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

Cohen DA, Farley TA. Eating as an automatic behavior. Prev Chronic Dis. 2008;5(1):A23. https://www.cdc.gov/pcd/issues/2008/jan/07_0046.htm

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

Haslam DW, Haslam F. Fat, Gluttony and Sloth: Obesity in Literature, Art and Medicine. Liverpool: Liverpool University Press; 2009. https://www.liverpooluniversitypress.co.uk/9781846311734/fat-gluttony-and-sloth/

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

Levine DI. Corpulence and correspondence: President William H. Taft and the medical management of obesity. Ann Intern Med. 2013;159(8):565-570. https://doi.org/10.7326/0003-4819-159-8-201310150-00012

Wright L, Davies NM, Bann D. The association between cognitive ability and body mass index: a sibling-comparison analysis in four longitudinal studies. PLoS Med. 2023;20(4):e1004207. https://doi.org/10.1371/journal.pmed.1004207

Mechanisms of GLP-1 receptor agonist-induced weight loss: a review of central and peripheral pathways. Am J Med. 2025 (review of hypothalamic arcuate nucleus and brainstem area postrema action). https://www.sciencedirect.com/science/article/pii/S0002934325000592

Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002. https://doi.org/10.1056/NEJMoa2032183

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

Grannell A, Fallon F, Al-Najim W, le Roux C. Obesity and responsibility: is it time to rethink agency? Obes Rev. 2021;22(8):e13270. https://doi.org/10.1111/obr.13270

Al Khatib HK, Harding SV, Darzi J, Pot GK. The effects of partial sleep deprivation on energy balance: a systematic review and meta-analysis. Eur J Clin Nutr. 2017;71(5):614-624. https://doi.org/10.1038/ejcn.2016.201

Helms ER, Aragon AA, Fitschen PJ. Evidence-based recommendations for natural bodybuilding contest preparation: nutrition and supplementation. J Int Soc Sports Nutr. 2014;11:20. https://doi.org/10.1186/1550-2783-11-20

Garthe I, Raastad T, Refsnes PE, Koivisto A, Sundgot-Borgen J. Effect of two different weight-loss rates on body composition and strength and power-related performance in elite athletes. Int J Sport Nutr Exerc Metab. 2011;21(2):97-104. https://doi.org/10.1123/ijsnem.21.2.97

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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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Most women in 2026 are told menopause affects everything, the weight, the belly fat, the bones, the heart, the brain, and that the fix is hormones, supplements, and a proprietary protocol. The data tell a different story. Menopause does some of it, but not all of it.

In this episode, Dr. Jordan Feigenbaum and Dr. Austin Baraki, with OB-GYN Dr. Loraine Baraki at the clinical handoffs, put real numbers on what menopause actually changes, e.g. body composition, the cardiometabolic shift around the final menstrual period, bone, cognition and sleep — and on the single biggest modifiable lever against what actually kills postmenopausal women.

This is Episode 3 of Barbell Medicine's four-part menopause series.

Timestamps:

• 01:23 Intro 
• 02:45 Body composition & the SWAN study 
• 04:16 How much weight gain is really menopause?
•  06:55 The answer: about 1.5 kg 08:14 Subcutaneous vs visceral fat
•  11:08 Why waist beats weight (and body-fat %) 
• 17:21 Does menopause crash your metabolism? 19:02 Clinic: MHT for body composition 
• 23:51 Dr. Loraine Baraki — MHT, weight & testosterone 
• 27:29 The cardiometabolic shift: cholesterol at the FMP 
• 30:18 Insulin resistance & metabolic syndrome 
• 33:12 Blood pressure & 10-year heart risk 
• 34:54 Clinic: the "estrogen crisis" lipid panic 
• 39:13 Bone: the advice vs the data 40:34 Why DXA misses most fractures 
• 41:24 LIFTMOR: lifting heavy with low bone density 
• 44:47 The LIFTMOR results 
• 46:53 Lifting vs Pilates, and falls 
• 52:17 Clinic: "Should I be deadlifting?" 
• 56:14 Cognition & brain fog 
• 57:50 Why brain fog is mostly a sleep problem 
• 59:17 Clinic: brain fog, night sweats, broken sleep 
• 1:03:06 Depression & dementia in midlife 
• 1:05:43 Does hormone therapy protect the brain? 
• 1:08:53 Clinic: "Am I getting early dementia?" 
• 1:13:19 Dr. Loraine Baraki — the timing hypothesis & the brain
• 1:16:15 What actually kills postmenopausal women 
• 1:17:31 Fitness: the biggest mortality lever 
• 1:20:21 Strength, power & grip 
• 1:25:15 Clinic: where to start when you're overwhelmed 
• 1:30:41 The detraining problem 
• 1:32:38 Trained vs untrained: what's recoverable 
• 1:34:53 The actual plan 
• 1:39:48 Takeaways

Resources:

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Body composition & metabolism

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

 Lovejoy et al., visceral fat across the transition, Int J Obes 2008: https://doi.org/10.1038/ijo.2008.25

 Pontzer et al., daily energy expenditure across life, Science 2021: https://doi.org/10.1126/science.abe5017

 Karppinen et al., metabolism in midlife women, Eur J Prev Cardiol 2023: https://doi.org/10.1093/eurjpc/zwad177

Cardiometabolic

Matthews et al., lipid changes & the menopause transition, JACC 2009: https://doi.org/10.1016/j.jacc.2009.10.009

Janssen et al., menopause & metabolic syndrome (SWAN), Arch Intern Med 2008: https://doi.org/10.1001/archinte.168.14.1568

 El Khoudary et al., AHA Scientific Statement on midlife women, Circulation 2020: https://doi.org/10.1161/CIR.0000000000000912

Bone

Greendale et al., SWAN bone loss across the FMP, JBMR 2012: https://doi.org/10.1002/jbmr.534

 Siris et al., undiagnosed low BMD & fractures (NORA), JAMA 2001: https://doi.org/10.1001/jama.286.22.2815

 Watson et al., LIFTMOR, JBMR 2018: https://doi.org/10.1002/jbmr.3284

Kemmler et al., EFOPS 16-year, Menopause 2017: https://doi.org/10.1097/GME.0000000000000720

Kistler-Fischbacher et al., MEDEX-OP, JBMR 2021: https://doi.org/10.1002/jbmr.4334

 Sherrington et al., exercise for preventing falls, Cochrane 2019: https://doi.org/10.1002/14651858.CD012424.pub2

ACSM Position Stand: Osteoporosis and Exercise, Med Sci Sports Exerc 1995;27(4):i–vii (no DOI)

Cognition & mood

Greendale et al., SWAN cognition, Neurology 2009: https://doi.org/10.1212/WNL.0b013e3181a71193

Kravitz et al., sleep in midlife women, Obstet Gynecol Clin North Am 2018: https://doi.org/10.1016/j.ogc.2018.07.008

Cohen et al., Harvard Study of Moods and Cycles, Arch Gen Psychiatry 2006: https://doi.org/10.1001/archpsyc.63.4.385

Bromberger & Kravitz, mood and menopause (SWAN), Obstet Gynecol Clin North Am 2011: https://doi.org/10.1016/j.ogc.2011.05.011

Livingston et al., Lancet Commission on dementia 2024: https://doi.org/10.1016/S0140-6736(24)01296-0

Shumaker et al., WHIMS (estrogen+progestin & dementia), JAMA 2003: https://doi.org/10.1001/jama.289.20.2651

 Espeland et al., WHIMS (estrogen-alone & cognition), JAMA 2004: https://doi.org/10.1001/jama.291.24.2959

Gleason et al., KEEPS-Cog, PLoS Med 2015: https://doi.org/10.1371/journal.pmed.1001833

 Henderson et al., ELITE (timing hypothesis & cognition), Neurology 2016: https://doi.org/10.1212/WNL.0000000000002980

USPSTF, hormone therapy for primary prevention, JAMA 2022: https://doi.org/10.1001/jama.2022.18625

Fitness & mortality

 Mandsager et al., cardiorespiratory fitness & mortality, JAMA Netw Open 2018: https://doi.org/10.1001/jamanetworkopen.2018.3605

Kodama et al., fitness & mortality meta-analysis, JAMA 2009: https://doi.org/10.1001/jama.2009.681

Sui et al., fitness & adiposity in older adults, JAMA 2007: https://doi.org/10.1001/jama.298.21.2507

Momma et al., muscle-strengthening activity & mortality, Br J Sports Med 2022: https://doi.org/10.1136/bjsports-2021-105061

Araújo et al., muscle power vs strength & mortality (CLINIMEX), Mayo Clin Proc 2025: https://doi.org/10.1016/j.mayocp.2025.02.015

Leong et al., grip strength & mortality (PURE), Lancet 2015: https://doi.org/10.1016/S0140-6736(14)62000-6

Detraining & trained-vs-untrained

Troiano et al., accelerometer-measured activity, Med Sci Sports Exerc 2008: https://doi.org/10.1249/mss.0b013e31815a51b3

Fleg et al., aerobic-capacity decline (BLSA), Circulation 2005: https://doi.org/10.1161/CIRCULATIONAHA.105.545459

Ratley et al. aerobic-capacity changes during menopause, 2025

https://pmc.ncbi.nlm.nih.gov/articles/PMC12358808/

Janssen et al., skeletal muscle mass across adulthood, J Appl Physiol 2000: https://doi.org/10.1152/jappl.2000.89.1.81

 Pollock et al., master athletes & aerobic capacity, J Appl Physiol 1987: https://doi.org/10.1152/jappl.1987.62.2.725

Latella et al., strength across ages in powerlifters, Sports Med 2024: https://doi.org/10.1007/s40279-023-01962-6

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The story goes that hard exercise is risky for women, and that the idea is ancient. Both halves fall apart on contact. In this solo episode, Dr. Jordan Feigenbaum follows the claim that physical effort harms the female body across twenty centuries, and shows that almost every version of it arrived as a verdict first, with the science bolted on afterward.

It runs from antiquity to the present: what Galen actually wrote, why Sparta trained its women on purpose, the Victorian “vital force” panic and Edward Clarke’s claim that studying would sterilize girls, the doctor who prescribed bed rest to women and the wilderness to men, and the 1928 Olympic 800m that was erased for 32 years over a collapse that never happened. Then the correction: the research that finally tested heavy training in older women and women with low bone mass, and what it found. The episode closes on 2026, where the guidelines say lift and the menopause market often says don’t.

What we cover

•    Why the “ancient Greeks” origin story for the no-hard-exercise rule doesn’t hold up.

•    How a Victorian energy-budget idea became a medical case against women lifting and studying.

•    The real story of the 1928 Olympic women’s 800m and the 32-year ban.

•    The strong women who were relabeled as freaks or exceptions instead of counted.

•    What Fiatarone’s nonagenarians and LIFTMOR actually showed about lifting heavy later in life.

•    The cortisol panic, the fasting scare, and cycle syncing, examined against the data.

•    Why the cautious messaging now comes from the market, not the medical guidelines.

Timestamps

• 00:00 The 1928 Olympic “massacre” that never happened
• 03:37 Antiquity: what the Greeks actually said
• 06:50 The Victorians and “vital force”
• 10:02 Mary Putnam Jacobi tests the claim, and is ignored
• 11:53 1928 in full: who killed the women’s 800m
• 13:53 The double standard, and Alice Milliat
• 15:39 The strong women history relabeled
• 20:26 The correction: what the evidence shows
• 22:27 LIFTMOR: lifting heavy with low bone mass
• 24:35 2026: guidelines, the market, and cortisol
• 28:34 Cycle syncing, and naming the pattern
• 30:40 What to take away

Subscribe to BBM Plus for the full unabridged Direct Line: https://barbellmedicine.supercast.com/

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

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

References

Cahn S. Coming on Strong: Gender and Sexuality in Twentieth-Century Women's Sport. Harvard University Press; 1994.

Clarke EH. Sex in Education; or, A Fair Chance for the Girls. Boston: James R. Osgood and Company; 1873.

Colenso-Semple LM, McKendry J, Lim C, et al. Menstrual cycle phase does not influence muscle protein synthesis or whole-body myofibrillar proteolysis in response to resistance exercise. J Physiol. 2025. PMID: 39630025.

Daly W, Hackney AC. Is exercise cortisol response of endurance athletes similar to levels of Cushing's syndrome? J Sports Med Phys Fitness. 2019. PMID: 31371847.

Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1595-1622. PMID: 30907953.

Fiatarone MA, Marks EC, Ryan ND, Meredith CN, Lipsitz LA, Evans WJ. High-intensity strength training in nonagenarians: effects on skeletal muscle. JAMA. 1990;263(22):3029-3034. PMID: 2342214.

Fiatarone MA, O'Neill EF, Ryan ND, et al. Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med. 1994;330(25):1769-1775.

Galen. On the Preservation of Health (De Sanitate Tuenda). 2nd century CE. Various translations.

Jacobi MP. The Question of Rest for Women During Menstruation. New York: G.P. Putnam's Sons; 1877. (Awarded the Harvard Boylston Prize.)

Latella C, Teo WP, Spathis J, et al. Using powerlifting athletes to determine strength adaptations across ages in males and females: a longitudinal growth modelling approach. Sports Med. 2024;54(3):753-774.

Maudsley H. Sex in mind and in education. Fortnightly Review. 1874;15:466-483.

Plutarch. Life of Lycurgus. Approx. 75 CE. Various translations.

Schultz J. Qualifying Times: Points of Change in U.S. Women's Sport. Urbana: University of Illinois Press; 2014.

Sinaki M, Mikkelsen BA. Postmenopausal spinal osteoporosis: flexion versus extension exercises. Arch Phys Med Rehabil. 1984;65(10):593-596. PMID: 6487063.

Soranus of Ephesus. Gynecology. Approx. 2nd century CE. Translated by Temkin O. Baltimore: Johns Hopkins University Press; 1991.

Switzer K. Marathon Woman: Running the Race to Revolutionize Women's Sports. Cambridge, MA: Da Capo Press; 2007.

Todd J. Various publications. Iron Game History. Stark Center for Physical Culture and Sports, University of Texas at Austin.

Tunis JR. Women and the Olympic Games. Harper's Magazine. July 1929. (And contemporaneous press coverage.)

Watson SL, Weeks BK, Weis LJ, Harding AT, Horan SA, Beck BR. High-intensity resistance and impact training improves bone mineral density and physical function in postmenopausal women with osteopenia and osteoporosis: the LIFTMOR randomized controlled trial. J Bone Miner Res. 2018;33(2):211-220. PMID: 30861219.

Xenophon. Constitution of the Lacedaemonians. Approx. 4th century BCE. Various translations.

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In 1889 a French physiologist injected himself with guinea pig and dog testicle extract and published a claim of self-rejuvenation in The Lancet. That announcement kicked off a 200-year medicalization of menopause that ran through leeches and bromides, Premarin, the 2002 Women's Health Initiative, and the contemporary menopause-content space. 

In Episode 1 of our three-part menopause series, Dr. Jordan Feigenbaum and Dr. Austin Baraki walk through what menopause actually is at the hormonal level, which midlife symptoms are menopause-driven and which are not, the KNDy neuron mechanism behind hot flashes (and the new medication that blocks it), and the 24-year follow-up on the WHI that substantially revised the original conclusions. OB-GYN Dr. Loraine Baraki walks the clinical workup, the lab panel she actually orders, and how she handles patients arriving with DUTCH panels and compounded hormone protocols.

If you have heard contradictory things about menopause hormone therapy from your primary care, your menopause coach, and your sister, that is not your fault. The evidence base has been revised in significant ways since the 2002 publication, and most patient-facing summaries are out of date.

Timestamps

• 00:00 Cold open: 200 years of menopause medicine
• 03:23 Welcome and roadmap
• 04:20 The HPG axis, follicles, and the FSH lag
• 09:11 STRAW+10 staging and the timing of perimenopause
• 13:47 Austin: the 49-year-old with a hormone panel
• 20:00 Loraine: the OB-GYN workup
• 28:00 Symptom attribution: what menopause actually causes
• 33:46 Austin: the all-estrogen patient
• 37:58 VMS duration and the KNDy mechanism (Avis, SKYLIGHT)
• 43:53 Austin: who actually gets fezolinetant
• 47:22 The WHI 24-year correction (Manson, Chlebowski, Boardman)
• 01:00:15 Modern prescribing today
• 01:06:52 Where the menopause-content space gets it right and wrong
• 01:11:50 Testosterone, compounded bioidenticals, and DUTCH panels
• 01:24:13 Takeaways

What we cover

• The HPG axis and the estrogen shield: what is happening across the 35-year reproductive era and what changes at perimenopause.
• STRAW+10 staging: how long perimenopause actually lasts and where most women fall in the timeline.
•  Symptom attribution: hot flashes and genitourinary syndrome are menopause. Weight gain, sleep, and joint pain are mostly other things.
• The KNDy neuron mechanism behind hot flashes and the new pharmacology that blocks it (fezolinetant, elinzanetant).
• The Women's Health Initiative: what the trial actually tested, what the 2002 result said, and what 24 years of follow-up have shown since then. The estrogen-alone arm reduced breast cancer incidence by 22% and mortality by 40% over 20 years.
• The timing hypothesis: hormone therapy started within 10 years of the final menstrual period vs more than 10 years out.
• Modern prescribing today: transdermal estradiol plus micronized progesterone, and why the formulations matter.
• Where the contemporary menopause-content space gets it right and wrong: the undertreatment problem, the zone-of-chaos framing, and the testosterone-for-everything marketing.
• Testosterone in women: one guideline-supported indication.
• Compounded bioidenticals and DUTCH panels.

Resources

• Subscribe to BBM Plus for the full unabridged Direct Line: https://barbellmedicine.supercast.com/
• Barbell Medicine coaching and templates: https://www.barbellmedicine.com/
• Signal book pre-order: https://www.barbellmedicine.com/shop/learning/signal
• Manson JE et al. 18-year mortality from the WHI. JAMA, 2017. https://pubmed.ncbi.nlm.nih.gov/28898378/
• Chlebowski RT et al. WHI estrogen-alone arm at 20 years. JAMA, 2020. https://pubmed.ncbi.nlm.nih.gov/32706854/
•  Boardman HMP et al. Hormone therapy for cardiovascular prevention. Cochrane, 2015. https://pubmed.ncbi.nlm.nih.gov/25754617/
• Avis NE et al. Duration of VMS in the SWAN cohort. JAMA Intern Med, 2015. https://pubmed.ncbi.nlm.nih.gov/25686030/
• Lederman S et al. SKYLIGHT 1, fezolinetant. The Lancet, 2023. https://pubmed.ncbi.nlm.nih.gov/36924778/
• Johnson KA et al. SKYLIGHT 2, fezolinetant. JCEM, 2023. https://pubmed.ncbi.nlm.nih.gov/37410020/
• USPSTF. Hormone therapy for primary prevention. JAMA, 2022. https://pubmed.ncbi.nlm.nih.gov/36318127/
• Davis SR et al. Global Consensus on testosterone in women. JCEM, 2019. https://pubmed.ncbi.nlm.nih.gov/31498871/

Our Sponsors:
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This is the free preview of the May 2026 Direct Line, our monthly AMA for Barbell Medicine Plus subscribers. Three reader questions answered in full.

We open with a mid-30s woman with bilateral shin pain and exertional foot numbness who started creatine a month ago and is asking whether the supplement is the cause. We walk through the compartment syndrome literature, the 2025 case report being passed around online and misinterpreted, what creatine actually does to total body water (and what it doesn’t), the four compartment pressure studies that exist, the Waterman 2013 demographic data on who actually gets chronic exertional compartment syndrome, and the workup we would actually run if this person walked into clinic.

Next, whether splitting your resistance training across the day affects strength and hypertrophy. We cover BBM’s general heuristic on frequency as a distribution tool for training load, the Schoenfeld meta-analyses on frequency (2016 and 2019), the wrinkle on cardiorespiratory fitness and exercise snacks, and where we go off the reservation compared to a strict evidence-based read.

We close with endometriosis for the lifter, including the seven-year average diagnostic delay, the 2022 ESHRE guideline shift away from required laparoscopy, what the menstrual cycle and performance literature actually says (McNulty 2020), why the anti-inflammatory diet narrative is mostly noise, the iron and protein levers that matter, post-operative return-to-lifting timelines, the meet-timing question, and Austin’s clinical case walk on supplement stacks and GLP-1 anti-inflammatory effects. A dedicated full episode on endometriosis is coming this summer.

The full unabridged Direct Line covers ten more questions, including where the GLP-1 strength trials actually are, why DEXA misleads on muscle mass loss, how we arrived at the Vital 5 weightings, the salt sermon for strongman, running shoes for casual runners, hernias and crunches in older lifters, the Bristol Stool Chart, Austin on coaching his residents, and a fresh reading list. Full episode on BBM Plus.

Timestamps:

Question 1 · Creatine and shin pain01:2713:21

Question 2 · Splitting your workout across the day13:2120:29

Question 3 · Endometriosis for the lifter20:29

What we cover:

The clinical workup for chronic exertional compartment syndrome and why creatine is rarely the culprit. The Schoenfeld frequency literature and why training load matters more than the day it’s distributed across. Endometriosis basics including diagnostic delay, prevalence, and the 2022 ESHRE guideline change. Why most endometriosis “diets” don’t have evidence behind them, and which nutrition levers actually matter (iron, protein, energy availability). Post-operative return to training, meet-timing options, supplement stacks, and the role of GLP-1 receptor agonists in chronic anti-inflammatory effects.

Resources:

Subscribe to BBM Plus for the full unabridged Direct Line: https://barbellmedicine.supercast.com/

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

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

Waterman B.R. et al. 2013. Risk factors for chronic exertional compartment syndrome in a physically active military population. Am J Sports Med 41(11):2545-2552.

https://pubmed.ncbi.nlm.nih.gov/24036570/

Powers M.E. et al. 2003. Creatine supplementation increases total body water without altering fluid distribution. J Athl Train 38(1):44-50.

https://pubmed.ncbi.nlm.nih.gov/12937471/

Antonio J. et al. 2021. Common questions and misconceptions about creatine supplementation (ISSN position). J Int Soc Sports Nutr 18(1):13.

https://pubmed.ncbi.nlm.nih.gov/33557850/

Bruneau A. et al. 2025. Creatine supplementation associated with chronic exertional compartment syndrome: case report. [TO ADD: PMID once indexed]

Schoenfeld B.J. et al. 2016. Effects of resistance training frequency on measures of muscle hypertrophy: a systematic review and meta-analysis. Sports Med 46(11):1689-1697.

https://pubmed.ncbi.nlm.nih.gov/27102172/

Schoenfeld B.J. et al. 2019. How many times per week should a muscle be trained to maximize hypertrophy? J Sports Sci 37(11):1286-1295.

https://pubmed.ncbi.nlm.nih.gov/30558493/

ESHRE Endometriosis Guideline Development Group. 2022. ESHRE guideline: endometriosis. Hum Reprod Open 2022(2):hoac009.

https://pubmed.ncbi.nlm.nih.gov/35350465/

McNulty K.L. et al. 2020. The effects of menstrual cycle phase on exercise performance in eumenorrheic women: systematic review and meta-analysis. Sports Med 50(10):1813-1827.

https://pubmed.ncbi.nlm.nih.gov/32661839/

Our Sponsors:
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Most cases of low testosterone in modern men are not a problem with the testes. The number is downstream of body composition, sleep, and energy availability. The wellness-clinic algorithm walks past every one of them.

Jordan and Austin walk through what actually drives men’s testosterone down, the mechanisms behind it, and the modifiable levers that bring it back up. MOSH, the leptin and Kisspeptin pathway, the aromatase loop, the sleep apnea picture most clinics never ask about, the GLP-1 and weight-loss data on testosterone recovery, the low energy availability case that hits high-volume lifters harder than they realize, and the closing question of when a standard-dose TRT prescription actually functions as a PED.

This is Episode 3 of our four-part Signal book launch series. Mark, the patient we have been threading from Episode 1, finally gets his diagnosis revealed.

Timestamps

• 00:00 The 9x stat and Mark's diagnosis revealed
•  02:10 How body fat suppresses testosterone (MOSH)
•  07:26 Primary vs secondary causes, and Klinefelter
•  11:35 Leptin and the Kisspeptin pathway
•  14:38 Mark: the body-composition picture
•  16:10 The 40-inch-waist case
•  20:01 Weight loss, GLP-1s, and does Ozempic raise testosterone?
•  24:21 T4DM: adding testosterone to lifestyle
•  28:35 Sleep, OSA, and Mark's diagnosis
•  38:39 TRT in untreated sleep apnea
•  41:47 Can you train your testosterone down? (LEA / EHMC)
•  50:12 Replacement dose vs PED
•  55:47 Four takeaways
•  57:46 Episode 4 preview and book pre-order

What we cover:

•         How body fat suppresses testosterone at two different points in the HPG axis, and why the loop is self-reinforcing

•         The leptin and Kisspeptin pathway most clinics never address

•         Mark’s case: a 45-year-old with a 240 ng/dL afternoon draw, no workup, and an immediate prescription

•         Primary versus secondary causes, and why Klinefelter syndrome is the under-recognized one to not miss

•         Weight loss dose-response: how much testosterone climbs on lifestyle alone, with GLP-1 agonists, and after bariatric surgery

•         T4DM: why adding testosterone to a structured weight-loss program produced no extra quality-of-life benefit over placebo

•         One week of sleep restriction drops testosterone by about 15 percent in healthy young men; eight days of military field exercises drop it by 50 percent

•         Why CPAP for obstructive sleep apnea reliably improves symptoms but does not always move the lab number

•         The opposite extreme: low energy availability, relative energy deficiency in sport, and the exercise-hypogonadal male condition

•         The lifter calculus: when a textbook replacement dose is functionally a PED in a chronically underfueled trainee

Resources mentioned:

• Signal book pre-order: https://barbellmedicine.com/signal
•  Training Plateau Action Plan (free): https://www.barbellmedicine.com/training-plateau-action-plan/
•  Barbell Medicine programs and coaching: https://www.barbellmedicine.com/
•  Episode 1 (Is the Testosterone Crisis Real?)
•  Episode 2 (Is Your Testosterone Actually Low?
• 
  

Referenced studies:

Wu F.C.W. et al. 2010. Identification of late-onset hypogonadism in middle-aged and elderly men (EMAS). N Engl J Med 363(2):123-135.

 https://pubmed.ncbi.nlm.nih.gov/20554979/

 

 Travison T.G. et al. 2011. The natural history of symptomatic androgen deficiency in men. J Am Geriatr Soc.

 https://pubmed.ncbi.nlm.nih.gov/18454751/

 

 Corona G. et al. 2013. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: systematic review and meta-analysis. Eur J Endocrinol 168(6):829-843.

 https://pubmed.ncbi.nlm.nih.gov/23482592/

 

 Kounatidis D. et al. 2025. The impact of GLP-1 receptor agonists on erectile function. Biomolecules 15(9):1284.

 https://doi.org/10.3390/biom15091284

 

 Grossmann M. et al. 2024. Testosterone treatment, weight loss, and health-related quality of life and psychosocial function in men: 2-year RCT (T4DM QoL arm). J Clin Endocrinol Metab 109(8):2019-2028.

 https://pubmed.ncbi.nlm.nih.gov/38311835/

 

 Leproult R., Van Cauter E. 2011. Effect of 1 week of sleep restriction on testosterone levels in young healthy men. JAMA 305(21):2173-2174.

 https://pubmed.ncbi.nlm.nih.gov/21632481/

 

 Penev P.D. 2007. Association between sleep and morning testosterone levels in older men. Sleep 30(4):427-432.

 https://pubmed.ncbi.nlm.nih.gov/17520785/

 

 Wittert G. 2014. The relationship between sleep disorders and testosterone in men. Asian J Androl 16(2):262-265.

 https://pubmed.ncbi.nlm.nih.gov/24435056/

 

 Alemany J.A. et al. 2008. Effects of dietary protein content on IGF-I, testosterone, and body composition during 8 days of severe energy deficit and arduous physical activity. J Appl Physiol 105(1):58-64.

 https://pubmed.ncbi.nlm.nih.gov/18450989/

 

 Mountjoy M., Sundgot-Borgen J.K., Burke L.M. et al. 2018. IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update. Br J Sports Med 52:687-697.

 https://pubmed.ncbi.nlm.nih.gov/29773536/

 

 Areta J.L. et al. 2021. Low energy availability: history, definition and evidence of its endocrine, metabolic and physiological effects in prospective studies in females and males. Eur J Appl Physiol 121(1):1-21.

 https://pubmed.ncbi.nlm.nih.gov/33095376/

 

 Mäestu J. et al. 2010. Anabolic and catabolic hormones and energy balance of the male bodybuilders during the preparation for the competition. J Strength Cond Res 24(4):1074-1081.

 https://pubmed.ncbi.nlm.nih.gov/20300023/

 

 Hooper D.R. et al. 2018. Treating exercise-associated low testosterone (EHMC). Phys Sportsmed 46(4):427-434.

 https://pubmed.ncbi.nlm.nih.gov/30074435/

 

 Hackney A.C. 2020. Hypogonadism in exercising males: dysfunction or adaptive-regulatory adjustment? Front Endocrinol 11:11.

 https://pubmed.ncbi.nlm.nih.gov/32082252/

Our Sponsors:
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Three weeks of stalled squats. The conventional answer is to switch programs because you've crossed into intermediate territory. The data says something else. In Part 3 of the Progressive Loading series, Dr. Jordan Feigenbaum and Dr. Austin Baraki walk through why the standard novice / intermediate / advanced framework runs into trouble in real training, what the four adaptive systems are actually doing across a training career, and why most of what gets called a stall is impatience with the noise floor at your current strength level.

This is Part 3 of the Progressive Loading series. Part 1 covered why loading should react to demonstrated adaptation. Part 2 covered RPE-based autoregulation and the artificial-momentum approach. Today is the mechanism layer.

Pre-order our book, Signal: barbellmedicine.com/signal

Timestamps

• 0:00 - Why your lifts aren't moving
• 1:52 - The novice / intermediate / advanced framework, three claims to test
• 13:23 - What 17 years of powerlifting data show about how long you keep getting stronger
• 32:28 - How getting stronger actually works (four systems on four clocks)
• 38:00 - What early growth is actually made of (the Damas 2016 deuterium study)
• 50:33 - The connective tissue lag and why early-training injuries happen
• 58:32 - Why heavy lifting works for bone density (and why "walk on a treadmill" advice misses)
• 1:05:10 - Why new lifters get hurt 3 to 10 times more than experienced lifters
• 1:12:56 - Fatigue is at least four different things (and most coaches treat it as one)
• 1:26:19 - The CNS fatigue myth (and what the data actually says)
• 1:33:52 - When the bar isn't moving: how to actually diagnose a stall
• 1:45:51 - Takeaways and next week's tease: leptin and low testosterone

What we cover 

- The novice / intermediate / advanced framework: three claims and why each one fails the data test

- The 17-year IPF strength curve and what the no-kink finding does and does not establish (Latella 2024)

- The four adaptive systems and their separate timescales (neural, muscle, connective tissue, bone)

- What early growth actually is, including the deuterium-oxide finding that most week-3 size is fluid (Damas 2016)

- Why connective tissue lags muscle by six to eight weeks, and why that produces patellar tendinopathy four months in

- The 9.5 vs 0.74 to 3.3 injury rate gap between novice and experienced CrossFit participants

- The CNS fatigue myth and the Skarabot 2018 finding that locates the fatigue in the muscle, not the brain

- Why the LIFTMOR trial result (heavy lifting for bone density in women in their 60s and 70s) is being missed by primary care

- A practical decision tree for stalls: environment first, then load, then program

- Tease for next week: leptin, the HPG axis, and the metabolic driver of low testosterone almost nobody connects

Resources 

Training Plateau Action Plan (free): https://www.barbellmedicine.com/training-plateau-action-plan/

Progressive Loading article series: https://www.barbellmedicine.com/blog/progressive-loading/

Beyond Progressive Overload (Part 2 article): https://www.barbellmedicine.com/blog/beyond-progressive-overload/

BBM Programs and Coaching: https://www.barbellmedicine.com/

Support our work on barbellmedicine.supercast.com

Latella C et al. Using powerlifting athletes to determine strength adaptations across ages in males and females. Sports Med. 2024. https://pubmed.ncbi.nlm.nih.gov/

Del Vecchio A et al. The increase in muscle force after 4 weeks of strength training is mediated by adaptations in motor unit recruitment and rate coding. J Physiol. 2019. https://pubmed.ncbi.nlm.nih.gov/30644584/

Lecce E et al. Resistance training-induced adaptations in the neuromuscular system. J Physiol. 2025.

Balshaw TG et al. Neural adaptations after 4 years vs 12 weeks of resistance training. Scand J Med Sci Sports. 2019. https://pubmed.ncbi.nlm.nih.gov/30474171/

Skarabot J et al. Voluntary activation and agonist EMG amplitude in resistance-trained men. J Appl Physiol. 2021.

Roberts MD et al. Mechanisms of mechanical overload-induced skeletal muscle hypertrophy. Physiol Rev. 2023.

Damas F et al. Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage. J Physiol. 2016. https://pubmed.ncbi.nlm.nih.gov/27219125/

Damas F et al. Early resistance training-induced increases in muscle cross-sectional area are concomitant with edema-induced muscle swelling. Eur J Appl Physiol. 2016. https://pubmed.ncbi.nlm.nih.gov/26280652/

Lazarczuk SL et al. Mechanical, material and morphological adaptations of healthy lower limb tendons. Sports Med. 2022. https://pubmed.ncbi.nlm.nih.gov/35657492/

Kubo K et al. Time course of changes in the human Achilles tendon properties. Eur J Appl Physiol. 2012. https://pubmed.ncbi.nlm.nih.gov/22105708/

Watson SL et al. High-intensity resistance and impact training improves bone mineral density in postmenopausal women: the LIFTMOR randomized controlled trial. J Bone Miner Res. 2018. https://pubmed.ncbi.nlm.nih.gov/28975661/

Aasa U et al. Injuries among weightlifters and powerlifters: a systematic review. Br J Sports Med. 2017. https://pubmed.ncbi.nlm.nih.gov/27445362/

Prieto-Gonzalez P et al. Injuries in novice participants during an eight-week start-up CrossFit program. Int J Environ Res Public Health. 2020. https://pubmed.ncbi.nlm.nih.gov/32155747/

Kanayama G et al. Tendon rupture in body builders. Sports Med. 2015.

Enoka RM, Duchateau J. Translating fatigue to human performance. Med Sci Sports Exerc. 2016. https://pubmed.ncbi.nlm.nih.gov/27015386/

Behrens M et al. Fatigue and human performance: an updated framework. Sports Med. 2023. https://pubmed.ncbi.nlm.nih.gov/

Halperin I et al. Accuracy in predicting repetitions to task failure: scoping review. Sports Med. 2022. https://pubmed.ncbi.nlm.nih.gov/

Skarabot J et al. Neuromuscular fatigue and recovery after heavy resistance, jump, and sprint training. Eur J Appl Physiol. 2018.

Garcia-Ramos A et al. Greater neuromuscular and perceptual fatigue after low-load to failure than heavy-load to failure. 2024.

Minor, Brian MS, CSCS1; Helms, Eric PhD, CSCS2; Schepis, Jacob3. RE: Mesocycle Progression in Hypertrophy: Volume Versus Intensity. Strength and Conditioning Journal 42(5):p 121-124, October 2020. | DOI: 10.1519/SSC.0000000000000581

Our Sponsors:
* Check out CovePure and use my code CovePure.com/bbm for a great deal: https://covepure.com
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Out of 32 symptoms commonly attributed to low testosterone, only 3 actually correlate with it. All three are sexual. The other 29 — fatigue, brain fog, low mood, weight you can't lose, feeling not quite like yourself — are real, but they are produced by something else, and the wellness-clinic funnel runs on getting that wrong.

 

Episode 2 of our Signal book launch series. Dr. Jordan Feigenbaum and Dr. Austin Baraki cover how testosterone actually works, what the number on your lab report is really measuring, and what a real evaluation of low T looks like.

Pre-order our book, Signal: barbellmedicine.com/signal

Timestamps:

00:00 Mark, revisited (cold open)

02:00 How testosterone actually works (HPG axis)

06:14 Why "in range" can still be abnormal

09:24 What your lab number actually measures

12:25 Case: total 230, low SHBG — does this guy need TRT?

17:04 The saturation model — why higher isn't better

21:11 A patient at 480 wants 900: how the conversation goes

28:57 What "in range" actually means (and why 264 is the cutoff)

34:41 The 3 symptoms that matter (out of 32)

37:16 Walking back a 10-symptom checklist

42:31 How a real testosterone workup gets done

46:42 Chasland trial — TRT vs. exercise at low-normal T

49:31 A warning for hard-training men

58:48 Takeaways, tease, and what's coming next 

What we cover:

The HPG axis explained — and why one low total testosterone reading tells you almost nothing about where the problem actually sits.

The difference between total, free, and bioavailable testosterone — and why SHBG, the binding protein the wellness-clinic workup almost always ignores, is what determines whether the number on your lab report is misleading you in either direction.

The saturation model: above roughly 250 ng/dL, the prostate androgen receptor is saturated. Libido follows the same plateau. Pushing a normal man from 500 to 900 isn't doing what the marketing implies.

The EMAS study finding: of 32 symptoms men commonly attribute to low testosterone, only 3 actually correlate. Every other symptom needs a different workup.

How a real testosterone workup gets done — morning sample, fasted, repeat draw, LH/FSH/SHBG to localize and contextualize.

The Chasland 2021 trial: when standard TRT is prescribed properly to middle-aged men with low-normal levels, does it beat exercise? The answer is what most of the wellness-clinic industry is built on getting wrong.

A note for hard-training men: the exercise-hypogonadal-male pattern, what "low-normal" means in someone whose levels are an adaptation to training load rather than a baseline deficit, and why a textbook TRT dose in that man may functionally act as a performance enhancer.

If you have a lab report on your kitchen counter right now, this is what we wrote for you. Signal, the book, drops in May. Pre-order available soon at barbellmedicine.com.

Resources & links

Signal — Feigenbaum & Baraki (Barbell Medicine, 2026): coming soon

Episode 1 (Is the Testosterone Crisis Real?): https://stream.redcircle.com/episodes/b25a8006-57e5-4dc3-b74c-203f6fbcebc1/stream.mp3

Training Plateau Action Plan (free): barbellmedicine.com/training-plateau-action-plan

Barbell Medicine programs and consultations: barbellmedicine.com

To support us and get ad free listening, plus special product discounts, and exclusive content, go to supercast.barbellmedicine.com

Referenced studies

Wu FCW et al. 2010 - Identification of late-onset hypogonadism in middle-aged and elderly men. NEJM 363(2):123-135. [The EMAS 3-of-32 finding]

https://pubmed.ncbi.nlm.nih.gov/20554979/

Bhasin S et al. 2018 - Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. JCEM 103(5):1715-1744. [264 ng/dL threshold; first-draw protocol]

https://pubmed.ncbi.nlm.nih.gov/29562364/

Travison TG et al. 2008 - The natural history of symptomatic androgen deficiency in men. JAGS 56(5):831-839. [MMAS: ~50% of initially low values normalize on repeat]

https://pubmed.ncbi.nlm.nih.gov/18308002/

Travison TG et al. 2006 - The relationship between libido and testosterone levels in aging men. JCEM 91(7):2509-2513. [Libido plateau data, Framingham + HIM]

https://pubmed.ncbi.nlm.nih.gov/16670164/

Brambilla DJ et al. 2009 - The effect of diurnal variation on clinical measurement of serum testosterone. JCEM 94(3):907-913. [Why morning, fasted matters]

https://pubmed.ncbi.nlm.nih.gov/19112025/

Morgentaler A & Traish AM. 2009 - Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 55(2):310-320. [The saturation model]

https://pubmed.ncbi.nlm.nih.gov/18838208/

Trost LW & Mulhall JP. 2016 - Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials. J Sex Med 13(7):1029-1046. [Free T unreliability at the low end; equilibrium dialysis as the reference method]

https://pubmed.ncbi.nlm.nih.gov/27210182/

Vermeulen A et al. 1999 - A critical evaluation of simple methods for the estimation of free testosterone in serum. JCEM 84(10):3666-3672. [Calculated free T methodology]

https://pubmed.ncbi.nlm.nih.gov/10523012/

Chasland LC et al. 2021 - Testosterone and exercise: effects on fitness, body composition, and strength in middle-to-older aged men with low-normal serum testosterone levels. Am J Physiol Heart Circ Physiol 320(5):H1985-H1998. [The 12-week trial]

https://pubmed.ncbi.nlm.nih.gov/33739153/

Arun AS et al. 2025 - Reevaluating the Threshold for Low Total Testosterone. Clin Chem 71(5):609-611. [2025 NHANES strength-dissociation reference]

https://pubmed.ncbi.nlm.nih.gov/40066943/

Baillargeon J et al. 2015 - Trends in Androgen Prescribing in the United States, 2001-2011. JAMA Intern Med 175(8):1413-1415. [25% no preceding lab; the 50% no follow-up monitoring gap - referenced from Episode 1]

https://pubmed.ncbi.nlm.nih.gov/26075486/

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Stop a GLP-1 and about two thirds of the weight loss comes back within a year. Three randomized withdrawal trials (SURMOUNT-4, STEP 1 extension, STEP 4) and a new BMJ 2026 systematic review of 37 RCTs and nearly 10,000 adults all land on the same signal. The cardiometabolic benefits, blood pressure, fasting glucose, lipids, drift back in parallel with the weight. The framing that actually fits the data: GLP-1s behave like a statin. There is a cumulative benefit during exposure, but this does not extend indefinitely,

This month's Direct Line covers two subscriber questions. The first asks what the new BMJ paper on GLP-1 cardiovascular protection after cessation actually shows, and how GLP-1 durability compares to lifestyle-only interventions. The second asks how a postmenopausal woman newly diagnosed with osteopenia should structure her lifting.

Studies referenced: SURMOUNT-4 (Jastreboff, JAMA 2024), STEP 1 extension (Wilding, Diabetes Obes Metab 2022), STEP 4 (Rubino, JAMA 2021), West et al. BMJ 2026 systematic review, Budini 2026 eClinicalMedicine regain meta-analysis, SELECT cardiovascular outcomes, FLOW renal outcomes, the Diabetes Prevention Program, Look AHEAD, POUNDS Lost, and LIFTMOR (Watson, JBMR 2018).

Full episode on BBM+ covers 8 additional subscriber questions. Join at https://barbellmedicine.supercast.com/

Timestamps

• 0:00 Intro
• 1:52 Q1: What happens when you stop a GLP-1
• 5:33 Lifestyle-only comparators: DPP, Look AHEAD, POUNDS Lost
• 8:15 Austin on the cessation conversation 1
• 2:41 BMJ 2026: weight and cardiometabolic regression
• 17:59 The statin framing
• 23:41 Austin: first 6 months off GLP-1
• 28:07 Q2: Osteopenia and heavy lifting
• 35:28 LIFTMOR protocol
• 38:00 Outro

Next Steps

• For evidence-based resistance training programs: barbellmedicine.com/training-programs
• For individualized training consultation: barbellmedicine.com/coaching
• Explore our full library of articles on health and performance: barbellmedicine.com/resources
• To consult with Drs. Baraki or Feigenbaum email us at support@barbellmedicine.com
• 
  

Resources

Aronne, Louis J., et al. "Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial." JAMA, vol. 331, no. 1, 2024, pp. 38–48. https://jamanetwork.com/journals/jama/fullarticle/2812936

Wilding, John P. H., et al. "Weight Regain and Cardiometabolic Effects After Withdrawal of Semaglutide: The STEP 1 Trial Extension." Diabetes, Obesity and Metabolism, vol. 24, no. 8, Aug. 2022, pp. 1553–1564. https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14725

Rubino, Domenica, et al. "Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial." JAMA, vol. 325, no. 14, 2021, pp. 1414–1425. https://jamanetwork.com/journals/jama/fullarticle/2777886

West, Sam, et al. "Weight Regain After Cessation of Medication for Weight Management: Systematic Review and Meta-Analysis." BMJ, vol. 392, 7 Jan. 2026, article e085304. https://www.bmj.com/content/392/bmj-2025-085304

Budini, Brajan, et al. "Trajectory of Weight Regain After Cessation of GLP-1 Receptor Agonists: A Systematic Review and Nonlinear Meta-Regression." eClinicalMedicine, vol. 93, 4 Mar. 2026, article 103796. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00043-X/fulltext

Lincoff, A. Michael, et al. "Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes." New England Journal of Medicine, vol. 389, no. 24, 11 Nov. 2023, pp. 2221–2232. https://www.nejm.org/doi/full/10.1056/NEJMoa2307563

Perkovic, Vlado, et al. "Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes." New England Journal of Medicine, vol. 391, no. 2, 24 May 2024, pp. 109–121. https://www.nejm.org/doi/full/10.1056/NEJMoa2403347

Knowler, William C., et al. "Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin." New England Journal of Medicine, vol. 346, no. 6, 7 Feb. 2002, pp. 393–403. https://www.nejm.org/doi/full/10.1056/NEJMoa012512

Look AHEAD Research Group. "Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes." New England Journal of Medicine, vol. 369, no. 2, 11 July 2013, pp. 145–154. https://www.nejm.org/doi/full/10.1056/NEJMoa1212914

Sacks, Frank M., et al. "Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates." New England Journal of Medicine, vol. 360, no. 9, 26 Feb. 2009, pp. 859–873. https://www.nejm.org/doi/full/10.1056/NEJMoa0804748

Watson, Shelley L., et al. "High-Intensity Resistance and Impact Training Improves Bone Mineral Density and Physical Function in Postmenopausal Women With Osteopenia and Osteoporosis: The LIFTMOR Randomized Controlled Trial." Journal of Bone and Mineral Research, vol. 33, no. 2, 2018, pp. 211–220. https://onlinelibrary.wiley.com/doi/10.1002/jbmr.3284

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Every week there's a new headline saying men are losing testosterone. A quarter of men now start testosterone replacement therapy without ever getting their blood tested. The supplement aisle is full of boosters that either do nothing or contain undisclosed steroids. And the lab test that gets everybody to the pharmacy? Half of low results normalize on their own.

In Episode 1 of the Signal launch series, Dr. Jordan Feigenbaum and Dr. Austin Baraki (both MDs and strength coaches) walk through the three-layer problem with how testosterone gets diagnosed and treated in 2026, then take apart the "testosterone is crashing" headline with the most current data available, including a 2025 meta-analysis of more than one million men.

Pre-order our book, Signal: barbellmedicine.com/signal

Timestamps

• 0:00 Mark's story: treating the number, not the patient
• 1:18 Welcome to the Barbell Medicine Podcast
• 1:41 Problem 1: A quarter of men start TRT with no lab work
• 3:36 Problem 2: Why testosterone boosters do not work (and what is in them)
• 13:40 Problem 3: Why one low testosterone lab is not a diagnosis
• 19:19 Setup: Is the testosterone crisis headline real?
• 20:04 The MMAS data and the 1%-per-year number
• 20:52 The 2025 meta-analysis of over 1 million men
• 22:02 Why the headline is inflated: three causes
• 22:27 Cause 1: The testing method changed (immunoassay to mass spec)
• 25:58 Cause 2: BMI cannot see visceral fat
• 29:37 The Nyante study: when you fix both problems, the decline vanishes
• 33:58 What this actually means for you
• 37:05 The broken testosterone system, summarized
• 38:24 Five takeaways from this episode
• 39:14 Next week: How testosterone actually works
• 39:39 About Signal and credits
• 
  

What you'll learn in this episode:

•  Why 25% of new TRT prescriptions are written without any pre-treatment lab work (JAMA, 2015)
• What actually happens when researchers test 50+ "testosterone booster" supplements (spoiler: 12% are contaminated with undisclosed steroids)
• Why a single low testosterone reading is not a diagnosis, and the Massachusetts Male Aging Study data that proves it
• The real size of the population-level testosterone decline (much smaller than 1% per year)
• Why BMI cannot see the visceral fat that is driving most of the genuine decline
• The Nyante study that shows the decline essentially vanishes when you use an accurate test and measure waist circumference
• Five practical takeaways you can apply before your next lab draw

This is Episode 1 of a four-part series built around our upcoming book, Signal. Over the next four weeks we cover what testosterone actually is, how to tell when it is genuinely low, what is really driving population-level changes, and what the evidence says you can do about it.

Next Steps

• Check out our new book, Signal (coming soon)
• For evidence-based resistance training programs: barbellmedicine.com/training-programs
• For individualized training consultation: barbellmedicine.com/coaching
• Explore our full library of articles on health and performance: barbellmedicine.com/resources
• To consult with Drs. Baraki or Feigenbaum email us at support@barbellmedicine.com
• To support us and get ad free listening, plus special product discounts, and exclusive content, go to supercast.barbellmedicine.com

Resources

Baillargeon, J., et al. (2015). Trends in Androgen Prescribing in the United States, 2001–2011. JAMA Intern Med, 175(8), 1413–1415. — 25% no preceding lab; post-prescription monitoring gap.

Rao, P.K., et al. (2017). Trends in Testosterone Replacement Therapy Use from 2003 to 2013 among Reproductive-Age Men in the United States. J Urol, 197(4), 1121–1126. — Prescription volume growth.

Selinger, S., & Thallapureddy, A. (2024). Cross-sectional analysis of national testosterone prescribing through prescription drug monitoring programs, 2018–2022. PLoS One, 19(8), e0309160. — Recent prescribing data, 3-4 million estimate.

Vesper, H.W., et al. (2015). Serum Total Testosterone Concentrations in the US Household Population from the NHANES 2011–2012 Study Population. Clin Chem, 61(12), 1495–1504. — Population testosterone levels, NHANES data.

Clemesha, C.G., et al. (2020). "Testosterone Boosting" Supplements Composition and Claims Are Not Supported by the Academic Literature. World J Men's Health, 38(1), 115–122. — 62% no published data, 10% decreased T.

Tucker, J., et al. (2018). Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US FDA Warnings. JAMA Network Open, 1(6), e183337. — 12% adulterated with undisclosed steroids.

Trost, L.W., & Mulhall, J.P. (2016). Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials. J Sex Med, 13(7), 1029–1046. — Half of low results normalize on repeat.

Travison, T.G., et al. (2008). The Natural History of Symptomatic Androgen Deficiency in Men: Onset, Progression, and Spontaneous Remission. JCEM. MMAS data — 50%+ spontaneous normalization.

Travison, T.G., et al. (2007). A Population-Level Decline in Serum Testosterone Levels in American Men. JCEM, 92(1), 196–202. — Original MMAS secular decline, 15–20% lower across cohorts.

Santi, D., et al. (2025). Meta-analysis of secular trend in total testosterone levels, 1971–2024. 1,256 studies, N > 1,000,000. — 0.56%/year adjusted; LH parallel decline; mass spec subgroup no significant decline.

 Methods note on the ~0.56% per year figure cited in this episode: the Santi paper does not report a single percentage rate. The headline adjusted meta-regression coefficient (−0.6 nmol/L/year) is inflated by the random-effects weighting scheme and is not a biological rate. The 0.5–0.6% per year approximation comes from the pre-2000 stratified subgroup (Fig. 5, coefficient −0.1 nmol/L/year) divided by the dataset mean of 18.5 nmol/L. The post-2000 stratum runs larger (~1.1%), and the age-stratified coefficients in Table 5 cluster in the 0.4–0.9% range. The mass spectrometry subgroup (Table 3, Group 4) showed no significant trend (p = 0.845). The episode uses the conservative end of this range as the most defensible estimate of the real population-level rate after accounting for assay drift.

Nyante, S.J., Graubard, B.I., Li, Y., McQuillan, G.M., Platz, E.A., Rohrmann, S., Bradwin, G., & McGlynn, K.A. (2012). Trends in sex hormone concentrations in US males: 1988–1991 to 1999–2004. Int J Androl, 35(3), 456–466. doi: 10.1111/j.1365-2605.2011.01230.x. — Archived NHANES samples, same platform, waist circumference added; no significant decline in total or free testosterone.

Our Sponsors:
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