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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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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.Connect With Peter on Twitter, Instagram, Facebook and YouTube
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