Barbell Medicine Podcast

Barbell Medicine
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Podcast by Barbell Medicine

  1. 6d ago

    Is Obesity A Muscle Problem?

    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 claim02:06   What obesity is, and the garage analogy05:06   How glucose gets into a muscle cell11:21   Insulin sensitivity improves without building muscle17:11   The best case for muscle-centric medicine21:13   What predicts falls and death: strength, not lean mass25:18   Separating muscle size from muscle function31:33   Liver fat: amount, type, and flux37:54   Should you build muscle first? The arithmetic42:37   Building muscle in a calorie deficit50:29   GLP-1s, DXA, and the lean mass panic58:23   Sarcopenic obesity, and why the name is wrong01:04:37 Why size still tells you something01:11:46 So what is obesity? Resources: Buy the book, Signal: https://www.barbellmedicine.com/shop/learning/signal/ New Barbell Medicine Hybrid 5K and 10K Run + Lift Programs Barbell Medicine coaching and templates: https://www.barbellmedicine.com 1.   Richter EA, Mikines KJ, Galbo H, Kiens B. Effect of exercise on insulin action in human skeletal muscle. J Appl Physiol (1985). 1989;66(2):876-885. doi:10.1152/jappl.1989.66.2.876. PMID: 2496078. https://doi.org/10.1152/jappl.1989.66.2.876 2.   Cawthon PM, Travison TG, Manini TM, et al. Establishing the link between lean mass and grip strength cut points with mobility disability and other health outcomes. J Gerontol A Biol Sci Med Sci. 2020;75(7):1317-1323. doi:10.1093/gerona/glz081. PMID: 30869772. https://doi.org/10.1093/gerona/glz081 3.   Bhasin S, Travison TG, Manini TM, et al. Sarcopenia definition: the position statements of the Sarcopenia Definition and Outcomes Consortium. J Am Geriatr Soc. 2020;68(7):1410-1418. doi:10.1111/jgs.16372. PMID: 32150289. https://doi.org/10.1111/jgs.16372 4.   Elgaddal N, Kramarow EA, Reuben C. Physical activity among adults aged 18 and over: United States, 2020. NCHS Data Brief No. 443. Hyattsville, MD: National Center for Health Statistics; 2022. PMID: 36043905. https://www.cdc.gov/nchs/products/databriefs/db443.htm 5.   Whitfield GP, Carlson SA, Ussery EN, Fulton JE, Galuska DA, Petersen R. Trends in meeting physical activity guidelines among urban and rural dwelling adults, United States, 2008-2017. MMWR Morb Mortal Wkly Rep. 2019;68(23):513-518. doi:10.15585/mmwr.mm6823a1. PMID: 31194722. https://doi.org/10.15585/mmwr.mm6823a1 6.   Wang T, Wang J, Hu X, Huang XJ, Chen GX. Current understanding of glucose transporter 4 expression and functional mechanisms. World J Biol Chem. 2020;11(3):76-98. doi:10.4331/wjbc.v11.i3.76. PMID: 33274014. https://doi.org/10.4331/wjbc.v11.i3.76 7.   DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care. 2009;32(Suppl 2):S157-S163. doi:10.2337/dc09-S302. PMID: 19875544. https://doi.org/10.2337/dc09-S302 8.   Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev. 2013;93(3):993-1017. doi:10.1152/physrev.00038.2012. PMID: 23899560. https://doi.org/10.1152/physrev.00038.2012 9.   Petersen KF, Dufour S, Savage DB, et al. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci U S A. 2007;104(31):12587-12594. doi:10.1073/pnas.0705408104. PMID: 17640906. https://doi.org/10.1073/pnas.0705408104 10. Rabøl R, Petersen KF, Dufour S, Flannery C, Shulman GI. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proc Natl Acad Sci U S A. 2011;108(33):13705-13709. doi:10.1073/pnas.1110105108. PMID: 21808028. https://doi.org/10.1073/pnas.1110105108 11. Perseghin G, Price TB, Petersen KF, et al. Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects. N Engl J Med. 1996;335(18):1357-1362. doi:10.1056/NEJM199610313351804. PMID: 8857019. https://doi.org/10.1056/NEJM199610313351804 12. Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H. Effect of physical exercise on sensitivity and responsiveness to insulin in humans. Am J Physiol. 1988;254(3 Pt 1):E248-E259. doi:10.1152/ajpendo.1988.254.3.E248. PMID: 3126668. https://doi.org/10.1152/ajpendo.1988.254.3.E248 13. Mikines KJ, Sonne B, Tronier B, Galbo H. Effects of acute exercise and detraining on insulin action in trained men. J Appl Physiol (1985). 1989;66(2):704-711. doi:10.1152/jappl.1989.66.2.704. PMID: 2496077. https://doi.org/10.1152/jappl.1989.66.2.704 14. Yu R, Duncombe SL, Nemoto Y, et al. Physical activity trajectories and mortality. Br J Sports Med. 2025;59(17):1228-1241. doi:10.1136/bjsports-2024-109122. PMID: 40639966. https://doi.org/10.1136/bjsports-2024-109122 15. Saint-Maurice PF, Coughlan D, Kelly SP, et al. Association of leisure-time physical activity across the adult life course with all-cause and cause-specific mortality. JAMA Netw Open. 2019;2(3):e190355. doi:10.1001/jamanetworkopen.2019.0355. PMID: 30848809. https://doi.org/10.1001/jamanetworkopen.2019.0355 16. Wang Y, Luo D, Liu J, Song Y, Jiang B, Jiang H. Low skeletal muscle mass index and all-cause mortality. PLoS One. 2023;18(6):e0286745. doi:10.1371/journal.pone.0286745. PMID: 37288745. https://doi.org/10.1371/journal.pone.0286745 17. Umpierre D, Ribeiro PAB, Kramer CK, et al. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes. JAMA. 2011;305(17):1790-1799. doi:10.1001/jama.2011.576. PMID: 21540423. https://doi.org/10.1001/jama.2011.576 18. Goodpaster BH, Carlson CL, Visser M, et al. Attenuation of skeletal muscle and strength in the elderly: the Health ABC Study. J Appl Physiol (1985). 2001;90(6):2157-2165. doi:10.1152/jappl.2001.90.6.2157. PMID: 11356778. https://doi.org/10.1152/jappl.2001.90.6.2157 19. Paquin J, Lagacé JC, Brochu M, Dionne IJ. Exercising for insulin sensitivity, is there a mechanistic relationship with quantitative changes in skeletal muscle mass? Front Physiol. 2021;12:656909. doi:10.3389/fphys.2021.656909. PMID: 34054574. https://doi.org/10.3389/fphys.2021.656909 20. Eriksson J, Taimela S, Eriksson K, Parviainen S, Peltonen J, Kujala U. Resistance training in the treatment of non-insulin-dependent diabetes mellitus. Int J Sports Med. 1997;18(4):242-246. doi:10.1055/s-2007-972627. PMID: 9231838. https://doi.org/10.1055/s-2007-972627 21. Cuff DJ, Meneilly GS, Martin A, Ignaszewski A, Tildesley HD, Frohlich JJ. Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Diabetes Care. 2003;26(11):2977-2982. doi:10.2337/diacare.26.11.2977. PMID: 14578226. https://doi.org/10.2337/diacare.26.11.2977 22. Bucci M, Huovinen V, Guzzardi MA, et al. Resistance training improves skeletal muscle insulin sensitivity in elderly offspring of overweight and obese mothers. Diabetologia. 2016;59(1):77-86. doi:10.1007/s00125-015-3780-8. PMID: 26486356. https://doi.org/10.1007/s00125-015-3780-8 23. Mavros Y, Kay S, Anderberg KA, et al. Changes in insulin resistance and HbA1c are related to exercise-mediated changes in body composition in older adults with type 2 diabetes: interim outcomes from the GREAT2DO trial. Diabetes Care. 2013;36(8):2372-2379. doi:10.2337/dc12-2196. PMID: 23474589. https://doi.org/10.2337/dc12-2196 24. Janssen I, Heymsfield SB, Wang ZM, Ross R. Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol (1985). 2000;89(1):81-88. doi:10.1152/jappl.2000.89.1.81. PMID: 10904038. https://doi.org/10.1152/jappl.2000.89.1.81 25. Orwoll ES, Peters KE, Hellerstein M, Cummings SR, Evans WJ, Cawthon PM. The importance of muscle versus fat mass in sarcopenic obesity: a re-evaluation using D3-creatine muscle mass versus DXA lean mass measurements. J Gerontol A Biol Sci Med Sci. 2020;75(7):1362-1368. doi:10.1093/gerona/glaa064. PMID: 32232396. https://doi.org/10.1093/gerona/glaa064 26. Holten MK, Zacho M, Gaster M, Juel C, Wojtaszewski JFP, Dela F. Strength training increases insulin-mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes. Diabetes. 2004;53(2):294-305. doi:10.2337/diabetes.53.2.294. PMID: 14747278. https://doi.org/10.2337/diabetes.53.2.294 27. Manca A, Dragone D, Dvir Z, Deriu F. Cross-education of muscular strength following unilateral resistance training: a meta-analysis. Eur J Appl Physiol. 2017;117(11):2335-2354. doi:10.1007/s00421-017-3720-z. PMID: 28936703. https://doi.org/10.1007/s00421-017-3720-z 28. Bilet L, Phielix E, van de Weijer T, et al. One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion. Diabetologia. 2020;63(6):1211-1222. doi:10.1007/s00125-020-05128-1. PMID: 32185462. https://doi.org/10.1007/s00125-020-05128-1 29. Lee J, Kim D, Kim C. Resistance training for glycemic control, muscular strength, and lean body mass in old type 2 diabetic patients: a meta-analysis. Diabetes Ther. 2017;8(3):459-473. doi:10.1007/s13300-017-0258-3. PMID: 28382531. https://doi.org/10.1007/s13300-017-0258-3 30. Goodpaster

    Is Obesity A Muscle Problem?

  2. Aug 27

    Who Needs Testosterone, and Who's Not Getting It I Signal Episode 4

    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 bookResources: 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/  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.xBaillargeon 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.2013.6895Bhasin 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.2018-00229Mulhall 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.2018.03.115Corona 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.12770Morgentaler 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.12546Mok 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/glz195Clift 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.250245Malik 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.2015.01.027Donatucci 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.12608Saad 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-11-0221Ly 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/deh834Liu 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)68614-5Ko 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.2011.10.137Kohn 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.2016.10.004Wenker 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.12890Basaria 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/NEJMoa1000485Vigen 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.2013.280386Basaria 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.2015.8881Budoff 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.2016.21043Lincoff 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/NEJMoa2215025Huggins 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.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.2008.09.024Khera 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.2013.08.015Bhasin 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.2023.48692Snyder 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 Our Sponsors: * Check out CovePure and use my code CovePure.com/bbm for a great deal: https://covepure.com * Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com * Check out Factor and use my code factormeals.com/bbm50off for a great deal: https://www.factor75.com * Check out Quince and use my code quince.com/BBM for a great deal: https://www.quince.com Advertising Inquiries: https://redcircle.com/brands

    Who Needs Testosterone, and Who's Not Getting It I Signal Episode 4

  3. Aug 20

    Your Fat Has a Storage Limit

    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/ New Barbell Medicine Hybrid 5K and 10K Run + Lift Programs Barbell Medicine coaching and templates: https://www.barbellmedicine.com Plus podcast subscription: https://www.barbellmedicine.com/shop/subscriptions/plus-podcast-subscription/ Barbell Medicine Premium: https://www.barbellmedicine.com/shop/subscriptions/barbell-medicine-premium/ Signal (now shipping): https://www.barbellmedicine.com/shop/learning/signal/ 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/NEJMoa033179Mohammed 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.2008.418Sommer 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/s41598-020-69498-7Donnelly 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/JCI23621Spalding KL, Arner E, Westermark PO, et al. Dynamics of fat cell turnover in humans. Nature. 2008;453(7196):783-787. doi:10.1038/nature06902Fabbrini 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.2010.04.056Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350(12):1220-1234. doi:10.1056/NEJMra025261Al 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/s13023-024-03084-2Petersen 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/JCI200215001Miyazaki 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.87.6.8567Cusi 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/M15-1774Taylor 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/CS20230586Martin 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/db21-0129Martin 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/dc21-1262Sanyal 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/s41591-024-03018-2Portillo-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.2015-1966Hagström 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.2017.07.027Rubino 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)00316-4Guerrero-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.2010-0288Sánchez-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:10.1155/2020/4678526McLaughlin 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:10.7326/0003-4819-139-10-200311180-00007McPherson 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.2016.453Mózes 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-2021-324243Bansal 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.0000000000001608Tomiyama 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.2016.17Wildman 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.168.15.1617Mongraw-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.2018.02.055Gujral 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/M16-1895Ruderman NB, Schneider SH, Berchtold P. The "metabolically-obese," normal-weight individual. Am J Clin Nutr. 1981;34(8):1617-1621. doi:10.1093/ajcn/34.8.1617Sims EA. Are there persons who are obese, but metabolically healthy? Metabolism. 2001;50(12):1499-1504. doi:10.1053/meta.2001.27213National 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.American Medical Association House of Delegates. Resolution 420 (A-13): Recognition of Obesity as a Disease. Adopted June 18, 2013.American Medical Association Council on Science and Public Health. Report 3-A-13: Is Obesity a Disease? 2013.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.12198Hinnouho 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/dc12-1654Herman 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 car

    Your Fat Has a Storage Limit

  4. Aug 12

    Lifting and longevity: is 1 hour a week really the limit? Plus GLP1s and mood, training with ME/CFS, and Protein vs. Calories

    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: https://www.barbellmedicine.com/shop/subscriptions/plus-podcast-subscription/ 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 New Barbell Medicine Hybrid 5K and 10K Run + Lift Programs Barbell Medicine coaching and templates: https://www.barbellmedicine.com Barbell Medicine Premium: https://www.barbellmedicine.com/shop/subscriptions/barbell-medicine-premium/ Signal (pre-order) 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/ Our Sponsors: * Check out CovePure and use my code CovePure.com/bbm for a great deal: https://covepure.com * Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com * Check out Factor and use my code factormeals.com/bbm50off for a great deal: https://www.factor75.com * Check out Quince and use my code quince.com/BBM for a great deal: https://www.quince.com Advertising Inquiries: https://redcircle.com/brands

    Lifting and longevity: is 1 hour a week really the limit? Plus GLP1s and mood, training with ME/CFS, and Protein vs. Calories

  5. Aug 7

    The FDA Voted for 6 Peptides. Its Own Scientists Said No

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

    The FDA Voted for 6 Peptides. Its Own Scientists Said No

  6. Jul 31

    The Man Who Couldn’t Stop Gaining Weight | A Medical Mystery

    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 weight00:01:49 Meet the case (and the rules of the game)00:02:36 The presentation: 21, headaches, unexplained weight gain00:03:57 Austin’s one-liner and how a clinician builds a differential00:05:10 Secondary headaches: what raises the red flag00:13:12 The exam: vitals, and the eye findings that matter00:14:37 The labs, one number at a time00:16:08 Raised pressure and a visual-field clue (bitemporal hemianopia)00:20:45 The MRI00:21:54 First diagnosis: craniopharyngioma00:25:32 The name: a tumor built from tooth tissue00:25:50 Surgery, and what it costs00:27:43 The new mystery: gaining weight faster than ever00:33:41 Second diagnosis: acquired hypothalamic obesity00:39:17 How your brain sets your weight: the POMC brake and the AgRP accelerator00:42:07 What about leptin?00:45:46 Monogenic vs common obesity00:50:30 Why GLP-1 drugs still worked: the brainstem backdoor00:52:11 Responders and non-responders00:55:40 Setmelanotide: a drug for the broken circuit00:56:53 TRANSCEND, and the new FDA approval00:58:55 What it costs01:01:32 Why we care about body fat at all: the garage01:04:36 Flux: which fat is actually dangerous01:09:15 Close Resources Barbell Medicine coaching and templates: https://www.barbellmedicine.com Plus podcast subscription: https://www.barbellmedicine.com/shop/subscriptions/plus-podcast-subscription/ Barbell Medicine Premium: https://www.barbellmedicine.com/shop/subscriptions/barbell-medicine-premium/ Signal (book pre-order): https://www.barbellmedicine.com/shop/learning/signal/ 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.  Our Sponsors: * Check out CovePure and use my code CovePure.com/bbm for a great deal: https://covepure.com * Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com * Check out Factor and use my code factormeals.com/bbm50off for a great deal: https://www.factor75.com * Check out Quince and use my code quince.com/BBM for a great deal: https://www.quince.com Advertising Inquiries: https://redcircle.com/brands

    The Man Who Couldn’t Stop Gaining Weight | A Medical Mystery

  7. Jul 24

    The Protein Scaries: What the Research Says About Your Kidneys, Cancer, Bones, and Body Fat

    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: Barbell Medicine coaching and templates: https://www.barbellmedicine.com Plus podcast subscription: https://www.barbellmedicine.com/shop/subscriptions/plus-podcast-subscription/ Barbell Medicine Premium: https://www.barbellmedicine.com/shop/subscriptions/barbell-medicine-premium/ Signal (book pre-order): https://www.barbellmedicine.com/shop/learning/signal/ Our Protein Content: https://www.barbellmedicine.com/blog/protein-and-weight-loss/ https://www.barbellmedicine.com/blog/protein-on-ozempic/ https://www.barbellmedicine.com/blog/barbell-medicine-protein-recommendations/ Studies Levine et al. Cell Metabolism 2014. doi:10.1016/j.cmet.2014.02.006Naghshi 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.2016030248Castaneda 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.2013.05.021Fenton et al. Nutrition Journal 2011. doi:10.1186/1475-2891-10-41Shams-White et al. Am J Clin Nutr 2017. doi:10.3945/ajcn.116.145110Witard et al. Am J Clin Nutr 2013. doi:10.3945/ajcn.112.055517 Macnaughton et al. Physiol Rep 2016. doi:10.14814/phy2.12893Trommelen 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.0020456Berryman 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 Our Sponsors: * Check out CovePure and use my code CovePure.com/bbm for a great deal: https://covepure.com * Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com * Check out Factor and use my code factormeals.com/bbm50off for a great deal: https://www.factor75.com * Check out Quince and use my code quince.com/BBM for a great deal: https://www.quince.com Advertising Inquiries: https://redcircle.com/brands

    The Protein Scaries: What the Research Says About Your Kidneys, Cancer, Bones, and Body Fat

  8. Jul 17

    Is It Really Just Calories In, Calories Out? Metabolism, Insulin, Hormones and Why Counting Fails

    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-line2:10 Thermodynamics: what sets both sides2:41 Your metabolism is three things4:05 Claim 1: my metabolism crashed4:24 No cliff at 40: the doubly labeled water study5:33 Real metabolic adaptation after weight loss6:56 Why your food diary lies7:49 Claim 2: it's my hormones8:07 Thyroid: mostly water9:36 Cortisol: explains about 1 percent11:12 PCOS is now PMOS13:06 Menopause14:18 Claim 3: a calorie isn't a calorie16:48 Absorption: nuts, cooking, eggs19:44 Why calorie counting fails21:12 Claim 4: it's not Calories, it's insulin22:02 Testing the carbohydrate-insulin model25:52 The GLP-1 drugs that should end it28:34 The whole list, claim by claim29:53 What to actually do30:42 Next week: are GLP-1s cheating? 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/ 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 Our Sponsors: * Check out CovePure and use my code CovePure.com/bbm for a great deal: https://covepure.com * Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com * Check out Factor and use my code factormeals.com/bbm50off for a great deal: https://www.factor75.com * Check out Quince and use my code quince.com/BBM for a great deal: https://www.quince.com Advertising Inquiries: https://redcircle.com/brands

    Is It Really Just Calories In, Calories Out? Metabolism, Insulin, Hormones and Why Counting Fails
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Podcast by Barbell Medicine

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  • Creator
    Barbell Medicine
  • Years Active
    2017 - 2026
  • Episodes
    446
  • Rating
    Clean
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