Mind & Matter

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. PUFAs, Energy Expenditure, Weight Gain & FeediSupport the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: 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. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. 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.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. 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 Support the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: 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. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. 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 | Richard Bazinet*Not medical aSupport the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: 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. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. 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 discussion, Manvir Singh, an anthropologist from UC Davis, explores the depths of shamanism as a universal human practice. He delves into shamanic techniques and their role in addressing uncertainty, ranging from healing to divination. Singh highlights the modern parallels of shamans in today’s world, such as tech gurus, and discusses the interplay between shamanism and organized religions. He also examines how shamanic practices can empower individuals while revealing the psychological benefits of rituals, illustrating their significance in both ancient and contemporary contexts.

Gary Miller, Professor of Environmental Health Sciences at Columbia University, dives into the crucial link between chemical exposures and neurodegenerative diseases like Parkinson's and Alzheimer's. He highlights how early detection and technology might improve outcomes. The conversation explores how lifestyle factors, such as caffeine and nicotine, could offer protective effects. Miller elaborates on exposomics—the study of lifetime chemical exposures—and its role in understanding the interplay between pollutants, diet, and health.

Mickey Pardo, a postdoctoral researcher at the Cornell Lab of Ornithology, dives deep into the fascinating world of animal communication. He discusses whether elephants have unique vocal 'names' and shares insights from his field research in Kenya. Pardo explores the complexities of elephant social structures and their emotional depth, including mourning behaviors. He also compares the communication of elephants with that of dolphins, revealing intriguing parallels and the evolution of language. It's a captivating look at animal sentience and the intricacies of nature.

Rahul Roychoudhuri, a Professor of Cancer Immunology at the University of Cambridge, dives deep into the fascinating interplay between the immune system and cancer. They discuss how cancer cells evolve to evade immune detection and the surprising role of low-dose aspirin in potentially preventing cancer metastasis. The conversation highlights the implications of inflammation on tumor growth and the prospects of new therapies enhancing immune responses. Aspirin's effects on T cells and its relationship with cancer treatment could reshape future cancer therapies.

Send us a textShort Summary: How dietary fructose affects the growth rate of cancer.About the guest: Gary Patti, PhD is a professor at Washington University in St. Louis, holding appointments in chemistry, medicine, and geneticsNote: 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 Jikomes talks to Dr. Patti, exploring how cancer cells metabolize sugars like glucose and fructose, focusing on a recent study showing fructose indirectly boosts tumor growth in mice via liver-produced lipids called LPCs. The discussion covers cancer biology basics, Warburg effect, tumor microenvironments, and systemic metabolic impacts of cancer, while also touching on dietary implications, fasting, and the complexities of nutrient use in cancer progression.Key Takeaways:Cancer cells often rely heavily on glucose, excreting it as lactate even when oxygen is available (Warburg effect), but take up more than their mitochondria can handle.In a study, high fructose diets accelerated tumor growth in mice by 4x, not because cancer cells use fructose directly, but because the liver converts it to LPCs, which tumors use to build membranes.Tumors are not just cancer cells; they recruit healthy cells in their microenvironment, and their metabolic effects ripple across the entire body, altering distant tissues.Excessive fructose consumption may worsen tumor growth, but cutting it poses little risk and could benefit cancer patients, pending human studies.Fasting may reduce cancer initiation risk in animals, but its effect on existing tumors is less clear and could worsen wasting (cachexia) in late stages.The body tightly regulates blood glucose via the liver, so simply cutting dietary glucose won’t starve tumors, highlighting cancer’s metabolic adaptability.Related episode:M&M #200: Dietary Fats & Seed Oils in Inflammation, Colon CancerSupport the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: 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. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. 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: How diet shapes the gut microbiome and impacts health, with microbiologist Dr. Peter Turnbaugh breaking down the complex science.About the guest: Peter Turnbaugh, PhD is a professor of microbiology and immunology at the University of California, San Francisco, where he leads a lab studying the gut microbiome’s role in nutrition and drug response.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 talks to Peter Turnbaugh discuss the pitfalls of oversimplified diet labels in research, Turnbaugh’s studies comparing plant-based and animal-based diets in humans, and how these shifts rapidly alter gut microbes and short-chain fatty acid profiles. Key Takeaways:The term “high-fat diet” in research is often misleading, as it can include high carbs and vary widely, complicating study comparisons.In a 2014 study, switching humans to a plant-based (high-fiber) or animal-based (ketogenic, no-fiber) diet changed their gut microbiome within one day, showing its remarkable adaptability.Ketogenic diets reduce Bifidobacterium in the gut, which may lower inflammation-linked immune cells (Th17), potentially aiding conditions like multiple sclerosis.Short-chain fatty acids (e.g., butyrate) don’t just come from fiber; they persist even on zero-fiber ketogenic diets, hinting at alternative microbial pathways.Gut microbes can activate or deactivate drugs, like antibiotics or digoxin, suggesting microbiomes may explain why drugs work differently across individuals.Ketone bodies like BHB alone can mimic some ketogenic diet effects on the microbiome and immunity, simplifying research and hinting at therapeutic potential.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, etc. at the M&M Substack Affiliates: 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. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. 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

Scott Soleimanpour, a physician-scientist from the University of Michigan, dives deep into the complex biology of diabetes. He sheds light on the critical roles of pancreatic beta cells in blood sugar regulation and the duality of the pancreas in digestion and metabolism. The conversation reveals the rising rates of type 1 diabetes, interconnected with environmental factors beyond genetics. Soleimanpour also discusses the multifaceted causes of type 2 diabetes, emphasizing lifestyle choices, dietary habits, and the need for improved treatment strategies.