Mind & Matter

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release: February 19, 2026. Not medical advice.TOPICS DISCUSSED:* Gene regulation basics: DNA transcribes to RNAs, including non-coding types like microRNAs that inhibit mRNA translation into proteins, influencing up to 60% of the proteome.* Non-coding RNAs in neuroplasticity: MicroRNAs and circular RNAs regulate synaptic changes, with activity-induced ones like miR-485-5p linked to rapid responses in drug cue memory and addiction reinforcement.* Opioid addiction models: Rats self-administer heroin or fentanyl via levers, showing compulsive seeking; fentanyl’s higher potency drives faster learning but similar long-term effects to heroin when doses are equated.* Differences between opioids: Heroin and fentanyl both activate mu-opioid receptors for euphoria and dopamine release, but fentanyl lingers longer; no major behavioral differences in seeking once potency is matched.* Psilocybin’s effects on addiction: A single psilocybin dose post-abstinence reduces heroin-seeking in rats by dampening neuroinflammation in brain regions like the nucleus accumbens and prefrontal cortex.* Brain Inflammation: Opioids induce pro-inflammatory changes via cytokines like IL-17A and pathways like TNF-alpha, leading to glial activation and blood-brain barrier leaks; psilocybin counters this.* MicroRNA biomarkers: Blood microRNAs reflect gene expression patterns tied to disease states, with potential to predict opioid relapse risk, treatment response, or neonatal withdrawal severity non-invasively.* Future research: Ongoing work links psilocybin’s serotonin 2A activation to anti-inflammatory gene changes, plus human studies on microRNAs for personalized addiction treatments.ABOUT THE GUEST: Stephanie Daws, PhD is an associate professor at Temple University in the Center for Substance Abuse Research and Department of Neurosciences, where she researches mechanisms of drug-seeking behavior with a focus on opioids and psychedelics.RELATED EPISODE:* M&M 2 | Psilocybin, LSD, Ketamine, Inflammation & Novel Psychedelic Medicines | Charles NicholsListen or watch on your favorite platform:* Audio version: [Apple] [Spotify] [Elsewhere]* Video version: [YouTube]* Support M&M if you find value in this content.PRACTICAL TAKEAWAYS:* For those in recovery, discuss medication options like buprenorphine or methadone with providers, as individual responses vary and biomarkers may one day guide choices.* Be aware of fentanyl’s extreme potency in street drugs, which heightens overdose risk.* Explore emerging psychedelic therapies under medical supervision, as psilocybin shows promise in reducing drug cravings via plasticity and inflammation modulation.SUBSCRIBER CONTENT BELOW: Reference paper + episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release: February 14, 2026. Not medical advice.TOPICS DISCUSSED:* Adipose tissue basics: White fat primarily stores energy in large lipid droplets, while brown fat burns fatty acids for heat via high mitochondrial density; white fat can “brown” with exercise or certain foods like capsaicin.* Fat distribution & health: Subcutaneous fat (under skin) is more insulin-sensitive and less problematic than visceral fat (around organs), which links to metabolic issues; females store more subcutaneously pre-menopause, shifting to visceral post-menopause.* Estrogen signaling: Estradiol binds nuclear and membrane receptors to regulate gene expression and mitochondrial function; it enhances insulin sensitivity and browning in fat cells, with receptors like ER-alpha feminizing fat distribution.* Fat storage: Fat cells enlarge (hypertrophy) more than multiply in obesity, leading to hypoxia, inflammation, and insulin resistance; excess fatty acids spill to liver and muscle, worsening metabolic dysfunction.* Menopause effects: Estrogen drop causes visceral fat gain, reduced energy expenditure, insulin resistance, and higher metabolic disease risk; symptoms include hot flashes and reduced exercise motivation, modeled in rodents via ovary removal.* Exercise & estrogen links: Exercise boosts estrogen receptor expression and mitochondrial density in fat, mimicking estrogen’s browning effects; synergism may explain reduced exercise responsiveness post-menopause.* Brain-fat connections: Estrogen in the nucleus accumbens influences exercise motivation and fat browning; manipulations there alter running behavior and adipose metabolism in rodents.ABOUT THE GUEST: Victoria Vieira-Potter, PhD leads a lab at the University of Missouri, studying how estrogen and exercise influence adipose cells.RELATED EPISODE:* M&M 174 | Adipose Tissue & Body Fat: Obesity, Insulin, Leptin, Fertility, Weight Loss & GLP-1 Drugs | Sean HartigListen or watch on your favorite platform:* Audio version: [Apple] [Spotify] [Elsewhere]* Video version: [YouTube]* Support M&M if you find value in this content.PRACTICAL TAKEAWAYS:* Regular exercise increases mitochondrial function and insulin sensitivity in fat cells, potentially aiding weight management and metabolic health for both sexes.* Post-menopausal women may benefit from maintaining physical activity to counter reduced energy expenditure and visceral fat gain, possibly buffering menopause symptoms.* Hormone therapy could improve metabolic outcomes like insulin sensitivity but requires physician consultation to weigh potential risks such as cancer.* Building lean muscle mass through resistance training supports basal metabolic rate as estrogen declines with age.SUBSCRIBER CONTENT BELOW: Reference paper + episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release: February 9, 2026. Not medical advice.TOPICS DISCUSSED:* Cerebral cortex structure: Described as a six-layered structure with pyramidal neurons and inhibitory interneurons; information flows between layers and regions to process sensory input and enable complex behaviors.* Claustrum anatomy & connectivity: A sheet-like subcortical structure embedded in white matter, bidirectionally connected to cortical areas, especially prefrontal regions in rodents, with broader connections in primates and humans suggesting an integrative role.* Claustrum function in cognition: Experiments show claustrum activation during task switches from easy to demanding modes, synchronizing cortical networks via inhibition and rebound excitation, potentially enabling flexible behavior.* Mouse models in neuroscience: Mice are used for genetic tractability to manipulate and monitor specific circuits, revealing claustrum’s role in vigilance tasks but not simple ones.* Alcohol’s effects on brain circuits: Chronic alcohol promotes inflexible behaviors by altering striatal interneurons and inhibitory inputs, leading to compulsive drinking despite aversive consequences.* Psychedelics & brain networks: Psilocybin disrupts default mode and other networks, inhibits claustrum via serotonin 1B receptors, with effects persisting 24 hours, possibly contributing to therapeutic benefits.* Evolution of claustrum: Connectivity expands from rodents to humans, shifting from cognitive-specific to broader network control, including anti-correlated states like default mode versus task-engaged.* Integration of claustrum & basal ganglia: Claustrum funnels prefrontal signals to basal ganglia for action selection; alcohol may impair this, exacerbating inflexibility in addiction.ABOUT THE GUEST: Brian Mathur, PhD is a professor in the Department of Pharmacology and Physiology at the University of Maryland School of Medicine, where he leads a neuroscience lab studying brain circuits underlying flexible and inflexible behaviors using mouse models, with a focus on alcohol use disorder.RELATED EPISODE:* M&M 226 | Psychedelics & Cerebral Cortex: Neuroplasticity, Psilocybin, Ketamine | Alex Kwan* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.PRACTICAL TAKEAWAYS:* Moderate alcohol consumption can impair decision-making and coordination by affecting prefrontal cortex and cerebellum, so limit intake during tasks requiring focus.* Chronic heavy drinking may lock in maladaptive habits; seeking therapy or support can help regain behavioral flexibility.* Psychedelics like psilocybin may reset rigid thought patterns in conditions like depression, but use under medical supervision for potential long-term benefits.SUBSCRIBER CONTENT BELOW: Reference paper + episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release: February 4, 2026. Not medical advice.TOPICS DISCUSSED:* Biased agonism: Different drugs activate the same receptor (e.g., 5-HT2A) but trigger varied intracellular pathways, explaining why LSD is psychedelic while similar lisuride is not.* Enantiomers & isomers: Mirror-image versions of drugs like MDMA (S and R forms) and LSD (four isomers) often produce distinct effects; only one LSD isomer is psychedelic, for example.* MDMA isomer effects: S-MDMA induces stronger head twitches (psychedelic proxy) via serotonin release, and increases dendritic spines in male mice but not females; R-MDMA has somewhat different effects.* Sex-specific drug responses: In mice, females show stronger psychedelic effects (head twitches) from psilocybin and DOI at the same dose, but males exhibit greater post-acute benefits like reduced opioid withdrawal.* Psilocybin in opioid addiction models: A single dose reduces place preference for oxycodone and withdrawal symptoms in male mice more than females, with opposite spine density effects in reward-related brain areas.* Mechanisms beyond 5-HT2A: Psychedelics involve other receptors like metabotropic glutamate receptors, forming dimers with 5-HT2A to enable dual signaling pathways; effects in subcortical regions like nucleus accumbens are 5-HT2A-independent.* Clinical implications: Street MDMA may vary in S/R ratios, affecting experiences; clinical trials often use racemic mixtures without weight-adjusted dosing, potentially missing sex differences.ABOUT THE GUEST: Javier Gonzalez-Maeso, PhD is a professor of pharmacology and toxicology at Virginia Commonwealth University, with a PhD in medicine from Spain focused on G-protein coupled receptors and human brain studies in depression and addiction.RELATED EPISODE:* M&M 230 | Psilocybin & MDMA: Inflammation, Stress & Brain-Body Communication | Michael Wheeler* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.SUBSCRIBER CONTENT BELOW: Practical takeaways, reference paper, episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release: January 25, 2026. Not medical advice.TOPICS DISCUSSED:* Cellular energy basics: ATP/ADP/AMP as energy currencies; AMP kinase activates on low ATP to conserve and redirect resources, like a budget manager.* AMP kinase mechanics: Heterotrimeric enzyme phosphorylating 100+ substrates; localizes dynamically in cytosol, mitochondria, nucleus to integrate signals.* Nutrient detection: Senses fatty acids in fasting/ketogenic states, boosting fat oxidation and mitochondria independent of energy drops.* Fasting/exercise impacts: Elevate AMP kinase for mitophagy, better fuel switching; mimic historical scarcity absent under modern constant feeding.* mTOR relationship: AMP kinase inhibits mTOR to stop growth in low energy states; feedback loop disrupted by abundance, promoting tissue buildup.* Disease links: Low AMP kinase in obesity/diabetes reduces flexibility; activation prevents cancer but may aid tumor survival in therapy.* Drugs/diets: Metformin and GLP-1s like Ozempic activate AMP kinase for glucose control/weight loss; ketogenic diets activate at intermediate levels for fat efficiency.ABOUT THE GUEST: Gregory Steinberg, PhD is a Professor of Medicine at McMaster University and co-directs the Centre for Metabolism, Obesity, and Diabetes Research, focusing on cellular energy sensors like AMP kinase.RELATED EPISODE:* M&M 260 | Energy Resistance Principle in Life, Healing & Disease | Martin Picard & Nirosha Murugan* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.SUBSCRIBER CONTENT BELOW: Practical takeaways, reference paper, episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release: January 19, 2026. Not medical advice.TOPICS DISCUSSED:* Soy’s rise in farming: Originating from paint uses and wartime chemicals, soy became dominant due to subsidies and large-scale farming practices, but introduces high PUFAs, phytoestrogens, and pesticides into animal feeds.* Feed’s impact on eggs: Chicken feeds high in soy and corn raise linoleic acid levels in eggs compared to low-soy alternatives; low-PUFA eggs improve digestibility for many.* PUFAs & health effects: Feeding PUFAs fattens animals faster and disrupts human gut lining and metabolism; body fat composition changes take time, linking to chronic issues like low energy.* Phytoestrogens in soy: These compounds pass into animal products, affecting estrogen signaling and gut health; mainstream nutrition often overlooks their risks despite historical low exposure.* Dairy variations: Raw milk retains lactoferrin for iron regulation and gut support, plus enzymes and probiotics destroyed in pasteurization; it may resolve dairy intolerances for some.* Regenerative farming model: Armstrong’s cooperative emphasizes traditional feeds to “resaturate” foods, reducing PUFAs; supports small farms amid declining farm numbers.* Ancestral diets insight: Traditional diets vary but share low PUFA levels, avoiding modern chronic illnesses tied to industrial fats.ABOUT THE GUEST: Ashley Armstrong, PhD co-founded Angel Acres Farm in Michigan and now runs Nourish Food Club, a cooperative of small farms producing low-PUFA, soy-free animal foods.RELATED EPISODE:* M&M 273: Nutrition Content of Animal & Plant Foods: Beef, Plant-Based Meat, Raw vs. Processed Milk* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.SUBSCRIBER CONTENT BELOW: Practical takeaways, reference paper, episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release: January 14, 2026. Not medical advice.TOPICS DISCUSSED:* Personalized health profiling: Snyder’s lab sequences genomes and measures molecules from blood, urine, and microbiomes to detect diseases early, emphasizing data-driven discovery over assumptions.* Fiber variations and effects: Responses to dietary fibers vary individually, with microbiome playing a key role.* Glycemic responses to carbs: People spike differently to foods like rice, potatoes, or bread; tied to insulin resistance subtypes in muscles, liver, or pancreas.* Type 2 diabetes heterogeneity: 90% of diabetes cases are type 2 with subtypes like muscle or hepatic resistance; triggers include genetics and infections, with prediabetes often undetected.* Continuous glucose monitors (CGMs): Affordable tools measure glucose every five minutes, revealing personal food triggers; spikes link to risks like cardiovascular disease and cancer.* Lipidomics: Lipids are diverse, serving as energy sources, structural components, and signaling molecules; understudied but key in metabolism and gene expression.* Maternal health & pregnancy: Metabolomics shows thousands of changes, including hormone shifts; cord blood analysis reveals fetal nutrient use and drug transfers, with markers for preterm birth or healthy outcomes.* Future research: Exploring epigenetic changes in diabetes, personalized nutrition mitigation, and digital markers from wearables for mental health tied to diet and gut-brain axis.ABOUT THE GUEST: Michael Snyder, PhD is the Stanford W. Ascherman Professor of Genetics and former chair of the Department of Genetics at Stanford University School of Medicine, where he directs the Center for Genomics and Personalized Medicine.RELATED EPISODE:* M&M 205: Systems Biology, Personalized Medicine, AI & the Future of Health | Lee Hood* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.SUBSCRIBER CONTENT BELOW: Practical takeaways, reference paper, episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release: January 9, 2026. Not medical advice.TOPICS DISCUSSED:* Nutrient density profiling: Labs analyze thousands of compounds beyond macros and vitamins; this “dark matter” includes phytonutrients that may support health despite not being essential.* Phytonutrients in foods: Plant secondary metabolites like polyphenols act as antioxidants and influence pathways like mTOR; animals convert plant compounds into bioactives humans access via meat.* Red meat definition: Refers to meats high in myoglobin, including beef and lamb; most meats are red in wild forms, but human intervention affects color and classification.* Ruminant animals: Animals like cows that have multi-chambered stomachs to digest plants; this metabolism differs from non-ruminants (e.g. chickens), affecting nutrient profiles in their meat.* Grass-fed vs. grain-fed beef: Grass-fed has higher omega-3 fats and phytonutrients from diverse plants; studies show it improves human omega-6:3 ratios and biomarkers from grass-fed, pastured-raised animals.* Farming practices & variations: Plant diversity boosts beef nutrients.* Upcoming research: Long-term trials on effects of pasture-raised foods on human health; interactive dashboards for farmers to profile nutrients and inform policy.ABOUT THE GUEST: Stephan Van Vliet, PhD is an Assistant Professor in the Department of Nutrition, Dietetics, and Food Sciences at Utah State University, where he directs the Center for Human Nutrition Studies, focusing on linking food production systems to nutrient profiles and conducting clinical trials on health impacts.RELATED EPISODE:* M&M 106: Diet, Macronutrients, Micronutrients, Taste, Whole vs. Processed Food, Obesity & Weight Loss, Comparative Biology of Feeding Behavior | Stephen Simpson & David Raubenheimer * Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.SUBSCRIBER CONTENT BELOW: Practical takeaways, reference paper, episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release: January 4, 2026. Not medical advice.TOPICS DISCUSSED:* Cellular growth vs. burning: Cells alternate between growing (using glucose for building blocks in low-oxygen environments) and burning (generating ATP in mitochondria with oxygen); dysregulation leads to metabolic issues.* Key regulatory enzymes: PI3 kinase imports glucose, AMP kinase builds mitochondria, and mTOR drives cell division; their synchronization determines healthy modes, while desynchronization causes diseases.* Fructose as a dose-dependent mitochondrial toxin: High fructose intake inhibits AMP kinase, reducing mitochondrial function and diverting energy to fat storage; it is dose-dependent, like alcohol, and unnecessary in the diet.* Obesogens & endocrine disruptors: Chemicals like tributyltin (TBT) alter gene expression across generations, promoting obesity unrelated to calories; modern exposures increase reactive oxygen species (ROS), burdening cells.* Fetal & neonatal development: Maternal diet, especially high sugar or formula feeding, can cause neonatal obesity and fatty liver; breastfeeding supports proper jaw development and oxygen intake.* Brain metabolism & Alzheimer’s: The brain’s high energy needs make it vulnerable to mitochondrial issues and ROS; energy deficits from diet, stress, and toxins lead to synapse loss and inflammation, treatable via prevention.* ROS & health: Mitochondria produce ROS as a byproduct of ATP generation; excess from diet or environment causes damage, but antioxidants and lifestyle can mitigate risks.ABOUT THE GUEST: Robert Lustig, MD is a pediatric endocrinologist and Professor Emeritus at the University of California, San Francisco, with a background in neuroendocrinology and obesity research.RELATED EPISODE:* M&M 145: Epigenetics, Hormones, Endocrine Disruptors, Microplastics, Xenoestrogens, Obesogens & Obesity, Inheritance of Acquired Characteristics | Bruce Blumberg* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.SUBSCRIBER CONTENT BELOW: Practical takeaways, reference paper, episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: December 31, 2025. Not medical advice.TOPICS DISCUSSED:* Insulin as a powerful metabolic hormone: regulates nutrient storage across tissues, overriding others like glucagon to promote fat and glucose storage during abundance.* Glucagon & GLP-1 roles in metabolism: Glucagon mobilizes liver glucose during scarcity; GLP-1, amplified in drugs like Ozempic, suppresses hunger but originated as a diabetes treatment.* Transition to ketosis in fasting or low-carb diets: Low insulin enables fat breakdown into ketones for brain fuel, allowing survival for weeks without food, with adaptation taking about four weeks.* Hypoglycemia vs. glycogen depletion: Low blood sugar causes fatigue and irritability due to brain energy deficit, while muscle glycogen levels do not directly limit performance.* Ketogenic diets & exercise performance: Studies show no difference in endurance after adaptation, with some athletes performing better on low-carb due to enhanced fat oxidation.* High-carb diets in athletes: In one study, about 30% developed prediabetes-like fasting glucose elevations, linked to total carb intake, despite leanness and fitness.* Misconceptions in sports nutrition: Guidelines recommend 60-90g carbs/hour, but evidence shows 10g suffices to maintain blood sugar and performance, avoiding insulin spikes that impair fat use.* Individual variability in diet response: Athletes vary in optimal fuel sources; it’s possible to by athletic and lean but also metabolically unhealthy.ABOUT THE GUEST: Andrew Koutnik, PhD earned a PhD in biomedical sciences with a focus on exercise physiology and metabolic health, informed by his personal diagnosis of type 1 diabetes in childhood.RELATED EPISODE:* M&M 267 | Ketosis & BHB: Metabolic Diet Therapies, Brain Cancer & Exercise | Dominic D’Agostino* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.SUBSCRIBER CONTENT BELOW: Practical takeaways, reference paper, episode transcript.

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: December 26, 2025.Topics Discussed:* Maternal care behavior in rodents: Nursing, pup retrieval, grooming, and nest-building, essential for altricial pups’ survival; conserved across mammals but varies by species.* Hormonal changes in pregnancy: Estradiol and progesterone surge then drop at birth, crossing the blood-brain barrier to enable infant attraction and care via gene expression and neuroplasticity.* Brain circuitry for parenting: Medial preoptic area acts as a central hub, coordinating motivation and sensory inputs; present in both sexes but activated differently by hormones and experience.* Stress impacts on mothers: Social stressors like male intruders dysregulate care, leading to frantic behaviors and avoidance; models human psychosocial stress linked to postpartum mood disorders.* Sex differences in pup care: Mothers groom male pups more, influencing sexual behaviors, which effects future behavior.* Psilocybin in postpartum mice: Single dose increased anxiety in mothers, showed no antidepressant effects, and transferred via milk, causing long-term anhedonia and impairments in offspring as adults.* Serotonin system development: Early exposure to serotonergic drugs like psilocybin or SSRIs alters lifelong behavior, highlighting sensitive periods in brain reorganization.Practical Takeaways:* Reduce postpartum stress through social support to enhance maternal bonding and minimize mood disorder risks.* Approach psychedelics cautiously during postpartum due to potential anxiety increases and offspring effects via milk.* Recognize hormonal shifts heighten sensitivity to infant cues, aiding natural caregiving instincts.* Monitor environmental factors like food availability or threats that could disrupt parental behaviors in high-stress scenarios.About the guest: Danielle Stolzenberg, PhD is an associate professor of psychology at the University of California, Davis, where her lab studies the neurobiology of maternal care.Reference Paper:* Study: Psilocybin during the postpartum period induces long-lasting adverse effects in both mothers and offspringRelated Episode:* M&M 180: Mother-Infant Bonding, Maternal Care & Breastfeeding, Neural Basis of Hunger & Social Behavior | Marcelo Dietrich*Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: December 21, 2025.Topics Discussed:* Historical trends in soybean oil use: Consumption increased dramatically since the 1960s due to farming subsidies, now providing over 10% of calories for many Americans, far exceeding the 1-2% required biologically.* Soybean oil’s effects in mice: Diets with 8-10% linoleic acid cause obesity, fatty liver, and diabetes over weeks, unlike coconut oil diets; effects persist even after diet switch unless combined with fasting.* Role of HNF4 protein: This conserved liver transcription factor binds linoleic acid, regulating gene expression for metabolism; variants shift between carbohydrate and fat processing, with imbalances linked to fatty liver and cancer.* Oxylipins from linoleic acid: Conversion in liver drives obesity; mice unable to produce them resist weight gain on soybean oil, suggesting these metabolites are key culprits.* Vitamin B1 & soybean oil: Diets deplete B1 in liver and blood, contributing to obesity; supplementation with B1 analogs prevents weight gain, unlike beef tallow diets which preserve B1 levels.* Gut & microbiome impacts: Soybean oil alters gut bacteria, potentially reducing B1 production and increasing permeability, leading to inflammation; farm animals fed soybean meal pass effects to consumers.* Broader health implications: Reanalysis of old human studies questions linoleic acid’s heart benefits; focus on reducing processed foods and seed oils, while noting olive oil’s advantages from historical contexts.Practical Takeaways:* Limit processed foods and seed oils like soybean to reduce linoleic acid intake, aiming for 1-2% of calories; read labels and opt for olive oil or home-cooked meals.* Incorporate intermittent fasting, such as 12-16 hours without eating daily, to help reverse obesity effects from high-linoleic diets, based on mouse reversibility studies.* Choose grass-fed or naturally fed animal products to avoid indirect soybean oil exposure from feed, potentially preserving nutrient levels like vitamin B1.* Monitor diet when traveling or changing habits, as shifts in oil types can affect medication metabolism via liver enzymes.About the guest: Frances Sladek, PhD is a professor whose research focuses on the nuclear receptor HNF4 and the health impacts of dietary fats, particularly soybean oil.Reference Paper:* Study: Diet high in linoleic acid dysregulates the intestinal endocannabinoid system and increases susceptibility to colitis in MiceRelated Episode:* M&M 200: Dietary Fats & Seed Oils in Inflammation, Colon Cancer & Chronic Disease | Tim Yeatman & Ganesh Halade*Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: December 17, 2025.Topics Discussed:* Evolutionary context of circadian rhythms: All organisms have adapted to Earth’s 24-hour day for survival, with internal clocks slightly offset and adjusted by environmental cues.* Molecular clock mechanism: Involves a feedback loop where proteins turn on/off genes, lasting ~24 hours, regulated by phosphorylation and degradation for timing precision.* Genetic variations in sleep: Families with mutations in clock genes like PER2 cause extreme morning lark behavior, altering protein stability and period length by hours.* Light entrainment: Morning light shortens human clocks (average 24.2 hours) to match 24-hour days; seasonal day length changes require gradual adjustments.* Food & metabolic links: Seasonal food scarcity/abundance affects clock via glucose and fatty acids competing for protein modifications, as shown in diabetic mouse models.* Role of unsaturated fats: Paper finds MUFA/PUFA ratios in diet alter phosphorylation of clock proteins, speeding or slowing adaptation to winter/summer light cycles in mice.* Modern environmental impacts: Artificial light extends “daytime” signals, while constant food access erases seasonal patterns, contributing to obesity and diabetes risks.* Jet lag & adaptations: Sudden time shifts mimic seasonal experiments; high-sugar/fat intake may phenocopy genetic effects to aid adjustment, though not recommended for health.Practical Takeaways:* Expose yourself to morning natural light to help synchronize your internal clock and improve daily energy.* Consume main meals during daylight hours and avoid late-night eating to align with natural metabolic rhythms.* Limit evening screen time to reduce artificial blue light disrupting sleep onset.* Consider varying diet seasonally, favoring diverse, whole foods to mimic natural availability patterns for better health.About the guest: Louis Ptacek, MD is a neurologist and professor at the University of California, San Francisco. He researches inherited neurological diseases and sleep traits, including genetic variations causing extreme early rising.Reference Paper:* Study: Unsaturated fat alters clock phosphorylation to align rhythms to the season in miceRelated Episode:* M&M 237: Circadian Biology: Genetics, Behavior, Metabolism, Light, Oxygen & Melatonin | Joseph Takahashi*Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: December 12, 2025.Topics Discussed:* Organs have different fuel preferences: brain strongly prefers glucose, heart prefers fatty acids, skeletal muscle is flexible and likes fat/ketones.* Humans evolved with high metabolic flexibility; regular ketosis was normal for ancestors, but today most people never experience it.* “Keto flu” is largely glucose withdrawal plus electrolyte/sodium loss; proper salt and hydration prevent most symptoms.* Classic medical ketogenic diet is ~90% fat (historically saturated); modern versions often use more monounsaturated fats, MCTs, and higher protein.* Saturated fat is not inherently atherogenic in the context of weight stability or caloric deficit; excess calories from any source can dysregulate metabolism.* Exogenous ketones (e.g. BHB) provide energy, reduce ROS, stabilize membranes, increase inhibitory tone (GABA), and have hormone-like signaling effects independent of diet.* Cancer cells often show Warburg effect (damaged mitochondrial respiration → heavy reliance on glycolysis); lowering glucose and raising ketones can stress cancer cells.* True keto-adaptation for athletic performance requires 6–12 weeks; after that, elite athletes can match or exceed prior high-carb performance at sub-maximal and endurance efforts.Practical Takeaways:* Therapeutic carbohydrate restriction (50–100 g/day for many people) plus occasional fasting or ketone supplements can restore metabolic flexibility with far fewer side effects than strict keto.* Prioritize whole-food fats (eggs, fatty fish, beef, olive oil, butter/lard) and minimize processed keto products loaded with seed oils.* Supplementing BHB (salts or esters) or MCT oil can ease the transition into ketosis, boost ketones without strict dieting, and may support brain and metabolic health.* Regularly check basic blood markers (glucose, lipids, electrolytes) and consider an OmegaQuant test; optimizing metabolic health is one of the strongest preventable steps against cancer, neurodegeneration, and heart disease.About the guest: Dominic D’Agostino, PhD, is an associate professor at the University of South Florida Morsani College of Medicine in the Department of Molecular Pharmacology and PhysiologyRelated Episode:* M&M 224: Cancer Biology: Metabolism, Mitochondria & Energy | Thomas SeyfriedSupplemental Ketone (BHB):* KetoCitra—Ketone body BHB with potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off.*Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Full AI-generated transcript below. Beware of typos & mistranslations!

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: December 7, 2025.Topics Discussed:* Polyunsaturated fatty acids (PUFAs): Omega-6 from seed oils like safflower and corn can convert to pro-inflammatory molecules, while omega-3s produce resolving ones; imbalance biases toward chronic inflammation.* Inflammation regulation: Acute inflammation aids healing but requires active “on” and “off” signals from lipid mediators; chronic inflammation arises from excess omega-6, delaying resolution.* Heart health & diet: High omega-6 diets worsen post-heart attack outcomes in mice by elevating pro-inflammatory lipids.* Evolution & historical context: PUFAs are essential but naturally balanced in pre-industrial diets; modern processing skews ratios, contributing to diseases, as shown in early rat experiments needing minimal fats for survival.* Aging & lifestyle factors: Excess omega-6 exacerbates inflammation in older mice; sleep, exercise, and balanced fats are crucial for metabolic health and enzyme function in processing lipids.* Cannabis & omega-6 interaction: In mice on high omega-6 diets, CBD-rich cannabis smoke reaches the heart quickly, suppresses immune response, and weakens cardiac strain, unlike in balanced-diet controls.* Genetic models: FAT-1 mice converting omega-6 to omega-3 show better healing and neuroprotection; FAT-2 mice doing the opposite exhibit liver fibrosis and metabolic issues, highlighting omega-6 excess harms.Practical Takeaways:* Balance omega-6 and omega-3 intake by reducing seed oils in processed foods and increasing sources like fish or algae to support inflammation resolution and heart health.* Monitor and adjust fat intake with age, as older individuals are more sensitive to omega-6 excess leading to immune dysregulation.* Avoid combining high omega-6 diets with smoking, as it may impair immune and cardiac responses based on animal data.About the guest: Ganesh Halade, PhD is a cardiovascular scientist and associate professor at the University of South Florida Morsani College of Medicine.Reference Paper: * Paper: Cannabis cigarette smoking disrupts mice multi-organ bioactive lipid metabolism and inflammation-resolution signaling in an obesogenic settingRelated Episode:* M&M 200: Seed Oils, Inflammation, Colon Cancer & Chronic Disease | Tim Yeatman & Ganesh Halade *Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Episode Chapters:00:03:38 Guest Introduction & Background 00:04:42 Polyunsaturated Fatty Acids Overview 00:08:31 Acute vs Chronic Inflammation 00:12:01 Inflammation Turn-On & Turn-Off Signals 00:17:59 Omega-6 & Omega-3 Imbalance in Modern Diet 00:23:39 Essential Fatty Acids & Natural Balance 00:28:09 Seed Oils & Heart Health Controversy 00:37:27 High Omega-6 Effects on Heart Health 00:45:32 Aging & Omega-6 Sensitivity 00:53:55 Healing Faster with Balanced Ratio 00:59:36 Cannabis Smoking & High Omega-6 Diet 01:11:19 Immune Dysregulation from Cannabis & Omega-6 01:15:00 Ongoing Heart Failure Research 01:21:26 FAT-1 & FAT-2 Mice Insights 01:28:10 Lifestyle Medicine & Final ThoughtsFull AI-generated transcript below. Beware of typos & mistranslations!

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: December 2, 2025.Topics Discussed:* Epidemiology basics: Studies disease influences using observational designs like case-control and prospective cohorts, plus trials, to identify patterns and test hypotheses.* Hierarchy of evidence critique: Rejects rigid pyramids favoring RCTs, as all studies can be biased; advocates triangulation integrating varied data types for robust conclusions.* RCT strengths & weaknesses: Randomization balances confounders, but issues like poor blinding, attrition, or subversion can undermine results; large samples may yield spurious precision if biased.* Confounding & reverse causation: Examples include yellow fingers and lung cancer (both from smoking) or early atherosclerosis inflating CRP-disease links; hard to fully control statistically.* Nutrition epidemiology pitfalls: Observational studies often overstate benefits (e.g., vitamin E for heart disease), leading to failed trials; incentives favor new findings over revisiting errors.* Mendelian randomization: Uses genetic variants as proxies for exposures (e.g., ALDH2 for alcohol metabolism) to mimic randomization; reveals no heart benefits from alcohol, unlike observational data.* Negative controls for validation: Tests implausible outcomes (e.g., smoking and murder) or exposures (e.g., paternal smoking in pregnancy) to check for confounding artifacts.* Evidence triangulation: Combines diverse studies with different biases (e.g., cross-cultural comparisons) for causality; applied to dismiss HDL-raising drugs despite initial promise.Practical Takeaways:* Scrutinize health claims by checking for negative controls or variety in evidence sources to avoid mistaking correlation for causation.* For personal decisions like alcohol intake, consider genetic studies showing risks at all levels, and aim for moderation or abstinence based on overall evidence.* When evaluating supplements or diets, prioritize trials over observational data, and question media hype that ignores confounding factors.* Use symmetrical analysis in reading studies: Treat exposures and confounders equally to assess true effects.About the guest: Dr. George Davey Smith, MD, DSc is a professor of clinical epidemiology at the University of Bristol and director of the MRC Integrative Epidemiology Unit, where he focuses on causal inference in health.Reference Paper: * Paper: Evidence triangulation in health researchRelated Episode:* M&M 212: How Science Really Works: Meta-Research, Publishing, Reproducibility, Peer Review, Funding | John Ioannidis*Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Episode Chapters:00:00:00 Intro 00:06:01 Hierarchy of Evidence 00:12:54 Sample Size & Precision 00:18:41 Vitamin E Supplements 00:25:05 Nutrition Epidemiology Pitfalls 00:32:01 Preclinical vs Clinical 00:38:04 Negative Controls 00:45:16 Negative Control Exposures 00:52:21 Alcohol Consumption Effects 00:59:00 Mendelian Randomization Example 01:05:16 MR Limitations & Pleiotropy 01:11:20 HDL Cholesterol Myths 01:18:21 Evidence Triangulation 01:23:36 Final Thoughts & ResourcesFull AI-generated transcript below. Beware of typos & mistranslations!

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: November 26, 2025.Topics Discussed:* Brain energy efficiency: Brains are much more energy-efficient than computers for similar processing, relying on adaptive metabolic strategies evolved under energy scarcity.* Metabolism vs. information processing: Core metabolites like glutamate bridge basic cellular energy production and neural signaling.* Lactate as a signal: Produced during exercise, lactate diffuses from muscles to brain, modulating neuronal excitability and providing neuroprotection.* BHB in ketosis: During fasting or ketogenic diets, beta-hydroxybutyrate displaces glucose as fuel, enhances antioxidant defenses, and activates protective potassium channels in neurons.* Adenosine and sleep: Accumulates from ATP breakdown during wakefulness, triggering sleep and locally inhibiting overactive neural networks for energy conservation.* Glial cells’ role: Astrocytes and oligodendrocytes handle sophisticated metabolism, release signaling molecules like lactate, and modulate synapses, and influence diseases like Alzheimer’s.Practical Takeaways:* Regular exercise elevates lactate, which signals the brain to adapt metabolism and may enhance neuroprotection against stress.* Intermittent fasting or ketogenic diets can induce ketosis with BHB, potentially boosting brain antioxidant defenses and preconditioning against metabolic stress.* Prioritizing sleep helps clear adenosine buildup, restoring energy balance and supporting long-term neural health.About the guest: Dr. Luis Felipe Barros, MD, PhD is a Chilean neurobiologist and professor at the Universidad de Valparaíso, where he leads a lab studying brain metabolism from glucose transport to mitochondrial function.Reference Paper: * Paper: Scale-spanning crosstalk between metabolism and information processingRelated Episode:* M&M 255 | Unlocking Energy: How Nutrition & Drugs Impact Your Mitochondria | Chris Masterjohn*Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Episode Chapters:00:00:00 Intro 00:06:00 Brain Efficiency & Computers 00:12:00 Metaphors for Brain Function 00:18:00 Core Metabolites & Signaling 00:24:00 Lactate in Exercise & Protection 00:30:00 Body-Brain Integration & Sensors 00:36:00 BHB, Ketosis & Fasting 00:42:00 Adenosine & Sleep Cycles 00:48:00 Neuroprotective Core Metabolites 00:54:00 Scale-Spanning Coordination 01:00:00 Neural Energy Demands 01:05:00 Expensive Tissue Hypothesis 01:08:00 Glial Cells & Astrocytes 01:13:00 Mitochondria in Cells 01:18:00 Future of Metabolism ResearchFull AI-generated transcript below. Beware of typos & mistranslations!

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: September 12, 2025Episode Summary: Dr. Christopher Morrison talks about how animals sense and prioritize nutrients like protein, discussing defense mechanisms for essentials such as oxygen, water, sodium, and energy; the brain's role in detecting protein deprivation via signals like FGF21; trade-offs between growth, reproduction, and longevity under protein restriction; and reconciling high-protein diets for satiety and muscle maintenance with low-protein benefits for metabolic health and lifespan extension.About the guest: Christopher Morrison, PhD is a professor and researcher at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, where he has worked for over 22 years focusing on nutrition, metabolism, and chronic diseases like obesity and diabetes.Discussion Points:* The body prioritizes nutrients hierarchically: oxygen and water first, then sodium, energy, and protein, with weaker defenses for carbs or fats.* Animals develop specific appetites for deprived nutrients, like salt or protein, often through post-ingestive learning rather than just taste.* Protein restriction (e.g., 5% vs. 20% in diets) increases food intake and energy expenditure in mice to maintain protein levels, even at the cost of extra calories.* FGF21, a liver hormone, signals protein deprivation to the brain (via NTS region), driving protein-seeking behavior and metabolic changes; it's essential for low-protein responses.* Protein restriction extends lifespan in lab animals by suppressing growth signals like IGF-1 and mTOR, but may impair immunity or wound healing in real-world conditions.* High protein aids satiety, weight loss, and muscle building, but overconsumption may shorten lifespan; optimal intake depends on age, activity, and goals (e.g., not for pregnant or elderly).* No one-size-fits-all for protein: mild restriction may benefit middle-aged sedentary people for health, while athletes need more; balance avoids excesses.Related content:* M&M 106: Diet, Macronutrients, Micronutrients, Taste, Whole vs. Processed Food, Obesity & Weight Loss, Comparative Biology of Feeding Behavior | Stephen Simpson & David Raubenheimer*Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Episode Chapters:00:00:00 Intro00:06:10 Nutrient Detection & Adequacy 00:11:11 Fluid & Sodium Defenses 00:16:20 Protein vs Other Macronutrients 00:21:21 Post-Ingestive Learning & Flavors 00:26:34 Hyperphagia on Low Protein 00:31:10 Restriction Effects on Growth 00:36:33 Longevity & Restriction Trade-Offs 00:41:47 Behavioral Changes & Choices 00:46:44 Preference in Choice Experiments 00:53:44 Innate vs Learned Appetite 00:58:39 Protein Digestion & Signals 01:04:40 FGF21 in Fasting & Restriction 01:10:40 FGF21 Knockouts & Relevance 01:15:20 Brain Receptors & Sites 01:20:49 Growth & Longevity Trade-Offs 01:25:04 High Protein Satiety & Muscle 01:30:33 FGF21 Scaling & Future Work 01:35:39 Final Thoughts & RecommendationsFull AI-generated transcript below. Beware of typos & mistranslations!

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: September 7, 2025Episode Summary: Dr. Michael Levin talks about cognition manifesting at scales beyond brains, including in cells and tissues via bioelectric networks; analog vs. digital coding in biology; how bioelectric patterns guide development and regeneration (e.g., in planarians); creation of novel life forms like xenobots and anthrobots; philosophical ideas on a "platonic space" of mathematical patterns influencing biology; evolutionary trade-offs in regeneration and implications for regenerative medicine.About the guest: Michael Levin, PhD is a biologist and computer scientist who directs the Allen Discovery Center at Tufts University, focusing on bioelectricity, regeneration, and cognition in non-neural systems.Discussion Points:* Cognition isn't limited to brains; tools from neuroscience reveal learning, memory, and goal-directed behavior in cells and tissues.* Bioelectricity acts as "cognitive glue," enabling collective intelligence in non-neural systems, predating multicellular life.* Analog coding in development uses slow voltage patterns across cells, contrasting fast digital spikes in neurons.* Planarians regenerate perfectly due to bioelectric "memories"; altering patterns creates stable two-headed worms without genetic changes.* Regeneration trade-offs: Mammals prioritize quick healing over full regrowth due to infection risks and load-bearing needs.* Xenobots (from frog cells) and anthropots (from human cells) self-assemble, replicate, and heal tissues, revealing untapped cellular potentials.* Patterns in biology may stem from a "platonic space" of mathematical truths, not just evolution or physics.* Neuroscience studies mind scaling, not just neurons; diverse intelligences could exist in non-cellular systems.Related content:* M&M 95: Purpose, Value, Evolution, Consciousness, Sentience, Life & Emergence of Mind From Matter | Terrence Deacon*Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Episode Chapters:00:00:00 Intro00:04:52 Cognition Definition 00:09:20 Development Timescales 00:12:01 Analog Signaling 00:15:12 Network Properties 00:18:03 Goals in Morphogenesis 00:21:40 Regeneration Mechanisms 00:25:41 Planarian Patterns 00:31:43 Regenerative Trade-offs 00:38:20 Pattern Sources 00:44:21 Xenobots 00:49:26 Anthropots 00:56:28 Platonic Space 01:02:47 Mind ScalingFull AI-generated transcript below. Beware of typos & mistranslations!

This is a free preview of a paid episode. To hear more, visit mindandmatter.substack.comWide release date: September 3, 2025Episode 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 rate* Phagocytosis 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 Patti* Article | Dietary Fructose & Metabolic Health: An Evolutionary PerspectiveReference Paper:* Study | Early life high fructose impairs microglial phagocytosis and neurodevelopment*Not medical advice.* Full audio version: [Apple] [Spotify] [Elsewhere]* Full video version: [YouTube]* Support M&M if you find value in this content.* Episode transcript below.Episode Chapters:00:00:00 IntroFull AI-generated transcript below. Beware of typos & mistranslations!