Muscle is where most of the glucose goes, and muscle insulin resistance is the first thing that breaks on the road to type 2 diabetes. Both of those are true, and neither one means that building more muscle is the treatment for obesity. This episode works through what actually decides whether a tissue handles fuel well: not how much of it you have, but how fast it's moving fuel through. We go through the one-legged exercise studies, the 18,000-person analysis of what body composition actually predicts, the athlete's paradox, the energy cost of building a kilogram of muscle, the GLP-1 lean mass panic, and why sarcopenic obesity is named after the wrong organ.

This is part two of a two-part series on storage capacity. Part one covered where body fat goes and what happens when the storage runs out. 

Timestamps

• 0:00   The one-leg study, and the muscle-centric claim
• 02:06   What obesity is, and the garage analogy
• 05:06   How glucose gets into a muscle cell
• 11:21   Insulin sensitivity improves without building muscle
• 17:11   The best case for muscle-centric medicine
• 21:13   What predicts falls and death: strength, not lean mass
• 25:18   Separating muscle size from muscle function
• 31:33   Liver fat: amount, type, and flux
• 37:54   Should you build muscle first? The arithmetic
• 42:37   Building muscle in a calorie deficit
• 50:29   GLP-1s, DXA, and the lean mass panic
• 58:23   Sarcopenic obesity, and why the name is wrong
• 01:04:37 Why size still tells you something
• 01:11:46 So what is obesity?

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Most men who start testosterone never needed it, and some who genuinely do never get treated. In the final episode of the Signal series, Dr. Jordan Feigenbaum and Dr. Austin Baraki work through who actually needs testosterone replacement, who got sold it, and what the evidence says about the risks that scared the field for a decade. We cover the blinded trial where men couldn't tell real testosterone from placebo, what the heart and prostate data actually show now that we have the trials, what testosterone does to fertility, and the framework we use to decide. We also close the story of Mark, the patient whose lab result started the series.

This is educational content, not medical advice. Talk to your physician about your personal situation.

Here we cover the real diagnosis of testosterone deficiency, primary versus secondary low testosterone, how the system both over- and under-prescribes, the SHBG trap that makes a normal level look low, the gray-zone crossover study, what replacement should actually target, why most men quit within a year, testosterone as a male contraceptive, the TRAVERSE cardiovascular results, the saturation model and prostate safety, the blood side effect worth monitoring, and when not to start at all.

Timestamps:

• 00:00 The study almost nobody mentions 
• 01:31 Who this episode is for 
• 03:35 What a real testosterone diagnosis requires 
• 07:18 Primary vs secondary low testosterone 
• 10:12 How testosterone gets over-prescribed 
• 11:35 The SHBG trap: when a low number misleads 
• 18:10 Would GLP-1 plus testosterone work better? 
• 22:19 Why genuine deficiency gets under-treated
•  24:15 The cardiovascular scare and where it came from 
• 34:11 The gray-zone study, in full 
• 41:02 What TRT should actually target, and the "900" myth 
• 47:38 Running TRT as a trial, and why 70% quit 
• 52:36 Testosterone as a contraceptive: the fertility cost 
• 57:19 Does TRT cause heart problems? The TRAVERSE trial 
• 01:01:40 Testosterone and the prostate 
• 01:09:13 The blood side effect worth watching 
• 01:12:02 When not to start testosterone 
• 01:14:26 Who actually benefits from TRT 
• 01:18:28 The Signal framework, and what happened to Mark
•  01:21:14 Five things to take away
•  01:23:33 Our conflict of interest, and the book
• 
  

Resources:

Buy the book, Signal: https://www.barbellmedicine.com/shop/learning/signal/

• Part 1: Is the testosterone crisis real?
• Part 2: Is you testosterone actually low?
• Part 3: What's actually driving your testosterone down?

New Barbell Medicine Hybrid 5K and 10K Run + Lift Programs

Barbell Medicine coaching and templates: https://www.barbellmedicine.com

Testosterone Action Plan: https://www.barbellmedicine.com/testosterone-action-plan/ 

1. Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60(7):762-769. doi:10.1111/j.1742-1241.2006.00992.x
2. Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS. Trends in androgen prescribing in the United States, 2001-2011. JAMA Intern Med. 2013;173(15):1465-1466. doi:10.1001/jamainternmed.2013.6895
3. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. doi:10.1210/jc.2018-00229
4. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432. doi:10.1016/j.juro.2018.03.115
5. Corona G, Goulis DG, Huhtaniemi I, et al. European Academy of Andrology (EAA) and European Society of Endocrinology (ESE) recommendations on the diagnosis and management of male hypogonadism. Andrology. 2020;8(5):970-987. doi:10.1111/andr.12770
6. Morgentaler A, Zitzmann M, Traish AM, et al. Commentary: who is a candidate for testosterone therapy? A synthesis of international expert opinions. J Sex Med. 2014;11(7):1636-1645. doi:10.1111/jsm.12546
7. Mok SF, Fennell C, Savkovic S, et al. Testosterone for androgen deficiency-like symptoms in men without pathologic hypogonadism: a randomized, placebo-controlled cross-over with masked choice extension clinical trial. J Gerontol A Biol Sci Med Sci. 2020;75(9):1723-1731. doi:10.1093/gerona/glz195
8. Clift AK, Johnson H, Huang DR, Morgentaler A. Real-world outcomes and safety of testosterone therapy: a longitudinal, retrospective cohort study of over 9,000 men. World J Mens Health. 2026;44(2):438-450. doi:10.5534/wjmh.250245
9. Malik RD, Wang CE, Lapin B, Lakeman JC, Helfand BT. Characteristics of men undergoing testosterone replacement therapy and adherence to follow-up recommendations in a metropolitan multicenter health care system. Urology. 2015;85(6):1382-1388. doi:10.1016/j.urology.2015.01.027
10. Donatucci C, Cui Z, Fang Y, Muram D. Long-term treatment patterns of testosterone replacement medications. J Sex Med. 2014;11(8):2092-2099. doi:10.1111/jsm.12608
11. Saad F, Aversa A, Isidori AM, Zafalon L, Zitzmann M, Gooren L. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol. 2011;165(5):675-685. doi:10.1530/EJE-11-0221
12. Ly LP, Liu PY, Handelsman DJ. Rates of suppression and recovery of human sperm output in testosterone-based hormonal contraceptive regimens. Hum Reprod. 2005;20(6):1733-1740. doi:10.1093/humrep/deh834
13. Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C; Hormonal Male Contraception Summit Group. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. Lancet. 2006;367(9520):1412-1420. doi:10.1016/S0140-6736(06)68614-5
14. Ko EY, Siddiqi K, Brannigan RE, Sabanegh ES Jr. Empirical medical therapy for idiopathic male infertility: a survey of the American Urological Association. J Urol. 2012;187(3):973-978. doi:10.1016/j.juro.2011.10.137
15. Kohn TP, Louis MR, Pickett SM, et al. Age and duration of testosterone therapy predict time to return of sperm count after human chorionic gonadotropin therapy. Fertil Steril. 2017;107(2):351-357.e1. doi:10.1016/j.fertnstert.2016.10.004
16. Wenker EP, Dupree JM, Langille GM, et al. The use of HCG-based combination therapy for recovery of spermatogenesis after testosterone use. J Sex Med. 2015;12(6):1334-1337. doi:10.1111/jsm.12890
17. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109-122. doi:10.1056/NEJMoa1000485
18. Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829-1836. doi:10.1001/jama.2013.280386
19. Basaria S, Harman SM, Travison TG, et al. Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels: a randomized clinical trial. JAMA. 2015;314(6):570-581. doi:10.1001/jama.2015.8881
20. Budoff MJ, Ellenberg SS, Lewis CE, et al. Testosterone treatment and coronary artery plaque volume in older men with low testosterone. JAMA. 2017;317(7):708-716. doi:10.1001/jama.2016.21043
21. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389(2):107-117. doi:10.1056/NEJMoa2215025
22. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1(4):293-297.
23. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. 2009;55(2):310-320. doi:10.1016/j.eururo.2008.09.024
24. Khera M, Crawford D, Morales A, Salonia A, Morgentaler A. A new era of testosterone and prostate cancer: from physiology to clinical implications. Eur Urol. 2014;65(1):115-123. doi:10.1016/j.eururo.2013.08.015
25. Bhasin S, Lincoff AM, Nissen SE, et al. Prostate safety events during testosterone replacement therapy in men with hypogonadism: a randomized clinical trial. JAMA Netw Open. 2023;6(12):e2348692. doi:10.1001/jamanetworkopen.2023.48692
26. Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611-624. doi:10.1056/NEJMoa1506119

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In 2004 a surgeon removed about ten kilograms of fat from fifteen women and measured everything that mattered. Nothing improved. Four years later, it still hadn't.

That result should have ended an argument about body fat. Instead the argument got more specific, and the version you've heard most recently is that visceral fat, the fat around your organs, is the dangerous kind. I've said a version of that myself on this show, and in this episode I expand upon it.

This one starts from the beginning: what your fat is actually for, what insulin is, and what insulin resistance means, in plain terms and assuming nothing. Then four experiments that all point the same direction. Fat removed surgically, and the disease doesn't follow. People born with no fat tissue at all, who get the entire disease anyway. A hormone that reversed a 48% fatty liver without adding a gram of fat. And a diabetes drug that made people heavier and healthier at the same time.

The second half is practical. What a fatty liver actually does over twenty years, what BMI can and can't do, why the Lancet Commission changed the definition of obesity in 2025, and the exact order of tests I'd use, including the TyG index, FIB-4, and where each one stops working.

Part one of two. Next episode is about muscle.

Timestamps:

00:00 The Liposuction Experiment

02:06 The Visceral Fat Correction

05:47 What Fat Is For

08:14 The Carb Insulin Model

10:51 Filling The Garage

14:35 Taking The Fat Out

17:57 Born Without Fat Tissue

22:52 Heavier And Healthier

25:05 Neptune And Vulcan

29:57 The Patient Nobody Checked

33:59 What Every Ruler Missed

36:00 What To Actually Order

40:29 What Obesity Actually Is

Resources:

Vital 5 (TyG , waist to height, etc. discussion):

https://www.barbellmedicine.com/vital-5-action-plan/

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1. Klein S, Fontana L, Young VL, et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med. 2004;350(25):2549-2557. doi:10.1056/NEJMoa033179
2. Mohammed BS, Cohen S, Reeds D, Young VL, Klein S. Long-term effects of large-volume liposuction on metabolic risk factors for coronary heart disease. Obesity (Silver Spring). 2008;16(12):2648-2651. doi:10.1038/oby.2008.418
3. Sommer I, Teufer B, Szelag M, et al. The performance of anthropometric tools to determine obesity: a systematic review and meta-analysis. Sci Rep. 2020;10(1):12699. doi:10.1038/s41598-020-69498-7
4. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005;115(5):1343-1351. doi:10.1172/JCI23621
5. Spalding KL, Arner E, Westermark PO, et al. Dynamics of fat cell turnover in humans. Nature. 2008;453(7196):783-787. doi:10.1038/nature06902
6. Fabbrini E, Tamboli RA, Magkos F, et al. Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults. Gastroenterology. 2010;139(2):448-455. doi:10.1053/j.gastro.2010.04.056
7. Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350(12):1220-1234. doi:10.1056/NEJMra025261
8. Al Yaarubi S, Alsagheir A, Al Shidhani A, et al. Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa. Orphanet J Rare Dis. 2024;19(1):118. doi:10.1186/s13023-024-03084-2
9. Petersen KF, Oral EA, Dufour S, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest. 2002;109(10):1345-1350. doi:10.1172/JCI200215001
10. Miyazaki Y, Mahankali A, Matsuda M, et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2002;87(6):2784-2791. doi:10.1210/jcem.87.6.8567
11. Cusi K, Orsak B, Bril F, et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med. 2016;165(5):305-315. doi:10.7326/M15-1774
12. Taylor R, Barnes AC, Hollingsworth KG, et al. Aetiology of type 2 diabetes in people with a 'normal' body mass index: testing the personal fat threshold hypothesis. Clin Sci (Lond). 2023;137(16):1333-1346. doi:10.1042/CS20230586
13. Martin S, Cule M, Basty N, et al. Genetic evidence for different adiposity phenotypes and their opposing influences on ectopic fat and risk of cardiometabolic disease. Diabetes. 2021;70(8):1843-1856. doi:10.2337/db21-0129
14. Martin S, Sorokin EP, Thomas EL, et al. Estimating the effect of liver and pancreas volume and fat content on risk of diabetes: a Mendelian randomization study. Diabetes Care. 2022;45(2):460-468. doi:10.2337/dc21-1262
15. Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30(7):2037-2048. doi:10.1038/s41591-024-03018-2
16. Portillo-Sanchez P, Bril F, Maximos M, et al. High prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and normal plasma aminotransferase levels. J Clin Endocrinol Metab. 2015;100(6):2231-2238. doi:10.1210/jc.2015-1966
17. Hagström H, Nasr P, Ekstedt M, et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol. 2017;67(6):1265-1273. doi:10.1016/j.jhep.2017.07.027
18. Rubino F, Cummings DE, Eckel RH, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025;13(3):221-262. doi:10.1016/S2213-8587(24)00316-4
19. Guerrero-Romero F, Simental-Mendía LE, González-Ortiz M, et al. The product of triglycerides and glucose, a simple measure of insulin sensitivity: comparison with the euglycemic-hyperinsulinemic clamp. J Clin Endocrinol Metab. 2010;95(7):3347-3351. doi:10.1210/jc.2010-0288
20. Sánchez-García A, Rodríguez-Gutiérrez R, Mancillas-Adame L, et al. Diagnostic accuracy of the triglyceride and glucose index for insulin resistance: a systematic review. Int J Endocrinol. 2020;2020:4678526. doi:10.1155/2020/4678526
21. McLaughlin T, Abbasi F, Cheal K, Chu J, Lamendola C, Reaven G. Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann Intern Med. 2003;139(10):802-809. doi:10.7326/0003-4819-139-10-200311180-00007
22. McPherson S, Hardy T, Dufour JF, et al. Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis. Am J Gastroenterol. 2017;112(5):740-751. doi:10.1038/ajg.2016.453
23. Mózes FE, Lee JA, Selvaraj EA, et al. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. Gut. 2022;71(5):1006-1019. doi:10.1136/gutjnl-2021-324243
24. Bansal MB, Patton H, Morgan TR, Carr RM, Dranoff JA, Allen AM. Semaglutide therapy for metabolic dysfunction-associated steatohepatitis: November 2025 updates to AASLD practice guidance. Hepatology. 2025;83(5):1326-1340. doi:10.1097/HEP.0000000000001608
25. Tomiyama AJ, Hunger JM, Nguyen-Cuu J, Wells C. Misclassification of cardiometabolic health when using body mass index categories in NHANES 2005-2012. Int J Obes (Lond). 2016;40(5):883-886. doi:10.1038/ijo.2016.17
26. Wildman RP, Muntner P, Reynolds K, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999-2004). Arch Intern Med. 2008;168(15):1617-1624. doi:10.1001/archinte.168.15.1617
27. Mongraw-Chaffin M, Foster MC, Anderson CAM, et al. Metabolically healthy obesity, transition to metabolic syndrome, and cardiovascular risk. J Am Coll Cardiol. 2018;71(17):1857-1865. doi:10.1016/j.jacc.2018.02.055
28. Gujral UP, Vittinghoff E, Mongraw-Chaffin M, et al. Cardiometabolic abnormalities among normal-weight persons from five racial/ethnic groups in the United States: a cross-sectional analysis of two cohort studies. Ann Intern Med. 2017;166(9):628-636. doi:10.7326/M16-1895
29. Ruderman NB, Schneider SH, Berchtold P. The "metabolically-obese," normal-weight individual. Am J Clin Nutr. 1981;34(8):1617-1621. doi:10.1093/ajcn/34.8.1617
30. Sims EA. Are there persons who are obese, but metabolically healthy? Metabolism. 2001;50(12):1499-1504. doi:10.1053/meta.2001.27213
31. National Heart, Lung, and Blood Institute. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. NIH Publication 98-4083. Bethesda, MD: National Institutes of Health; September 1998.
32. American Medical Association House of Delegates. Resolution 420 (A-13): Recognition of Obesity as a Disease. Adopted June 18, 2013.
33. American Medical Association Council on Science and Public Health. Report 3-A-13: Is Obesity a Disease? 2013.
34. Rey-López JP, de Rezende LF, Pastor-Valero M, Tess BH. The prevalence of metabolically healthy obesity: a systematic review and critical evaluation of the definitions used. Obes Rev. 2014;15(10):781-790. doi:10.1111/obr.12198
35. Hinnouho GM, Czernichow S, Dugravot A, Batty GD, Kivimaki M, Singh-Manoux A. Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes Care. 2013;36(8):2294-2300. doi:10.2337/dc12-1654
36. Herman WH, Ye W, Griffin SJ, et al. Early detection and treatment of type 2 diabetes reduce cardiovascular morbidity and mortality: a simulation of the results of the Anglo-Danish-Dutch study of intensive treatment in people with screen-detected diabetes in primary care (ADDITION-Europe). Diabetes Care. 2015;38(8):1449-1455. doi:10.2337/dc14-2459
37. Le MH, Yeo YH, Cheung R, Wong VW, Nguyen MH. Ethnic influence on nonalcoholic fatty liver disease prevalence and lack of disease awareness in the United States, 2011-2016. J Intern Med. 2020;287(6):711-722. doi:10.1111/joim.13035
38. Sutin AR, Stephan Y, Terracciano A. Weight discrimination and risk of mortality. Psychol Sci. 2015;26(11):1803-1811. doi:10.1177/0956797615601103
39. Amy NK, Aalborg A, Lyons P, Keranen L. Barriers to routine gynecological cancer screening for White and African-American obese women. Int J Obes (Lond). 2006;30(1):147-155. doi:10.1038/sj.ijo.0803105
40. Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions? A systematic review and meta-analysis. Ann Intern Med. 2013;159(11):758-769. doi:10.7326/0003-4819-159-11-201312030-00008

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A popular paper claimed the longevity benefit of lifting disappears once you train more than an hour a week. It's a real paper, but the claim is a misread. This is the free cut of this month's Direct Line, where Drs. Feigenbaum and Baraki also take on whether GLP-1s affect your mood, the "same calories, more weight loss" protein argument, and what you can actually do in the gym when you have chronic fatigue syndrome.

For education and infotainment, not medical advice.

To become a member and have us answer YOUR questions, join today:

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Timestamps:

0:00 Intro

0:38 The paper: does lifting stop helping after an hour?

3:19 The newer 147,000-person, 30-year study

13:21 GLP-1s, mood, and motivation

14:50 The FDA reverses the suicide warning

19:29 What happened when they gave people a GLP-1 in a bar

24:54 Is a calorie just a calorie?

28:17 The "same calories, more weight loss" protein study

30:48 Does keto break the laws of physics?

34:56 Lifting with chronic fatigue syndrome

36:14 The identical-twin experiment

37:36 Can lifting in bed do anything?

45:33 Get the full Direct Line

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https://www.barbellmedicine.com/shop/learning/signal/

1. Momma H, Kawakami R, Honda T, Sawada SS. Muscle-strengthening activities are associated with lower risk and mortality in major non-communicable diseases: a systematic review and meta-analysis of cohort studies. *Br J Sports Med*. 2022;56(13):755-763. doi:10.1136/bjsports-2021-105061

2. Dankel SJ, Loenneke JP, Loprinzi PD. Dose-dependent association between muscle-strengthening activities and all-cause mortality: prospective cohort study among a national sample of adults in the USA. *Arch Cardiovasc Dis*. 2016;109(11):626-633. doi:10.1016/j.acvd.2016.04.005

3. Zhang Y, Lee DH, Rezende LFM, Ma Y, Giovannucci E. Long-term resistance training with all-cause and cause-specific mortality: assessing dose-response and joint associations with aerobic physical activity. *Br J Sports Med*. Published online June 2, 2026. doi:10.1136/bjsports-2025-110503

4. US Food and Drug Administration. FDA requests removal of suicidal behavior and ideation warning from glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications. Drug Safety Communication. January 13, 2026. Accessed August 12, 2026. https://www.fda.gov/drugs/drug-safety-communications/fda-requests-removal-suicidal-behavior-and-ideation-warning-glucagon-peptide-1-receptor-agonist-glp

5. Hendershot CS, Bremmer MP, Paladino MB, et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. *JAMA Psychiatry*. 2025;82(4):395-405. doi:10.1001/jamapsychiatry.2024.4789

6. Klausen MK, Justesen SK, Pedersen JN, et al. Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial. *Lancet*. 2026;407(10540):1687-1698. doi:10.1016/S0140-6736(26)00305-3

7. Haghighat N, Ashtary-Larky D, Bagheri R, et al. The effect of 12 weeks of euenergetic high-protein diet in regulating appetite and body composition of women with normal-weight obesity: a randomised controlled trial. *Br J Nutr*. 2020;124(10):1044-1051. doi:10.1017/S0007114520002019

8. Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Board on the Health of Select Populations, Institute of Medicine. *Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness*. National Academies Press; 2015. Accessed August 12, 2026. https://www.ncbi.nlm.nih.gov/books/NBK274235/

9. Giloteaux L, Hanson MR, Keller BA. A pair of identical twins discordant for myalgic encephalomyelitis/chronic fatigue syndrome differ in physiological parameters and gut microbiome composition. *Am J Case Rep*. 2016;17:720-729. doi:10.12659/AJCR.900314

10. Rangan A, Brealey SD, Keding A, et al. Management of adults with primary frozen shoulder in secondary care (UK FROST): a multicentre, pragmatic, three-arm, superiority randomised clinical trial. *Lancet*. 2020;396(10256):977-989. doi:10.1016/S0140-6736(20)31965-6

11. Millar NL, Meakins A, Struyf F, et al. Frozen shoulder. *Nat Rev Dis Primers*. 2022;8(1):59. doi:10.1038/s41572-022-00386-2

12. US Department of Agriculture, US Department of Health and Human Services. *Dietary Guidelines for Americans, 2025-2030*. January 2026. Accessed August 12, 2026. https://www.dietaryguidelines.gov/

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An FDA advisory committee just voted to open a legal compounding supply line for six of seven peptides, including BPC-157 and TB-500, over the objection of the FDA's own scientists, who recommended against all seven. Dr. Jordan Feigenbaum walks through what the Pharmacy Compounding Advisory Committee actually voted on, why a vote about ulcerative colitis ends up governing tendon and joint use, what the single human BPC-157 trial does and doesn't show, and why "a pharmacy makes it safe" and "there's no money to study it" don't hold up. Evidence-based, no hype, no nocebo.

Timestamps:

 | 00:00:00 | The FDA voted 8-6. What it actually means

 | 00:01:25 | What I am, and am not, claiming

 | 00:03:21 | How they got here: Category 2 and the paperwork

 | 00:07:17 | Who was in the room: the panel that flipped

 | 00:10:57 | What they voted on: compounding and the bulks list

 | 00:15:37 | "No money in it, you can't patent it"

 | 00:18:24 | The trials already run: Plevna and MK-677

 | 00:22:55 | "I took it and it worked": placebo and fake surgery

 | 00:27:02 | The one human trial: Ruenzi 2005

 | 00:32:28 | Is it natural? Is it even a drug?

 | 00:36:58 | Harm reduction, or follow the money?

 | 00:42:45 | Three times a missing trial went wrong

 | 00:50:58 | Safety: known, unknown, and unknowable

 | 00:55:22 | The other six peptides

 | 00:58:22 | What I'd actually tell you

 | 01:02:08 | What actually works, and what would change my mind

Resources:

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1. US Food and Drug Administration. FDA Briefing Document: Pharmacy Compounding Advisory Committee Meeting. July 23-24, 2026. Silver Spring, MD: FDA; 2026.

2. US Food and Drug Administration. FDA review of BPC-157-related bulk drug substances. PCAC Briefing Document. July 23-24, 2026. Media 193343. Accessed July 24, 2026. https://www.fda.gov/media/193343/download

3. US Food and Drug Administration. FDA review of TB-500-related bulk drug substances. PCAC Briefing Document. July 23-24, 2026. Media 193349.

4. US Food and Drug Administration. FDA review of KPV-, MOTS-c-, Semax-, Epitalon-, and Emideltide-related bulk drug substances. PCAC Briefing Documents. July 23-24, 2026.

5. US Food and Drug Administration. Questions for the Pharmacy Compounding Advisory Committee. July 23-24, 2026.

6. US Food and Drug Administration. Pharmacy Compounding Advisory Committee meeting roster. July 23-24, 2026. Media 193772.

7. US Food and Drug Administration. Pharmacy Compounding Advisory Committee meeting roster. 2022. Media 159040.

8. openFDA. FAERS adverse event reports for BPC-157. Accessed July 24, 2026. https://open.fda.gov

9. Pharmacy compounding; 503A bulk drug substances. 21 CFR §216.23 (2026).

10. Federal Food, Drug, and Cosmetic Act §503A, 21 USC §353a (pharmacy compounding).

11. Abigail Alliance for Better Access to Developmental Drugs v von Eschenbach, 495 F3d 695 (DC Cir 2007).

12. United States v Rutherford, 442 US 544 (1979).

13. Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017, Pub L No. 115-176, 132 Stat 1372 (2018).

14. US Food and Drug Administration. Regulatory considerations for human drug products containing peptides. Guidance for Industry (draft). 2020.

15. Ruenzi M, Stolte M, Veljaca M, et al. Efficacy and safety of PL 14736 (BPC 157) in patients with active ulcerative colitis [abstract]. Gastroenterology. 2005. Meeting abstract; full study not published.

16. Staresinic M, Petrovic I, Novinscak T, et al. Effective therapy of transected quadriceps muscle in rat: gastric pentadecapeptide BPC 157. J Orthop Res. 2006;24(5):1109-1117. doi:10.1002/jor.20089

17. Gwyer D, Wragg NM, Wilson SL. Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell Tissue Res. 2019;377(2):153-159. doi:10.1007/s00441-019-03016-8

18. Sikiric P, Skrtic A, Gojkovic S, et al. Stable gastric pentadecapeptide BPC 157 and hemorrhage/thrombosis. Pharmaceuticals (Basel). 2026;19(3):463. doi:10.3390/ph19030463

19. Stavchansky VV, Filippenkov IB, Dergunova LV, Limborska SA. The role of glyprolines in the regulation of gene expression: focus on Semax. Genes (Basel). 2022;13(12):2380. doi:10.3390/genes13122380

20. Mendias CL, Awan TM. The safety and efficacy of approved and unapproved peptides. Sports Med. 2026. doi:10.1007/s40279-026-02437-0

21. Moseley JB, O'Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347(2):81-88. doi:10.1056/NEJMoa013259

22. Cobb LA, Thomas GI, Dillard DH, Merendino KA, Bruce RA. An evaluation of internal-mammary-artery ligation by a double-blind technic. N Engl J Med. 1959;260(22):1115-1118.

23. Dimond EG, Kittle CF, Crockett JE. Comparison of internal mammary artery ligation and sham operation for angina pectoris. Am J Cardiol. 1960;5:483-486.

24. Alfredson H, Pietila T, Jonsson P, Lorentzon R. Heavy-load eccentric calf muscle training for the treatment of chronic Achilles tendinosis. Am J Sports Med. 1998;26(3):360-366. doi:10.1177/03635465980260030301

25. Kongsgaard M, Kovanen V, Aagaard P, et al. Corticosteroid injections, eccentric decline squat training and heavy slow resistance training in patellar tendinopathy. Scand J Med Sci Sports. 2009;19(6):790-802. doi:10.1111/j.1600-0838.2009.00949.x

26. Langberg H, Skovgaard D, Karamouzis M, Bulow J, Kjaer M. Metabolism and inflammatory mediators in the peritendinous space measured by microdialysis during intermittent isometric exercise in humans. J Physiol. 1999;515(Pt 3):919-927. doi:10.1111/j.1469-7793.1999.919ab.x

27. Coombes BK, Bisset L, Brooks P, Khan A, Vicenzino B. Effect of corticosteroid injection, physiotherapy, or both on clinical outcomes in patients with unilateral lateral epicondylalgia: a randomized controlled trial. JAMA. 2013;309(5):461-469. doi:10.1001/jama.2013.129

28. Kearney RS, Ji C, Warwick J, et al. Effect of platelet-rich plasma injection vs sham injection on tendon dysfunction in chronic midportion Achilles tendinopathy: a randomized clinical trial. JAMA. 2021;326(2):137-144. doi:10.1001/jama.2021.6986

29. Pavlova AV, Shim JSC, Moss R, et al. Effect of resistance exercise dose components for tendinopathy management: a systematic review with meta-analysis. Br J Sports Med. 2023;57(20):1327-1334. doi:10.1136/bjsports-2022-105754

30. Weintraub M, Sundaresan PR, Madan M, et al. Long-term weight control study I (weeks 0 to 34): fenfluramine plus phentermine versus placebo. Clin Pharmacol Ther. 1992;51(5):586-594. doi:10.1038/clpt.1992.69

31. Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997;337(9):581-588. doi:10.1056/NEJM199708283370901

32. Centers for Disease Control and Prevention. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: interim public health recommendations, 1997. MMWR Morb Mortal Wkly Rep. 1997;46(45):1061-1066.

33. Bombardier C, Laine L, Reicin A, et al; VIGOR Study Group. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med. 2000;343(21):1520-1528. doi:10.1056/NEJM200011233432103

34. Graham DJ, Campen D, Hui R, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365(9458):475-481. doi:10.1016/S0140-6736(05)17864-7

35. Smith RM, Schaefer MK, Kainer MA, et al; Multistate Fungal Infection Outbreak Response Team. Fungal infections associated with contaminated methylprednisolone injections. N Engl J Med. 2013;369(17):1598-1609. doi:10.1056/NEJMoa1213978

36. Adunsky A, Chandler J, Heyden N, et al. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Arch Gerontol Geriatr. 2011;53(2):183-189. doi:10.1016/j.archger.2010.10.004 [Trial terminated early for a congestive-heart-failure safety signal.]

37. Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. 2008;149(9):601-611. doi:10.7326/0003-4819-149-9-200811040-00003

38. Van Wagoner RM, Eichner A, Bhasin S, Deuster PA, Eichner D. Chemical composition and labeling of substances marketed as selective androgen receptor modulators and sold via the internet. JAMA. 2017;318(20):2004-2010. doi:10.1001/jama.2017.17069

39. ECRI and Institute for Safe Medication Practices. Unapproved peptide products: safety and quality concerns [white paper]. Plymouth Meeting, PA: ECRI; April 2026.

40. Center for Science in the Public Interest. What are injectable peptides, and are they safe? Accessed July 24, 2026. https://www.cspinet.org

41. World Anti-Doping Agency. The 2026 Prohibited List. Montreal, QC: WADA; 2026. Accessed July 24, 2026. https://www.wada-ama.org

42. US Anti-Doping Agency. BPC-157: a prohibited peptide. Accessed July 24, 2026. https://www.usada.org

43. FDA committee votes in favor of compounding several peptides. Time. July 23, 2026. Accessed July 24, 2026. https://time.com

44. FDA advisory committee backs controversial peptides. Regulatory Affairs Professionals Society (RAPS). 2026. Accessed July 24, 2026. https://www.raps.org

45. FDA panel okays peptides for compounding, including BPC-157 and KPV. STAT News. July 23, 2026. Accessed July 24, 2026. https://www.statnews.com

46. FDA panel recommends easing peptide restrictions over agency scientists' objections. NBC News. 2026. Accessed July 24, 2026. https://www.nbcnews.com

47. Associated Press. Financial ties reported among FDA peptide advisory panel members. 2026. Accessed July 24, 2026.

48. Leerink Partners. Equity research note: PCAC peptide vote and the telehealth compounding market. 2026.

49. Examine.com. BPC-157 research breakdown. Accessed July 24, 2026. https://examine.com/supplements/bpc-157/

50. Jarry J. Body protection compound: no proof required. McGill Office for Science and Society. Accessed July 24, 2026. https://www.mcgill.ca/oss

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A previously healthy 21-year-old shows up with seven months of headaches and 30-plus pounds of weight gain he can’t explain. He’s eating the same and training more, and the scale climbs anyway. We hand the case to Dr. Austin Baraki cold and work it in real time: the exam, the labs, the MRI, and two diagnoses that turn a headache workup into the clearest proof we’ve got that body weight is set by the brain, not by character. This is the capstone of our weight series (willpower, calories, protein), and it ends on the drug that, this year, did something for these patients that nothing had done before.

Timestamps

• 00:00:00 Cold open: the man who couldn’t stop gaining weight
• 00:01:49 Meet the case (and the rules of the game)
• 00:02:36 The presentation: 21, headaches, unexplained weight gain
• 00:03:57 Austin’s one-liner and how a clinician builds a differential
• 00:05:10 Secondary headaches: what raises the red flag
• 00:13:12 The exam: vitals, and the eye findings that matter
• 00:14:37 The labs, one number at a time
• 00:16:08 Raised pressure and a visual-field clue (bitemporal hemianopia)
• 00:20:45 The MRI
• 00:21:54 First diagnosis: craniopharyngioma
• 00:25:32 The name: a tumor built from tooth tissue
• 00:25:50 Surgery, and what it costs
• 00:27:43 The new mystery: gaining weight faster than ever
• 00:33:41 Second diagnosis: acquired hypothalamic obesity
• 00:39:17 How your brain sets your weight: the POMC brake and the AgRP accelerator
• 00:42:07 What about leptin?
• 00:45:46 Monogenic vs common obesity
• 00:50:30 Why GLP-1 drugs still worked: the brainstem backdoor
• 00:52:11 Responders and non-responders
• 00:55:40 Setmelanotide: a drug for the broken circuit
• 00:56:53 TRANSCEND, and the new FDA approval
• 00:58:55 What it costs
• 01:01:32 Why we care about body fat at all: the garage
• 01:04:36 Flux: which fat is actually dangerous
• 01:09:15 Close

Resources

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1. Brijmohan A, et al. Acquired hypothalamic obesity following craniopharyngioma resection in a young adult [case report]. 2025. PMCID: PMC12268545; PMID: 40677794. 

2. Miller JL, et al; TRANSCEND investigators. Setmelanotide in acquired hypothalamic obesity: a phase 3 randomized trial. N Engl J Med. 2026. 

3. Rhythm Pharmaceuticals. FDA approves IMCIVREE (setmelanotide) for acquired hypothalamic obesity. News release. March 19, 2026.

4. US Food and Drug Administration. FDA approves first treatment for weight management for people with certain rare genetic conditions (setmelanotide). 2020.

5. Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387(6636):903-908.

6. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341(12):879-884.

7. Krude H, Biebermann H, Luck W, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19(2):155-157.

8. Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348(12):1085-1095.

9. Clément K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998;392(6674):398-401.

10. Fabbrini E, Tamboli RA, Magkos F, et al. Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults. Gastroenterology. 2010;139(2):448-455.

11. Klein S, Fontana L, Young VL, et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med. 2004;350(25):2549-2557.

12. Guyenet SJ. The Hungry Brain: Outsmarting the Instincts That Make Us Overeat. Flatiron Books; 2017. 

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Every couple of years a new headline warns that the protein you eat is quietly hurting you. This year the target is your kidneys. Before that it was cancer, then your bones, then the claim that your body can only use twenty or thirty grams of protein at a meal. In this episode, Dr. Jordan Feigenbaum goes through the actual studies behind each scare: the kidney trials, the 2014 IGF-1 and cancer paper that started the panic, the acid-ash bone hypothesis, and the per-meal "cap." Each fear starts from a real mechanism, and each one was run straight to a frightening conclusion the clinical outcomes never supported.

The take home is simple. For a healthy adult, protein is not the lever people think it is, and where a real signal exists (processed and red meat, or a kidney that is already diseased) it tracks the whole dietary pattern more than the protein number. The two things that actually decide your health here are whether you eat mostly real food and whether you train.

Timestamps

• 00:00 The protein scare cycle 
• 01:23 The four fears 
• 01:59 Kidneys: healthy kidneys under higher protein 
• 06:22 Kidney disease: does cutting protein help? 
• 09:38 Red meat and the dietary pattern, not protein 
• 12:00 Muscle, aging, and lifting on a restricted diet 
• 13:54 Cancer: IGF-1 and the 2014 study everyone cites 
• 16:22 The age reversal, and what travels with protein 
• 18:48 Bigger data, processed meat, and the IGF-1 tell 
• 22:15 Bones and the acid-ash myth 
• 25:13 The 30-gram cap 
• 27:17 What protein actually does, and how much you need 
• 32:20 The two questions that matter

Resources:

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Studies

• Levine et al. Cell Metabolism 2014. doi:10.1016/j.cmet.2014.02.006
• Naghshi et al. BMJ 2020. doi:10.1136/bmj.m2412 
• Devries et al. J Nutr 2018. doi:10.1093/jn/nxy197 
• Antonio et al. J Nutr Metab 2016. doi:10.1155/2016/9104792 
• Knight et al. Ann Intern Med 2003. doi:10.7326/0003-4819-138-6-200303180-00009 
• Klahr et al. (MDRD). NEJM 1994. doi:10.1056/NEJM199403313301301
•  Hahn, Hodson & Fouque. Cochrane 2020. doi:10.1002/14651858.CD001892.pub5 
• Obeid, Hiremath & Topf. Kidney360 2022. doi:10.34067/KID.0001002022 
• Lew et al. J Am Soc Nephrol 2017. doi:10.1681/ASN.2016030248
• Castaneda et al. Ann Intern Med 2001. doi:10.7326/0003-4819-135-11-200112040-00008 
• Bauer et al. (PROT-AGE). JAMDA 2013. doi:10.1016/j.jamda.2013.05.021
• Fenton et al. Nutrition Journal 2011. doi:10.1186/1475-2891-10-41
• Shams-White et al. Am J Clin Nutr 2017. doi:10.3945/ajcn.116.145110
• Witard et al. Am J Clin Nutr 2013. doi:10.3945/ajcn.112.055517
•  Macnaughton et al. Physiol Rep 2016. doi:10.14814/phy2.12893
• Trommelen et al. Cell Reports Medicine 2023. doi:10.1016/j.xcrm.2023.101324 
• Wycherley et al. Am J Clin Nutr 2012. doi:10.3945/ajcn.112.044321
•  Moore et al. JAMA Intern Med 2016. doi:10.1001/jamainternmed.2016.1548 
• Larsson et al. Cancer Med 2020. doi:10.1002/cam4.3345 
• Brenner, Meyer & Hostetter. NEJM 1982. doi:10.1056/NEJM198209093071104 
• Chan et al. PLoS One 2011. doi:10.1371/journal.pone.0020456
• Berryman et al. Am J Clin Nutr 2018. doi:10.1093/ajcn/nqy088 
• Morton et al. Br J Sports Med 2018. doi:10.1136/bjsports-2017-097608

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Is weight loss really just Calories in, Calories out? The equation is true, but "just count your Calories" is bad advice for most people, and almost every objection to it is pointing at something real. In part two of our energy balance series, Jordan Feigenbaum takes the biggest "it's not Calories, it's ___" claims (metabolism, thyroid, cortisol, PCOS, insulin, the type of food) and tests each against the best evidence. The verdict: none of them breaks the equation. Every one is a hand on a lever that moves Calories in or Calories out, not a hole in the math.

In this episode: why your metabolism does not crash at 40, how small real metabolic adaptation actually is after weight loss, why hypothyroid weight is mostly water, what the cortisol and PCOS (now PMOS) data show, how absorption and cooking move Calories only at the edges, why even dietitians miscount their own intake, and why the carbohydrate-insulin model fails three tests, including the GLP-1 drugs that raise insulin and still produce the biggest weight loss we have ever approved.

Part two of three: willpower, Calories in Calories out, then GLP-1 drugs. Next week: are GLP-1s cheating?

Timestamps

• 0:00 Is it really just calories in, calories out?
• 0:18 The willpower episode and the through-line
• 2:10 Thermodynamics: what sets both sides
• 2:41 Your metabolism is three things
• 4:05 Claim 1: my metabolism crashed
• 4:24 No cliff at 40: the doubly labeled water study
• 5:33 Real metabolic adaptation after weight loss
• 6:56 Why your food diary lies
• 7:49 Claim 2: it's my hormones
• 8:07 Thyroid: mostly water
• 9:36 Cortisol: explains about 1 percent
• 11:12 PCOS is now PMOS
• 13:06 Menopause
• 14:18 Claim 3: a calorie isn't a calorie
• 16:48 Absorption: nuts, cooking, eggs
• 19:44 Why calorie counting fails
• 21:12 Claim 4: it's not Calories, it's insulin
• 22:02 Testing the carbohydrate-insulin model
• 25:52 The GLP-1 drugs that should end it
• 28:34 The whole list, claim by claim
• 29:53 What to actually do
• 30:42 Next week: are GLP-1s cheating?

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Pontzer et al., Science 2021. https://doi.org/10.1126/science.abe5017

Muller et al., Am J Clin Nutr 2015. https://doi.org/10.3945/ajcn.115.109173

Lichtman et al., N Engl J Med 1992. https://doi.org/10.1056/NEJM199212313272701

Karmisholt et al., J Clin Endocrinol Metab 2011. https://doi.org/10.1210/jc.2010-1521

Lee et al., Endocr Pract 2014. https://doi.org/10.4158/EP14072.OR

van der Valk et al., Obes Rev 2022. https://doi.org/10.1111/obr.13376

Nikokavoura et al., Diabetes Metab Syndr Obes 2015. https://doi.org/10.2147/DMSO.S85134

Greendale et al., JCI Insight 2019. https://doi.org/10.1172/jci.insight.124865

Lejeune et al., Am J Clin Nutr 2006. https://doi.org/10.1093/ajcn/83.1.89

Bray et al., JAMA 2012. https://doi.org/10.1001/jama.2011.1918

Novotny et al., Am J Clin Nutr 2012. https://doi.org/10.3945/ajcn.112.035782

Baer et al., J Nutr 2016. https://doi.org/10.3945/jn.115.217372

Baer et al., Br J Nutr 2012. https://doi.org/10.1017/S0007114511002649

Evenepoel et al., J Nutr 1998. https://doi.org/10.1093/jn/128.10.1716

Hall et al., Cell Metabolism 2019. https://doi.org/10.1016/j.cmet.2019.05.008

Champagne et al., J Am Diet Assoc 2002. https://doi.org/10.1016/S0002-8223(02)90316-0

Hall et al., Cell Metabolism 2015. https://doi.org/10.1016/j.cmet.2015.07.021

Wilding et al., N Engl J Med 2021. https://doi.org/10.1056/NEJMoa2032183

Jastreboff et al., N Engl J Med 2022. https://doi.org/10.1056/NEJMoa2206038

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Obesity roughly tripled in about 60 years, and the genes didn't change in that time. So if body weight isn't a willpower problem, what is it? Dr. Jordan Feigenbaum and Dr. Austin Baraki walk through what actually sets your weight: the adoption and twin studies behind the genetics, the "defended range" your biology fights to hold, the food environment that does most of the eating for you, and where GLP-1 medications actually work. Along the way — why diets regain after you white-knuckle them, what The Biggest Loser six-year data show about resting metabolism, and four willpower myths worth retiring. 

Hosted by Dr. Jordan Feigenbaum and Dr. Austin Baraki, co-founders of Barbell Medicine.

Timestamps

• 00:00 Cold open: Danny Cahill and The Biggest Loser
• 01:03 What we mean by "willpower"
• 05:48 Obesity tripled in ~60 years: the one number
• 06:31 Adoption and twin studies: genes vs. household
• 09:37 Set point vs. the defended range
• 10:37 Gene–environment mismatch
• 14:03 In the clinic: a lifelong weight history
• 19:18 Losing weight vs. keeping it off
• 20:26 Appetite doesn't reset (Sumithran)
• 25:52 Metabolic adaptation and the Biggest Loser data
• 34:07 Part 2: eating on autopilot
• 35:10 Portion size runs the meal
• 39:12 What changed in the food supply
• 40:42 Same genes, new environment: Pima and immigrants
• 43:20 Why ultra-processed food is easy to overeat
• 50:28 Processing vs. calories: the Hall ward study
• 52:36 When the brain changes eating: gourmand syndrome
• 1:00:01 Why the willpower story stuck
• 1:01:08 Taft, Churchill, and the intelligence myth
• 1:02:43 Does intelligence predict weight? (sibling study)
• 1:11:16 Are GLP-1s cheating? What they actually do
• 1:15:10 Beyond the scale: muscle, health, nutrition
• 1:24:21 Myth-busting: lightning round
• 1:39:04 Three takeaways: what to actually do
• 1:41:00 Danny Cahill, revisited 

Resources

 

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Prevalence of Overweight, Obesity, and Severe Obesity Among Adults Age 20 and Older: United States, 1960-1962 Through August 2021-August 2023. NCHS Health E-Stats. 2024. https://www.cdc.gov/nchs/data/hestat/hestat111.htm

Obesity and Severe Obesity Prevalence in Adults: United States, August 2021-August 2023. NCHS Data Brief No. 508. Hyattsville, MD: National Center for Health Statistics; 2024. https://www.cdc.gov/nchs/products/databriefs/db508.htm

Hill JO, Peters JC. Environmental contributions to the obesity epidemic. Science. 1998;280(5368):1371-1374. https://doi.org/10.1126/science.280.5368.1371

Morton RW, Murphy KT, McKellar SR, et al. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018;52(6):376-384. https://doi.org/10.1136/bjsports-2017-097608

Stunkard AJ, Sorensen TIA, Hanis C, et al. An adoption study of human obesity. N Engl J Med. 1986;314(4):193-198. https://doi.org/10.1056/NEJM198601233140401

Stunkard AJ, Harris JR, Pedersen NL, McClearn GE. The body-mass index of twins who have been reared apart. N Engl J Med. 1990;322(21):1483-1487. https://doi.org/10.1056/NEJM199005243222102

Speakman JR, Levitsky DA, Allison DB, et al. Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity. Dis Model Mech. 2011;4(6):733-745. https://doi.org/10.1242/dmm.008698

Kalm LM, Semba RD. They starved so that others be better fed: remembering Ancel Keys and the Minnesota Experiment. J Nutr. 2005;135(6):1347-1352. https://doi.org/10.1093/jn/135.6.1347

Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597-1604. https://doi.org/10.1056/NEJMoa1105816

Fothergill E, Guo J, Howard L, et al. Persistent metabolic adaptation 6 years after 'The Biggest Loser' competition. Obesity (Silver Spring). 2016;24(8):1612-1619. https://doi.org/10.1002/oby.21538

Hall KD. Energy compensation and metabolic adaptation: 'The Biggest Loser' study reinterpreted. Obesity (Silver Spring). 2022;30(1):11-13. https://doi.org/10.1002/oby.23308

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Rolls BJ, Morris EL, Roe LS. Portion size of food affects energy intake in normal-weight and overweight men and women. Am J Clin Nutr. 2002;76(6):1207-1213. https://doi.org/10.1093/ajcn/76.6.1207

Diliberti N, Bordi PL, Conklin MT, Roe LS, Rolls BJ. Increased portion size leads to increased energy intake in a restaurant meal. Obes Res. 2004;12(3):562-568. https://doi.org/10.1038/oby.2004.64

Hollands GJ, Shemilt I, Marteau TM, et al. Portion, package or tableware size for changing selection and consumption of food, alcohol and tobacco. Cochrane Database Syst Rev. 2015;(9):CD011045. https://doi.org/10.1002/14651858.CD011045.pub2

Hall KD, Ayuketah A, Brychta R, et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake. Cell Metab. 2019;30(1):67-77.e3. https://doi.org/10.1016/j.cmet.2019.05.008

Pontzer H, Raichlen DA, Wood BM, et al. Hunter-gatherer energetics and human obesity. PLoS One. 2012;7(7):e40503. https://doi.org/10.1371/journal.pone.0040503

Careau V, Halsey LG, Pontzer H, et al. Energy compensation and adiposity in humans. Curr Biol. 2021;31(20):4659-4666.e2. https://doi.org/10.1016/j.cub.2021.08.016

Miller WC, Koceja DM, Hamilton EJ. A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention. Int J Obes Relat Metab Disord. 1997;21(10):941-947. https://doi.org/10.1038/sj.ijo.0800499

Gaesser GA, Angadi SS. Obesity treatment: weight loss versus increasing fitness and physical activity for reducing health risks. iScience. 2021;24(10):102995. https://doi.org/10.1016/j.isci.2021.102995

US Department of Agriculture, Economic Research Service. Food Availability (Per Capita) Data System, Loss-Adjusted Food Availability. https://www.ers.usda.gov/data-products/food-availability-per-capita-data-system/

Steele EM, Baraldi LG, Louzada ML, Moubarac JC, Mozaffarian D, Monteiro CA. Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study. BMJ Open. 2016;6(3):e009892. https://doi.org/10.1136/bmjopen-2015-009892

Wang L, Martinez Steele E, Du M, et al. Trends in consumption of ultraprocessed foods among US youths aged 2-19 years, 1999-2018. JAMA. 2021;326(6):519-530. https://doi.org/10.1001/jama.2021.10238

Schulz LO, Bennett PH, Ravussin E, et al. Effects of traditional and western environments on prevalence of type 2 diabetes in Pima Indians in Mexico and the US. Diabetes Care. 2006;29(8):1866-1871. https://doi.org/10.2337/dc06-0138

Goel MS, McCarthy EP, Phillips RS, Wee CC. Obesity among US immigrant subgroups by duration of residence. JAMA. 2004;292(23):2860-2867. https://doi.org/10.1001/jama.292.23.2860

Papavramidou NS, Papavramidis ST, Christopoulou-Aletra H. Galen on obesity: etiology, effects, and treatment. World J Surg. 2004;28(6):631-635. https://doi.org/10.1007/s00268-004-7458-5

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Townend L. The moralizing of obesity: a new name for an old sin? Crit Soc Policy. 2009;29(2):171-190. https://doi.org/10.1177/0261018308101625

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Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216. https://doi.org/10.1056/NEJMoa2206038

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Once a month we answer Barbell Medicine Plus subscribers’ questions on the Direct Line. This is a free look at June’s episode. We start with GLP-1 drugs and muscle: why DEXA overstates the loss, what resistance training actually does, and whether creatine is worth taking. Then whether bulking and cutting does anything the scale can’t already tell you, how to get real benefit from one training hour a week, and what happens to your muscle, strength, tendons, and bone when you take time off, including why muscle memory brings it back faster than you built it.

What we cover:

•   GLP-1s and muscle: the DEXA problem, resistance training, and creatine

•   Bulking vs cutting vs just maintaining, and a health-first way to choose

•   Training on one hour a week: the least that still moves the needle

•   How fast you lose muscle when you stop, and why it comes back fast

The full two-hour episode and every back episode are on Barbell Medicine Plus, which can bundled with Premium. Resources and full references below.

Timestamps

0:00 Intro + GLP-1 and the DEXA muscle-loss myth

3:00 Do GLP-1s spare or waste muscle?

8:03 Does creatine help on a GLP-1?

10:45 Does bulking and cutting do anything?

13:18 Health first: when to lose fat before gaining

22:30 Training on one hour a week

36:22 How fast you lose muscle when you stop

43:19 Muscle memory: why it comes back

48:25 The full episode on Plus

Resources

• Barbell Medicine coaching and templates: https://www.barbellmedicine.com
• https://www.barbellmedicine.com/shop/subscriptions/plus-podcast-subscription/
• https://www.barbellmedicine.com/shop/subscriptions/barbell-medicine-premium/
• Signal book pre-order: https://www.barbellmedicine.com/shop/learning/signal/
• 
  

https://www.barbellmedicine.com/blog/glp-1-muscle-loss/

https://www.barbellmedicine.com/blog/creatine-on-ozempic-does-it-prevent-muscle-loss/

https://www.barbellmedicine.com/blog/novice-intermediate-advanced-strength-training/

Lundgren JR, et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined (S-LITE). N Engl J Med 2021;384:1719-1730. nejm.org · NEJMoa2028198

T-REX trial: tirzepatide with or without resistance training (Univ. of Western Australia). Preliminary. ANZCTR ACTRN12623001236684

Creatine + GLP-1 pilot (Univ. of Saskatchewan). Ongoing, results expected 2027. ClinicalTrials.gov NCT07625202

Momma H, et al. Muscle-strengthening activities and lower risk/mortality in major non-communicable diseases. Br J Sports Med 2022. PubMed 35228201

Wall BT, et al. 2014. Immobilization and disuse muscle atrophy (quadriceps −3.5% at 5 days, −8% at 14 days). PubMed 24168489

Gaffney CJ, et al. 2021. Grip strength loss with short-term arm immobilization. PMC8107283

Farthing JP, et al. 2009. Cross-education and preservation of the immobilized limb. PubMed 19150859

Marusic U, et al. 2021. Bed rest: strength loss outpaces size loss. PMC8325614

Yoshihara, et al. 2023. Sepsis-associated muscle wasting (−26% in a week). PMC10003568

Warren GL, et al. 2017. Strength loss and recovery after muscle injury (meta-analysis). PMC5214801

Hortobágyi T, et al. 1993. Short-term detraining in strength athletes. PubMed 8371654

Gavanda S, et al. 2020. Training cessation in previously untrained adolescents. PMC7241623

Lovell DI, et al. 2010. Detraining strength loss in older adults. PubMed 20140683

Mujika I, Padilla S. 2001. Physiology of detraining (review). PubMed 11474330

Smith K, et al. 2003. Two years of training, then detraining, in older adults. PubMed 12955872

Staron RS, et al. 1991. Detraining and muscle cross-sectional area in women. PubMed 1827108

Ivey FM, et al. 2000. Detraining across age and sex. PubMed 10795719

Taaffe DR, et al. 2009. Training and detraining in older adults. PMC2756799

Grgic J, et al. 2022. Muscle size loss with detraining (meta-analysis). PubMed 36360927

Bosquet L, et al. 2013. Detraining effects on strength and power. PubMed 23347054

Bruusgaard JC, et al. 2010. Myonuclei acquired by overload persist after detraining (muscle memory). PMC2930527

Weakley J, et al. 2017. Day-to-day variation in strength performance. PubMed 28277425

McGuigan MR, et al. 2004. Strength performance variability. PubMed 15320651

Andreoli A, et al. 2009. DEXA precision and assumptions. PMC9263164

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Is there really a “menopause-specific” way to train, eat, and supplement — or is most of it marketing? In the finale of our 4-part menopause series, Drs. Jordan Feigenbaum and Austin Baraki go straight to the evidence on building muscle and bone before, during, and after the transition.

We cover whether menopause blunts your response to lifting (the Isenmann 2023 head-to-head trial and the 2026 meta-analysis of ~4,000 women say it doesn’t), the one-index-card prescription that actually works. Then we work through the loudest claims in the space — cortisol “wrecking” your fat loss, anabolic resistance, the protein and creatine hype, hormone therapy as a cure-all, and “you need a different paradigm” — steelmanning each before we push back. We close with the strongest case in the whole space: heavy lifting for bone density (the LIFTMOR trial), the pelvic-floor evidence, your three biggest fears answered, and how to tell a good coach or clinician from a bad one.

Claims discussed are associated with Stacey Sims, Mary Claire Haver, Mindy Pelz, and the broader functional-medicine space. We push back on the claims, not the people.

Timestamps:

• 0:00 The 90-year-olds who tripled their strength
•  1:10 Why this matters: heart disease and falls, not vanity
•  2:28 Can women still build muscle after menopause? (Isenmann 2023)
•  7:31 Does menopause blunt your gains? The 2026 meta-analysis
•  8:49 Is it menopause, or just individual variation?
•  14:42 The estrogen "shield" and the mechanical override
•  18:31 Does hormone therapy replace training? (the 2021 estradiol trial)
•  22:44 What actually works: the whole prescription
•  24:18 Program details: frequency, volume & insulin sensitivity
•  30:22 Nutrition: protein and the 2026 review
•  35:06 Creatine, vitamin D & calcium
•  43:29 Anabolic resistance: mostly overstated
•  47:22 Clinical case: the supplement-stack patient
•  52:23 A short history of wrong advice for women
•  53:38 Claim 1: "Lift heavy or lose your bones" (Stacey Sims)
•  1:01:09 Claim 2: the cortisol myth
•  1:15:18 Clinical case: the cortisol-anxious patient
•  1:18:20 Claim 3: "It's all hormonal, HRT fixes it" (Mary Claire Haver)
•  1:20:45 Testosterone in women: what it does and doesn't do
•  1:21:51 Claim 4: "Menopause needs its own paradigm" & the SWAN data
•  1:24:48 Bone density done right: the LIFTMORE trial
•  1:33:07 Does heavy lifting wreck your pelvic floor?
•  1:38:59 Your three biggest fears, answered
•  1:40:44 Green flags & red flags 

Resources:

• Menopause Series Part 1 : https://www.youtube.com/watch?v=yzk0IkTy0WM
• Menopause Series Part 2 — https://www.youtube.com/watch?v=YKAlamIOiwU
•  Menopause Series Part 3 — https://www.youtube.com/watch?v=jzoNMQaBAcI 
• Hypercortisolism episode - https://open.spotify.com/episode/7tDdUi8dDFWjMYx0fRJdOz 

Barbell Medicine coaching and templates: https://www.barbellmedicine.com

Signal book pre-order: https://www.barbellmedicine.com/shop/learning/signal/

Isenmann (2023) https://doi.org/10.1186/s12905-023-02671-y

Isenmann (2026) https://doi.org/10.1016/j.jsams.2026.01.004

Fiatarone (1990) https://doi.org/10.1001/jama.1990.03440220053029

Fiatarone (1994) https://doi.org/10.1056/NEJM199406233302501

Dam (2021) https://doi.org/10.3389/fphys.2020.596130

Markofski (2015) https://doi.org/10.1016/j.exger.2015.02.015

Orsatti (2022) https://doi.org/10.1016/j.exger.2022.111904

Walter (2026) https://doi.org/10.1186/s40798-025-00954-2

dos Santos (2021) https://doi.org/10.3390/nu13113757

Myung (2021) https://doi.org/10.3390/nu13020368

Dote-Montero (2021) https://doi.org/10.1111/sms.13999

Ravussin (2015) https://doi.org/10.1093/gerona/glv057

Cadegiani (2016) https://doi.org/10.1186/s12902-016-0128-4

Greising (2009) https://doi.org/10.1093/gerona/glp082

Islam (2019) https://doi.org/10.1016/S2213-8587(19)30189-5

Testosterone in women review (2026) https://doi.org/10.1080/09513590.2025.2592402

NAMS nonhormone position statement (2023) https://doi.org/10.1097/GME.0000000000002200

Vasomotor exercise meta-analysis (2022) https://doi.org/10.1080/13697137.2022.2097865

Greendale (2019) https://doi.org/10.1172/jci.insight.124865

Watson, LIFTMOR (2018) https://doi.org/10.1002/jbmr.3284

Skaug (2024) https://doi.org/10.1249/MSS.0000000000003278

Skaug (2021) https://doi.org/10.1007/s00192-021-04739-5

Dumoulin (2018) https://doi.org/10.1002/14651858.CD005654.pub4

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* Check out Quince and use my code quince.com/BBM for a great deal: https://www.quince.com


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