Mind & Matter

Send us a textEpisode Summary: Dr. Eugene Chang talks about the microbiome’s role as a vital organ, the impacts of antibiotics and Western diets on microbial health, and strategies for restoring a damaged microbiome through diet and fecal microbial transplants. They delve into microbiome dysbiosis, its links to modern diseases, and Chang’s research on personalized microbiome interventions.About the guest: Eugene Chang, MD is a physician-scientist and Professor of Medicine at the University of Chicago, specializing in gastroenterology. His research focuses on the gut microbiome as a vital organ influencing metabolic and immune health.Discussion Points:The gut microbiome is a vital organ, acquired early in life, that supports metabolic and immune functions, but can be disrupted by antibiotics, leading to diseases like C. difficile colitis.Western diets, high in saturated fats and low in fiber, contribute to microbiome dysbiosis, linked to modern conditions like inflammatory bowel diseases, obesity, and allergies.Microbiome health is better assessed by functional markers (e.g., short-chain fatty acid production) than taxonomic diversity, as diversity varies widely among healthy individuals.A patient with severe food intolerance due to antibiotic-induced microbiome damage was treated over 50 weeks with a tailored diet, restoring healthy microbiome function.Different dietary fibers (e.g., beans vs. seaweed) are metabolized at varying rates, affecting gut health; fermented foods like kefir can bypass digestion issues.Diet can rapidly reshape the microbiome within 24-48 hours, but severe dysbiosis may require microbial transplants if key microbes are extinct.Chang’s research shows a high-fiber, low-fat diet outperforms fecal microbial transplants in restoring microbiome resilience in mice post-antibiotics.Future microbiome medicine may involve personalized “omni microbial transplants” targeting both small and large intestines for comprehensive restoration.Related episode:M&M 203: Metagenomics, Microbiome Transmission, Gut Microbiome in Health & Disease | Nicola Segata*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. 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 Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Send us a textThe genetics of sleep duration and sleep timing.Episode Summary: Dr. Ying-Hui Fu discusses her research on the genetics of sleep, focusing on natural short sleepers who thrive on 4-6 hours of sleep and the heritability of sleep traits like duration and timing. She explores how sleep efficiency, rather than just duration, may explain why some need less sleep without health deficits, and delves into the molecular and circadian mechanisms regulating sleep. About the guest: Ying-Hui Fu, PhD is a neuroscientist and professor at UCSF, where her lab studies the genetics of human sleep behaviors, particularly sleep duration and schedule.Discussion Points:Sleep Traits Are Genetic: Sleep duration (how long you sleep) and sleep schedule (when you sleep) are partially heritable, with most people needing 7-9 hours, while rare natural short sleepers thrive on 4-6 hours.Natural Short Sleepers: These individuals fall asleep quickly, have high sleep efficiency, and live healthy, active lives without deficits, possibly due to faster toxin clearance and repair during sleep.Sleep Efficiency Matters: Short sleepers may complete restorative sleep processes (e.g., clearing toxins, repairing damage) more efficiently, allowing them to need less sleep.Circadian & Entrainment Pathways: Sleep timing is regulated by a molecular clock and environmental cues like light, with mutations in entrainment pathways causing extreme schedules (e.g., early bedtime or night owl tendencies).Modern Lifestyle Harms Sleep: Stimuli like blue light and tense media disrupt sleep patterns, leading to widespread sleep deprivation and health risks.Shift Work Risks: Shift workers face higher risks of diseases like cancer and neurodegeneration due to disrupted sleep cycles, though genetic background influences susceptibility.Finding Your Sleep Rhythm: A two-week vacation without stimulants or artificial light can help determine your natural sleep schedule and duration.Sleep’s Health Impact: Poor sleep is a major factor in aging and diseases like Alzheimer’s, making it as critical as diet and exercise for health.Related episode:M&M 237: Circadian Biology: Genetics, Behavior, Metabolism, Light, OxygenSupport the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. 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 Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Send us a textA blend of biology, philosophy, and history exploring how hormones and endocrine disruptors affect social behavior and society.Episode Summary: Dr. Charles Cornish-Dale discusses the decline of masculinity in modern society, linking it to falling testosterone levels, environmental endocrine disruptors, and the limitations of liberal democracy. Drawing on Francis Fukuyama’s “End of History & the Last Men” and historical perspectives, Cornish-Dale argues that biological and societal factors, including diet and hormonal interventions like birth control, are reshaping male and female behaviors, with profound implications for health and social structures.About the guest: Charles Cornish-Dale, PhD is a medieval historian and anthropologist with a PhD from Oxford. His new book is, “The Last Men: Liberalism and the Death of Masculinity.”Discussion Points:Thymos & Masculinity: Cornish-Dale uses the ancient Greek concept of thymos, meaning spiritedness, to explain male drives for recognition and distinction, which he ties to testosterone-driven behaviors.Testosterone Decline: Studies like the Massachusetts Male Aging Study show a ~20% drop in male testosterone levels over 17 years, correlating with reduced reproductive health and social withdrawal.Endocrine Disruptors: Chemicals in plastics, pesticides, and soy products mimic estrogen, disrupting hormonal balance and potentially causing developmental and behavioral issues.Diet & Behavior: Historical shifts to grain-based diets, as noted by Plato, and modern plant-based trends may suppress thymos and alter hormonal profiles, impacting societal dynamics.Hormonal Contraceptives: Birth control can thin the ventromedial prefrontal cortex in women, affecting emotional regulation, especially if taken during teenage years, with potential permanent effects.Fukuyama’s End of History Framework: Cornish-Dale critiques liberal democracy’s inability to satisfy megalothymia (the desire to be better), contributing to a crisis of purpose for men.Related episode:M&M 193: History of Diet & Food, Population Density & Social Stability, Psychological Pandemics, Physical & Mental Health in Civilizational CyclesSupport the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. 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 Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Send us a textHow our biological clocks shape biology from the molecular to behavioral level.Episode Summary: Dr. Joseph Takahashi discusses circadian rhythms, exploring their biological basis, from molecular mechanisms to their impact on metabolism and health; the discovery of circadian clock genes; role of the suprachiasmatic nucleus, and how light, feeding, and oxygen influence these rhythms. The conversation highlights practical implications, such as the effects of artificial light and meal timing on health, and touches on emerging research linking stronger circadian clocks to longevity.About the guest: Joseph Takahashi, PhD is a renowned neuroscientist at UT Southwestern Medical Center, where he leads research on circadian clock genes.Discussion Points:The suprachiasmatic nucleus in the hypothalamus acts as the brain's central clock, syncing with light via the retina.Key circadian genes like CLOCK and BMAL regulate thousands of genes, especially those involved in metabolism, impacting health outcomes.Internal desynchronization, when brain and organ clocks misalign (e.g., from eating at night), can lead to metabolic issues like pre-diabetes.In mice, eating at the right time (night for nocturnal animals) extends lifespan by up to 35% under caloric restriction, compared to 10% with spread-out feeding.Artificial light, especially blue light at night, disrupts melatonin and circadian rhythms, while natural sunlight supports healthy eye development.Melatonin, a darkness-signaling hormone, is best for resetting rhythms (e.g., jet lag) at low doses, not as a sedative, and U.S. supplements vary widely in quality.Oxygen-sensing proteins interact with circadian clock components, hinting at links between altitude, metabolism, and health.Learning and memory show diurnal variations, with better performance at certain times, influenced by circadian modulation of synaptic activity.A stronger circadian clock, created genetically in mice, led to 16% longer lifespan and resistance to weight gain (unpublished research).Related episode:M&M 202: Why Do Animals Sleep? | Vlad Vyazovskiy*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. 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 Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Send us a textCellular self-organization, cytoskeleton dynamics, and membrane wound healing.Episode Summary: Cell Biologist Dr. Bill Bement explains the dynamic world of the cell cortex, discussing how actin filaments and microtubules drive processes like cell division and wound healing through self-assembly and self-organization; energy dynamics of these processes; the role of rho GTPases in patterning; the implications for diseases such as cancer and muscular dystrophy, using vivid analogies and video demonstrations to make complex concepts accessible.About the guest: Bill Bement, PhD is a cell biology professor at the University of Wisconsin-Madison, where he has studied cellular processes for over 30 years. He leads a lab focused on the cell cortex, investigating cell division and repair. His work emphasizes self-organization and cytoskeletal dynamics, contributing to insights into diseases like muscular dystrophy.Discussion Points:The cell cortex, the outer layer of a cell, includes the plasma membrane & underlying proteins like actin & myosin, which enable dynamic shape changes.Actin filaments self-assemble without energy input, growing & shrinking to facilitate cell movement and division, while microtubules, stiffer hollow tubes, aid in chromosome separation.Self-organization in cells, driven by energy-dependent feedback loops, creates complex patterns like mitotic spindles.Cellular wound healing involves concentric rings of rho GTPases and actin, closing wounds rapidly, a process critical for surviving natural damage from mechanical stress or toxins.Energy costs of cytoskeletal rearrangements are significant but likely less than protein synthesis, though precise measurements remain challenging.Cancer metastasis may rely on enhanced cell repair, allowing metastatic cells to survive mechanical damage while squeezing through tissues.Muscular dystrophy involves excessive damage or impaired repair, highlighting the importance of cell repair mechanisms.Bement’s lab is developing tools for synthetic self-organization, aiming to manipulate cellular processes to address repair deficits in diseases.Related episode:M&M 220: Cell Death, Oxidative Stress, PUFAs & Antioxidants | Pamela Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. 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 Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Send us a textHow brains compute and learn, blending neuroscience with AI insights.Episode Summary: Dr. Marius Pachitariu discusses how the brain computes information across scales, from single neurons to complex networks, using mice to study visual learning. He explains the differences between supervised and unsupervised learning, the brain’s high-dimensional processing, and how it compares to artificial neural networks like large language models. The conversation also covers experimental techniques, such as calcium imaging, and the role of reward prediction errors in learning.About the guest: Marius Pachitariu, PhD is a group leader at the Janelia Research Campus, leading a lab focused on neuroscience with a blend of experimental and computational approaches.Discussion Points:The brain operates at multiple scales, with single neurons acting as computational units and networks creating complex, high-dimensional computations.Pachitariu’s lab uses advanced tools like calcium imaging to record from tens of thousands of neurons simultaneously in mice.Unsupervised learning allows mice to form visual memories of environments without rewards, speeding up task learning later.Brain activity during sleep or anesthesia is highly correlated, unlike the high-dimensional, less predictable patterns during wakefulness.The brain expands sensory input dimensionality (e.g., from retina to visual cortex) to simplify complex computations, a principle also seen in artificial neural networks.Reward prediction errors, driven by dopamine, signal when expectations are violated, aiding learning by updating internal models.Large language models rely on self-supervised learning, predicting next words, but lack the forward-modeling reasoning humans excel at.Related episode:M&M 44: Consciousness, Perception, Hallucinations, Selfhood, Neuroscience, Psychedelics & "Being You" | Anil Seth*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. 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 Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Send us a textHow dietary fats and cannabinoids shape brain function and mental well-being.Episode Summary: Dr. Steven Laviolette discusses the role of lipids, particularly endocannabinoids and fatty acids, in brain signaling and mental health, discussing how dietary omega-3 and omega-6 imbalances, prenatal THC exposure, and fatty acid binding proteins (FABPs) impact mood, anxiety, and neuroinflammation, while highlighting potential dietary interventions to mitigate these effects.About the guest: Steven Laviolette, PhD is a professor at the University of Western Ontario, holding a PhD, and his lab focuses on the brain’s cannabinoid system and its role in mental health. He investigates how cannabinoids and fatty acids influence brain development and disorders like anxiety and schizophrenia.Discussion Points:The brain uses fats like endocannabinoids (e.g., anandamide, 2-AG) not just for structure but as signaling molecules to regulate emotional and cognitive processing.Prenatal THC exposure in rodents skews the omega-3/omega-6 balance toward pro-inflammatory omega-6, leading to cognitive and mood issues in offspring, but omega-3 supplementation can mitigate these effects.Fatty acid binding proteins (FABPs), especially FABP5, shuttle endocannabinoids like anandamide to degradation sites, and inhibiting FABP5 increases anandamide levels, reducing anxiety and depression without addictive side effects.FABP5 inhibitors show promise as safer alternatives to benzodiazepines.Both THC and CBD can induce problems during early development, challenging the notion that CBD is universally safe, especially during pregnancy.Dietary interventions, like omega-3 supplementation or antioxidants (e.g., L-theanine, N-acetylcysteine), may counteract the negative psychiatric effects of cannabinoid exposure, particularly during adolescence.The North American diet, high in omega-6, contributes to neuroinflammation and mental health issues, underscoring the need for nutritional neuroscience to address these imbalances.Related episode:M&M 165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. 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 Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Brian Kerley, a family medicine-trained hospitalist known as the 'Seed Oil Disrespecter', dives into the health impacts of seed oils. He reveals their role in chronic diseases like heart disease, linking them to oxidative stress and lipid peroxidation. The discussion touches on the evolutionary mismatch between modern diets and traditional food patterns. Kerley also highlights challenges in studying long-term effects and explores the cultural implications of dietary choices, all while advocating for better patient education on nutrition.

Dr. David Healy, a seasoned psychiatrist and pharmacologist, dives into the contentious world of SSRIs and their significant side effects, including post-SSRI sexual dysfunction and vulnerabilities to suicidality. He critiques how pharmaceutical companies manipulate clinical trials and ghostwrite research, overshadowing patient experiences. Healy emphasizes the urgent need for individualized patient care and transparency in medical practices, raising concerns about the ethical implications of SSRIs and the power dynamics in healthcare.

Andrew Chadeayne, a chemist and patent lawyer, dives into the fascinating world of psychedelics. He explains the chemistry behind psilocybin and its psychoactive counterparts, debunking myths like 'lemon tekking.' Chadeayne discusses innovative drug development aimed at enhancing therapeutic benefits while minimizing hallucinogenic effects. He also explores the booming, unregulated market for products like kratom and synthetic psilocybin sold in vape shops, raising crucial questions about safety and regulation in this evolving industry.