Whether food, drugs or ideas, what you consume influences who you become. Learn directly from the best scientists & thinkers alive today about how your mind-body reacts to what you feed it.
The weekly M&M podcast features conversations with the most interesting scientists, thinkers, and technology entrepreneurs alive today.
Not medical advice.
At M&M, we are interested in trying to figure out how things work, not affirming our existing beliefs. We prefer consulting primary rather than secondary sources and independent rather than institutional voices. If we encounter uncomfortable truths or the evidence suggests unfashionable ideas may be valid, so be it.
As the host, my aim is to help you better understand how the body & mind work by curating & synthesizing information in a way that yields science-based insights that you can choose to use or disregard in your own life. Taking ownership of your health starts with taking ownership of your information diet.
I am motivated to connect the dots and distill general principles from what I learn, preferring to ask questions and play devil’s advocate to debating or incessantly pushing my own viewpoint.
All knowledge is provisional and we must work hard to prevent ourselves from becoming attached to our favorite ideas & preferred conclusions.
Wisdom comes from an iterative, trial-and-error process of learning and unlearning. Letting go of pre-conceived notions can be painful, but pain is information.
Sometimes modern discoveries teach us we must unlearn received wisdom. Other times, modern information overload & historical chauvinism cause us to forget ancient wisdom which stills applies. The framework for learning that I embody is inspired by three Ancient Greek maxims inscribed in the Temple of Apollo at Delphi:
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Send us Fan Mail Fructose survival hypothesis: how fructose metabolism in the liver triggers ATP depletion, uric acid production, oxidative stress, lipogenesis & leptin resistance. TOPICS DISCUSSED: Glucose vs Fructose Metabolism: Fructose is rapidly metabolized in the liver by fructokinase without feedback, causing ATP depletion and uric acid production, unlike glucose metabolism. Liver Effects: Fructose induces uric acid production, NADPH oxidase activation, mitochondrial oxidative stress,...
Nick Jikomes and Tucker Goodrich scrutinize a 2026 cardiology review paper that falsely asserts seed oils, like sunflower oil, reduce inflammation. They meticulously dissect the cited randomized controlled trial, revealing that only olive and canola oils (with lower omega-6 profiles) showed benefits, directly contradicting the review's claims. The discussion extends into the fundamental biology of C-reactive protein (CRP) and how oxidized omega-6 fats trigger "sterile inflammation," akin to bacterial threats, and highlights systemic issues of scientific misrepresentation, undeclared conflicts of interest from industry funders like Unilever, and data manipulation by prominent authors in nutrition research. This episode emphasizes the critical need for deep scrutiny of scientific literature, particularly for clinicians and the public.
Dr. Floyd Chilton discusses human genetic variation in dietary fat metabolism, revealing how different ancestral populations process omega-6 linoleic acid and omega-3s distinctly, leading to varying susceptibilities to chronic diseases. He highlights major methodological issues in nutrition research, such as compositional data analysis and lack of genetic stratification, which have contributed to misleading public health narratives. Chilton emphasizes the ethical imperative for accurate, diverse research to address health disparities.
Dr. Sherwood Brown, Vice Chair for Clinical Research in Psychiatry at UT Southwestern, explores the critical role of pregnenolone, a neurosteroid derived from cholesterol. He delves into its biosynthesis, diverse cellular mechanisms—including modulating NMDA and CB1 cannabinoid receptors—and its potential as a treatment for conditions like bipolar depression, postpartum depression, and cannabis use disorder. The discussion also touches upon the broader impact of corticosteroids on brain health, the dynamics of hormone levels across the lifespan, and safety considerations for pregnenolone supplementation.
Dr. Bill Harris discusses the critical role of omega-3 fatty acids like EPA and DHA in cardiovascular and brain health. He delves into their unique chemistry, how they function in cell membranes and signaling, and the impact of dietary intake versus optimal levels. The episode also covers the OmegaQuant test, offering a practical way to measure and manage personal omega-3 status for improved longevity and disease prevention.
Dr. Philip Calder, a professor of Nutritional Immunology, explores the intricate relationship between dietary fatty acids and inflammation. He details the historical evolution of parenteral nutrition, emphasizing the shift from simple lipid sources to complex blends containing omega-3s. The discussion highlights the three phases of inflammation – initiation, propagation, and active resolution – and how omega-3s derived resolvins and protectins are crucial for actively terminating inflammatory responses. Calder also explains the competition between omega-3 and omega-6 fatty acids in cell membranes and their metabolism, advocating for a nuanced understanding beyond simplistic
Dr. Andrew Pieper discusses his lab's novel findings on reversing advanced Alzheimer's disease in mice through compounds that restore mitochondrial health and normalize NAD/NADH ratios. The conversation delves into the history and limitations of the amyloid hypothesis, emphasizing a metabolic perspective where brain energy failure is a tipping point. Lifestyle interventions, genetics, and the high energy demands of neurons are explored, alongside the cautious approach to translating these promising animal model results into human clinical trials.
Send us Fan Mail How exercise in parents can improve the metabolic and cardiovascular health of their offspring through epigenetic mechanisms. TOPICS DISCUSSED: Parental exercise & offspring metabolic health: exercise before and during pregnancy improves glucose tolerance and reduces fat gain in offspring. Paternal effects via sperm: moderate voluntary wheel running alters small non-coding RNAs, especially tRNA fragments, in sperm and enhances glucose clearance, with stronger benefits in fem...
Dr. Kevin Tracey, a neurosurgeon, explains inflammation's role in diseases like heart disease, diabetes, and cancer. He details the vagus nerve's anatomical reach and its crucial function in balancing immune responses through a natural anti-inflammatory reflex. The conversation explores the limitations of broad anti-cytokine drugs and highlights the promise of emerging bioelectronic medicine, exemplified by FDA-approved vagus nerve stimulation for refractory rheumatoid arthritis, which offers targeted immunomodulation.
Send us Fan Mail How light regulate circadian rhythms, mitochondrial function, hormones, and appetite. Nick & Dr. Alexis Cowan discuss non-image-forming effects of light on the body, from melanopsin-driven circadian signaling in the eye to UV-stimulated pathways in skin and brain that influence melatonin, cortisol, melanin production, and energy balance. TOPICS DISCUSSED: Melanopsin & non-image-forming light: blue light signals daytime to the SCN master clock, suppressing melatonin and p...
Dr. Amita Sehgal explores the essential function of sleep, highlighting her lab's work with fruit flies to demonstrate that wakefulness produces oxidized lipids in neurons. These damaged fats are then transferred to glia and subsequently cleared by macrophage-like cells during sleep. This crucial metabolic cleanup protects mitochondria, enhances memory, and provides a core biological reason for sleep across species, distinguishing it from sickness-induced rest.
Send us Fan Mail The science, hype, and unknowns surrounding popular peptides like BPC-157 & TB-500 ("Wolverine stack") for injury recovery & tissue repair. Nick & Dr. Flynn McGuire discuss the surge in peptide use for injury recovery. They cover peptide basics, the preclinical evidence for BPC-157 and TB-500, mechanisms like angiogenesis and tissue repair, the lack of robust human trials, sourcing risks, regulatory bans, and the gap between anecdotal reports and scientific certainty...
Send us Fan Mail Biology of obesity resistance and factors influencing weight gain in humans and animals. TOPICS DISCUSSED: Historical views on obesity: In some cultures, like northern Africa or Stone Age societies, high body fat signaled status or attractiveness due to food scarcity, unlike today’s focus on leanness amid calorie abundance. Energy balance components: Metabolizable energy (95% absorption on average, but varying 1-11%) and unabsorbed nutrients excreted as waste significantly influ...
Dr. Douglas Wallace, a leading geneticist, delves into the endosymbiotic origin of mitochondria and their unique maternal inheritance, explaining how mitochondrial DNA haplogroups have driven human adaptation to diverse climates and diets. The discussion highlights the impact of mitochondrial heteroplasmy on aging and disease, exploring conditions like Parkinson's and cancer through a bioenergetic lens, and emphasizes the need for personalized approaches to health based on individual mitochondrial genetics.
Send us Fan Mail Role of bile acids in cholesterol regulation, digestion & metabolic diseases like diabetes. TOPICS DISCUSSED: Bile acids basics: They enable cholesterol excretion, with about half of bodily cholesterol eliminated this way, and also aid digestion by emulsifying fats to increase enzyme access. Bile production & pathway: Synthesized in liver hepatocytes, bile flows via ducts to the gallbladder for storage or directly to the small intestine; post-meal, cholecystokinin trigge...
Send us Fan Mail How the body's internal circadian clocks regulate metabolism, energy balance, and health. TOPICS DISCUSSED: Master circadian clock in the brain: Light detection via retina entrains the suprachiasmatic nucleus, which coordinates body-wide rhythms; intrinsic period slightly deviates from 24 hours, allowing seasonal flexibility. Peripheral clocks in organs: Nearly all cells have autonomous clocks; liver and fat clocks rapidly adjust to feeding time, while brain clock aligns more ti...
Send us Fan Mail Gene regulation through RNAs, the neurobiology of opioid addiction, and how psychedelics affect drug-seeking by modulating inflammation and plasticity. 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 ...
Send us Fan Mail The biology of fat tissue, estrogen's role in metabolism and health, and how exercise interacts with these processes, especially during menopause. 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 l...
Send us Fan Mail The brain's mysterious claustrum region, its role in cognitive flexibility, and how substances like alcohol and psychedelics affect neural circuits and behavior. 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 stru...
Send us Fan Mail Pharmacology & neurobiology of psychedelics & MDMA, focusing on isomers, sex-specific effects, and mechanisms in animal models. 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 distin...
Send us Fan Mail The AMP kinase pathway's role in cellular energy sensing, nutrient allocation, and its connections to health practices like fasting, exercise, and diet. 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...
Send us Fan Mail How industrial farming, seed oils, soy, and pesticides impact food nutrition and health. 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-PU...
Dr. Michael Snyder discusses individual variability in metabolic responses to different foods, highlighting the heterogeneity of Type 2 diabetes and how personal genetics, epigenetics, and microbiome influence glucose spikes. He advocates for the use of continuous glucose monitors (CGMs) to identify personal food triggers and mitigate risks for conditions like cardiovascular disease and cancer. The conversation also delves into the complex roles of fiber, short-chain fatty acids, and various lipids, and how AI can revolutionize personalized health management.
Send us Fan Mail How agricultural practices influence the nutrient density of foods, particularly meat, and the importance of hidden compounds beyond standard nutrition labels. 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...
Send us Fan Mail Cellular metabolism, mitochondrial health, and the roles of diet and environment in metabolic health, fetal & child development, and Alzheimer's. 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...
Send us Fan Mail Deep dive into how ketogenic diets and carbohydrate intake effect exercise performance, and misconceptions in sports nutrition. 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 ...
Send us Fan Mail Neurobiology of maternal care in mammals: hormonal influences, stress effects & a study on psilocybin's unexpected effects during the postpartum period. Sponsor: SporesMD . Use code TRIKOMES for 20% off pharmaceutical-grade mushroom liquid cultures & mycology products. 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 ch...
Send us Fan Mail Metabolic effects of soybean oil and linoleic acid on obesity, fatty liver, and liver function. 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 pers...
Send us Fan Mail How seasonal changes in light and dietary unsaturated fats affect circadian rhythms in mammals. 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 variatio...
Send us Fan Mail How ketosis and ketogenic diets work and how these tools can improve metabolic health, brain function, and even cancer management. 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 elect...
