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    In this special episode of The Drive, Peter tackles a wide range of listener questions submitted over the past year. The discussion spans essential topics such as exercise—covering grip strength, traveling workouts, and why Peter doesn’t consider exercise an ideal weight-loss strategy—and the top biomarkers everyone should track. He also explores promising new longevity research, his evolving views on longevity, and frameworks like “objective, strategy, tactics” for personalized decision-making. The episode wraps up with insights on building good habits and a glimpse into Peter’s recent reading list.

    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 Special AMA 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 Peter’s car stereo saga) [1:45]; The importance of grip strength and the best methods for training it effectively [3:45]; Exercise while traveling: strategies for staying active and maintaining an exercise routine [14:45]; Why women should prioritize strength training [18:00]; The limited role of exercise in weight loss and its greater importance in improving health, body composition, and insulin sensitivity [19:45]; The “top five most important biomarkers” for assessing health [22:45]; Promising developments in longevity research [28:15]; The development of Klotho as a neuroprotective drug: challenges, timelines of trials, and more [34:00]; Peter’s updated view on the potential of epigenome manipulation to restore aged cells to their youthful state [39:45]; How reversing age-related epigenetic changes in immune cells could revolutionize our approach to aging and disease [43:30]; The “objective, strategy, tactics” framework, and the importance prioritizing impactful lifestyle habits over less significant health trends [49:30]; Strategies for building and maintaining good habits [56:45]; How to think about drugs and supplements as part of a longevity toolkit [1:02:00]; Peter’s recent reading list [1:05:15]; and More.

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    In this "Ask Me Anything" (AMA) episode, Peter dives deep into one of the most frequently discussed and often misunderstood topics: nutrition. From weight loss and maintenance to the intricate relationship between nutrition and exercise and body composition, Peter addresses the complexities of nutrition research and explores the perennial question of whether there is a "best diet." He provides practical insights on how to choose the right diet for your unique needs, discusses the role of protein and processed foods, and outlines the key questions to help you optimize your approach to eating.

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

    We discuss:

    The key nutrition-related topics to be discussed [1:30]; Why Peter is not fond of discussing nutrition: limitations of nutrition research, the pitfalls of extreme certainty in dietary discussions, and the body's adaptability to varied diets [3:30]; Key health metrics to monitor to evaluate the effects of nutrition [9:30]; The relationship between nutrition and exercise as they relate to weight loss, maintenance, and gain [12:30]; How increased muscle mass from resistance training impacts calorie burn, body composition, glucose metabolism, and overall health benefits [19:45]; Comparing the impact of fitness and nutrition on lifespan and healthspan: data showing fitness to be a more significant predictor of mortality than nutrition [23:30]; The myth of a “best diet,” factors that determine the effectiveness of a diet, and data suggesting benefits of the Mediterranean diet [39:00]; How long to trial a new diet, the importance of measurable goals, and the appropriate timescales for observing meaningful changes [48:30]; The inherent challenges in nutrition research: variability in dietary exposures, limitations in study design, the body’s adaptive nature which dampen the effects, and more [51:15]; Nutritional approaches for chronic diseases like cardiovascular disease and type 2 diabetes [58:45]; Emerging studies on dietary interventions for non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) [1:02:45]; Practical considerations for individuals to identify the best diet for them: protein intake, energy balance, macronutrient adjustments, and micronutrient levels [1:06:00]; Understanding processed vs. ultra-processed foods [1:09:15]; The effects of ultra-processed foods on health [1:12:30]; Questions that someone should ask themselves if they’re looking to fine-tune their diet [1:18:15]; and More.

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    Dr. Saum Sutaria is the Chairman and CEO of Tenet Healthcare and a former leader in McKinsey & Company’s Healthcare and Private Equity Practices, where he spent almost two decades shaping the field. In this episode, Saum unpacks the complexities of the U.S. healthcare system, providing a detailed overview of its structure, financial flows, and historical evolution. They delve into topics such as private insurance, Medicare, Medicaid, employer-sponsored coverage, drug pricing, PBMs and the administrative burdens impacting the system. Saum’s insights help connect healthcare spending to broader economic issues while exploring potential reforms and the role of technology in improving efficiency. Saum highlights how choice and innovation distinguish the U.S. healthcare system, explores the reasons behind exorbitant drug prices, and examines the potential solutions, challenges, and trade-offs involved in lowering costs while striving to improve access, quality, and affordability. The opinions expressed by Saum in this episode are his own and do not represent the views of his employer.

    We discuss:

    The US healthcare system: financial scale, integration with economy, and unique challenges [5:00]; Overview of how the US healthcare system currently works and how we got here [9:45]; The huge growth and price impact due to the transition from out-of-pocket payments in the 1950s to the modern, third-party payer model [18:30]; The unique structure and challenges of the US healthcare system compared to other developed nations [22:00]; Overview of Medicare and Medicaid: who they cover, purpose, and impact on healthcare spending [27:45]; Why the US kept a employer-sponsored insurance system rather than pursue universal healthcare [32:00]; The evolution of healthcare insurance: from catastrophic coverage to chronic disease management [36:00]; The challenge of managing healthcare costs while expanding access and meeting increased demand for chronic illness care [44:15]; Balancing cost, choice, and access: how the US healthcare system compares to Canada [48:45]; The role of the US in pharmaceutical innovation, it’s impact on drug pricing, and the potential effects of price controls on innovation and healthcare costs [56:15]; How misaligned incentives have driven up drug prices in the US [1:05:00]; The cost of innovation and choice, and the sustainability of the current healthcare cost expenditures in the US in the face of a shrinking workforce and aging population [1:11:30]; Health outcomes: why life expectancy is lower in the US despite excelling at extending lifespan beyond 70 [1:18:45]; Potential solutions and challenges to controlling drugs costs in the US while balancing choice and access and preserving innovation [1:26:15]; Balancing GLP-1 drug innovation with affordability and healthcare spending sustainability [1:40:00]; Reducing healthcare spending: complexities, trade offs, and implications of making needed cuts to healthcare expenditures [1:46:45]; The role of government regulation, opportunities for cost savings, and more [1:56:15]; Hospital billing: costs, charges, complexities, and paths to simplification [2:01:15]; How prioritizing access and choice increased expenditures: reviewing the impact of healthcare exchanges and the Affordable Care Act [2:08:00]; Feasibility of a universal Medicare program, and what a real path to sustainable healthcare looks like [2:15:45]; The challenge of long-term care and the potential of innovation, like device-based therapies and AI, to improve health [2:23:15]; and More.

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    Bill Perkins is one of the world’s most successful hedge fund managers and entrepreneurs, and the author of the bestseller, Die With Zero. In this episode, Bill unpacks the Die With Zero philosophy which challenges conventional thinking related to the balance between health, wealth, and time—the three variables important for fulfillment. Bill makes the case that we should strive for maximum net fulfillment rather than net worth (or even health). He argues that we need to optimize our life to have memorable experiences before it’s too late and that most people are over-saving and under-living. Bill also explains how one can apply the principles in Die With Zero to break out of “autopilot” and optimize their life to achieve maximum net fulfillment.

    We discuss:

    Bill’s upbringing, background, and first job on Wall Street [2:45]; A missed experience and feeling of regret that shaped Bill’s thinking [13:45]; Thinking in terms of time, and the relationship between money, time, and health [16:30]; Solving for net fulfillment and allocating your time based on the seasons of life [26:45]; How Bill thinks about risk, opportunity costs, and the difference between fear and risk tolerance [35:00]; Optimizing for fulfillment, finding purpose outside of work, and more [41:15]; Thinking about the order of experiences you want to have based on seasons of life [49:30]; Bill’s unique perspective on philanthropy and a more impactful way to give money away [54:15]; Applying the principles in ‘Die With Zero’ to maximize fulfillment [1:03:30]; How to break out of living life on autopilot [1:13:45]; When should your net worth peak? [1:17:30]; Taking calculated risks [1:21:00]; Bill shares a lesson from his incredible birthday [1:24:45]; How Bill’s philosophy has evolved since writing Die With Zero [1:33:30]; and More.

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    In this “Ask Me Anything” (AMA) episode, Peter dives into the world of red light therapy in response to frequent questions from listeners. Peter provides a comprehensive exploration, starting with the basics of red light therapy and why it’s getting so much attention. The conversation examines the latest data on various applications, including aging, skin health, acne, wound healing, hair loss, eye health, exercise performance, metabolic health, weight loss, inflammation, injury recovery, and menstrual cramps. Peter analyzes the scientific literature on each use case and concludes with a summary table that provides an easy-to-follow breakdown of the potential benefits of red light therapy across these areas.

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

    We discuss:

    Overview of topics and the motivation behind exploring red light therapy [1:45]; The basic science of red light therapy [3:15]; The unique penetration properties of red light [6:00]; What happens when tissue is exposed to red light [9:30]; Exploring red light therapy’s potential to combat aging [11:00]; Red light therapy for treating acne [13:00]; Red light therapy for aiding in wound healing [18:45]; Red light therapy for hair loss: promising benefits and practical advice [24:15]; Analyzing the evidence of a positive or negative effect of red light therapy on the eyes [28:00]; Red light therapy’s impact on performance and recovery [30:30]; Red light therapy’s impact on metabolic health: analyzing the limited evidence for improved glucose metabolism [32:45]; Red light therapy for weight loss and targeted fat reduction [36:45]; Red light therapy for inflammation, chronic pain, and injury rehabilitation [41:00]; Red light therapy as a treatment for menstrual cramps [43:45]; Summary: promising applications of red light therapy, unsupported claims, and costs to consider [46:45]; and More.

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    In this quarterly podcast summary (QPS) episode, Peter summarizes his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from his discussions on diverse topics such as dopamine and addiction with Anna Lembke, the current state and exciting future of CRISPR-mediated gene editing with Feng Zhang, how to build and maintain strong bones from youth to old age with Belinda Beck, how calorie restriction may influence longevity and metabolic health with Eric Ravussin, and the role of testosterone and TRT in prostate cancer with Ted Schaeffer. 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 #325 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

    We discuss:

    Overview of topics to be covered [1:45]; Anna Lembke episode: addiction, dopamine's role in pleasure and pain, and managing addictive behaviors [4:15]; Follow-up questions about addiction: heritability, cold therapy, exercise, and strategies for breaking addictive behaviors [14:45]; Feng Zhang episode: the potential of gene editing with CRISPR technology for treating diseases, and the challenges ahead [21:00]; Feng Zhang’s impactful education experience, and how early exposure and curiosity-driven learning can develop scientific interest for kids [28:30]; The future of CRISPR: weighing the scientific potential to combat complex diseases against ethical considerations around genetic modification [33:45]; Belinda Beck episode: how to build and maintain strong bones from youth to old age [37:30]; How both nutrition and exercise are crucial for bone health at all ages, and why it’s never too late to start [54:45]; Eric Ravussin episode: calorie restriction, energy expenditure, exercise for weight maintenance, and more [59:00]; Measuring energy intake and energy expenditure: techniques and challenges [1:09:45]; ed Schaeffer episode: the nuance role of testosterone in prostate cancer, TRT, and the need for better cancer biomarkers [1:14:30]; Peter’s favorite bands [1:25:45]; and More.

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    Eric Ravussin is a world-renowned expert on obesity, metabolism, and aging whose pioneering research has shaped much of what we understand today about energy balance and caloric restriction. In this episode, Eric shares insights from his cutting-edge work on energy expenditure—a critical factor in understanding how our bodies regulate weight and appetite. He discusses methods for measuring energy output, energy balance, food intake, and appetite regulation, and explores key studies on macronutrient manipulation. Eric then delves into the CALERIE study on caloric restriction, highlighting insights related to biomarkers of both primary and secondary aging. The conversation also covers the potential of GLP-1 agonists to replicate these effects and looks ahead to how AI and technology could transform metabolic research in the coming years.

    We discuss:

    Eric’s background and current work metabolism and measuring energy expenditure [3:00]; The science behind metabolic chambers for measuring energy expenditure, and the complexities of indirect and direct calorimetry [8:00]; The body's regulatory systems for maintaining energy balance and the primary influence of energy intake on body weight [18:30]; The epidemic of obesity and a discussion of resting metabolic rate [24:45]; The impact of exercise, appetite, gut hormones, and eating patterns on weight regulation [28:45]; Experiments looking at how macronutrient composition affects energy expenditure [38:45]; The challenges of studying diet in real-life settings, the potential of personalized nutrition, and how public health policy could play a role in guiding nutritional habits [51:00]; The importance of protein in the diet, the limitations of dietary data collection, and how AI could potentially transform nutrition science [1:08:15]; How Eric’s interest in caloric restriction (CR) began with Biosphere 2, metabolic efficiency's role in aging, and goals of the CALERIE study [1:15:15]; The CALERIE study: exploring the real-world impact of caloric restriction [1:28:00]; Notable findings from the CALERIE study after two years: sustained weight loss, participant retention, and more [1:40:00]; The effect of caloric restriction on the hallmarks of aging [1:47:00]; The challenge of applying CR to the general population, the potential of drugs and exercise to mimic the effects of CR [1:55:45]; Upcoming study comparing caloric restriction to time-restricting eating, and Peter’s takeaways from the discussion [2:02:45]; and More.

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    Feng Zhang, a professor of neuroscience at MIT and a pioneering figure in gene editing, joins Peter to discuss his groundbreaking work in CRISPR technology, as well as his early contributions to optogenetics. In this episode, they explore the origins of CRISPR and the revolutionary advancements that have transformed the field of gene editing. Feng delves into the practical applications of CRISPR for treating genetic diseases, the importance of delivery methods, and the current successes and challenges in targeting cells specific tissues such as those in the liver and eye. He also covers the ethical implications of gene editing, including the debate around germline modification, as well as reflections on Feng’s personal journey, the impact of mentorship, and the future potential of genetic medicine.

    We discuss:

    Feng’s background, experience in developing optogenetics, and his shift toward improving gene-editing technologies [2:45]; The discovery of CRISPR in bacterial DNA and the realization that these sequences could be harnessed for gene editing [10:45]; How the CRISPR system fights off viral infections and the role of the Cas9 enzyme and PAM sequence [21:00]; The limitations of earlier gene-editing technologies prior to CRISPR [28:15]; How CRISPR revolutionized the field of gene editing, potential applications, and ongoing challenges [36:45]; CRISPR’s potential in treating genetic diseases and the challenges of effective delivery [48:00]; How CRISPR is used to treat sickle cell anemia [53:15]; Gene editing with base editing, the role of AI in protein engineering, and challenges of delivery to the right cells [1:00:15]; How CRISPR is advancing scientific research by fast-tracking the development of transgenic mice [1:06:45]; Advantages of Cas13’s ability to direct CRISPR to cleave RNA and the advances and remaining challenges of delivery [1:11:00]; CRISPR-Cas9: therapeutic applications in the liver and the eye [1:19:45]; The ethical implications of gene editing, the debate around germline modification, regulation, and more [1:30:45]; Genetic engineering to enhance human traits: challenges, trade-offs, and ethical concerns [1:40:45]; Feng’s early life, the influence of the American education system, and the critical role teachers played in shaping his desire to explore gene-editing technology [1:46:00]; Feng’s optimism about the trajectory of science [1:58:15]; and More.

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    Belinda Beck, founder of The Bone Clinic and a leading authority on exercise physiology and bone health, delves into the science of osteoporosis, bone density, and the lifelong importance of maintaining skeletal health. In this episode, she explains how the foundation for strong bones is established during childhood, offering valuable advice for parents on optimizing bone health for their kids. She also explores how bone remodeling occurs throughout life, driven by activity, nutrition, and hormones. Belinda highlights the power of resistance training in improving bone strength, even for those at risk of bone loss, and emphasizes the role of essential vitamins and minerals in maintaining bone health. She shares practical strategies, backed by research, for preventing fractures and combating osteoporosis.

    We discuss:

    Belinda’s journey into bone health research and training [2:45]; The physiology of bone and how bones adapt to mechanical loading [8:15]; Bone development from birth to adulthood, why early life is a crucial period, the functions of osteoblasts and osteoclasts, and gender differences in BMD [14:00]; How parents can optimize their children’s bone health through diet (calcium and vitamin D), sunlight exposure, and physical activity [27:30]; The best sports and activities for promoting bone health, weight training for kids, and advice for parents [36:30]; The impact of corticosteroid use on bone health in children and strategies to minimize negative effects [48:30]; Advice for people in middle age to preserve bone density: physical activity and bone-loading exercises [52:00]; Bone loss during the menopause transition for women: hormone replacement therapy and other strategies to mitigate BMD losses [59:30]; Interpreting the bone mineral density results from a DEXA scan: T-score, Z-score, and more [1:03:00]; The LIFTMOR study: testing the effects of heavy weightlifting on bone health in postmenopausal women with low bone density [1:10:15]; Profound benefits of weight training outside of BMD improvements: exploring the broader impacts on patients in the LIFTMOR study [1:19:30]; Guidance for people wanting to use exercise designed to improve their bone health [1:29:30]; and More.

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    Anna Lembke is the Chief of the Stanford Addiction Medicine Dual Diagnosis Clinic and author of Dopamine Nation: Finding Balance in the Age of Indulgence. In this episode, Anna dives deep into the biochemistry and neurobiology of addiction, exploring the critical role of dopamine and the prefrontal cortex. She shares her framework for diagnosing and treating addiction, providing real-world examples involving alcohol, gambling, cannabis, social media, and more. Anna outlines the risk factors for addiction, including inherited and nurture-based risks, explores the rise of addictions in younger generations, and discusses effective ways to address these issues with children. Additionally, she touches on healthy coping strategies, the evolution of the “marshmallow experiment,” and provides insights into GLP-1 agonists as a possible tool for addiction treatment. Finally, she reflects on the value of 12-step programs and how she navigates the emotional challenges of her work.

    We discuss:

    The role of dopamine and the prefrontal cortex in addiction [3:00]; The clinical definition of addiction and the behavioral criteria for diagnosing it [13:00]; Assessing alcohol use: patterns, risks, and addiction diagnosis [17:15]; Applying the addiction diagnosis framework using gambling as an example [21:45]; Exploring addiction variability: how nature, nurture, and access shape individual vulnerability and drug of choice [25:15]; How abstinence from addictive behaviors can help reset the brain’s reward system and improve mental health [41:15]; Safely abstaining from addiction substances, drugs needing medical supervision, and other key considerations [51:30]; Transitioning from abstinence to long-term recovery: tools and considerations [59:00]; Exploring behavioral addictions like sex addiction, and the gender differences in addiction patterns [1:08:30]; Factors contributing to the increasing levels of addiction across the world [1:13:45]; How online pornography can affect young boys' developing brains and lead to addictive behaviors, and strategies for parents to address this issue [1:23:30]; The link between social media use and declines in mental health, potential solutions, and protective measures [1:34:45]; How exercise affects brain chemistry, the role of dopamine and endorphins, and how exercise can become addictive [1:44:00]; Cold-water immersion for mood regulation, and other healthy coping strategies [1:47:15]; The “marshmallow experiment”: how broken promises affect behavior and trustworthy environments help children develop self-control [1:54:00]; Can GLP-1 agonists be useful in treating addiction? [1:58:30]; The benefits of 12-step programs [2:06:00]; Why understanding a patient’s story is essential for meaningful psychiatric care [2:11:45]; and More.

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    In this “Ask Me Anything” (AMA) episode, Peter dives back into the increasingly popular topic of GLP-1 agonists, such as Ozempic and Mounjaro, which have garnered widespread attention for their ability to promote weight loss. Peter covers the latest findings in this rapidly evolving landscape, including new insights into their long-term efficacy, side effects, and what happens when the drug is discontinued. Peter also explores their impact on body composition and how resistance training interacts with these treatments. Additionally, he compares different GLP-1 receptor agonists and discusses promising new drugs in the pipeline. Finally, Peter addresses questions about the role of compounding pharmacies in the GLP-1 agonist market, compares oral vs. injectable options, and provides key considerations for anyone deciding whether to use a GLP-1 agonist for weight 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 #64 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

    We discuss:

    The rapidly evolving landscape of GLP-1 agonists [2:15]; The mechanism of GLP-1 agonists, their origin as diabetes treatments, and how they evolved into weight-loss drugs [6:45]; Overview of new data and open questions related to the benefits and risks of GLP-1 agonists [10:30]; New insights into the long-term safety of GLP-1 agonists, side effects, and more [16:45]; The long-term efficacy of GLP-1 agonists, financial barriers, and more [19:45]; The mechanisms behind GLP-1 agonists' ability to promote weight loss [22:00]; New data on body weight changes after discontinuing the drug [26:00]; Effects of GLP-1 agonists on lean mass and body composition, and the role of protein and resistance training in preserving muscle [31:30]; Semaglutide vs. tirzepatide: comparing benefits and side effects [36:30]; How compounding pharmacies affect availability of GLP-1 drugs and the types of formulations that are available [39:15]; How do oral formulations of GLP-1 drugs compare to injectable formulations? [44:15]; How do sublingual (under tongue) formulations of GLP-1 drugs compare to injectable formulations? [46:15]; Guidance for using compounding pharmacies to purchase GLP-1 agonists [47:15]; Data on retatrutide—a promising new triple receptor agonist in the pipeline [50:15]; Can GLP-1 agonists be beneficial for sleep apnea and immune function? [57:00]; Potential neuroprotective benefits of GLP-1 agonists: impact on dementia risk [1:00:45]; Exploring why GLP-1 agonists may reduce the risk of cancer, kidney disease, and cardiovascular disease [1:04:00]; How GLP-1 agonists might boost fertility in women [1:10:15]; Early indications that GLP-1 agonists may help treat substance abuse disorders [1:12:00]; Potential health risks of GLP-1 agonists: addressing thyroid cancer concerns and the unknowns due to lack of data [1:14:00]; Examining the potential link between GLP-1 agonists and increased depression or suicidal ideation [1:16:00]; Major remaining questions: the effects of cyclic use, rebound appetite, impact on adolescents' development, and more [1:19:30]; Key considerations when deciding whether to use a GLP-1 agonist for weight loss [1:23:45]; and More.

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    In this quarterly podcast summary (QPS) episode, Peter summarizes 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 liver health with Julia Wattacheril, heart rate variability with Joel Jamieson, artificial intelligence with Zak Kohane, klotho for brain health with Dena Dubal, and lactate and lactate metabolism with George Brooks. 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 #319 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

    We discuss:

    Overview of topics, and the positive feedback on the quarterly podcast summary format [2:00]; Julia Wattacheril episode: liver health and disease [4:00]; Noninvasive methods to diagnose liver conditions, and how to manage and improve liver health [16:00]; Joel Jamieson episode: heart rate variability (HRV) for training and health [27:15]; Practical tools for measuring HRV and how it informs training and recovery decisions [37:00]; Zak Kohane episode: artificial intelligence and medicine [47:15]; The current role of AI in medicine and how it could revolutionize medicine in the future [53:45]; The limitations and concerns pertaining to AI [1:00:15]; Dena Dubal episode: the potential benefits of klotho for brain health [1:05:00]; Animal studies on klotho and brain health [1:11:00]; Genetics-based variations in klotho levels in humans and their impact on cognition, disease risk, and longevity [1:14:15]; Testing klotho levels, the significance of the KL-VS variant, the role of exercise in increasing klotho, and more [1:17:30]; The potential of klotho as a treatment for cognitive decline and Alzheimer's disease [1:23:15]; George Brooks episode: a new paradigm to think about lactate and lactate metabolism [1:27:45]; The potential for lactate infusions to aid in brain recovery following a head injury [1:34:00]; The relationship between lactate and cancer, and the impact of exercise on lactate levels and cancer risk [1:36:30]; and More.

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    Tadej Pogačar is a three-time Tour de France champion and one of the most dominant cyclists of his generation. In this episode, he shares insights into his 2020 Tour de France victory, his historic 2024 season winning both the Giro d’Italia and Tour de France, and the struggles he faced in 2022 and 2023. He also dives into his training regimen, nutrition, and the key metrics he tracks, like power, VAM, and heart rate variability. Tadej offers a glimpse into his goals for the future and what it takes to stay at the top of the sport.

    We discuss:

    2020 Tour de France win [4:30]; Learning from previous mistakes [8:45]; Training: simulating steep climbs and other challenging race conditions [10:30]; Tadej’s historic 2024 season and what contributed to his success [12:30]; Nutrition for optimal performance: offseason diet and carbohydrate intake during intense training sessions [15:30]; Training metrics: heart rate, power output, VAM, and HRV, and his approach to zone 2 training [18:15]; Epic climbs in the Tour de France, mindset after challenging stages, and rebuilding confidence after the 2023 Tour [25:45]; Racing dynamics, media criticism, and Tadej’s reflections on racing records [32:15]; Training in the off-season [39:00]; and More.

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    Marty Makary, a Johns Hopkins surgeon and New York Times bestselling author, returns to The Drive to discuss his latest book, Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health. In this episode, Marty explores how a new generation of doctors is challenging long-held medical practices by asking critical new questions. He discusses the major problems of groupthink and cognitive dissonance in the medical community and delves into several of the "blind spots" raised in the book, including treatments for appendicitis, the peanut allergy epidemic, misunderstandings about HRT and breast cancer, antibiotic use, and the evolution of childbirth. He explains the urgent need for reform in medical education and the major barriers standing in the way of innovative medical research. Throughout the conversation, Marty offers insightful reflections on where medicine has succeeded and where there’s still room to challenge historic practices and embrace new approaches.

    We discuss:

    The issue of groupthink and cognitive dissonance in science and medicine [2:30]; How a non-operative treatment for appendicitis sheds light on cognitive dissonance [7:00]; How cognitive dissonance and effort justification shape beliefs and actions [13:15]; How misguided peanut allergy recommendations created an epidemic [17:45]; The enduring impact of misinformation and fear-based messaging around hormone replacement therapy allegedly causing breast cancer [25:15]; The dangers of extreme skepticism and blind faith in science, and the importance of understanding uncertainty and probability [28:00]; The overuse of antibiotics and the rise of antibiotic resistant infections and poor gut health [33:45]; The potential correlations between early antibiotic use and chronic diseases [40:45]; The historical and evolving trends in childbirth and C-section rates [50:15]; Rethinking ovarian cancer: recent data challenging decades of medical practice and leading to new preventive measures [1:05:30]; Navigating uncertainty as a physician [1:19:30]; The urgent need for reform in medical education [1:21:45]; The major barriers to innovative medical research [1:27:30]; The dogmatic culture of academic medicine: why humility and challenging established norms are key for progress [1:38:15]; The major successes and ongoing challenges of modern medicine [1:51:00]; and More.

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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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