Mind & Matter

• Fructose, Microglia, Anxiety & Brain Development | Justin Perry | 249

  Send us a textCellular clean up by immune cells and how early-life fructose exposure leads to neurodevelopmental problems.Episode Summary: Dr. Justin Perry talks about the body's constant cellular turnover—about 3 million cells die per second in adults (double in children and women)—handled by phagocytes like macrophages that engulf and digest debris to prevent diseases like lupus. They explore phagocytosis steps, macrophage adaptations in tissues like the brain (microglia), and how high fructose intake impairs microglial function in developing mice, leading to uncleared brain cells and anxiety-like behaviors, with implications for human neurodevelopmental disorders amid rising fructose consumption.About the guest: Justin Perry, PhD is an immunologist and clinical psychologist who leads a lab at Memorial Sloan Kettering Cancer Center focusing on how the body clears dead cells and debris to maintain homeostasis.Discussion Points:The body turns over 1-2% of its 30 trillion cells daily, mostly blood cells, but neurons in kids and endometrium in women turnover at ~2x this ratePhagocytosis involves "find me," "eat me," and digestion signals; failures can cause autoimmunity.Microglia are brain macrophages that uptake fructose via GLUT5 transporter.Early high fructose exposure (comparable to one soda daily) impairs the pruning of synapses and dead neurons.In mice, prenatal or postnatal fructose causes phagocytosis deficits in the prefrontal cortex, leading to heightened fear responses and poor fear extinction, mimicking anxiety disorders.Fructose correlates with rising neurodevelopmental issues like autism and anxiety; it's passed via breast milk, and liquid forms (e.g., sodas) overwhelm metabolic shields more than solid fruits.Macrophages may hold keys to diseases from atherosclerosis to cancer; deleting GLUT5 in microglia reverses fructose's effects, hinting at evolutionary roles in aging or low-oxygen states.Related content:M&M 215: Cancer Metabolism: Sugar, Fructose, Lipids & Fasting | Gary PattiArticle | Dietary Fructose & Metabolic Health: An Evolutionary PerspectiveReference Paper:Study | Early life high fructose impairs microglial phagocytosis and neurodevelopment*Not medical advice.Support the showAffiliates: Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. For all the ways you can support my efforts

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• Autism, Acetaminophen (Tylenol) & Oxidative Stress | William Parker | 248

  Send us a textThe potential link between acetaminophen (Tylenol) and autism, with a surprise phone call from RFK partway through.Episode Summary: Dr. William Parker talks about autism spectrum disorder (ASD), its rising prevalence since the 1980s, and the controversial hypothesis that acetaminophen exposure in susceptible infants and children triggers most cases via oxidative stress. They discuss ASD's clinical definition; historical misconceptions like the "refrigerator mother" theory; genetic susceptibilities; acetaminophen's metabolism, which produces toxic byproducts in underdeveloped livers, leading to brain effects.About the guest: William Parker, PhD spent nearly 30 years as a professor at Duke University researching underlying causes of chronic conditions, including discovering the immune function of the human appendix and pioneering studies on immune systems in wild animals.Discussion Points:Autism is a spectrum disorder with core symptoms like social deficits, repetitive behaviors, and aversion to new stimuli.Parker argues overwhelming evidence points to acetaminophen as the primary trigger in susceptible individuals, causing oxidative stress via toxic metabolite NAPQI.Acetaminophen, marketed as Tylenol or paracetamol, was not tested for neurodevelopmental effects in neonatal animals until 2014, despite widespread use since 1886; it's metabolized differently in babies, whose livers lack mature detox pathways.Susceptibility factors include low glutathione (an antioxidant), poor sulfation/glucuronidation metabolism, folate receptor autoantibodies, and events like immune reactions that prompt acetaminophen use during oxidative stress.Regressive autism, where children lose milestones after seeming normal, often follows acetaminophen given for fevers or illnesses, explaining parental vaccine suspicions (as shots coincide with drug use).Adult acetaminophen is generally safe but causes liver toxicity in overdoses or with alcohol; antidote is NAC to boost glutathione.Parker has suggested to policymakers that we should avoid acetaminophen during pregnancy, birth, and early childhood (under age 3-5); parents should plan ahead for fevers/pain without it, but seek medical help for unusual symptoms.*Not medical advice.Support the showAffiliates: Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. For all the ways you can support my efforts

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• Cholesterol: Immune Benefits, Heart Health, Statins & Research Malpractice | Uffe Ravnskov | 247

  Send us a textWide release date: August 25, 2025Episode Summary: Dr. Uffe Ravnskov talks about his decades-long career challenging the idea that high cholesterol causes heart disease, discussing LDL's protective role in the immune system by binding to bacteria, the harms and biases in statin research influenced by pharmaceutical companies, evidence that high cholesterol benefits the elderly and reduces infection/cancer risks, and how mental stress or infections elevate cholesterol as a response rather than a cause.About the guest: Uffe Ravnskov, MD, PhD is a physician and independent researcher who earned his MD from the University of Copenhagen in 1961 and a PhD in nephrology. He has worked in various clinics in Sweden since the 1960s, focusing his research on challenging the cholesterol hypothesis in heart disease. Now 91, he has published over 200 papers, authored books like "The Cholesterol Myths.”Discussion Points:LDL cholesterol helps the immune system by sticking to bacteria, clumping them for removal; low LDL increases infection risk.Animal studies show injecting LDL protects against lethal infections, while historical data links severe infections to worse atherosclerosis.Elderly people with high cholesterol live longer; low cholesterol raises mortality risk more than high levels.Familial hypercholesterolemia (FH) doesn't cause early death via cholesterol alone—co-inherited coagulation factors are the issue, and FH patients often have lower infection rates.Statins lower LDL but increase infection risk, cause muscle weakness/brain issues (often blamed on aging), and show no clear benefit in unbiased meta-analyses.Research biases include cherry-picking studies, exaggerating benefits via relative (not absolute) risk, and pharma funding suppressing critical views.Mental stress can raise cholesterol by 10-50% in 30 minutes, often misread as a heart disease cause rather than an effect.Saturated fat and high cholesterol aren't proven harmful; Ancel Keys' claims ignored contradictory evidence.Stopping statins often reverses side effects quickly, improving quality of life.Related episode:M&M 244: Seed Oils & Heart Disease: Oxidized LDL, Cholesterol, Fat & Cardiology | Tucker GoodrichReference Paper:LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature*Not medical advice.Support the showAffiliates: Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. For all the ways you can support my efforts

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• Appendix, Gut Worms, Allergies & Autoimmunity | William Parker | 246

  Send us a textThe appendix's hidden role and how "good" parasites like helminths shape immune health.Episode Summary: Dr. William Parker discusses gut anatomy, the appendix's role in harboring beneficial bacterial biofilms and immune tissue, and how modern hygiene depletes helminths (intestinal worms), causing immune overreactions like allergies, autoimmunity, and psychiatric conditions. He explores helminth self-therapy for treating relapsing MS, depression, and allergies; challenges in clinical trials due to patent issues; and why COVID-19 was milder in low-income, helminth-rich regions.About the guest: William Parker, PhD conducted research at Duke University for over 27 years on immunology, appendicitis, and the hygiene hypothesis. After retiring from Duke, he serves as a visiting scholar at the University of North Carolina at Chapel Hill, leading efforts on biome reconstitution via helminths.Discussion Points:Appendix is not vestigial; it concentrates immune tissue and biofilms to cultivate good gut bacteria, preventing pathogens via mucus and IgA antibodies.Hygiene hypothesis: Soap, toilets, and clean water reduce helminths/protozoa, leading to untrained, hyperactive immunity and rising allergies/autoimmunity since the 1800s.Helminths (worms) stimulate immune "exercise," training immunity; biohackers use hookworms (cheap, skin-entry), porcine whipworms, or rat tapeworms orally for relief from allergies, MS flares, depression/anxiety.Effects are temporary; need ongoing exposure (e.g., replenish every 6 months); immigrants from helminth-rich areas develop Western diseases within a few years.COVID-19: Hyper-immunity caused severe reactions in hygienic West, but helminth presence in low-income Africa/Asia prevented cytokine storms, leading to empty clinics.Therapy barriers: Non-patentable organisms require $100M+ trials; push for open-source, government-funded biome restoration over crude immunosuppressants.Related episode:M&M 144: Inflammation, Innate Immunity, Allergies & Allergens, Immune System Evolution, Fasting & Metabolism | Clare Bryant*Not medical advice.Support the showAffiliates: Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. For all the ways you can support my efforts

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• Cannabinoid System: Metabolism, Evolution & Energy Storage | Giovanni Marsicano | 245

  Send us a textWhat is the core evolved function of the endocannabinoid system?Episode Summary: Dr. Giovanni Marsicano is a neuroscientist based in Bordeaux, France, where he leads a research group at INSERM focusing on the endocannabinoid system.About the guest: Giovanni Marsicano, PhD discusses the endocannabinoid system, starting with its core components like CB1 receptors and lipid-based molecules derived from omega-6 fatty acids; its cellular signaling, evolutionary role in energy storage for uncertain futures (exostasis vs. homeostasis); effects across tissues; motivation, appetite, pain relief, and anxiety regulation; biphasic effects of cannabinoids.Discussion Points:The endocannabinoid system acts as an "exostatic" regulator, promoting energy accumulation for future needs by enhancing food palatability, nutrient absorption, and fat storage, unlike "endostatic" systems that address immediate hunger.CB1 receptors appear in vertebrates with adipose tissue, suggesting an evolutionary link to storing fat for survival in unstable environments.Endocannabinoids are lipids from omega-6 fats; high intake boosts their levels, potentially fueling obesity by creating a self-perpetuating cycle of overeating.Activation of CB1 can have biphasic effects due to receptors on different cell types like excitatory vs. inhibitory neurons.Pregnenolone, a steroid precursor, acts as a natural CB1 inhibitor to prevent excessive activation, blocking harmful effects like psychosis from high THC doses.The system influences motivation beyond food, including sex and even human activities like sports or storytelling, by rewarding actions for potential future benefits.In the brain, CB1 on mitochondria and astrocytes modulates energy use, olfaction, and social stress transmission, with implications for disorders like Alzheimer's.Reference Paper:CB1 Receptor as the Cornerstone of ExostasisRelated episode:M&M 123: Endocannabinoids, Stress, Anxiety, Cannabis | Matthew Hill*Not medical advice.Support the showAffiliates: Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. For all the ways you can support my efforts

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