Mind & Matter

Nikos Koundouros, a postdoctoral fellow at Weill Cornell Medicine, joins John Blenis, a prominent pharmacology professor, to unravel how omega-6 fatty acids like linoleic acid may drive triple-negative breast cancer by activating the mTOR pathway. They discuss the critical role of the FABP5 protein, uniquely enhancing cancer cell sensitivity to these fats. The conversation reveals alarming shifts in modern diets, emphasizing the need for tailored nutrition approaches based on genetic variations and cancer subtypes to improve health outcomes.

György Buzsáki, a renowned NYU professor, explores how the hippocampus transcends mere memory and spatial navigation functions to influence action planning and abstract thought. He discusses the impact of brain rhythms, particularly sharp wave ripples, which enhance communication and affect overall bodily health like glucose regulation. Delving into the interconnectedness of memory, sleep, and neural dynamics, Buzsáki challenges existing neuroscience paradigms while illuminating the evolutionary context shaping cognitive processes.

Send us a textThe biophysics of life, exploring how light & energy shape biology, with biophysicist Dr. Nirosha Murugan.Episode Summary: Dr. Murugan discusses the role of biophysics in biology, focusing on how light, particularly biophotons emitted by cells, influences processes like wound healing, neural activity, and cancer detection; how microtubules may act as biological fiber optics, the impact of modern light environments on health; her work inducing limb regeneration in frogs using silk hydrogels and growth factors; cancer as an energetic dysfunction; potential of non-invasive photonic diagnostics; the need for new tools to study these phenomena.About the guest: Nirosha Murugan, PhD is a biophysicist and assistant professor at Wilfrid Laurier University in Waterloo, Ontario. Her lab investigates the biophysics of life.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.Key Conversation Points:Cells emit biophotons, ultra-weak light tied to metabolism, which may carry information for processes like immune response and neural communication.Microtubules might function as biological fiber optics, potentially guiding light within cells for signaling purposes.Red and near-infrared light can accelerate wound healing and reduce inflammation, likely by modulating mitochondrial activity.Cancer cells emit distinct photonic signatures, which could enable non-invasive diagnostics by detecting light differences from healthy tissues.Modern light environments, unlike natural sunlight, may subtly affect health by altering biological responses to electromagnetic signals.Biological systems act as metamaterials, patterning energy flow in ways that constrain and shape molecular and behavioral outcomes.Related episode:M&M 221: Regenerative Energy & the Light Inside You | Jack Kruse*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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

Send us a textShort Summary: Dr. Alex Kwan unpacks the latest neuroscience research on how psychedelics like ketamine & psilocybin reshape the brain.About the guest: Alex Kwan, PhD, is an associate professor of biomedical engineering at Cornell University. His lab employs advanced imaging to study how psychedelics and other drugs affect the mammalian brain.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.Episode Summary: Dr. Alex Kwan discusses how psychedelics like ketamine and psilocybin induce rapid neuroplastic changes in the brain, particularly in the prefrontal cortex, contrasting their effects with traditional antidepressants like SSRIs, and exploring their potential for treating depression and chronic pain through structural and functional brain alterations.Key Takeaways:Ketamine & psilocybin rapidly increase dendritic spine density in the prefrontal cortex, enhancing neural connections within days, unlike SSRIs, which take weeks.These drugs show sustained neuroplastic changes in mice, lasting weeks to months after a single dose, suggesting long-term brain rewiring.Serotonin 2A receptor is critical for psilocybin’s neuroplastic effects, as precise genetic knockouts in adult mice eliminate spine growth.Unlike ketamine, psilocybin activates the insula, a brain region linked to chronic pain processing, hinting at new therapeutic potential.Both drugs induce similar gene expression patterns in areas like the prefrontal cortex and amygdala, but differ in specific regions like the insula.Related episode:M&M #30: Psilocybin, Ketamine, Neuroplasticity & Imaging the Brain | Alex Kwan*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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

Send us a textShort Summary: The flaws of nutrition epidemiology with Dr. John SpeakmanAbout the guest: John Speakman, PhD is a professor at the University of Aberdeen and runs a lab in Shenzhen, China, focusing on energy balance, obesity, and aging. Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.Episode Summary: Dr. John Speakman explores the pitfalls of nutrition epidemiology, a field that links diet to health outcomes like cancer and obesity but often produces contradictory results. They discuss flawed methods like 24-hour recalls and food frequency questionnaires, which rely on memory and are prone to bias, and introduce Speakman’s new tool using doubly labeled water to screen implausible dietary data. The conversation highlights systematic biases, such as under-reporting by heavier individuals, and emerging technologies like photo diaries and AI for better dietary tracking.Key Takeaways:Nutrition epidemiology studies often contradict each other due to unreliable methods.Common techniques like 24-hour recalls & food frequency questionnaires suffer from memory issues, portion size issues, and systematic biases, often underestimating food intake.Heavier individuals (higher BMI) under-report food intake more, skewing associations between diet & obesity.Speakman’s tool, based on 6,500 doubly labeled water measurements, predicts energy expenditure to flag implausible dietary survey data.Emerging technologies, like smartphone photo diaries and AI food identification, promise more accurate dietary tracking than traditional surveys.Randomized controlled trials, not surveys, provide the most reliable dietary insights; single-day intake surveys linked to outcomes years later are dubious.Speakman advises ignoring most nutrition epidemiology headlines due to their inconsistency and lack of prognostic value for behavior change.Related episode: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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

In this engaging discussion, Thomas Seyfried, a Boston College biology professor specializing in cancer metabolism, delves into the mitochondrial metabolic theory of cancer. He challenges the conventional genetic mutation perspective, highlighting how cancer cells primarily rely on fermentation for energy. Seyfried advocates for ketogenic diets as a potential method to combat cancer by depriving tumor cells of glucose. The conversation also touches on environmental factors contributing to rising cancer rates and the importance of understanding metabolic flexibility for prevention.

Send us a textShort Summary: Heart health and the ketogenic diet, with expert insights from a cardiologist and researcher.About the guest: Matthew Budoff, MD, is a preventive cardiologist and professor of medicine at UCLA School of Medicine.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.Episode Summary: Dr. Matthew Budoff discusses cholesterol, heart disease, and his study on the ketogenic diet’s impact on lean, metabolically healthy individuals with high LDL cholesterol. He explains LDL, HDL, and triglycerides, debunking myths about their direct link to heart disease, and emphasizes the importance of coronary calcium scans to assess plaque buildup. Budoff also covers statins, dietary cholesterol, and personalized heart health strategies.Key Takeaways:LDL cholesterol is not a definitive predictor of heart disease; plaque buildup, assessed via coronary calcium scans, is a better indicator.Lean metabolically healthy people on a ketogenic diet may have high LDL without increased plaque progression after one year.Coronary calcium scans, costing ~$100, are recommended for men around age 40 and women around 45-50 to evaluate heart disease risk.Statins effectively lower LDL and can reverse soft plaque, but may be overprescribed for those without plaque buildup.Dietary cholesterol has minimal impact on blood cholesterol, as the liver produces ~85% of it.Ketogenic diet can aid weight loss & diabetes control but may cause high LDL in some lean individuals, known as lean mass hyper-responders.Plaque progression depends more on existing plaque than LDL levels in metabolically healthy ketogenic diet followers.Heart health varies widely due to genetics and other unknown factors, underscoring the need for personalized assessments.Related episode:M&M #158: Ketosis & Ketogenic Diet: Brain & Mental Health, Metabolism, Diet 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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

Send us a textShort Summary: The science of obesity and appetite regulation, blending genetics and neurobiology with practical insightsAbout the guest: Giles Yeo, PhD is a professor of molecular neuroendocrinology at the University of Cambridge. He leads a lab studying obesity and appetite regulation.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.Episode Summary: Nick interviews Dr. Giles Yeo about the genetics and neurobiology of obesity, starting with the discovery of leptin in the obese mouse model, detailing its role in appetite regulation via the hypothalamus, and discussing GLP-1 drugs like Ozempic for weight loss. It delves into how genetic factors, like the leptin-melanocortin pathway, influence hunger, the heritability of body weight, and societal factors driving the obesity epidemic, emphasizing the interplay of biology and environment.Key Takeaways:Leptin, discovered through the obese mouse, signals fat levels to the brain, but its absence causes severe obesity and infertility, as seen in rare human mutations.The hypothalamus, a key brain region, senses hormones like leptin and GLP-1, balancing hunger and satiety through POMC (anorexigenic) and AgRP (orexigenic) neurons.Body weight heritability is 40-70% at the population level, but this does not mean that 40-70% of someone’s body fat composition is due to genetic factors outside human control. Dr. Yeo unpacks how to think about it.GLP-1 drugs (e.g., Ozempic) mimic gut hormones to reduce appetite, offering some people 15-25% weight loss, but require long-term safety monitoring.According to Dr. Yeo, obesity reflects energy imbalance, but nutritional density matters more than calorie counting for health, and societal changes are needed to prevent it.Related episode:M&M #132: Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUSupport 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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

Send us a textShort Summary: A mind-bending dive into evolutionary biology and health through a biophysicist’s lens, with Dr. Jack Kruse delivering provocative insights about biology, medicine, and health.About the guest: Jack Kruse, MD, is a neurosurgeon known for integrating biophysics into medicine. He challenges conventional biochemistry with his “leptin prescription” and decentralized health approach.Episode Summary: Dr. Jack Kruse joins host Nick Jikomes to explore the Great Oxygenation Event’s role in shaping life, linking it to modern health via biophysics over biochemistry. They discuss oxygen’s impact on metabolism, the significance of deuterium-depleted water, and sunlight’s influence on the leptin-melanocortin pathway. Kruse shares his dramatic weight loss journey using sunlight and cold therapy, critiques modern tech-driven obesity, and unveils a controversial history of SV40 in vaccines, tying it to cancer spikes.Key Takeaways:The Great Oxygenation Event (2.1-2.4 billion years ago) drove life’s shift to oxygen-based metabolism, with cyanobacteria as key players.Kruse argues biophysics, not biochemistry, explains evolution, spotlighting light as life’s fundamental driver.Deuterium-depleted water is important for enabling our cells and mitochondria to use energy from the TCA cycle without “shocking” the body.Sunlight exposure boosts nitric oxide, reducing food needs via the leptin pathway, challenging diet norms.Kruse lost 133 pounds in 11 months using sunlight and cold therapy, inspiring his “leptin prescription.”He links obesity to indoor tech lifestyles, disrupting heme proteins and mitochondrial function.SV40, a virus in 1950s polio vaccines, may connect to cancer rises, a story Kruse says was buried by centralized science.Related episode:M&M #196: Vaccine Contamination & Fiat Science | Kevin McKernan*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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

Send us a textShort Summary: A deep dive into the science of oxidative stress, antioxidants, aging, and neurodegenerative diseases like Alzheimer’s.About the guest: Pamela Maher, PhD is a professor at the Salk Institute in San Diego, California, with a focus on neurodegenerative diseases, oxidative stress, and antioxidants.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.Episode Summary: Dr. Pamela Maher discusses her research on cell death mechanisms, including apoptosis and ferroptosis, and their roles in health and disease. They discuss how oxidative stress from reactive oxygen species can damage cells, the body’s antioxidant defenses like glutathione and studies on natural compounds—fisetin, curcumin, and cannabinol (CBN)—that may protect against brain cell loss. The conversation covers CBN’s mitochondrial benefits in aging mouse models and broader risk factors for dementia, like obesity and hearing loss, emphasizing early intervention.Key Takeaways:Apoptosis is a controlled cell death process vital for development, while ferroptosis, linked to oxidative stress and iron, causes cells to burst and is tied to diseases like Alzheimer’s.Oxidative stress arises when reactive oxygen species overwhelm antioxidants, damaging DNA, proteins, and cell membranes, especially polyunsaturated fats.Glutathione, a key antioxidant, relies on cysteine and declines with age, but supplements like N-acetylcysteine might help, though tolerability varies.Cannabinol (CBN), a THC byproduct, protects mitochondria and improves memory in aging mice, hinting at therapeutic potential beyond cannabinoid receptors.Middle-age risk factors like visceral obesity, type 2 diabetes, and hearing loss significantly increase dementia risk, but hearing aids can reduce it.Related episode:M&M #165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition 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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts