimes ouzo and they’re all in their nineties and hundreds, they’re in the blue zone. So it’s a universal characteristic.”

— Dr. Dominic D’Agostino

Want to hear the last time Dom was on the show? Listen to our previous conversation in which we discussed disease prevention, longevity, cancer, ketogenic diet mastery, the detoxifying effects of ketosis on pre-cancerous cells, how to jumpstart daily ketogenic cycles, “cheat” meals, and much more.

The post Dr. Dominic D’Agostino — All Things Ketones, How to Protect the Brain and Boost Cognition, Sardine Fasting, Diet Rules, Revisiting Metformin and Melatonin, and More (#825) appeared first on The Blog of Author Tim Ferriss.

Kevin J. Tracey, MD (@KevinJTraceyMD), is president and CEO of the Feinstein Institutes for Medical Research at Northwell Health, a pioneer of vagus-nerve research, and author of the recent book The Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes. 

His contributions include identifying the therapeutic action of monoclonal anti-TNF antibodies and discovering the specific reflex control of immunity by the nervous system, called the “inflammatory reflex.” These discoveries launched the new scientific field called bioelectronic medicine, which investigates the therapeutic applications of vagus-nerve stimulation to cure disease.

Dr. Tracey, a neurosurgeon, pursued studies of inflammation after the mysterious death, from sepsis, of a toddler who was in his care. His lab has since revealed molecular mechanisms of inflammation and identified the use of vagus-nerve stimulation to treat it. An inventor on more than 120 US patents and the author of more than 450 scientific publications, he is among the most highly cited scientists in the world. He co-founded the Global Sepsis Alliance, is the author of Fatal Sequence, and is a national and international lecturer.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube. The transcript of this episode can be found here. Transcripts of all episodes can be found here.

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SELECTED LINKS FROM THE EPISODEConnect with Dr. Kevin Tracey:

X | The Feinstein Institutes of Northwell Health | SetPoint Medical | LinkedIn

The transcript of this episode can be found here. Transcripts of all episodes can be found here.

Publications & MediaThe Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes by Kevin J. Tracey: A groundbreaking book exploring the potential of the vagus nerve to regulate the body’s vital systems and heal medical conditions without drugs.The Polyvagal Theory: Neurophysiological Foundations of Emotions, Attachment, Communication, and Self-regulation by Stephen W. Porges: A comprehensive compilation of decades of research on the polyvagal theory and its implications for understanding the autonomic nervous system. STEM-Talk : A bi-weekly interview podcast produced by the Florida Institute for Human and Machine Cognition featuring conversations with groundbreaking scientists, engineers, and technologists. The New York Times : A major American daily newspaper that featured coverage on SetPoint Medical and other medical developments. HuffPost : An American progressive news and opinion website where Dr. Tracey was interviewed about his research. Cell : A prestigious peer-reviewed scientific journal that published research on topics including gut microbiota and the ketogenic diet.Explain Pain by David Butler and G. Lorimer Moseley: An evidence-based book designed for therapists, patients, and students that explains the science behind pain and recovery strategies.The Integrative Action of the Nervous System by Charles Sherrington: A classic 1906 work in neuroscience that established fundamental concepts about how the nervous system functions as an integrated whole.Medical ConditionsRheumatoid Arthritis: An autoimmune disease that causes inflammation in the joints.Crohn’s Disease: A type of inflammatory bowel disease that affects the digestive tract.PTSD (Post-Traumatic Stress Disorder): A mental health condition triggered by experiencing or witnessing a traumatic event.Chronic Fatigue Syndrome: A long-term illness characterized by extreme fatigue that doesn’t improve with rest and may worsen with physical or mental activity.Depression: A mood disorder that causes persistent feelings of sadness, hopelessness, and loss of interest in activities.Lyme Disease: An infectious disease caused by bacteria transmitted through the bite of infected ticks.Neurodegenerative Disease: A range of conditions that primarily affect the neurons in the human brain, leading to progressive deterioration of function.Anaphylaxis: A severe, potentially life-threatening allergic reaction that can occur rapidly after exposure to an allergen.Asthma: A respiratory condition in which airways become inflamed, narrow, and produce excess mucus, making breathing difficult.Sepsis: A life-threatening condition that arises when the body’s response to infection causes widespread inflammation and organ dysfunction.Psoriatic Arthritis: A form of inflammatory arthritis that affects some people who have the skin condition psoriasis.Autoimmune Conditions: Disorders in which the immune system mistakenly attacks the body’s own healthy tissues and organs.COVID-19: A contagious respiratory illness caused by the SARS-CoV-2 virus that can range from mild to severe symptoms.Alzheimer’s Disease: A progressive neurodegenerative disease that destroys memory and other important mental functions.Parkinson’s Disease: A progressive disorder of the central nervous system that affects movement, often causing tremors, stiffness, and difficulty with balance.Metabolic Syndrome: A cluster of conditions including high blood pressure, high blood sugar, excess abdominal fat, and abnormal cholesterol levels that increase the risk of heart disease, stroke, and diabetes.Diabetes: A chronic disease that occurs when the body cannot properly produce or use insulin, leading to elevated blood sugar levels.Cancer: A group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body.Malaria: A life-threatening disease caused by parasites transmitted through the bites of infected female Anopheles mosquitoes.Tuberculosis: A serious infectious bacterial disease that primarily affects the lungs but can spread to other parts of the body.Peptic Ulcer Disease: A condition characterized by painful sores or ulcers that develop in the lining of the stomach or the first part of the small intestine.Epilepsy: A neurological disorder in which brain activity becomes abnormal, causing seizures, unusual behavior, sensations, and sometimes loss of consciousness.Cluster Headaches: A series of extremely painful headaches that occur in cyclical patterns or clusters, often at the same time each day for weeks or months.Migraines: Intense headaches that cause severe throbbing or pulsing pain, typically on one side of the head, often accompanied by nausea and sensitivity to light and sound.Sciatica: Pain that radiates along the sciatic nerve pathway from the lower back through the hips and down one or both legs.Treatments & TherapiesVagus Nerve Stimulation (VNS): A medical treatment that involves delivering electrical impulses to the vagus nerve.Audio Chakra Cleanse Soundtracks: A type of alternative therapy mentioned as an example of “nonsense.”Biologics: Medications made from living organisms or their components.Ketogenic Diet: A very low-carb, high-fat diet.Exogenous Ketones: Ketones that are ingested through a nutritional supplement.GLP-1 Agonists (e.g., Ozempic, Mounjaro): A class of medications used to treat type 2 diabetes and obesity.Microbiome Transplants: The transfer of fecal matter from a healthy donor to a recipient to restore a healthy gut microbiome.TMS (Transcranial Magnetic Stimulation): A noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression.Focused Ultrasound: A non-invasive therapeutic technology that uses focused sound waves to target and treat a variety of medical conditions.Psychedelics (e.g., LSD, 2C-B, Ayahuasca): A class of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness.TENS (Transcutaneous Electrical Nerve Stimulation) units: A non-invasive method of pain relief that uses a mild electrical current.Auricular Therapy: A form of alternative medicine based on the idea that the ear is a microsystem which reflects the entire body.Famotidine (Pepcid): An over-the-counter antacid that Dr. Tracey describes as a pharmacological vagus nerve stimulator.Antibiotics: Medications that fight bacterial infections.SSRIs (Selective Serotonin Reuptake Inhibitors): A class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.Ibuprofen: A nonsteroidal anti-inflammatory drug (NSAID).Monoclonal Antibodies: Laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses.Optogenetics: A biological technique that involves the use of light to control cells in living tissue, typically neurons, that have been genetically modified to express light-sensitive ion channels.Key Concepts & TheoriesPolyvagal Theory: A theory that links the evolution of the autonomic nervous system to social behavior and emphasizes the importance of physiological state in the expression of behavioral problems and psychiatric disorders.Heart Rate Variability (HRV): The variation in the time interval between consecutive heartbeats.Sympathetic Overdrive: A condition where the sympathetic nervous system is overactive.Inflammatory Reflex: A physiological reflex that controls the inflammatory response.Bioelectronic Medicine: A field of medicine that uses electronic devices to treat diseases and injuries.Blood-Brain Barrier: A highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside.Cytokines (e.g., TNF, IL-1, IL-6): A broad and loose category of small proteins that are important in cell signaling.Cytokine Storm: A severe immune reaction in which the body releases too many cytokines into the blood too quickly.Inflammaging: Chronic, low-grade inflammation that develops with advanced age.Neuroinflammation: Inflammation of the nervous tissue.Neuroplasticity: The ability of the brain to form and reorganize synaptic connections, especially in response to learning or experience or following injury.Interoception: The sense of the internal state of the body.Engram: A physical trace of memory in the brain.M1 and M2 Macrophages: Two different types of white blood cells with different functions in the inflammatory response.PeopleKelly Owens: A patient of Dr. Tracey’s who suffered from Crohn’s disease and rheumatoid arthritis and was successfully treated with a vagus nerve stimulation device.Murthy Simhambhatla: The CEO of SetPoint Medical, a bioelectronic medicine company developing vagus nerve stimulation therapies.Dave Chernoff: The Chief Medical Officer of SetPoint Medical, overseeing clinical development of bioelectronic therapies.Nolan Williams: A psychiatry professor and director of the Stanford Brain Stimulation Lab who pioneered Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an FDA-approved treatment for treatment-resistant depression using accelerated TMS.Nora Volkow: Director of the National Institute on Drug Abuse (NIDA) who pioneered the use of brain imaging to investigate addiction as a brain disorder and is researching focused ultrasound therapies for addiction treatment.Steve Liberles: A professor of cell biology at Harvard Medical School and Howard Hughes Medical Institute investigator who studies the molecular neuroscience of vagus nerve sensory systems and identified specific vagal neuron subtypes that control breathing and digestion in mice.K. Frank Austen: A leading expert on asthma research and respiratory medicine.Barry Jacobs: A researcher at Princeton University who studied the effects of LSD on cats and contributed to early psychedelic research.Andrew Weil: A physician and author with a background in ethnobotany who has written about his experiences with psychedelics including LSD and integrative medicine approaches.Ulf Andersson: A retired professor of pediatric rheumatology at the Karolinska Institute and friend of Dr. Tracey’s who used a TENS unit to treat his own inflammation-related depression.Paul Nogier: A French physician who created the first auricular acupuncture maps in 1957, pioneering modern ear acupuncture techniques.Kenneth M. Ford: Founder and CEO Emeritus of the Florida Institute for Human and Machine Cognition (IHMC), and co-host of the STEM-Talk podcast.Geoff Ling: Retired colonel who founded the biology technology office at DARPA.Richard Feynman: Nobel Prize-winning American theoretical physicist known for his work in quantum mechanics, quantum electrodynamics, and superfluidity.Charles Sherrington: One of the founders of modern neuroscience, known for his groundbreaking work on neural reflexes and The Integrative Action of the Nervous System, for which he won the Nobel Prize in Physiology or Medicine in 1932.Santiago Ramón y Cajal: The other founding father of modern neuroscience, known for his pioneering studies of the structure of the nervous system and the neuron doctrine, Nobel Prize winner in Physiology or Medicine in 1906.Asya Rolls: A professor who discovered that inflammation in the colon can form a neural network connection to the brain, advancing our understanding of the gut-brain axis.Sangeeta Chavan: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, contributing to bioelectronic medicine research.Stavros Zanos: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, specializing in neural engineering and bioelectronics.Okito Hashimoto: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, working in the field of bioelectronic medicine.Eric Chang: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, contributing to neuroscience and bioelectronics research.Martine Rothblatt: A friend of Dr. Tracey’s and CEO of United Therapeutics, she is a renowned polymath who founded SiriusXM satellite radio before entering biotechnology to develop treatments for her daughter’s pulmonary hypertension, becoming the highest-paid female CEO in America.Lorimer Moseley: Co-author with David Butler of the book Explain Pain and a leading researcher in pain neuroscience and clinical neurosciences at the University of South Australia.William Bushell: A scientist who works with the Dalai Lama on studies involving meditation, consciousness, and human potential.Elizabeth Blackburn: A scientist who won both the Lasker Prize and the Nobel Prize in Physiology or Medicine in 2009 for her work on telomeres and telomerase.Bob Thurman: Uma Thurman’s father and a professor of Tibetan studies at Columbia University, known for his scholarship on Buddhist philosophy.The Dalai Lama: The spiritual leader of Tibet and global advocate for compassion, peace, and interfaith dialogue.Bill Murray: Formidably funny man and serial-striking bowler.Kevin Rose: Probably not the Kevin you’re looking for, but Kevin, by any other name, would smell as sweet.Institutions & CompaniesSetPoint Medical: A commercial-stage medical technology company that developed the first FDA-approved neuroimmune modulation device to treat rheumatoid arthritis using vagus nerve stimulation.Feinstein Institutes for Medical Research: The research arm of Northwell Health and home to 50 research labs, 3,000 clinical research studies, and 5,000 researchers where Dr. Tracey and his colleagues work.Mayo Clinic: A world-renowned nonprofit American medical organization dedicated to integrated healthcare, education, and research.Stanford University: A prestigious private research university in California known for its groundbreaking research, including work on accelerated TMS and other medical innovations.Centers for Disease Control and Prevention (CDC): The national public health agency of the United States, responsible for protecting public health and safety through disease prevention and health promotion.Karolinska Institute: A prestigious medical research institute and university in Sweden, home to the Nobel Committee for Physiology or Medicine.Defense Advanced Research Projects Agency (DARPA): A research and development agency of the United States Department of Defense responsible for developing emerging technologies for military use.Defense Language Institute: A United States Department of Defense educational and research institution that provides language training to military personnel and federal employees.United Therapeutics: A biotechnology company focused on creating innovative products to address the medical needs of patients with chronic and life-threatening conditions, including pulmonary arterial hypertension and organ transplantation technologies.World Health Organization (WHO): A specialized agency of the United Nations responsible for international public health, setting global health standards, and coordinating international health responses.Columbia University: A prestigious private Ivy League research university in New York City, renowned for its contributions to medicine, science, and other fields of study.Pendulum: A science-backed biotechnology company founded by doctors and scientists that produces next-generation probiotics, including the only commercially available live Akkermansia supplement.WHOOP: 24/7 monitoring across sleep, strain, stress, and heart health.Oura Ring: A smart ring that monitors over 20 biometrics that directly impact how you feel.Fitbit: Wearables designed to “keep you close to your goals, boost your motivation, and show your progress throughout your health and fitness journey.”Relevant Research & ResourcesKevin Tracey on Neuro-Immunology and the Treatment of Inflammatory Diseases | STEM-TalkKevin Tracey, MD, Reveals Vagus Nerve’s Power in New Book | Northwell HealthSetPoint Medical Receives FDA Approval for Novel Neuroimmune Modulation Therapy for Rheumatoid Arthritis | SetPoint MedicalNew Implant Offers Hope for Easing Rheumatoid Arthritis | The New York TimesI Tried 22 Different Medications Before an Electrical Implant Healed My Crohn’s Disease | PreventionNolan Williams — A Glimpse of the Future: Electroceuticals for 70%–90% Remission of Depression, Brain Stimulation for Sports Performance, and De-Risking Ibogaine for TBI/PTSD | The Tim Ferriss ShowDr. Nora Volkow — Director of the National Institute on Drug Abuse (NIDA) | The Tim Ferriss ShowReappraising the Role of the Vagus Nerve in GLP-1-Mediated Regulation of Eating | British Journal of PharmacologyRole of Vagus Nerve Signaling in CNI-1493-Mediated Suppression of Acute Inflammation | Autonomic NeuroscienceGood-bye to Drugs? Kevin Tracey, MD on the Bioelectronics Revolution at the Dysautonomia International Conference | Health RisingNo Audible Wheezing: Nuggets and Conundrums from Mouse Asthma Models | Journal of Experimental MedicineHere’s What Happens When Animals Eat LSD | DoubleBlindSome Practical Thoughts on Suicide | Tim FerrissThe Evolution of Inflammation | PfizerFDA Black Box Warning Raises Awareness of Medication Risk | GoodRxEffects of Anti-Inflammatory Vagus Nerve Stimulation in Endotoxemic Rats on Blood and Spleen Lymphocyte Subsets | Inflammation ResearchVagus Nerve Stimulation for Epilepsy and Depression | NeurotherapeuticsVagus Nerve Active during Exercise, Research Finds | The University of AucklandJumping into the Ice Bath Trend! Mental Health Benefits of Cold Water Immersion | Stanford Lifestyle MedicineThe Thermoregulatory Theory of Yawning: What We Know from over Five Years of Research | Frontiers in NeurosciencePrevalence of Autoimmune Diseases Is Strongly Associated with Average Annual Temperatures: Systematic Review and Linear Regression Analysis | BMC RheumatologyNobel Prize Is Awarded to Doctors Who Discovered H Pylori | The British Medical JournalWhat Happens to Your Blood Sugar While You Sleep? | WebMDType A Personality Traits vs. Type B | Simply PsychologyFocused Ultrasound Neuromodulation of the Spleen Activates an Anti-Inflammatory Response in Humans | Brain StimulationHistory of Auriculotherapy: Additional Information and New Developments | Medical AcupunctureThe Medial Surface of the Auricle: Historical and Recent Maps. What Are the Possible Expectations of the “Thumb-Index Technique” | MedicinesOur Ears Share a Common Ancestry with Fish Gills | Scientific AmericanJP Errico Explains How Vagus-Nerve Stimulation Reduces Inflammation and Chronic Diseases | STEM-TalkVagus Nerve Stimulation May Enhance Language Learning, DoD Study Reports | Practical NeurologyGeoffrey Ling: From DARPA to Life | Twin GlobalVagus Nerve Stimulation (VNS) Therapy | Epilepsy SocietyThe Gut Microbiota Mediates the Anti-seizure Effects of the Ketogenic Diet | CellDr. Andrew Weil — Optimal Health, Plant Medicine, and More | The Tim Ferriss ShowThe Hidden Flaws of HRV Tracking | The Unlazy WayBreathe to Directly Control Heart Rate via Huberman Lab | InstagramFamotidine Activates the Vagus Nerve Inflammatory Reflex to Attenuate Cytokine Storm | Molecular MedicineWHOOP Adds Psychedelics Tracking | Fitt InsiderWhy Don’t We Know How Antidepressants Work Yet? | Chemistry WorldUlf’s Case Study: VAGUS Smartwatch ECG Test | VAGUS Health Ltd.Study of the Transcutaneous Auricular Vagus Nerve Stimulation May Advance Outcome in Chronic Pediatric Inflammatory Diseases | Medical Research ArchivesAcupuncture Enhances Chances of Pregnancy in Unexplained Infertile Patients Who Undergo a Blastocyst Transfer in a Fresh-Cycle | Chinese Journal of Integrative MedicineAcupuncture as Treatment for Female Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | Evidence-Based Complementary and Alternative MedicineDr. Martine Rothblatt — A Masterclass on Asking Better Questions and Peering into the Future | The Tim Ferriss ShowImmunoception: The Insular Cortex Perspective | Cellular & Molecular ImmunologyNew Science Shows Immune “Memory” in the Brain | Quanta MagazineJennifer Aniston Strikes a Nerve | NatureQuantum Physics — His Holiness the Dalai Lama Participates in the 26th Mind & Life Meeting at Drepung | The Office of His Holiness The Dalai LamaSHOW NOTES[00:00:00] Start.[00:06:34] Factors alleviating my skepticism about vagus nerve stimulation.[00:11:12] SetPoint Medical receives FDA approval for vagus nerve stimulation device to treat rheumatoid arthritis.[00:13:24] How Crohn’s disease sufferer Kelly Owens went from a wheelchair to running up stairs in Amsterdam.[00:20:36] Placebo effect concerns and the conditions driving my interest in bioelectric medicine.[00:25:31] Vagus nerve anatomy 101.[00:32:53] Cytokines and inflammation: What happens when the vagus nerve is stimulated.[00:33:45] Discovery story: Accidental finding of brain-body inflammation connection.[00:35:39] Bioelectronic medicine approach vs. pharmaceutical approach.[00:38:18] Mice don’t wheeze.[00:40:13] Depression and inflammation connection: SSRIs may work through anti-inflammatory effects.[00:42:46] My personal experience with vagus nerve stimulation and mood stability.[00:44:22] The pros and cons of inflammation, and how controlling it may lead to even longer lifespans.[00:50:56] Weighing the safety of VNS vs. biologics in cytokine suppression.[00:56:27] Cold exposure, meditation, and breathing practices affecting the vagus nerve.[00:59:01] A population-level increase in chronic inflammatory diseases: Nature vs. nurture.[01:00:48] H. pylori: For when you can’t blame stress, God, or the patient for that nagging ulcer.[01:03:13] Stress, cortisol, and inflammation connections.[01:05:42] SetPoint device vs. non-invasive alternatives for different patient populations.[01:11:09] Auricular therapy’s curious French origins.[01:13:28] There’s something fishy about this vestigial vagus nerve pathway.[01:16:03] Overlapping activation patterns from brain imaging studies of ear stimulation.[01:19:01] DARPA support and Geoff Ling’s “What if it’s yes?” attitude.[01:21:58] Neurocognition and vagus nerve inputs.[01:27:20] How Ulf Andersson turned his depression around with a TENS unit.[01:31:55] Heart rate variability complexity and measurement challenges.[01:33:05] A breathing exercise for directly controlling heart rate.[01:35:30] Using a common antacid as a pharmacological vagus nerve stimulator during COVID.[01:36:23] A call for more inflammation-based depression research and patient stratification.[01:39:52] SSRIs and anti-inflammatory mechanisms in depression treatment.[01:42:20] Interoception: The body’s inflammatory signals reaching the brain via vagus nerve.[01:43:22] Ulf’s published protocol for TENS unit ear stimulation.[01:44:37] VNS, acupuncture, fertility, and Martine Rothblatt.[01:47:16] Chronic low back pain and an inflammatory overreaction analogy.[01:48:35] Implications of Asya Rolls’ engram research and inflammation memories in the brain.[02:02:35] Cervical TENS vs. true VNS.[02:07:12] Charles Sherrington’s reflex theory and nervous system integration.[02:12:15] Blue energy meditation and vagus nerve pathways with the Dalai Lama.[02:16:47] Parting thoughts: Serious medical conditions vs. self-help approaches.DR. KEVIN TRACEY QUOTES FROM THE INTERVIEW

“60 million people die on the planet Earth every year. And 40 million of them die from heart disease, stroke, neurodegeneration, Alzheimer’s, Parkinson’s, metabolic syndrome, diabetes, and cancer. So two thirds of the people that die every year on the planet Earth die of those conditions. And that’s according to the WHO. Those conditions all have one thing in common: they’re either caused by inflammation or made worse by inflammation.”

— Dr. Kevin Tracey

“It was just announced that the company SetPoint Medical, which will now be marketing a device to stimulate the vagus nerve to treat rheumatoid arthritis, has received FDA approval. So there’ll be a product launch underway for everything we’re about to talk about in the context of using a medical device that activates an evolutionarily conserved and ancient reflex through which the brain can suppress inflammation when it’s running out of control.”

— Dr. Kevin Tracey

“We’ve discovered that signals travel from the brain through the vagus nerve. … These signals traveling in the vagus nerve are like the brakes on your car. And when you tap those brakes to slow your car barreling down the hill, this device activates what we call the inflammatory reflex.”

— Dr. Kevin Tracey

“If we can find such nerves, then we can build devices to control the nerves, and the devices become the therapy. The bioelectronic medicine story works as long as you know the molecular mechanism, and that’s where people have to be really careful with vagus-nerve stimulation.”

— Dr. Kevin Tracey

“Almost everybody until a hundred years ago, 150 years ago, almost everybody died by the time they were 30. And what happened in the last 150 years can be summarized in a very simple sentence. The human race in the last 150 years removed infection as the leading cause of death. … I think something similar will happen maybe in the next 20 years if we can really understand how to modify inflammation.”

— Dr. Kevin Tracey

“My adage for this thing is, when you don’t understand a disease, think of epilepsy. You start off, you blame God. So they did exorcisms, and that doesn’t work. So if it’s not God’s fault, the next thing you do is you blame the patient. And when you realize it’s not the patient’s fault, in today’s era, oftentimes we find out it’s actually caused, there’s some infectious cause of this thing. And so autoimmune disease may have an infectious cause, it may have an environmental cause. People talk about genetic causes. You inherit some level of risk for autoimmune diseases, but in very few of these conditions do you actually inherit the condition.”

— Dr. Kevin Tracey

Want to hear another episode about the future of electroceuticals and brain stimulation? Listen to my conversation with Stanford’s Dr. Nolan Williams, in which we discussed 70%–90% remission rates for treatment-resistant depression, brain stimulation for sports performance, accelerated TMS protocols, de-risking ibogaine for TBI/PTSD, the future of “electroceuticals,” and much more.

The post What Most Has My Attention Right Now — Credible (vs. Bogus) Vagus Nerve Stimulation (#824) appeared first on The Blog of Author Tim Ferriss.

Kevin J. Tracey, MD (@KevinJTraceyMD), is president and CEO of the Feinstein Institutes for Medical Research at Northwell Health, a pioneer of vagus-nerve research, and author of the recent book The Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes. 

His contributions include identifying the therapeutic action of monoclonal anti-TNF antibodies and discovering the specific reflex control of immunity by the nervous system, called the “inflammatory reflex.” These discoveries launched the new scientific field called bioelectronic medicine, which investigates the therapeutic applications of vagus-nerve stimulation to cure disease.

Dr. Tracey, a neurosurgeon, pursued studies of inflammation after the mysterious death, from sepsis, of a toddler who was in his care. His lab has since revealed molecular mechanisms of inflammation and identified the use of vagus-nerve stimulation to treat it. An inventor on more than 120 US patents and the author of more than 450 scientific publications, he is among the most highly cited scientists in the world. He co-founded the Global Sepsis Alliance, is the author of Fatal Sequence, and is a national and international lecturer.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube. The transcript of this episode can be found here. Transcripts of all episodes can be found here.

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SELECTED LINKS FROM THE EPISODEConnect with Dr. Kevin Tracey:

X | The Feinstein Institutes of Northwell Health | SetPoint Medical | LinkedIn

The transcript of this episode can be found here. Transcripts of all episodes can be found here.

Publications & MediaThe Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes by Kevin J. Tracey: A groundbreaking book exploring the potential of the vagus nerve to regulate the body’s vital systems and heal medical conditions without drugs.The Polyvagal Theory: Neurophysiological Foundations of Emotions, Attachment, Communication, and Self-regulation by Stephen W. Porges: A comprehensive compilation of decades of research on the polyvagal theory and its implications for understanding the autonomic nervous system. STEM-Talk : A bi-weekly interview podcast produced by the Florida Institute for Human and Machine Cognition featuring conversations with groundbreaking scientists, engineers, and technologists. The New York Times : A major American daily newspaper that featured coverage on SetPoint Medical and other medical developments. HuffPost : An American progressive news and opinion website where Dr. Tracey was interviewed about his research. Cell : A prestigious peer-reviewed scientific journal that published research on topics including gut microbiota and the ketogenic diet.Explain Pain by David Butler and G. Lorimer Moseley: An evidence-based book designed for therapists, patients, and students that explains the science behind pain and recovery strategies.The Integrative Action of the Nervous System by Charles Sherrington: A classic 1906 work in neuroscience that established fundamental concepts about how the nervous system functions as an integrated whole.Medical ConditionsRheumatoid Arthritis: An autoimmune disease that causes inflammation in the joints.Crohn’s Disease: A type of inflammatory bowel disease that affects the digestive tract.PTSD (Post-Traumatic Stress Disorder): A mental health condition triggered by experiencing or witnessing a traumatic event.Chronic Fatigue Syndrome: A long-term illness characterized by extreme fatigue that doesn’t improve with rest and may worsen with physical or mental activity.Depression: A mood disorder that causes persistent feelings of sadness, hopelessness, and loss of interest in activities.Lyme Disease: An infectious disease caused by bacteria transmitted through the bite of infected ticks.Neurodegenerative Disease: A range of conditions that primarily affect the neurons in the human brain, leading to progressive deterioration of function.Anaphylaxis: A severe, potentially life-threatening allergic reaction that can occur rapidly after exposure to an allergen.Asthma: A respiratory condition in which airways become inflamed, narrow, and produce excess mucus, making breathing difficult.Sepsis: A life-threatening condition that arises when the body’s response to infection causes widespread inflammation and organ dysfunction.Psoriatic Arthritis: A form of inflammatory arthritis that affects some people who have the skin condition psoriasis.Autoimmune Conditions: Disorders in which the immune system mistakenly attacks the body’s own healthy tissues and organs.COVID-19: A contagious respiratory illness caused by the SARS-CoV-2 virus that can range from mild to severe symptoms.Alzheimer’s Disease: A progressive neurodegenerative disease that destroys memory and other important mental functions.Parkinson’s Disease: A progressive disorder of the central nervous system that affects movement, often causing tremors, stiffness, and difficulty with balance.Metabolic Syndrome: A cluster of conditions including high blood pressure, high blood sugar, excess abdominal fat, and abnormal cholesterol levels that increase the risk of heart disease, stroke, and diabetes.Diabetes: A chronic disease that occurs when the body cannot properly produce or use insulin, leading to elevated blood sugar levels.Cancer: A group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body.Malaria: A life-threatening disease caused by parasites transmitted through the bites of infected female Anopheles mosquitoes.Tuberculosis: A serious infectious bacterial disease that primarily affects the lungs but can spread to other parts of the body.Peptic Ulcer Disease: A condition characterized by painful sores or ulcers that develop in the lining of the stomach or the first part of the small intestine.Epilepsy: A neurological disorder in which brain activity becomes abnormal, causing seizures, unusual behavior, sensations, and sometimes loss of consciousness.Cluster Headaches: A series of extremely painful headaches that occur in cyclical patterns or clusters, often at the same time each day for weeks or months.Migraines: Intense headaches that cause severe throbbing or pulsing pain, typically on one side of the head, often accompanied by nausea and sensitivity to light and sound.Sciatica: Pain that radiates along the sciatic nerve pathway from the lower back through the hips and down one or both legs.Treatments & TherapiesVagus Nerve Stimulation (VNS): A medical treatment that involves delivering electrical impulses to the vagus nerve.Audio Chakra Cleanse Soundtracks: A type of alternative therapy mentioned as an example of “nonsense.”Biologics: Medications made from living organisms or their components.Ketogenic Diet: A very low-carb, high-fat diet.Exogenous Ketones: Ketones that are ingested through a nutritional supplement.GLP-1 Agonists (e.g., Ozempic, Mounjaro): A class of medications used to treat type 2 diabetes and obesity.Microbiome Transplants: The transfer of fecal matter from a healthy donor to a recipient to restore a healthy gut microbiome.TMS (Transcranial Magnetic Stimulation): A noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression.Focused Ultrasound: A non-invasive therapeutic technology that uses focused sound waves to target and treat a variety of medical conditions.Psychedelics (e.g., LSD, 2C-B, Ayahuasca): A class of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness.TENS (Transcutaneous Electrical Nerve Stimulation) units: A non-invasive method of pain relief that uses a mild electrical current.Auricular Therapy: A form of alternative medicine based on the idea that the ear is a microsystem which reflects the entire body.Famotidine (Pepcid): An over-the-counter antacid that Dr. Tracey describes as a pharmacological vagus nerve stimulator.Antibiotics: Medications that fight bacterial infections.SSRIs (Selective Serotonin Reuptake Inhibitors): A class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.Ibuprofen: A nonsteroidal anti-inflammatory drug (NSAID).Monoclonal Antibodies: Laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses.Optogenetics: A biological technique that involves the use of light to control cells in living tissue, typically neurons, that have been genetically modified to express light-sensitive ion channels.Key Concepts & TheoriesPolyvagal Theory: A theory that links the evolution of the autonomic nervous system to social behavior and emphasizes the importance of physiological state in the expression of behavioral problems and psychiatric disorders.Heart Rate Variability (HRV): The variation in the time interval between consecutive heartbeats.Sympathetic Overdrive: A condition where the sympathetic nervous system is overactive.Inflammatory Reflex: A physiological reflex that controls the inflammatory response.Bioelectronic Medicine: A field of medicine that uses electronic devices to treat diseases and injuries.Blood-Brain Barrier: A highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside.Cytokines (e.g., TNF, IL-1, IL-6): A broad and loose category of small proteins that are important in cell signaling.Cytokine Storm: A severe immune reaction in which the body releases too many cytokines into the blood too quickly.Inflammaging: Chronic, low-grade inflammation that develops with advanced age.Neuroinflammation: Inflammation of the nervous tissue.Neuroplasticity: The ability of the brain to form and reorganize synaptic connections, especially in response to learning or experience or following injury.Interoception: The sense of the internal state of the body.Engram: A physical trace of memory in the brain.M1 and M2 Macrophages: Two different types of white blood cells with different functions in the inflammatory response.PeopleKelly Owens: A patient of Dr. Tracey’s who suffered from Crohn’s disease and rheumatoid arthritis and was successfully treated with a vagus nerve stimulation device.Murthy Simhambhatla: The CEO of SetPoint Medical, a bioelectronic medicine company developing vagus nerve stimulation therapies.Dave Chernoff: The Chief Medical Officer of SetPoint Medical, overseeing clinical development of bioelectronic therapies.Nolan Williams: A psychiatry professor and director of the Stanford Brain Stimulation Lab who pioneered Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an FDA-approved treatment for treatment-resistant depression using accelerated TMS.Nora Volkow: Director of the National Institute on Drug Abuse (NIDA) who pioneered the use of brain imaging to investigate addiction as a brain disorder and is researching focused ultrasound therapies for addiction treatment.Steve Liberles: A professor of cell biology at Harvard Medical School and Howard Hughes Medical Institute investigator who studies the molecular neuroscience of vagus nerve sensory systems and identified specific vagal neuron subtypes that control breathing and digestion in mice.K. Frank Austen: A leading expert on asthma research and respiratory medicine.Barry Jacobs: A researcher at Princeton University who studied the effects of LSD on cats and contributed to early psychedelic research.Andrew Weil: A physician and author with a background in ethnobotany who has written about his experiences with psychedelics including LSD and integrative medicine approaches.Ulf Andersson: A retired professor of pediatric rheumatology at the Karolinska Institute and friend of Dr. Tracey’s who used a TENS unit to treat his own inflammation-related depression.Paul Nogier: A French physician who created the first auricular acupuncture maps in 1957, pioneering modern ear acupuncture techniques.Kenneth M. Ford: Founder and CEO Emeritus of the Florida Institute for Human and Machine Cognition (IHMC), and co-host of the STEM-Talk podcast.Geoff Ling: Retired colonel who founded the biology technology office at DARPA.Richard Feynman: Nobel Prize-winning American theoretical physicist known for his work in quantum mechanics, quantum electrodynamics, and superfluidity.Charles Sherrington: One of the founders of modern neuroscience, known for his groundbreaking work on neural reflexes and The Integrative Action of the Nervous System, for which he won the Nobel Prize in Physiology or Medicine in 1932.Santiago Ramón y Cajal: The other founding father of modern neuroscience, known for his pioneering studies of the structure of the nervous system and the neuron doctrine, Nobel Prize winner in Physiology or Medicine in 1906.Asya Rolls: A professor who discovered that inflammation in the colon can form a neural network connection to the brain, advancing our understanding of the gut-brain axis.Sangeeta Chavan: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, contributing to bioelectronic medicine research.Stavros Zanos: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, specializing in neural engineering and bioelectronics.Okito Hashimoto: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, working in the field of bioelectronic medicine.Eric Chang: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, contributing to neuroscience and bioelectronics research.Martine Rothblatt: A friend of Dr. Tracey’s and CEO of United Therapeutics, she is a renowned polymath who founded SiriusXM satellite radio before entering biotechnology to develop treatments for her daughter’s pulmonary hypertension, becoming the highest-paid female CEO in America.Lorimer Moseley: Co-author with David Butler of the book Explain Pain and a leading researcher in pain neuroscience and clinical neurosciences at the University of South Australia.William Bushell: A scientist who works with the Dalai Lama on studies involving meditation, consciousness, and human potential.Elizabeth Blackburn: A scientist who won both the Lasker Prize and the Nobel Prize in Physiology or Medicine in 2009 for her work on telomeres and telomerase.Bob Thurman: Uma Thurman’s father and a professor of Tibetan studies at Columbia University, known for his scholarship on Buddhist philosophy.The Dalai Lama: The spiritual leader of Tibet and global advocate for compassion, peace, and interfaith dialogue.Bill Murray: Formidably funny man and serial-striking bowler.Kevin Rose: Probably not the Kevin you’re looking for, but Kevin, by any other name, would smell as sweet.Institutions & CompaniesSetPoint Medical: A commercial-stage medical technology company that developed the first FDA-approved neuroimmune modulation device to treat rheumatoid arthritis using vagus nerve stimulation.Feinstein Institutes for Medical Research: The research arm of Northwell Health and home to 50 research labs, 3,000 clinical research studies, and 5,000 researchers where Dr. Tracey and his colleagues work.Mayo Clinic: A world-renowned nonprofit American medical organization dedicated to integrated healthcare, education, and research.Stanford University: A prestigious private research university in California known for its groundbreaking research, including work on accelerated TMS and other medical innovations.Centers for Disease Control and Prevention (CDC): The national public health agency of the United States, responsible for protecting public health and safety through disease prevention and health promotion.Karolinska Institute: A prestigious medical research institute and university in Sweden, home to the Nobel Committee for Physiology or Medicine.Defense Advanced Research Projects Agency (DARPA): A research and development agency of the United States Department of Defense responsible for developing emerging technologies for military use.Defense Language Institute: A United States Department of Defense educational and research institution that provides language training to military personnel and federal employees.United Therapeutics: A biotechnology company focused on creating innovative products to address the medical needs of patients with chronic and life-threatening conditions, including pulmonary arterial hypertension and organ transplantation technologies.World Health Organization (WHO): A specialized agency of the United Nations responsible for international public health, setting global health standards, and coordinating international health responses.Columbia University: A prestigious private Ivy League research university in New York City, renowned for its contributions to medicine, science, and other fields of study.Pendulum: A science-backed biotechnology company founded by doctors and scientists that produces next-generation probiotics, including the only commercially available live Akkermansia supplement.WHOOP: 24/7 monitoring across sleep, strain, stress, and heart health.Oura Ring: A smart ring that monitors over 20 biometrics that directly impact how you feel.Fitbit: Wearables designed to “keep you close to your goals, boost your motivation, and show your progress throughout your health and fitness journey.”Relevant Research & ResourcesKevin Tracey on Neuro-Immunology and the Treatment of Inflammatory Diseases | STEM-TalkKevin Tracey, MD, Reveals Vagus Nerve’s Power in New Book | Northwell HealthSetPoint Medical Receives FDA Approval for Novel Neuroimmune Modulation Therapy for Rheumatoid Arthritis | SetPoint MedicalNew Implant Offers Hope for Easing Rheumatoid Arthritis | The New York TimesI Tried 22 Different Medications Before an Electrical Implant Healed My Crohn’s Disease | PreventionNolan Williams — A Glimpse of the Future: Electroceuticals for 70%–90% Remission of Depression, Brain Stimulation for Sports Performance, and De-Risking Ibogaine for TBI/PTSD | The Tim Ferriss ShowDr. Nora Volkow — Director of the National Institute on Drug Abuse (NIDA) | The Tim Ferriss ShowReappraising the Role of the Vagus Nerve in GLP-1-Mediated Regulation of Eating | British Journal of PharmacologyRole of Vagus Nerve Signaling in CNI-1493-Mediated Suppression of Acute Inflammation | Autonomic NeuroscienceGood-bye to Drugs? Kevin Tracey, MD on the Bioelectronics Revolution at the Dysautonomia International Conference | Health RisingNo Audible Wheezing: Nuggets and Conundrums from Mouse Asthma Models | Journal of Experimental MedicineHere’s What Happens When Animals Eat LSD | DoubleBlindSome Practical Thoughts on Suicide | Tim FerrissThe Evolution of Inflammation | PfizerFDA Black Box Warning Raises Awareness of Medication Risk | GoodRxEffects of Anti-Inflammatory Vagus Nerve Stimulation in Endotoxemic Rats on Blood and Spleen Lymphocyte Subsets | Inflammation ResearchVagus Nerve Stimulation for Epilepsy and Depression | NeurotherapeuticsVagus Nerve Active during Exercise, Research Finds | The University of AucklandJumping into the Ice Bath Trend! Mental Health Benefits of Cold Water Immersion | Stanford Lifestyle MedicineThe Thermoregulatory Theory of Yawning: What We Know from over Five Years of Research | Frontiers in NeurosciencePrevalence of Autoimmune Diseases Is Strongly Associated with Average Annual Temperatures: Systematic Review and Linear Regression Analysis | BMC RheumatologyNobel Prize Is Awarded to Doctors Who Discovered H Pylori | The British Medical JournalWhat Happens to Your Blood Sugar While You Sleep? | WebMDType A Personality Traits vs. Type B | Simply PsychologyFocused Ultrasound Neuromodulation of the Spleen Activates an Anti-Inflammatory Response in Humans | Brain StimulationHistory of Auriculotherapy: Additional Information and New Developments | Medical AcupunctureThe Medial Surface of the Auricle: Historical and Recent Maps. What Are the Possible Expectations of the “Thumb-Index Technique” | MedicinesOur Ears Share a Common Ancestry with Fish Gills | Scientific AmericanJP Errico Explains How Vagus-Nerve Stimulation Reduces Inflammation and Chronic Diseases | STEM-TalkVagus Nerve Stimulation May Enhance Language Learning, DoD Study Reports | Practical NeurologyGeoffrey Ling: From DARPA to Life | Twin GlobalVagus Nerve Stimulation (VNS) Therapy | Epilepsy SocietyThe Gut Microbiota Mediates the Anti-seizure Effects of the Ketogenic Diet | CellDr. Andrew Weil — Optimal Health, Plant Medicine, and More | The Tim Ferriss ShowThe Hidden Flaws of HRV Tracking | The Unlazy WayBreathe to Directly Control Heart Rate via Huberman Lab | InstagramFamotidine Activates the Vagus Nerve Inflammatory Reflex to Attenuate Cytokine Storm | Molecular MedicineWHOOP Adds Psychedelics Tracking | Fitt InsiderWhy Don’t We Know How Antidepressants Work Yet? | Chemistry WorldUlf’s Case Study: VAGUS Smartwatch ECG Test | VAGUS Health Ltd.Study of the Transcutaneous Auricular Vagus Nerve Stimulation May Advance Outcome in Chronic Pediatric Inflammatory Diseases | Medical Research ArchivesAcupuncture Enhances Chances of Pregnancy in Unexplained Infertile Patients Who Undergo a Blastocyst Transfer in a Fresh-Cycle | Chinese Journal of Integrative MedicineAcupuncture as Treatment for Female Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | Evidence-Based Complementary and Alternative MedicineDr. Martine Rothblatt — A Masterclass on Asking Better Questions and Peering into the Future | The Tim Ferriss ShowImmunoception: The Insular Cortex Perspective | Cellular & Molecular ImmunologyNew Science Shows Immune “Memory” in the Brain | Quanta MagazineJennifer Aniston Strikes a Nerve | NatureQuantum Physics — His Holiness the Dalai Lama Participates in the 26th Mind & Life Meeting at Drepung | The Office of His Holiness The Dalai LamaSHOW NOTES[00:00:00] Start.[00:06:34] Factors alleviating my skepticism about vagus nerve stimulation.[00:11:12] SetPoint Medical receives FDA approval for vagus nerve stimulation device to treat rheumatoid arthritis.[00:13:24] How Crohn’s disease sufferer Kelly Owens went from a wheelchair to running up stairs in Amsterdam.[00:20:36] Placebo effect concerns and the conditions driving my interest in bioelectric medicine.[00:25:31] Vagus nerve anatomy 101.[00:32:53] Cytokines and inflammation: What happens when the vagus nerve is stimulated.[00:33:45] Discovery story: Accidental finding of brain-body inflammation connection.[00:35:39] Bioelectronic medicine approach vs. pharmaceutical approach.[00:38:18] Mice don’t wheeze.[00:40:13] Depression and inflammation connection: SSRIs may work through anti-inflammatory effects.[00:42:46] My personal experience with vagus nerve stimulation and mood stability.[00:44:22] The pros and cons of inflammation, and how controlling it may lead to even longer lifespans.[00:50:56] Weighing the safety of VNS vs. biologics in cytokine suppression.[00:56:27] Cold exposure, meditation, and breathing practices affecting the vagus nerve.[00:59:01] A population-level increase in chronic inflammatory diseases: Nature vs. nurture.[01:00:48] H. pylori: For when you can’t blame stress, God, or the patient for that nagging ulcer.[01:03:13] Stress, cortisol, and inflammation connections.[01:05:42] SetPoint device vs. non-invasive alternatives for different patient populations.[01:11:09] Auricular therapy’s curious French origins.[01:13:28] There’s something fishy about this vestigial vagus nerve pathway.[01:16:03] Overlapping activation patterns from brain imaging studies of ear stimulation.[01:19:01] DARPA support and Geoff Ling’s “What if it’s yes?” attitude.[01:21:58] Neurocognition and vagus nerve inputs.[01:27:20] How Ulf Andersson turned his depression around with a TENS unit.[01:31:55] Heart rate variability complexity and measurement challenges.[01:33:05] A breathing exercise for directly controlling heart rate.[01:35:30] Using a common antacid as a pharmacological vagus nerve stimulator during COVID.[01:36:23] A call for more inflammation-based depression research and patient stratification.[01:39:52] SSRIs and anti-inflammatory mechanisms in depression treatment.[01:42:20] Interoception: The body’s inflammatory signals reaching the brain via vagus nerve.[01:43:22] Ulf’s published protocol for TENS unit ear stimulation.[01:44:37] VNS, acupuncture, fertility, and Martine Rothblatt.[01:47:16] Chronic low back pain and an inflammatory overreaction analogy.[01:48:35] Implications of Asya Rolls’ engram research and inflammation memories in the brain.[02:02:35] Cervical TENS vs. true VNS.[02:07:12] Charles Sherrington’s reflex theory and nervous system integration.[02:12:15] Blue energy meditation and vagus nerve pathways with the Dalai Lama.[02:16:47] Parting thoughts: Serious medical conditions vs. self-help approaches.DR. KEVIN TRACEY QUOTES FROM THE INTERVIEW

“60 million people die on the planet Earth every year. And 40 million of them die from heart disease, stroke, neurodegeneration, Alzheimer’s, Parkinson’s, metabolic syndrome, diabetes, and cancer. So two thirds of the people that die every year on the planet Earth die of those conditions. And that’s according to the WHO. Those conditions all have one thing in common: they’re either caused by inflammation or made worse by inflammation.”

— Dr. Kevin Tracey

“It was just announced that the company SetPoint Medical, which will now be marketing a device to stimulate the vagus nerve to treat rheumatoid arthritis, has received FDA approval. So there’ll be a product launch underway for everything we’re about to talk about in the context of using a medical device that activates an evolutionarily conserved and ancient reflex through which the brain can suppress inflammation when it’s running out of control.”

— Dr. Kevin Tracey

“We’ve discovered that signals travel from the brain through the vagus nerve. … These signals traveling in the vagus nerve are like the brakes on your car. And when you tap those brakes to slow your car barreling down the hill, this device activates what we call the inflammatory reflex.”

— Dr. Kevin Tracey

“If we can find such nerves, then we can build devices to control the nerves, and the devices become the therapy. The bioelectronic medicine story works as long as you know the molecular mechanism, and that’s where people have to be really careful with vagus-nerve stimulation.”

— Dr. Kevin Tracey

“Almost everybody until a hundred years ago, 150 years ago, almost everybody died by the time they were 30. And what happened in the last 150 years can be summarized in a very simple sentence. The human race in the last 150 years removed infection as the leading cause of death. … I think something similar will happen maybe in the next 20 years if we can really understand how to modify inflammation.”

— Dr. Kevin Tracey

“My adage for this thing is, when you don’t understand a disease, think of epilepsy. You start off, you blame God. So they did exorcisms, and that doesn’t work. So if it’s not God’s fault, the next thing you do is you blame the patient. And when you realize it’s not the patient’s fault, in today’s era, oftentimes we find out it’s actually caused, there’s some infectious cause of this thing. And so autoimmune disease may have an infectious cause, it may have an environmental cause. People talk about genetic causes. You inherit some level of risk for autoimmune diseases, but in very few of these conditions do you actually inherit the condition.”

— Dr. Kevin Tracey

Want to hear another episode about the future of electroceuticals and brain stimulation? Listen to my conversation with Stanford’s Dr. Nolan Williams, in which we discussed 70%–90% remission rates for treatment-resistant depression, brain stimulation for sports performance, accelerated TMS protocols, de-risking ibogaine for TBI/PTSD, the future of “electroceuticals,” and much more.

The post Dr. Kevin Tracey — Stimulating the Vagus Nerve to Tame Inflammation, Alleviate Depression, Treat Autoimmune Disorders (e.g., Rheumatoid Arthritis), and Much More (#824) appeared first on The Blog of Author Tim Ferriss.

Kevin J. Tracey, MD (@KevinJTraceyMD), is president and CEO of the Feinstein Institutes for Medical Research at Northwell Health, a pioneer of vagus nerve research and author of the recent book, The Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes. 

His contributions include identifying the therapeutic action of monoclonal anti-TNF antibodies and discovering the specific reflex control of immunity by the nervous system, called the “inflammatory reflex.” These discoveries launched the new scientific field called bioelectronic medicine, which investigates the therapeutic applications of vagus nerve stimulation to cure disease.

Dr. Tracey, a neurosurgeon, pursued studies of inflammation after the mysterious death, from sepsis, of a toddler who was in his care. His lab has since revealed molecular mechanisms of inflammation and identified the use of vagus nerve stimulation to treat it. An inventor on more than 120 US patents and the author of more than 450 scientific publications, he is among the most highly cited scientists in the world. He co-founded the Global Sepsis Alliance, is the author of Fatal Sequence, and is a national and international lecturer.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube.

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SELECTED LINKS FROM THE EPISODEConnect with Dr. Kevin Tracey:

The Feinstein Institutes of Northwell Health | SetPoint Medical | LinkedIn

Publications & MediaThe Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes by Kevin J. Tracey: A groundbreaking book exploring the potential of the vagus nerve to regulate the body’s vital systems and heal medical conditions without drugs.The Polyvagal Theory: Neurophysiological Foundations of Emotions, Attachment, Communication, and Self-regulation by Stephen W. Porges: A comprehensive compilation of decades of research on the polyvagal theory and its implications for understanding the autonomic nervous system. STEM-Talk : A bi-weekly interview podcast produced by the Florida Institute for Human and Machine Cognition featuring conversations with groundbreaking scientists, engineers, and technologists. The New York Times : A major American daily newspaper that featured coverage on SetPoint Medical and other medical developments. HuffPost : An American progressive news and opinion website where Dr. Tracey was interviewed about his research. Cell : A prestigious peer-reviewed scientific journal that published research on topics including gut microbiota and the ketogenic diet.Explain Pain by David Butler and G. Lorimer Moseley: An evidence-based book designed for therapists, patients, and students that explains the science behind pain and recovery strategies.The Integrative Action of the Nervous System by Charles Sherrington: A classic 1906 work in neuroscience that established fundamental concepts about how the nervous system functions as an integrated whole.Medical ConditionsRheumatoid Arthritis: An autoimmune disease that causes inflammation in the joints.Crohn’s Disease: A type of inflammatory bowel disease that affects the digestive tract.PTSD (Post-Traumatic Stress Disorder): A mental health condition triggered by experiencing or witnessing a traumatic event.Chronic Fatigue Syndrome: A long-term illness characterized by extreme fatigue that doesn’t improve with rest and may worsen with physical or mental activity.Depression: A mood disorder that causes persistent feelings of sadness, hopelessness, and loss of interest in activities.Lyme Disease: An infectious disease caused by bacteria transmitted through the bite of infected ticks.Neurodegenerative Disease: A range of conditions that primarily affect the neurons in the human brain, leading to progressive deterioration of function.Anaphylaxis: A severe, potentially life-threatening allergic reaction that can occur rapidly after exposure to an allergen.Asthma: A respiratory condition in which airways become inflamed, narrow, and produce excess mucus, making breathing difficult.Sepsis: A life-threatening condition that arises when the body’s response to infection causes widespread inflammation and organ dysfunction.Psoriatic Arthritis: A form of inflammatory arthritis that affects some people who have the skin condition psoriasis.Autoimmune Conditions: Disorders in which the immune system mistakenly attacks the body’s own healthy tissues and organs.COVID-19: A contagious respiratory illness caused by the SARS-CoV-2 virus that can range from mild to severe symptoms.Alzheimer’s Disease: A progressive neurodegenerative disease that destroys memory and other important mental functions.Parkinson’s Disease: A progressive disorder of the central nervous system that affects movement, often causing tremors, stiffness, and difficulty with balance.Metabolic Syndrome: A cluster of conditions including high blood pressure, high blood sugar, excess abdominal fat, and abnormal cholesterol levels that increase the risk of heart disease, stroke, and diabetes.Diabetes: A chronic disease that occurs when the body cannot properly produce or use insulin, leading to elevated blood sugar levels.Cancer: A group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body.Malaria: A life-threatening disease caused by parasites transmitted through the bites of infected female Anopheles mosquitoes.Tuberculosis: A serious infectious bacterial disease that primarily affects the lungs but can spread to other parts of the body.Peptic Ulcer Disease: A condition characterized by painful sores or ulcers that develop in the lining of the stomach or the first part of the small intestine.Epilepsy: A neurological disorder in which brain activity becomes abnormal, causing seizures, unusual behavior, sensations, and sometimes loss of consciousness.Cluster Headaches: A series of extremely painful headaches that occur in cyclical patterns or clusters, often at the same time each day for weeks or months.Migraines: Intense headaches that cause severe throbbing or pulsing pain, typically on one side of the head, often accompanied by nausea and sensitivity to light and sound.Sciatica: Pain that radiates along the sciatic nerve pathway from the lower back through the hips and down one or both legs.Treatments & TherapiesVagus Nerve Stimulation (VNS): A medical treatment that involves delivering electrical impulses to the vagus nerve.Audio Chakra Cleanse Soundtracks: A type of alternative therapy mentioned as an example of “nonsense.”Biologics: Medications made from living organisms or their components.Ketogenic Diet: A very low-carb, high-fat diet.Exogenous Ketones: Ketones that are ingested through a nutritional supplement.GLP-1 Agonists (e.g., Ozempic, Mounjaro): A class of medications used to treat type 2 diabetes and obesity.Microbiome Transplants: The transfer of fecal matter from a healthy donor to a recipient to restore a healthy gut microbiome.TMS (Transcranial Magnetic Stimulation): A noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression.Focused Ultrasound: A non-invasive therapeutic technology that uses focused sound waves to target and treat a variety of medical conditions.Psychedelics (e.g., LSD, 2C-B, Ayahuasca): A class of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness.TENS (Transcutaneous Electrical Nerve Stimulation) units: A non-invasive method of pain relief that uses a mild electrical current.Auricular Therapy: A form of alternative medicine based on the idea that the ear is a microsystem which reflects the entire body.Famotidine (Pepcid): An over-the-counter antacid that Dr. Tracey describes as a pharmacological vagus nerve stimulator.Antibiotics: Medications that fight bacterial infections.SSRIs (Selective Serotonin Reuptake Inhibitors): A class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.Ibuprofen: A nonsteroidal anti-inflammatory drug (NSAID).Monoclonal Antibodies: Laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses.Optogenetics: A biological technique that involves the use of light to control cells in living tissue, typically neurons, that have been genetically modified to express light-sensitive ion channels.Key Concepts & TheoriesPolyvagal Theory: A theory that links the evolution of the autonomic nervous system to social behavior and emphasizes the importance of physiological state in the expression of behavioral problems and psychiatric disorders.Heart Rate Variability (HRV): The variation in the time interval between consecutive heartbeats.Sympathetic Overdrive: A condition where the sympathetic nervous system is overactive.Inflammatory Reflex: A physiological reflex that controls the inflammatory response.Bioelectronic Medicine: A field of medicine that uses electronic devices to treat diseases and injuries.Blood-Brain Barrier: A highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside.Cytokines (e.g., TNF, IL-1, IL-6): A broad and loose category of small proteins that are important in cell signaling.Cytokine Storm: A severe immune reaction in which the body releases too many cytokines into the blood too quickly.Inflammaging: Chronic, low-grade inflammation that develops with advanced age.Neuroinflammation: Inflammation of the nervous tissue.Neuroplasticity: The ability of the brain to form and reorganize synaptic connections, especially in response to learning or experience or following injury.Interoception: The sense of the internal state of the body.Engram: A physical trace of memory in the brain.M1 and M2 Macrophages: Two different types of white blood cells with different functions in the inflammatory response.PeopleKelly Owens: A patient of Dr. Tracey’s who suffered from Crohn’s disease and rheumatoid arthritis and was successfully treated with a vagus nerve stimulation device.Murthy Simhambhatla: The CEO of SetPoint Medical, a bioelectronic medicine company developing vagus nerve stimulation therapies.Dave Chernoff: The Chief Medical Officer of SetPoint Medical, overseeing clinical development of bioelectronic therapies.Nolan Williams: A psychiatry professor and director of the Stanford Brain Stimulation Lab who pioneered Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an FDA-approved treatment for treatment-resistant depression using accelerated TMS.Nora Volkow: Director of the National Institute on Drug Abuse (NIDA) who pioneered the use of brain imaging to investigate addiction as a brain disorder and is researching focused ultrasound therapies for addiction treatment.Steve Liberles: A professor of cell biology at Harvard Medical School and Howard Hughes Medical Institute investigator who studies the molecular neuroscience of vagus nerve sensory systems and identified specific vagal neuron subtypes that control breathing and digestion in mice.K. Frank Austen: A leading expert on asthma research and respiratory medicine.Barry Jacobs: A researcher at Princeton University who studied the effects of LSD on cats and contributed to early psychedelic research.Andrew Weil: A physician and author with a background in ethnobotany who has written about his experiences with psychedelics including LSD and integrative medicine approaches.Ulf Andersson: A retired professor of pediatric rheumatology at the Karolinska Institute and friend of Dr. Tracey’s who used a TENS unit to treat his own inflammation-related depression.Paul Nogier: A French physician who created the first auricular acupuncture maps in 1957, pioneering modern ear acupuncture techniques.Kenneth M. Ford: Founder and CEO Emeritus of the Florida Institute for Human and Machine Cognition (IHMC), and co-host of the STEM-Talk podcast.Geoff Ling: Retired colonel who founded the biology technology office at DARPA.Richard Feynman: Nobel Prize-winning American theoretical physicist known for his work in quantum mechanics, quantum electrodynamics, and superfluidity.Charles Sherrington: One of the founders of modern neuroscience, known for his groundbreaking work on neural reflexes and The Integrative Action of the Nervous System, for which he won the Nobel Prize in Physiology or Medicine in 1932.Santiago Ramón y Cajal: The other founding father of modern neuroscience, known for his pioneering studies of the structure of the nervous system and the neuron doctrine, Nobel Prize winner in Physiology or Medicine in 1906.Asya Rolls: A professor who discovered that inflammation in the colon can form a neural network connection to the brain, advancing our understanding of the gut-brain axis.Sangeeta Chavan: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, contributing to bioelectronic medicine research.Stavros Zanos: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, specializing in neural engineering and bioelectronics.Okito Hashimoto: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, working in the field of bioelectronic medicine.Eric Chang: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, contributing to neuroscience and bioelectronics research.Martine Rothblatt: A friend of Dr. Tracey’s and CEO of United Therapeutics, she is a renowned polymath who founded SiriusXM satellite radio before entering biotechnology to develop treatments for her daughter’s pulmonary hypertension, becoming the highest-paid female CEO in America.Lorimer Moseley: Co-author with David Butler of the book Explain Pain and a leading researcher in pain neuroscience and clinical neurosciences at the University of South Australia.William Bushell: A scientist who works with the Dalai Lama on studies involving meditation, consciousness, and human potential.Elizabeth Blackburn: A scientist who won both the Lasker Prize and the Nobel Prize in Physiology or Medicine in 2009 for her work on telomeres and telomerase.Bob Thurman: Uma Thurman’s father and a professor of Tibetan studies at Columbia University, known for his scholarship on Buddhist philosophy.The Dalai Lama: The spiritual leader of Tibet and global advocate for compassion, peace, and interfaith dialogue.Bill Murray: Formidably funny man and serial-striking bowler.Kevin Rose: Probably not the Kevin you’re looking for, but Kevin, by any other name, would smell as sweet.Institutions & CompaniesSetPoint Medical: A commercial-stage medical technology company that developed the first FDA-approved neuroimmune modulation device to treat rheumatoid arthritis using vagus nerve stimulation.Feinstein Institutes for Medical Research: The research arm of Northwell Health and home to 50 research labs, 3,000 clinical research studies, and 5,000 researchers where Dr. Tracey and his colleagues work.Mayo Clinic: A world-renowned nonprofit American medical organization dedicated to integrated healthcare, education, and research.Stanford University: A prestigious private research university in California known for its groundbreaking research, including work on accelerated TMS and other medical innovations.Centers for Disease Control and Prevention (CDC): The national public health agency of the United States, responsible for protecting public health and safety through disease prevention and health promotion.Karolinska Institute: A prestigious medical research institute and university in Sweden, home to the Nobel Committee for Physiology or Medicine.Defense Advanced Research Projects Agency (DARPA): A research and development agency of the United States Department of Defense responsible for developing emerging technologies for military use.Defense Language Institute: A United States Department of Defense educational and research institution that provides language training to military personnel and federal employees.United Therapeutics: A biotechnology company focused on creating innovative products to address the medical needs of patients with chronic and life-threatening conditions, including pulmonary arterial hypertension and organ transplantation technologies.World Health Organization (WHO): A specialized agency of the United Nations responsible for international public health, setting global health standards, and coordinating international health responses.Columbia University: A prestigious private Ivy League research university in New York City, renowned for its contributions to medicine, science, and other fields of study.Pendulum: A science-backed biotechnology company founded by doctors and scientists that produces next-generation probiotics, including the only commercially available live Akkermansia supplement.WHOOP: 24/7 monitoring across sleep, strain, stress, and heart health.Oura Ring: A smart ring that monitors over 20 biometrics that directly impact how you feel.Fitbit: Wearables designed to “keep you close to your goals, boost your motivation, and show your progress throughout your health and fitness journey.”Relevant Research & ResourcesKevin Tracey on Neuro-Immunology and the Treatment of Inflammatory Diseases | STEM-TalkKevin Tracey, MD, Reveals Vagus Nerve’s Power in New Book | Northwell HealthSetPoint Medical Receives FDA Approval for Novel Neuroimmune Modulation Therapy for Rheumatoid Arthritis | SetPoint MedicalNew Implant Offers Hope for Easing Rheumatoid Arthritis | The New York TimesI Tried 22 Different Medications Before an Electrical Implant Healed My Crohn’s Disease | PreventionNolan Williams — A Glimpse of the Future: Electroceuticals for 70%–90% Remission of Depression, Brain Stimulation for Sports Performance, and De-Risking Ibogaine for TBI/PTSD | The Tim Ferriss ShowDr. Nora Volkow — Director of the National Institute on Drug Abuse (NIDA) | The Tim Ferriss ShowReappraising the Role of the Vagus Nerve in GLP-1-Mediated Regulation of Eating | British Journal of PharmacologyRole of Vagus Nerve Signaling in CNI-1493-Mediated Suppression of Acute Inflammation | Autonomic NeuroscienceGood-bye to Drugs? Kevin Tracey, MD on the Bioelectronics Revolution at the Dysautonomia International Conference | Health RisingNo Audible Wheezing: Nuggets and Conundrums from Mouse Asthma Models | Journal of Experimental MedicineHere’s What Happens When Animals Eat LSD | DoubleBlindSome Practical Thoughts on Suicide | Tim FerrissThe Evolution of Inflammation | PfizerFDA Black Box Warning Raises Awareness of Medication Risk | GoodRxEffects of Anti-Inflammatory Vagus Nerve Stimulation in Endotoxemic Rats on Blood and Spleen Lymphocyte Subsets | Inflammation ResearchVagus Nerve Stimulation for Epilepsy and Depression | NeurotherapeuticsVagus Nerve Active during Exercise, Research Finds | The University of AucklandJumping into the Ice Bath Trend! Mental Health Benefits of Cold Water Immersion | Stanford Lifestyle MedicineThe Thermoregulatory Theory of Yawning: What We Know from over Five Years of Research | Frontiers in NeurosciencePrevalence of Autoimmune Diseases Is Strongly Associated with Average Annual Temperatures: Systematic Review and Linear Regression Analysis | BMC RheumatologyNobel Prize Is Awarded to Doctors Who Discovered H Pylori | The British Medical JournalWhat Happens to Your Blood Sugar While You Sleep? | WebMDType A Personality Traits vs. Type B | Simply PsychologyFocused Ultrasound Neuromodulation of the Spleen Activates an Anti-Inflammatory Response in Humans | Brain StimulationHistory of Auriculotherapy: Additional Information and New Developments | Medical AcupunctureThe Medial Surface of the Auricle: Historical and Recent Maps. What Are the Possible Expectations of the “Thumb-Index Technique” | MedicinesOur Ears Share a Common Ancestry with Fish Gills | Scientific AmericanJP Errico Explains How Vagus-Nerve Stimulation Reduces Inflammation and Chronic Diseases | STEM-TalkVagus Nerve Stimulation May Enhance Language Learning, DoD Study Reports | Practical NeurologyGeoffrey Ling: From DARPA to Life | Twin GlobalVagus Nerve Stimulation (VNS) Therapy | Epilepsy SocietyThe Gut Microbiota Mediates the Anti-seizure Effects of the Ketogenic Diet | CellDr. Andrew Weil — Optimal Health, Plant Medicine, and More | The Tim Ferriss ShowThe Hidden Flaws of HRV Tracking | The Unlazy WayBreathe to Directly Control Heart Rate via Huberman Lab | InstagramFamotidine Activates the Vagus Nerve Inflammatory Reflex to Attenuate Cytokine Storm | Molecular MedicineWHOOP Adds Psychedelics Tracking | Fitt InsiderWhy Don’t We Know How Antidepressants Work Yet? | Chemistry WorldUlf’s Case Study: VAGUS Smartwatch ECG Test | VAGUS Health Ltd.Study of the Transcutaneous Auricular Vagus Nerve Stimulation May Advance Outcome in Chronic Pediatric Inflammatory Diseases | Medical Research ArchivesAcupuncture Enhances Chances of Pregnancy in Unexplained Infertile Patients Who Undergo a Blastocyst Transfer in a Fresh-Cycle | Chinese Journal of Integrative MedicineAcupuncture as Treatment for Female Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | Evidence-Based Complementary and Alternative MedicineDr. Martine Rothblatt — A Masterclass on Asking Better Questions and Peering into the Future | The Tim Ferriss ShowImmunoception: The Insular Cortex Perspective | Cellular & Molecular ImmunologyNew Science Shows Immune “Memory” in the Brain | Quanta MagazineJennifer Aniston Strikes a Nerve | NatureQuantum Physics — His Holiness the Dalai Lama Participates in the 26th Mind & Life Meeting at Drepung | The Office of His Holiness The Dalai LamaSHOW NOTES[00:00:00] Start.[00:06:34] Factors alleviating my skepticism about vagus nerve stimulation.[00:11:12] SetPoint Medical receives FDA approval for vagus nerve stimulation device to treat rheumatoid arthritis.[00:13:24] How Crohn’s disease sufferer Kelly Owens went from a wheelchair to running up stairs in Amsterdam.[00:20:36] Placebo effect concerns and the conditions driving my interest in bioelectric medicine.[00:25:31] Vagus nerve anatomy 101.[00:32:53] Cytokines and inflammation: What happens when the vagus nerve is stimulated.[00:33:45] Discovery story: Accidental finding of brain-body inflammation connection.[00:35:39] Bioelectronic medicine approach vs. pharmaceutical approach.[00:38:18] Mice don’t wheeze.[00:40:13] Depression and inflammation connection: SSRIs may work through anti-inflammatory effects.[00:42:46] My personal experience with vagus nerve stimulation and mood stability.[00:44:22] The pros and cons of inflammation, and how controlling it may lead to even longer lifespans.[00:50:56] Weighing the safety of VNS vs. biologics in cytokine suppression.[00:56:27] Cold exposure, meditation, and breathing practices affecting the vagus nerve.[00:59:01] A population-level increase in chronic inflammatory diseases: Nature vs. nurture.[01:00:48] H. pylori: For when you can’t blame stress, God, or the patient for that nagging ulcer.[01:03:13] Stress, cortisol, and inflammation connections.[01:05:42] SetPoint device vs. non-invasive alternatives for different patient populations.[01:11:09] Auricular therapy’s curious French origins.[01:13:28] There’s something fishy about this vestigial vagus nerve pathway.[01:16:03] Overlapping activation patterns from brain imaging studies of ear stimulation.[01:19:01] DARPA support and Geoff Ling’s “What if it’s yes?” attitude.[01:21:58] Neurocognition and vagus nerve inputs.[01:27:20] How Ulf Andersson turned his depression around with a TENS unit.[01:31:55] Heart rate variability complexity and measurement challenges.[01:33:05] A breathing exercise for directly controlling heart rate.[01:35:30] Using a common antacid as a pharmacological vagus nerve stimulator during COVID.[01:36:23] A call for more inflammation-based depression research and patient stratification.[01:39:52] SSRIs and anti-inflammatory mechanisms in depression treatment.[01:42:20] Interoception: The body’s inflammatory signals reaching the brain via vagus nerve.[01:43:22] Ulf’s published protocol for TENS unit ear stimulation.[01:44:37] VNS, acupuncture, fertility, and Martine Rothblatt.[01:47:16] Chronic low back pain and an inflammatory overreaction analogy.[01:48:35] Implications of Asya Rolls’ engram research and inflammation memories in the brain.[02:02:35] Cervical TENS vs. true VNS.[02:07:12] Charles Sherrington’s reflex theory and nervous system integration.[02:12:15] Blue energy meditation and vagus nerve pathways with the Dalai Lama.[02:16:47] Parting thoughts: Serious medical conditions vs. self-help approaches.DR. KEVIN TRACEY QUOTES FROM THE INTERVIEW

“60 million people die on the planet Earth every year. And 40 million of them die from heart disease, stroke, neurodegeneration, Alzheimer’s, Parkinson’s, metabolic syndrome, diabetes, and cancer. So two thirds of the people that die every year on the planet Earth die of those conditions. And that’s according to the WHO. Those conditions all have one thing in common — they’re either caused by inflammation or made worse by inflammation.”

— Dr. Kevin Tracey

“It was just announced that the company SetPoint Medical, which will now be marketing a device to stimulate the vagus nerve to treat rheumatoid arthritis, has received FDA approval. So there’ll be a product launch underway for everything we’re about to talk about in the context of using a medical device that activates an evolutionarily conserved and ancient reflex through which the brain can suppress inflammation when it’s running out of control.”

— Dr. Kevin Tracey

“We’ve discovered that signals travel from the brain through the vagus nerve. … These signals traveling in the vagus nerve are like the brakes on your car. And when you tap those brakes to slow your car barreling down the hill, this device activates what we call the inflammatory reflex.”

— Dr. Kevin Tracey

“If we can find such nerves, then we can build devices to control the nerves, and the devices become the therapy. The bioelectronic medicine story works as long as you know the molecular mechanism, and that’s where people have to be really careful with vagus nerve stimulation.”

— Dr. Kevin Tracey

“Almost everybody until a hundred years ago, 150 years ago, almost everybody died by the time they were 30. And what happened in the last 150 years can be summarized in a very simple sentence. The human race in the last 150 years removed infection as the leading cause of death. … I think something similar will happen maybe in the next 20 years if we can really understand how to modify inflammation.”

— Dr. Kevin Tracey

“My adage for this thing is, when you don’t understand a disease, think of epilepsy. You start off, you blame God. So they did exorcisms, and that doesn’t work. So if it’s not God’s fault, the next thing you do is you blame the patient. And when you realize it’s not the patient’s fault, in today’s era, oftentimes we find out it’s actually caused, there’s some infectious cause of this thing. And so autoimmune disease may have an infectious cause, it may have an environmental cause. People talk about genetic causes. You inherit some level of risk for autoimmune diseases, but in very few of these conditions do you actually inherit the condition.”

— Dr. Kevin Tracey

Want to hear another episode about the future of electroceuticals and brain stimulation? Listen to my conversation with Stanford’s Dr. Nolan Williams, in which we discussed 70%–90% remission rates for treatment-resistant depression, brain stimulation for sports performance, accelerated TMS protocols, de-risking ibogaine for TBI/PTSD, the future of “electroceuticals,” and much more.

The post #824: Dr. Kevin Tracey — Stimulating The Vagus Nerve to Tame Inflammation, Alleviate Depression, Treat Autoimmune Disorders (e.g., Rheumatoid Arthritis), and Much More (#824) appeared first on The Blog of Author Tim Ferriss.

Dr. Jeffrey Goldberg is Professor and Chair of Ophthalmology and Director of the Byers Eye Institute at Stanford University, a leading scientist in the development and degeneration of the visual system from eye to brain, and a practicing ophthalmologist and surgeon.

He is a member of the National Academy of Medicine, and has won a number of prestigious awards, like the Scientist of the Year by the Hope For Vision foundation and the Cogan award from the Association for Research in Vision and Ophthalmology. Dr. Goldberg received his B.S. magna cum laude from Yale University, and his M.D. and Ph.D. from Stanford University where he made significant discoveries about the failure of optic nerve regeneration. 

Dr.Goldberg’s research is directed at vision restoration, including neuroprotection and regeneration of the retina and optic nerve, a major unmet need in glaucoma and other eye diseases. His laboratory is developing novel molecular, stem cell and nanotherapeutics approaches for eye repair, and he is widely recognized for translating advances in the lab into clinical trials for patients. 

A number of his innovations have spun out into startups and clinical-stage companies, and he serves as medical and scientific advisor to a number of ophthalmic startup, pharma and device companies. His goal is to translate scientific discoveries to patient therapies.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube.

This episode is brought to you by:

Gamma  AI design partner for effortless presentations, websites, social media posts, and more (use code TIM at checkout for one month off on their annual plan) Helix Sleep  premium mattresses AG1  all-in-one nutritional supplementListen onApple Podcasts[image error]Listen onSpotify[image error]Listen onOvercastDr. Jeffrey Goldberg — Creating Supranormal Vision, Cutting-Edge Science for Eye Health, Supplements, Red Light Therapy, and The Future of Eyesight Restoration

This episode is brought to you by AG1! I get asked all the time, “If you could use only one supplement, what would it be?” My answer is usually AG1, my all-in-one nutritional insurance. I recommended it in The 4-Hour Body in 2010 and did not get paid to do so. I do my best with nutrient-dense meals, of course, but AG1 further covers my bases with vitamins, minerals, and whole-food-sourced micronutrients that support gut health and the immune system. 

I have always admired AG1’s commitment to improving one product over many years, which is why I am excited about their latest upgrade: AG1 Next Gen. It’s the same—but improved—single-scoop, once-a-day product to support your mental clarity, immune health, and energy. Right now, you’ll get a 1-year supply of Vitamin D free with your first subscription purchase—a vital nutrient for a strong immune system and strong bones. Visit DrinkAG1.com/Tim to claim this special offer today and receive your 1-year supply of Vitamin D (and 5 free AG1 travel packs) with your first subscription purchase! That’s up to a one-year supply of Vitamin D as added value when you try their delicious and comprehensive daily, foundational nutrition supplement that supports whole-body health.

This episode is brought to you by Gamma! Readers of The 4-Hour Workweek know I recommend delegating and automating tasks that can be done better by someone or something else. It’s why I recommend this episode’s sponsor, Gamma, for creating incredible, professional slide decks better, cheaper, and faster than you ever thought possible. I polled many of you about Gamma on social media, and some of you called it “a game changer,” “mind-blowing,” and “far and away the best product in the category.”

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With more than 50 million users, it’s already the most popular AI presentation platform in the world. Explore Gamma today at gamma.app. Listeners get one month free of Gamma Pro’s annual plan by using promo code TIM at checkout.

This episode is brought to you by Helix Sleep! Helix was selected as the best overall mattress of 2024 by Forbes, Fortune, and Wired magazines and many others. With Helix, there’s a specific mattress to meet each and every body’s unique comfort needs. Just take their quiz—only two minutes to complete—that matches your body type and sleep preferences to the perfect mattress for you. They have a 10-year warranty, and you get to try it out for a hundred nights, risk-free. They’ll even pick it up from you if you don’t love it. And now, Helix is offering 20% off all mattress orders at HelixSleep.com/Tim.

Want to hear another podcast episode with a Stanford neuroscientist who won awards for vision research? Listen to my conversation with Dr. Andrew Huberman, in which we discussed the foundations of physical and mental performance, core supplements, sleep optimization, psychedelics, neural plasticity, and much more.

SELECTED LINKS FROM THE EPISODEConnect with Dr. Jeffrey Goldberg:

Faculty Profile | Stanford Ophthalmology | Clinical Trials

Conditions and Key ConceptsPresbyopia: Age-related decline in near vision due to the stiffening of the lens.Myopia: Nearsightedness; an epidemic condition, especially in children, that can be slowed with red or violet light.Glaucoma: A neurodegenerative disease and the leading cause of irreversible blindness, characterized by damage to the optic nerve, often associated with high eye pressure.Age-Related Macular Degeneration (AMD): An eye disease that can cause blurred or no vision in the center of the visual field.Cataracts: A clouding of the lens in the eye that leads to a decrease in vision.Dry Eye: A common condition where the eyes don’t produce enough quality tears.Neuroplasticity: The brain’s ability to reorganize itself by forming new neural connections, a key concept for vision training and restoration.Supranormal Vision: Vision that is better than the “normal” 20/20 standard, such as 20/12.Mitochondrial Health: The proper functioning of mitochondria, the “powerhouses” of the cell, which is crucial for the health of neurons in the eye and brain.Metabolic Syndrome: A cluster of conditions (high blood pressure, high blood sugar, etc.) that increase the risk of heart disease, stroke, and type 2 diabetes.APOE3/4: A genetic variant that increases the risk of developing Alzheimer’s disease.Three-Parent Technique: An IVF method that cleverly avoids passing along mitochondrial disease to the offspring by incorporating DNA from three parents.Anatomy of the EyeCornea: The clear front window of the eye that does most of the light bending.Iris: The colored part of the eye (brown, blue, etc.) that controls the size of the pupil.Pupil: The opening in the center of the iris that light passes through.Lens: The structure behind the iris that performs fine-focusing; it stiffens with age, causing presbyopia.Vitreous: The gel-like substance that fills the middle of the eye.Retina: The light-sensitive tissue at the back of the eye that contains photoreceptors.Rods and Cones: The two types of photoreceptor cells in the retina. Rods are for low-light vision, and cones are for daytime color vision.Retinal Ganglion Cells: The neurons that collect visual information from the retina and send it to the brain.Optic Nerve: The bundle of nerve fibers (axons) from the retinal ganglion cells that connects the eye to the brain.Supplements, Treatments, and TechnologiesAREDS 2: An over-the-counter supplement formulation clinically proven to slow vision loss in moderate age-related macular degeneration.Vitamin B3 (Nicotinamide): A vitamin supplement being studied for its potential to restore vision in diseases like glaucoma.CoQ10 and Ginkgo: Other supplements mentioned as having been studied for vision, with less conclusive evidence.Pilocarpine: The active ingredient in some FDA-approved eye drops that constricts the pupil to improve focus and treat presbyopia temporarily.Red Light and Violet Light Therapy: The use of specific wavelengths of light for minutes a day, shown to slow myopia progression in children and potentially support mitochondrial health.Strobe Goggles: Eyewear that reduces the visual frame rate (e.g., by strobing or flickering) to train an athlete’s reflexes and hand-eye coordination.Visual Perception Training: Computer-based exercises that aim to improve vision by training the brain’s processing abilities.Cannabis (THC/CBD): Mentioned for its ability to temporarily lower eye pressure in glaucoma patients, though continuous use is impractical.Low-Dose Psychedelics: Compounds like LSD mentioned for their potential to increase visual acuity and induce neuroplasticity.Stem Cells: Mentioned as a future, but not yet ready, therapy for replacing damaged retinal cells.Serum Tears: Custom eye drops made from a patient’s own blood serum, rich in growth factors to treat severe dry eye.Preservative-Free Artificial Tears: Recommended for frequent use to treat dry eye, as preservatives in standard drops can be irritating.Media and ResourcesAndrew Huberman’s Podcast: Where I first heard Dr. Goldberg speak.Clinicaltrials.gov: A US government website for finding and learning about clinical trials for various conditions.Stanford Ophthalmology Website: Mentioned by Dr. Goldberg as a resource for finding clinical trials related to vision.Science is Real: A song by They Might Be Giants.Institutions, Companies, and FoundationsStanford University: The institution where Dr. Goldberg, Dr. Huberman, Dr. Eagleman, and Dr. Williams work or have worked.FDA (Food and Drug Administration): The US agency responsible for approving medical treatments, mentioned in relation to eye drops and red light therapy.Cognito Therapeutics: A company developing a headset using light and sound to treat Alzheimer’s disease.MIT (Massachusetts Institute of Technology): The university where Ed Boyden and Li-Huei Tsai conducted foundational research.Harvard University: The institution where researcher Dongfeng Chen works.Holobiome: A company mentioned for creating a comprehensive library of gut microbiota.Glaucoma Research Foundation: A San Francisco-based non-profit organization.The Glaucoma Foundation: A New York City-based non-profit organization.DARPA (Defense Advanced Research Projects Agency): Mentioned for using devices to improve language acquisition.PeopleAndrew Huberman: A neuroscientist at Stanford and a mutual friend.David Eagleman: A neuroscientist at Stanford mentioned in the context of sensory substitution tools.Aaron Rodgers: A professional athlete mentioned in connection with using low-dose psychedelics for performance.Nolan Williams: A researcher at Stanford known for work on accelerated TMS for depression.Ed Boyden: A neuroscientist at MIT who co-developed the technology behind Cognito Therapeutics.Li-Huei Tsai: A neuroscientist at MIT who co-developed the technology behind Cognito Therapeutics.Dongfeng Chen: A professor at Harvard whose research linked the immune system and gut bacteria to glaucoma in mice.Gul Dolen: A researcher, formerly at Johns Hopkins and now at UC Berkeley, known for work on reopening critical periods of brain plasticity with psychedelics.Andreas Tolias: A researcher mentioned for creating a “digital twin” of the brain.Matthew McConaughey: American actor, author, and producer.SHOW NOTES[00:00:00] Start.[00:05:30] How do you solve a problem like presbyopia?[00:08:34] The athletic benefits of training supranormal (better than 20/20) vision.[00:11:49] Indigenous eye drops and FDA-approved pilocarpine for presbyopia.[00:14:05] Understanding basic eye anatomy.[00:17:27] Exploring AREDS 2, CoQ10, ginkgo, vitamin B3, and other supplements for vision.[00:23:00] Visual training devices and psychedelic-prompted brain plasticity.[00:25:12] Thoughts on visual training effectiveness and motor action requirements.[00:28:29] Concussion rehabilitation and visual perception exercises.[00:32:36] Red light and violet light therapy for myopia and mitochondrial health.[00:36:07] Vision loss correlation with cognitive decline and depression.[00:39:36] Presbyopia progression and psychological dependence on readers.[00:41:15] Cognito Therapeutics headset for Alzheimer’s treatment.[00:46:46] Glaucoma basics: neurodegenerative disease and risk factors.[00:48:53] Eye pressure variability and diurnal cycles.[00:50:02] Cannabis effects on eye pressure and compound isolation.[00:51:47] Stem cell research for vision restoration.[00:53:09] Anti-inflammatory effects and immune system role in eye diseases.[00:55:15] Gut microbiome connection to glaucoma in animal models.[00:58:43] Metabolic syndrome and GLP-1 receptor agonists.[01:00:50] Microbiome sharing and future therapeutic possibilities.[01:03:31] Dry eye treatment: preservative-free tears and serum drops.[01:08:43] Vision screening recommendations and UV protection.[01:11:22] Full-spectrum light benefits vs. UV exposure.[01:13:27] Paradigm shifts: irreversible vision loss becoming reversible.[01:17:18] Convergence of neuroscience advances and biotech investment.[01:21:58] Miraculous mitochondria: health, transplants, and three-parent babies.[01:26:24] My family history concerns and metabolic health screening.[01:29:26] Exercise’s biggest gain: going from none to some.[01:33:03] Clinical trial participation resources and parting thoughts.DR. JEFFREY GOLDBERG QUOTES FROM THE INTERVIEW

“I have gone my whole life without needing glasses until I hit around age 40. And when everyone hits around age 40, our lens inside the eye won’t compress and reshape to focus up close.”

— Dr. Jeffrey Goldberg

“Professional athletes get studied, they have better vision. They have better reflex time, they have sharper vision. We talk about 20/20 vision. That means I can see at 20 feet what a ‘normal’ person can see at 20 feet, so I have normal vision. But you can have 20/12 vision, which means you can see at 20 feet what normal people can see at 12 feet.”

— Dr. Jeffrey Goldberg

“Glaucoma is the number one cause of irreversible blindness in the world. That I think is going to be the piece that we overturn. We have always said, ‘Hey, we’ve got to prevent you from losing vision. We’ve got to slow down the disease because once you’ve lost whatever vision you’ve lost, I can’t get that back for you.’ And I think that is about to topple. We are about to get into vision restoration at a level that has been totally unexpected and totally unprecedented, and the science supporting these directions in these diseases is getting really, really juicy.”

— Dr. Jeffrey Goldberg

“Cannabis, whether you smoke it, or eat it in the brownie, or take the chewy, it lowers your eye pressure if you’re using the version … where you feel a little high from it, you get that good feeling. The problem is that it only really lowers the eye pressure during that time that you’re getting high. So I tell patients, ‘It works, but you’d have to be high 24/7, so maybe you should just use this eye drop instead.”

— Dr. Jeffrey Goldberg

“A small dose of daily red light can slow down progression of myopia in young people. We’re talking about teens and younger, even. So what’s even more shocking to me is that it also works with violet light. So how’s it work with light at the two ends of the visible spectrum? And definitely mitochondria are implicated.”

— Dr. Jeffrey Goldberg

“There’s an important myth to dispel, especially when it comes to presbyopia and wearing reading glasses. Between age 40 and around 60 or so, that lens stiffens, and stiffens, and stiffens… That’s the refractive, the glasses difference between viewing something at infinity, which from an optics perspective is actually just three feet away or further, and viewing something at 14 inches, comfortable reading distance, right in front of us.”

— Dr. Jeffrey Goldberg

“If we all live to a hundred, we’re all going to need cataract surgery, some people younger, some people older. But if you do cataract surgery and restore vision in an older person who … is suffering with cognitive decline and/or depression, you can reverse a significant amount of that decline in either of those domains. It speaks to the interplay of vision with our mental health, our cognitive health, and this is long-term, important stuff.”

— Dr. Jeffrey Goldberg

“The important thing to remember [about exercise] is that the biggest gain comes from going from none to some.”

— Dr. Jeffrey Goldberg

The post Dr. Jeffrey Goldberg — Creating Supranormal Vision, Cutting-Edge Science for Eye Health, Supplements, Red Light Therapy, and The Future of Eyesight Restoration (#823) appeared first on The Blog of Author Tim Ferriss.

Welcome to another wide-ranging “Random Show” episode I recorded with my close friend Kevin Rose (digg.com)!

We cover Kevin’s sobriety journey and marking 100 days without alcohol, my results with the ketogenic diet and intermittent fasting, GLP-1 agonists, home defense and security, the future of Venture Capital, authenticating yourself online, AI, the cultural shift toward human-to-human connection, Roblox, and more. Enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube.

This episode is brought to you by Momentous high-quality creatine to sharpen the mind; David Protein Bars with 28g of protein, 150 calories, and 0g of sugar; and AG1 all-in-one nutritional supplement.

Listen onApple Podcasts[image error]Listen onSpotify[image error]Listen onOvercastThe Random Show — Ketones for Cognition, Tim’s Best Lab Results in 10+ Years, How Kevin Hit 100 Days Sober, Home Defense, Vibe Coding Unleashed, and More

This episode is brought to you by AG1! I get asked all the time, “If you could use only one supplement, what would it be?” My answer is usually AG1, my all-in-one nutritional insurance. I recommended it in The 4-Hour Body in 2010 and did not get paid to do so. I do my best with nutrient-dense meals, of course, but AG1 further covers my bases with vitamins, minerals, and whole-food-sourced micronutrients that support gut health and the immune system. 

I have always admired AG1’s commitment to improving one product over many years, which is why I am excited about their latest upgrade: AG1 Next Gen. It’s the same—but improved—single-scoop, once-a-day product to support your mental clarity, immune health, and energy. Right now, you’ll get a 1-year supply of Vitamin D free with your first subscription purchase—a vital nutrient for a strong immune system and strong bones. Visit DrinkAG1.com/Tim to claim this special offer today and receive your 1-year supply of Vitamin D (and 5 free AG1 travel packs) with your first subscription purchase! That’s up to a one-year supply of Vitamin D as added value when you try their delicious and comprehensive daily, foundational nutrition supplement that supports whole-body health.

This episode is brought to you by David Protein Bars! I’m always on the hunt for protein sources that don’t require sacrifices in taste or nutrition. That’s why I love the protein bars from David. With David protein bars, you get the fewest calories for the most protein, ever. David has 28g of protein, 150 calories, and 0g of sugar. I was first introduced to David by my friend Peter Attia, MD, who is their Chief Science Officer. Many of you know of Peter, and he does his due diligence. And David tastes great. Their bars come in six delicious flavors, all worth trying, and I’ll often throw them in my bag for protein on the go. And now, listeners of The Tim Ferriss Show who buy four boxes get a fifth box for free. Try them for yourself at DavidProtein.com/Tim.

This episode is brought to you by Momentous high-quality creatine and more! Momentous offers high-quality supplements and products across a broad spectrum of categories, and I’ve been testing their products for months now. I’ve been using their magnesium threonate, apigenin, and L-theanine daily, all of which have helped me improve the onset, quality, and duration of my sleep. I’ve also been using Momentous creatine, and while it certainly helps physical performance, including poundage or wattage in sports, I use it primarily for mental performance (short-term memory, etc.). In fact, a new pilot study in Alzheimer’s patients, found that supplementing can increase brain creatine levels by 11% in just 8 weeks and improve measures of memory, reasoning, and attention—domains that typically decline over time.

Momentous’s products are third-party tested (Informed-Sport and/or NSF certified), so you can trust that what is on the label is in the bottle and nothing else. Use code TIM at checkout and enjoy 35% off your first subscription order or 14% off your first one-time purchase! And not to worry, my non-US friends, Momentous ships internationally and has you covered. 

Want to hear the last time KevKev and I did one of these Random Shows? Listen to our conversation here in which we discussed maintaining sobriety with a partner who still drinks, Taiwanese tea, finding magic in the ordinary, the ups and downs of accelerated TMS, the intersection of AI and life sciences, deepfaked side hustlers, when meditation retreats go right (and wrong), and much more.

SELECTED LINKS FROM THE EPISODEConnect with Kevin Rose:

Website | Instagram | Twitter | Threads | Bluesky | Digg.com

PeopleSigmund Freud: Austrian neurologist and founder of psychoanalysis who revolutionized our understanding of the human psyche.Hokusai: Japanese ukiyo-e artist of the Edo period, famous for “The Great Wave off Kanagawa” and influential woodblock prints.Craig Mod: Writer, photographer, and publisher known for his thoughtful explorations of Japan, walking, and digital publishing.: Irish actor known for dramatic roles in films like Schindler’s List and action films like the Taken series.: American actor known for eccentric characters including Captain Jack Sparrow and Willy Wonka in Tim Burton’s adaptation.Gene Wilder: American actor and comedian famous for his iconic portrayal of Willy Wonka in the 1971 classic film.Dr. Rhonda Patrick: PhD scientist and host of the FoundMyFitness podcast, specializing in nutrition, aging, and health optimization.Martin Berkhan: Fitness expert and founder of the Leangains intermittent fasting protocol that revolutionized flexible dieting.Dr. Peter Attia: Physician and longevity expert focusing on the science of healthspan and lifespan optimization.Desmond Tutu: South African Anglican archbishop and Nobel Peace Prize winner renowned for his anti-apartheid activism.Taran Butler: Competitive shooter and founder of Taran Tactical Innovations, known for custom firearm modifications.: Canadian actor beloved for roles in The Matrix trilogy and the John Wick action franchise.Jim Jefferies: Australian stand-up comedian and actor known for his provocative and observational comedy style.: American actor, screenwriter, and martial artist known for action films in the 1980s and 1990s.Marc Andreessen: Co-founder of Andreessen Horowitz venture capital firm and co-creator of the Mosaic web browser.Josh Cook: Digital strategist and entrepreneur known for his work in technology and social media engagement.Sam Altman: CEO of OpenAI and prominent figure in artificial intelligence development and governance.Alexis Ohanian: Co-founder of Reddit and venture capitalist focused on early-stage technology investments.Justin Mezzell: Digg CEO, designer, and creative director known for his distinctive illustration style and branding work.Movies, TV, and MediaShaun of the Dead: A 2004 British horror-comedy film that brilliantly parodies zombie movies while delivering genuine scares and laughs.Jason Bourne: An action-thriller film series following the amnesiac super-spy created by Robert Ludlum, starring Matt Damon.Snatch: A 2000 British crime-comedy film by Guy Ritchie featuring interconnected criminal plots and memorable characters.Babe: A 1995 family comedy-drama about a pig who learns to herd sheep, combining live-action with groundbreaking animatronics.The Naked Gun: A comedy film series starring Leslie Nielsen as the bumbling Detective Frank Drebin, known for its slapstick humor.Taken: An action-thriller film series starring Liam Neeson as a former CIA operative with “a very particular set of skills.”Willy Wonka & The Chocolate Factory: A 1971 musical fantasy film starring Gene Wilder as the eccentric chocolatier in Roald Dahl’s beloved story.John Wick: An action film series starring Keanu Reeves as a legendary assassin seeking vengeance, known for stylized fight choreography.Slow TV: A television genre featuring real-time, unedited coverage of lengthy events like train journeys or knitting marathons.Playboy: An American men’s lifestyle and entertainment magazine founded by Hugh Hefner in 1953.Wired: A monthly magazine covering how emerging technologies impact culture, the economy, and politics.BooksThe 4-Hour Workweek by Timothy Ferriss: A step-by-step guide to escaping the 9-5 grind through lifestyle design, automation, and the principles of working smarter rather than harder.The 4-Hour Body by Timothy Ferriss: An uncommon guide to rapid fat-loss, incredible sex, and becoming superhuman through data-driven body hacking and minimally effective dose principles.The 4-Hour Chef by Timothy Ferriss: A meta-learning manual disguised as a cookbook that teaches how to master any skill quickly using cooking as the vehicle for accelerated learning principles.Brands, Companies, and ProductsNanoblocks: A micro-sized building block system from Japan that makes LEGO look like giant boulders.LEGO: A line of plastic construction toys that bare feet have been stepping on since 1958.Coyote: A card game I made for strategic thinking and decision-making.Qitone: A brand of ketone supplement powder for metabolic optimization.N.O.-Xplode: A pre-workout supplement that promises to turn your gym session into a controlled explosion.Bronkaid / Primatene Mist: Over-the-counter medications containing ephedrine for respiratory relief.Belsomra: A prescription sleep medication (a DORA) that helps quiet the brain’s wake signal.Mounjaro / Zepbound: Brand names for Tirzepatide, a GLP-1 agonist medication for diabetes and weight management.Thorne: A health and technology company that sells research-backed supplements.Taser: A brand of conducted energy weapon manufactured by Axon Enterprise.Ring: A home security and smart home company owned by Amazon.Taran Tactical: A firearms training company specializing in competitive shooting techniques.Anduril: A defense technology company building autonomous systems for military applications.Cloudflare: A web infrastructure and website security company that keeps the internet running smoothly.Tools for Humanity: The company behind Worldcoin and the retina-scanning Orb for global identity verification.Oura Ring: A smart ring that tracks sleep and physical activity with impressive accuracy.Peloton: An exercise equipment and media company that brought the boutique fitness experience home.Fitbit: A company producing activity trackers and smartwatches, now owned by Google.Domino’s Pizza: An American multinational pizza restaurant chain known for delivery innovation.Coca-Cola: A multinational beverage corporation that has been refreshing the world since 1886.Andreessen Horowitz (a16z): A venture capital firm that backs bold entrepreneurs building the future.True Ventures: A venture capital firm focused on early-stage technology companies.Roblox: An online game platform and game creation system where users build virtual worlds.Amazon / Amazon Prime / Amazon Pharmacy: E-commerce and technology company that started with books and now sells everything.Costco: A multinational corporation that operates a chain of membership-only big-box retail stores.Walmart / Target: Multinational retail corporations competing for America’s shopping dollars.UPS: A multinational shipping and receiving and supply chain management company in distinctive brown trucks.1-800-FLOWERS: A floral and gourmet foods gift retailer that pioneered phone-based ordering.Etsy: An e-commerce website focused on handmade or vintage items and craft supplies.Bugatti: A luxury sports car manufacturer that creates automotive art for the ultra-wealthy.Institutions and OrganizationsAlcoholics Anonymous (AA): An international fellowship of people who share their experience, strength and hope with each other that they may solve their common problem and help others to recover from alcoholism.Stanford University: A private research university in Stanford, California, founded in 1885 and consistently ranked among the world’s top academic institutions.Johns Hopkins University: A private research university in Baltimore, Maryland, founded in 1876 and widely considered America’s first research university.TSA (Transportation Security Administration): A federal agency within the US Department of Homeland Security responsible for protecting the nation’s transportation systems and ensuring freedom of movement for people and commerce.Websites, Platforms, and AppsLeangains: Martin Berkhan’s website on intermittent fasting.YouTube: An online video sharing and social media platform.TikTok: A short-form video hosting service.Instagram: A photo and video sharing social networking service.Facebook: An online social media and social networking service.Reddit: A social news aggregation, content rating, and discussion website.Wikipedia: A free, multilingual online encyclopedia.Digg: A news aggregator with a curated front page.Coyote: The official website for the card game Coyote.River: An in-person event and social platform for communities.Cursor / Claude Code: AI-powered coding tools.Lovable (formerly Base44): “Vibe coding” platforms for building apps.Vercel: A cloud platform for frontend frameworks and static sites.Concepts and Terms12-Step Programs: A set of guiding principles for recovery from addiction, most famously used by Alcoholics Anonymous and other recovery organizations worldwide.Ketogenic Diet (Keto): A high-fat, low-carbohydrate diet that forces the body to burn fat for fuel instead of glucose, originally developed to treat epilepsy.Intermittent Fasting (16/8): An eating pattern that cycles between periods of eating and fasting, with the 16/8 method involving 16 hours of fasting and an 8-hour eating window.Zone 2 Training: Low-intensity aerobic exercise performed at a specific heart rate zone that maximizes fat burning and mitochondrial efficiency.APoE (Apolipoprotein E) Gene: A gene associated with the risk of developing Alzheimer’s disease, with the APOE4 variant significantly increasing susceptibility to cognitive decline.Oral Glucose Tolerance Test (OGTT): A medical test to assess how the body processes glucose over time, commonly used to diagnose diabetes and prediabetes.ApoB (Apolipoprotein B): A primary protein component of LDL (“bad”) cholesterol particles, considered a more accurate marker for cardiovascular disease risk than traditional cholesterol tests.Autophagy: The body’s cellular “housekeeping” process of breaking down and recycling damaged proteins and organelles to maintain cellular health and longevity.Exogenous Ketones: Ketone supplements taken orally to rapidly induce ketosis without following a strict ketogenic diet, though their effectiveness remains debated.GLP-1 Agonists: A class of medications that mimic the hormone GLP-1, used for treating type 2 diabetes and obesity by regulating blood sugar and appetite.DORA (Dual Orexin Receptor Antagonist): A newer class of sleep medications that work by blocking orexin receptors in the brain to promote natural sleep patterns with fewer side effects than traditional sleep aids.ECA Stack: A controversial and now largely banned supplement combination of ephedrine, caffeine, and aspirin once popular among bodybuilders for fat loss but associated with serious health risks.Vibe Coding: A modern approach to programming that relies heavily on AI tools and intuitive problem-solving rather than traditional computer science fundamentals, enabled by advanced code generation AI.Dead Internet Theory: A conspiracy theory suggesting that the internet is now predominantly populated by bots and AI-generated content rather than authentic human interaction.ZK Proofs (Zero-Knowledge Proofs): A cryptographic method that allows one party to prove they know specific information without revealing the information itself, crucial for privacy-preserving blockchain applications.DEXA Scan: A low-radiation X-ray scan that precisely measures bone density, body fat percentage, and lean muscle mass, considered the gold standard for body composition analysis.Venture Capital: A form of private equity financing where investors provide capital to startups and early-stage companies with high growth potential in exchange for equity ownership.SHOW NOTES[00:00:00] Start.[00:06:54] Kevin celebrates 100 days sober! Why and how?[00:15:16] Nanoblocks: Kevin’s new Japanese micro-building hobby.[00:18:16] The Slow TV movement and Craig Mod’s ambient recordings.[00:20:58] Craving analog experiences and wilderness trekking.[00:22:24] Writing with background movies.[00:23:42] High hopes for The Naked Gun reboot.[00:24:35] Kevin’s improved communication since quitting alcohol.[00:26:28] My health interventions for cognitive protection.[00:29:00] How ketogenic diet and 16/8 intermittent fasting led to my best lab results in 10+ years.[00:33:35] Weight control regimens we don’t recommend.[00:39:51] Exogenous ketones: Qitone vs. premium options.[00:50:32] How glucose tolerance tests work.[00:51:58] Microdosing GLP-1 (tirzepatide) for glucose control.[00:54:12] DORA sleep medications and neuroprotective effects.[00:56:55] Belsomra trial and cost considerations.[00:57:52] Sauna temperature optimization based on Rhonda Patrick’s research.[01:00:28] There are no biological free lunches.[01:03:27] The time Kevin found a homeless person in his closet.[01:06:11] Modern home security and privacy measures.[01:19:42] Pondering how we survived childhood.[01:24:23] AI-driven venture capital landscape changes.[01:28:59] Vibe coding revolution: $250k projects now cost $50.[01:34:28] Education advice for kids in the AI age.[01:36:27] Empowering creative minds vs. traditional technical roles.[01:38:29] What Kevin’s crystal balls say about Cloudflare’s data marketplace for content creators.[01:42:02] The Digg reboot with Alexis Ohanian: a focus on in-person connections.[01:42:59] Dead internet theory and bot content proliferation.[01:43:25] Verifying humanity: the trust gradient.[01:54:28] My relief at the successful launch of Coyote.[01:58:03] Kevin’s Roblox addiction and Grow a Garden expenses.[01:59:56] Future meetup plans and parting thoughts.

The post The Random Show — Ketones for Cognition, Tim’s Best Lab Results in 10+ Years, How Kevin Hit 100 Days Sober, Home Defense, Vibe Coding Unleashed, and More (#822) appeared first on The Blog of Author Tim Ferriss.

This is a very special episode for me, one I’ve been looking forward to publishing for months.

COYOTE is a fast, casual card game I created with the amazing Elan Lee and Exploding Kittens team. It has been my obsession for two years.

Here is a demo:

I worked really hard on every aspect of this one (concept, mechanics, art, you name it)!

You can finally buy it everywhere, including Amazon, Target, Walmart, and 8,000+ retail locations worldwide. It’s been a hit with 100+ test families, my friends, and at conferences around the world. It now produces guaranteed laughs with kids, adults, tipsy people, serious people… who all enjoy unleashing their inner trickster.

If you’ve benefited from my podcast, newsletter, books, or anything at all, please grab a copy or two! It only costs $10-12 and can provide hours upon hours of fun. It takes minutes to learn and 10 minutes to play. Under the hood, it’s also designed to be a good workout for your brain.

I hope you enjoy this conversation with Elan Lee, the co-creator and chief executive officer of Exploding Kittens.

We discuss the behind-the-scenes story of making COYOTE, including early misses, finding the right idea, developing it, navigating mass retail, and much, much more.

If you’ve ever wanted to learn how to get a product on the shelves of something like Walmart and Target, or simply create a game, this podcast covers it all.

P.S. One last thing: stick around to the end for a very fun surprise that involves a mystery Hollywood party.

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform.

This episode is brought to you by:

Gamma  AI design partner for effortless presentations, websites, social media posts, and more
Shopify  global commerce platform, providing tools to start, grow, market, and manage a retail business
Wealthfront  high-yield cash accountListen onApple Podcasts[image error]Listen onSpotify[image error]Listen onOvercastMy Two-Year Secret Project, COYOTE — The Strategies and Tactics for Building a Bestseller from Nothing with Elan Lee of Exploding Kittens

Want to hear the last time Elan Lee was on this show? Listen to our conversation here, in which we discussed the secrets behind Exploding Kittens’ record-breaking Kickstarter success, core gameplay loops, the power of positive constraints, craftsmanship in game design, building superfan communities, and much more.

This episode is brought to you by Gamma! Readers of The 4-Hour Workweek know I recommend delegating and automating tasks that can be done better by someone or something else. It’s why I recommend this episode’s sponsor, Gamma, for creating incredible, professional slide decks better, cheaper, and faster than you ever thought possible. I polled many of you about Gamma on social media, and some of you called it “a game changer,” “mind-blowing,” and “far and away the best product in the category.”

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With more than 50 million users, it’s already the most popular AI presentation platform in the world. Explore Gamma today at gamma.app. Listeners get one month free of Gamma Pro’s annual plan by using promo code TIM at checkout.

This episode is brought to you by Wealthfront! Wealthfront is a financial services platform that offers services to help you save and invest your money. Right now, you can earn 4.00% APY—that’s the Annual Percentage Yield—with the Wealthfront Brokerage Cash Account. That’s nearly 10x more interest than if you left your money in a savings account at the average bank, with savings rates at 0.42%, according to FDIC.gov, as of 05/19/2025. It takes just a few minutes to sign up, and then you’ll immediately start earning 4.00% APY from program  banks on your uninvested cash. And when new clients open an account today, they’ll get an extra $50 bonus with a deposit of $500 or more. Terms and Conditions apply.  Visit Wealthfront.com/Tim to get started.

Cash Account offered by Wealthfront Brokerage LLC, member FINRA/SIPC. Wealthfront is not a bank. The APY on cash deposits, as of 04/30/2025, is representative, subject to change, and requires no minimum. Funds in the Cash Account are swept to program banks, where they earn a variable APY. Tim receives cash compensation from Wealthfront Brokerage for advertising and holds a non-controlling equity interest in the corporate parent of Wealthfront Brokerage. Tim and Wealthfront Brokerage have no other affiliation. Tim reflects his own opinions and Wealthfront does not endorse, sponsor, or promote them. See full disclosures here.

This episode is brought to you by Shopify! Shopify is one of my favorite platforms and one of my favorite companies. Shopify is designed for anyone to sell anywhere, giving entrepreneurs the resources once reserved for big business. In no time flat, you can have a great-looking online store that brings your ideas to life, and you can have the tools to manage your day-to-day and drive sales. No coding or design experience required.

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What was your favorite quote or lesson from this episode? Please let me know in the comments.

SELECTED LINKS FROM THE EPISODEConnect with Elan Lee:

Twitter | LinkedIn

Connect with Exploding Kittens:

Website | Twitter | Instagram | TikTok | YouTube

Elan Lee’s Past AppearanceElan Lee, Co-Creator of Exploding Kittens — How to Raise Millions on Kickstarter, Deconstructing Mega-Successes, Secrets of Game Design, The Power of Positive Constraints, The Delights of Craftsmanship, and The Art of Turning Fans into Superfans | The Tim Ferriss Show #653GamesCoyote: The card game created by Elan and me!Dungeons & Dragons: The pioneering tabletop role-playing game that launched the entire RPG genre, featuring collaborative storytelling, character development, and dice-based mechanics that have influenced countless games since 1974.Rock Paper Scissors (RPS) / Rochambeau: The classic hand game involving simultaneous choices and circular dominance (rock beats scissors, scissors beats paper, paper beats rock), serving as core mechanical inspiration for Coyote’s strategic decision-making framework.Sorry!: Classic family board game where players race their pawns around the board while drawing cards that can either help them advance or force opponents backward, teaching lessons about both strategy and accepting setbacks gracefully.Monopoly: The iconic property-trading board game that has dominated family game nights since 1935, teaching economic principles through real estate acquisition, rent collection, and strategic resource management, while often ending in dramatic family arguments.Poetry for Neanderthals: A hilarious Exploding Kittens party game where players must describe complex concepts using only single-syllable words or get “bonked” with an inflatable club, demonstrating how simple mechanics can create engaging casual gameplay that inspired the author’s approach to accessible game design.Magic: The Gathering: The groundbreaking collectible card game that created the entire TCG industry, featuring deep strategic gameplay, customizable decks, and a complex economy that has sustained competitive play and collecting for over 30 years.Hanabi: An innovative cooperative card game (Japanese for “fireworks”) where players work together to create perfect firework displays while being unable to see their own cards, requiring communication, memory, and trust to succeed as a team.UNO: The beloved family card game where players race to empty their hands by matching colors or numbers, featuring special action cards that can reverse play direction, skip opponents, or force card draws, making it accessible yet surprisingly strategic.Mario Kart: Nintendo’s iconic racing video game series specifically cited for its brilliant catch-up mechanics (like blue shells targeting the leader) that keep all players competitive throughout the race, serving as an example of how “attack cards” can balance gameplay.Exploding Kittens Original Edition: The flagship game of Elan’s company that became the most-backed Kickstarter project in history, featuring simple yet hilarious gameplay where players draw cards until someone draws an exploding kitten and loses, unless they have a defuse card.Hurry Up Chicken Butt: The best-selling Exploding Kittens game designed collaboratively with Elan’s daughter, featuring fast-paced card-slapping action where players race to match cards while dealing with silly interruptions and challenges.Throw Throw Burrito: A revolutionary Exploding Kittens game that combines card gameplay with physical dodgeball elements, where players collect matching sets while literally throwing soft foam burritos at each other, creating a unique hybrid of tabletop and active play.CATAN Board Game: The award-winning strategy game that popularized modern European-style board gaming, featuring resource management, trading, and modular board setup that creates different experiences each game, specifically cited as an example of successful iterative design and development.Warhammer: The complex tabletop miniature wargame system requiring detailed painted armies, intricate rules, and substantial time investment, mentioned as an example of a fundamentally different game type from casual, accessible party games.Game Types Mentioned: Card Games, Role-Playing Games (RPGs), Casual Games, Party Games, Trading Card Games (TCGs), Collectible Card Games (CCGs), Tabletop Games, Board Games, Cooperative Games.Crowdfunding OptionsKickstarter: An American public benefit corporation that maintains a global crowdfunding platform for creative projects.Craigstarter: Open-source crowdfunding tool and methodology by Craig Mod for transparent project funding.KickstarTrends: Receive exclusive discounts on the latest projects before anyone else.Backerlead: Stay ahead of the curve in technology and design.Kickstargo: Showcasing the best crowdfunding products.Companies, Brands, and OrganizationsExploding Kittens: A game company founded by Elan Lee that creates card games and mobile apps.The Legend of CØCKPUNCH: My early NFT project.Walmart: An American multinational retail corporation that operates a chain of hypermarkets, discount department stores, and grocery stores.Sam’s Club: A membership-only warehouse club owned by Walmart that offers bulk merchandise at discounted prices.Barnes & Noble: An American bookseller with the largest number of retail outlets in the United States.Target: An American big box department store chain headquartered in Minneapolis, Minnesota.Amazon: An American multinational technology company focusing on e-commerce, cloud computing, and digital streaming.Xbox: A video gaming brand created and owned by Microsoft that consists of gaming consoles and services.TSR: A defunct American game publishing company that was the original publisher of Dungeons & Dragons.Wizards of the Coast: An American publisher of games, primarily role-playing games and trading card games including Magic: The Gathering and Dungeons & Dragons.Hasbro: An American multinational toy, board game, and media company known for brands like Monopoly and Transformers.Mattel: An American multinational toy manufacturing and entertainment company known for brands like Barbie and Hot Wheels.PickFu: A market research platform that provides instant consumer feedback through polls and surveys.Intellivy: A market research and consumer insights platform for product testing and validation.Stickybeak: A market research platform that provides consumer insights and product testing services.Vimeo: An American video hosting, sharing, and services platform used for high-quality video content.Google: An American multinational technology company specializing in internet-related services and products including search and advertising.LinkedIn: A business and employment-focused social networking platform owned by Microsoft.Shopify: A Canadian multinational e-commerce company that provides a platform for online stores and retail point-of-sale systems.Atari: An American video game developer and home computer company that was a pioneer in the arcade and video console industries.PeopleGary Gygax: Co-creator of Dungeons & Dragons and pioneer of tabletop role-playing games.Jean-Claude Van Damme: Belgian martial artist and actor known for his action films and exceptional flexibility.Justin Gary: Author of Think Like a Game Designer: The Step-By-Step Guide to Unlocking Your Creative Potential  and host of the Think Like A Game Designer podcast.Reid Hoffman: Co-founder of LinkedIn and venture capitalist, mentioned regarding delegation and his “10% footfall rate” philosophy.Seth Godin: Bestselling author, entrepreneur, and marketing expert who reframed questions about failure and innovation.Ken Gruhl: Expert game designer and mechanic specialist involved in Coyote’s development in Toronto.Raph Koster: Game designer and author of A Theory of Fun for Game Design , expert on game mechanics and virtual worlds.Karen Pryor: Author of Don’t Shoot the Dog! and pioneer of clicker training and positive reinforcement methods.Stephen Key: Inventor, author of One Simple Idea , and expert in product licensing with over 20 patents to his name.Nolan Bushnell: Founder of Atari and Chuck E. Cheese, creator of Bushnell’s Law: “Easy to learn, difficult to master.”Klaus Teuber: German board game designer best known for creating Settlers of Catan.Penn Jillette: Magician from Penn & Teller duo who partnered with Exploding Kittens on a game.Jeff Probst: Emmy-winning host of Survivor who partnered with Exploding Kittens on a game.Carly McGinnis: President of Exploding Kittens.Matthew Inman: Cartoonist and creator of The Oatmeal webcomic, artist for Exploding Kittens who helped launch the game through his massive online audience.Doug McMillon: President and CEO of Walmart, leading the world’s largest retailer.Sam Walton: Founder of Walmart and Sam’s Club, revolutionary retail entrepreneur.Alex Cutler and AJ Brandon: Hosts of the Fun Problems game design podcast, experts in tabletop game mechanics.Craig Mod: Writer, photographer, and creator of Craigstarter, known for his walks across Japan and innovative book publishing approaches.Brandon Sanderson: Fantasy author known for his record-breaking $41+ million Kickstarter campaign and prolific writing in the Cosmere universe.Gary Keller: Real estate mogul and co-founder of Keller Williams, known for the principle “Agreements are Disagreements.”BooksPlayers Handbook (Advanced Dungeons & Dragons, 1st Edition) by Gary GygaxDungeon Masters Guide (Advanced Dungeons & Dragons, 1st Edition) by Gary Gygax One Simple Idea: Turn Your Dreams into a Licensing Goldmine While Letting Others Do the Work by Stephen Key A Theory of Fun for Game Design by Raph Koster Don’t Shoot the Dog!: The New Art of Teaching and Training by Karen Pryor The 4-Hour Chef: The Simple Path to Cooking Like a Pro, Learning Anything, and Living the Good Life by Timothy FerrissConcepts and IdeasProduct Line Review: A retail buying meeting process where manufacturers present to retailers to validate merchandising plans, educate on market opportunities, and secure shelf space for their products.Bushnell’s Law: A video game design principle attributed to Atari founder Nolan Bushnell stating that “all the best games are easy to learn and difficult to master” and should reward both first-time and experienced players.Prisoner’s Dilemma: A game theory thought experiment involving two rational agents who can either cooperate for mutual benefit or betray their partner for individual gain, illustrating the tension between self-interest and collective benefit.Zero Sum Game: A situation in game theory and economics where one participant’s gain or loss is exactly balanced by the losses or gains of other participants, with the total value remaining constant.Past Year Review: A personal reflection process that involves systematically evaluating the previous year’s experiences, accomplishments, and lessons learned to gain insights for future goal-setting and personal development.Non-Fungible Token (NFT): Blockchain-tied assets behind The Legend of CØCKPUNCH.Wisconsin Card Sorting Test (WCST): Neuropsychological test compared to Coyote‘s potential cognitive effects.PlacesLake Geneva, Wisconsin: A picturesque lakeside city in southeastern Wisconsin that served as the original location of Gen Con gaming convention.Indianapolis, Indiana: The capital and most populous city of Indiana, currently hosting the annual Gen Con gaming convention since 2003.Austin, Texas: The capital city of Texas known for its vibrant gaming scene and as a location for podcast recordings in the gaming industry.Bentonville, Arkansas: A city in northwest Arkansas that serves as the global headquarters of Walmart Inc.Toronto, Canada: Canada’s largest city and provincial capital of Ontario, notable as a location for key development sprints for the Coyote game project.Germany: A European country known for its strong board gaming culture and conventions where games like Coyote have been well-received.Movies, Podcasts, and MediaHow to Play Coyote: Coyote how-to-play video.Think Like A Game Designer: Podcast by Justin Gary focused on game design principles and business.Fun Problems: Game design podcast covering industry insights.Elan Lee’s YouTube Channel: Resource for game design instruction and industry insights from the Exploding Kittens co-creator.Kickstarter: Crowdfunding platform for creative projects including board games and product launches.PickFu: Market testing and consumer polling platform for product validation and feedback.Google Ads: Online advertising platform used for testing book titles and market validation.Vimeo: Video hosting platform used for playtest video review and content sharing.D&D Beyond: Digital platform for Dungeons & Dragons modules, Player’s Handbook, and DM Guide resources.Prototyping Supplies: Blank cards, Sharpies, and game creation kits for rapid game prototyping and testing.QR Code Generator: Technology used on game packaging for linking to video pitches and digital instructions.Zero Effect: A 1998 mystery-comedy film starring Bill Pullman as eccentric private detective Daryl Zero, whose investigative methodology emphasizes pure observation and objectivity to uncover unexpected connections and solutions.“We Will Rock You” by Queen: Brian May’s anthemic contribution to arena-based sporting events the world over.Downton Abbey: A British historical drama television series that follows the lives of the Crawley family and their servants in an Edwardian country house in the early 20th century.Poetry for Neanderthals player tries to convey “garage”: Popular video showing the game in action.EventsGen Con: The largest tabletop game convention in North America featuring role-playing games, board games, card games, and miniatures with nearly 70,000 attendees annually in Indianapolis.South by Southwest (SXSW): An annual conglomeration of interactive media, music, and film festivals and conferences held each March in Austin, Texas since 1987, celebrating the convergence of technology, film, and music industries.SHOW NOTES[00:00:00] Start.[00:05:21] Coyote: a game 47 years in the making.[00:08:41] Who is Elan Lee?[00:09:37] How our motivations behind game creation intersect.[00:12:41] The nutshell view of pitching a game to a retailer.[00:14:40] Salesmanship is a learnable skill, but Elan’s a natural.[00:15:53] Why I’ve always wanted to make my own game and how development began in earnest.[00:26:00] First contact with Elan and our fast-forged, fun-focused friendship.[00:32:28] The Hanabi and Rock, Paper, Scissors-inspired Toronto trip breakthrough.[00:39:40] Early prototyping and testing.[00:45:34] The Zero Effect.[00:47:37] Recommended game design rationales, resources, and reading.[00:53:00] The beginner’s mind approach to writing effective game instructions.[00:56:26] A simple fact: less complication = more fun.[00:57:49] Cooperative vs. competitive play.[00:58:24] Leveling the playing field with attack cards and sabotage mechanics.[01:01:34] Tricking people into cognitively bettering themselves by gaming.[01:08:04] Finding the sweet spot.[01:10:44] It takes a lot of work to make a game effortlessly fun.[01:13:40] How many games does Exploding Kittens publish per year?[01:14:36] Exploding Kittens’ number-one seller was designed by Elan’s four-year-old daughter.[01:18:30] Prototypes and pitching.[01:22:26] Improving on the industry’s fundamentally flawed testing procedure.[01:24:58] Analyzing passing/failure with play testers’ video and feedback.[01:28:41] Risks of internal testing.[01:31:47] Coyote’s first positive signs from the wild.[01:34:22] Online vs. physical store sales and tweaking variables to gauge market interest.[01:41:22] What a successful line review looks like.[01:43:51] Line review hoops through which lesser-proven companies have to hop.[01:48:04] Elan’s field-tested line review meeting strategies.[01:54:15] The importance of finding proper agent representation.[01:59:35] In modern marketing, social media (especially short-form video) is king.[02:04:48] The best and worst ways for an aspiring designer to sell a game.[02:13:05] Crowdfunding pros and cons, and Kickstarter alternatives.[02:19:57] Dealing with deal terms.[02:23:56] The Exploding Kittens attitude toward rare partnerships.[02:25:45] The types of games that capture Elan’s attention.[02:27:40] Common game design mistakes.[02:29:49] How we tried to avoid these mistakes when packaging Coyote.[02:33:55] Self-publishing vs. conventional publishing.[02:38:40] Business considerations and risks.[02:44:59] Parting thoughts and a tantalizing offer.ELAN LEE QUOTES FROM THE INTERVIEW

“We don’t make games that are entertaining. We make games that make the players entertaining.”

— Elan Lee

“Your reaction should not be, ‘I’m going to buy that game.’ That’s not our goal. Your reaction is, ‘I’m going to pick up this game, and I’m going to turn it over, and I’m going to read the back of the box.'”

— Elan Lee

“It’s like saying, ‘Is there still space in the book industry? In the movie industry?’ All a game is is an idea delivered in a new way. When are we going to run out of ideas? When are we going to run out of delivery mechanisms? The answer to both of those, individually, is never.”

— Elan Lee

“70 percent of our sales are in-person retail. Only 30 percent are online sales. Totally backwards than what you’d expect for almost any industry.”

— Elan Lee

“We probably work on a hundred games a year, and less than 20 make the cut.”

— Elan Lee

“The way that you build the most effective videos for [games] is you need to inspire, I think, two emotions. One, ‘I understand what those people are experiencing right now,’ And two, ‘I would like to experience that.’ And it took me forever to get to those two sentences. At first it was, ‘Let’s show gameplay, let’s show setup, let’s show a memorable moment. Let’s show people screaming and yelling because they’re having so much fun.’ None of that matters. None of that works. ‘That looks like fun. I could have that much fun.’ That’s it. That’s what you’re trying to show.”

— Elan Lee

The post My Two-Year Secret Project, COYOTE — The Strategies and Tactics for Building a Bestseller from Nothing with Elan Lee of Exploding Kittens (#821) appeared first on The Blog of Author Tim Ferriss.

Rhonda Patrick, Ph.D. (@foundmyfitness) is a biomedical scientist and the founder of FoundMyFitness, a platform dedicated to delivering rigorous, evidence-based insights on improving healthspan and mitigating age-related diseases. Through her podcast, website, and YouTube channel, reaching millions globally, she translates complex science into actionable strategies for metabolic health, brain aging, and overall improved healthspan.

Dr. Patrick’s research explores genetic determinants of nutritional response, metabolic health, micronutrient deficiencies, sleep biology, and hormetic stressors, such as exercise, heat, cold exposure, fasting, and phytochemicals. She is an associate scientist and board member at the Fatty Acid Research Institute, where her work focuses on the role of omega-3 fatty acids in metabolic health and brain aging. Her peer-reviewed publications have appeared in top-tier journals, including Nature Cell Biology, The FASEB Journal, and Experimental Gerontology.

By uniting scientific integrity with protocol-driven precision, Dr. Patrick equips individuals and organizations alike with practical, scientifically sound strategies for optimizing health and longevity.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform.

This episode is brought to you by:

Momentous  high-quality creatine David Protein Bars  28g of protein, 150 calories, and 0g of sugar Monarch Money  track, budget, plan, and do more with your money Helix Sleep  premium mattressesListen onApple Podcasts[image error]Listen onSpotify[image error]Listen onOvercastRhonda Patrick, Ph.D. — Protocols for Fasting, Lowering Dementia Risk, Reversing Heart Aging, Using Sauna for Longevity (Hotter is Not Better), and a Few Supplements That Might Actually Matter

Want to hear the last time Rhonda Patrick was on the podcast? Listen to our conversation here in which we discussed simple methods for extending a healthy lifespan, minimizing cancer risks, the dangers of some common supplements, dietary effects on genetics, and much more.

This episode is brought to you by Momentous high-quality supplements! Momentous offers high-quality supplements and products across a broad spectrum of categories, and I’ve been testing their products for months now. I’ve been using their magnesium threonate, apigenin, and L-theanine daily, all of which have helped me improve the onset, quality, and duration of my sleep. I’ve also been using Momentous creatine, and while it certainly helps physical performance, including poundage or wattage in sports, I use it primarily for mental performance (short-term memory, etc.).

Their products are third-party tested (Informed-Sport and/or NSF certified), so you can trust that what is on the label is in the bottle and nothing else. Use code TIM at checkout and enjoy 35% off your first subscription order or 14% off your first one-time purchase! And not to worry, my non-US friends, Momentous ships internationally and has you covered. 

This episode is brought to you by David Protein Bars! I’m always on the hunt for protein sources that don’t require sacrifices in taste or nutrition. That’s why I love the protein bars from this episode’s sponsor, David. With David protein bars, you get the fewest calories for the most protein, ever. David has 28g of protein, 150 calories, and 0g of sugar. I was first introduced to David by my friend Peter Attia, MD, who is their Chief Science Officer. Many of you know of Peter, and he does his due diligence. And David tastes great. Their bars come in six delicious flavors, all worth trying, and I’ll often throw them in my bag for protein on the go. And now, listeners of The Tim Ferriss Show who buy four boxes get a fifth box for free. Try them for yourself at DavidProtein.com/Tim.

This episode is brought to you by Helix Sleep! Helix was selected as the best overall mattress of 2024 by Forbes, Fortune, and Wired magazines and many others. With Helix, there’s a specific mattress to meet each and every body’s unique comfort needs. Just take their quiz—only two minutes to complete—that matches your body type and sleep preferences to the perfect mattress for you. They have a 10-year warranty, and you get to try it out for a hundred nights, risk-free. They’ll even pick it up from you if you don’t love it. And now, Helix is offering 20% off all mattress orders at HelixSleep.com/Tim.

This episode is brought to you by Monarch Money! Traditional budgeting apps can help, but they don’t compare to the complete financial command center you get with this episode’s sponsor, Monarch Money. Monarch is like your own personal CFO, giving you full visibility and control so you can stop merely earning and start growing.

Monarch was named The Wall Street Journal’s Best Budgeting App of 2025, and it’s the top-recommended personal finance app by users and experts, with more than 30,000 5-star reviews. Get control of your overall finances with Monarch Money. Use code TIM at monarchmoney.com/Tim for half off your first year.

What was your favorite quote or lesson from this episode? Please let me know in the comments.

SELECTED LINKS FROM THE EPISODEConnect with Dr. Rhonda Patrick:

Website | Podcast | Twitter | Instagram | Facebook

Health Protocols and Lifestyle InterventionsSauna Use: Linked to a 65-66% lower risk of dementia and Alzheimer’s disease when used four to seven times weekly. Optimal protocol: 174°F (79°C) for 20 minutes. Temperatures above 190°F (88°C) may be less beneficial.Hot Baths: Provide similar cardiovascular benefits to sauna use, with daily hot baths linked to 28% lower cardiovascular disease risk. Protocol: 104°F (40°C) water temperature for 20 minutes.Intermittent Fasting (IF) — Specifically 16:8: Time-restricted eating with a 16-hour fast and eight-hour eating window, shown to improve metabolic health, blood sugar control, and activate cellular autophagy.Extended Fasting: Water-only fasts lasting seven to 30 days that can trigger profound autophagy and provide anti-inflammatory benefits, though requiring medical supervision for safety.Fasting-Mimicking Diet (FMD): A low-calorie, low-protein, plant-based eating pattern for five consecutive days that aims to provide fasting benefits while allowing some food intake.Norwegian 4×4 Protocol: High-intensity interval training method involving four minutes at 85-95% maximum heart rate followed by three minutes active recovery, repeated four times to maximize VO2 max improvements.Zone 2 Training: Moderate-intensity aerobic exercise performed at conversational pace below the lactate threshold, optimizing fat oxidation, and building aerobic base for endurance and longevity.Tabata: A form of high-intensity interval training (HIIT) that involves short, intense bursts of exercise followed by brief rest periods.Seniors CrossFit: Adapted functional fitness program emphasizing scalable movements, strength training, and community engagement specifically designed for older adults to maintain independence and health.Key Health Concepts and TermsVO2 Max: The maximum rate of oxygen consumption during exercise, considered the gold standard measure of cardiorespiratory fitness and a key predictor of longevity.APOE4: A genetic allele that significantly increases the risk for Alzheimer’s disease, with those carrying two copies developing brain pathology predictably by age 55.Klotho: A longevity-related protein that acts as an anti-aging factor, boosted by exercise and vitamin D, and associated with improved cognitive function and extended lifespan.Heat Shock Proteins (HSPs): Protective proteins activated by heat stress such as sauna use that help repair misfolded proteins, prevent protein aggregation, and provide cellular protection against damage.Autophagy and Mitophagy: The body’s cellular cleanup processes that clear out damaged proteins, organelles, and mitochondria, activated by fasting and intense exercise to maintain cellular health.NRF2 Pathway: A genetic pathway that controls the cellular response to oxidative stress and inflammation, strongly activated by compounds like sulforaphane from cruciferous vegetables.Ketosis / Beta-Hydroxybutyrate (BHB): A metabolic state where the body uses fat and ketones for fuel, with BHB acting as a clean energy source and signaling molecule with anti-inflammatory effects.Glymphatic System: The brain’s waste clearance system that is most active during deep sleep, helping clear amyloid-beta plaques and other toxic proteins from brain tissue.Advanced Glycation End Products (AGEs): Harmful compounds formed when sugar binds to proteins, causing tissues such as blood vessels and organs to become stiff and contributing to aging and disease.Microplastics and Nanoplastics: Pervasive environmental contaminants found in food, water, and packaging that can cross biological barriers including the blood-brain barrier and potentially cause cellular damage.Sick Quitter Hypothesis: A confounding factor in alcohol studies where people who quit drinking due to illness are miscategorized as healthy non-drinkers, potentially skewing research results on alcohol’s health effects.Supplements, Compounds, and ProductsCentrum Silver: A multivitamin specifically formulated for adults 50+ that was used in randomized controlled trials showing it could reduce global cognitive aging by ~2 years and episodic memory aging by ~5 years in older adults.Vitamin D: Recommended dose is individualized based on blood tests, aiming for a level of 40-60 ng/mL. A common starting dose is 5,000 IU/day, but some may need more.Omega-3 Fish Oil: Crucial for brain health. A dose of ~2 grams/day is mentioned. For APOE4 carriers, the phospholipid form (found in salmon roe, krill oil, or created by the body at higher doses) is recommended for better brain delivery.Ubiquinol (Coenzyme Q10): A form of CoQ10 that supports mitochondrial health. Dr. Patrick gives it to her father for his Parkinson’s disease. The VESIsorb formulation by Pure Encapsulations is mentioned for higher bioavailability (and cost).Sulforaphane: A compound from cruciferous vegetables (especially broccoli sprouts) that activates the NRF2 pathway, boosting glutathione and aiding detoxification of pollutants like benzene and BPA. Best taken on an empty stomach unless it causes GI distress.Creatine Monohydrate: The “gold standard” form. Recommended for muscle performance (increasing exercise volume) and cognitive benefits. A 5g/day dose saturates muscles, while higher doses (10-20g/day, in divided doses) are suggested for cognitive enhancement and combating sleep deprivation.Curcumin: Used as a natural anti-inflammatory alternative to NSAIDs for headaches and delayed onset muscle soreness (DOMS). The Meriva (phytosomal) formulation is recommended for bioavailability, with a suggested dose of four 500mg capsules (2g total).Magnesium: Essential for over 300 enzymes, including those that convert Vitamin D. Recommended forms include magnesium glycinate, citrate, and malate. Magnesium Threonate is mentioned for its potential to cross the blood-brain barrier. Typical supplemental dose is around 300-450mg/day.Lutein and Zeaxanthin: Polyphenols important for eye and brain health, found in multivitamins and supplements studied in the AREDS2 trials.Exogenous Ketones: Mentioned as a potential intervention for cognitive decline in aging, as seen in some case studies. The ketone monoester used in studies is noted as very expensive.Psilocybin: Discussed as a non-addictive alternative to ketamine for treating depression and for its potent anti-inflammatory effects, which can be achieved at sub-perceptual doses.Momentous: Brand for NSF-certified creatine, used by Tim.Avmacol: The brand of sulforaphane supplement Dr. Patrick gives to her mother.Xyrem: Oral prescription solution that may be used to treat excessive daytime sleepiness (EDS) in adults and children aged seven years and older with narcolepsy.Thorne: Recommended for Meriva Curcumin and NSF-certified Creatine Monohydrate.Pure Encapsulations: Recommended for O.N.E. Omega-3 Fish Oil, VESIsorb Vitamin D3, and Magnesium Glycinate.Xymogen: Recommended for high-DHA fish oil and Magnesium Threonate.Big Berkey: Water filtration system.Blue Bottle Coffee: Noted for using plastic-free, sugarcane-lined cups that don’t leach microplastics into hot beverages.Foods and BeveragesBroccoli Sprouts: The most potent dietary source of sulforaphane, containing 10-100 times higher levels than mature broccoli plants, with powerful anti-cancer and detoxification properties.Sardines and Salmon Roe: Excellent dietary sources of omega-3 fatty acids EPA and DHA in highly bioavailable phospholipid form, with 40-70% of DHA in salmon roe being phospholipid-bound compared to just 1-3% in regular fish.Xylitol Gum/Mints: Sugar alcohol sweetener with proven dental health benefits, reducing harmful oral bacteria and preventing tooth decay when consumed at 6-10 grams daily, though most commercial gum contains problematic “gum base” polymers.Heavy Cream / MCT Oil: Fat sources commonly used in “dirty fasting” that have minimal impact on insulin levels compared to protein or carbohydrates, with MCTs rapidly converting to ketones while preserving most fasting benefits.PeopleDr. Mark Mattson: A neuroscientist and adjunct professor at Johns Hopkins School of Medicine known for his pioneering research on intermittent fasting and its effects on brain health and neuroplasticity.Dr. Valter Longo: A biogerontologist and professor at USC who directs the Longevity Institute and is renowned for his research on fasting, longevity, and the development of the Fasting-Mimicking Diet (FMD).Dr. Ben Levine: A cardiovascular exercise physiologist and Distinguished Professor at UT Southwestern who demonstrated that a 2-year exercise program can reverse heart aging by up to 20 years in middle-aged adults.Dr. George Brooks: A professor of integrative biology at UC Berkeley who pioneered the “lactate shuttle hypothesis,” revolutionizing our understanding of how lactate serves as a crucial fuel for the brain and muscles during exercise.Dr. Darren Candow: A professor at the University of Regina who directs the Aging Muscle and Bone Health Laboratory and is recognized as a leading expert on creatine monohydrate supplementation and its effects on muscle health.Dr. John Krystal: A psychiatrist and chair of the Department of Psychiatry at Yale School of Medicine who led the groundbreaking discovery of ketamine’s rapid antidepressant effects, revolutionizing depression treatment.Chuck Nichols: A professor of pharmacology at Louisiana State University Health Sciences Center who discovered the potent anti-inflammatory effects of psychedelic compounds through novel 5-HT2A receptor mechanisms.Kevin Rose: A technology entrepreneur, podcaster, and mutual friend who is known for his early trend identification and has been mentioned in the context of third-party testing fish oil supplements.Relevant ResourcesFoundMyFitness: Dr. Rhonda Patrick’s science-based website, podcast, and newsletter providing evidence-based health information on nutrition, aging, exercise, and disease prevention through deeper understanding of biology.Are Saunas the Next Big Performance-Enhancing “Drug?” by Dr. Rhonda Patrick | Tim FerrissDr. Rhonda Patrick on Life Extension, Performance, and Much More | The Tim Ferriss Show #12Exploring Smart Drugs, Fasting, and Fat Loss — Dr. Rhonda Patrick | The Tim Ferriss Show #237Dr. Rhonda Patrick’s Supplement Routine (2025) | FoundMyFitnessVitamin D | FoundMyFitnessDr. Rhonda Patrick’s Omega-3 Supplementation Guide | FoundMyFitnessDr. Mark Mattson on the Benefits of Stress, Metabolic Switching, Fasting, and Hormesis | FoundMyFitness Podcast #66Exactly What Happened When We Tried Hugh Jackman’s ’16:8 Diet’ | Men’s HealthWe Did a 10-Day Fast at Buchinger Wilhelmi Clinic So You Don’t Have To | Robb ReportIntermittent Fasting: Does a New Study Show Downsides — Or Not? | Harvard HealthHow Does VO2 Max Correlate with Longevity? | Peter AttiaPeter Attia on Zone 2 and Zone 5 Training | Peter AttiaFacts And Myths Of Male Fertility: Tight Underwear, Hot Tubs, Marijuana, And More | Office for Science and Society | McGill UniversityDarren Candow, PhD on the Optimal Creatine Protocol for Strength, Brain, and Longevity | FoundMyFitness Podcast #100Reverse Osmosis Water Filter: The most effective filtration technology for removing microplastics and nanoplastics from tap water, with membrane pore sizes capable of filtering particles as small as 0.001 micrometers. Big Berkey systems also provide effective filtration in the 24-26 nanometer range.Loose-Leaf Tea and Tea Steeper: Brewing method recommended to avoid the billions of microplastic particles released by plastic tea bags, using stainless steel, glass, or food-grade silicone infusers for a plastic-free tea experience.NSF Certified for Sport: Third-party certification program that tests supplements for 290+ banned substances and verifies accurate labeling, ensuring products are free of contaminants and safe for athletic use.Sustainability at Blue Bottle: A Timeline | Blue Bottle Coffee LabAlcohol | FoundMyFitnessDr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever | The Tim Ferriss Show #625Relevant ResearchEffect of Cocoa Extract and a Multivitamin on Cognitive Function: A Randomized Clinical Trial | JAMA Network OpenAge-Related Eye Disease Studies (AREDS/AREDS2) | National Eye InstitutePsilocybin Promotes Neuroplasticity and Reduces Neuroinflammation in a Mouse Model of Alzheimer’s Disease | Journal of NeuroinflammationReversing the Cardiac Effects of Sedentary Aging in Middle Age — A Randomized Controlled Trial | CirculationThe Lactate Shuttle During Exercise and Recovery | Medicine & Science in Sports & ExerciseAssociation Between Sauna Bathing and Fatal Cardiovascular and All-Cause Mortality Events | JAMA Internal MedicineSauna Bathing Is Inversely Associated with Dementia and Alzheimer’s Disease in Middle-Aged Finnish Men | Age and AgeingDoes Sauna Bathing Protect Against Dementia? | Preventive Medicine ReportsCreatine Supplementation Improves Cognitive Performance After Sleep Deprivation | PsychopharmacologyAssociation of Daily Step Count and Step Intensity With Mortality Among US Adults | JAMABrief Bursts of High-Intensity Exercise and Cardiovascular Risk | Mayo Clinic ProceedingsMicroplastics and Cardiovascular Disease | New England Journal of MedicineMicroplastics in Beverages: Glass and Plastic Bottles | Science of the Total EnvironmentThe Effect of Xylitol on Dental Caries and Oral Flora | Clinical, Cosmetic and Investigational DentistryInteraction Between Alcohol Consumption and Apolipoprotein E (APOE) Genotype with Cognition in Middle-Aged Men | Journal of the International Neuropsychological SocietyPsilocybin Increases Lifespan and Health-Span of Drosophila via Mechanisms Related to Autophagy | AgingSHOW NOTES[00:00:00] Start.[00:04:54] Dealing with aging parents and other topics on the table.[00:10:43] How a common multivitamin helps reverse cognitive and memory aging.[00:12:04] The importance of supplementation — especially as we age.[00:13:10] Effectively supplementing with omega-3 fish oil to counter APOE4 and Alzheimer’s risks.[00:16:50] The CoQ10 and omega-3 protocol that has helped Rhonda’s father manage Parkinson’s symptoms for nearly a decade.[00:19:28] Sulforaphane: a potent NRF2 activator with an unexpected benefit for Rhonda’s mother’s tremors.[00:25:34] How Rhonda convinced her mom to start CrossFit and the power of community-based, senior-focused fitness.[00:26:52] The earlier the intervention, the better the outcomes.[00:32:25] Intermittent fasting vs. extended fasting and my own results.[00:44:31] Does fasting destroy muscle mass? Debunking the catabolism fear and understanding the crucial role of the re-feeding phase.[00:57:24] “Dirty” fasting: what really happens to autophagy and metabolic benefits when you add a splash of cream or MCT oil to your coffee?[01:00:44] VO2 max: the one metric that may predict lifespan more accurately than anything else, and how we work to improve it.[01:12:07] How a two-year exercise program reversed heart aging by 20 years in previously sedentary, middle-aged adults.[01:16:18] Lactate isn’t the enemy: how vigorous exercise creates a superfuel that protects and grows the brain.[01:20:30] The optimal sauna protocol (temperature and frequency) for slashing dementia risk by 66%.[01:29:17] If you’re human, you’ll find a use for curcumin.[01:30:43] Creatine for cognition: moving beyond the gym with a powerful, science-backed tool for focus and combating sleep deprivation.[01:42:41] Still vitamin D deficient despite taking supplements? Here’s the critical cofactor you’re probably missing.[01:53:52] Shocking sources of microplastics in our daily lives, including chewing gum and teabags.[02:04:10] The uncomfortable truth about “moderate” alcohol consumption, cancer risk, and why the “sick quitter” hypothesis makes most older studies unreliable.[02:17:03] The ups and downs of ketamine and psilocybin on cognition and longevity.[02:24:19] Parting thoughts and where to find more from Rhonda.DR. RHONDA PATRICK QUOTES FROM THE INTERVIEW

“After two years of taking the multivitamin, they had improved cognition on a battery of different tests that equated to reducing global cognitive aging by about two years. And on top of that, they reduced their episodic aging by five years. Almost five years. It was 4.8 years.”

— Dr. Rhonda Patrick

“A 70-year-old makes about four times less vitamin D than their former 20-year-old self.”

— Dr. Rhonda Patrick

“There have now been enough studies that have come out looking at cardiorespiratory fitness in the sense of VO2 max and how people with a higher cardiorespiratory fitness have a five-year increased life expectancy compared to people with a low cardiorespiratory fitness.”

— Dr. Rhonda Patrick

“People end up eating about 200 fewer calories per day when they’re doing some form of intermittent fasting.”

— Dr. Rhonda Patrick

“If you have a low cardiorespiratory fitness and you go anywhere above that from low to low normal, it’s associated with a two-year increased life expectancy. And people with a low cardiorespiratory fitness actually have a higher all-cause mortality that’s comparable or worse than people with known diseases like type 2 diabetes or cardiovascular disease or smokers, for example. So in other words, being sedentary is a disease and we need to think about it as a disease and we should be trying to train to improve our VO2 max.”

— Dr. Rhonda Patrick

“Over the last few years, intermittent fasting has kind of gotten a bad rap because people now equate it with, ‘Oh, loss of muscle mass. I’m going to be catabolic.’ Well, in order to be in a repair mode, you actually do need to be in a catabolic mode.”

— Dr. Rhonda Patrick

“50 percent of the US population has insufficient levels of magnesium. So you’re talking about a coin toss here, right? One out of two.”

— Dr. Rhonda Patrick

“A woman has a lifetime risk of one in eight of getting breast cancer. So if you have a room with eight people, one of those women, if you’re at a dinner party, and eight women are there, then one of those women will come down and be diagnosed with breast cancer in her lifetime. So when you add alcohol consumption on top of that, if you’re talking about moderate alcohol consumption, that risk can go to one in six, which is very significant for lifetime risk.”

— Dr. Rhonda Patrick

The post Rhonda Patrick, Ph.D. — Protocols for Fasting, Lowering Dementia Risk, Reversing Heart Aging, Using Sauna for Longevity (Hotter is Not Better), and a Few Supplements That Might Actually Matter (#819) appeared first on The Blog of Author Tim Ferriss.

“Do I choose myself in the face of the world offering me all of this temptation to be something else?”
— Charlie Houpert

Charlie Houpert (@charliehoupert) is the co-founder of Charisma on Command, a company that helps people develop confidence, charisma, and strong social skills. Originally launched as a 4-Hour Workweek-inspired “muse,” it has since grown into one of the largest platforms for social skills and confidence training, with more than 10 million YouTube subscribers worldwide and more than a billion views across its content in six languages. His flagship course, Charisma University, has guided more than 30,000 members through practical steps to become more magnetic.

Charlie was once voted “Most Likely to Break Out of His Shell” and began studying charisma to overcome his own social anxiety. He now explores the deeper roots of confidence through archetypal psychology, embodiment practices, and more.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the interview on YouTube here. The transcript of this episode can be found here. Transcripts of all episodes can be found here.

This episode is brought to you by Patagonia ’s call-to-action to protect America’s public lands.  Go to Patagonia.com/Tim to learn more and act now .

The episode is also brought to you by Monarch Money’s all-in-one financial tool to help you track, budget, plan, and do more with your money and by LinkedIn Jobs recruitment platform with 1B+ users.

Listen onApple Podcasts[image error]Listen onSpotify[image error]Listen onOvercast4-Hour Workweek Success Stories — Charlie Houpert on Building “Charisma on Command” to 10M+ Subscribers, From Charging $10 for Seminars to Making Millions, Living in Brazil, Critical Early Decisions, and The Secret to Freedom

This message is brought to you by Patagonia. I’m always asked by listeners what helps me reset, feel grounded, recover from setbacks, or simply feel at peace. Without a doubt, it’s going into nature, usually with my pup Molly. For many millions of Americans, myself included, our national-park system is the best place to do just that.  Our public lands cover nearly a third of our country’s landmass. With more than 433 national-park sites, there’s a ton to explore, whether you’re fishing, hiking, or just camping with family.

And the best thing about our parks? As Americans, we collectively own them. This means we can visit and enjoy them any time we want.  For more than a century, our government has protected our public lands by holding them in a public trust. But it’s becoming harder and less safe for us to access these awe-inspiring places. 

Congress is preparing to vote on a bill that would force the sale of millions of acres of public lands to, among other things, fund tax breaks for billionaires. If approved, the bill could trigger the largest single sale of national public lands in modern history. 

Please join me and thousands of other Americans who are speaking up to protect our public lands. Visit patagonia.com/Tim to learn more.

This episode is brought to you by Monarch Money! Traditional budgeting apps can help, but they don’t compare to the complete financial command center you get with this episode’s sponsor, Monarch Money. Monarch is like your own personal CFO, giving you full visibility and control so you can stop merely earning and start growing.

Monarch was named The Wall Street Journal’s Best Budgeting App of 2025, and it’s the top-recommended personal finance app by users and experts, with more than 30,000 5-star reviews. Get control of your overall finances with Monarch Money. Use code TIM at monarchmoney.com/Tim for half off your first year.

This episode is brought to you by LinkedIn Jobs. Whether you are looking to hire now for a critical role or thinking about needs that you may have in the future, LinkedIn Jobs can help. LinkedIn screens candidates for the hard and soft skills you’re looking for and puts your job in front of candidates looking for job opportunities that match what you have to offer.

Using LinkedIn’s active community of more than 1 billion professionals worldwide, LinkedIn Jobs can help you find and hire the right person faster. When your business is ready to make that next hire, find the right person with LinkedIn Jobs. And now, you can post a job for free. Just visit LinkedIn.com/Tim.

Want to hear another episode with someone who understands social dynamics and influenced Charlie’s entrepreneurial path? Listen to my conversation with bestselling author Neil Strauss, in which we discussed his creative process, conducting engaging interviews, overcoming writer’s block, maximizing creative output, and much more.

What was your favorite quote or lesson from this episode? Please let me know in the comments.

SELECTED LINKS FROM THE EPISODEConnect with Charlie Houpert:

Charisma on Command | Charisma University | Dropping In Podcast | Improv & Dragons | YouTube | Twitter | Instagram | LinkedIn

The transcript of this episode can be found here. Transcripts of all episodes can be found here.

Companies, Organizations, and BrandsCharisma on Command: a personal development company and YouTube channel focused on enhancing charisma and communication skills through online courses and content.Skillshare: an online learning platform offering thousands of creative and business courses taught by industry experts.TrepStar: an on-demand media fulfillment service specializing in short-run CD, DVD, and USB manufacturing and shipping.Chipotle: a fast-casual Mexican restaurant chain known for customizable burritos, bowls, and tacos made with responsibly sourced ingredients.Airbnb: a global online marketplace connecting travelers with hosts offering unique accommodations and experiences.Google (Adwords): Google’s online advertising platform, now called Google Ads, that enables businesses to display ads across Google’s network.SamCart: an e-commerce platform designed specifically for selling digital products with conversion-optimized checkout experiences and upselling features.Marvel: a multimedia entertainment company famous for its superhero franchises, comic books, and blockbuster film universe.Lexus: Toyota’s luxury vehicle division known for premium cars, SUVs, and hybrid technology with emphasis on craftsmanship and reliability.Patek Philippe: a prestigious Swiss luxury watch manufacturer renowned for creating some of the world’s most expensive and collectible timepieces.Boeing: an American multinational aerospace corporation that designs, manufactures, and sells commercial airplanes, defense systems, and space technology.Whole Foods: an upscale grocery chain specializing in organic and natural products, known for high-quality foods and health-conscious shopping experience.Blogs, Websites, and Online PlatformsKickAss Academy: the original domain name for Charlie’s personal development blog and business before rebranding to Charisma on Command.Reddit: a social news aggregation and discussion platform where users can share content and engage in community discussions across thousands of topics.Clarity.fm: an on-demand consulting platform that connects entrepreneurs with industry experts for paid phone consultations, featuring advisors like Mark Cuban and Eric Ries.WordPress: the world’s most popular content management system, powering over 40% of websites with flexible themes and plugins for building any type of site.vBulletin: a commercial forum software package that enables communities to create feature-rich discussion boards with advanced moderation and customization tools.The Last Psychiatrist: an influential anonymous blog by psychiatrist Dr. Chris Ballas that offered penetrating cultural criticism and psychological analysis from 2007-2014.Cracked: a humor website known for its comedic articles, lists, and videos that blend entertainment with surprising insights and historical facts.Courses and ProgramsCharisma University: Charlie’s flagship online course teaching practical charisma and communication skills through step-by-step training modules, exercises, and real-world application techniques.Marketing Step-by-Step: Eben Pagan’s comprehensive entrepreneurial marketing course covering psychology-driven strategies for customer acquisition, conversion, and business growth.Art of Accomplishment: Joe Hudson’s transformational coaching program blending neuroscience, psychology, and spiritual practices to help high-performers break through limiting patterns and emotional barriers.Books The 4-Hour Workweek: Escape 9-5, Live Anywhere, and Join the New Rich by Timothy Ferriss The 4-Hour Body: An Uncommon Guide to Rapid Fat-Loss, Incredible Sex, and Becoming Superhuman by Timothy Ferriss The Game: Penetrating the Secret Society of Pickup Artists by Neil Strauss I Hope They Serve Beer in Hell by Tucker Max Essentialism: The Disciplined Pursuit of Less by Greg McKeown Influence: The Psychology of Persuasion by Robert Cialdini The Six Pillars of Self-Esteem: The Definitive Work on Self-Esteem by the Leading Pioneer in the Field by Nathaniel Branden The Prophet by Kahlil Gibran Running Lean: Iterate from Plan A to a Plan That Works by Ash Maurya How to Win Friends and Influence People: Updated For the Next Generation of Leaders by Dale Carnegie The 80/20 Principle: The Secret to Achieving More with Less by Richard Koch Who: The A Method for Hiring by Geoff Smart and Randy Street Entrepreneur Magazine’s Young Millionaires: Inspiring Stories to Ignite Your Entrepreneurial Dreams by Rieva Lesonsky History of the Peloponnesian War by Thucydides Tested Advertising Methods by John Caples Joint Ventures: From Mediocrity to Millions by Jay Abraham (PDF) Let My People Go Surfing: The Education of a Reluctant Businessman by Yvon Chouinard Losing My Virginity: How I Survived, Had Fun, and Made a Fortune Doing Business My Way by Richard Branson The Angels Knocking on the Tavern Door: Thirty Poems of Hafez by HafezMovies, TV Shows, and Media Inception : Christopher Nolan’s mind-bending heist thriller about extracting and planting ideas through shared dreaming, featuring layered dream sequences within dreams and Leonardo DiCaprio’s reality-questioning performance.Casino Royale (2006): the James Bond reboot featuring an iconic eight-minute parkour chase sequence with freerunner Sébastien Foucan that inspired Charlie’s first business idea for parkour training DVDs. Game of Thrones : HBO’s fantasy epic whose complex characters like Jon Snow and Tyrion Lannister became perfect subjects for Charlie’s “fame-jacking” YouTube strategy, borrowing existing audience attention. The Tim Ferriss Experiment : My reality TV show where I attempted to master various skills in record time, including a particularly cringe-worthy episode about dating and cold approach techniques. True Detective : the philosophical crime drama that was referenced in one of The Last Psychiatrist‘s characteristically penetrating blog post titles, blending pop culture with psychological analysis. Improv & Dragons : Charlie’s own YouTube series combining improvisational comedy with Dungeons & Dragons gameplay, showcasing his evolution from consumer to creator of entertaining content.PeopleNeil Strauss: author of The Game, a controversial exploration of pickup artist culture that inadvertently became a masterclass in social psychology and persuasion techniques.Neville Medhora: a copywriter and entrepreneur who founded Copywriting Course after helping AppSumo achieve their highest sales days through psychological email marketing.Tony Robbins: legendary motivational speaker and life coach known for transforming human potential through neurolinguistic programming and peak performance strategies.Tucker Max: bestselling author of I Hope They Serve Beer in Hell and master of provocative personal branding who provided Charlie crucial early feedback on his business positioning.Eben Pagan: marketing strategist and entrepreneur who created the “Marketing Step-by-Step” course that influenced Charlie’s rebranding to Charisma on Command, known for alliterative branding techniques.David DeAngelo: Eben Pagan’s pseudonym under which he wrote Double Your Dating, demonstrating early personal branding strategies in the dating advice industry.Ryan Holiday: bestselling author and marketing expert who was working as Tucker Max’s research assistant when I first encountered Tucker’s unconventional approach.Brian Chesky: co-founder and CEO of Airbnb, renowned for his philosophy of “doing things that don’t scale” in the early stages of building disruptive businesses.Clay Collins: online course creator who developed influential frameworks for pre-selling courses before creating them, providing Charlie with strategic product launch methodologies.Avicii: Swedish DJ and electronic music producer whose live performance Charlie witnessed during his transformational first visit to Las Vegas.Bill Clinton: 42nd President of the United States whose masterful eye contact techniques in political debates became the subject of one of Charlie’s breakthrough YouTube videos.Greg McKeown: author of Essentialism, advocating for the disciplined pursuit of less but better through systematic prioritization and elimination strategies.Herbie: fictional character from Greg McKeown’s Essentialism representing the bottleneck principle – that improving the slowest part of any system dramatically improves overall performance.Donald Trump: businessman and 45th President whose communication style Charlie analyzed in a viral 2016 video predicting his electoral success, which tripled Charlie’s business.Scott Adams: creator of the Dilbert comic strip and master persuader who also predicted Trump’s victory early, demonstrating advanced understanding of cognitive biases.Conor McGregor: Irish UFC fighter whose psychological warfare tactics and charismatic self-promotion became frequent subjects of Charlie’s behavioral analysis videos.Robert Downey Jr.: Academy Award-nominated actor whose quick wit and magnetic interview presence provided rich material for Charlie’s charisma breakdowns.Gary Vaynerchuk: entrepreneur and social media expert who popularized the “jab, jab, jab, right hook” content strategy of providing value before making sales pitches.Mr. Beast: YouTube phenomenon whose data-driven approach to viral content creation and psychological thumbnail optimization represents modern digital storytelling mastery.David Ogilvy: legendary advertising executive known as the “Father of Advertising” whose timeless principles of persuasion continue influencing modern marketing.Keanu Reeves: the perfect example of an introvert who exudes confidence despite being quiet and somewhat reclusive.Brené Brown: research professor and author whose insights on vulnerability and courage include the wisdom that healthy relationships are never truly 50/50.Thucydides: ancient Greek historian whose philosophy inspired Charlie’s tattoo: “The secret to freedom is courage” — representing the intersection of wisdom and personal transformation.Joe Hudson: executive coach and creator of Art of Accomplishment who guided Charlie through the complex emotional and strategic challenges of buying out his business co-founder.Sam Altman: CEO of OpenAI who publicly endorsed Joe Hudson’s work through social media, validating the psychological frameworks Charlie was learning.Nathaniel Branden: psychologist and author of The Six Pillars of Self-Esteem whose sentence completion exercises helped Charlie excavate limiting beliefs and unconscious patterns.Jay Abraham: business strategist and “old-school” marketing coach who challenged Charlie to create content worthy of being consumed by the people who had influenced him.Kahlil Gibran: Lebanese-American writer and philosopher, author of The Prophet, whose poetic wisdom on human nature continues influencing spiritual and personal development.Dale Carnegie: author of the timeless classic How to Win Friends and Influence People, establishing foundational principles for human relationship dynamics and social influence.Hafez: Persian lyrical poet from Shiraz, considered one of the greatest masters of the ghazal form, whose mystical and romantic verses exploring love, wine, and spiritual yearning have influenced literature for over 600 years.Martha Beck: life coach and author known for integrating ancient wisdom with modern psychological techniques.Brandon Sanderson: prolific fantasy author whose systematic approach to world-building and storytelling demonstrates the intersection of creativity and methodical execution.Richard Koch: author of The 80/20 Principle, advocating for identifying the vital few inputs that generate the majority of meaningful outputs in any system.Yvon Chouinard: founder of Patagonia and author of Let My People Go Surfing, demonstrating how authentic values can drive both business success and environmental activism.Ricardo Semler: Brazilian CEO who revolutionized corporate culture through radical workplace democracy, inspiring alternative approaches to business leadership and organizational design.Richard Branson: founder of Virgin Group whose scrappy, unconventional approach to starting an airline exemplifies entrepreneurial resourcefulness and bold risk-taking.Diana Chapman: executive coach whose interview on this show explored advanced techniques for integrating emotional intelligence with rational decision-making.Sigmund Freud and Carl Jung: pioneering psychoanalysts whose exploration of the unconscious mind inspired Charlie’s Dungeons & Dragons character “Sigmund,” blending psychology with creative expression.Charlie Hoehn: entrepreneur, 4x New York Times bestselling editor, co-founder of Author.Inc, and my former Director of Special Projects.Places and VenuesWashington, DC: the capital of the United States, known for its federal government, historic monuments, and vibrant political and cultural scene.H Street (in DC): a historic corridor in Northeast Washington DC known for its diverse dining scene, nightlife, and cultural venues stretching from Union Station to the Anacostia River.New York City, NY: the most populous city in the United States, renowned as a global center for finance, arts, fashion, and culture.Lower East Side, NYC: a historic Manhattan neighborhood known for its immigrant heritage, trendy restaurants, bars, and mix of affordable and luxury housing.Brazil: the largest country in South America, famous for its Amazon rainforest, vibrant culture, beaches, and cities like Rio de Janeiro and São Paulo.Rio de Janeiro, Brazil: Brazil’s iconic coastal city famous for its stunning beaches, Christ the Redeemer statue, Carnival celebration, and dramatic mountain landscapes.Floripa (Florianópolis), Brazil: the capital of Santa Catarina state, known as the “Magic Island” for its beautiful beaches, technology hub, and high quality of life.Las Vegas, NV: the entertainment capital of the world, famous for its casinos, shows, nightlife, and extravagant themed hotels along the Las Vegas Strip.Vancouver, Canada: a major West Coast seaport city known for its natural beauty, mild climate, diverse culture, and proximity to mountains and ocean.Colombia: a South American country known for its diverse landscapes from Caribbean coastlines to Amazon rainforest, vibrant cities, and rich cultural heritage.Pennsylvania: a Mid-Atlantic U.S. state known for its historical significance, including Philadelphia’s Independence Hall and the Liberty Bell.Los Angeles, CA: the second-largest city in the United States, famous for Hollywood, entertainment industry, beaches, and diverse neighborhoods.XS (Nightclub in Las Vegas): an upscale nightclub at Encore Las Vegas known for its luxurious indoor-outdoor design, celebrity DJ performances, and high-end bottle service.UNLV (University of Nevada, Las Vegas): a public research university known for its hospitality, business, and engineering programs, as well as its Runnin’ Rebels basketball team.South by Southwest (SXSW): an annual conglomeration of interactive media, music, and film festivals and conferences held in Austin, Texas.UT Austin: the University of Texas at Austin, a top-tier public research university known for its academics, athletics, and vibrant campus culture.San Francisco / Bay Area: a northern California region known for its tech industry, iconic Golden Gate Bridge, diverse culture, and steep hills.Concepts, Ideas, and FrameworksManagement Consulting: a professional service where experts analyze organizational problems and provide strategic solutions to improve business performance and efficiency.The Muse: concept from The 4-Hour Workweek for creating an automated, low-maintenance business that generates passive income while requiring minimal ongoing involvement.Scratch-Your-Own-Itch: the entrepreneurial philosophy of solving a problem you personally experience, ensuring product-market fit by building something you genuinely want and need.Moonlighting: the practice of working a side business or project while maintaining full-time employment, allowing entrepreneurs to test ideas with reduced financial risk.Burn the Ships: a commitment strategy inspired by historical military tactics, meaning to eliminate all options for retreat and force complete dedication to a new venture.Fear-Setting: My systematic exercise for defining worst-case scenarios, prevention strategies, and recovery plans to overcome decision paralysis and take calculated risks.The Game: Neil Strauss’ exploration of pickup artist culture and social dynamics, revealing psychological techniques for attraction and social influence.10 out of 10 Upside: the component of fear-setting that focuses on envisioning and quantifying the best possible outcomes of taking action on a decision.Fame-Jacking: Charlie’s term for his YouTube strategy of creating content analyzing famous personalities to attract their fans and leverage existing audience interest.Tripwire: an online marketing strategy using a low-cost, high-value initial product to convert prospects into paying customers and establish a buying relationship.Jab, Jab, Jab, Right Hook: Gary Vaynerchuk’s content marketing philosophy of providing value repeatedly (jabs) before making sales pitches (right hooks) to build trust and engagement.The Herbie Parable: a story from Essentialism about identifying and addressing the primary bottleneck in any system to improve overall performance and efficiency.Audience Capture: the phenomenon where content creators become trapped by their audience’s expectations, leading to creative stagnation and burnout as they chase engagement over authenticity.50/50 Partnership Split: the commonly problematic business arrangement where two partners share equal ownership despite rarely contributing equally, often leading to disputes and power struggles.Sentence Completion Exercises: a psychological technique from The Six Pillars of Self-Esteem using open-ended prompts to uncover subconscious thoughts and limiting beliefs.Shotgun Deal: a business partnership buyout mechanism where one partner names a price and the other must either accept or buy them out at the same price, forcing fair valuation.Mimetic Desire: René Girard’s theory that humans copy the desires of others rather than developing authentic wants, creating cycles of competition and social imitation.Relevant ResourcesBC-X Parkour Philosophy of Continuous Learning | Charlie HoupertFear-Setting: The Most Valuable Exercise I Do Every Month | Tim FerrissStep 1 for Living a Kickass Life: Stop “Just Being Yourself” | KickAss AcademyI Hired a Pickup Artist to Help Me Find a Girlfriend | The Tim Ferriss Experiment #7The Secret Of Bill Clinton’s Charisma | Charisma on CommandThe Listener by James Christensen | The Collection ShopWhy Trump Will SMASH Hillary | Charisma on CommandHow To Build Unwavering Confidence | Charisma on CommandRanking the Most Charismatic Players In Game of Thrones | Charisma on CommandHow to Make a Disrespectful Person Look Insecure for Insulting You | Charisma on CommandHow to Look Extremely Confident (Even if You’re Quiet) | Charisma on CommandBrené Brown — Striving versus Self-Acceptance, Saving Marriages, and More | The Tim Ferriss Show #409The Maintenance of Certification Exam as Fetish | The Last PsychiatristTen Extra Seconds Would Have Saved True Detective’s Finale | The Last PsychiatristAdvertising’s Collateral Damage | The Last PsychiatristIf You’re Watching, It’s For You | The Last PsychiatristJoe Hudson: How to be More Emotionally Intelligent (Without Trying so Hard) | TwitterFilling the Void: Thoughts on Learning and Karma | Tim FerrissMartha Beck — The Amazing and Brutal Results of Zero Lies for 365 Days, How to Do a Beginner “Integrity Cleanse,” Lessons from Lion Trackers, and Novel Tactics for Reducing Anxiety | The Tim Ferriss Show #732Brandon Sanderson on Building a Fiction Empire, Creating $40M+ Kickstarter Campaigns, Unbreakable Habits, The Art of World-Building, and The Science of Magic Systems | The Tim Ferriss Show #794Diana Chapman — How to Get Unstuck, Do “The Work,” Take Radical Responsibility, and Reduce Drama in Your Life | The Tim Ferriss Show #536SHOW NOTES[00:00:00] Start.[00:06:44] Charlie meets the boogeyman (me).[00:10:11] Why defaulting to management consulting after college felt like daily self-betrayal.[00:13:21] Leaping into parkour training via DVD as a first business attempt.[00:15:45] Moonlighting vs. burning-ships entrepreneurship.[00:16:54] Negotiating remote work with a 90% raise.[00:21:22] Charlie moves to New York and kicks off KickAss Academy.[00:22:16] Airbnb survival tactics while living in a 396 sq. ft. apartment.[00:23:26] Using the fear-setting exercise and other disaster-mitigation strategies.[00:26:11] Charlie’s first blog post and crossing the publishing Rubicon.[00:28:26] How Charlie’s first in-person class prompted an accidental business model.[00:34:21] 10 go-getters make an ambitious move to Brazil.[00:32:14] The daily growth whiteboard system.[00:37:58] How a harsh Tucker Max consultation galvanized the rebranding to Charisma on Command.[00:44:39] From financial downturn to pre-selling a course for $12,500.[00:50:44] Finally making enough money to chase summer in six-to-eight-month increments.[00:52:00] Enjoying the sustainable benefits of creating timeless content.[00:54:05] How Bill Clinton seduced 7,000 people into following Charlie on YouTube.[00:55:46] How Greg McKeown’s Essentialism helped solve Charlie’s “Herbie” problem.[00:58:26] Evolving funnel flow and fame-jacking.[01:03:46] YouTube algorithm changes, short-form content, and maintaining audience trust for the long term.[01:10:58] Why I still create this podcast.[01:19:30] The dangers of succumbing entirely to audience expectation over authenticity.[01:21:42] The catalysts that led to time off, an ayahuasca retreat, and a seven-year transformation process.[01:30:26] Making the transition from 50/50 partner to sole owner.[01:35:16] Recommended reading: Six Pillars of Self-Esteem by Nathaniel Branden[01:37:32] The influence of The Last Psychiatrist blog.[01:41:46] Jay Abraham coaching: “Make it good enough for Tim Ferriss.”[01:43:52] How testimonials added a 4x conversion lift.[01:44:31] Coming to an agreement with the co-founder.[01:47:20] Joe Hudson and the Art of Accomplishment.[01:51:57] Why I stand by The 4-Hour Workweek without further revision, warts and all.[01:55:06] Exercising gratitude even when receiving praise is difficult.[01:59:15] Relationship with earlier work: video vs. writing.[02:02:05] Don’t miss “Filling the Void.”[02:03:56] More recommended reading.[02:06:43] Improv & Dragons.[02:08:06] Charlie’s billboard: “Don’t think, feel.”[02:08:57] Parting thoughts.MORE CHARLIE HOUPERT QUOTES FROM THE INTERVIEW

“Do I choose myself in the face of the world offering me all of this temptation to be something else?”
— Charlie Houpert

“If you don’t believe in it fully, you’re going to sell it with hesitancy.”
— Charlie Houpert

“Don’t think, feel. I know that’s counterintuitive to a lot of people, but lately, that’s been my guiding principle is feel my heart, feel my gut, think from my mind, and try to find some union of the three to move forward.”
— Charlie Houpert

“When you start trading your beliefs for cash or approval, you’re just sending a signal that, ‘I can’t be relied on to be myself and be safe and earn.'”
— Charlie Houpert

The post 4-Hour Workweek Success Stories — Charlie Houpert on Building “Charisma on Command” to 10M+ Subscribers, From Charging $10 for Seminars to Making Millions, Living in Brazil, Critical Early Decisions, and The Secret to Freedom (#817) appeared first on The Blog of Author Tim Ferriss.