Episode Summary: The Cardiometabolic Revolution of Semaglutide, Tirzepatide, and Beyond

This episode provides a comprehensive, evidence-based update on GLP-1 receptor agonists (anti-obesity medications), featuring Dr. Jordan Feigenbaum, Dr. Austin Baraki, and Dr. Spencer Nadolsky. The hosts review the rapid evolution of these drugs—from short-acting injectables to potent multi-agonists like Tirzepatide (Mounjaro/Zepbound) and Retatrutide—which now achieve weight loss efficacy rivaling bariatric surgery.

The discussion clarifies the broad, weight-independent benefits these drugs offer for cardiovascular, renal, and liver health (CKM Syndrome). The experts address common concerns, including the high incidence of gastrointestinal side effects and the heavily debated risk of muscle mass loss, concluding the risk is often overblown and easily mitigated by resistance training and adequate protein intake. Finally, they discuss the biggest hurdle to access: cost, and the role of newer oral and compounded options in the evolving landscape.

⏱️ Episode Timestamps

• 00:00 Welcome and Introductions
• 00:05:48 Defining GLP-1 and the Incretin Effect
• 00:08:06 Debunking "Nature's Ozempic" (DPP-4 resistance)
• 00:11:17 Evolution of GLP-1 Drugs (Longer duration, higher potency)
• 00:14:35 Defining and Discussing "Food Noise"
• 00:19:43 Semaglutide Efficacy (STEP & SUSTAIN Trials)
• 00:22:36 Tirzepatide Efficacy (SURMOUNT Trials)
• 00:24:50 Triple Agonist Pipeline (Retatrutide)
• 00:28:04 Oral Options and Future Accessibility (Orforglipron)
• 00:33:10 Weight-Independent Cardio Benefits (SELECT Trial)
• 00:38:12 Benefits for Kidney and Liver Health (CKM Syndrome)
• 00:41:47 Emerging Benefits (Sleep Apnea, Addiction, Cancer)
• 00:48:20 Common Side Effects (Nausea, Constipation, Fatigue)
• 00:52:59 Rare/Serious Risks (Pancreatitis, NAION)
• 00:58:36 Muscle Mass Loss Concern (Hype vs. Data)
• 01:13:44 Biggest Hurdle: Cost and Prior Authorization
• 01:16:50 Compounded Versions vs. Research Chemicals
• 01:19:57 Role of Older Anti-Obesity Medications and Microdosing
• 01:24:41 Final Summary

🔗 Resources and Next Steps

Work with Experts on Cardiometabolic Health:

Connect with Dr. Austin Baraki and Dr. Spencer Nadolsky: https://joinvineyard.com/ 

For evidence-based resistance training programs: barbellmedicine.com/training-programs

For individualized medical and training consultation: barbellmedicine.com/coaching

Explore our full library of articles on health and performance: barbellmedicine.com/resources

To join Barbell Medicine Plus and get ad-free listening, product discounts, exclusive content, and more: https://barbellmedicine.supercast.com/

I. Basic Science and The Evolution of Anti-Obesity Medication

Defining GLP-1 and the Incretin Effect

GLP-1 (Glucagon-like peptide 1) is a naturally occurring peptide hormone released by the intestines after food ingestion.1 It plays a role in the incretin effect, which enhances insulin secretion from the pancreas.2 However, natural GLP-1 is quickly broken down by the DPP-4 enzyme, limiting its efficacy.3 Modern GLP-1 receptor agonists (like Semaglutide and Tirzepatide) are synthetic analogs engineered to be resistant to DPP-4 breakdown, allowing them to stick around longer and reach receptors in the brain to modulate appetite.

The concept of food noise describes the persistent, relentless, non-hunger-related thoughts about food that many individuals with obesity experience.5 Patients often report that the cessation of this food noise is one of the most profound effects of the medication, freeing up cognitive energy previously dedicated to ruminating over food.

The Rapidly Advancing Pipeline

The evolution of this drug class has been defined by three trends:

1. Duration: Moving from twice-daily injections (Exenatide) to weekly injections (Ozempic) and future monthly options.
2. Potency: Increasing efficacy through molecular engineering and multi-agonist targeting (e.g., Tirzepatide hitting GLP-1 and GIP receptors).7
3. Tolerability: Improving the side effect profile, making newer agents easier to tolerate.

Upcoming agents include oral options like Orforglipron and high-dose oral Semaglutide, which promise easier administration and potentially lower costs.8 Triple agonists like Retatrutide are showing efficacy in the mid-20% total weight loss range, rivaling metabolic surgery outcomes.

II. Efficacy and Broad Health Benefits

Weight Loss Efficacy

The clinical data demonstrates significant efficacy, classifying these drugs as game-changers:

• Semaglutide (Ozempic/Wegovy): Averages around 15% total body weight loss.10
• Tirzepatide (Mounjaro/Zepbound): Averages 20-21% total body weight loss, generally showing superiority and improved tolerability compared to Semaglutide.11
• Pipeline Agents (Retatrutide): Showing potential for 24-25% total weight loss, pushing pharmacological intervention into the same league as bariatric surgery.

Weight-Independent Organ Protection (CKM Syndrome)

A significant portion of the benefit derived from these medications is weight-independent, meaning it's separate from the mass lost.12 The drugs exert pleiotropic (multiple) effects across organ systems, leading to the coining of CKM Syndrome (Cardiovascular-Kidney-Metabolic Syndrome).

• Cardiovascular Health: The SELECT trial demonstrated a radical reduction in Major Adverse Cardiovascular Events (MACE), with evidence suggesting at least two-thirds of this benefit is independent of the weight lost.
• Renal and Liver Health: Trials like FLOW are demonstrating benefits for Chronic Kidney Disease (CKD) progression.14 Furthermore, resolution or significant improvement of Fatty Liver Disease is commonly observed once weight loss exceeds the 7.5-10% threshold.

Emerging and Future Benefits

Research is exploring the impact of GLP-1 agonists on:

• Obstructive Sleep Apnea (OSA): Leading to resolution or reduction in severity, confirmed in trials.
• Addiction: Early anecdotal and some retrospective data show reduced alcohol consumption, with potential benefits being explored for gambling and opioid addiction due to strong effects in the brain's reward center.
• Neuroprotection and Cancer: The potential for favorable effects on neurodegenerative disease and certain adiposity-associated cancers is under investigation.

III. Side Effects and Mitigating Muscle Loss Concerns

Common and Rare Side Effects

The vast majority of side effects are Gastrointestinal and highest during the initial dose escalation:

• Nausea: Most common, but typically resolves over time. Management includes smaller, more frequent meals and temporarily lower-fat diets.
• Constipation: Persistent and requires active management with fiber and potentially laxatives.
• Rare Risks: Pancreatitis is a common concern but has shown no increased incidence compared to placebo in trials. Gallstone development is linked to rapid weight loss by any mechanism, including bariatric surgery.

Muscle Mass Loss: Hype vs. Data

The concern that these agents cause a unique, disproportionate amount of skeletal muscle loss is largely overblown hype.

• Initial Subgroup Analysis: Early analysis of Semaglutide trials suggested a higher proportion of fat-free mass loss (around 38%) than expected (25%). This was often cited as evidence of muscle catabolism.
• Physiological Reality: Experts suggest that much of the observed fat-free mass loss includes fluid shifts (glycogen, water) rather than pure skeletal muscle. Tirzepatide trials showed fat-free mass loss closer to the expected 25%.
• Muscle Quality Improves: Studies like SEMI-LEAN have shown that in patients with sarcopenia/obesity, muscle function (quality) actually improves despite some lean mass loss.
• Mitigation: The solution to minimizing any proportional muscle loss is simple: resistance training (2-3 days per week) and high protein intake (1.0 to 1.2 g/kg of body weight). Exercise is the primary controller here, minimizing the effect of the agents on the muscle compartment.

IV. Access, Cost, and Future Outlook

The Biggest Hurdle: Cost

The primary barrier to access remains cost, with list prices for branded medications often exceeding $1,000 per month, despite lower net costs for manufacturers.18 Insurance approval often requires complex Prior Authorization (PA) processes, which overwhelm standard primary care practices.

The Role of Compounding and Older Medications

• Compounded Versions: Compounded versions are cheaper but lack safety and efficacy data from controlled trials. There are risks associated with the source and purity of the active pharmaceutical ingredient.19
• Older Medications: Older anti-obesity medications (e.g., Phentermine/Topiramate) still have a role, offering proven efficacy (though less potent) and significantly lower cost, serving as a bridge until GLP-1 prices decline.
• Future Trend: Prices are expected to drop significantly in the next 5-10 years, making the FDA-approved versions more accessible and rendering compounded versions largely obsolete.

Our Sponsors:
* Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com
* Check out Factor: https://factormeals.com/bbm50off
* Check out Quince: https://quince.com/BBM
* Check out Rosetta Stone and use my code TODAY for a great deal: https://www.rosettastone.com
* Check out Uncommon Goods: https://uncommongoods.com/bbm
* Check out Washington Red Raspberries: https://redrazz.org


Support this podcast at — https://redcircle.com/barbell-medicine-podcast/donations

Advertising Inquiries: https://redcircle.com/brands

Privacy & Opt-Out: https://redcircle.com/privacy

Cycle Syncing, Cardio Myths, and Iron Deficiency: A Barbell Medicine Review of Viral Claims

Episode Summary: Debunking Women's Health Claims and Setting Optimal Targets

In this in-depth episode, Dr. Jordan Feigenbaum, joined by Dr. Lauren Colenso-Semple and Dr. Austin Baraki, breaks down the viral women's health claims made on a popular podcast, separating misleading mechanistic theory from actionable, evidence-based advice.

They tackle three major topics: the idea that Cycle Syncing is necessary for performance (spoiler: it's not); the confused messaging surrounding HIIT and Zone 2 cardio (consistency is key); and a critical discussion on Iron Deficiency, clarifying why standard lab cutoffs for ferritin are too low and why treating to an optimal target (greater than or equal to 50 ng/mL) is essential for managing fatigue and optimizing exercise performance in women.

⏱️ Episode Timestamps

• 1:29 I. Cycle Syncing: The Claim and the Mechanistic Logic
• 18:54 II. Conditioning Confusion: High Intensity, Zone 2, and Zone Definitions
• 21:10 Polarized vs. Pyramidal Training (Context)
• 47:08 III. Iron Deficiency: Normalizing Low Ferritin
• 51:52 Evidence Review: Setting Accurate Ferritin Cutoffs

⭐ Get More Value: Exclusive Content and Resources

Connect with Dr. Lauren Colenso-Semple: @drlaurencs1

Want to support the show and get early, ad-free access to all episodes plus exclusive bonus content? Subscribe to Barbell Medicine Plus and get ad-free listening, product discounts, and more. Try it free for 30-days.

Unsure which training plan is right for you? Take the free Barbell Medicine Template Quiz to be matched with the ideal program for your goals and experience level.

For media, support, or general questions, please contact us at [email protected]

I. Cycle Syncing: Why Consistency Trumps Hormone Status

The Problem with Mechanistic Reductionism

The viral claim that women must systematically adjust their training volume and intensity based on fluctuating hormones (estrogen and progesterone) to optimize performance or avoid harm is based on a reductionist and largely unproven hypothesis. While hormone changes are real, relying solely on mechanistic data (what happens in isolated cells or textbook diagrams) is insufficient, as the complex, interactive nature of human physiology often overrides these single-factor effects.

Dr. Feigenbaum and Dr. Colenso-Semple clarify that no reliable human evidence supports the idea that cycle syncing leads to superior athletic performance or adaptation. The fundamental flaw in the advice is that it confuses a plausible mechanism with a meaningful outcome.

Harm Assessment: The Cost of Inconsistency

The primary harm in cycle syncing is that it leads to missed training opportunities. Adaptation is driven by consistent training load (mechanotransduction), not a temporary hormone profile. Planning to proactively reduce training intensity or volume based on an unproven hormone schedule is detrimental to long-term strength and endurance gains.

Training modifications should be reactive—if a person genuinely feels symptoms of fatigue, pain, or discomfort on a given day (regardless of their cycle status), they should adjust or skip the workout. The advice to only exercise or train hard when you "feel awesome" is inconsistent with the reality of progressive training and often sets unrealistic expectations.

II. Conditioning Confusion: Context is Everything

Debunking Zone 2 and HIIT Extremism

The hosts address the confusing and contradictory advice regarding high-intensity interval training (HIIT) and Zone 2 cardio, particularly the claim that Zone 2 is "bro science" and should be avoided.

The issue lies in a lack of context. The discussion on polarized (80/20) versus pyramidal training only becomes relevant for high-volume endurance athletes (those training for 10+ hours per week) where managing fatigue via intensity distribution is critical.

For the general population—the vast majority of people consuming the viral content—the goal is simple: consistency. Adhering to the minimum physical activity guidelines (150 minutes of moderate or 75 minutes of vigorous activity per week) is the priority. For this audience, almost any combination of volume and intensity works, as long as it is challenging enough and sustainable. The complex debate over intensity distribution is entirely non-actionable for people simply trying to start or maintain an exercise habit.

The advice was non-actionable because it:

1. Used incorrect zone definitions ("Zone 1 is sitting around").
2. Failed to integrate high-load resistance training into the cardio recommendation.
3. Ignored the relationship between training frequency, volume, and total training load.

III. Iron Deficiency: Treating to Optimal Physiology

Normalizing Deficiency: The Problem with Lab Cutoffs

Dr. Baraki addresses the critical issue of Iron Deficiency, emphasizing that many standard laboratory cutoffs for ferritin are misleadingly low. Labs often set the lower limit of "normal" (e.g., 12–15 ng/mL) based on population averages, not optimal physiology. This is problematic because upwards of 50% of young women in these samples may have completely depleted iron stores (non-anemic iron deficiency) due to menstrual blood loss and insufficient dietary intake. By accepting these low limits, the medical system is effectively normalizing deficiency.

Optimal Ferritin Targets and Clinical Management

The consequences of non-anemic iron deficiency include significant symptoms like fatigue, impaired exercise performance, and restless leg syndrome. The body strips iron from other tissues, including muscle, to prioritize red blood cell production, masking the deficiency until it reaches the end stage of anemia.

Clinical guidelines are evolving, recognizing that higher ferritin levels are necessary for optimal health:

• General Target: A ferritin target of greater than or equal to 50 ng/mL is reasonable for most patients, especially those experiencing fatigue.
• Restless Leg Syndrome (RLS): A higher target of greater than or equal to 75 ng/mL may be necessary to address RLS, which is strongly linked to low iron stores in the brain.
• Treatment: Management often involves oral or IV iron supplementation to treat to this optimal target, while also investigating and treating the underlying causes of blood loss or malabsorption.
• 
  

The idea that we are accepting lower levels due to a "sicker population" is a misconception; in reality, cutoffs are being increased (e.g., American Gastroenterology Association: 45 ng/mL; American Society of Hematology: 50 ng/mL) as clinicians learn more about optimal physiology and the necessity of managing non-anemic iron deficiency.

IV. Conclusion: Core Takeaways

The goal of reviewing this viral content is to provide a vital filter for the public, differentiating between a simple mechanism and an outcome that truly matters to long-term health and training.

1. Consistency is King: For health, find a training program you can adhere to consistently. Do not let fear of cortisol or unproven hormone matching keep you from moving your body.
2. Lift Weights: If your goal is to get stronger and improve bone mineral density, you must lift weights.
3. Address Fatigue: Do not overlook iron deficiency; address fatigue by targeting optimal ferritin levels.

V. Citations

• https://pmc.ncbi.nlm.nih.gov/articles/PMC6120973/ 
• https://pubmed.ncbi.nlm.nih.gov/30559681/ 
• https://pubmed.ncbi.nlm.nih.gov/30559681/ 
• https://pmc.ncbi.nlm.nih.gov/articles/PMC6120973/ 
• https://pubmed.ncbi.nlm.nih.gov/30559681/ 
• https://www.nature.com/articles/s41467-025-63475-2  
• https://journals.lww.com/acsm-msse/pages/articleviewer.aspx?year=2025&issue=11000&article=00025&type=Fulltext 
• https://onlinelibrary.wiley.com/doi/10.1155/tsm2/2008291  
• https://pubmed.ncbi.nlm.nih.gov/40010355/ 
• https://pubmed.ncbi.nlm.nih.gov/33955140/ 
• https://pubmed.ncbi.nlm.nih.gov/37084486/
• https://pubmed.ncbi.nlm.nih.gov/39576887/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC7497427/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC10300696/
• https://pubmed.ncbi.nlm.nih.gov/38066931/

Our Sponsors:
* Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com
* Check out Factor: https://factormeals.com/bbm50off
* Check out Quince: https://quince.com/BBM
* Check out Rosetta Stone and use my code TODAY for a great deal: https://www.rosettastone.com
* Check out Uncommon Goods: https://uncommongoods.com/bbm
* Check out Washington Red Raspberries: https://redrazz.org


Support this podcast at — https://redcircle.com/barbell-medicine-podcast/donations

Advertising Inquiries: https://redcircle.com/brands

Privacy & Opt-Out: https://redcircle.com/privacy

Episode Summary

This is a preview of our subscriber-only Ask Us Anything episode, where Dr. Jordan Feigenbaum and Dr. Austin Baraki tackle the most persistent problems in training and nutrition. Hear the science behind managing pain in the gym—determining the threshold for acceptable discomfort versus a true programming error. They also analyze why short-term study findings often fail in the real world, cover the science of pre-exhaust training, and give practical advice on the psychology of managing dietary cravings when transitioning to a healthier diet.

Takeaways

• Pain Threshold: Learn the 3/10 rule for pain in training: low-level, self-limiting discomfort is common, but anything more should be addressed.
• Programming Fix: Recurrent pain (e.g., every 5-6 weeks) is often a programming issue caused by a lack of training tolerance, not a technique fault. The solution is modifying the total load, not just changing your form.
• Training Philosophy: Stop "pushing" harder every session. The best way to progress is to wait for fitness to show up (the lift feels easier) before increasing the load.
• Pre-Exhaust Science: Find out why techniques like leg extensions before squats are suboptimal for both strength and hypertrophy because they compromise the necessary total training load.
• Cravings Are Transient: The intense difficulty experienced when switching from ultra-processed, hyper-palatable foods to home-cooked meals is normal (hedonic adaptation) and transient. Understanding that this discomfort will fade is key to long-term adherence.

⏱️ Preview Timestamps

• 00:00 Introduction & Plus Subscriber Offer
• 00:40 How Often Should I Feel Pain in Training? (Pain Threshold & Training Tolerance)
• 09:31 The Science of Pre-Exhaust Training (Why it compromises total load)
• 16:54 Managing Dietary Cravings When Switching Habits (Hedonic Adaptation)
• 27:49 Conclusion: Barbell Medicine Plus Offer

🔓 Unlock the Full Episode & Exclusive Benefits

The topics above are only a fraction of what's covered in the full Ask Us Anything episode, which also includes:

• How to structure high-intensity conditioning intervals and why heart rate is often a poor metric.
• The science behind Powerlifting peaking and tapering for non-elite athletes.
• The latest, large-scale meta-analysis on Vitamin D and respiratory infections and why the real-world benefit is highly modest.
• A full discussion on the discrepancy between short-term studies and real-world results in diet and exercise.

Subscribe Today to Barbell Medicine Plus

When you join Barbell Medicine Plus, you get the full ad-free episode, access to our bonus content library, and major discounts:

• 25% off all courses and seminars
• 15% off consultations
• 10% off all our programs

Want to support the show and get early, ad-free access to all episodes plus exclusive bonus content? Subscribe to Barbell Medicine Plus and get ad-free listening, product discounts, and more. Try it free for 30-days.

Unsure which training plan is right for you? Take the free Barbell Medicine Template Quiz to be matched with the ideal program for your goals and experience level.

For media, support, or general questions, please contact us at [email protected]

Resources

Pain

It is normal and acceptable for lifters to experience low-level, self-limiting discomfort during training. The threshold for acceptable pain is generally considered to be less than 3/10 on the pain scale, provided the discomfort is not sharp, does not cause fear, and is gone within 24 to 48 hours.

The real warning sign is recurrent pain—when the same tweak flares up every 5 to 6 weeks. This is typically not a technique fault but a programming issue—the lifter is demanding more from their body than their current training tolerance allows. The solution is usually to reduce the overall training load, modify the volume/intensity, and rebuild capacity gradually.

• www.barbellmedicine.com/blog/training-with-pain-a-practical-approach
• www.barbellmedicine.com/blog/the-barbell-medicine-guide-to-tendinopathy 
• Shrier, I. (2004). Does stretching help prevent injuries? Clinical Journal of Sports Medicine. DOI: {10.1097/00042752-200405000-00002} (Review discussing prior injury as a key risk factor).
• Gabbett, T. J. (2016). The training—injury prevention paradox: should athletes be training smarter and harder? British Journal of Sports Medicine. DOI: {10.1136/bjsports-2016-096319} (Discusses role of prior injury and training load).
• Siewe et al. (2014). Injuries in powerlifting: how common are they and what are their causes? Sports Medicine - Open. DOI: {10.1186/s40798-014-0016-x} (Epidemiology and common injury sites in powerlifting).
• Calhoon, N. L., & Fry, A. C. (1999). Injury rates and profiles of elite competitive weightlifters. Journal of Strength and Conditioning Research. DOI: {10.1519/00124278-199902000-00010} (Injury rates in weightlifting).
• Raske, Å., & Norlin, R. (2002). Injury incidence and prevalence among elite weight and powerlifters. Scandinavian Journal of Medicine & Science in Sports. DOI: {10.1034/j.1600-0838.2002.01188.x} (Injury sites in powerlifting).
• Nijs et al. (2014). Treatment of central sensitization in patients with chronic musculoskeletal pain: new insights and practical implications. Physical Therapy. DOI: {10.2522/ptj.20130360} (Discusses non-mechanical factors like stress on pain).

Pre-Exhaustion

The technique of pre-exhastion training (e.g., leg extensions before squats) is generally suboptimal for both strength and hypertrophy.

Compromised Load: Pre-fatiguing the muscle compromises the ability to perform the subsequent compound lift with high intensity and high volume, thereby reducing the total training load. This directly hurts both muscle growth (less mechanical tension) and strength (less high-fidelity force production).

Limited Use Case: This technique is primarily useful in rehab (as a load-limiting or desensitization tool) or for highly specific muscular endurance challenges (e.g., preparing for certain high-rep CrossFit workouts).

• https://www.barbellmedicine.com/blog/how-to-exercise-when-you-have-no-time/ (training load preservation)
• Schoenfeld, B. J., et al. (2018). Differential effects of attentional focus strategies during long-term resistance training. European Journal of Sport Science. DOI:10.1080/17461391.2018.1500632 (Discusses mind-muscle connection effectiveness).
• Schoenfeld, B. J. (2010). The mechanisms of muscle hypertrophy and their application to resistance training. Journal of Strength and Conditioning Research. DOI: 10.1519/JSC.0b013e3181e840f3(Reviews mechanical tension as the primary driver).
• Fisher, J. P., et al. (2013). The effects of pre-exhaustion, exercise order, and rest intervals in resistance training. Journal of Applied Sports Science Reports. DOI: 10.1016/j.jassr.2013.06.002 (Discusses pre-exhaustion's impact on load).
• Gentil, P., et al. (2007). Effect of exercise order on upper-body strength and muscle thickness in untrained men. Journal of Strength and Conditioning Research. DOI: 10.1519/R-20415.1 (Found pre-exhaustion did not enhance hypertrophy over traditional training).

Cravings

Switching from ultra-processed, hyper-palatable foods (e.g., pizza, fast food) to a whole-food, home-cooked diet involves temporary challenges due to hedonic adaptation (the brain is adapting away from high food reward).

The difficulty of managing cravings is complex. Switching is often easier when the body is in an energy surplus (biologically supported).

The tension and cravings intensify when the lifter moves into a calorie deficit, activating biological defense mechanisms (hormonal signaling increases hunger). Recognizing that the acute cravings are transient is crucial for maintaining self-efficacy and adherence, as it reinforces the belief that the new, healthier habit will eventually become easier.

• https://www.barbellmedicine.com/blog/how-to-eat-a-healthy-diet/ 
• https://www.barbellmedicine.com/blog/how-to-train-while-losing-weight/ 
• https://www.youtube.com/watch?v=oYeh1xTnlxU&themeRefresh=1 
• https://www.barbellmedicine.com/blog/does-your-metabolism-change-with-weight-loss/ 
•  Rosenbaum, M., & Leibel, R. L. (2010). Adaptive thermogenesis in humans. International Journal of Obesity. DOI: {10.1038/ijo.2010.184}
• Considine, R. V. (2012). Leptin and the regulation of body weight. The Journal of Clinical Investigation. DOI: {10.1172/JCI65051}
• Sumithran, P., et al. (2011). Long-term persistence of hormonal adaptations to weight loss. New England Journal of Medicine. DOI: {10.1056/NEJMoa1005813}
• Finlayson, G., et al. (2011). The role of palatability in appetite regulation. Journal of Physiology and Behavior. DOI: {10.1016/j.physbeh.2011.08.016}
•  Lally, P., et al. (2010). How are habits formed: modelling habit formation in the real world. European Journal of Social Psychology. DOI: {10.1002/ejsp.674}
• Baumeister, R. F., et al. (1998). Ego depletion: Is the active self a limited resource? Journal of Personality and Social Psychology. DOI: {10.1037/0022-3514.74.5.1252}
• Spiegel, K., et al. (2004). Brief sleep restriction alters the neuroendocrine profile of ghrelin and leptin. Annals of Internal Medicine. DOI: {10.7326/0003-4811-141-11-200412070-00008}

Our Sponsors:
* Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com
* Check out Factor: https://factormeals.com/bbm50off
* Check out Quince: https://quince.com/BBM
* Check out Rosetta Stone and use my code TODAY for a great deal: https://www.rosettastone.com
* Check out Uncommon Goods: https://uncommongoods.com/bbm
* Check out Washington Red Raspberries: https://redrazz.org


Support this podcast at — https://redcircle.com/barbell-medicine-podcast/donations

Advertising Inquiries: https://redcircle.com/brands

Privacy & Opt-Out: https://redcircle.com/privacy

Barbell Medicine Q&A: Cholesterol, Hypertrophy Volume, and Training Efficiency

Episode Summary

In this Q&A session, Dr. Jordan Feigenbaum addresses listener questions on optimizing training, managing health metrics, and navigating supplement use. Key topics include the latest evidence on cholesterol management (statins vs. PCSK9 inhibitors), why routine Vitamin D supplementation is usually unnecessary, and the mechanics of hypertrophy, emphasizing that volume is superior to intensity once a functional threshold is met. Dr. Feigenbaum also offers practical coaching advice on dynamic volume regulation, the importance of efficiency in the deadlift, and why training models like Pilates do not offer the same benefits as traditional strength work.

⏱️ Episode Timestamps

• 00:00 Introduction
• 00:43 Cholesterol Lowering Medication (Statins vs. PCSK9 Inhibitors)
• 03:27 Volume vs. Intensity for Hypertrophy
• 06:48 Regulating Training Volume and the 5% Rule
• 11:43 Barbell Medicine Supplement Philosophy and Safety
• 14:14 Pilates as a Training Modality
• 16:31 Is Zone 2 Cardio Really That Amazing?
• 
  

⭐ Get More Value: Exclusive Content and Resources

Want to support the show and get early, ad-free access to all episodes plus exclusive bonus content? Subscribe to Barbell Medicine Plus and get ad-free listening, product discounts, and more. Try it free for 30-days.

Unsure which training plan is right for you? Take the free Barbell Medicine Template Quiz to be matched with the ideal program for your goals and experience level.

For media, support, or general questions, please contact us at [email protected]

⚕️ Section I: Clinical and Healthspan Optimization

Cholesterol Management: The Lower is Better Philosophy

The core principle of managing atherogenic risk is that the risk of heart disease is proportional to the overall lifetime exposure (level $\times$ duration) to atherogenic lipoproteins, specifically LDL, triglycerides, and particles tagged with Apolipoprotein B (ApoB). These particles constitute the "atherogenic load."

Lowering this load is beneficial, and the data suggests that lower is better for cardiovascular health. While powerful medications like PCSK9 inhibitors offer an immense magnitude of cholesterol lowering and are proven for both primary and secondary prevention of major adverse cardiac events, the general population will often achieve substantial risk reduction with statins or statin/ezetimibe combinations, which are more accessible and cost-effective.

This approach is validated by observing individuals with genetic mutations who maintain low cholesterol levels throughout their lives—they demonstrate the lowest risk of heart disease, period. Therefore, for active lifters seeking to optimize healthspan and longevity, the goal should be active management and mitigation of this exposure. This requires understanding how to interpret blood work for active lifters and working with a physician to find the most appropriate and sustainable treatment plan, which may include setting targets to lower LDL cholesterol to near-neonatal levels.

Vitamin D Supplementation: Questioning the Routine Recommendation

Routine, widespread Vitamin D supplementation for the general, otherwise healthy population is generally not recommended due to a lack of strong evidence showing that replacing low levels improves actual health outcomes. While low Vitamin D levels frequently coexist with various medical conditions, simply replacing the vitamin doesn't mitigate the primary disease trajectory.

The potential risks of routine supplementation, though low, include supplement contamination and the risk of overdosing (leading to unwanted calcium deposits). Unless an individual has a specific medical condition (like chronic kidney disease, severe malabsorption issues, or high risk of fall and fracture due to osteoporosis), the benefits of routine supplementation are questionable. Barbell Medicine favors interventions where the clinical benefit is clearly demonstrated to improve meaningful health outcomes, not just laboratory values.

🏋️ Section II: Hypertrophy and Training Load Optimization

Volume is the Dose: The Hypertrophy Principle

The relationship between resistance training and hypertrophy (muscle growth) is a dose-dependent relationship on volume, provided a functional threshold is met. This threshold means training must involve a load greater than approximately 30% of a lifter's one-rep maximum (1RM) and be taken relatively close to failure (around 4-5 repetitions left in reserve, RIR).

Advising low volume training to failure, as some influencers do, is sub-optimal for muscle growth because it generates insufficient total training load. Once a lifter has achieved this functional threshold, volume is superior to intensity. High training volume is optimal for muscle growth, and only when volume has been maximized does pulling the intensity lever (training even closer to failure) provide an additional, albeit smaller, benefit.

Optimal hypertrophy and how to structure a strength program for longevity relies on maximizing training load—the total volume of effective work—within the constraints of a person's time and physiological tolerance.

Dynamic Volume Regulation and The 5% Rule

Coaching requires dynamic volume regulation—adjusting the training plan based on a person's current performance and recovery status. One method is to use RPE (Rate of Perceived Exertion) caps to autoregulate volume within a session. For example, prescribing back-off sets that terminate once the prescribed RPE is reached means a lifter performs more work on a good day and less work on a slow day, ensuring sufficient training stimulus without causing excessive fatigue or burnout.

For long-term progression, true strength gain must exceed day-to-day performance fluctuations. A strength gain greater than $\pm 5\%$ over a multi-week period is considered a "real" or minimal clinically important difference in strength. Tracking this trend, rather than session-to-session RPE, is how a coach determines whether to increase the overall training load, which is necessary to continue achieving fitness adaptations.

🧘 Section III: Training Modalities and Applications

Deadlift Technique: Efficiency Over Absolute Neutrality

The belief that any slight movement in the thoracic or lumbar spine during a heavy deadlift is uniquely injurious is not supported by evidence. The human body is highly adaptable, provided the training load is progressed gradually.

The primary coaching concern is not achieving an absolute "neutral spine" (which is difficult to define and rarely achieved in heavy lifting) but maintaining efficiency. Excessive spinal movement can compromise the lockout, making the lift harder than necessary. Coaching should focus on improving the efficiency of the lift to maximize the load that can be lifted strongly, not reducing an overstated injury risk.

Pilates: Recreation, Not Resistance Training

Pilates is generally not a valuable addition to an individual's training if the goal is to drive the primary adaptations of resistance training: increases in strength, hypertrophy, muscle function, or bone mineral density.

Pilates is simply not designed to apply the necessary loading stress to the musculoskeletal system to achieve these benefits. It is best viewed as an enjoyable recreational activity or accouterment, not a replacement for "real exercise." For individuals seeking true physical adaptations, the focus should remain on evidence-based resistance training for older adults and other populations that meet or exceed the established physical activity guidelines.

Zone 2 Cardio: Efficiency and Application

While Zone 2 cardio is popular, it is not a panacea. Evidence shows that vigorous physical activity (higher intensity work, Zone 3/Zone 4) is actually more efficient for disease risk reduction than moderate intensity (Zone 2).

Zone 2 work is most useful for individuals performing high volumes of conditioning (three or more hours per week), as it allows them to accumulate volume without causing undue systemic fatigue. For most people performing less than 150 minutes of moderate-to-vigorous activity per week, incorporating more vigorous work is the most time-efficient way to achieve health benefits.

Our Sponsors:
* Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com
* Check out Factor: https://factormeals.com/bbm50off
* Check out Quince: https://quince.com/BBM
* Check out Rosetta Stone and use my code TODAY for a great deal: https://www.rosettastone.com
* Check out Uncommon Goods: https://uncommongoods.com/bbm
* Check out Washington Red Raspberries: https://redrazz.org


Support this podcast at — https://redcircle.com/barbell-medicine-podcast/donations

Advertising Inquiries: https://redcircle.com/brands

Privacy & Opt-Out: https://redcircle.com/privacy

 Mental Strategies: Neuroscience, Visualization, and Developing Resilience

Episode Summary: Training Your Brain for Performance and Health

Dr. Jordan Feigenbaum welcomes Anne-Sophie Fluri, a neuroscientist with a background in experimental neuroscience and Parkinson's disease research, who now runs Brain Wave, focusing on mental fitness and performance workshops.

This episode leverages Anne-Sophie's expertise to discuss powerful mental strategies applicable to life, stress management, and athletic performance. The conversation provides an evidence-based breakdown of meditation (what it is and what it isn't), the neurological mechanisms behind visualization (process vs. outcome imagery), and how these practices contribute to mental resilience and improved self-efficacy—a core component of the Barbell Medicine definition of health.

⏱️ Episode Timestamps

• [00:00] Introduction, Guest Background, and Barbell Medicine Plus Offer
• [00:41] What is Anne-Sophie currently focusing on at Brain Wave
• [04:41] Meditation: What it is (and isn't) & Training Attentional Focus
• [08:31] Why people start meditating (Sleep issues, anxiety, stress relief)
• [12:28] Legitimate Health Benefits of Meditation (Focus, stress, health behaviors)
• [19:35] Meditation in Sport and Performance Enhancement
• [23:14] How to Start Meditating Today (Apps, YouTube, and the 5-minute approach)
• [33:30] II. Visualization: Mental Imagery and Performance Rehearsal
• [35:04] Visualization in Sport (F1, Michael Phelps, and mentally rehearsing failure)
• [37:02] Process vs. Outcome Visualization & Multi-sensory Engagement
• [43:03] How to Start Visualization Practices (Aphantasia caveat)
• [46:47] The Power of Immediacy and Mind-Muscle Connection
• [56:48] III. Mental Resilience: Self-Efficacy and the Six Components

⭐ Get More Value: Exclusive Content and Resources

Want to support the show and get early, ad-free access to all episodes plus exclusive bonus content? Subscribe to Barbell Medicine Plus and get ad-free listening, product discounts, and more. Try it free for 30-days.

Unsure which training plan is right for you? Take the free Barbell Medicine Template Quiz to be matched with the ideal program for your goals and experience level.

For media, support, or general questions, please contact us at [email protected]

 I. Meditation: Training Focus and Battling Distraction

Dr. Feigenbaum and Anne-Sophie begin by clarifying that meditation is not about emptying the mind or achieving spiritual transcendence. It is a simple mental practice used to train attention and awareness by focusing on an anchor (breath, sound, sensation). When the mind inevitably wanders, the practice is to bring focus back to the anchor.

The True Benefits of Training Attention

While many people turn to meditation for sleep issues and stress relief, the strongest evidence points to its benefit as a tool to train focused attention.

• Focus is a Skill: Anybody can be told to "focus" on their training or work, but meditation provides the concrete skill development needed to counter distraction. Focusing on a mundane anchor like breathing forces the brain (which seeks productive activity) to practice recentering.
• Positive Externalities: Meditation’s primary value may be its "knock-on effects." By helping manage or reduce stress, it creates the self-awareness necessary to participate in other health-promoting behaviors (like eating mindfully, exercising, or making healthier decisions).
• Sports Application: Athletes, from powerlifters to soccer players, can use this training to focus on the task at hand and minimize distraction from external noise (crowds) or internal noise (self-doubt, fear of failure).

 II. Visualization: Mental Rehearsal for Performance

Visualization, or mental imagery, is a form of meditation used to create mental images of desired outcomes or processes. Research suggests this practice can have a direct carry-over to performance by activating overlapping areas in the brain as if the action were happening in real life.

Process, Outcome, and Safety

• Process Visualization: This is ideal for technical tasks (like a squat or a race car lap). The athlete visualizes the step-by-step execution of the task (e.g., foot placement, bar path, gear changes), creating a "brain memory" that shortens the decision-making process during competition.
• Outcome Visualization: Visualizing the moment of success (winning the competition, achieving a PR) can flood the brain with motivating chemicals and endorphins, bridging the gap between present reality and future possibility. However, caution is advised: for some, feeling the outcome too intensely can lead to lower motivation because the brain feels satisfied without doing the work.
• Mind-Muscle Connection: Visualization during a lift may be the mechanism behind the highly sought-after "mind-muscle connection." By actively diverting focused attention toward the specific muscle groups being activated, athletes may recruit a greater amount of muscle tissue, improving activation and potentially long-term gains.

 III. Mental Resilience and the Definition of Health

Anne-Sophie defines mental resilience mechanistically: the ability to return to an original form after force or pressure is applied. This aligns closely with the Barbell Medicine definition of health (from Huber, 2011) as the ability to adapt and self-manage in the face of social, physical, and emotional challenges.

Self-Efficacy and Control

Mental resilience is directly linked to self-efficacy (confidence in one's ability to exert control over one's life). Those with high self-efficacy feel in control, have good insight into their circumstances, and feel they have the resources to change the outcome.

The key components of mental resilience include:

1. Health: Physical health, sleep, and nutrition.
2. Vision: Having a clear goal and direction for the future.
3. Tenacity: The ability to keep going after setbacks.
4. Composure: Self-regulation and staying level-headed under stress.
5. Collaboration: Social support and community.

The Path to Resilience

To develop mental resilience, Anne-Sophie recommends developing self-awareness and reflection through regular practice:

• Practice Self-Awareness: Meditation improves the connectivity between the prefrontal cortex (executive function) and the amygdala (emotional center), allowing you to approach problems with a more level head and less emotional reactivity.
• 
  
• Start Mono-tasking: Stop multitasking (which is actually just costly task switching) and start mono-tasking. Turn mundane activities (cooking, cleaning) into opportunities for mindfulness—focusing on one task and actively paying attention to the senses involved. This is the best nootropic for memory and cognition.
• 
  
• Consistency: Structural changes in the brain (neuroplasticity) and lasting behavioral changes are seen after at least eight weeks of consistent practice (20–40 minutes daily).

Connect With Anne-Sophie Fluri and Barbell Medicine

• Guest Substack: Read Anne-Sophie’s neuroscience insights and thought pieces at Rewire Me with Anne-Sophie (rewireme.substack.com).
• 
  
• Guest Instagram: Follow Anne-Sophie for "not so serious content" and wellness trend critiques: @coochiebygucci (instagram.com/coochiebygucci).
• 
  
• Support the Show & Save: Join Barbell Medicine Plus for ad-free listening and discounts on all courses and consultations!
• 
  

Our Sponsors:
* Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com
* Check out Factor: https://factormeals.com/bbm50off
* Check out Quince: https://quince.com/BBM
* Check out Rosetta Stone and use my code TODAY for a great deal: https://www.rosettastone.com
* Check out Uncommon Goods: https://uncommongoods.com/bbm
* Check out Washington Red Raspberries: https://redrazz.org


Support this podcast at — https://redcircle.com/barbell-medicine-podcast/donations

Advertising Inquiries: https://redcircle.com/brands

Privacy & Opt-Out: https://redcircle.com/privacy