Mind & Matter
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. My beliefs: Taking ownership of your health starts with taking ownership of your information diet. 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: “Γνῶθι σεαυτόν” (Know thyself) “Μηδὲν ἄγαν” (Nothing in excess) “Ἐγγύα πάρα δ Ἄτα” (Certainty brings insanity)
Episodes
The biology of endogenous cannabinoids & history of cannabinoid-based therapeutics
TOPICS DISCUSSED:
- Anandamide vs 2-AG: The two major endocannabinoids with a shared arachidonic acid backbone but distinct head groups biological roles.
- On-demand production: Calcium-dependent enzymes release cannabinoids from membranes in response to neuronal activity patterns.
- Trafficking: Fatty acid binding proteins and extracel...
Mitochondrial peptides act as stress signals that regulate metabolism, muscle mass, and neurodegeneration.
TOPICS DISCUSSED:
- Mitochondria as Communication Hubs: Beyond ATP production, mitochondria encode peptides that regulate cell death, immunity, and inter-organ communication.
- Humanin Discovery: Identified independently by three labs; neuroprotective, longevity-linked, and capable of neutralizing APOE4 effects vi...
How the nervous and immune systems communicate, using peptides and other signals, to regulate pain, itch, and inflammation.
TOPICS DISCUSSED:
- Nociception & Pathogens: Sensory neurons detect bacterial toxins within seconds, enabling rapid host-defense coordination ahead of immune-cell recruitment.
- CGRP & neutrophils: Nociceptor-release the peptide CGRP, which blocks neutrophil (immune cell) recruitment; path...
Mitochondrial peptide MOTS-c is a stress-induced signal that reprograms cell metabolism.
TOPICS DISCUSSED:
- Mitochondrial Roles: Not just ATP production, but “speaker of the house” via communication molecules that “talk” to the rest of the cell.
- Origin of Communication: Mitochondrial peptides were likely co-opted from ancient antimicrobial factors to synchronize nuclear and mitochondrial geno...
GHK-Copper and peptides in skin care, aging, and general health.
TOPICS DISCUSSED:
- Endogenous Decline: GHK-copper levels peak in young adulthood then fall with age, reducing natural support for skin repair and collagen maintenance.
- Skin Penetration: Effective topical delivery depends on molecular size under and fat solubility, often improved by procedures such as microneedling that briefly disrupt the barrier.
- Mecha...
Blood-brain barrier as a dynamic interface allowing selective passage of nutrients, peptides, and gut hormones.
TOPICS DISCUSSED:
- Blood-Brain Barrier Structure: Capillary endothelial cells with tight junctions, absent fenestrae, and minimal vesicles create a selective interface; supported by astrocytes and pericytes.
- Crossing Mechanisms: Lipid-soluble small molecules diffuse passively; glucose, amino acids, and reg...
Ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation; chronoferoptosis, in which chronic stress sensitizes neurons gradually.
TOPICS DISCUSSED:
- Cell Death Pathways: Apoptosis proceeds through regulated steps with surface “eat me” signals that enable non-inflammatory clearance by phagocytes, whereas ferroptosis and related pathways release cellular contents that can amplify loc...
Endogenous peptide diversity, GLP-1 drugs, and methods for novel peptide discovery.
TOPICS DISCUSSED:
- Peptide Structure & Production: Short amino acid chains (3-50 residues) cleaved from larger precursors by PCSK enzymes, stored in dense-core vesicles, and released upon stimuli rather than acting as folded enzymes like proteins.
- Tissue-Specific Processing: The same precursor yields different peptides by tissue;...
The possible role of deuterium (heavy isotope of hydrogen) in regulating cell division, mitochondrial metabolism & cancer.
TOPICS DISCUSSED:
- Deuterium Basics: Deuterium is twice as massive as regular hydrogen; natural water contains ~150 ppm, with stronger oxygen-deuterium bonds slowing reactions compared to oxygen-hydrogen.
- Mitochondrial Role: Healthy mitochondria produce deuterium-depleted metabolic water (~1...
New research finds that excess antioxidants can support tumor growth in preexisting cancers.
TOPICS DISCUSSED:
- Oxidative Stress: Reactive oxygen species (ROS) generated by mitochondrial metabolism cause damage; context determines whether they promote or suppress cancer.
- Glutathione Biology: Primary cellular antioxidant made from cysteine, glycine, and glutamate; works with peroxidase enzymes to protect against ROS.
- ...
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 prod...
Deep-dive into a 2026 cardiology review paper claiming seed oils reduce inflammation, exposing misrepresentations of cited clinical trials, and detailing how oxidized Ω-6 fats trigger inflammation.
Companion article: Click HERE
TOPICS DISCUSSED:
- Seed Oil Profiles: Typical seed oils like sunflower are high in linoleic acid (omega-6 PUFA), while canola is higher in monounsaturated fats and resembles olive oil.
- Review ...
Human genetic variation in dietary fat metabolism and its implications for health & disease.
TOPICS DISCUSSED:
- Linoleic Acid Rise: Linoleic acid now comprises 6-8% or more of energy in Western diets.
- Metabolic Pathways: Omega-6 linoleic acid converts to arachidonic acid and pro-inflammatory oxylipins; omega-3 ALA converts via shared enzymes to EPA/DHA with anti-inflammatory effects.
- FADS Genetic Variants: Ancest...
Pregnenolone, a neurosteroid derived from cholesterol, affects brain activity and shows promise for treating mood and substance abuse disorders.
TOPICS DISCUSSED:
- Steroid Biosynthesis: Cholesterol converted to pregnenolone, the precursor for all steroid hormones including cortisol, aldosterone, and sex hormones.
- Corticosteroids: Synthetic versions like prednisone primarily target glucocorticoid receptors for anti-i...
How omega-3 fats in human health, including dietary intake needs, supplements, & omega fat testing.
TOPICS DISCUSSED:
- ω-3 chemistry: EPA and DHA differ from plant ALA in chain length and double-bond count, making them structurally and biologically distinct — and largely irreplaceable by ALA conversion.
- ALA-to-EPA/DHA conversion: A small percentage of dietary ALA converts to EPA, and conversion to DHA is e...
How dietary fatty acids regulate the initiation, propagation, and resolution of inflammation.
TOPICS DISCUSSED:
- Parenteral nutrition history: IV nutrition evolved from soybean oil alone in the 1960s to complex blends including fish oil as the biology of ω-3s became understood.
- Three phases of inflammation: Initiation, propagation (driven by ω-6–derived prostaglandins and leukotrienes), and active resolution (...
A metabolic view of Alzheimer's disease & the recent discovery of compounds that reverse advanced disease symptoms in mouse models by restoring mitochondrial health.
TOPICS DISCUSSED:
- Classic Alzheimer’s pathology: amyloid plaques and tau tangles identified over 120 years ago, long assumed to drive irreversible neuron loss.
- Limitations of amyloid focus: plaques appear in some cognitively normal brains; an...
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 sp...
How the vagus nerve regulates inflammation; bioelectronic therapies to treat inflammatory conditions.
Nick speaks with Dr. Kevin Tracey about inflammation as a major driver of modern diseases, the vagus nerve’s role in balancing immune responses via reflexes, limitations of anti-cytokine drugs, and emerging bioelectronic medicine using targeted nerve stimulation.
TOPICS DISCUSSED:
- Inflammation is related to d...
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 sig...
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