Mind & Matter

• Cancer Biology: Metabolism, Mitochondria & Energy | Thomas Seyfried | 224

  Send us a textShort Summary: Cancer’s metabolic roots with Dr. Thomas Seyfried.About the guest: Thomas Seyfried, PhD is a professor of biology at Boston College. He has researched cancer metabolism, epilepsy, and lipid biochemistry for over 40 years.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. Thomas Seyfried discusses the mitochondrial metabolic theory of cancer, challenging the dominant somatic mutation theory. He explores how cancer cells rely on fermentation due to defective oxidative phosphorylation, drawing on Otto Warburg’s work. Seyfried explains how ketogenic diets and nutritional ketosis can starve cancer cells by limiting glucose and glutamine, while sharing evidence from nuclear transfer experiments and clinical studies. The conversation also covers environmental factors driving cancer and the importance of metabolic flexibility for prevention.Key Takeaways:Cancer is characterized by dysregulated cell growth, but Seyfried argues it stems from mitochondrial dysfunction, not just genetic mutations.Cancer cells ferment glucose & glutamine, unable to use fatty acids or ketones, making ketogenic diets a potential therapeutic tool.Nuclear transfer experiments show cancer traits reside in the cytoplasm, not the nucleus, challenging the somatic mutation theory.Environmental factors like processed foods, stress, and poor sleep disrupt mitochondrial function, increasing cancer risk.Seyfried’s glucose-ketone index helps monitor metabolic states to manage cancer & chronic diseases.Cancer rates are rising in younger people, possibly due to obesity, inflammation, and environmental toxins.Metabolic flexibility, cycling between ketosis and carb-based states, may mimic ancestral patterns and reduce chronic disease risk.Related episode:M&M #215: Cancer Metabolism: Sugar, Fructose, Lipids & Fasting | Gary PattiSupport 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

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• Ketogenic Diet: Cholesterol, Plaque & Heart Heart | Matthew Budoff | 223

  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 & Exercise, Cancer, Diabetes | Dominic D'AgoSupport 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

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• Genetics & Neurobiology of Obesity: Hypothalamus, Leptin, Gut Hormones, Weight Loss Drugs | Giles Yeo | 222

  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

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• Regenerative Energy & the Light Inside You | Jack Kruse | 221

  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

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• Cell Death, Oxidative Stress, PUFAs & Antioxidants | Pamela Maher | 220

  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

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