Mind & Matter
- Episodes
- 316
- Released
- weekly
- Latest episode
- Nov 10, 2026
About the podcast
Weekly science podcast by neuroscientist Nick Jikomes, PhD. Long-form interviews with researchers on the brain, nutrition, metabolism, drugs and aging. Not medical advice.
At M&M, we are interested in trying to figure out how things work, not affirming our existing beliefs. We prefer consulting primary rather than secondary sources and independent rather than institutional voices. If we encounter uncomfortable truths or the evidence suggests unfashionable ideas may be valid, so be it.
As the host, my aim is to help you better understand how the body & mind work by curating & synthesizing information in a way that yields science-based insights that you can choose to use or disregard in your own life. Taking ownership of your health starts with taking ownership of your information diet.
I am motivated to connect the dots and distill general principles from what I learn, preferring to ask questions and play devil’s advocate to debating or incessantly pushing my own viewpoint.
My beliefs:
- Taking ownership of your health starts with taking ownership of your information diet.
- All knowledge is provisional and we must work hard to prevent ourselves from becoming attached to our favorite ideas & preferred conclusions.
- Wisdom comes from an iterative, trial-and-error process of learning and unlearning. Letting go of pre-conceived notions can be painful, but pain is information.
Sometimes modern discoveries teach us we must unlearn received wisdom. Other times, modern information overload & historical chauvinism cause us to forget ancient wisdom which stills applies. The framework for learning that I embody is inspired by three Ancient Greek maxims inscribed in the Temple of Apollo at Delphi:
- “Γνῶθι σεαυτόν” (Know thyself)
- “Μηδὲν ἄγαν” (Nothing in excess)
- “Ἐγγύα πάρα δ Ἄτα” (Certainty brings insanity)
Contributors
Episodes 316
Tendons, Collagen, mTOR & Exercise Adaptation | Keith Baar | 312
Send us Fan MailKeith Baar explains why tendons stop adapting after 10 minutes of loading, why long low-load holds beat fast reps for connective tissue, and how vitamin C, collagen, caffeine and mTOR shape …
Show notes
Keith Baar explains why tendons stop adapting after 10 minutes of loading, why long low-load holds beat fast reps for connective tissue, and how vitamin C, collagen, caffeine and mTOR shape training.
SPONSOR:
- Brain Bean: Smart-roasted coffee with high polyphenol content, ultra-pure grass-fed colostrum, and more. Use code MINDMATTER15 for 15% off.
TOPICS DISCUSSED:
• Signal Architecture: The same total exercise split into two sessions spaced about six to eight hours apart gives bones and tendons two stimuli and fewer injuries than one long session.
• Tendon Design: Tendons grade from compliant at the muscle to stiff at the bone to avoid stress concentrations; people over about 45 are roughly five times more likely to rupture a tendon than 18-year-olds.
• Collagen & Vitamin C: Collagen is a glycine–X–proline triple helix; vitamin C is consumed by prolyl hydroxylase, which collagen needs before it can leave the cell, and scurvy is a failure of collagen export.
• Force Transfer: Strength depends on muscle size, neural drive, and the connective tissue that transmits force; lean “sinewy” climbers can out pull bigger bodybuilders.
• Soreness Is Not Growth: Soreness signals damage from unaccustomed or poorly matched loading, not a stronger anabolic signal.
• mTOR, Failure & Strength: Mechanical load activates mTOR by moving its inhibitor TSC2 away from Rheb; training to failure recruits every fiber for growth, while heavy loads drive strength through other pathways.
• Whey + Collagen: Whey alone lowers glycine after exercise; adding about 5 g of collagen raised both muscle and connective tissue protein synthesis in work by Luc van Loon.
• Caffeine, Keto & GLP-1 Drugs: High-dose caffeine lowered collagen and muscle protein synthesis and blunted adaptation in mice; a saturated-fat ketogenic diet extended median mouse lifespan with less cancer but can weaken bone; GLP-1 lean-mass loss looks larger when a shrinking fatty liver is counted as lean mass.
*Not medical advice.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
GDF15, Morning Sickness & Mitochondrial Stress | Stephen O'Rahilly | 311
Send us Fan MailDr. Stephen O'Rahilly explains GDF15, a stress hormone that makes us feel sick and eat less, and why morning sickness, and its severe form hyperemesis gravidarum (HG), comes from GDF15 made …
Show notes
Dr. Stephen O'Rahilly explains GDF15, a stress hormone that makes us feel sick and eat less, and why morning sickness, and its severe form hyperemesis gravidarum (HG), comes from GDF15 made by the fetus.
SPONSOR:
- Brain Bean: Smart-roasted coffee with high polyphenol content, ultra-pure grass-fed colostrum, and more. Use code MINDMATTER15 for 15% off.
TOPICS DISCUSSED:
• What GDF15 Is: A hormone made by stressed cells, sensed only in two small regions of the brainstem.
• A Warning Hormone: It rises with toxins, chemotherapy and cellular stress, not with ordinary meals or overfeeding.
• Rate of Change Matters: The brain tracks how fast GDF15 rises, and chronic exposure desensitizes it.
• Mitochondria and Mortality: GDF15 helps diagnose mitochondrial disease and predicts mortality.
• Metformin and GLP-1 Drugs: GDF15 explains metformin's modest weight loss and may overlap with GLP-1 nausea.
• Morning Sickness and Hyperemesis Gravidarum: The fetus makes nearly all the GDF15; women with low prior GDF15 are most sensitive.
• Drugs That Raise or Block GDF15: Disappointing weight-loss drugs, and blockers for cachexia and hyperemesis gravidarum.
• Healthy vs. Unhealthy Fat Storage: Why fat cells largely decide who gets sick with weight gain.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
Psilocybin vs. SSRIs for Depression, Emotional Blunting & How Psychedelics Work | Robin Carhart-Harris | Ep 310
Send us Fan MailRobin Carhart-Harris explains why his trial of psilocybin therapy vs. the SSRI escitalopram for depression missed one primary measure but favored psilocybin on almost everything else, and why …
Show notes
Robin Carhart-Harris explains why his trial of psilocybin therapy vs. the SSRI escitalopram for depression missed one primary measure but favored psilocybin on almost everything else, and why SSRIs can blunt emotion.
SPONSOR:
- Brain Bean: Smart-roasted coffee with high polyphenol content, ultra-pure grass-fed colostrum, and more. Use code MINDMATTER15 for 15% off.
TOPICS DISCUSSED:
• Consciousness Matters: Why the mind can drive biology, with placebo as the clearest example.
• Expectancy and Response: How beliefs and the quality of the experience shape outcomes.
• The Psilocybin vs. Escitalopram Trial: Not significantly different on the primary measure, but ahead on nearly every other outcome.
• The Blinding Problem: Why double-blind designs barely work here, and the case for open-label trials.
• Emotional Blunting: SSRIs dampened brain responses to emotional faces; psilocybin did not.
• Sexual Dysfunction: Worse on the SSRI, improved after psilocybin therapy.
• What's Next: Metabolic markers, fibromyalgia and a new trial in young adults with depression.*Not medical advice.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
This Animal Survives 18 Minutes Without Oxygen | Gary Lewin | Ep 309
Send us Fan MailNick talks with Prof. Gary Lewin (Max Delbrück Center, Berlin) about naked mole-rats, which in lab tests survived 18 minutes in pure nitrogen by shutting down brain activity, keeping the heart …
Show notes
Nick talks with Prof. Gary Lewin (Max Delbrück Center, Berlin) about naked mole-rats, which in lab tests survived 18 minutes in pure nitrogen by shutting down brain activity, keeping the heart beating, and switching to fructose for fuel.
TOPICS DISCUSSED:
• From Pain Research to Mole-Rats: The work began when the animals turned out not to feel the burn of capsaicin.
• Ecology & Eusociality: Colonies with a queen, one breeding male, workers, and soldiers, spread across semi-arid East Africa.
• Where the Low Oxygen Comes From: Piling into one sleeping chamber, rather than the burrow air itself.
• 18 Minutes in Pure Nitrogen: In lab tests they pass out, gasp about once a minute, and fully revive.
• Brain Off, Heart On: Brain activity drops to zero while the heart holds 50 beats per minute.
• Fructose as Backup Fuel: Fructose transporters in brain and heart let glycolysis keep running without oxygen.
• Queens, Odor & Longevity: One queen molecule (IPM) suppresses breeding; a queen can live 39 years.
• Pain, Acid & Navigation: Acid insensitivity, about 80% fewer pain receptors, and navigation by about 90 hairs.
*Not medical advice.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
Low Selenium Doubles Your Heart Attack Risk | Lutz Schomburg | Ep 308
Send us Fan MailNick talks with Prof. Lutz Schomburg about selenium biology in the endocrine system: selenoprotein P as the liver’s selenium transport protein and status biomarker, autoantibodies that can …
Show notes
Nick talks with Prof. Lutz Schomburg about selenium biology in the endocrine system: selenoprotein P as the liver’s selenium transport protein and status biomarker, autoantibodies that can impair delivery despite normal blood selenium, thyroid autoimmunity (Hashimoto’s and Graves’), diabetes, aging, and what selenium supplementation trials show.
TOPICS DISCUSSED:
• Selenoprotein P: Liver-made transport protein that delivers selenium to tissues and serves as a status biomarker beyond total serum selenium.
• Autoantibodies & Delivery: Anti-SELENOP antibodies can impair selenium delivery even when blood selenium looks normal.
• Thyroid Autoimmunity: Links between selenium status and Hashimoto’s / Graves’ disease risk and course.
• Supplementation Trials: What controlled selenium trials do and do not show for thyroid and metabolic outcomes.
• Diabetes & Aging: How selenium biology intersects with diabetes risk and aging.
• Practical Context: Interpreting selenium blood tests and why a “normal” result can still miss tissue delivery problems.
*Not medical advice.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
What we're getting WRONG about cane sugar & corn syrup | Kimber Stanhope | Ep 307
Send us Fan MailControlled human feeding trials show added fructose raises liver fat, triglycerides, uric acid, and insulin resistance at real-world doses.TOPICS DISCUSSED:Glucose vs Fructose in the Liver …
Show notes
Controlled human feeding trials show added fructose raises liver fat, triglycerides, uric acid, and insulin resistance at real-world doses.
TOPICS DISCUSSED:
- Glucose vs Fructose in the Liver: Glucose and fructose are handled by the liver in distinct ways.
- Natural Sugars vs Processed Sugars: Whole fruit is mostly water, fiber, and micronutrients at modest sugar density; cookies and sodas pack far more sugar per weight and are easier to overconsume.
- HFCS on Store Shelves: Industry cites 55% fructose for beverages, but independent assays of sodas often land higher (around 60% on average, up to ~68%) with no tight standard of identity.
- Sucrose vs HFCS: In head-to-head controlled feeding, matched-calorie sucrose (~50/50) and HFCS (55/45) moved risk factors similarly versus an aspartame control; total dose mattered more than that small ratio gap.
- Dose Response: At roughly 10%, 17.5%, and 25% of energy as HFCS beverages, LDL, triglycerides, apoB, uric acid, liver fat, and insulin sensitivity worsen in a dose-dependent way.
- Fructose vs Glucose Beverages (10 Weeks): Fructose—not matched glucose—raised 24-h uric acid, RBP-4, and other biomarkers in overweight/obese adults.
- Fructose × Glucose Interaction: In some comparisons, HFCS raised LDL/apoB more than fructose alone, consistent with glucose amplifying the lipid signal.
- Orange Juice vs Sucrose Beverage: On a fully provided diet, both raised apoB/LDL/postprandial triglycerides even with slight weight loss; OJ lowered uric acid while sucrose did not.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
Why Bigger Brains Get More Mutations | Christopher Walsh | Ep 306
Send us Fan MailHow genomics is used to study what makes a human brain, and how genetically damaged neurons get removed.TOPICS DISCUSSED:Scale & Size: A human brain is about three times a chimpanzee brain by …
Show notes
How genomics is used to study what makes a human brain, and how genetically damaged neurons get removed.
TOPICS DISCUSSED:
- Scale & Size: A human brain is about three times a chimpanzee brain by mass, but the larger change is extra association cortex and extra upper-layer circuits that talk mostly to other cortex.
- When Development Ends: Most cortical neurons are born before birth. Myelin and other glia keep forming into the twenties. Synapses keep changing after that.
- Broken Genomes Get Edited: Walsh describes forthcoming work in which ~25–30% of late-fetal cortical neurons carry genetic defects, falling to ~5% by birth, with smaller defects still being removed through adult life.
- Regulation vs. New Genes: Humans and mice both have ~20,000 genes. Most human-specific change is in when and where those genes turn on, not in inventing new proteins.
- Human Accelerated Regions: About half of HARs involve the brain. Rare mutations in them show up more often in kids with intellectual disability and autism.
- ASPM & Microcephaly: Loss of one conserved cell-division gene can shrink a human brain toward chimpanzee volume and shape. The same knockout barely shrinks a mouse.
- Heritability of Genetic Disorders: Autism is highly heritable in twin studies. A whole-genome test today still finds a specific cause in only about a quarter to a third of kids.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
Why THC Users Eat More but Don't Gain Weight | Nephi Stella | Ep 305
Send us Fan MailThe biology of endogenous cannabinoids & history of cannabinoid-based therapeuticsTOPICS DISCUSSED:Anandamide vs 2-AG: The two major endocannabinoids with a shared arachidonic acid backbone but …
Show notes
The biology of endogenous cannabinoids & history of cannabinoid-based therapeutics
TOPICS DISCUSSED:
- Anandamide vs 2-AG: The two major endocannabinoids with a shared arachidonic acid backbone but distinct head groups biological roles.
- On-demand production: Calcium-dependent enzymes release cannabinoids from membranes in response to neuronal activity patterns.
- Trafficking: Fatty acid binding proteins and extracellular microvesicles traffic endocannabinoids within and between cells.
- Adolescent THC: Global receptor activation during circuit wiring may contribute to cannabis use disorder and psychosis vulnerability in susceptible individuals.
- Enzyme inhibitors: Early FAAH clinical trial halted by off-target toxicity; MAGL inhibitors advancing in phase 2 for anxiety and addiction.
- Peripheral CB1: Liver receptors regulate metabolism; restricted antagonists aim to reduce weight without central psychiatric risks of the weight loss drug rimonabant.
ABOUT THE GUEST: Nephi Stella, PhD is a professor at the University of Washington School of Medicine. He has studied endocannabinoid signaling for more than 25 years, focusing on therapeutic strategies that separate beneficial effects from side effects of cannabinoid-system modulation.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
The Gene Variant Linked to Living to 100 | Pinchas Cohen | Ep 304
Send us Fan MailMitochondrial peptides act as stress signals that regulate metabolism, muscle mass, and neurodegeneration.TOPICS DISCUSSED:Mitochondria as Communication Hubs: Beyond ATP production, mitochondria …
Show notes
Mitochondrial peptides act as stress signals that regulate metabolism, muscle mass, and neurodegeneration.
TOPICS DISCUSSED:
- Mitochondria as Communication Hubs: Beyond ATP production, mitochondria encode peptides that regulate cell death, immunity, and inter-organ communication.
- Humanin Discovery: Identified independently by three labs; neuroprotective, longevity-linked, and capable of neutralizing APOE4 effects via a rare Jewish variant.
- Ethnic Genetic Variants: Ancestry-specific mutations in MOTS-c, MENTSH, and SHMOOSE influence diabetes, obesity, sarcopenia, and Alzheimer’s risk.
- MOTS-c & Muscle Preservation: Exercise-induced peptide prevents atrophy and may offset muscle loss seen with GLP-1 drugs.
- Peptide Classes: Fragments of larger proteins, endogenous microproteins from small genes, and emerging AI-designed artificial peptides.
- Diet Modulation: Mediterranean diet adherence raises circulating levels of the peptides humanin and SHMOOSE.
- Clinical Reality Check: Early MOTS-c trials showed metabolic benefits; unregulated products often contain inaccurate doses.
ABOUT THE GUEST: Pinchas Cohen, MD is Dean of the USC Leonard Davis School of Gerontology and a leading researcher on mitochondrial peptides in aging, metabolism, and neurodegeneration.
RELATED CONTENT:
- Article | Metabolic Stress & the Peptide MOTS-c: How Much is Too Much?
- Podcast | MOTS-c & Mitochondrial Peptides in Health & Aging | David Lee
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
Pain, Inflammation, Peptides & Healing | Isaac Chiu | Ep 303
Send us Fan MailHow the nervous and immune systems communicate, using peptides and other signals, to regulate pain, itch, and inflammation.TOPICS DISCUSSED:Nociception & Pathogens: Sensory neurons detect …
Show notes
How the nervous and immune systems communicate, using peptides and other signals, to regulate pain, itch, and inflammation.
TOPICS DISCUSSED:
- Nociception & Pathogens: Sensory neurons detect bacterial toxins within seconds, enabling rapid host-defense coordination ahead of immune-cell recruitment.
- CGRP & neutrophils: Nociceptor-release the peptide CGRP, which blocks neutrophil (immune cell) recruitment; pathogens exploit this in necrotizing fasciitis and meningitis.
- Pain sensitization: Inflammation can lower neuronal thresholds for pain, which sometimes becomes a chronic problem.
- Gut barrier protection: CGRP from gut nociceptors drives goblet-cell mucus secretion, supporting the protective “weep and sweep” response.
- Skin-to-gut allergy priming: Early skin exposure to allergens plus scratching may promote food allergies.
- Vagus nerve circuits: Distinct vagal sensory neurons selectively suppress TNF or induce IL-10, allowing precise inflammatory control.
- Brain inflammatory memory: Insular neurons encode site-specific immune responses that can later be recalled by reactivating those circuits. The brain remembers past inflammatory events.
ABOUT THE GUEST: Isaac Chiu, PhD is a professor in the Department of Immunology at Harvard Medical School. His lab studies nervous-immune system crosstalk in pain, itch, infection, and inflammatory disease.
RELATED CONTENT:
Article | Inflammation Regulation by Omega Fats: How High ω-6 Intake Impacts ω-3 Levels
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
Mitochondrial Peptide That Doubled Running | David Lee | Ep 302
Send us Fan MailMitochondrial peptide MOTS-c is a stress-induced signal that reprograms cell metabolism.TOPICS DISCUSSED:Mitochondrial Roles: Not just ATP production, but “speaker of the house” via …
Show notes
Mitochondrial peptide MOTS-c is a stress-induced signal that reprograms cell metabolism.
TOPICS DISCUSSED:
- Mitochondrial Roles: Not just ATP production, but “speaker of the house” via communication molecules that “talk” to the rest of the cell.
- Origin of Communication: Mitochondrial peptides were likely co-opted from ancient antimicrobial factors to synchronize nuclear and mitochondrial genomes.
- MOTC Discovery: Identified in mitochondrial ribosomal RNA regions linked to interferon responses.
- Stress Induction: MOTS-c is produced in response to exercise, immune activation, and nutrient withdrawal; circulates as a mitokine.
- Nuclear Regulation: MOTS-c translocates to the nucleus under stress and acts as a nonspecific cofactor that shapes chromatin accessibility and gene expression.
- Metabolic Effects: Prevents diet-induced obesity and fatty liver in mice without altering baseline weight; engages AMPK and suppresses anabolic pathways.
- Immune Modulation: Shifts immune cell programs to reduce autoimmune attack in type 1 diabetes models.
- Aging Phenotypes: Daily or intermittent dosing doubles running capacity and preserves walking ability in old mice.
ABOUT THE GUEST: Changhan David Lee, PhD is Associate Professor at the University of Southern California Leonard Davis School of Gerontology. His laboratory investigates mitochondrial communication and microproteins in the biology of aging.
RELATED CONTENT:
- Article | MOTS-c & Cellular Energy Homeostasis
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
What we're getting WRONG about copper peptides | Rahi Sarbaziha | Ep 301
Send us Fan MailGHK-Copper and peptides in skin care, aging, and general health.TOPICS DISCUSSED:Endogenous Decline: GHK-copper levels peak in young adulthood then fall with age, reducing natural support for …
Show notes
GHK-Copper and peptides in skin care, aging, and general health.
TOPICS DISCUSSED:
- Endogenous Decline: GHK-copper levels peak in young adulthood then fall with age, reducing natural support for skin repair and collagen maintenance.
- Skin Penetration: Effective topical delivery depends on molecular size under and fat solubility, often improved by procedures such as microneedling that briefly disrupt the barrier.
- Mechanisms of Action: The peptide upregulates fibroblasts and vascular endothelial growth factor, stimulates glycosaminoglycan production, and alters expression of genes involved in tissue regeneration and oxidative stress reduction.
- Lasting Remodeling: Gene expression changes produce sustained collagen rebuilding that develops over weeks to months rather than delivering only transient effects.
- Administration Routes: Topical use is accessible and pairs well with hyaluronic acid for hydration; injectables may reach higher local concentrations but lack extensive human trial data and FDA approval for this purpose.
- Safety & Protocols: The compound is generally well tolerated with mild transient injection-site reactions; typical approaches use daily microgram doses for one to two months followed by off periods.
- Hair & Other Uses: Clinical observations indicate potential for hair shaft strengthening comparable to minoxidil with a favorable side-effect profile, alongside exploratory work in wound healing and neurological contexts.
- Research Needs: Expanded human studies are required to standardize dosing, confirm long-term safety, and evaluate value in neurodegeneration, lung repair, and related areas.
ABOUT THE GUEST: Rahi Sarbaziha, MD is a physician in Beverly Hills, California whose practice focuses on regenerative aesthetics, hormone therapies, peptides, and interventions that support vitality, tissue repair, and overall wellness.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
What we're getting WRONG about the "leaky" aging brain | William Banks | Ep 300
Send us Fan MailBlood-brain barrier as a dynamic interface allowing selective passage of nutrients, peptides, and gut hormones.TOPICS DISCUSSED:Blood-Brain Barrier Structure: Capillary endothelial cells with …
Show notes
Blood-brain barrier as a dynamic interface allowing selective passage of nutrients, peptides, and gut hormones.
TOPICS DISCUSSED:
- Blood-Brain Barrier Structure: Capillary endothelial cells with tight junctions, absent fenestrae, and minimal vesicles create a selective interface; supported by astrocytes and pericytes.
- Crossing Mechanisms: Lipid-soluble small molecules diffuse passively; glucose, amino acids, and regulatory peptides use saturable transporters whose rates vary by need.
- Peptide Transport: Many peptides cross via lipid solubility or specific transporters; rate, not all-or-none presence, determines biological relevance; efflux systems remove some (e.g. certain enkephalins).
- Dynamic Regulation: Transporters for leptin and insulin are modulated by epinephrine, triglycerides, and brain demand; changes occur in aging and Alzheimer’s (reduced glucose uptake, impaired Aβ efflux).
- Circumventricular Organs: Leaky capillary regions allow rapid sampling of blood signals while tanycytes limit spread to surrounding brain tissue.
- Drug Delivery Challenges: Small lipid-soluble drugs, barrier disruption (e.g. focused ultrasound), and “Trojan-horse” strategies each have limitations; intranasal delivery shows rapid brain distribution.
- Peptides & Brain Effects: Gut peptides like GLP-1 analogs, insulin, and ghrelin influence cognition and memory; brain entry predicts central effects.
GUEST: William Banks, MD is a physician-scientist and leading researcher on the blood-brain barrier. He has focused on humoral brain-body communication, peptide transport, and the barrier’s role in health and disease.
RELATED CONTENT:
- M&M 298 | GLP-1s & Novel Peptides in Obesity, Diabetes & Metabolic Health | Katrin Svensson
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
Too Much Iron and the Aging Brain | Dr. Pamela Maher | Ep 299
Send us Fan MailFerroptosis, an iron-dependent cell death pathway driven by lipid peroxidation; chronoferoptosis, in which chronic stress sensitizes neurons gradually.TOPICS DISCUSSED:Cell Death Pathways …
Show notes
Ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation; chronoferoptosis, in which chronic stress sensitizes neurons gradually.
TOPICS DISCUSSED:
- Cell Death Pathways: Apoptosis proceeds through regulated steps with surface “eat me” signals that enable non-inflammatory clearance by phagocytes, whereas ferroptosis and related pathways release cellular contents that can amplify local damage and inflammation.
- Ferroptosis Discovery: Work on glutamate toxicity in neuronal cell lines first identified a glutathione-depletion pathway termed oxytosis; parallel studies in cancer cells renamed and generalized it as ferroptosis to highlight iron’s catalytic role.
- Lipid Peroxidation: Polyunsaturated fatty acids in membranes are oxidized non-enzymatically when ferrous iron reacts with hydrogen peroxide in the Fenton reaction, generating hydroxyl radicals that produce toxic lipid peroxides and reactive carbonyls that modify proteins.
- GPX4 & Glutathione: Glutathione peroxidase-4 is an enzyme that reduces lipid peroxides within membranes and requires glutathione as cofactor; depletion of either component removes this critical line of defense.
- Chronoferoptosis: Nine-day treatment of differentiated neuronal cells with chronic iron or glutathione synthesis inhibitor reduced GPX4 protein, raised basal lipid peroxidation, and increased cell death after addition of otherwise sublethal secondary stressors.
- Protective Compounds: Screening identified flavonoids such as fisetin and sterubin plus synthetic molecules J-147 and CMS-121 that block lipid peroxidation directly or indirectly and, in several cases, also raise glutathione levels.
- Human Disease Evidence: Postmortem brain tissue from Alzheimer’s and Parkinson’s patients shows elevated lipid peroxidation markers and altered iron handling in vulnerable regions; similar changes appear in animal models of multiple diseases.
- Dietary & NRF2 Links: Compounds that activate the NRF2 transcription factor, including sulforaphane from broccoli and certain flavonoids, upregulate antioxidant enzymes including GPX4 and may support long-term cellular resilience.
ABOUT THE GUEST: Pamela Maher, PhD is a research professor at the Salk Institute for Biological Studies in La Jolla, California. Her laboratory studies ferroptosis mechanisms in neurodegenerative diseases and works to identify compounds that inhibit iron-dependent lipid peroxidation.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
Ozempic Reaches Your Brain in Ways Your Own GLP-1 Can't | Katrin Svensson | Ep 298
Send us Fan MailEndogenous peptide diversity, GLP-1 drugs, and methods for novel peptide discovery.TOPICS DISCUSSED:Peptide Structure & Production: Short amino acid chains (3-50 residues) cleaved from larger …
Show notes
Endogenous peptide diversity, GLP-1 drugs, and methods for novel peptide discovery.
TOPICS DISCUSSED:
- Peptide Structure & Production: Short amino acid chains (3-50 residues) cleaved from larger precursors by PCSK enzymes, stored in dense-core vesicles, and released upon stimuli rather than acting as folded enzymes like proteins.
- Tissue-Specific Processing: The same precursor yields different peptides by tissue; preproglucagon produces glucagon in pancreas but GLP-1 in gut L-cells due to distinct cleavage patterns.
- Signaling Timescales: Peptides act over minutes via GPCRs and can drive longer transcriptional changes such as FOS expression, yet are cleared rapidly by proteases and kidneys.
- Endogenous GLP-1: Meal-stimulated incretin from gut that boosts insulin secretion with a half-life of only minutes, limiting primary action to periphery rather than deep brain structures.
- GLP-1 Engineering for Brain Access: DPP4 site mutations plus lipid conjugation enable albumin binding, extend half-life, and raise brain exposure.
- Dose-Dependent Effects: Low GLP-1 doses mainly lower blood glucose via pancreas; higher doses engage hindbrain and hypothalamic neurons to suppress appetite and alter food preference.
- Novel Peptide Discovery: Computational scans across the genome flag hundreds of uncharacterized precursors, facilitating new peptide discovery.
- BRP Peptide: This newly discovered brain-derived peptide suppresses feeding in GLP-1 receptor knockout mice, activates non-overlapping neurons, and does not slow gastric emptying.
ABOUT THE GUEST: Katrin Svensson, PhD, is a biochemist and physiologist who leads a laboratory at Stanford University focused on peptide hormone physiology and the regulation of energy balance.
PRACTICAL TAKEAWAYS:
- GLP-1 drugs require higher doses to engage brain satiety circuits for meaningful weight loss; lower doses primarily improve glucose control with little effect on appetite.
- Response varies widely across individuals, with some losing over 25% body weight while others see minimal change.
- Emerging peptides under study may suppress appetite via brain pathways that avoid the gastric slowing responsible for common GI side effects of current GLP-1 drugs.
- Research peptides purchased online frequently show variable purity below pharmaceutical standards and may contain unsafe formulation components or aggregates.
Support my work:
- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
- Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health.
For all the ways you can support my efforts.
Can Water Low in Deuterium Slow Cancer? | Gábor Somlyai | Ep 297
Send us Fan MailThe possible role of deuterium (heavy isotope of hydrogen) in regulating cell division, mitochondrial metabolism & cancer.TOPICS DISCUSSED:Deuterium Basics: Deuterium is twice as massive as …
Show notes
The possible role of deuterium (heavy isotope of hydrogen) in regulating cell division, mitochondrial metabolism & cancer.
TOPICS DISCUSSED:
- Deuterium Basics: Deuterium is twice as massive as regular hydrogen; natural water contains ~150 ppm, with stronger oxygen-deuterium bonds slowing reactions compared to oxygen-hydrogen.
- Mitochondrial Role: Healthy mitochondria produce deuterium-depleted metabolic water (~110 ppm from fat oxidation vs. ~150 ppm from carbs), helping maintain low cellular D:H ratios.
- Cell Growth Regulation: Lower deuterium slows cell division in vitro; cells sense small D:H changes, with higher levels (near/above 150 ppm) promoting growth.
- In Vitro Evidence: DDW (e.g., 25-125 ppm) can reduce proliferation and alters cancer-related gene expression.
- Animal Models: DDW caused tumor regression in mice with transplanted human cancers and showed possible efficacy in veterinary use for dogs and cats.
- Human Prostate Cancer: Phase 2 randomized study showed greater Prostate-Specific Antigen (PSA) reduction, tumor shrinkage, and better 1-year survival with DDW plus standard therapy vs. placebo.
- Dietary Modulation: Ketogenic/high-fat diets lower body deuterium from lipid oxidation.
- Broader Implications: Potential in neurodegeneration models; larger trials needed for registration as adjunct cancer therapy.
ABOUT THE GUEST: Gábor Somlyai, PhD is a molecular biologist who pioneered deuterium depletion studies at the National Institute of Oncology in Hungary. His primary work focuses on the role of deuterium in living organisms and the development of deuterium-depleted water for cancer therapy.
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Antioxidant Supplements Raised Cancer Rates in Major Trials. Here's Why | Isaac Harris | Ep 296
Send us Fan MailNew research finds that excess antioxidants can support tumor growth in preexisting cancers.TOPICS DISCUSSED:Oxidative Stress: Reactive oxygen species (ROS) generated by mitochondrial metabolism …
Show notes
New research finds that excess antioxidants can support tumor growth in preexisting cancers.
TOPICS DISCUSSED:
- Oxidative Stress: Reactive oxygen species (ROS) generated by mitochondrial metabolism cause damage; context determines whether they promote or suppress cancer.
- Glutathione Biology: Primary cellular antioxidant made from cysteine, glycine, and glutamate; works with peroxidase enzymes to protect against ROS.
- Antioxidant Paradox: Clinical trials (SELECT vitamin E, beta-carotene) showed supplements increased cancer rather than preventing it.
- Cancer Antioxidant Hijacking: Tumors ramp up antioxidant systems to handle high metabolic rates and survive stress including metastasis.
- Extracellular Glutathione Catabolism: Cancer cells break down external glutathione into amino acids, particularly cysteine, to fuel growth (new findings).
- Therapeutic Window: Blocking glutathione breakdown slows tumors in models while sparing normal cells.
- Diet vs Supplements: Balanced diets support glutathione needs; excess isolated antioxidants may enrich the tumor microenvironment.
ABOUT THE GUEST: Isaac Harris, PhD is a biologist working on the role of antioxidants in health, disease, and cancer metabolism.
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Your Body Makes Fructose From Glucose, and It Turns On Fat Storage | Richard Johnson | Ep 295
Send us Fan MailFructose survival hypothesis: how fructose metabolism in the liver triggers ATP depletion, uric acid production, oxidative stress, lipogenesis & leptin resistance.TOPICS DISCUSSED:Glucose vs …
Show notes
Fructose survival hypothesis: how fructose metabolism in the liver triggers ATP depletion, uric acid production, oxidative stress, lipogenesis & leptin resistance.
TOPICS DISCUSSED:
- Glucose vs Fructose Metabolism: Fructose is rapidly metabolized in the liver by fructokinase without feedback, causing ATP depletion and uric acid production, unlike glucose metabolism.
- Liver Effects: Fructose induces uric acid production, NADPH oxidase activation, mitochondrial oxidative stress, and de novo lipogenesis even under caloric restriction.
- Fructose Survival Hypothesis: Fructose signaling promotes fat storage, leptin resistance, foraging behavior, and metabolic syndrome as adaptations for hibernation or starvation, including metabolic water production.
- Brain Impacts: Endogenous fructose production from glucose (polyol pathway) triggered by high glucose, salt, or stress leads to insulin resistance, mitochondrial damage, and neuroinflammation in Alzheimer’s-vulnerable regions.
- Evolutionary Context: Human uricase mutation ~12 million years ago enhanced fructose effects for fat storage during seasonal starvation but increases vulnerability today.
- Modern Triggers: Added sugars, high fructose corn syrup, salt-sugar combinations, and omega-6 fats synergize with fructose to amplify inflammation, appetite, and disease risk.
- Alzheimer’s Link: Fructose-driven brain changes mirror Alzheimer’s pathology, with high brain fructose in patients and potential for fructokinase inhibitors as therapy.
ABOUT THE GUEST: Richard Johnson MD, is a professor of medicine who has conducted clinical practice and NIH-funded research on sugar metabolism since the late 1990s. His work focuses on the role of fructose in metabolic syndrome, obesity, and related diseases.
RELATED CONTENT:
- Article | Dietary Fructose & Metabolic Health: An Evolutionary Perspective
- M&M 249: Fructose, Microglia, Anxiety & Brain Development | Justin Perry | 249
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How to Lie With Science: Seed Oils & Inflammation | Livestream
Send us Fan MailDeep-dive into a 2026 cardiology review paper claiming seed oils reduce inflammation, exposing misrepresentations of cited clinical trials, and detailing how oxidized Ω-6 fats trigger …
Show notes
Deep-dive into a 2026 cardiology review paper claiming seed oils reduce inflammation, exposing misrepresentations of cited clinical trials, and detailing how oxidized Ω-6 fats trigger inflammation.
Companion article: Click HERE
TOPICS DISCUSSED:
- Seed Oil Profiles: Typical seed oils like sunflower are high in linoleic acid (omega-6 PUFA), while canola is higher in monounsaturated fats and resembles olive oil.
- Review Paper Critique: The 2026 JACC review falsely claims sunflower oil reduce inflammation like olive oil, citing an RCT that showed benefits only for canola and olive.
- RCT Analysis: In Iranian women with metabolic issues, switching to canola or olive oil lowered CRP by increasing MUFA and decreasing PUFA intake; sunflower oil produced no change.
- CRP Biology: CRP responds to oxidized lipids and cellular damage patterns, rising with exercise or infection and marking oxidized Ω-6 metabolites in modern diets.
- Oxidized Lipids: Ω-6 fats in LDL and cardiolipin oxidize easily, generating 4-HNE, MDA, and other signals that trigger immune clearance, similar to bacterial threats.
- Sterile Inflammation: High dietary linoleic acid causes chronic immune activation without pathogens, potentially contributing to metabolic and cardiovascular issues.
PRACTICAL TAKEAWAYS:
- Prioritize monounsaturated fats from olive or avocado oil over high-linoleic seed oils like standard sunflower or soybean for lower oxidative stress potential.
- Check labels for high-oleic versions of sunflower oil, which shift the profile toward monounsaturated fats.
- Evaluate nutrition claims by examining original studies and fatty acid compositions rather than accepting review summaries at face value.
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- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
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Your Ancestry Changes How Your Body Handles Omega-3 and Omega-6 Fats | Floyd Chilton | Ep 294
Send us Fan MailHuman genetic variation in dietary fat metabolism and its implications for health & disease.TOPICS DISCUSSED:Linoleic Acid Rise: Linoleic acid now comprises 6-8% or more of energy in Western …
Show notes
Human genetic variation in dietary fat metabolism and its implications for health & disease.
TOPICS DISCUSSED:
- Linoleic Acid Rise: Linoleic acid now comprises 6-8% or more of energy in Western diets.
- Metabolic Pathways: Omega-6 linoleic acid converts to arachidonic acid and pro-inflammatory oxylipins; omega-3 ALA converts via shared enzymes to EPA/DHA with anti-inflammatory effects.
- FADS Genetic Variants: Ancestry-linked haplotypes in the FADS cluster create large “pipe” size differences, altering fatty acid by up to 40% between ancestral and derived versions.
- Population Differences: African ancestry populations often have high-conversion “big pipe” genotypes; Indigenous American ancestry populations have low-conversion “small pipe” genotypes; European ancestry comes with a mix of both.
- Omega-3 Deficiency: High linoleic intake suppresses EPA production, especially in small-pipe populations, contributing to hypertriglyceridemia and fatty liver in Mexican cohorts.
- Clinical Evidence: Reanalysis of VITAL trial showed 83% reduction in myocardial infarction with omega-3 supplementation in African Americans; Mexican data link low EPA to unique diabetes forms.
- Methodological Issues: Compositional data (from GC-FID measurements) versus absolute concentration measurements can flip relationships between linoleic acid and key biomarkers.
ABOUT THE GUEST: Floyd Chilton PhD is Professor and Director of the Center for Precision Nutrition and Wellness at the University of Arizona. His research focuses on functional genomics, fatty acid metabolism, and precision nutrition, particularly how genetic ancestry influences responses to dietary fats.
RELATED EPISODE:
- M&M 291: Omega Polyunsaturated Fats & Inflammation | Philip Calder
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A Brain Steroid Showed Antidepressant Effects in Bipolar Disorder | Sherwood Brown | Ep 293
Send us Fan MailPregnenolone, a neurosteroid derived from cholesterol, affects brain activity and shows promise for treating mood and substance abuse disorders.TOPICS DISCUSSED:Steroid Biosynthesis: Cholesterol …
Show notes
Pregnenolone, a neurosteroid derived from cholesterol, affects brain activity and shows promise for treating mood and substance abuse disorders.
TOPICS DISCUSSED:
- Steroid Biosynthesis: Cholesterol converted to pregnenolone, the precursor for all steroid hormones including cortisol, aldosterone, and sex hormones.
- Corticosteroids: Synthetic versions like prednisone primarily target glucocorticoid receptors for anti-inflammatory uses but can impact mood and cognition.
- Pregnenolone Mechanisms: Positive allosteric modulator of NMDA receptors for cognition and negative allosteric modulator of CB1 cannabinoid receptors.
- Allopregnanolone: GABAergic derivative of pregnenolone; its IV form Brexanolone is FDA-approved for postpartum depression.
- Clinical Trials: Pregnenolone at 100-500 mg improved depressive symptoms in placebo-controlled studies of bipolar disorder patients.
- Cannabis Interaction: THC robustly induces brain pregnenolone production; supplementation may reduce cannabis and alcohol use.
- Corticosteroid Brain Impact: Prednisone use associated with smaller hippocampal volumes and memory deficits.
ABOUT THE GUEST: Sherwood Brown, MD, PhD is Vice Chair for Clinical Research in the Department of Psychiatry at the University of Texas Southwestern Medical Center in Dallas. With a background in chemistry, his research focuses on steroids and comorbidities in people with mood disorders.
RELATED EPISODE:
- M&M 124: Hormonal Contraception, Sex Hormones, Menstruation, Pregnancy, Puberty, Estrogens, Androgens, Effects of Birth Control on Cognition | Adriene Beltz
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Most Americans Fall Far Below the Omega-3 Levels Linked to Better Health | Bill Harris | Ep 292
Send us Fan MailHow omega-3 fats in human health, including dietary intake needs, supplements, & omega fat testing.TOPICS DISCUSSED:ω-3 chemistry: EPA and DHA differ from plant ALA in chain length and …
Show notes
How omega-3 fats in human health, including dietary intake needs, supplements, & omega fat testing.
TOPICS DISCUSSED:
- ω-3 chemistry: EPA and DHA differ from plant ALA in chain length and double-bond count, making them structurally and biologically distinct — and largely irreplaceable by ALA conversion.
- ALA-to-EPA/DHA conversion: A small percentage of dietary ALA converts to EPA, and conversion to DHA is even lower; vegans rely on this inefficient pathway for all long-chain omega-3s.
- Cardiovascular mechanisms: ω-3s lower triglycerides, reduce platelet stickiness, improve endothelial function, and slow resting heart rate, reducing cardiovascular risk.
- ω-3 Index: Defined as red blood cell EPA+DHA as a percent of total fatty acids; 8–12% is the target range, while most Americans sit around 4–5%.
- Brain & dementia risk: Higher DHA blood levels are associated with significantly lower risk of dementia and Alzheimer’s in large cohorts including the UK Biobank and Framingham.
- Linoleic acid nuance: Higher blood levels of dietary linoleic acid (omega-6) associate with lower dementia and cardiovascular risk; downstream omega-6 metabolites — not linoleic acid itself — associate with adverse outcomes.
- Supplementation practicalities: Most people need 1–2 g/day of EPA+DHA to reach an ω-3 Index >8%; oxidation concerns with fish oil supplements may be overstated.
ABOUT THE GUEST: Bill Harris, PhD is founder of both OmegaQuant Laboratory and the Fatty Acid Research Institute (Sioux Falls, SD), where his work centers on blood fatty acid biomarkers as predictors of disease risk in large population cohort studies.
KNOW YOURSELF:
- OmegaQuant: At-home blood testing to see fatty acid profiles, including omega-3 fatty acids. Use link to see options and support M&M.
RELATED EPISODE:
- M&M 134: Omega Fats, Vegetable & Seed Oils, Sugar, Processed Food, Metabolic Health & Dietary Origins of Chronic Inflammatory Disease | Artemis Simopoulos
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Inflammation Doesn't Just Fade. Omega-3s Help Your Body Switch It Off | Philip Calder | Ep 291
Send us Fan MailHow dietary fatty acids regulate the initiation, propagation, and resolution of inflammation.TOPICS DISCUSSED:Parenteral nutrition history: IV nutrition evolved from soybean oil alone in the …
Show notes
How dietary fatty acids regulate the initiation, propagation, and resolution of inflammation.
TOPICS DISCUSSED:
- Parenteral nutrition history: IV nutrition evolved from soybean oil alone in the 1960s to complex blends including fish oil as the biology of ω-3s became understood.
- Three phases of inflammation: Initiation, propagation (driven by ω-6–derived prostaglandins and leukotrienes), and active resolution (driven by ω-3-derived resolvins and protectins).
- Pro-resolving mediators: Resolution is an active biological process, not passive; EPA and DHA generate resolvins and protectins that actively terminate inflammation.
- Aspirin’s ω-3 mechanism: Aspirin inhibits arachidonic acid metabolism but allows EPA/DHA to access COX-2, upregulating pro-resolution mediators — a likely underappreciated mechanism of action.
- Cell membrane competition: EPA and DHA physically displace arachidonic acid in membranes, shifting the balance of mediators produced and improving resolution capacity.
- Linoleic acid & EPA synthesis: High linoleic acid intake saturates shared desaturase enzymes, inhibiting the body’s conversion of ALA to EPA — meaning reducing ω-6 can raise ω-3 levels without supplementation.
- Dose & timing of ω-3 incorporation: ~2g/day of EPA+DHA shifts the arachidonic acid-to-EPA ratio enough to measurably reduce prostaglandin E2 production; white blood cells reflect changes within a month.
ABOUT THE GUEST: Philip Calder, PhD is Professor of Nutritional Immunology in the Faculty of Medicine at the University of Southampton. His research focuses on how dietary fatty acids — particularly omega-3s — modulate immune responses and inflammatory processes across clinical and healthy populations.
RELATED EPISODE:
- M&M 200: Dietary Fats & Seed Oils in Inflammation, Colon Cancer & Chronic Disease | Tim Yeatman & Ganesh Halade
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Reversing Alzheimer's Memory Loss in Mice Without Clearing Plaques | Andrew Pieper | Ep 290
Send us Fan MailA metabolic view of Alzheimer's disease & the recent discovery of compounds that reverse advanced disease symptoms in mouse models by restoring mitochondrial health.TOPICS DISCUSSED:Classic …
Show notes
A metabolic view of Alzheimer's disease & the recent discovery of compounds that reverse advanced disease symptoms in mouse models by restoring mitochondrial health.
TOPICS DISCUSSED:
- Classic Alzheimer’s pathology: amyloid plaques and tau tangles identified over 120 years ago, long assumed to drive irreversible neuron loss.
- Limitations of amyloid focus: plaques appear in some cognitively normal brains; antibody therapies have shown limited clinical benefit.
- Metabolic perspective: brain energy failure as a tipping point where repair mechanisms are overwhelmed, linking genetics, injury, and aging.
- Neuroprotection via P7C3 compounds: discovered through hippocampal neurogenesis screen; preserves mitochondrial function and normalizes NAD/NADH ratio without elevating NAD excessively.
- Recovery in models: treatment after symptom onset reversed cognitive deficits, blood-brain barrier damage, oxidative stress, and axon issues in amyloid and tau mouse models, despite persistent plaques.
- Broader implications: energy restoration enables surviving neurons to function; similar protective effects seen in TBI and other organs under stress.
ABOUT THE GUEST: Andrew Pieper, MD, PhD, is a board-certified psychiatrist and neuroscientist, professor at Case Western Reserve University, and director of the Brain Health Medicines Center at the Harrington Discovery Institute. He directs a research group focused on neuroprotection after brain injury and neurodegenerative disease.
RELATED EPISODE:
- M&M 208: Glyphosate, Choline & Alzheimer’s: Toxins & Nutrition to Prevent Neurodegeneration | Ramon Velazquez
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Parents' Exercise Improves Offspring Metabolism via Sperm and Milk | Kristin Stanford | Ep 289
Send us Fan MailHow exercise in parents can improve the metabolic and cardiovascular health of their offspring through epigenetic mechanisms.TOPICS DISCUSSED:Parental exercise & offspring metabolic health …
Show notes
How exercise in parents can improve the metabolic and cardiovascular health of their offspring through epigenetic mechanisms.
TOPICS DISCUSSED:
- Parental exercise & offspring metabolic health: exercise before and during pregnancy improves glucose tolerance and reduces fat gain in offspring.
- Paternal effects via sperm: moderate voluntary wheel running alters small non-coding RNAs, especially tRNA fragments, in sperm and enhances glucose clearance, with stronger benefits in female offspring.
- Maternal exercise mechanisms: benefits arise from in utero environment, placental changes, and breast milk composition rather than major oocyte alterations.
- Human milk oligosaccharides: exercise increases 3’-sialyllactose in milk, linked to better offspring microbiome and metabolic outcomes.
- Sex-biased & intergenerational effects: maternal exercise impacts male offspring metabolism more; effects can transmit to F2 generation depending on the transmitting parent’s sex.
ABOUT THE GUEST: Kristin Stanford, PhD is an associate professor in the Department of Physiology and Cell Biology at The Ohio State University Wexner Medical Center, where she serves as associate director of the Diabetes and Metabolism Research Center. Her lab investigates molecular mechanisms by which exercise enhances metabolic and cardiovascular health, with a focus on intergenerational effects.
RELATED EPISODE:
- M&M 145: Epigenetics, Endocrine Disruptors, Obesogens & Obesity, Inheritance of Acquired Characteristics | Bruce Blumberg
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Your Vagus Nerve Can Switch Off Inflammation | Kevin Tracey | Ep 288
Send us Fan MailHow the vagus nerve regulates inflammation; bioelectronic therapies to treat inflammatory conditions.Nick speaks with Dr. Kevin Tracey about inflammation as a major driver of modern diseases …
Show notes
How the vagus nerve regulates inflammation; bioelectronic therapies to treat inflammatory conditions.
Nick speaks with Dr. Kevin Tracey about inflammation as a major driver of modern diseases, the vagus nerve’s role in balancing immune responses via reflexes, limitations of anti-cytokine drugs, and emerging bioelectronic medicine using targeted nerve stimulation.
TOPICS DISCUSSED:
- Inflammation is related to diseases that contribute to most deaths today: heart disease, diabetes, neurodegeneration, and cancer.
- Molecular signals involved in inflammation, such as cytokines.
- Homeostasis is maintained by push-pull mechanisms, with excitatory and inhibitory responses co-deployed in ways that maintains balance.
- The vagus nerve’s anatomy, sensory/motor fibers, and the inflammatory reflex that suppresses cytokine production in the spleen via acetylcholine and norepinephrine.
- Vagus nerve stimulation devices delivering brief daily pulses to reduce inflammation without broad immunosuppression, now FDA-approved for refractory rheumatoid arthritis.
- Challenges in measuring inflammation and oversimplifications online about “stimulating” the vagus nerve.
ABOUT THE GUEST: Kevin Tracey, MD is a neurosurgeon, president and CEO of the Feinstein Institutes for Medical Research at Northwell Health, and professor of molecular medicine and neurosurgery. He discovered the inflammatory reflex, showing how the vagus nerve controls immune responses, and co-founded SetPoint Medical to develop FDA-approved vagus nerve stimulation for rheumatoid arthritis.
RELATED EPISODE:
- M&M 143: Gut-Brain Communication, Vagus Nerve, Fats & Sugars, Food Addiction, Gut Hormones & Weight Loss Drugs | Will de Lartigue
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- Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly.
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Sunlight Curbs Appetite Through a Hormone Unrelated to Vitamin D | Alexis Cowan | Ep 287
Send us Fan MailHow light regulate circadian rhythms, mitochondrial function, hormones, and appetite.Nick & Dr. Alexis Cowan discuss non-image-forming effects of light on the body, from melanopsin-driven …
Show notes
How light regulate circadian rhythms, mitochondrial function, hormones, and appetite.
Nick & Dr. Alexis Cowan discuss non-image-forming effects of light on the body, from melanopsin-driven circadian signaling in the eye to UV-stimulated pathways in skin and brain that influence melatonin, cortisol, melanin production, and energy balance.
TOPICS DISCUSSED:
- Melanopsin & non-image-forming light: blue light signals daytime to the SCN master clock, suppressing melatonin and promoting alertness.
- UV light, POMC & peptide hormones: UVB exposure in skin and hypothalamus produces alpha-MSH (reduces appetite, boosts energy expenditure) and beta-endorphin (improves mood), independent of vitamin D.
- Mitochondrial effects of light: red/infrared supports function like a gas pedal; isolated blue light acts as brakes, impairing energy production and biophoton signaling.
- Artificial light: Evening blue light from screens inhibits melatonin, poisons mitochondria, and creates discordant timing signals versus balanced natural sunlight.
- Melanin beyond skin: produced via UVB, it harnesses energy, buffers oxidative stress, and links to dopamine pathways; low sun exposure ties to metabolic issues and conditions like Parkinson’s.
- Vitamin D as biomarker: supplementation shows limited benefits because it reflects broader UVB-driven processes, not a standalone fix.
ABOUT THE GUEST: Alexis Cowan, PhD earned her PhD in molecular biology at Princeton in the Rabinowitz lab, a leading metabolism research group, where she studied fasting, ketogenic diets, and exercise; she completed a postdoc at UPenn before shifting focus to circadian and quantum biology. She now educates on light, mitochondria, and quantum biology.
RELATED EPISODE:
- M&M 221: Regenerative Energy & the Light Inside You | Jack Kruse
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Being Awake Damages Brain Fats, and Sleep Clears Them Out | Amita Sehgal | Ep 286
Send us Fan MailIs the fundamental purpose of sleep to remove oxidized fats from the brain?Nick & Dr. Amita Sehgal talk about the latest science on why animals sleep. Using fruit flies, her lab shows that …
Show notes
Is the fundamental purpose of sleep to remove oxidized fats from the brain?
Nick & Dr. Amita Sehgal talk about the latest science on why animals sleep. Using fruit flies, her lab shows that waking generates oxidized lipids in neurons that are shuttled to glia and then cleared by macrophage-like cells during sleep. This process protects mitochondria, supports memory, and links sleep to metabolic cleanup rather than just rest.
TOPICS DISCUSSED:
- Drosophila as a model: Fruit flies sleep with immobility, reduced responsiveness, and homeostatic rebound; their genetics reveal conserved mechanisms found in humans.
- Circadian vs homeostatic sleep: Circadian timing sets when we sleep; homeostatic drive builds need from prolonged wakefulness independent of time of day.
- Metabolic waste during wake: Neuronal activity oxidizes lipids in mitochondria; these damaged lipids transfer to glial support cells via apolipoproteins.
- Immune cells clear brain trash: Macrophage-like hemocytes dock at the brain during sleep, phagocytose oxidized lipids, and remove them; blocking this docking reduces sleep and impairs memory.
- Peroxisomes & oxidative stress: These organelles handle specific fats and rise with wakefulness; disrupting them increases brain oxidation that can be partially rescued by antioxidants like N-acetylcysteine.
- Sickness sleep differs from normal sleep: Infection-induced sleep redirects energy to immune defense and depletes rather than restores brain energy stores.
ABOUT THE GUEST: Amita Sehgal, PhD is the John Herr Musser Professor of Neuroscience at the University of Pennsylvania, an HHMI Investigator, and director of the Chronobiology and Sleep Institute. She uses Drosophila genetics to uncover basic mechanisms of circadian rhythms and sleep.
RELATED EPISODE:
- M&M 257: Sleep, Mitochondrial Metabolism & Oxidative Stress | Gero Miesenbock
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BPC-157 Heals Rats but Has Barely Been Tested in Humans | Flynn McGuire | Ep 285
Send us Fan MailThe science, hype, and unknowns surrounding popular peptides like BPC-157 & TB-500 ("Wolverine stack") for injury recovery & tissue repair.Nick & Dr. Flynn McGuire discuss the surge in peptide …
Show notes
The science, hype, and unknowns surrounding popular peptides like BPC-157 & TB-500 ("Wolverine stack") for injury recovery & tissue repair.
Nick & Dr. Flynn McGuire discuss the surge in peptide use for injury recovery. They cover peptide basics, the preclinical evidence for BPC-157 and TB-500, mechanisms like angiogenesis and tissue repair, the lack of robust human trials, sourcing risks, regulatory bans, and the gap between anecdotal reports and scientific certainty.
TOPICS DISCUSSED:
- Peptide basics: Short amino acid chains (e.g., insulin, GLP-1 agonists); BPC-157 derived from gastric juice, TB-500 a fragment of thymosin beta-4.
- Rise in popularity: Driven by podcasts, social media, biohacking culture, and post-COVID distrust in institutions; “bro science” often precedes formal research.
- BPC-157 mechanisms: Pleiotropic effects including VEGF upregulation, nitric oxide pathways, angiogenesis, reduced fibrosis, and possible neuromuscular stabilization.
- TB-500 & “stacking”: Often combined with BPC-157 for presumed synergy; marketed as “Wolverine stack” for rapid healing.
- Evidence limitations: Strong rodent data for tendon/muscle repair, but almost no high-quality human trials; one small retrospective study and ongoing phase 2 trial in China.
- Safety and risks: Unknown long-term effects, potential cancer concerns via angiogenesis; no established dosing, potency, or administration route in humans.
- Sourcing & quality issues: Often obtained as “research chemicals” online; variable purity, stability concerns, no reliable regulation or third-party verification for most users.
ABOUT THE GUEST: Flynn Mcguire, MD is a physical medicine and rehabilitation resident at the University of Utah; he conducts clinical work in neurologic recovery and musculoskeletal care and has authored a narrative reviews on peptides for musculoskeletal healing.
RELATED EPISODE:
- M&M 252: Scarring, Fibrosis, Oxidative Stress, and Psilocybin & Aging | Louise Hecker
Reference Paper:
- Paper | Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing
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Why Some People Stay Thin Even When They Overeat | Jens Lund | Ep 284
Send us Fan MailBiology of obesity resistance and factors influencing weight gain in humans and animals.TOPICS DISCUSSED:Historical views on obesity: In some cultures, like northern Africa or Stone Age …
Show notes
Biology of obesity resistance and factors influencing weight gain in humans and animals.
TOPICS DISCUSSED:
- Historical views on obesity: In some cultures, like northern Africa or Stone Age societies, high body fat signaled status or attractiveness due to food scarcity, unlike today’s focus on leanness amid calorie abundance.
- Energy balance components: Metabolizable energy (95% absorption on average, but varying 1-11%) and unabsorbed nutrients excreted as waste significantly influence weight.
- Obesity resistance in animals: Inbred mouse strains show wide variation in weight gain on high-fat diets, often somewhat uncoupled from overeating, suggesting roles for feed efficiency, energy expenditure, or waste rather than intake alone.
- Genetic & twin studies: Monozygotic twins overfed 1,000 extra calories daily vary widely in weight gain (4-13 kg), indicating genetic influences, while mouse litter size affects lifelong obesity propensity via early-life programming.
- Bloodborne factors & hormones: Parabiosis studies led to leptin’s discovery for defending against weight loss, but evolutionary logic suggests systems also prevent excess gain, though modern environments may weaken this.
- Human thinness research: Constitutionally thin people snack more, move less, yet have better cardiometabolic health, but we don’t yet understand why.
- GLP-1 drugs & future directions: These slow gut transit and suppress appetite, but obesity’s root causes remain unclear; emerging thinness studies could inform prevention beyond drugs.
ABOUT THE GUEST: Jens Lund, PhD is a postdoctoral researcher at the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research.
RELATED EPISODE:
- M&M 132 | Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUFAs, Energy Expenditure, Weight Gain & Feeding Behavior | John Speakman
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