The Peter Attia Drive

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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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In this “Ask Me Anything” (AMA) episode, Peter delves into two topics that have generated a lot of questions over the years: skin cancer and sunscreen. He begins by exploring the basics of UV radiation, discussing its effects on vitamin D conversion, photoaging, and its role in skin cancer. He examines various skin types, discussing their implications for sun exposure and vitamin D levels, as well as how to determine where you fall on the skin type scale. He then delves into the various types of skin cancer, with a particular emphasis on melanoma, exploring its complex relationship with UV exposure and other contributing risk factors. Additionally, he covers tanning beds, the importance of early skin cancer detection through regular skin checks, and the often confusing topic of sunscreen. He explains how sunscreen affects UV radiation and skin cancer risk, what SPF levels to choose, the differences between organic and mineral sunscreens, and what to consider when selecting the best sunscreen for your needs.

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 #61 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• The impact of UV radiation on the skin [2:00];
• Understanding solar UV: from the electromagnetic spectrum to skin health [3:45];
• The role of sunlight in vitamin D production [8:30];
• Factors contributing to vitamin D deficiency: insufficient UV exposure, magnesium levels, and more [9:45];
• Sun exposure needs for different skin types, and the limitations of current studies in defining vitamin D deficiency [12:45];
• The acute and long-term effects of excessive UV exposure: sunburn, photoaging, and the increased risk of skin cancer [15:30];
• Types of skin cancer and associations with UV exposure [17:45];
• The complex relationship between melanoma and UV exposure [22:15];
• Why UV exposure alone doesn’t necessarily explain the risk for melanoma [25:15];
• Other risk factors for melanoma [29:15];
• Tanning beds and skin cancer risk [34:45];
• Balancing sun exposure: benefits and risks [38:15];
• Tattoos and sun exposure [40:30];
• The importance of regular skin checks, dermatologists, and emerging technologies showing promise for early detection of cancer [41:45];
• Self-skin checks: what to look for [46:30];
• Prevalence of skin cancer and the importance of early detection [49:30];
• Summary of the major risk factors for melanoma [54:15];
• The role of sunscreen in reducing skin cancer risk [55:45];
• How sunscreen works, the differences between chemical and mineral sunscreens, an explanation of SPF, and more [58:30];
• How to determine the appropriate sunscreen SPF to use based on the UV index [1:04:45];
• Choosing the right sunscreen for your individual needs [1:07:00];
• The impact of water and perspiration on sunscreen effectiveness [1:12:00];
• Chemical vs. mineral sunscreens: safety concerns and recommendations [1:14:00];
• Concerns about hormone effects from chemical sunscreens [1:19:15];
• Sunscreen summary: skin types, key considerations, recommended brands, and more [1:23:15]; and
• More.

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In this special episode, Peter addresses the common questions about starting or returning to an exercise routine over the age of 50. Individuals in this age group have frequently reached out with questions about whether it's too late to start exercising and often express concern over a lack of prior training, a fear of injury, or uncertainty about where to begin. Peter delves into the importance of fitness for older adults, examining all four pillars of exercise, and provides practical advice on how to start exercising safely, minimize injury risk, and maximize potential benefits. Although this conversation focuses on people in the “older” age category, it also applies to anyone of any age who is deconditioned and looking to ease into regular exercise.

We discuss:

• Key points about starting exercise as an older adult [2:45];
• Why it’s never too late to begin exercising and incorporating the four pillars of exercise [5:45];
• The gradual, then sharp, decline in muscle mass and activity level that occur with age [10:00];
• The decline of VO2 max that occurs with age [15:30];
• Starting a training program: exercise variability, movement quality, realistic goals, and more [18:30];
• Improving aerobic capacity: the malleability of the system, the importance of consistency, and setting long-term fitness goals [25:15];
• Starting cardio training: base building, starting with low volume, and zone 2 training [30:45];
• The critical role of VO2 max in longevity [36:45];
• How to introduce VO2 max training to older or deconditioned individuals [46:15];
• Options for performing zone 2 and VO2 max training [53:45];
• The ability to make gains in strength and muscle mass as we age [57:00];
• How to implement strength training for older individuals [1:01:00];
• Advice for avoiding injury when strength training [1:07:30];
• Risk of falls: the devastating consequences and the factors that increase fall risk [1:12:15];
• Mitigating fall risk: the importance of foot and lower leg strength, ankle mobility, and balance [1:19:45];
• Improving bone mineral density through resistance training [1:24:30];
• The importance of protein in stimulating muscle protein synthesis, especially in older adults [1:31:00];
• Parting advice from Peter [1:34:00]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter provides insights on a broad range of important topics. He delves into the prevention of cognitive decline, the link between cardiovascular disease and Alzheimer's disease, and methods to lower blood glucose, insulin, and apoB. He also addresses nutrition-related queries, exploring the impact of dietary habits on weight loss and longevity, how a person can identify the best diet for themselves, and common nutrition myths. Additional discussions include optimal blood pressure, daily step goals, the benefits of standing versus sitting desks, and much more.

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 #60 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Overview of topics and episode format [1:40];
• Preventing cognitive decline [5:00];
• How to lower blood glucose and insulin [13:30];
• The relationship between lipids, CVD, and Alzheimer’s disease, and whether statins can increase the risk of neurodegenerative disorders and AD [23:15];
• Reducing apoB levels through exercise and diet [31:45];
• Pharmacological options for lowering apoB [38:00];
• How nutrition impacts longevity via metabolic health, muscle mass, BMD and more [40:15];
• How can someone determine the best diet for themselves? [43:45];
• Nutrition myth: All weight loss is good [46:45];
• Nutrition myth: Metabolic rates are dramatically different among individuals based on genetics [49:00];
• Nutrition myth: Losing weight after a brief period of overeating is impossible [53:45];
• Nutrition myth: GLP-1 agonists are a replacement for a healthy lifestyle [57:45];
• Nutrition myth: There is a single best diet for weight loss [1:03:00];
• Nutrition oversimplification: All calories are created equal [1:05:45];
• Daily step goals [1:06:45];
• The benefits of standing versus sitting throughout the day [1:10:45];
• How to identify the most impactful and easiest-to-implement ways to improve your health [1:12:30];
• The critical importance of emotional health [1:14:30];
• Why supplements should be considered as supportive aids rather than primary solutions in one’s strategy to improve longevity [1:18:00];
• Strategies for reducing high blood pressure [1:20:45];
• Peter’s biggest frustrations with "mainstream health advice" [1:28:00];
• Peter’s chaotic, yet cherished, morning routine [1:31:00]; and
• More.

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Joel Jamieson is a conditioning expert who developed Morpheus to give people a smarter way to build their conditioning regimen and improve their recovery. In this episode, Joel dives deep into the world of heart rate variability (HRV), explaining its scientific foundation, how it measures the balance between the sympathetic and parasympathetic nervous systems, the various methods of measurement, and how it can guide healthier lifestyle choices and improved training performance. He explores the nuances of HRV calculation, the impact of aging on HRV, and the roles of genetics, exercise, and other lifestyle factors in this process. He also covers Morpheus, the innovative training tool that won Peter over after his initial skepticism, highlighting its practicality and effectiveness in guiding training and optimizing fitness outcomes.

We discuss:

• Heart rate variability (HRV): evolution, science, and practical applications of HRV in athletic training [4:00];
• Methods of measuring HRV: EKG, wrist-based sensors, and more [11:30];
• How HRV is calculated from the data [22:30];
• The role of the autonomic nervous system (ANS) in regulating HRV [25:45];
• The decline in HRV with age, and the mitigating effects of fitness and other lifestyle factors [33:30];
• The role of genetics in HRV, the modifiability of HRV, and a comparison of VO2 max and HRV as predictors of mortality [37:00];
• How aging affects HRV and sympathetic drive, and the importance of spontaneous movement and exercise in maintaining the body's adaptability [43:30];
• How Morpheus measures HRV using RMSSD and normalizes it to a 100-point scale for easier interpretation [49:45];
• The Morpheus system: development, integration with various metrics, and personalized daily training recommendations to optimize fitness and recovery [51:30];
• The benefits of morning HRV readings for assessing daily readiness compared to overnight HRV measurements [1:03:00];
• Why Morpheus recommends using a chest strap rather than an arm band [1:10:00];
• The impact of consistent exercise, stress, alcohol, and other lifestyle factors on HRV [1:11:15];
• Optimizing zone 2 training with Morpheus [1:18:15];
• Using heart rate recovery (HRR) as an indicator of athletic conditioning and the balance between aerobic and anaerobic systems [1:22:45];
• The importance of tracking HRV trends over time rather than focusing on data from a given day [1:29:00];
• Effect of GLP-1 agonists on heart rate and HRV [1:34:45];
• Where HRV belongs in the hierarchy of health metrics [1:42:00];
• Parting thoughts [1:46:30]; and
• More.

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In this quarterly podcast summary (QPS) episode, Peter introduces a new format aimed at summarizing his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from each episode, covering diverse topics such as protein and muscle building with Luc van Loon, toe strength with Courtney Conley, VO2 max with Olav Aleksander Bu, liquid biopsies for cancer with Alex Aravanis, gut health and probiotics with Colleen Cutcliffe, and road safety with Mark Rosekind. Additionally, Peter shares any personal behavioral adjustments or modifications to his patient care practices that have arisen from these engaging discussions.

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 episode #304 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• How Peter keeps track of his takeaways from each podcast episode [5:15];
• Luc van Loon episode: fat utilization, muscle protein synthesis, dietary protein, aging and inactivity, and more [8:45];
• Behavioral changes that have come about from the conversation with Luc van Loon [23:45];
• Courtney Conley episode: importance of toe strength and the impact of dedicated foot training [26:45];
• Olav Aleksander Bu episode: the importance of VO2 max for lifespan, and the practicalities of measuring and improving VO2 max [36:45];
• Behavioral changes that have come about from the conversation with Olav [56:00];
• Alex Aravanis episode: liquid biopsies for cancer detection [1:01:30];
• Colleen Cutcliffe episode: the importance of gut bacteria balance, and the potential therapeutic uses of probiotics, particularly Akkermansia [1:16:45];
• Mark Rosekind: the significant issue of road fatalities and injuries, their causes, and practical safety measures to reduce risks [1:27:00]; and
• More.

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Dena Dubal is a physician-scientist and professor of neurology at UCSF whose work focuses on mechanisms of longevity and brain resilience. In this episode, Dena delves into the intricacies of the longevity factor klotho: its formation and distribution in the body, the factors such as stress and exercise that impact its levels, and its profound impact on cognitive function and overall brain health. Dena shares insights from exciting research in animal models showing the potential of klotho in treating neurodegenerative diseases as well as its broader implications for organ health and disease prevention. She concludes with an optimistic outlook for future research in humans and the potential of klotho for the prevention and treatment of Alzheimer’s disease.

Disclosure: Peter is an investor in Jocasta Neuroscience, a company working to develop klotho as a therapy for people with Alzheimer’s disease.

We discuss:

• Dena’s fascination with aging and how she came to study klotho [3:30];
• Biological properties of klotho: production, regulation, decline with age, and factors influencing its levels [11:45];
• Potential benefits of klotho on brain health [22:00];
• The relationship between soluble klotho protein, platelet factors, and cognitive enhancement [33:45];
• The role of platelet factor 4 (PF4) and it’s interaction with GluN2B in mediating cognitive enhancement [46:45];
• Benefits of klotho observed in a mouse model of Parkinson’s disease [55:45];
• Benefits of klotho observed in a mouse model of Alzheimer’s disease [1:03:00];
• Promising results of klotho in primate models, and the importance of finding an appropriate therapeutic dose before moving to human trials [1:08:00];
• Speculating why a single klotho injection has such long-lasting effects [1:25:30];
• Potential cognitive benefits of klotho in humans, the impact of the KL-VS genetic variant on klotho levels, and the need for human trials to confirm these effects [1:27:45];
• The interaction between the KL-VS genetic variant and APOE4 and how it impacts risk of Alzheimer’s disease [1:34:45];
• The significance of klotho levels: studies linking lower levels to increased mortality and the broader implications for organ health and disease prevention [1:47:15];
• Measuring klotho levels and determining an individual’s KL-VS status [1:52:15];
• The promising potential of klotho for Alzheimer’s disease treatment, and the importance of philanthropy for funding research [1:58:00]; and
• More.

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Julia Wattacheril is a physician scientist and director of the Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) program at Columbia University Irving Medical Center. In this episode, Julia delves deep into the complex world of liver health, beginning with a foundational overview of liver physiology. She provides an in-depth look at how alcohol impacts liver function, breaking down the metabolism of ethanol and its detrimental effects. Julia then shifts the focus to understanding liver function tests and optimal enzyme levels, providing a detailed explanation of AST and ALT and elucidating why fluctuations in these levels may or may not be concerning. She provides a primer on the four major stages of liver disease, discussing risk and emphasizing the importance of early diagnosis. Julia highlights the role of liver disease in increasing the risk of cancer and cardiovascular disease and covers in detail the various strategies for diagnosing, treating, and preventing the progression of liver disease.

We discuss:

• Julia’s training, the importance of liver health, and the challenges and innovations of hepatology [3:15];
• The complex and crucial functionality of the liver, its four most essential functions, and more [8:45];
• Liver injuries: historical and evolving understanding of causal factors, and the progression to liver diseases and cancer [13:15];
• How the liver metabolizes nutrients and what happens in the presence of excess calories or alcohol [24:45];
• Methods of diagnosing liver disease and how insights guide treatment and management strategies [33:30];
• The poisonous nature of ethanol to the liver [40:30];
• Varied responses to alcohol, damaging effects of alcohol beyond the liver, and the process of advising patients on their alcohol consumption [47:15];
• Understanding liver enzymes AST and ALT—interpreting levels, lifestyle factors that affect them, and diagnostic approaches [58:30];
• Interpreting liver function tests for fatty liver disease, and the challenges of diagnosing liver pathologies, particularly in children versus adults [1:13:15];
• Comprehensive liver health assessments via imaging and various diagnostic tools to prevent overlooking potential liver pathologies [1:18:45];
• Potential impact of recreational drugs, statins, and other medications on liver function test results [1:26:45];
• Shifting nomenclature from NAFLD to MASLD to reflect accuracy in the underlying pathophysiology and understanding of liver diseases [1:30:30];
• Pathophysiology of MASLD, the need for proactive screening, and the significance of liver fat percentage as an indicator of metabolic health [1:36:30];
• The importance of screening for rare conditions alongside common metabolic diseases associated with fatty liver accumulation [1:42:45];
• Practical strategies for managing MAFLD [1:45:30];
• The impact of fructose consumption on liver health and the challenges of disentangling its effects from other factors like obesity and insulin resistance [1:52:45];
• The potential of GLP-1 agonists for the treatment of MASLD [1:57:45];
• How the four stages of liver disease have evolved [2:00:30];
• Increased cancer and heart disease risk associated with early-stage MAFLD [2:05:15];
• Emerging drugs and therapies for addressing fat accumulation and fibrosis related to MAFLD [2:12:15];
• Peter’s major takeaways [2:18:45]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter delves into the often misunderstood concept of inflammation. He first defines inflammation and differentiates between acute inflammation and chronic inflammation, the latter of which is linked to aging and a plethora of age-related diseases. Peter breaks down the intricate relationship between chronic inflammation, obesity, and metabolic health, and highlights the signs that might suggest someone may be suffering from chronic inflammation. From there, the conversation centers on actionable advice and practical steps one can take to manage and minimize chronic inflammation. He explores how diet plays a crucial role, including the potential benefits of elimination diets, and he examines the impact of lifestyle factors such as exercise, sleep, and stress management. Additionally, he discusses the relevance of food inflammatory tests and concludes by examining the potential benefits and drawbacks of drugs and supplements in managing inflammation.

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 #59 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Defining inflammation (and the cultural impact of Napoleon Dynamite) [1:45];
• Acute vs chronic inflammation [8:00];
• The connection between chronic inflammation, aging, and age-related diseases [11:00];
• The impact of inflammation on metabolic health [18:30];
• Understanding and diagnosing chronic inflammation: blood tests and other approaches, and challenges with measurement [20:00];
• Factors that contribute to low-level chronic inflammation [28:00];
• Minimizing inflammation through diet [29:45];
• The important role of fiber for gut health and inflammation [33:45];
• A closer look at the impact of trans fats and saturated fats on overall health [34:45];
• Why Peter prefers dietary fiber from food sources over supplements [38:30];
• Debunking “superfoods”: emphasizing proven methods over marketing claims for reducing inflammation [39:00];
• Is there any value in over-the-counter food inflammatory tests? [42:30];
• Food elimination diets: how they work, symptoms and markers to watch, challenges and limitations [45:15];
• Identifying dietary triggers for gut-related symptoms through low-FODMAP diets like the “carnivore diet” [51:15];
• Dairy: the complex role of dairy on inflammation and individual responses [55:00];
• Wheat: the complexities and conflicting evidence around wheat's inflammatory effects [57:45];
• How exercise influences inflammation [1:02:00];
• How sleep quality and duration impacts inflammation [1:07:00];
• The potential impact of chronic psychological stressors on inflammation [1:13:00];
• The impact of oral health on inflammation and overall well-being [1:15:00];
• The role of medications in managing chronic inflammation [1:18:15];
• Supplements: evaluating the efficacy of various anti-inflammatory supplements [1:22:15];
• Parting thoughts and takeaways [1:27:00]; and
• More.

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In this special edition celebrating 300 episodes of The Drive, Peter discusses a variety of popular topics and health interventions and classifies them based on their level of evidence and relevance using the following categories: proven, promising, fuzzy, noise, and nonsense. Peter first delves into the topic of geroprotective molecules, covering rapamycin, metformin, NAD and its precursors, and resveratrol. Next, he explores the significance of metrics like VO2 max and muscle mass, as well as emerging concepts like blood flow restriction and stem cells. The conversation extends to nutrition, addressing questions surrounding long-term fasting, sugar consumption, sugar substitutes, and the contentious role of red meat in cancer. Peter not only provides his current stance on each topic—most of which have been covered in great detail in the previous 300 episodes—but also reflects on how his opinion may have evolved over the years.

We discuss:

• Defining the categories of “proven, promising, fuzzy, noise, and nonsense” [3:15];
• Rapamycin [9:30];
• Metformin [17:00];
• NAD and its precursors [24:30];
• Resveratrol [32:45];
• The importance of VO2 max, muscle mass, and muscular strength for lifespan [38:15];
• Blood flow restriction (BFR) training [44:00];
• Using stem cells to treat osteoarthritis or injury [51:30];
• Fasting as a tool for longevity (and why Peter stopped his fasting protocol) [55:45];
• The energy balance theory [1:06:30];
• The idea that sugar is poison [1:12:00];
• The idea that sugar substitutes are dangerous [1:22:15];
• The debate on red meat and cancer [1:28:45]; and
• More.

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This is a special episode of The Drive with Peter’s friend and fellow car enthusiast Dax Shepard. In this podcast, which commemorates the 30th anniversary of the death of Brazilian Formula One legend Ayrton Senna, Dax sits down with Peter to better understand what made Senna so special and why Peter remains an enormous fan. This conversation focuses on Senna’s life, the circumstances of his death, and his lasting impact and legacy on the sport of F1.

We discuss:

• Peter’s interest in motorsports began as a child [2:30];
• The drama and dangers of F1 [6:00];
• What made Senna special [13:00];
• What Senna meant to Brazilians [24:00];
• The cause of the fatal crash [28:15];
• Why Peter is obsessed with Senna [40:30];
• Being the best versus having the best record [43:30];
• Senna’s unique driving style and incredible intuition about automotive engineering [46:30];
• Back to the day of the dreadful race [53:00];
• What Peter believes caused the crash [1:02:45];
• Views on dying young, in the prime of life [1:13:00];
• Senna lives on in his foundation and in safety changes adopted by F1 [1:21:00];
• Statistics aren’t enough for fandom, and why people like who they do [1:24:15];
• The biggest difference between F1 today and F1 in the 80s [1:28:30];
• Senna’s driving superpower [1:30:30];
• The fastest drivers currently in F1 [1:38:30];
• Current F1 obsessions [1:45:00];
• How hard it is to do what the top F1 drivers do [1:50:15];
• Dax’s love of motorcycles and his AMG E63 station wagon [1:52:15];
• Awesome Senna mementos from Etsy [2:01:15];
• What makes specialists interesting, and Max’s devotion to F1 [2:10:15];
• What Senna might have done if he had not died that day [2:14:00];
• Michael Schumacher and Max Verstappen are also top F1 drivers [2:17:30];
• Interlagos in Sao Paulo Brazil is always an incredible experience [2:18:45]; and
• More.

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Luc van Loon is an internationally renowned expert in skeletal muscle metabolism. In this episode, Luc starts with an exploration of the roles of insulin and triglycerides in endurance exercise, highlighting their impact on skeletal muscle metabolism, and he offers profound insights into the significance of protein in this context. He elucidates how different protein types and forms influence muscle protein synthesis rates, exploring the nuances of protein absorption, digestibility, amino acid quality, and their implications for performance and recovery. Delving deeper, he differentiates between animal and plant protein sources, unraveling the distinctive properties of various protein types, from the differences between whey and casein to the emerging trends in collagen protein supplementation. Moreover, Luc dissects the intricate connections among physical activity, lean muscle mass, muscle protein synthesis induced by resistance training, and dietary protein.

We discuss:

• Luc’s background and insights about fuel selection during exercise [3:30];
• Fuel utilization during endurance exercise [9:30];
• Fat metabolism, intramuscular lipids, and the nutritional dynamics of endurance sports [17:15];
• The optimal window for replenishing intramuscular fat stores and glycogen post-exercise [25:15];
• Luc’s interest in protein metabolism and exploration of amino acids' dual role as building blocks and signaling molecules in driving muscle protein synthesis [32:15];
• How protein metabolism differs between sedentary individuals and those engaged in predominantly strength training or endurance training [38:45];
• The basics of how proteins are digested and absorbed, and how muscle protein synthesis is measured [50:30];
• How factors like food texture, cooking methods, and protein composition impact muscle protein synthesis, and the importance of protein distribution throughout the day [59:45];
• Differences in whey and casein proteins, and the ability of ingested protein to stimulate muscle protein synthesis [1:03:30];
• Dietary protein distribution and quantity for the maximization of muscle protein synthesis [1:09:00];
• Muscle loss with age and inactivity and the importance of resistance exercise to maintain type II muscle fibers [1:17:15];
• Differences between whey and casein proteins, and the importance of both quantity and quality of protein sources [1:28:30];
• Optimizing muscle protein synthesis: exercise, timing of protein intake, protein quality, and more [1:37:00];
• How to preserve muscle while trying to lose weight [1:46:00];
• Anabolic resistance and overcoming it with physical activity [1:55:45];
• Importance of protein intake and physical activity in hospitalized patients [2:06:30];
• Reviewing the efficacy of collagen supplements [2:13:30];
• Plant-based diets: how to ensure a balance of amino acids, and other considerations [2:20:30];
• Future research: understanding protein metabolism in the brain [2:23:45]; and
• More.

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