#184 - AMA #29: GLP-1 Agonists—The Future of Treating Obesity?

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In this “Ask Me Anything” (AMA) episode, Peter dives deep into the topic of hair loss, exploring its relationship with aging and its impact on quality of life. The conversation focuses on androgenic alopecia, the most common form of hair loss in both men and women, and covers the differences in patterns and causes between the sexes. Peter delves into the right timing for treatment, breaking down various options such as minoxidil and finasteride, low-level laser therapy, platelet-rich plasma injections, and more. Additionally, Peter outlines the pros and cons of the two primary hair transplantation methods and concludes with practical advice on selecting the right specialist or treatment team for those facing hair loss.

If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #63 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• The impact of hair loss on emotional health [2:15];
• The prevalence, patterns, and causes of hair loss in men and women [5:15];
• The genetic and hormonal causes of hair loss, and the role of dihydrotestosterone (DHT) in androgenic alopecia [8:45];
• The visual differences in hair loss patterns between men and women, and the importance of consulting a specialist to rule out non-genetic causes of hair loss [13:30];
• How genetic predisposition influences the risk of androgenic alopecia, and how early detection through diagnostic tools and blood tests can help manage risk more effectively [16:45];
• Ideal timing for starting treatment: why early treatment is crucial for effectively managing hair loss [19:30];
• The various FDA-approved treatments for androgenic alopecia, their mechanisms, and additional off-label treatments commonly used to manage hair loss [24:30];
• Topical minoxidil—the most commonly recommended starting treatment for hair loss [30:15];
• Oral vs. topical minoxidil: efficacy, ease of use, and potential side effects that must be considered [33:45];
• Finasteride for treating hair loss: efficacy, potential side effects on libido, and the need for careful PSA monitoring in men to avoid missing early signs of prostate cancer [37:15];
• Other effective hair loss treatments for women: boosting hair density with spironolactone gel and ketoconazole shampoo as part of a comprehensive strategy [41:30];
• Low-level laser therapy: effectiveness, costs, practicality, and a comparison of in-office treatments with at-home devices [49:00];
• Platelet-rich plasma (PRP) as a treatment for hair loss: potential effectiveness, varying protocols, and significant costs [53:45];
• Hair transplant for advanced hair loss: criteria and considerations [58:00];
• Types of hair transplants: follicular unit transplantation (FUT) vs. follicular unit extraction (FUE) [1:02:00];
• The financial cost of hair transplant surgery, and what to consider when seeking affordable options [1:06:15];
• The potential risks and downsides of the various hair transplant procedures [1:09:30];
• Post-procedure care for hair transplants and whether the procedure must be repeated periodically [1:16:30];
• Combining different hair loss treatments: benefits, risks, and considerations [1:18:30];
• Emerging hair loss treatments with limited data [1:21:00];
• Key considerations for selecting the right treatment plan for hair loss [1:22:00];
• A summary of the different considerations for men and women facing hair loss [1:24:30];
• Practical advice on selecting the right specialist or treatment team [1:26:15]; and
• More.

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In this episode, former World Series of Poker champion and author Annie Duke explains how poker is a pertinent model system for decision-making in the real world, a system which blends imperfect information with some unknown percentage of both luck and skill. Annie breaks down the decision-making matrix, revealing how we often focus too narrowly on just one of the four quadrants, missing out on valuable learning opportunities in the remaining 75% of situations. She delves into how our tendency to evaluate only negative outcomes leads to a culture of risk aversion. This mindset, she argues, stifles the kind of bold decision-making necessary for progress and innovation across various fields, from poker and sports to business and medicine. Annie also introduces a robust framework for learning and the levels of thought required to excel in any domain. Finally, she discusses a strategy called “backcasting”, a concept that resonated deeply with Peter in terms of how he thinks about extending healthspan.

We discuss:

• Annie’s background, favorite sports teams, and Peter’s affinity for Bill Belichick [1:30];
• Chess vs. poker: Which is a better metaphor for decision-making in life (and medicine)? [6:45];
• Thinking probabilistically: Why we aren’t wired that way, and how you can improve it for better decision-making [12:30];
• Variable reinforcement: The psychological draw of poker that keeps people playing [19:15];
• The role of luck and skill in poker (and other sports), and the difference between looking at the short run vs. long run [32:15];
• A brief explanation of Texas hold ‘em [41:00];
• The added complexity of reading the behavior of others players in poker [47:30];
• Why Annie likes to “quit fast,” and why poker is still popular despite the power of loss aversion [52:45];
• Limit vs. no-limit poker, and how the game has changed with growing popularity [55:15];
• The advent of analytics to poker, and why Annie would get crushed against today’s professionals [1:04:45];
• The decision matrix, and the “resulting” heuristic: The simplifier we use to judge the quality of decisions —The Pete Carroll Superbowl play call example [1:10:30];
• The personal and societal consequences of avoiding bad outcomes [1:21:45];
• Poker as a model system for life [1:31:30];
• How many leaders are making (and encouraging) status-quo decisions, and how Bill Belichick’s decision-making changed after winning two Super Bowls [1:35:15];
• What did we learn about decision-making from the Y2K nothingburger? And how about the D-Day invasion? [1:39:30];
• The first step to becoming a good decision maker [1:43:00];
• The difference between elite poker players and the ones who make much slower progress [1:49:45];
• Framework for learning a skill, the four levels of thought, and why we hate digging into our victories to see what happened [1:52:15];
• The capacity for self-deception, and when it is MOST important to apply four-level thinking [2:00:30];
• Soft landings: The challenge of high-level thinking where there is subtle feedback and wider skill gaps [2:11:00];
• The benefits of “backcasting” (and doing pre-mortems) [2:13:30];
• Parting advice from Annie for those feeling overwhelmed (and two book recommendations) [2:21:30]; and
• More.

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Sebastian Junger is an award-winning journalist, bestselling author, and previous guest on The Drive. In this episode, Sebastian returns to discuss his latest book, In My Time of Dying: How I Came Face to Face with the Idea of an Afterlife. This episode delves into Sebastian's profound near-death experience and how it became the catalyst for his exploration of mortality, the afterlife, and the mysteries of the universe. They discuss the secular meaning of what it means to be sacred, the intersection of physics and philosophy, and how our beliefs shape our approach to life and death. He also shares how this experience has profoundly changed him, giving him a renewed perspective on life—one filled with awe, gratitude, deeper emotional awareness, and a more engaged approach to living.

We discuss:

• How Sebastian’s near-death experience shaped his thinking about mortality and gave him a reverence for life [3:00];
• The aneurysm that led to Sebastian’s near-death experience [6:30];
• Emergency room response, his subsequent reflections on the event, and the critical decisions made by the medical team [16:30];
• Sebastian’s reaction to first learning he nearly died, and the extraordinary skill of the medical team that save his life [26:00];
• Sebastian’s near-death experience [37:00];
• The psychological impact of surviving against overwhelming odds [48:00];
• Ignored warning signs: abdominal pain and a foreshadowing dream before the aneurysm rupture [54:30];
• Sebastian's recovery, his exploration of near-death experiences, and the psychological turmoil he faced as he questioned the reality of his survival [58:15];
• A transformative encounter with a nurse who encouraged Sebastian to view his near-death experience as sacred [1:03:30];
• How Sebastian has changed: a journey toward emotional awareness and fully engaging with life [1:08:45];
• The possibility of an afterlife, and how quantum mechanics challenges our understanding of existence [1:15:15];
• Quantum paradoxes leading to philosophical questions about the nature of reality, existence after death, and whether complete knowledge could be destructive [1:26:00];
• The sweet spot of uncertainty: exploring belief in God, post-death existence, and meaning in life [1:37:00];
• The transformative power of experiencing life with awe and gratitude [1:53:00]; and
• More.

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David Allison, a leading expert in obesity and nutrition, quantitative genetics, clinical trials, and research methodology, returns to The Drive to explore the evolving landscape of nutrition science and obesity treatment. In this episode, David begins by discussing the intricate relationship between nutrition, obesity, and body composition, emphasizing the multifaceted impacts of food beyond mere calorie intake. David provides a critical analysis of the complexities in nutrition research and their practical implications for tackling obesity. He critiques historical public health policies, addresses the trust issues plaguing nutrition science, and underscores the need for a paradigm shift to more effectively combat obesity. The conversation also delves into the rise of GLP-1 receptor agonists like Ozempic and Mounjaro, exploring their ethical and practical considerations in obesity treatment. The episode concludes with an in-depth look at protein intake recommendations and highlights the significant research gaps that remain in the field.

We discuss:

• The complex relationship between nutrition, body weight, and body composition [2:30];
• The slow progress in addressing obesity and public health despite substantial effort and investment [7:30];
• The very limited success of public health initiatives in curbing obesity [17:15];
• The evolving landscape of obesity research: public health initiatives and the impact of pharmacological success [26:30];
• Rethinking obesity solutions: the need for a paradigm shift [32:45];
• Understanding environmental triggers and embracing a balanced approach to addressing obesity that includes both pharmacological treatments and realistic lifestyle changes [41:45];
• The need for higher standards in obesity research [51:45];
• The rapid success of GLP-1 receptor agonists for weight loss: a discussion on the societal impact and controversy of their growing usage [1:02:15];
• The ethical and practical considerations of obesity drugs: risks, benefits, and motivations for usage [1:11:30];
• The use of GLP-1 agonists by athletes as performance enhancers [1:23:45];
• Unanswered questions about protein intake and health [1:30:45];
• Future research needed to understand basic questions around protein intake [1:45:00];
• David’s weekly newsletter: “Obesity and Energetics Offerings” [1:50:45]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter dives into two important health topics: uric acid and protein, examining them from unique perspectives. For uric acid, he explores its metabolic role and connection to various diseases, focusing on the potential causal link with cardiovascular disease. He also discusses factors influencing uric acid levels, such as diet, genetics, and lifestyle, providing practical tips for effective management. Shifting to protein, Peter delves into its role in appetite and weight management, the consequences of insufficient protein, and the “protein leverage hypothesis” linking protein deficiency to obesity. He covers optimal protein intake and its impact on energy expenditure, and he compares the satiety effects of solid versus liquid protein. Finally, Peter shares his strategy for incorporating protein into a comprehensive weight management plan.

If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #62 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Overview of episode topics (and an important discussion on fanny packs) [2:00];
• Understanding uric acid: its role in metabolic processes, its association with gout and kidney stones, its impact on blood pressure, and more [6:00];
• Non-modifiable factors that influence uric acid levels [11:00];
• Modifiable factors that influence uric acid levels [14:15];
• Association between high uric acid levels and cardiovascular disease [20:00];
• Evidence suggesting a causal link between high uric acid levels and cardiovascular disease [24:00];
• Inconclusive evidence about the cardiovascular benefits of lowering uric acid pharmacologically [28:15];
• Exploring the potential risks of low uric acid levels in neurodegenerative diseases [37:00];
• Managing uric acid levels: dietary interventions and pharmacological approaches [42:00];
• The impact of protein on appetite and weight management [44:00];
• The consequences of insufficient protein on eating behaviors and satiety [52:15];
• The relationship between protein deficiency and obesity: exploring the “protein leverage hypothesis” [57:15];
• The impact of protein intake on energy expenditure [1:02:15];
• Determining optimal protein intake to avoid deficiency and support health [1:05:45];
• The role of different amino acids and protein sources in promoting satiety [1:08:15];
• Comparing the satiety effects of solid vs. liquid protein sources [1:10:30];
• Peter’s framework for incorporating protein intake into a strategy for controlling body weight [1:12:00]; and
• More.

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George A. Brooks is a renowned professor of integrative biology at UC Berkeley. Known for his groundbreaking "lactate shuttle" theory proposed in the 1980s, George revolutionized our understanding of lactate as a crucial fuel source rather than just a byproduct of exercise. In this episode, George clarifies common misconceptions between lactate and lactic acid, delves into historical perspectives, and explains how lactate serves as a fuel for the brain and muscles. He explores the metabolic differences in exceptional athletes and how training impacts lactate flux and utilization. Furthermore, George reveals the significance of lactate in type 2 diabetes, cancer, and brain injuries, highlighting its therapeutic potential. This in-depth conversation discusses everything from the fundamentals of metabolism to the latest research on lactate's role in gene expression and therapeutic applications.

We discuss:

• Our historical understanding of lactate and muscle metabolism: early misconceptions and key discoveries [3:30];
• Fundamentals of metabolism: how glucose is metabolized to produce ATP and fuel our bodies [16:15];
• The critical role of lactate in energy production within muscles [24:00];
• Lactate as a preferred fuel during high-energy demands: impact on fat oxidation, implications for type 2 diabetes, and more [30:45];
• How the infusion of lactate could aid recovery from traumatic brain injuries (TBI) [43:00];
• The effects of exercise-induced lactate [49:30];
• Metabolic differences between highly-trained athletes and insulin-resistant individuals [52:00];
• How training enhances lactate utilization and facilitates lactate shuttling between fast-twitch and slow-twitch muscle fibers [58:45];
• The growing recognition of lactate and monocarboxylate transporters (MCT) [1:06:00];
• The intricate pathways of lactate metabolism: isotope tracer studies, how exceptional athletes are able to utilize more lactate, and more [1:09:00];
• The role of lactate in cancer [1:23:15];
• The role of lactate in the pathophysiology of various diseases, and how exercise could mitigate lactate's carcinogenic effects and support brain health [1:29:45];
• George’s current research interests involving lactate [1:37:00];
• Questions that remain about lactate: role in gene expression, therapeutic potential, difference between endogenous and exogenous lactate, and more [1:50:45]; and
• More.

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In this special episode, Peter provides a comprehensive introduction to longevity, perfect for newcomers or those looking to refresh their knowledge. He lays out the foundational concepts of lifespan, healthspan, and the marginal decade. Additionally, Peter discusses the four main causes of death and their prevention, as well as detailing the five key strategies in his longevity toolkit to improve lifespan and healthspan. Detailed show notes provide links for deeper exploration of these topics, making it an ideal starting point for anyone interested in understanding and improving their longevity.

We discuss:

• Key points about starting exercise as an older adult [2:45];
• Overview of episode topics and structure [1:45];
• How Peter defines longevity [3:45];
• Why healthspan is a crucial component of longevity [11:15];
• The evolution of medicine from medicine 1.0 to 2.0, and the emergence of medicine 3.0 [15:30];
• Overview of atherosclerotic diseases: the 3 pathways of ASCVD, preventative measures, and the impact of metabolic health [26:00];
• Cancer: genetic and environmental factors, treatment options, and the importance of early and aggressive screening [33:15];
• Neurodegenerative diseases: causes, prevention, and the role of genetics and metabolic health [39:30];
• The spectrum of metabolic diseases [43:15];
• Why it’s never too late to start thinking about longevity [44:15];
• The 5 components of the longevity toolkit [46:30];
• Peter’s framework for exercise—The Centenarian Decathlon [47:45];
• Peter’s nutritional framework: energy balance, protein intake, and more [58:45];
• Sleep: the vital role of sleep in longevity, and how to improve sleep habits [1:08:30];
• Drugs and supplements: Peter’s framework for thinking about drugs and supplements as tools for enhancing longevity [1:13:30];
• Why emotional health is a key component of longevity [1:17:00];
• Advice for newcomers on where to start on their longevity journey [1:19:30]; and
• More.

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Ted Schaeffer is an internationally recognized urologist specializing in prostate cancer and a returning guest on The Drive. In this episode, Ted provides insights into the role testosterone plays, or doesn't play, in the initiation and progression of prostate cancer. He unpacks the findings and limitations of the recent TRAVERSE trial, exploring the complex relationship between testosterone and prostate cancer. Ted delves into the molecular nature of prostate cancer, explaining the androgen receptor saturation theory and the potential impact of testosterone on cancer growth. He also discusses the use of the Decipher test to predict cancer aggressiveness and guide targeted treatment. Furthermore, Ted shares how he counsels patients regarding testosterone replacement therapy (TRT), including its safe administration in patients with low-grade prostate cancer. Additionally, he highlights advancements in prostate cancer therapies and biomarkers that help develop precise treatment strategies while minimizing the need for broad androgen deprivation therapy.

We discuss:

• Background on the TRAVERSE trial: insights into exogenous testosterone and prostate cancer risk [3:00];
• The androgen receptor saturation theory: how different organs respond to varying levels of testosterone [10:30];
• The relationship between testosterone levels and prostate cancer aggressiveness: how aggressive prostate tumors have lower androgen receptor activity and rely on different growth mechanisms [16:15];
• Using the Decipher score to assess prostate cancer aggressiveness and guide personalized treatment strategies [23:45];
• Considerations for testosterone replacement therapy: how Ted counsels patients, how TRT can be safely administered in patients with low-grade prostate cancer, and more [31:15];
• Advancements in prostate cancer therapies and PSA as a biomarker for precise treatment decisions, minimizing the need for broad androgen deprivation therapy [38:30]; and
• More.

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Isaac "Zak" Kohane, a pioneering physician-scientist and chair of the Department of Biomedical Informatics at Harvard Medical School, has authored numerous papers and influential books on artificial intelligence (AI), including The AI Revolution in Medicine: GPT-4 and Beyond. In this episode, Zak explores the evolution of AI, from its early iterations to the current third generation, illuminating how it is transforming medicine today and unlocking astonishing possibilities for the future. He shares insights from his unconventional journey and early interactions with GPT-4, highlighting significant AI advancements in image-based medical specialties, early disease diagnosis, and the potential for autonomous robotic surgery. He also delves into the ethical concerns and regulatory challenges of AI, its potential to augment clinicians, and the broader implications of AI achieving human-like creativity and expertise.

We discuss:

• Zak’s unconventional journey to becoming a pioneering physician-scientist, and his early interactions with GPT-4 [2:15];
• The evolution of AI from the earliest versions to today’s neural networks, and the shifting definitions of intelligence over time [8:00];
• How vast data sets, advanced neural networks, and powerful GPU technology have driven AI from its early limitations to achieving remarkable successes in medicine and other fields [19:00];
• An AI breakthrough in medicine: the ability to accurately recognize retinopathy [29:00];
• Third generation AI: how improvements in natural language processing significantly advanced AI capabilities [32:00];
• AI concerns and regulation: misuse by individuals, military applications, displacement of jobs, and potential existential concerns [37:30];
• How AI is enhancing image-based medical specialties like radiology [49:15];
• The use of AI by patients and doctors [55:45];
• The potential for AI to augment clinicians and address physician shortages [1:02:45];
• The potential for AI to revolutionize early diagnosis and prediction of diseases: Alzheimer’s disease, CVD, autism, and more [1:08:00];
• The future of AI in healthcare: integration of patient data, improved diagnostics, and the challenges of data accessibility and regulatory compliance [1:17:00];
• The future of autonomous robotic surgery [1:25:00];
• AI and the future of mental health care [1:31:30];
• How AI may transform and disrupt the medical industry: new business models and potential resistance from established medical institutions [1:34:45];
• Potential positive and negative impacts of AI outside of medicine over the next decade [1:38:30];
• The implications of AI achieving a level of creativity and expertise comparable to exceptional human talents [1:42:00];
• Digital immortality and legacy: the potential to emulate an individual's personality and responses and the ethical questions surrounding it [1:45:45];
• Parting thoughts [1:50:15]; and
• More.

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Iñigo San-Millán is an internationally renowned applied physiologist and a previous guest on The Drive. His research and clinical work focuses on exercise-related metabolism, metabolic health, diabetes, cancer metabolism, nutrition, sports performance, and critical care. In this episode, Iñigo describes how his work with Tour de France winner Tadej Pogačar has provided insights into the amazing potential of elite athletes from a performance and metabolic perspective. He speaks specifically about lactate levels, fat oxidation, how carbohydrates in food can affect our lactate and how equal lactate outputs between an athlete and a metabolically unhealthy individual can mean different things. Next, he discusses how Zone 2 training boosts mitochondrial function and impacts longevity. He explains the different metrics for assessing one’s Zone 2 threshold and describes the optimal dose, frequency, duration, and type of exercise for Zone 2. Additionally, he offers his thoughts on how to incorporate high intensity training (Zone 5) to optimize health, as well as the potential of metformin and NAD to boost mitochondrial health. Finally, he discusses insights he’s gathered from studying the mitochondria of long COVID patients in the ICU.

We discuss:

• The amazing potential of cyclist Tadej Pogačar [2:00];
• Metrics for assessing athletic performance in cyclists and how that impacts race strategy [7:30];
• The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [16:15];
• Tadej Pogačar’s race strategy and mindset at the Tour de France [23:15];
• Defining Zone 2, fat oxidation, and how they are measured [26:00];
• Using fat and carbohydrate utilization to calculate the mitochondrial function and metabolic flexibility [35:00];
• Lactate levels and fat oxidation as it relates to Zone 2 exercise [39:15];
• How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:00];
• Bioenergetics of the cell and what is different in elite athletes [56:30];
• How the level of carbohydrate in the diet and ketogenic diets affects fuel utilization and power output during exercise [1:07:45];
• Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:14:15];
• How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:20:15];
• Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:24:00];
• Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:40:30];
• How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:50:30];
• Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:00];
• The effects of metformin, NAD, and supplements on mitochondrial function [2:04:30];
• The role of lactate and exercise in cancer [2:12:45];
• How assessing metabolic parameters in long COVID patients provides insights into this disease [2:18:30];
• The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise [2:25:00];
• Metabolomics reveals how cellular metabolism is altered in sedentary individuals [2:33:00];
• Cellular changes in the metabolism of people with diabetes and metabolic syndrome [2:38:30]; and
• More.

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With Semalgutide and weight loss medications becoming all the rage, people all around us are losing weight at a fast rate, and with rapid weight loss comes skin laxity. In this episode, Dr. Franco, Nurse Sarah, PA Gilbert, and Aesthetician Andrea talk about non-surgical procedures that patients can have done to tighten loose skin and help them achieve the look they want when they are at their goal weight. Patients can get RF micro needling done to tighten loose skin, filler to create a snatched, youthful, full face, and neurotoxin to prevent and help with wrinkles and fine lines. Listen to this episode to learn how to achieve the body of your dreams after weight loss through nonsurgical treatments.

even at very small some would argue barely even treating doses of testosterone patients had an increase rate of fractures with a NNH of 100—when you add this to the 1 risk of aki and 2 percent risk of arthymia the harms vs benefit conversation to use testosterone seems to be leaning heavy towards harms

https://www.nejm.org/doi/full/10.1056/NEJMoa2308836?query=recirc_curatedRelated_article

• How long do injections take and do they hurt?
• Is there any downtime?
• How different do you feel after?
• What labs are required?
• Will you notice a difference after one cycle?
• What are the advantages of going to an aesthetic practice for BioTE rather than going to a testosterone replacement clinic?