Muscle is Not What We Thought (ft’ Dr Gabrielle Lyon)
These notes were generated by AI and may contain inaccuracies.
Muscles secrete hormones that affect the brain and entire body physiology, including thyroid and adrenals. Muscle becomes healthier simply by moving. Muscles are not thought of as endocrine organs, a huge oversight in the literature. Markers of unhealthy skeletal muscle include fasting blood glucose, fasting insulin, fasting triglycerides—a fingerprint for poor muscle quality. We're at the precipice of real advancement in understanding muscle.
Dr. Gabrielle Lyon discusses muscle-centric medicine. We don't have an obesity epidemic but a midlife muscle crisis. Personal story: Host's dad, an international rugby player from South Africa, played against the All Blacks. Became a high-risk obstetrician with high stress, sleep deprivation, poor diet. At 44, had occlusion of a major heart vessel but survived due to extra vessels from his athletic past—muscle as health insurance. Introduces Dr. Lyon's Forever Stronger Playbook, practical with key insights. Two-part conversation: Part one on practicals, foundations, philosophy; Part two to nerd out.
Dr. Lyon: Thanks for having me.
Host tried rugby but started too late. Teaser: Question on athletic background to stump exercise physiologists.
Number one misconception: It's too late to start building muscle. Muscle can become healthier simply by moving, regardless of body composition changes. This is underappreciated. Body fat percentage as a biomarker is becoming outdated. Certain body fat percentages (e.g., 30%) associate with comorbidities, but it's not body fat driving disease—it's IMAT (intramuscular adipose tissue), fat infiltrated into skeletal muscle through inactivity and diet outpacing muscle health. This contributes to insulin resistance and cardometabolic diseases, not overall body fat percentage. Athlete's paradox: triglycerides around mitochondria used for exercise are different.
Clinically, do not yet measure IMAT vs. overall body fat. Literature on body composition relies on DEXA, which does not measure lean mass or muscle mass directly—extrapolates and ignores quality. Higher muscle mass in obesity was thought due to carrying extra weight, but says nothing about health of skeletal muscle. Healthy muscle mass (quality and quantity) is more important than total mass—a glaring oversight. Influx of MRI data will shift this.
BMI is a weak proxy; body composition is better but nuanced. Fat distribution matters (visceral, abdominal, gluteal) with different hormonal profiles. Muscle can have infiltrated fat and varying qualities.
Without MRIs, high-quality muscle defined by strength (relative, individual baseline, progress) and metabolic profile: fasting blood glucose, fasting insulin, fasting triglycerides as markers of unhealthy skeletal muscle first, root of metabolic syndrome. Metabolic dysregulation occurs when diet and activity outpace muscle health.
Quote: "They're basically a fingerprint for poor muscle quality."
Decades of literature focused on obesity, highly processed foods, calories—ignored skeletal muscle and movement. Physical activity hadn't changed much then. Next 50 years focused on weight loss, treating obesity as primary problem. Obesity is secondary to unhealthy skeletal muscle. Liver dysregulation leads to muscle dysregulation. Skeletal muscle is primary site for glucose disposal.
Resistance training not great for weight loss. Muscle at rest burns 2-3 calories or grams of carbs per hour, primarily fatty acids—not metabolically active. Muscle's value: voluntary control to increase energy expenditure via physical activity (resistance or endurance)—only organ system under voluntary control. Focusing on skeletal muscle improves body composition, power, strength, hypertrophy, metabolism, brain health.
Dr. Lyon's training: geriatrics at WashU, geriatric nutritional science fellow. Body composition changes affected brain function and volume; more physical activity led to better brain outcomes.
Host's training: neurodegenerative diseases, Alzheimer's. Paper on Alzheimer's brains: not amyloid/tau, but NAD levels (key energy molecule in mitochondrial metabolism, etc.). Brains with high amyloid but higher NAD had fine cognition. Predictors of higher NAD independent of age: V2 max and lean mass.
Muscles not just mechanical—endocrine aspect: secrete hormones like thyroid, adrenals, impacting whole body. Grossly overlooked; muscles as endocrine organs highlighted ~2000 by Bente Pedersen (Copenhagen, Denmark; exercise physiologist, immunologist, MD). Myokines released based on contraction intensity/duration: cytokines like IL-6, TNF-alpha (pleiotropic, balance inflammation). IL-6 aids fuel utilization, sensitizes liver, directs fuel partitioning.
Exercise benefits via inter-organ crosstalk. Future: test exercise effectiveness via blood biomarkers, right type for individual's biochemical needs.
Michael Snyder (Stanford): longitudinal multiomics. Paper "Molecular Choreography of Acute Exercise" (Cell): exercise induces fitness inflammatory signature—beneficial spike for adaptation, not chronic inflammation. Precision exercise: gene expression changes invert based on insulin sensitivity (e.g., insulin resistant: down; sensitive: up). Within 5 years: multi-metabolite continuous meters + AI for personalized exercise.
Dr. Lyon: Digital twin modeling outcomes. Shift focus to muscle. GLP-1s risk trading obesity for sarcopenia epidemic. Obesity epidemic failure: 50 years circling without fix. Ran weight management clinic. GLP-1s extraordinary for diabetes/obesity but overlook muscle—accelerate aging via muscle loss. Most stop within 2 years, regain fat weight, worse long-term. Reorient to skeletal muscle metrics/imaging, get dose right—transformative.
Difficulty shifting from weight/calorie focus; resistance training doesn't aid weight loss much. Incentive structures: business models for GLP-1s, statins drive research/dialogue—not conspiracies, but direct compass to patient health.
Dr. Lyon (graduated med school 2006, fellowship 2015; psychiatry, family medicine): Careful with words due to information velocity. Studies need funding, doesn't guarantee outcomes. Was at dietary guidelines discussion (emotional). GLP-1s around 20 years for other diseases before weight loss approval. People say GLP-1s make weight loss easy, it's cheating—people still eat whatever they
GLP-1 agonists are the most effective agents for weight loss. Evidence shows better cardiovascular outcomes ahead. Studies emerging for PCOS treatment from a metabolic perspective are extraordinary. These agents are here to stay. Patients can now request medication for weight loss from doctors without much resistance.
Doctors would not readily prescribe medication for stronger muscles, better recovery, or more healthy muscle mass, such as testosterone or anabolic agents, due to lack of education. Medical school does not cover muscle health or prescribing anabolic agents. Anabolic agents are FDA-approved for anemia, HIV cachexia, and muscle wasting, saving many lives, yet carry huge stigma. Testosterone perceptions have shifted, but bias remains.
Why did I write a playbook for muscle health? Because we're going to need it. And the medical establishment has not kept up.
Education allows people to make their own decisions on biases around GLP-1s, anabolic agents, and hormone replacement.
Host provokes discussions on topics like LDL and Oreo diet with undoctinated opinions, collaborating with Alexis Cowan (PhD, Princeton). Giveaway: Five signed free copies of Gabrielle Lyon's Forever Stronger Playbook for Stay Curious Metabolism community members who read the new letter on mTor muscle paradox, muscle aging, slowing or reversing it, and leave a comment.
New guidelines upped recommended protein from 0.8 g/kg (0.36 g/lb) to 1.2-1.6 g/kg. Dietary guidelines inform federally funded organizations every 5 years, providing ranges, not hard numbers. RDA for minimum to prevent deficiency remains 0.8 g/kg; it has not doubled. Current median intake for Americans is 1.1 g/kg (50% above, 50% below).
Guidelines reorient conversation to prioritize protein in the 1.2-1.6 g/kg healthy range. For a 70 kg person, median 55g means 50% below that.
Protein needs vary by age (more above 35), physical activity (more sedentary need more absolute protein), not as percentage of calories but total grams. Never go below 100g for metabolic advantages.
Why Sedentary People Need More Absolute Protein
Skeletal muscle stimulated by resistance training and amino acids (primarily leucine). Aging causes anabolic resistance: less efficient protein utilization and sensing. Sedentary individuals lose resistance training stimulus, so compensate with higher dietary protein to maintain muscle. Prioritize protein as calories and activity decrease with age.
Evidence supports up to 2.2 g/kg (1 g/lb); no strong evidence above that. Range 0.8-2.2 g/kg; no single number fits all.
Protein won't fully replace exercise. Bed rest data: after 7 days fully inactive, protein does not fully protect against muscle mass and strength loss.
Gabrielle Lyon's go-to: lean beef for food matrix (whole foods, not isolated protein + fat).
Nick's go-to: sardines for micronutrients, omega-3s (muscle, heart, brain healthy). Anecdote: sardine experiment as major food source led to metabolic changes but skin emitting fish volatiles even when fasted, upsetting girlfriend and replicators' spouses.
Junk protein (protein Starbucks, bars with franken fats, artificial sweeteners) is misleading. Adding protein to high-calorie diet is disingenuous unless usable biological dose (all utilized). Protein distribution matters, especially in aging data based on first meal response (bolus). Plant protein often from wheat, low quality. Prioritize high-quality dietary protein, not junk.
- Chest: Push-up.
Nick's anecdote: High school freshman broke push-up record (prior 72 by senior football player at 3-second military cadence); trained to 240, then 427 in a set. Muscles don't fatigue (endurance, not power); can run marathons but poor 5K; hard to hypertrophy despite power/mass training (possibly more endurance fibers, fewer glycolytic; genetic limit per Benikio). Muscle biopsy needed to quantify fibers (painful; Lyon did for 2 years).
Hard gainers exist; genetic limits without agents.
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Back: Pull-up (Y-grip chin-up).
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Glutes: Hip thrust machine (better isolation than squats).
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Quads: Leg extensions (satisfying isolation); jumping alternating lunge for compound.
Both beneficial, hard to compare head-to-head. For time-short people, high-intensity interval training (HIIT) preferred (Martin Gibala's one-minute workout, Stu Phillips). Nick uses vertical ski ergs: 2-min sprints (500m pace, 1:52/500m by fatiguing 5th set). Teaser: Upcoming part two on randomized crossover trial with pharmacological agent (sourced placebo, grated off signs).
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