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After more than six years of research, planning, and writing, Peter’s book, Outlive: The Science and Art of Longevity, is officially available as of March 28th. In this episode, Peter sits down with co-author Bill Gifford to provide a behind-the-scenes look into the writing process, including the motivation for making it happen, how the book evolved over the course of the writing process, and why certain topics were chosen (and omitted). Additionally, they discuss how the book is structured and touch on a few of the book’s main themes to give potential readers an idea of what they can expect.

We discuss:

• The meaning of the book’s title and subtitle [3:00];
• Finding the right art for the book cover [9:00];
• Who is Bill Gifford, and how did he get involved in the book? [16:15];
• How Peter’s writing evolved over the six years it took to write this book [25:00];
• The structure of the book and what people can expect to learn [29:00];
• How the writing of the book and the podcast interviews have shaped Peter’s thinking and approach to translating science [32:45];
• Making the book stand the test of time despite the constant evolution of science and medicine [36:00];
• Objective, strategy, and tactics [39:30];
• Exciting possible progressions in science and medicine over the next decade [42:15];
• What is holding back “medicine 3.0” from being the norm? [46:00];
• How the book compares to the podcast in terms of technicality and readability for the layman [49:00];
• Motivation to write the book and insights into challenges around the writing process [57:15];
• Peter’s decision to be the reader for the audiobook [1:10:30];
• The many painstaking last-minute changes and edits that brought the book together and made it better [1:19:00];
• Peter and Bill’s favorite parts of the book [1:27:30];
• The incredible team of people supporting the book [1:31:30]; and
• More.

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Ethan Weiss is a preventative cardiologist at UCSF, an entrepreneur-in-residence at Third Rock Ventures, where he is working on a project related to cardiometabolic disease, and a previous guest on The Drive. In this episode, Ethan compares and contrasts the diagnostic imaging tools, CAC (coronary artery calcium score) and CTA (CT angiography), used to image plaque—including the latest in CTA software—and how these tools inform our understanding of ASCVD risk and guide clinical decision-making. Ethan discusses the types of plaque that cause events and the data that make a case for optimal medical therapy over stenting outside of particular cases. He explains why high blood pressure is problematic and walks through the data from clinical trials testing aggressive treatment. He talks about the best way to actually measure blood pressure, why we shouldn’t simply accept that blood pressure rises with age, and how he uses different pharmaceutical agents to treat hypertension. Additionally, Ethan explains our current, but limited, understanding of the role of metabolic health in ASCVD. He discusses the impact of fat storage capacity and the location of fat storage and explains how and why there is still a residual risk, even in people who have seemingly normal lipids, don't smoke, and have normal blood pressure.

We discuss:

• Ethan’s entrepreneurial work in the cardiometabolic disease space [4:30];
• Calcium scans (CAC scores) and CT angiography (CTA), and how it informs us about ASCVD risk [6:00];
• Peter’s historical CAC scores, CTA results, and how one can be misled [10:45];
• How Peter’s CTA results prompted him to lower his apoB [14:45];
• Calcium scans vs. CT angiogram (CTA) [21:15];
• How Ethan makes clinical decisions based on CTA results and plaque burden, and the importance of starting treatment early to prevent ASCVD [28:15];
• Improved methods of CTA to grade plaque lesions and how it’s shaped medical decisions such as stenting [33:45];
• Why Ethan favors optimal medical therapy over stenting outside of particular situations [41:45];
• The need for FFR CTA, and the potential for medical therapy to eliminate ASCVD [54:00];
• The fat attenuation index (FAI) and other ways to measure inflammation in a plaque [57:30];
• Statins and exercise may increase the risk of calcification, but what does this mean for risk? [59:45];
• The root cause of statin hesitation despite evidence that statins are a profoundly important intervention [1:05:30];
• Importance of keeping blood pressure in check, defining what’s normal, and whether we should just accept higher blood pressure with age [1:10:45];
• Blood pressure variability, how to best measure it, and data suggesting the enormous impact of keeping blood pressure down [1:21:00];
• Drugs for treating high blood pressure recommended by the ALLHAT trial [1:35:15];
• What the SPRINT trial says about the aggressive treatment of hypertension, and the risks of such treatment [1:38:15];
• Confirmatory results in the STEP trial for blood pressure, and how Ethan uses the various pharmacological agents to lower blood pressure in patients [1:43:15];
• The role metabolic health in ASCVD: what we do and don’t know [1:51:00];
• The impact of fat storage capacity and the location of fat storage on metabolic health and coronary artery disease [1:56:15]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter focuses the discussion on two topics getting a lot of attention recently. He first dives deep into GLP-1 agonists, most notably semaglutide and tirzepatide, which originally came to market as diabetes drugs but are now being studied and prescribed for weight loss. He walks through the data and compares the effectiveness of the two drugs, the side effects, and perhaps more importantly, his reservations around wide use of these drugs and who he would consider to be a candidate for them. Next, Peter discusses how metformin, another drug originally brought to market for diabetes management, gained popularity as a potential longevity drug even for non-diabetics. Peter gives his take on this possibility and reviews data from a more recent study investigating the question of whether metformin should be used for general “geroprotection.”

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

We discuss:

• The hype around semaglutide, tirzepatide, and other GLP-1 agonists for weight loss [2:30];
• Overview of GLP-1 agonists and why these drugs are getting so much attention [6:15];
• Defining the term “geroprotective” [13:30];
• Semaglutide: background, brand names, indications, and more [15:15];
• Tirzepatide: background, brand names, indications, and more [19:15];
• How semaglutide and tirzepatide compare in their efficacy in terms of weight loss and other metabolic health metrics [23:45];
• Data showing sustained weight loss and improved metabolic metrics with after more than a year of using semaglutide and tirzepatide [29:00];
• What happens to body weight when a patient discontinues the medication? [34:45];
• Noteworthy side effects of GLP-1 agonists and similar classes of drugs [40:45];
• Increased resting heart rate and other concerning trends in patients using GLP-1 agonists [45:15];
• Changes in body composition (body fat and lean muscle) in patients on GLP-1 agonists [50:45];
• Possible reasons for the loss of lean muscle mass and tips for protecting lean mass [59:00];
• GLP-1 agonists and thyroid cancer [1:01:30];
• Who might be a candidate for GLP-1 agonists? [1:03:45];
• The large financial cost of this class of drugs [1:08:30];
• Metformin as a geroprotective drug: origin of the idea that metformin could be a longevity agent even for non-diabetic patients [1:11:30];
• A 2022 study on metformin sheds more light on the question of whether metformin should be used for “geroprotection” in non-diabetics [1:21:00];
• Peter’s current approach with metformin for his patients [1:25:15]; and
• More.

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Lewis Howes is a New York Times best-selling author, entrepreneur, speaker, and host of the popular podcast, The School of Greatness. In this episode, Lewis opens up about the various hardships and traumatic events he experienced starting at a very young age and reveals the valuable lessons he learned as he worked through those traumas to improve his emotional health. He talks about how his past hardships likely contributed to his success in business and athletics, only to leave him feeling unsatisfied and unfulfilled. Next, he discusses how many aspects of his life were suffering, the inflection point that drove Lewis to seek help, and the long but beautiful healing journey that followed. Lewis makes the case that adversity, and even trauma, can be beneficial if one finds meaning in tribulations and has the courage to face one’s fears and insecurities. Finally, Lewis shares the many modalities of therapy that helped him along the way and gives advice for those wanting to find inner peace and live a fulfilling, rich, abundant, joyful life.

We discuss:

• Lewis’s upbringing and the impact of his older brother going to prison [2:45];
• Finding lessons in tragedy and adversity [10:45];
• Lasting trauma from being sexually abused at age 5 [13:15];
• Inflection point that drove Lewis to seek help, and a beautiful experience at a therapeutic workshop [16:45];
• A powerful workshop on emotional intelligence jump started Lewis’s healing journey [27:30];
• How being authentic can strengthen bonds with family and bring inner peace [39:30];
• Comparing adversity with trauma and finding meaning in struggle [45:15];
• Association between adverse childhood events and diseases in adulthood [56:15];
• How addressing his issues with intimate relationships helped Lewis overcome physical pain related to his past trauma [59:15];
• Healing is a journey that takes time and requires courage to face your fears and insecurities [1:08:45];
• How Lewis thinks about mortality and uses it as motivation to pursue his dreams [1:13:00];
• How anyone can benefit from therapy or coaching, and Lewis’s advice for finding inner peace [1:22:45];
• Lewis’s newest book, The Greatness Mindset [1:29:15]; and
• More.

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Siddhartha Mukherjee is an oncologist, Pulitzer Prize-winning author, and previous guest on The Drive. In this episode, Sid discusses many of the subjects of his latest book, The Song of the Cell, including the incredible discovery of the cell and how it transformed medicine. He explains the evolutionary drive to go from single-cell to multicellular life and unpacks the four different types of cell-based therapies and the problems they are attempting to solve. He also provides the latest in gene therapy, such as CRISPR, and the ethical questions around human gene editing. Additionally, he touches on a number of fascinating topics, such as the challenges of medical science, the human brain, learning styles, his writing process, mental health, and more.

We discuss:

• How the cell brings the genome to life, and how Sid’s recent book fits into his prior work to tell a story [2:30];
• How the germ theory of disease and an understanding of the cell fueled a big leap in medicine [9:45];
• What is the evolutionary drive for multicellular life? [17:15];
• Four types of cell therapies and the challenges of gene therapy [26:00];
• CAR T-cell therapy: promising gene therapy for cancer [36:30];
• The possibility of using gene therapy to treat germline mutations like sickle cell disease [41:45];
• The incredible revolution of gene editing with CRISPR [45:15];
• Ethical questions around human gene editing [52:30];
• The complex role of genetics in mental illness [1:01:30];
• Two types of problems in science: the “eye in the sandstorm” problem and the “sand in the eye” problem [1:06:15];
• Understanding neural networks: an example of the “sand in the eye” problem being solved [1:08:45];
• Importance of learning by doing: comparing the learning styles of a doctoral student to a medical student [1:16:30];
• Sid’s unique and brilliant style of writing [1:20:45];
• Falling as the leading cause of accidental death: a liability of multicellular existence [1:25:00];
• Sid’s struggle with depression and his desire to change the stigma around mental illness [1:29:15]; and
• More.

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Anthony Hipolito is a sheriff’s deputy in Hays County, Texas with over 24 years of experience in law enforcement. In this episode, Anthony discusses his work to spread awareness about illicit fentanyl use and the drastic increase in accidental overdoses, especially in young people. Anthony explains the deadly nature of fentanyl, including how many counterfeit drugs are now being laced with deadly doses of fentanyl. He breaks down how fentanyl is being brought to the US and how younger and younger kids are being targeted. Additionally, Anthony discusses his goal of spreading awareness to our communities and provides important advice for what parents can do.

We discuss:

• Anthony’s life of service in law enforcement [5:30];
• Fentanyl: medical use, recreational use, and the recent rise in prevalence [8:30];
• The story of a teenager dying from an accidental overdose of fentanyl [16:30];
• The scope of deaths being caused by accidental overdoses (the majority of which are from fentanyl) [23:00];
• How young kids are being targeted, and how fentanyl makes it across our borders and gets distributed [28:30];
• What happens to a person when they overdose [35:30];
• Whether laws around drug possession are helping or hurting, and the need to focus on helping people that feel the need to take these counterfeit drugs [37:00];
• How fentanyl is being added to all kinds of drugs that you wouldn’t expect [42:45];
• What can we do as parents? [47:15];
• Narcan: a treatment for opioid overdoses [50:15];
• Importance of awareness, having conversations with kids early in life, and other key takeaways for parents [56:30]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter reviews the last 12+ years of his DEXA scan results revealing the changes to his body composition, lean muscle mass, visceral adipose tissue, and more. He explains how his body composition and blood biomarkers were impacted by the various dietary approaches (ketosis, fasting, high protein, etc.) and training protocols (primarily endurance, primarily strength training, etc.) he has undertaken over the years. Furthermore, Peter explains his planned approach moving forward following his most recent DEXA scan in late 2022.

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

We discuss:

• DEXA scans and other methods for tracking body composition [2:30];
• Importance of tracking data over time to see trends [10:15];
• DEXA scans in 2011: swimming, lifting, and a carb-restricted diet [12:45];
• DEXA scans 2012-2014 during Peter’s time on a strict ketogenic diet [18:30];
• Blood biomarkers for evaluating metabolic health [25:15];
• DEXA scan in 2020 after several years of regularly engaging in time-restricted feeding and prolonged fasting protocols [28:45];
• DEXA scan in 2021: shifting focus to adding muscle, high-protein diet, and more strength training [40:00];
• DEXA scan in early 2022: eating additional calories and adding blood flow restriction (BFR) to his workouts [44:45];
• DEXA scan in late 2022: a dramatic change following shoulder surgery, and the impact of stress [48:30];
• Peter’s approach moving forward following his most recent DEXA scan [59:15];
• A rundown of the various nutritional methods of energy restriction [1:06:15];
• Current thoughts on fasting and key takeaways [1:09:45]; and
• More.

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Ric Elias, the founder of Red Ventures and previous guest on The Drive, returns to discuss his evolving insights on time, relationships, parenting, and how to make the most of the gift of life. In this episode, he reflects on the changes he’s made since his near-death experience during the crash landing of Flight 1549 on the Hudson River in 2009. Ric reveals many keys to living a rich life, such as aiming for continuous growth, approaching life with true intentionality, and valuing our time in accordance with that. He talks about relationships as the core of a rich life and provides insights on parenting and how we should think about our relationship with our kids as they grow older. Finally, Ric discusses the importance of staying true to yourself, the value in struggle, and finding meaning in helping others.

We discuss:

• Reflecting on the tumultuous last few years and how his experience on Flight 1549 helped him [2:30];
• Parenting: a game of tug of war that you must ultimately lose [5:00];
• Importance of friendship and Ric’s motivation for his recent “Friends summit” [8:00];
• The impact of looking forward and focusing on growth on finishing life well [13:00];
• How our relationships with our children evolve as they grow, and a new perspective on purpose [21:15];
• Living with complete intention for a rich life, valuing your time, and other life lessons inspired by Ric’s near-death experience on Flight 1549 [31:15];
• How society’s relationship with work has changed, the pros and cons of remote and hybrid working environments, and an update on his company “Red Ventures” [37:45];
• Ric’s dedication to philanthropy [44:45];
• The Golden Door Scholars program aiming to help undocumented students with education and a future career [50:30];
• Ric’s journey in health and longevity [59:15];
• Letting go of guilt and loving yourself [1:02:30];
• The relationship between happiness and wealth [1:06:45];
• Playing the “infinite game,” staying true to oneself, and ignoring the negative [1:09:15];
• Speculating on the meaning of success, the drivers of greatness, and the value of struggle [1:16:00]; and
• More.

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Dan Rader is a Professor at the Perelman School of Medicine at the University of Pennsylvania, where he conducts translational research on lipoprotein metabolism and atherosclerosis with a particular focus on the function of high-density lipoproteins (HDLs). In this episode, Dan goes in-depth on HDL biology, including the genesis of HDL, its metabolism, function, and how this relates to atherosclerotic cardiovascular disease (ASCVD). He explains why having high HDL-C levels does not directly translate to a low risk of cardiovascular disease and reveals research pointing to a better way to measure the functionality of HDL and predict disease risk. He also goes into detail on the role of HDL in reverse cholesterol transport and the benefits this has for reducing ASCVD. Additionally, Dan discusses the latest thinking around the association between HDL cholesterol and neurodegenerative diseases and ends the conversation with a discussion of how the latest research on HDL provides a promising outlook for ongoing trials and future therapeutic interventions.

We discuss:

• The lipidology of apoB and apoA [4:00];
• A primer on the high-density lipoprotein (HDL): genesis, structure, and more [9:30];
• How the lipoprotein system differs in humans compared to other mammals [20:00];
• Clarifying the terminology around HDL and apoA [25:30];
• HDL metabolism [31:45];
• CETP inhibitors for raising HDL-C: does it reduce CVD risk? [34:45];
• Why it’s so important to have hard outcome trials in the field of cardiovascular medicine [42:30];
• SR-B1: an HDL receptor important for cholesterol efflux [48:00];
• The association between HDL levels and atherosclerosis: are they causally linked? [53:15];
• How insulin resistance is impacting HDL, and how HDL-C provides insights into triglyceride metabolism [58:00];
• Disappointing results from the studies of niacin—a drug that raises HDL-C and lowers apoB [1:08:15];
• HDL lipidation, dilapidation, and reverse cholesterol transport [1:12:00];
• Measuring the cholesterol efflux capacity of HDL: a better predictor of ASCVD risk than HDL-C? [1:22:00];
• A promising new intervention that may promote cholesterol efflux and reverse cholesterol transport [1:32:45];
• The association between HDL cholesterol and neurodegenerative diseases [1:34:00];
• Challenges ahead, a promising outlook, and the next frontier in lipidology [1:44:45]; and
• More.

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Andy Galpin is a Professor of Kinesiology at California State University at Fullerton, where he studies muscle adaptation and applies his research to work with professional athletes. In this episode, Andy sets the foundation for the conversation by discussing the anatomy, microanatomy, and physiology of the muscle, including explaining what it actually means to undergo hypertrophy of the muscle. He then explains the difference between power, strength, speed, and hypertrophy and how those differences relate to what's happening at the cellular level and the functional unit level. Additionally, he discusses energy sources for muscles, the importance of protein for muscle synthesis, the various types of muscle fibers, and the factors that determine one’s makeup of muscle fibers. Finally, Andy wraps the conversation with how he would design a program for an untrained person committed to adding muscle and functional strength for longevity.

We discuss:

• Andy’s path to expertise in exercise [3:30];
• Contrasting strength, power, and force production and how they inform us about training for longevity [9:30];
• Muscle energetics: Fuels that provide energy to muscles, and the importance of protein [17:45];
• The structure and microanatomy of muscle, muscle fibers, and more [29:30];
• Energy demands of skeletal muscle compared to other tissues in the body [39:45];
• How a muscle contraction works and why it requires ATP [48:00];
• Muscle fibers: modulation between fiber types with movement and changes in fibers with training and aging [53:15];
• Andy’s study of twins demonstrating the difference in muscle fibers between a trained and untrained individual [1:02:30];
• Microanatomy of fast-twitch and slow-twitch muscle fibers [1:11:15];
• Factors that determine one’s makeup of muscle fibers and how adaptable they are with training [1:22:15];
• Hypertrophy and what happens at the cellular level when a muscle grows [1:30:00];
• How athletes quickly cut water weight and the rehydration process [1:37:30];
• Different types of athletes [1:47:30];
• Training advice for a hypothetical client who’s untrained and wants to add muscle and functional strength for longevity [1:49:45];
• Changes in muscle and muscular function that occur with aging [1:53:45];
• Training plan for the hypothetical client [1:59:30];
• What drives muscle hypertrophy? [2:12:15];
• How to properly incorporate isometric exercises into a workout [2:19:00];
• Additional training tips: movement patterns, how to finish a workout, and more [2:25:45];
• Ways to incorporate high heart rate exercise into a workout plan [2:28:45]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter answers questions related to the leading cause of death in both men and women—atherosclerotic cardiovascular disease (ASCVD). He highlights the most important risk factors for ASCVD, such as apoB, LDL, hyperinsulinemia, and Lp(a), and explains the mechanism by which they confer risk and how these factors are interrelated. Peter also dives deep into the data around apoB to try to answer the question of how much residual risk is conferred for ASCVD through metabolic dysfunction once you correct for apoB. He also looks at the data around lifetime risk reduction of ASCVD in the context of low apoB.

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

We discuss:

• A racecar analogy for understanding atherosclerotic cardiovascular disease [2:00];
• Defining and differentiating apoB and LDL-C [10:00];
• The interrelated nature of insulin levels, apoB, triglycerides, and ASCVD parameters [13:00];
• Another way that hyperinsulinemia plays a role in endothelial dysfunction [18:00];
• Why Peter uses the oral glucose tolerance test (OGTT) with all patients [20:15];
• Is there any evidence that hyperinsulinemia is an independent contributor to ASCVD? [23:00];
• Thinking through risk in the context of high-fat diets resulting in improved metabolic metrics but with an elevation of apoB/LDL-C [27:30];
• Thinking through risk in the context of low apoB but higher than normal triglyceride levels [32:15];
• The importance of lowering apoB for reducing ASCVD risk [38:15];
• Data on men and women with familial hypercholesterolemia that demonstrates the direct impact of high apoB and LDL-C on ASCVD risk [47:45];
• Importance of starting prevention early, calcium scores, and explaining causality [52:30];
• Defining Lp(a), its impact on ASCVD risk, and what you should know if you have high Lp(a) [56:30];
• Lp(a) and ethnic differences in risk [1:00:30];
• Why someone with elevated Lp(a) should consider being more aggressive with apoB lowering strategies [1:05:00];
• Addressing the common feeling of hesitancy to taking a pharmacologic approach to lower ASCVD risk [1:07:15];
• Peter’s take on the 2022 Formula 1 season and thoughts on 2023 [1:15:15]; 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 [3:15];
• A missed experience and feeling of regret that shaped Bill’s thinking [14:15];
• Thinking in terms of time, and the relationship between money, time, and health [17:00];
• Solving for net fulfillment and allocating your time based on the seasons of life [27:15];
• How Bill thinks about risk, opportunity costs, and the difference between fear and risk tolerance [35:30];
• Optimizing for fulfillment, finding purpose outside of work, and more [41:45];
• Thinking about the order of experiences you want to have based on seasons of life [50:00];
• Bill’s unique perspective on philanthropy and a more impactful way to give money away [54:45];
• Applying the principles in ‘Die With Zero’ to maximize fulfillment [1:04:00];
• How to break out of living life on autopilot [1:14:30];
• When should your net worth peak? [1:18:00];
• Taking calculated risks [1:21:30];
• Bill shares a lesson from his incredible birthday [1:25:15];
• How Bill’s philosophy has evolved since writing Die With Zero [1:34:00]; and
• More.

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Kellyann Niotis is a neurologist specializing in risk reduction strategies for the prevention or slowing of neurodegenerative disorders. In this episode, Kellyann provides an overview of the various diseases associated with neurodegeneration, including, but not limited to, Alzheimer’s disease, Lewy body dementia, and Parkinson’s disease. She goes in-depth on Parkinson’s disease, explaining its pathology, role in movement capacity, very early warning signs, and the role of anxiety and sleep. Similarly, she provides an in-depth discussion of Alzheimer’s disease, including the latest in screening, genetics, and tools/strategies for prevention. She ties the discussion together by explaining the differences and commonalities among the various diseases of neurodegeneration and the potential causative triggers, and she highlights the importance of early screening, cognitive testing, and taking the proper steps to lowering the risk of disease.

We discuss:

• Kellyann’s background, training, and interest in the brain [2:30];
• A primer on neurodegeneration: different types, prevalences, interventions, and more [5:30];
• Overview of Parkinson’s disease and neuromuscular disorders including ALS [16:00];
• Parkinson’s disease: early signs, diagnosis, genetics, causative triggers, and more [17:30];
• Interventions to delay or avoid Parkinson’s disease, and the role of sleep and anxiety [31:15];
• The challenge of standardizing early interventions for Parkinson’s disease without a clear biomarker [39:45];
• Alzheimer’s disease: pathophysiology and the role of the amyloid and tau proteins [47:45];
• Can PET scans be informative for diagnosing Alzheimer’s disease? [51:15];
• Tau accumulation in the brain, tau scans, serum biomarkers, and possible early detection of Alzheimer’s disease pathology [57:00];
• Cognitive testing explained [1:03:30];
• The challenge of identifying the stage of the disease and why drugs have not shown efficacy [1:14:45];
• The association between hearing loss and dementia [1:17:45];
• The relationship between oral health and neurodegenerative diseases [1:21:30];
• Genetic risk for Alzheimer’s disease [1:24:45];
• What one’s mitochondrial haplotype can reveal about their risk of neurodegenerative disease [1:32:30];
• The positive impact of exercise on brain health [1:37:00];
• High blood pressure as a risk factor [1:40:00];
• Why women are disproportionately affected by Alzheimer’s disease [1:44:15];
• Final takeaways: the future of understanding neurodegenerative disease and further reducing risk [1:46:45]; and
• More.

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James Clear is the author of the New York Times bestseller Atomic Habits. His extensive research into human behavior has helped him identify key components of habit formation and develop the “Four Laws of Behavioral Change.” In this episode, James provides insights into how both good and bad habits are formed, including the influence of genetics, environment, social circles, and more. He points to changes one can make to cultivate more perseverance and discipline and describes the profound impact habits can have when tying them into one’s self-identity. Finally, James breaks down his “Four Laws of Behavioral Change” and how to use them to create new habits, undo bad habits, and make meaningful changes in one’s life.

We discuss:

• Why James became deeply interested in habits [1:45];
• Viewing habits through an evolutionary lens [6:00];
• The power of immediate feedback for behavior change, and why we tend to repeat bad habits [9:15];
• The role of genetics and innate predispositions in determining one’s work ethic and success in a given discipline [14:30];
• How finding one’s passion can cultivate perseverance and discipline [23:15];
• Advantages of creating systems and not just setting goals [29:15];
• The power of habits combined with self-identity to induce change [36:30];
• How a big environmental change or life event can bring on radical behavioral change [50:30];
• The influence of one’s social environment on their habits [54:15];
• How and why habits are formed [1:00:30];
• How to make or break a habit with the “Four Laws of Behavior Change” [1:09:30];
• Practical tips for successful behavioral change—the best strategies when starting out [1:16:15];
• Self-forgiveness and getting back on track immediately after slipping up [1:30:30];
• Law #1: Make it obvious—Strategies for identifying and creating cues to make and break habits [1:39:45];
• Law #2: Make it attractive—examples of ways to make a new behavior more attractive [1:47:45];
• Law #3: Make it easy—the 2-minute rule [1:58:45];
• Law #4: Make it satisfying—rewards and reinforcement [2:03:30];
• Advice for helping others to make behavioral changes [2:06:00]; and
• More.

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Layne Norton holds a Ph.D. in nutritional sciences and is a physique coach, natural bodybuilder and powerlifter, and two-time previous podcast guest. In this episode, Layne discusses his training as a powerlifter and shares training principles that non-powerlifters can apply to improve muscle strength and mass. Layne goes in-depth on creatine supplementation, including the benefits for lean mass and strength, and addresses the common arguments against its regular usage. Additionally, Layne touches on many areas of nutrition, including how his opinions have changed on certain topics. Layne also touches on the subjects of protein, fiber, and fat in the diet, as well as the different tools and dietary approaches for energy restriction.

We discuss:

• The sport of powerlifting and Layne’s approach during competitions [2:30];
• Training for strength: advice for beginners and non-powerlifters [13:15];
• Low-rep training, compound movements, and more tips for the average person [23:15];
• How strength training supports longevity and quality of life: bone density, balance, and more [28:15];
• Peak capacity for strength as a person ages and variations in men and women [33:00];
• Effects of testosterone (endogenous and exogenous) on muscle gain in the short- and long-term [36:45];
• How Layne is prepping for his upcoming IPF World Masters Powerlifting competition [44:00];
• Creatine supplementation [54:30];
• How important is rep speed and time under tension? [1:05:30];
• Validity of super slow rep protocols, and the overall importance of doing any exercise [1:12:45];
• Navigating social media: advice for judging the quality of information from “experts” online [1:23:00];
• Layne’s views on low-carb diets, the tribal nature of nutrition, and the importance of being able to change opinions [1:34:45];
• Where Layne has changed his views: LDL cholesterol, branched-chain amino acid supplementation, intermittent fasting, and more [1:42:00];
• The carnivore diet, elimination diets, and fruits and vegetables [1:55:15];
• Fiber: Layne’s approach to fiber intake, sources of fiber, benefits, and more [2:00:15];
• Confusion around omega-6 polyunsaturated fatty acids and the Minnesota Coronary Experiment [2:05:00];
• Layne’s views on fats in the diet [2:13:00];
• Flexible dieting, calorie tracking, and the benefits of tracking what you eat to understand your baseline [2:18:00];
• The nutritional demands of preparing for a bodybuilding show [2:30:45];
• The psychological effects of aging and changes to one’s identity [2:42:00]; and
• More.

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Chris Hemsworth, best known for his role as Thor in the Marvel movies, joins Peter to discuss his recent work in the docuseries called Limitless. In the docuseries, Chris undertook extreme challenges to explore his physical and emotional limits and gain insights into longevity. In this episode, Chris discusses these many challenges—from fasting to arctic swims to 100-foot rope climbs—as well as the insights that he gained from each. Peter, who also played a role in the docuseries, guides Chris through the science of longevity, including what Chris’s APOE-ε4 genotype means for his risk of Alzheimer’s disease. Additionally, Chris describes how his outlook on health, happiness, work-life balance, and more have changed from his experience on Limitless.

We discuss:

• Limitless: how Chris got involved and his overall experience filming the docuseries [3:00];
• “Fasting” ‒ ep. 3 of Limitless in which Chris attempts a 4-day fast [8:15];
• “Shock” ‒ ep. 2 of Limitless in which Chris swims in the Arctic Ocean [12:15];
• Cold exposure: the potential physical and mental benefits [19:30];
• “Strength” ‒ ep. 4 of Limitless in which Chris explores how muscle can improve longevity [21:15];
• The APOE-ε4 genotype and Alzheimer’s disease risk [31:30];
• How Chris uses sauna [39:45];
• “Acceptance” - ep. 6 of Limitless in which Chris explores the meaning of life by contemplating death [42:15];
• Chris’s new perspective on work-life balance [52:00];
• “Stress-Proof” - ep. 1 of Limitless in which Chris learns about the impact of stress and how to manage it [54:30];
• Chris reflects on his intrinsic motivation driven by both fear and purpose [58:00];
• Chris reflects on his career arc and how his presence as an actor has evolved [1:01:15];
• How Chris’s outlook has changed since filming Limitless [1:05:00]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter answers a number of questions on optimizing sleep. He describes his pre-bedtime routine, how he utilizes a sauna, and his current regimen of medicines and supplements for improving sleep time and quality. He goes in depth on each of the molecules that have shown promise in boosting sleep, including their mechanisms of action as well as any noteworthy contraindications. Peter also discusses sleep wearables, including both the positives and potential negatives of using such trackers, 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 on our website at the AMA #42 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Peter’s current pre-bedtime routine [3:30];
• Sauna: Peter’s routine, sleep benefits, and tradeoffs [10:45];
• Importance of keeping an open mind as new information arrives [16:15];
• Importance of reducing stimulation leading up to bedtime [19:30];
• Medications that can enhance sleep: mechanisms of action, contraindications, risks, and Peter’s regimen [20:30];
• Why medications can enhance sleep, but should not replace good sleep habits [34:45];
• Sleep supplements: mechanisms of action, contraindications, and Peter’s regimen [37:30];
• Temperature during sleep, cooling devices, mattresses, and more [53:00];
• A tip to help avoid straining your back in the morning [59:15];
• Contrasting polysomnography with wearable sleep trackers [1:00:45];
• Sleep tracking wearables: interpreting metrics, and the pros and cons of trackers [1:04:30];
• Final takeaways on sleep [1:16:30]; and
• More.

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Alton Barron is an orthopedic surgeon specializing in the shoulder, elbow, and hand. In this episode, Alton breaks down the anatomy of the upper extremities and discusses the most common injuries associated with this area of the body. He explains in detail how he examines the shoulder, elbow, and hand to find the source of the pain and lays out the non-surgical and surgical treatment options as well as the factors that determine whether surgery is appropriate. Additionally, Alton describes the surgical procedures that, when done appropriately, can lead to tremendous reduction of pain and improvement in function.

We discuss:

• Alton’s path to orthopedic surgery [3:45];
• Evolution of orthopedics and recent advances [8:45];
• Anatomy of the upper extremities [13:30];
• Rotator cuff injuries, shoulder joint dislocation, and more [21:15];
• Peter’s shoulder problems [31:30];
• The structure of the biceps and common injuries [35:30];
• Labrum tears in the shoulder and natural loss of cartilage with usage and time [38:15];
• Shoulder evaluation with MRI vs. physical exam, diagnosing pain, and when to have surgery [41:30];
• How anatomical variation can predispose one to injury and how screening may help [50:30];
• Pain generators in the shoulder, and the important nuance of the physical exam [56:00];
• Frozen shoulder [1:05:15];
• Shoulder pain that originates in the neck [1:11:15];
• Surgical treatments for a labral tear, and factors that determine whether surgery is appropriate [1:16:00];
• Repairing the rotator cuff [1:29:15];
• Are platelet-rich plasma (PRP) injections or stem cells beneficial for healing tears? [1:38:15];
• Repair of an AC joint separation [1:45:15];
• Total shoulder replacement [1:55:45];
• The elbow: anatomy, pain points, common injuries, treatments, and more [2:05:30];
• How Tommy John surgery revolutionized Major League Baseball [2:17:15];
• History of hand surgery and the most significant advancements [2:22:15];
• The hand: anatomy, common injuries, and surgeries of the hand and wrist [2:29:30];
• Carpal tunnel syndrome [2:40:00];
• Other common injuries of the hand and forearm [2:47:15];
• Grip strength [2:55:15];
• Arthritis in the hands [2:59:30];
• Trigger finger [3:07:45];
• Nerve pain, numbness, and weakness in the upper limbs [3:14:00];
• The Musician Treatment Foundation [3:22:00];
• Gratitude and rucking [3:34:15]; and
• More.

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Gerald Shulman is a Professor of Medicine, Cellular & Molecular Physiology, and the Director of the Diabetes Research Center at Yale. His pioneering work on the use of advanced technologies to analyze metabolic flux within cells has greatly contributed to the understanding of insulin resistance and type 2 diabetes. In this episode, Gerald clarifies what insulin resistance means as it relates to the muscle and the liver, and the evolutionary reason for its existence. He goes into depth on mechanisms that lead to and resolve insulin resistance, like the role of diet, exercise, and pharmacological agents. As a bonus, Gerald concludes with insights into Metformin’s mechanism of action and its suitability as a longevity agent.

We discuss:

• Gerald’s background and interest in metabolism and insulin resistance (2:30);
• Insulin resistance as a root cause of chronic disease (6:30);
• How Gerald uses NMR to see inside cells (10:00);
• Defining and diagnosing insulin resistance and type 2 diabetes (17:15);
• The role of lipids in insulin resistance (29:15);
• Confirmation of glucose transport as the root problem in lipid-induced insulin resistance (38:15);
• The role of exercise in protecting against insulin resistance and fatty liver (48:00);
• Insulin resistance in the liver (1:05:00);
• The evolutionary explanation for insulin resistance—an important tool for surviving starvation (1:15:15);
• The critical role of gluconeogenesis, and how it’s regulated by insulin (1:20:30);
• Inflammation and body fat as contributing factors to insulin resistance (1:30:15);
• Treatment approaches for fatty liver and insulin resistance, and an exciting new pharmacological approach (1:39:15);
• Metformin’s mechanism of action and its suitability as a longevity agent (1:56:15); and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter answers a wide variety of questions, starting with a discussion on the evolution of medicine and the hopeful transition to “Medicine 3.0.” Peter recounts his unique career path and explains how he assesses risk and utilizes frameworks for decision-making. He also describes how he prioritizes his health while navigating the stresses of life, and he reviews the most exciting developments in the aging and longevity space. He finishes with some rapid-fire questions on cold plunging, strategies for lowering apoB levels, designing an exercise program for beginners, and 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 on our website at the AMA #41 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• The evolution of medicine and the transition to “Medicine 3.0” [3:00];
• Peter’s unorthodox career arc and what led him to this point [11:45];
• What does Peter consider to be his superpowers? [22:15];
• How Peter thinks about risk and explains it to his patients when making medical decisions [26:45];
• The advantage of using frameworks for decision-making [37:00];
• What advice would Peter give his 30-year old self? [42:15];
• Why longevity is such a hard problem to solve [42:30];
• The most impactful developments in the field of longevity and aging in the last 5 to 10 years [46:15];
• What is Peter most excited to see develop in the health and longevity space in the next few years? [51:30];
• Prioritizing healthy habits while navigating the stresses of life and time constraints [53:45];
• How Peter navigates periods of high stress [58:00];
• What fitness watch did Peter recently purchase? [1:03:45];
• Potential benefits of cold plunging [1:05:15];
• Advice for someone beginning an exercise program [1:07:30];
• Strategies and tactics to lower apoB levels [1:09:00];
• Interesting studies and books Peter has recently read [1:11:30]; and
• More.

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Erin Michos is an internationally-known leader in preventive cardiology and women’s cardiovascular health. In this episode, Erin discusses current trends in cardiovascular disease (CVD) through the lens of female biology and the observation that major adverse cardiac events in both sexes are on the rise. She walks through risk factors including LDL-cholesterol, apoB, and Lp(a) and makes the case for the importance of early preventative measures. She explains various interventions for reducing risk including a discussion of statins, GLP-1 agonists, PCSK9-inhibitors, and drugs that lower Lp(a). She goes in-depth on female-specific factors that contribute to CVD risk such as pregnancy, grand multiparity (having five or more children), oral contraceptives, menopause, and polycystic ovary syndrome (PCOS). Additionally, she explains her approach with patients as it relates to the use of hormone replacement therapy and provides advice for people wanting to lower risk both through lifestyle changes and medications.

We discuss:

• Erin’s background in preventive cardiology and women’s health [2:30];
• Recent trends in cardiovascular disease in women, mortality data, and how it compares to cancer [5:15];
• Why early preventative measures are critical for cardiovascular disease risk [13:15];
• ApoB as a causal agent of CVD, and why high apoB levels are not being aggressively treated in most cases [19:45];
• The rising trend of metabolic syndrome and other factors contributing to the regression in progress of reducing cardiac events [27:00];
• GLP-1 agonists—Promising drugs for treating diabetes and obesity [33:30];
• Female-specific risk factors for ASCVD (pre- and post-menopause) [37:15];
• Polycystic ovary syndrome (PCOS): prevalence, etiology, and impact on metabolic health, lipids and fertility [47:00];
• The effect of grand multiparity (having 5+ children) on cardiovascular disease risk for women [52:30];
• The impact of oral contraceptives on cardiovascular disease risk [55:00];
• The effect of pregnancy on lipids and other metabolic parameters [58:45];
• The undertreatment of women with familial hypercholesterolemia (FH) and how it increases lifetime risk of ASCVD [1:02:00];
• How concerns around statins have contributed to undertreatment, and whether women should stop statins during pregnancy [1:09:45];
• How Erin approaches the prescription of statins to patients [1:16:00];
• PCSK9 inhibitors and other non-statin drugs [1:21:15];
• Advice for the low- and high-risk individual [1:28:30];
• The impact of nutrition, stress, and lifestyle on lipids and CVD risk [1:31:00];
• Lp(a) as a risk enhancer for cardiovascular disease [1:41:15];
• The effect of menopause on cardiovascular disease risk [1:50:30];
• How Erin approaches decisions regarding hormone replacement therapy (HRT) for her patients [1:55:30];
• The urgent need for more data on women’s health [2:03:30];
• Erin’s goal of running a marathon in every state [2:09:45]; and
• More.

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In this special episode of The Drive, we have pulled together a variety of clips from previous podcasts about cardiovascular disease to help listeners understand this topic more deeply, as well as to identify previous episodes which may be of interest. In this episode, Peter highlights the importance of understanding cardiovascular disease and why early intervention is critical. He also provides a primer on lipoproteins and explains the fallacy of the terms “good cholesterol” and “bad cholesterol.” Allan Sniderman discusses the metrics measured in routine blood work – along with the limitations of those standard panels – before explaining why apoB is a superior metric for determining risk. Additionally, Tom Dayspring explains the causal role of apoB in atherosclerotic cardiovascular disease (ASCVD) and the therapeutic goals for apoB concentration, and Peter explains how early and aggressive lowering of apoB could change the landscape of cardiovascular disease prevention.

We discuss:

• The importance of understanding atherosclerosis early in life [2:25]
• Defining ASCVD, its causes, and the role of cholesterol [8:00];
• Why early prevention of atherosclerosis is critical [13:45];
• Preventing atherosclerosis—two fatal flaws with the “10-Year Risk” approach [16:00];
• Intro to lipids and lipoproteins: why there is no “bad” or “good” cholesterol [23:00];
• Limitations of standard blood panels [35:45];
• How Mendelian randomization is bolstering the case for apoB as the superior metric for risk prediction [39:30];
• Therapeutic goals for apoB concentration [58:15];
• How early and aggressive lowering of apoB could change the course of ASCVD [1:10:45]; and
• More.

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Holly Baxter is an accredited practicing dietician (APD), competitive bodybuilder, fitness and nutrition educator, and coach. In this episode, Holly discusses her experience as an athlete and competitive bodybuilder. She also opens up about her struggles with mental health, her long battle with an eating disorder, and the important steps she’s taken in her road to recovery. From there, she explains how she would design a nutrition and training program for a hypothetical female client wanting to improve her physique through the addition of lean muscle and loss of body fat. She explains reasonable expectations for gaining muscle and the value of a “reverse diet” for maintaining weight loss, and she shares her favorite exercises. She also talks through some female-specific training considerations such as programming, reps, volume, hormone replacement therapy, and more.

We discuss:

• Holly’s background and passion for sports and nutrition [2:00];
• Holly’s struggle with depression and an eating disorder [4:30];
• Reflecting on her eating disorder, body image, and a wake up call [18:15];
• Road to recovery: therapy, meditation, self-compassion, and a breakthrough [27:45];
• The effect of competitive bodybuilding on women [39:00];
• Holly’s competition prep and how she guides her clients wanting to improve their physique [46:45];
• Training principles for muscle hypertrophy [57:00];
• Training advice for an inexperienced person wanting to build muscle [1:01:30];
• Training program for a hypothetical woman wanting to add lean muscle and lose body fat [1:04:15];
• Lower body lifts: Holly’s approach to leg workouts with clients [1:14:00];
• Upper body exercises: Holly’s approach with her clients [1:24:45];
• Importance of nutrition and protein during the muscle building phase [1:34:00];
• Changes to nutrition and training during a fat loss phase [1:40:30];
• A “reverse diet” after a cutting phase to help prevent weight gain [1:49:45];
• Female-specific training considerations: programming, reps, volume, sex hormones, and more [1:53:15];
• Holly’s future in bodybuilding and helping struggling women [2:05:45];
• Looking forward: Holly’s focus on longevity, bone mineral density, and wellness [2:08:15]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter discusses the importance of understanding body composition and explains how to interpret the most important metrics revealed by a DEXA scan, such as lean muscle tissue mass, visceral adiposity tissue mass, bone mineral density, and more. He discusses common concerning trends in these metrics as well as strategies to address them. He goes through DEXA scan results of both male and female patient case studies and explains the prescribed intervention for each patient. Additionally, Peter answers numerous questions about dietary protein including how much we need, when we need it, and how intake should be divided throughout the day to optimize muscle protein synthesis. Finally, Peter provides his updated point of view on time-restricted feeding and fasting and how his personal approach and recommendations for patients has evolved.

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 on our website at the AMA #40 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Interpreting DEXA scans: important metrics, radiation levels, and more [2:15];
• DEXA metrics: Bone mineral density (BMD) [12:00];
• DEXA metrics: Visceral adipose tissue (VAT) [14:30];
• DEXA metrics on lean tissue: appendicular lean mass index (ALMI) and fat-free mass index (FFMI) [20:45];
• Concerning trends in BMD, VAT, & muscle mass revealed through DEXA scans [24:15];
• Muscle and lean tissue loss with age and how to overcome anabolic resistance [29:15];
• Female patient case studies: DEXA scan results and prescribed interventions [35:00];
• Male patient case studies: DEXA scan results and prescribed interventions [42:45];
• Protein consumption: recommended daily intake, Peter’s personal approach, timing around workouts, and more [48:15];
• What to look for with protein supplements [53:15];
• Protein intake: optimal timing and how it should be divided throughout the day [55:30];
• Time-restricted feeding (TRF): Peter’s updated perspective [57:45];
• Three strategies for reducing energy intake in over-nourished patients [1:03:15];
• Prolonged fasting: potential benefits and tradeoffs [1:07:15];
• A protein-supplemented version of time-restricted feeding (TRF) [1:09:30];
• Theories about time-restricted feeding (TRF) and its positive influence on sleep and circadian rhythm [1:12:00]; and
• More.

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Arthur Brooks is a social scientist, professor at Harvard University, a columnist for The Atlantic, and the bestselling author of From Strength to Strength. In this episode, Arthur explains how intelligence changes as we get older, and how to take advantage of this to maximize our happiness and success. He distills truths about the meaning of happiness and its three main components: enjoyment, satisfaction, and purpose. He goes into detail about many of the keys to a happy life, including the importance of cultivating virtuous relationships. On the flip side, Arthur warns of the dangers of social comparison, “success addition,” and the four worldly idols—money, fame, power, and pleasure—that drive many of us. Additionally, Arthur provides examples of exercises that can guide one in the right direction, overcome fear, and cultivate habits that can lead to a happier life.

We discuss:

• Insights from Arthur’s career as a professional French horn player [2:15];
• A radical shift away from music to a Ph.D. in quantitative policy [12:00];
• Personal experience with shifting intelligence: fluid vs. crystallized intelligence [16:45];
• An epiphany from a chance encounter on an airplane that shaped Arthur’s thinking [22:00];
• The three main “macronutrients” of happiness [25:00];
• Exploring the “purpose” component of happiness [29:00];
• The importance of having a partner and true friendships [32:00];
• The makeup of a true friendship, and why men tend to struggle with making real friends [36:45];
• The “satisfaction” component of happiness and the importance of “wants management” [42:15];
• The tyranny of social comparison [47:45];
• Insights into happiness through Chinese art, and the concept of a “reverse bucket list” [51:45];
• An exercise demonstrating the importance of relationships with others and the need to work on them [55:30];
• The four main idols that drive us: money, fame, power, and pleasure [1:01:15];
• Success addiction, workaholism, and their detriment to happiness [1:04:00];
• A radical approach to overcome fear—the antithesis to love and happiness [1:14:00];
• Ancient Hindu advice for the perfect life [1:26:30];
• The end result of getting caught in the 4 idols [1:31:45];
• The complexity of happiness [1:33:30]; and
• More.

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Michael Easter is the author of the bestseller, The Comfort Crisis. He’s also a journalist, Professor of Journalism at UNLV, and a leading voice on how humans can integrate modern science and evolutionary wisdom for improved health, meaning, and performance in life and at work. In this episode, Michael first talks about his upbringing, including his parents' struggle with alcoholism, his father leaving when he was young, and how these things impacted Michael's own struggle with alcoholism. He explains what led to his realization that we are in a “crisis of comfort” and how the removal of many of life’s discomforts through advancements in modern society may actually be a leading contributor to many of our most urgent physical and mental health issues. He explains the benefits of challenging oneself and the immense positive carryover which can come from doing things we find difficult. He describes the consequences of technology like smartphones, which have effectively eliminated boredom—a discomfort that comes with many benefits. He tells the story of a profound experience at an elk hunt that changed Michael’s thoughts around life and death, how happiness can thrive in places without all of the modern comforts of the West, and why we’re hardwired for stress and what to do about it. They conclude with a conversation around rucking, an activity with many physical and mental benefits.

We discuss:

• The value in doing something difficult [2:30];
• Michael’s upbringing with a single parent and alcoholism [5:45];
• Michael’s battle with alcoholism and his experience with quitting drinking [10:00];
• Origin of the idea that we are in a crisis of comfort [20:30];
• The death of boredom in modern society [28:45];
• The benefits of boredom [36:00];
• The value of disconnecting and being in nature [39:15];
• Changing the dynamic of how we think about food and the story of Peter’s daughter’s first hunt [43:45];
• How a profound experience at an elk hunt changed Michael’s thoughts about life and death [49:15];
• How happiness can thrive in places without all of the modern comforts of the West [57:15];
• Why we’re hardwired for stress, and the responsibility that comes with our level of comfort [1:05:30];
• How perspective on the timescale of our lives in relation to history can impart positive changes [1:14:00];
• The benefit of challenging oneself and the positive carryover it can have [1:19:45];
• The many benefits of rucking [1:28:45];
• Tips for rucking: ideal load, type of pack, and other considerations [1:38:00];
• Parting thoughts on the downside of comfort and benefits of difficult things [1:43:00]; and
• More.

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Don Layman is a Professor of Food Science and Human Nutrition at the University of Illinois Urbana-Champaign. He has spent the past 40 years investigating the role of dietary protein in muscle protein synthesis. In this episode, Don describes how his decades of research have shaped his thinking around protein, muscle, anabolic factors, metabolism, and more. He explains the recommended dietary allowance (RDA) for protein: what it is, how it came about, and how it should serve only as a guide for the minimum protein necessary for survival rather than as an optimal level of protein intake. He provides an overview of the essential amino acids, explains the nuances of animal versus plant protein, and provides insights for determining protein quality, absorption rates, and how to best track your intake. He discusses the ideal timing of protein intake in relation to resistance exercise, how protein should be distributed among meals, and how limitations in protein utilization per sitting can impact those practicing time-restricted eating. Additionally, Don shares results from his clinical trials, including how a high-protein diet fared in terms of fat loss, and explains the differences in protein utilization between adolescents and adults and how the problem of reduced efficiency of protein utilization in older adults can be overcome.

We discuss:

• Don’s background: from growing up on a farm to studying nutritional biochemistry [2:30];
• Don’s philosophy on nutrition, muscle, and metabolism [6:30];
• The controversial relationship between saturated fat and atherosclerosis [18:15];
• The basics of protein and amino acids [25:45];
• Origin and limitations of the current recommended dietary allowance (RDA) for protein intake [32:15];
• Protein sources: determining quality, absorption rates, and how to track intake [41:15];
• Leucine, lysine, and methionine: three important essential amino acids [48:00];
• The vital role of ruminant animals in the production of quality protein [53:15];
• The differing needs and impacts of dietary protein for a 16-year old compared to a 65-year old [59:30];
• Consequences of protein deficiency in childhood [1:06:30];
• Muscle protein synthesis: ideal timing, small meals vs. big meals, and more [1:12:45];
• Protein needs of children [1:19:45];
• How important is timing protein intake around training? [1:24:15];
• The role of leucine in fatty acid oxidation by muscle [1:28:15];
• High protein diets for fat loss: Results from Don’s clinical trials [1:31:30];
• Influence of industry funding on nutrition studies [1:43:45];
• Don’s thoughts on plant-based and synthetic “meats” [1:48:45];
• Problems with epidemiological studies of dietary protein [1:56:30];
• More.

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In this “Ask Me Anything” (AMA) episode, Peter describes what it means to exercise with the goal of longevity in mind, including his personal goals, exercise framework, and how he is optimizing for what he refers to as the “Centenarian Decathlon.” He explains the various types of cardiovascular training and how to partition your time between intensity levels (i.e., zone 2 training vs. zone 5 training) to optimize cardiorespiratory benefit. Additionally, Peter dives deep into questions around VO2 max, such as why it’s critical for longevity, how to improve it, and the value in starting VO2 max optimization early in life.

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 on our website at the AMA #39 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Exercise topics to be discussed [1:45];
• Peter’s exercise goals, and the Centenarian Decathlon [4:00];
• Peter’s exercise framework, and how he tracks his MET hours [8:30];
• How to partition your time between low and high intensity exercise to optimize results [13:15];
• Zone 2 exercise: ideal training methods and how to determine your zone 2 level [23:15];
• Rucking as a versatile mode of exercise [31:45];
• Zone 5 exercise: modalities of training, time per week, and other considerations [34:30];
• The importance of knowing your VO2 max, and methods for estimating it [38:15];
• Training methods for improving VO2 max, and realistic targets for improvement [46:00];
• Relationship of VO2max with age and the required fitness levels for daily life activities and exercise [52:30];
• The training necessary to maintain an elite VO2 max throughout life [58:45];
• The value in starting early: the compounding nature of fitness [1:01:45]; and
• More.

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Dr. Matt Kaeberlein is a globally recognized expert on the biology of aging and recurring on The Drive. In this episode, Matt explains his research findings on nutrition as it relates to aging and longevity, including the results from his recent review article in Science. From there, he and Peter dive deep into the literature on calorie restriction (CR), explaining the nuance, benefits for lifespan and healthspan, and potential downsides of CR. He discusses the epigenetic changes that occur with age and potential benefits and downsides of epigenetic reprogramming, often viewed as a panacea for reversing aging. Matt also explains the impact of dietary protein on aging, including the interesting dichotomy around how protein, a critical macronutrient, and rapamycin, a geroprotective molecule, have opposite effects on mTOR. Additionally, he talks about low-protein vs. high-protein diets and their effects on muscle mass and mortality, as well as the impact of IGF-1 signaling and growth hormone on lifespan.

We discuss:

• Challenges with understanding the effects of nutrition and studying interventions for aging [3:30];
• How Peter’s and Matt’s convictions on nutrition and thoughts optimal health have evolved [8:15];
• Calorie restriction for improving lifespan in animal models [16:15];
• Utility of epigenetic clocks and possibility of epigenetic reprogramming [22:00];
• Mutations and changes to the epigenome with aging [31:45];
• Epigenetic reprogramming: potential benefits and downsides and whether it can work in every organ/tissue [35:15];
• First potential applications of anti-aging therapies and tips for aging well [43:00];
• Impact of calorie restriction on the immune system, muscle mass, and strength [47:00];
• Insights from famous calorie restriction studies in rhesus macaques [55:00];
• An evolutionary perspective of the human diet [1:03:45];
• Antiaging diets: Separating fact from fiction—Matt’s 2021 review in Science [1:12:30];
• Mouse models of time-restricted feeding in the context of calorie restriction [1:19:30];
• Nutritional interventions that consistently impact lifespan in mice, and concerns around efficacy in humans [1:27:00];
• Differing impact of calorie restriction when started later in life [1:31:00];
• Lifespan extension with rapamycin in older mice [1:37:15];
• Relationship between protein intake and aging, and mouse studies showing protein restriction can extend lifespan [1:43:30];
• Impact of protein intake on mTOR, and why inhibition of mTOR doesn’t cause muscle loss [1:50:45];
• Low-protein vs. high-protein diets and their effects on muscle mass, mortality, and more [1:55:30];
• The impact of IGF-1 signaling and growth hormone on lifespan [2:06:30];
• Parting thoughts on the contribution of nutrition to healthspan and lifespan [2:19:45];
• More.

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In this special episode of The Drive, we have pulled together a variety of clips from previous podcasts with sleep expert Dr. Matthew Walker to help listeners understand this topic more deeply, as well as to identify which previous episodes featuring Matt may be of interest. In this episode, Matt gives an overview of why we sleep, the stages of sleep, and sleep chronotypes, and he provides tips to those looking to improve their total sleep and sleep efficiency. Additionally, Matt discusses the pros and cons of napping, and gives his current thinking on the effects of blue light and caffeine on sleep. Finally, Matt explains the dangers of sleeping pills and reveals what he believes are the most useful alternatives for someone struggling with sleep, such as those with insomnia.

We discuss:

• Evolutionary reasons to sleep [2:15];
• Stages of sleep, sleep cycles, and brainwaves [10:00];
• Understanding sleep chronotypes and how knowing yours could help you [25:45];
• Defining sleep efficiency and how to improve it [36:15];
• Correcting insomnia: a counterintuitive approach [38:45];
• Pros and cons of napping, and insights from the sleep habits of hunter-gatherer tribes [41:30];
• Sleep hygiene, wind-down routine, and tips for better sleep [50:15];
• The optimal room temperature and body temperature for the best sleep [59:30];
• Blue light: how Matt shifted his thinking [1:08:30];
• Caffeine: how Matt has adjusted his hypothesis [1:14:45];
• The dangers of sleeping pills, useful alternatives, and cognitive behavioral therapy for insomnia [1:19:45];
• More.

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Celia Morgan is a Professor of Psychopharmacology at the University of Exeter who has authored numerous publications on the potential therapeutic uses of ketamine in mental healthcare. In this episode, Celia dives deep into the neurobiology of ketamine, how it affects users, and how it differs from other, more classical psychedelics (LSD, MDMA, PCP, and psilocybin). She explains the potential promise of ketamine as a treatment for recalcitrant depression and addiction, and she details the results from her clinical trials in these areas. She discusses the importance of using ketamine in combination with psychotherapy to maximize its benefits, the potential risks associated with ketamine use, and advice for those interested in the therapeutic use of ketamine.

We discuss:

• Celia’s training and interest in ketamine [2:15];
• The history of ketamine, medical uses, and use as a party drug [3:30];
• Neurobiology and pharmacology of ketamine [8:15];
• Ketamine regulation and abuse, and how it compares with psychedelics and other molecules [18:15];
• Ketamine as a therapeutic for depression [30:45];
• The brain under the influence of ketamine and theoretical mechanisms for its anti-depressive effects [48:00];
• Risks and concerns with overusing ketamine, and what an intermittent or maintenance dose might look for a patient [57:15];
• Treating addiction with ketamine: Celia’s studies of alcohol dependance [1:04:00];
• Advice for people considering the therapeutic use of ketamine [1:19:45];
• More.

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Shireen Rizvi is a Professor of Clinical Psychology and Psychiatry at Rutgers University, where she is also the Director of the Dialectical Behavior Therapy Clinic. This episode focuses specifically on dialectical behavior therapy (DBT), a skills-based technique which was originally developed to treat borderline personality disorder (BPD) and has since been adapted to treat depression and other mental health conditions, as well as to help people who have difficulty with emotional regulation and self-destructive behaviors. Shireen explains the origins of DBT and how its creator, Dr. Marsha Linehan, came to find a need for something beyond cognitive behavioral therapy (CBT) when attempting to treat patients with suicidal behavior. From there, Shireen dives into how DBT works to resolve the apparent contradiction between self-acceptance and change to bring about positive changes in emotional regulation, interpersonal effectiveness, mindfulness, distress tolerance, and more. She also provides examples for how one can apply specific skills taught with DBT such as accessing the “wise mind,” applying radical acceptance, using the “DEAR MAN” technique, and utilizing an emotion regulation skill called “opposite action.” Finally, she explains how the tenets of DBT offer benefits to anyone, and she provides insights and resources for people wanting to further explore DBT.

We discuss:

• The basics of dialectical behavior therapy (DBT) and how it differs from cognitive behavioral therapy (CBT) [3:00];
• Treating depression with CBT: history, effectiveness, and how it laid the groundwork for DBT [8:15];
• Marsha Linehan’s inspiration for developing DBT [16:00];
• Explaining borderline personality disorder (and associated conditions) through the lens of DBT [20:00];
• How work with suicidal patients led to the development of DBT—a dialectic between change and acceptance [35:30];
• Details of DBT: defining the term “dialectical” and how to access the “wise mind” [44:30];
• Practicing mindfulness and radical acceptance in the context of DBT [51:00];
• Applying “radical acceptance” to tragic scenarios [1:02:00];
• The five domains of skills taught in DBT [1:07:15];
• Why Marsha chose borderline personality disorder as her focus when developing DBT [1:13:30];
• Is there any benefit in doing DBT for someone without a pathological condition? [1:15:45];
• The DEAR MAN skill of DBT [1:20:00];
• Adapting DBT skills for adolescents and families [1:31:00];
• Identifying vulnerability factors, increasing distress tolerance, and the impact of physical pain [1:33:45];
• The DBT chain analysis: assessing problem behaviors and identifying vulnerability factors [1:44:30];
• Why the regulation of emotions can be so challenging [1:50:30];
• The importance of mindfulness skills in DBT [1:53:30];
• Opposite action: an emotion regulation skill [1:57:00];
• Advice for those wanting to explore DBT [2:03:15];
• Finding a well-trained DBT therapist [2:08:15];
• More.

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In this “Ask Me Anything” (AMA) episode, Peter dives deep into the question of whether there is such a thing as “too much exercise.” He explores the theoretical “J-curve” relationship between exercise and longevity, whereby mortality risk declines with increasing activity levels only to see an uptick above a certain exercise volume threshold. While Peter maintains that exercise is perhaps the single most important tool we have to live longer and live better, he explains the challenges involved in identifying an optimal dose. He takes a hard look at studies—many of which have contradictory results—to highlight major limitations in methodology and how readers could be misled. Additionally, he discusses the rare, but real, risks associated with extreme levels of physical activity and concludes by weighing the benefits against the risks of exercise.

If you’re not a subscriber and 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 on our website at the AMA #38 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• How exercise reduces risk for all-cause mortality [2:40];
• Defining the metric called “MET” and how it’s useful for evaluating different exercises [8:00];
• The challenge in determining the optimal exercise doses and the limitations of methods used to study the effect of exercise [13:45];  
• Using VO2 max as a proxy for fitness to better predict mortality risk [19:30];
• Reviewing data which support the theory of a “J-curve” relationship between exercise and longevity [25:00];
• Importance of understanding p-values and statistical significance [33:45];
• Deconstructing the studies that show a J-curve: major limitations and how one could be misled [37:00];
• Peter’s takeaways on the theoretical “J-curve” relationship between exercise and longevity [51:30];
• Risk of sudden cardiac death from vigorous physical exertion [54:00];
• Atrial fibrillation associated with extreme levels of exercise [1:00:15];
• Parting thoughts: benefits of exercise far outweigh the risks [1:04:15]; and
• More.

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Mike Joyner is a physician-researcher and one of the world’s leading experts on human performance and exercise physiology. In this episode, Mike discusses how to combat age-related declines in health and fitness levels by using various modes of exercise to improve lifespan and healthspan. Mike explains the impact of exercise on the autonomic nervous system, blood pressure, heart rate, heart rate variability, heart rate recovery, and max heart rate. He dives deep into VO2 max, including how it’s measured, what is driving it, and how to improve it. Mike provides training insights for the average person, including training volume and exercise intensity as well as simple metrics to track. Furthermore, he gives his take on the theoretical “J-curve” relationship between exercise and longevity, as well as whether possible health dangers may be associated with excessive exercise.

We discuss:

• Mike’s training as an anesthesiologist and interest in exercise physiology [2:30];
• How exercise increases longevity [7:00];
• The impressive data on the benefits of exercise [9:45];
• The Centenarian Olympics and other ways to mitigate age-related decline in strength and stability [15:00];
• The violent dropoff in strength and activity with age and how exercise preserves fitness in old age [19:00];
• Benefits of exercise on mortality and fracture risk, and the interplay of nutrition and exercise [22:00];
• How exercise benefits the autonomic nervous system and why this plays an important role in our health [26:30];
• VO2 max, heart rate recovery, heart rate variability, and other metrics of fitness positively impacted by exercise [28:30];
• Reduction in all-cause mortality with increased fitness levels and VO2 max [32:45];
• Does the relationship between exercise and longevity follow a J-curve? [40:00];
• Mitigating age-related decline in fitness by elevating your VO2 max at a young age [46:15];
• Breaking down the variables that drive VO2 max [54:30];
• Learning from elite athletes: Training regimens, aerobic efficiency, and other impressive metrics [1:00:15];
• Health benefits of light exercise for the average person [1:09:00];
• Simple training metrics to track, and Mike’s current exercise regimen [1:11:15];
• How to boost your VO2 max, and the importance of form and tempo with interval training [1:18:15];
• Training advice for the average person [1:25:15];
• Why professional athletes have longer careers than they’ve had in the past [1:27:30];
• Use of performance-enhancing drugs in professional sports [1:29:45];
• Can the miracle of exercise be put in a pill? [1:36:00];
• Mike’s current research and questions he’s most interested in answering [1:39:00];
• Use of convalescent plasma to treat COVID-19 [1:41:15];
• Parting thoughts on the current state of fitness and exercise in society [1:47:15];
• More.

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Josh Rabinowitz is a Professor of Chemistry and Integrative Genomics at Princeton University, where his research focuses on developing a quantitative, comprehensive understanding of cellular metabolism through the study of metabolites and their fluxes. In this episode, Josh focuses the discussion on three main topics: metabolomics, NAD (and its precursors), and cancer metabolism. The metabolomics discussion starts with a broad definition of metabolism, metabolites, and fluxomics before diving deep into glucose metabolism, lactate as a fuel, movement of lactate, and the regulation of these substrates. He then gives a detailed explanation of the electron transport chain and Krebs cycle and their implications with respect to both drugs and nutrition while also explaining how NAD is central to the process of energy generation. He then discusses the age-related decline in NAD and what current literature says about efforts to increase NAD through intravenous or oral supplementation with the precursors NMN and NR, including whether doing so provides any advantage to lifespan or healthspan. Finally, Josh ends the conversation talking about cancer metabolism and how one particular intersection between cancer metabolism and immunotherapy might provide a hopeful outlook on the future of cancer treatment.

We discuss:

• Josh’s background and unique path to becoming a research scientist at Princeton [3:30];
• What sparked Josh’s early interest in metabolism [11:15];
• Metabolomics 101: defining metabolites and how they are regulated [16:30];
• Fluxomics: metabolism as a system in action [26:00];
• The Randle Hypothesis: glucose and fatty acids compete as substrates for oxidation [33:30];
• The important role of lactate as an alternate fuel [36:30];
• Fasting lactate levels as a potential early indicator of metabolic dysfunction [48:00];
• The beauty of the Krebs cycle and the role of NAD in energy production [53:15];
• How the drug metformin acts on complex I of the electron transport chain [1:05:00];
• The difference between NADH and NADPH [1:08:45];
• NAD levels with age, and the efficacy of supplementing with intravenous NAD [1:10:45];
• The usefulness of restoring NAD levels and efficacy of oral supplementation with NAD precursors NR and NMN [1:22:15];
• Exploring the hypothesis that boosting NAD levels is beneficial [1:32:30];
• Cancer metabolism and the intersection with immunotherapy [1:39:00];
• Making cancer a chronic disease: exploiting the metabolic quirks of cancer, augmenting the immune system, and more [1:46:15];
• The challenge of treating pancreatic cancer [1:50:30];
• Epithelial cancers that might respond to metabolic approaches to therapy [1:56:30];
• Josh’s hopeful outlook on the future of cancer treatment [1:59:00];
• Nutritional approaches to cancer attenuation [2:00:15];
• What makes Princeton University special [2:06:15];
• More.

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Mike Gershon is a Professor of Pathology and Cell Biology at Columbia University and has been at the forefront of studying neural control of the gut for the past 60 years. In this episode, Mike gives a tour de force on the pathways of gut-brain communication but first sets the stage with an overview of gastrointestinal tract development and anatomy. He then explains how the gut communicates with the brain and vice versa, from early observations in physiology and anatomy up to our present understanding of what makes the GI tract so unique and complex relative to other organs. He talks about how the gut responds to meals of different food qualities and how that affects satiety signaling to the brain. Additionally, he explains how antidepressants and other drugs impact digestion through effects on serotonin signaling, and he discusses the effects of antibiotics, and what’s really going on with “leaky gut.” Finally, Mike offers his thoughts on the utility—or lack thereof—of gut microbiome diagnostic tests, and wraps up the discussion by considering how diet, probiotics, and prebiotics impact the microbiome and GI tract.

We discuss:

• The basics of the gastrointestinal (GI) system [3:45];
• The very early development of the GI system [9:30];
• The unique properties of the blood supply and portal system in the GI tract [12:45];
• An overview of gut anatomy and innervation [16:30];
• Turnover of the epithelial lining and why cancer rarely develops in the small intestine [26:45];
• Nutrient and water absorption in the small and large intestine [30:30];
• Ways in which the gut and brain communicate [34:30];
• The gut's role in the regulation of appetite [43:30];
• The impact of gastric bypass surgery on satiety signals [51:15];
• How varicella-zoster virus (VZV) can infect neurons in the gut and create issues later in life [54:30];
• The relationship between autism and gastrointestinal illness [1:02:45];
• The important role of serotonin in the gut, and the impact of SSRIs on serotonin in the gut [1:09:45];
• Defining “leaky gut” and its most common causes [1:16:45];
• The gut microbiome [1:30:45];
• Fecal transplants: use cases, limitations, and how they illustrate the importance of gut microbes [1:40:45];
• Gut microbiome diagnostic tests: why they aren’t useful outside of special cases such as cancer detection [1:50:30];
• Nutritional approaches to a maintain optimal flora in the gut [1:55:00];
• Prebiotics and probiotics, and getting your GI system back on track after a course of antibiotics [2:02:30];
• More.

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In this “Ask Me Anything” (AMA) episode, Peter dives deep into the topic of bone health and explains why this is an important topic for everyone, from children to the elderly. He begins with an overview of bone mineral density, how it's measured, how it changes over the course of life, and the variability between sexes largely due to changes in estrogen levels. From there he provides insights into ways that one can improve bone health, from exercise to nutrition supplements to drugs. Additionally, Peter discusses what happens when one may be forced to be sedentary (e.g., bedrest) and how you can work to minimize the damage during these periods.

If you’re not a subscriber and 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 on our website at the AMA #37 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Overview of bone health topics to be discussed [1:45];
• Bones 101: bone function, structure, and more [5:15];
• Bone mineral density (BMD), minerals in bone, role of osteoblasts and osteoclasts, and more [8:30];
• The consequences of poor bone health [13:30];
• The devastating nature of hip fractures: morbidity and mortality data [17:00];
• Where fractures tend to occur in the body [23:00];
• Defining osteopenia and osteoporosis [24:30];
• Measuring BMD with DEXA and how to interpret scores [27:00];
• Variability in BMD between sexes [34:15];
• When should people have their first bone mineral density scan? [36:45];
• How BMD changes throughout the life and how it differs between men and women [39:00];
• How changes in estrogen levels (e.g., menopause) impact bone health [44:00];
• Why HRT is not considered a standard of care for postmenopausal bone loss [47:30];
• Factors determining who may be at higher risk of poor bone health [50:30];
• Common drugs that can negatively impact BMD [54:15];
• How children can optimize bone health and lay the foundation for the future [57:45];
• Types of physical activity that can positively impact bone health [1:02:30];
• How weight loss can negatively impact bone health and how exercise can counteract those effects [1:10:45];
• Nutrition and supplements for bone health [1:14:15];
• Pharmaceutical drugs prescribed for those with low BMD [1:17:15];
• Impact of extreme sedentary periods (e.g., bedrest) and how to minimize their damage to bone [1:22:00]; and
• More.

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Max Diehn is a Professor of Radiation Oncology at Stanford and a clinical radiation oncologist specializing in lung cancer. Max’s research focuses on developing novel methods for detecting circulating tumor DNA in the blood of cancer patients and on elucidating the molecular pathways and genes associated with cancer. His interests also include uncovering biomarkers that can predict patient survival, responses to therapy, and disease recurrence. In this packed episode, Max discusses the history of blood-based cancer screening and the importance of understanding the predictive value of tests—sensitivity, specificity, negative predictive value, positive predictive value – and how these metrics play into cancer screening. Max then goes in depth on the topic of liquid biopsies, including the history, current landscape, and possible future of liquid biopsies as a cancer detection tool. He discusses how these non-invasive blood tests can detect DNA/RNA from tumor cells released into the blood as well as the different methods one can use to predict if a cancer is present. He gets granular on the topic of cell-free DNA/RNA signature, methylation patterns, and the importance of knowing mutation information, and he ends with a discussion on the exciting future of liquid biopsies and how we can possibly get to the panacea of cancer screening.

We discuss:

• Max’s training that planted the seeds for development of liquid biopsies [4:30];
• Max’s decision to specialize in radiation oncology [11:45];
• A culture at Stanford that values research and physician scientists [17:00];
• The motivation to develop liquid biopsies [19:15];
• History of blood-based cancer screening and understanding the predictive value of tests [25:30];
• Current state of lung cancer and the need for better screening [32:45];
• Low-dose CT scans: an important tool for managing lung cancer but with limitations [42:00];
• Using liquid biopsies to identify circulating tumor cells [47:00];
• Liquid biopsy research moves from circulating tumor cells to cell-free DNA [1:03:00];
• Zeroing-in on circulating tumor DNA in cell-free DNA [1:10:48];
• Cell-free RNA and Max’s vision for cancer detection from a blood sample [1:22:00];
• Methylation patterns and other informative signatures found in DNA [1:24:30];
• Mutation-based methods of liquid biopsies [1:26:30];
• Understanding the sensitivity and specificity of a diagnostic test [1:30:30];
• Existing clinical liquid biopsy tests and their limitations [1:37:30];
• The future of liquid biopsies [1:44:00];
• How we get to the panacea of cancer screening [1:52:00];
• More.

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In this episode, Ric Elias, founder of Red Ventures, opens up about the fateful day he knew for certain that he was going to die as a passenger on US Airways Flight 1549. Ric dives deep into how that day impacted his life, greatly changed his perspective, and improved his relationship with his family and the broader community. We also talk about his incredible role as CEO of an enormous company, his remarkable work in philanthropy, and all the wisdom he has acquired in his extraordinary life.

We discuss: 

• Ric’s life leading up to the day of the plane crash [2:15];
• The plane crash—What it’s like knowing you’re about to die, feelings of regret and sadness [8:00];
  
• The improbable plane landing in the Hudson River [15:45];
  
• Emotions after the safe landing (and a story he’s never told before) [22:15];
  
• A powerful story about Captain Sully [26:15];
  
• Earning his second chance at life, and playing the “infinite game” [35:15];
  
• Why time is the ultimate currency, and how (and why) to say “no” [43:00];
  
• Raising kids in an achievement culture, Ric’s definition of life success, and what Ric wants to instill in his kids [49:45];
  
• What Ric believes is actually worth getting upset about, and the organizations that are taking steps to help people [1:05:45];
  
• The core principles of Red Ventures (Ric’s company) [1:16:00];
  
• Ric’s tips for developing business acumen and negotiation skills [1:26:15];
  
• What qualities does Ric look for in people he wants to work with? [1:29:15];
  
• What is the next big problem that Ric wants to solve? [1:32:15];
  
• What is the most challenging part of your business today? [1:34:15];
  
• If Ric could go back and talk to himself in the morning before getting on that plane, what would he say? [1:36:00]; and
  
• More.

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Stephan Guyenet is a neuroscientist focused on the neuroscience of obesity and energy homeostasis.  He is the author of the book, The Hungry Brain and founder/director of Red Pen Reviews. In this episode, Stephan explains how obesity has changed phenotypically over the course of human history as well as what might explain the dramatic increase in prevalence of obesity in the last few decades. He talks in depth about the role of genetics, the brain, and hormones like leptin play in the regulation of fat mass. He dives deep into two common theories of obesity—the carbohydrate-insulin model and the energy balance model and provides his take on which theory has stronger evidence. Additionally, he provides insights on how we’re hard-wired to think about food and the consequences of modern foods designed for maximal pleasure. Finally, he goes through the factors that affect body weight, set points, and provides takeaways for people wanting to take advantage of what we know about the brain’s role in regulating our body weight.

We discuss:

• Stephan’s neuroscience background and his focus on the nuances of obesity [2:15];
• How obesity has changed for humans throughout history [8:00];
• The association between obesity and adverse health outcomes, the “obesity paradox,” and confounders when relating BMI to longevity [14:00];
• The sharp increase in obesity across demographics [23:30];
• The hypothalamus and its role in obesity [30:00]; 
• The role of the hormone leptin in obesity [40:00];
• The genetic component of obesity [46:30];
• Understanding the tendency of humans to store fat through an evolutionary lens [57:00];  
• The hedonic aspect of food, and how the brain reacts to modern, highly-rewarding foods [1:03:30];
• How we are hard-wired to think about food [1:14:30];
• A review of the “Carnivore diet” [1:21:45];
• The energy balance model, carbohydrate-insulin model, and unifying the theories around adiposity [1:34:15];
• Body weight set points: a hypothetical comparison of two individuals [1:41:45];
• Takeaways for people who want to lose weight and keep it off [1:48:30];
• Evidence that favors the energy balance model of weight gain [1:56:00];
• The synergistic effect of fat and carbohydrates and observations that a low-fat diet or a low-carb diet can cause weight loss [2:04:30];
• Red Pen Reviews [2:11:00];
• More.

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In this “Ask Me Anything” (AMA) episode, Peter discusses the nutritional profiles of various fruits and vegetables as a means of assessing their relative value. He explains the difference between eating them vs. drinking them, how processing fruits and vegetables can change their properties, and how one’s current state of health affects nutrition strategy when it comes to fruits and vegetable consumption. Additionally, Peter explains the potential benefits and negative effects of certain phytochemicals found in produce and concludes with a discussion of supplementing with green powders, multivitamins, and more.

If you’re not a subscriber and 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 on our website at the AMA #36 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• The limitations of nutritional data and challenges of making broad recommendations [2:00];
• How one’s current state of health impacts their “optimal” diet [11:30];
• Defining “metabolic health” [14:45];
• The wide-ranging nutrition profiles of various fruits and vegetables [16:30];
• The benefits of fiber [20:45];
• Eating whole fruits vs. drinking fruit juice or smoothies [22:30];
• Drinking alcohol: metabolic effects, calories in alcohol, and more [28:30];
• Can excess fruit consumption lead to insulin resistance? [30:30];
• Glycemic impact of different fruits, using CGM data to assist decision making, and how fruit is fundamentally different from what we evolved to eat [31:30];
• Dietary approaches for people with a carbohydrate tolerance disorder (TD2, NAFLD, etc.), and when it makes sense to restrict fruit consumption [34:30];
• Nutrition profile of select vegetables: sugar content, micronutrients, and more [40:00];
• Phytochemicals in produce: potential positive health impacts on inflammation, cardiovascular (CV) risk, and cancer [44:30];
• Phytochemicals with potential negative health impacts [50:45];
• Nightshades and inflammation [53:15];
• How important is it to eat organic foods? [56:00];
• How necessary is it to wash fruits and vegetables? [1:00:45];
• How does food preparation change the nutritional composition? [1:03:45];
• Considerations when eating canned and frozen food, and paying attention to processed food additives [1:04:45];
• Supplementing vitamins and nutrients as an alternative to eating whole fruits and vegetables [1:06:15];
• Green powder supplements [1:11:15];
• Important takeaways [1:16:00]; and
• More.

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Benoît Arsenault is a research scientist focused on understanding how lifestyle and genetic factors contribute to cardiovascular disease risk. In this episode, the discussion casts a spotlight on Lp(a)—the single most important genetically-inherited trait when it comes to atherosclerotic cardiovascular disease (ASCVD) risk. Benoît explains the biology of Lp(a), how it’s inherited, the importance of measuring Lp(a) levels, and the diseases most associated with high Lp(a). He dives into data on the possible treatments for lowering Lp(a) such niacin, statins, and PCSK9 inhibitors, as well as the most exciting new potential therapeutic—antisense oligonucleotides.

We discuss:

• How Benoît came to study Lp(a)—a new marker for cardiovascular risk [3:15];
• The relationship between Lp(a) and CVD risk [6:45];
• What genome-wide association studies (GWAS) revealed about Lp(a) [16:00];
• Clinical tests to measure Lp(a) [22:00];
• The biology of Lp(a) [25:45];
• How statins lower LDL-cholesterol and why this doesn't work for an Lp(a) [29:15];
• The structure of LDL-p and Lp(a) and what makes Lp(a) more atherogenic than an equivalent LDL particle [34:00];
• The role of Lp(a) in aortic valve disease [42:45];
• How greater numbers of Lp(a) particles are associated with increased risk of disease [48:00];
• The genetics and inheritance of Lp(a) and how and when to measure Lp(a) levels [52:00];
• Niacin and other proposed therapies to lower Lp(a), apoB, and CVD risk [1:00:45];
• Why awareness of Lp(a) among physicians remains low despite the importance of managing risk factors for ASCVD [1:14:00];
• The variability of disease in patients with high Lp(a) [1:19:00];
• Diseases most associated with high Lp(a) [1:26:30];
• The biology of PCSK9 protein, familial hypercholesterolemia, and the case for inhibiting PCSK9 [1:35:00];
• The variability in PCSK9 inhibitors’ ability to lower Lp(a) and why we need more research on individuals with high levels of Lp(a) [1:50:30];
• Peter’s approach to managing patients with high Lp(a), and Benoît’s personal approach to managing his risk [1:54:45];
• Antisense oligonucleotides—a potential new therapeutic for Lp(a) [1:57:15]; and
• More.

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Marty Makary is a surgeon, public policy researcher, and author of the New York times best-sellers Unaccountable and The Price We Pay. In this episode, Marty dives deep into the topic of patient safety. He describes the risk of medical errors that patients face when they walk into the hospital and how those errors take place, and he highlights what amounts to an epidemic of medical mistakes. He explains how the culture of patient safety has advanced in recent decades, the specific improvements driven by a patient safety movement, and what’s holding back further progress. The second half of this episode discusses the high-profile case of RaDonda Vaught, a nurse at Vanderbilt Hospital convicted of negligent homicide after she mistakenly gave a patient the wrong medication in 2017. He discusses the fallout from this case and how it has in some ways unraveled decades of progress in patient safety. Furthermore, Marty provides insights in how to advocate for a loved one in the hospital, details the changes needed to meaningfully reduce the death rate from medical errors, and provides a hopeful vision for future improvements to patient safety.

We discuss:

• Brief history of patient safety, preventable medical mistakes, and catalysts for major changes to patient safety protocols [0:12];
• Advancements in patient safety and the dramatic reduction in central line infections [14:55];
• A surgical safety checklist—a major milestone in patient safety [23:03];
• A tragic case stimulates a culture of speaking up about concerns among surgical teams [25:19];
• Studies showing the ubiquitous nature of medical mistakes leading to patient death [29:42];
• The medical mistake of over-prescribing of opioids [33:48];
• Other types of errors—electronic medical records, nosocomial infections, and more [35:43];
• Importance of honesty from physicians and what really drives malpractice claims [40:26];
• A high-profile medical mistake case involving nurse RaDonda Vaught [47:31];
• Investigations leading to the arrest of RaDonda Vaught [59:48];
• Vaught’s trial—a charge of “negligent homicide” [1:05:16];
• A guilty charge and an outpouring of support for Vaught [1:12:09];
• Concerns from the nursing profession over the RaDonda Vaught conviction [1:18:09];
• How to advocate for a friend or family member in the hospital [1:20:22];
• Changes needed for meaningful reduction in the death rate from medical errors [1:26:42];
• Blind spots in our current national funding mechanism and the need for more research into patient safety [1:31:42];
• Parting thoughts—where do we go from here? [1:35:48];
• More.

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Beth Lewis is a former professional dancer and a self-described “educator of movement” who has an unmatched ability to assimilate information and customize training plans from multiple training systems. In this episode, Beth describes how she identifies problematic movement patterns and postures to help individuals relieve pain, avoid injury, and move better within all types of exercise. She explains how movement is a trainable skill and provides suggestions for ways that people can modify or supplement their exercise routine to benefit their health and longevity.

We discuss:

• Beth’s “way of no way” training philosophy [2:15]
• Beth’s background in dancing and how she ended up in New York City [5:00]
• Beth’s transition to fitness coaching and how her training philosophy has evolved [10:15];
• Functional Range Conditioning and scapular mobility [19:20];
• An overview of the Postural Restoration Institute, and Peter’s squat assessment [33:00];
• The important connection between the ribs and breathing [37:15];
• The role of sitting and external stress in chronic muscular tension [40:00];
• The important role of your toes, minimalist footwear, and toe yoga [42:00];
• Dynamic Neuromuscular Stabilization (DNS) [46:00];
• A different view on knee valgus [50:15];
• Is there such a thing as “bad posture”? [54:00];
• How Beth identifies an issue, addresses it, and keeps clients motivated [56:15];
• Lifting weights, the Centenarian Olympics, and dancing into old age [1:08:30];
• The importance of the hamstrings versus abs [1:18:45];
• Benefits of rowing, and why everyone should add it to their exercise regimen [1:24:45]
• Different roles of concentric versus eccentric strength [1:32:45];
• Flexibility and high-intensity interval training (HIIT) [1:37:10];
• Training versus playing sports, and the best type of activity for kids [1:40:30]; and
• More.

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Kelsey Chittick is the author of Second Half: Surviving Loss and Finding Magic in the Missing. In this episode, Kelsey describes her long healing process following the sudden death of her husband, former NFL player Nate Hobgood-Chittick. She describes her life with Nate before and after football, including her premonitions that something was off about Nate and the subsequent finding that he suffered from chronic traumatic encephalopathy (CTE). She speaks openly about how she handled his death with her children, the trauma and grief they faced in the aftermath, and how she’s found ways to be happy in her new life. She shares deep insights into her healing process, including her experience with psychedelics and how the concept of “radical acceptance” has helped her to find joy once again.

We discuss:

• Kelsey’s childhood in Florida as an athlete [2:15];
• Meeting Nate and early relationship with him [7:45];
• Nate’s unbelievable work ethic and desire to play in the NFL [12:30];
• Life with a professional football player, playing through pain, and head injuries related to football [17:00];
• Nate’s final days of football and early retirement struggles [23:30];
• The tough transition from the NFL to a “regular life” and how Nate found a way to serve others [28:45];
• Nate’s struggle with his weight and overall health after retirement [34:45];
• Kelsey’s anxiety and premonitions of Nate’s impending death, and Nate’s changing demeanor [37:30];
• The traumatic experience of learning of Nate’s death during her own spiritual journey to Jamaica [45:30];
• Breaking the news to her children of their father’s death [51:00];
• The darkest days following Nate’s passing and how her children were handling grief [55:30];
• A new relationship with death, finding happiness, and the duality of feelings [1:02:45];
• Nate’s autopsy results showing evidence of CTE [1:07:00];
• The grieving process [1:15:00];
• Dealing with grief with kids and how children grieve differently [1:19:15];
• Healing through her first psychedelic experience [1:23:00];
• The therapeutic potential of psychedelics, meditation, and more [1:33:45];
• The concept of “radical acceptance” and the peace that comes with it [1:42:30];
• The up and down experience of writing her book [1:47:45];
• More.

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In this “Ask Me Anything” (AMA) episode, Peter is joined by special guest, Dr. Matt Kaeberlein. Together they answer many questions around the field of aging with an emphasis on three specific molecules—NAD, metformin, and rapamycin—and their purported geroprotective qualities. They first discuss aging biomarkers and epigenetic clocks before breaking down the advantages and limitations of the most common experimental models being used today to study aging and pharmacological possibilities for extending lifespan. Next they dive deep into NAD and the much-hyped NAD precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). They compare data from NAD precursors to studies on metformin and rapamycin, assessing how they stack up against each other and using the comparison as an opportunity to illustrate how to make sense of new experimental data and make smart decisions about how to approach future research.

If you’re not a subscriber and 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 on our website at the AMA #35 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Logic behind comparing NAD precursors to rapamycin and metformin [3:40];
• Aging biomarkers: current state, usefulness, and future promise [7:00];
• Epigenetic clocks: definition, use case, and limitations [14:45];  
• Advantages and limitations of studying aging in non-humans and the strengths and weaknesses of different model systems [26:30];
• Aging studies: importance of control lifespans and the problems with reproducibility [34:15];
• Intro to NAD, potential role in aging, relationship to sirtuins, and more [48:15];
• NAD precursors (NR and NMN): current data [1:10:00];
• Human studies with NAD precursors [1:25:45];
• Comparing NAD lifespan data to data from metformin and rapamycin [1:28:30];
• Defining a “clean drug” and a “dirty drug” [1:38:00];
• Reason for the lack of rapamycin studies in humans compared to NAD and metformin [1:41:00];
• Ranking the geroprotective molecules in terms of risk and reward [1:48:00]; and
• More.

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In this special episode of The Drive, we have pulled together a variety of clips from previous podcasts about exercise to help listeners understand this topic more deeply, as well as to identify previous episodes which may be of interest. In this episode, Peter discusses his framework for exercise, what he’s really optimizing for, and how to train today to be prepared for a good life at age 100. He describes the importance of strength and stability, and why deadlifting is an important tool to consider for longevity. Additionally, he details why training in zone 2 and zone 5 is important, gives a primer on VO2 max, and describes the most effective ways to engage in those types of exercise. Finally, Peter reveals his current exercise routine.

We discuss:

• What is Peter optimizing for with his exercise? [3:00];
• Preparing for a good life at age 100: Training for the “Centenarian Olympics” [6:00];
• The importance of preserving strength and muscle mass as we age [21:45];
• The value of deadlifts for stability and longevity when done properly [27:30];
• The importance of zone 2 aerobic training [35:45];
• The most effective ways to engage in zone 2 exercise [40:00];
• Zone 5 training and VO2 max [44:15];
• A primer on VO2 max [52:00];
• Stability—the cornerstone upon which all exercise and movement relies [1:03:00];
• Peter’s current exercise routine [1:07:45];
• More.

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Layne Norton holds a Ph.D. in nutritional sciences and is a physique coach, natural bodybuilder, and previous guest on The Drive. In the first half of this episode, Layne dives deep into the topic of energy balance, including the role that macronutrients and calories play in weight loss. He describes how many people struggle with tracking food and calories on their own across a variety of diets and how all of this can impact nutritional habits and behaviors. In the second half of the episode, Layne discusses the importance of protein and weightlifting for improving one’s body composition and increasing muscle mass. He explains how he would prescribe different training and nutrition programs for two hypothetical clients—a 50-year-old female who is entering menopause and wants to improve her health, and a 40-to-50-year-old male who wants to maximize muscle mass. Additionally, Layne discusses a number of supplements that could potentially benefit a training program including whey protein, branch chain amino acids, creatine, nitric oxide boosters, and more.

We discuss:

• Defining energy balance and the role of calories [2:30];
• Defining a calorie, whether they are all created equal, and how much energy you can extract from the food you eat [8:00];
• Factors influencing total daily energy expenditure [12:15]:
• The challenge of tracking energy expenditure accurately, and the thermic effect of different macronutrients [23:30];
• Challenges of sustained weight loss: metabolic adaptation, set points, and more [34:45];
• Weight loss strategies: tracking calories, cheat meals, snacks, fasting, exercise, and more [40:45];
• Sitting in discomfort, focusing on habits, and other lessons Layne learned as a natural bodybuilder [52:15];
• Commonalities in people who maintain long-term weight-loss [1:01:15];
• Does a ketogenic diet result in greater energy expenditure? [1:03:15];
• The metabolic benefits of exercise, muscle mass, and protein intake [1:15:00];
• The impact of lean muscle and strength on lifespan and healthspan [1:20:00];
• Hypothetical case study #1: Training program for 50-year-old female [1:27:45];
• Muscle protein synthesis in a trained athlete vs. untrained individual following a resistance training program [1:31:30];
• Protein and amino acids needed to build and maintain muscle mass [1:37:15];
• Nutrition plan for the hypothetical 50-year-old woman starting to build lean muscle [1:42:45];
• Dispelling myths that excess protein intake increases cancer risk through elevations in mTOR and IGF [1:55:30];
• Hypothetical case study #2: Training program for a 50-year-old, trained male wanting to increase muscle mass [2:04:00];
• Maximizing hypertrophy while minimizing fatigue—is it necessary to train to muscular failure? [2:11:30];
• Ideal sets and reps for the hypothetical 50-year-old male interested in hypertrophy [2:16:15];  
• Maximizing hypertrophy by working a muscle at a long muscle length [2:22:15];
• Recommended lower body exercise routines and tips about training frequency [2:24:00];
• Nutrition plan for the hypothetical 50-year old male wanting to add muscle [2:29:00];
• Cycling weight gain and weight loss when building lean muscle mass, and expectations for progress over time [2:33:30];
• Supplements to aid in hypertrophy training [2:38:30];
• More.

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Nir Barzilai, Director of the Institute for Aging Research at the Albert Einstein College of Medicine, is back for his third appearance on The Drive. In this episode, Nir divulges insights into lifespan and healthspan through the lens of his extensive research on centenarians as well as the latest from the TAME trial (Targeting/Taming Aging with Metformin), a multi-center study investigating the concept that the multi-morbidities of aging can be delayed in humans. He discusses common gene variants found in centenarians, important pathways for longevity, and ultimately what we can learn from centenarians about extending lifespan while also trying to improve healthspan. Additionally, Nir goes into depth on metformin as a longevity tool for humans, including studies with positive and negative results. He discusses the impact metformin can have on exercise for both strength training and cardiovascular training, as well as future research facilitated by data from the TAME Trial. He also touches on epigenetic clocks and concludes with his take on the usefulness of NAD precursors as a potential gero-protective agent.

We discuss:

• Insights from genetic studies of centenarians and twins [3:00];
• Genes with protective variants that aid longevity [13:00];
• The relationship between growth hormone and IGF-1 [22:45];
• Use of growth hormone as a longevity tool [34:00];
• Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP [41:45];
• The correlation between high TSH and longevity [46:30];
• Important pathways for longevity [52:00];
• Insights from centenarian studies, nature vs. nurture, and more [59:00];
• The contraction of morbidity that comes with improved healthspan [1:08:00];
• Defining healthspan [1:13:13];
• Unique perspectives and positive attitudes of centenarians [1:17:30];
• Lessons to take away from centenarians [1:24:00];
• Metformin overview: history, studies, and potential for gero-protection [1:28:45];
• The TAME trial (Targeting Aging with Metformin) [1:39:00];
• The challenge of studying metformin in animals models [1:46:45];
• How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics [1:53:30];
• The search for biomarkers to identify who can benefit from treatment [2:00:30];
• The impact of metformin on exercise, and finding the right indication for the use of metformin [2:10:30];
• Are NAD precursors geroprotective? [2:21:30]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter dives deep into the topic of atherosclerotic cardiovascular disease (ASCVD)—the number one killer in the developed world. Peter argues for the importance of paying attention to and understanding ASCVD given its ubiquity and inevitability. He goes into great detail about the development of atherosclerosis and how it can take hold at a very early age, the role of cholesterol, and the causal factors of ASCVD that determine prevention strategies. Additionally, he discusses the important metrics and biomarkers found in blood work, as well as diagnostic tests such as coronary artery calcium scores (CAC) and CT angiograms which help to determine the level of arterial damage present. Finally, Peter lays out the keys to understanding and interpreting calcium scores before wrapping up the conversation with his key takeaways regarding prevention.

If you’re not a subscriber and 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 on our website at the AMA #34 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• The importance of understanding atherosclerosis early in life [2:15];
• Defining atherosclerotic cardiovascular disease (ASCVD), its causes, and the role of cholesterol [9:00];
• The process of developing ASCVD, part 1 [15:00]; 
• The process of developing ASCVD, part 2 [24:00];
• The process of developing ASCVD, part 3 [32:45];
• How early in life ASCVD can start to develop [40:30];
• Case studies of atherosclerosis and figures showing real pathology [43:00];
• Coronary artery lesions present in autopsies of different age groups [49:15];
• The causal factors of ASCVD that determine prevention strategies [52:15];
• Labs to identify biomarkers of ASCVD ]59:00];
• Diagnostic tests to determine the level of arterial damage present—CAC, CTA, CIMT, and more [1:00:30]
• Keys to understanding and interpreting a CAC score and/or CTA results [1:05:15];
• Is there a risk from cholesterol levels being too low? [1:13:00];
• Key takeaways regarding prevention [1:15:45];
• More.

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In this second edition of the “Strong Convictions, Loosely Held” episode, Peter discusses topics on which his thoughts have evolved as a result of his interviews with podcast guests and other information he’s gained since episode 100. Peter covers topics including cancer therapy and screening, as well as prevention strategies for cardiovascular disease and Alzheimer’s disease. He also describes changes in his perspectives on time-restricted feeding and protein consumption and on the therapeutic use of psychedelics, and he discusses some sleep supplements with remarkable efficacy. He ends with a special discussion on all things Formula 1 racing.

We discuss:

• The concept of “strong convictions, loosely held” [3:10];
• Update on Peter’s upcoming book [8:30];
• Cancer: the promise of immunotherapy [14:15];
• Cancer: how aggressive screening for gastrointestinal cancers could save lives [24:30];
• Cardiovascular disease: how early and aggressive lowering of apoB could change the course of ASCVD [31:30];
• Alzheimer’s disease: genes that modify risk associated with the APOE4 variant [40:15];
• Time-restricted feeding: where the benefit comes from, and when this practice can be problematic [44:00];
• The common problem of protein underconsumption [51:45];
• The tremendous impact of exercise on lifespan and healthspan [54:45];
• Peter’s shoulder surgery [1:00:15];
• An uninspiring viewpoint on NAD precursors as a longevity tool [1:06:15];
• Psychedelics: a powerful therapeutic tool in the right setting [1:09:30];
• Sleep: updated thoughts on blue light and a remarkable drug for aiding sleep quality [1:13:15];
• Book recommendation from Peter [1:20:45];
• Formula 1: the 5 variables that determine the winner [1:22:00];
• F1: the drivers [1:26:00];
• F1: the tires [1:27:30];
• F1: the engine and chassis [1:32:00];
• F1: rule changes around cars [1:34:15];
• F1: importance of qualifying races [1:41:15];
• F1: racing strategy [1:47:30];
• F1: season outlook and predictions [1:51:00]; and
• More.

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Episode Description:

Today’s episode of The Drive is a rebroadcast of the conversation with Sarah Hallberg (released on May 17th, 2021). It's with great sadness that we report that Sarah recently lost her battle with lung cancer, and as such we've decided to republish her episode to honor her amazing work in challenging the status quo in the treatment of metabolic disease.

Sarah Hallberg was the Medical Director at Virta Health and a physician who spent nearly two decades treating patients with obesity and type 2 diabetes. In the first half of this episode, Sarah discusses how she became a huge believer in the efficacy of carbohydrate restriction for the treatment of type 2 diabetes through her research and clinical experience. Sarah challenges the common beliefs about the role of dietary fat and carbohydrate on the plasma makeup of fatty acids and triglycerides. She also expresses the importance of understanding early predictors of metabolic illness—highlighting one particular fatty acid as the most important early predictor—before finishing with a discussion about how doctors might be able to personalize patients’ metabolic management in the future. In the second half of this episode, Sarah tells the personal story of her own lung cancer diagnosis. She talks about dealing with her grief, deciding to continue her work while prioritizing her family, and how she devised a plan to extend her survival as long as possible. 

We discuss:

• How Sarah discovered the profound impact of carbohydrate restriction for reversing obesity and type 2 diabetes [2:00];
• Prediabetes and metabolic syndrome: prevalence, early signs, and the importance of treating early [14:45];
• Overview of fatty acids, how they are metabolized, and understanding what you see in a standard blood panel [28:00];
• The relationship between diet composition and metabolic markers [34:00];
• Why palmitoleic acid is such an important biomarker [47:00];
• The best early indicators of metabolic disease [58:45];
• Personalized management of metabolic illness [1:05:45];
• Sarah’s cancer diagnosis and the beginning of her journey [1:14:00];
• The emotional impact of a devastating diagnosis [1:26:00];
• Sarah’s plan to extend survival [1:35:30];
• Sarah’s aggressive treatment plan [1:46:15];
• Life-threatening complications and the return of her cancer [1:57:45];
• Sarah’s reflections on her approach to life with chronic cancer and balancing her time [2:09:45]; and
• More.

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Episode Description:

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 [3:00];
• Metrics for assessing athletic performance in cyclists and how that impacts race strategy [8:30];
• The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [17:00];
• Tadej Pogačar’s race strategy and mindset at the Tour de France [24:00];
• Defining Zone 2, fat oxidation, and how they are measured [26:45];
• Using fat and carbohydrate utilization to calculate mitochondrial function and metabolic flexibility [35:45];
• Lactate levels and fat oxidation as it relates to Zone 2 exercise [40:00];
• How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:45];
• Bioenergetics of the cell and what is different in elite athletes [57:30];
• How the level of carbohydrate in the diet affects fuel utilization and power output during exercise [1:08:30];
• Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:15:00];
• How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:21:00];
• Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:25:00];
• Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:41:15];
• How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:51:15];
• Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:45];
• The effects of metformin, NAD, and supplements on mitochondrial function [2:05:15];
• The role of lactate and exercise in cancer [2:13:30];
• How assessing metabolic parameters in long COVID patients provides insights into this disease [2:19:00];
• The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise [2:25:45];
• Metabolomics reveals how cellular metabolism is altered in sedentary individuals [2:33:45];
• Cellular changes in the metabolism of people with diabetes and metabolic syndrome [2:39:15]; and
• More.

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Episode Description:

In this “Ask Me Anything” (AMA) episode, Peter discusses all things related to hydration, starting with how water is distributed in the body and the important concept of tonicity. He explains the difference between dehydration and volume depletion and their respective health consequences and implications. He describes the different conditions which affect our daily water needs, as well as the signs of dehydration and how it can affect performance. Next, he discusses all the ways in which we can rehydrate and when it makes sense to add electrolytes, glucose—or a combination of both—to rehydration fluids. Additionally, Peter gives his take on the plethora of sports drinks on the market and which ones stand out from the rest. Finally, he concludes with some key takeaways related to hydration. 

If you’re not a subscriber and 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 on our website at the AMA #33 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Peter’s incident leading to a renewed interest in hydration [3:15];
• Water in the human body: percentage, location, and implications [6:00];
• Defining tonicity—isotonic, hypotonic, and hypertonic [11:45];
• Defining dehydration and volume depletion [19:00];
• The health consequences of dehydration and volume depletion [21:45];
• How do we actually lose water? [25:30];
• How much water do we need every day? [28:00];
• Signs of dehydration during exercise and how it can affect performance [32:45];
• Is it possible to be overhydrated? [43:15];
• Electrolytes: benefits and when to include them in rehydration fluids [47:00];
• Glucose: benefits and when to include it in rehydration fluids 51:15];
• The ability of glucose to improve absorption of sodium [58:45];
• The type of carbohydrates in drinks than actually impact performance [1:02:00];
• Sodium during workouts: is there an optimal ratio of carbohydrate to sodium? [1:05:00];
• Pros and cons of sports drinks and which ones stand out [1:09:15];
• How much hydration comes from the food we eat? [1:14:30];
• Is there a downside to drinking electrolytes throughout the day even without exercise? [1:15:15];
• Key takeaways related to hydration [1:18:15]; and
• More. 

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Episode Description:

Ryan Hall is the fastest American ever to run the marathon (2:04:58) and half marathon (59:43) and is the author of the book Run the Mile You’re In. In this episode, Ryan discusses his amazing successes and epic failures during his remarkable running career and what he's learned through these experiences. Ryan explains not only the physical aspects of running - including his training routine, fueling regimen, and recovery process - but he also emphasizes the mental aspect of the sport. He discusses how accepting and reframing negative thoughts can empower you to take on challenges and reach your potential. Additionally, Ryan discusses the traits that make the best competitors, the keys to overcoming setbacks, and his amazing feat of 7 marathons in 7 days as a goodbye to the sport that gave him so much.

We discuss:

• How Ryan got into running and his formative years of training [4:45];
• The advantages of altitude—living high and training low [9:45];
• Progressive overload, blood flow restriction, and switching up your workout routine [14:15];
• Lessons learned from competing in the Beijing Olympics [16:45];
• Importance of speed, power, and strength for runners [22:15];
• The crazy idea that got Ryan hooked on running [35:15];
• The mental aspect of training and the power of reframing negative thoughts [37:45];
• The importance of fueling, and Ryan’s marathon diet [52:00];
• Boosting performance with Tylenol and keeping core temperature down [59:00];
• Ryan’s early struggles and later success at Stanford [1:09:45];
• Keys to overcoming difficulty: faith, mindset, and being a better teammate [1:15:45];
• Ryan’s professional running career and his discovery of his gift for marathon distances [1:22:00];
• Reflections after breaking the American half marathon record, and challenges faced by retired athletes [1:32:45];
• Ryan’s marathon training regimen at the Mammoth Track Club in 2010 [1:39:45];
• Optimal body weight for competition and the pros and cons of going below your natural weight [1:48:45];
• Training volume, importance of mixing up intensity level, and zone 2 and zone 5 for longevity [1:53:45];
• The most impactful adjustments Ryan made to his training leading up the to 2011 Boston Marathon [1:58:15];
• A new personal record at the 2011 Boston Marathon and lessons on maximizing your own potential [2:03:30];
• Learning from failure and takeaways from his disappointing performance at the 2012 Olympics [2:12:30];
• Utilizing cardio and strength training for overall health, and how Ryan uses blood flow restriction in his workouts [2:24:45];
• Performance enhancing drugs (or lack thereof) in marathon runners [2:29:15];
• Traits of the greatest marathon runners [2:32:30];
• 7 marathons in 7 days on 7 continents—saying goodbye to the sport [2:38:45];
• Reflections on what running has given Ryan [2:49:30]; and
• More.

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Episode Description:

Steven Dell is an ophthalmologist, current Medical Director of Dell Laser Consultants, and a leader in refractive eye surgery with over 20 patents to his name. In this episode, Steven explains the anatomy and functional mechanics of the eye and how they relate to common variations in vision. He discusses changes in vision that occur with aging, the fundamentals of different types of vision loss, and provides an in-depth look into the various treatments and procedures available for corrective eye surgery. Additionally, Steven explains how one might protect the eyes and prevent vision loss—a topic particularly important for children in light of the epidemic of myopia. 

We discuss:

• Why Steven chose ophthalmology, and the crossovers to other medical disciplines [3:45];
• Anatomy of the eye, common types of vision loss, and age-related vision changes [14:15];
• Eye drops that can potentially improve vision [27:30];
• The explanation for different eye colors [33:15];
• Physiology of the eye and its connections to the brain [34:45];
• Understanding human vision through an evolutionary lens [41:00];
• Enhancing vision beyond 20/20 [47:00];
• Astigmatism: definition, cause, and high prevalence [51:30];
• Nearsightedness (myopia): causes, epidemic in children, and prevention strategies [54:15];
• Cataracts: impact of aging and how they can be repaired [1:05:00];
• Lens implants that can correct and improve vision [1:19:30];
• Effects of eye trauma [1:26:45];
• Corneal abrasion from ‘dry eye’: causes, treatment, and prevention strategies [1:29:00];
• Sunglasses for eye protection [1:35:00];
• Solutions to correct nearsightedness [1:42:00];
• Laser eye surgery—photorefractive keratectomy (PRK) [1:45:45];
• Laser eye surgery—LASIK [2:02:00];
• Laser eye surgery—small incision lenticule extraction (SMILE) [2:11:45];
• Glaucoma: definition, causes, symptoms, and care [2:13:45];
• Tips for preserving eye health [2:20:00];
• Screen time and eye health [2:24:15];
• Contact lenses: good hygiene and considerations [2:27:45];
• A bonus benefit from repairing cataracts [2:29:00];
• Questions about corrective eye surgery [2:31:30];
• How an eye exam can be a window into metabolic illness [2:33:45]; and
• More.

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Episode Description:

David Allison is an award-winning scientific writer who has been at the forefront of obesity research for the last 20 years. Currently the Dean of the Indiana University School of Public Health, he has also authored many publications on statistical and research methodology and how to improve research rigor and integrity. David’s focus on evidence and data brings forth an interesting discussion of what we know (and don’t know) about the science of obesity. He provides an insightful and unemotional explanation of the potential impact of nutritional epidemiology in public health while also explaining its many pitfalls and limitations. He offers his take on the path forward in addressing the obesity epidemic, and he closes with a lucid explanation for the evident lack of credibility in science and the steps we can take to change that. 

We discuss:

• David’s background, interest in obesity, and focus on evidence [5:00];
• The moment when the obesity crisis was recognized, and the sloppy science that ensued [13:00];
• What twins studies tell us about the genetics of obesity [20:30];
• How doctors and scientists have historically approached obesity treatment [23:45];
• Do surgical procedures for obesity prolong life? [32:00];
• The ‘Obesity Paradox’ [36:00];
• Interpreting BMI and mortality data and considering confounders [43:15];
• How body composition and ethnicity factor into consideration of BMI data [50:30];
• Superior tools for measuring obesity at the individual level [57:15];
• Using BMI data for actionable steps to combat obesity [1:02:00];
• Why maintaining weight loss is more challenging than losing weight [1:06:00];
• Differing perspectives on the utility of nutritional epidemiology [1:16:30];
• A mouse study illustrating the impossibility of fully controlling for confounds in observational studies [1:22:15];  
• Limitations of nutritional epidemiology and how it can improve [1:26:30];
• Addressing the obesity epidemic—the path forward and obstacles to overcome [1:37:15];
• What David believes to be the most promising interventions we could take to address obesity and improve public health [1:47:30];
• Reproducibility in science, normative and non-normative errors explained [1:51:30];
• Rebuilding trust in science and differentiating between science and advocacy [1:59:00];
• More.

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Episode Description:

In this “Ask Me Anything” (AMA) episode, Peter shares his current workout regimen and how he incorporates blood flow restriction (BFR). He walks through the mechanics and fundamentals of some of his favorite lifts including squats, deadlifts, and hip thrusters and stresses the relative importance of each in the context of longevity. He touches on the relative importance of muscle size vs. muscle strength and discusses the impact of fasting on muscle mass and the potential tradeoffs during aging. Peter then dives into the topic of testosterone replacement therapy (TRT) for both men and women, starting with a clinical discussion around how he actually replaces testosterone in patients. He explains the targets of this therapy as well as the risks and benefits, and he gives his interpretation of current data on the association between TRT and heart disease.

If you’re not a subscriber and 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 on our website at the AMA#32 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Peter’s current exercise routine [2:25];
• How Peter incorporates blood flow restriction (BFR) into his workouts [5:45];
• Relative importance of muscle size vs. muscle strength [16:45];
• Comparing squats to deadlifts and why both are important [22:00];
• Squatting technique and fundamentals [31:15];
• Important cues to look for while lifting weights [38:30];
• Proper mechanics of a deadlift [42:00];
• Hip thrusters as an alternative to the squat or deadlift [44:00];
• Split-leg work for simulating activities of daily living [47:00];
• The impact of fasting/calorie restriction on muscle mass and the potential tradeoffs to consider [49:45];
• Testosterone replacement therapy: considerations when contemplating TRT and Peter’s approach with patents [54:30];
• Data on the association between TRT and heart disease [1:04:15];
• TRT for women—risks and benefits [1:06:45];
• Impact of fasting on testosterone levels [1:13:45]; and
• More.

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Episode Description:

Sebastian Junger is an award-winning journalist, documentary filmmaker, and New York Times best-selling author. In this wide-ranging discussion, Sebastian shares stories from his time as a war reporter and how it shaped his understanding of the psychological effects of combat, including the sacred bond of soldiers, the forces that unify a tribe, and the psychological mechanisms that protect humans from painful experiences. He draws upon his personal struggle with PTSD as he discusses trauma as an all-too-common consequence of war and the importance of community in the healing process. He explains his interest in viewing human behavior through an evolutionary lens, including how it influences his parenting style, and he voices concerns over society’s continuous shift away from our evolutionary roots. Sebastian also tells the story of his near-death experience and his new perspective on the possibility of an afterlife.  Additionally, Sebastian shares his thoughts on the mental health implications of current events, such as the pandemic and the withdrawal of troops from Afghanistan, and contemplates what it really means to be “free” in modern society. 

We discuss:

• Sebastian’s upbringing and early lessons about the evil of fascism [3:20];
• Sebastian’s search for a career, interest in writing, and what he loved about tree removal [11:30];
• How Sebastian became a great writer [19:30];
• Sebastian’s experience with his Achilles injuries [25:30];
• Work as a war reporter and his experience in combat in Afghanistan [28:00];
• Psychological effects of war and Sebastian’s own experience with PTSD [36:30];
• The sacred bond of soldiers and what Sebastian learned from his time with troops in Afghanistan [48:30];
• An evolutionary perspective on the forces that unify and bind tribes [1:00:00];
• Hunter-gatherer societies, dealing with loss, and the ancestral connection to the spiritual realm [1:08:30];
• Psychological mechanisms that protect humans from painful experiences and the power in giving thanks [1:13:15];
• How parenting has changed Sebastian, and the incredible pain of losing a child [1:21:15];
• PTSD and the influence of community on healing [1:32:15];
• Isolation of modern society and the debate over young kids sleeping in bed with their parents [1:37:45];
• Why Sebastian doesn’t own a smartphone [1:43:30];
• Parenting through an evolutionary lens [1:50:00];
• Sebastian’s near-death experience and new perspective on the possibility of an afterlife [1:54:00];
• Sebastian’s experience with depression and anxiety [2:12:00];
• The pandemic’s impact on mental health [2:16:45];
• Sebastian’s thoughts on the withdrawal of troops from Afghanistan [2:22:00];
• Sebastian’s latest book—Freedom, and knowing when to quit [2:27:00];
• Defining freedom in modern society [2:44:30];
• More.

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Episode Description:

Rick Johnson, Professor of Nephrology at the University of Colorado and a previous guest on The Drive, returns for a follow-up about unique features of fructose metabolism, and how this system that aided the survival of human ancestors has become potentially hazardous based on our culture’s dietary norms. In this episode, Rick explains how the body can generate fructose from glucose and how circulating glucose and salt levels can activate this conversion. He discusses the decline in metabolic flexibility associated with aging, as well as how factors such as sugar intake or menopause-associated hormone changes can alter responses to sugar across a lifetime. In addition, Rick lays out strategies for combating the development of metabolic illness using dietary changes and pharmaceutical therapies, and he discusses the impact of fructose metabolism and uric acid on kidney function and blood pressure. He concludes with a discussion of vasopressin, a hormone that facilitates fructose’s effects on weight gain and insulin resistance.

We discuss:

• Unique features of fructose metabolism and why it matters [2:45];
• A primer on fructose metabolism and uric acid [10:30];
• Endogenous fructose production, the polyol pathway, and the effect of non-fructose sugars [22:00];
• Findings from animal studies of glucose and fructose consumption [29:00];
• What calorie-controlled studies say about the claim that a “calorie is a calorie” [42:15];
• Implications for aging and disease [51:15];
• Impact of endogenous fructose production on obesity and metabolic syndrome [1:01:30];
• Why vulnerability to the negative effects of sugar increases with age and menopause [1:04:30];
• Dietary strategies to reduce the negative impact of fructose [1:16:30];
• The role of hypertension in chronic disease and tips for lowering blood pressure [1:30:45];
• The impact of fructose and uric acid on kidney function and blood pressure [1:39:45];
• The potential role of sodium in hypertension, obesity, and metabolic syndrome [1:49:00];
• The role of vasopressin in metabolic disease [1:54:00];
• More.

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Episode Description:

In this “Ask Me Anything” (AMA) episode, Peter and Bob first answer a variety of questions related to heart rate variability (HRV): what it means, why it matters, and how to measure, interpret, and potentially elevate it. Next, they dive deep into the topic of alcohol, beginning with a discussion on the negative impact that it can have on sleep. They then break down the confusing body of literature suggesting potential health benefits to moderate levels of drinking compared to complete abstinence and point out the limitations of these studies. Finally, they conclude by analyzing data on the impact of moderate and heavy drinking on the liver and on risk for Alzheimer’s disease and dementia.

Please note: this AMA is audio only. If you’re not a subscriber and 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 on our website at the AMA #31 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• What is heart rate variability (HRV), and why do we measure it? [2:10];
• The association between low HRV and mortality risk [10:00];
• What high and low HRV means and why athletes strive for a high HRV [15:30];
• Factors that can raise or lower HRV [18:00];
• How and when to measure HRV, and the best wearables [19:15];
• Interpreting your personal HRV number and why there’s so much individual variation [23:15];
• How Peter’s morning HRV reading impacts his decision to train [28:30];
• Alcohol’s impact on sleep [31:30];
• Metrics to track the impact of alcohol on your sleep [34:00];
• Alcohol’s impact on the need to urinate during the night [39:00];
• Alcoholic fatty liver disease (AFLD) [41:30];
• Individual differences in the way people metabolize and react to alcohol consumption [44:15];
• Analysis of epidemiology studies suggesting moderate alcohol consumption lowers mortality risk [52:00];
• Alcohol consumption and Alzheimer’s disease [1:05:15];
• Heavy alcohol consumption and risk of dementia [1:08:30];
• Chronic effects of alcohol on the liver [1:17:45];
• The relationship between alcohol, sleep, and automotive deaths [1:20:45]; and
• More.

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Episode Description:

This episode is a follow-up to our recent COVID-19 podcast with Drs. Marty Makary and Zubin Damania (aka ZDoggMD). Here, we address many of the listener questions we received about our original discussion. In addition to Marty and ZDoggMD, we are also joined by Dr. Monica Gandhi, an infectious disease specialist and Professor of Medicine at the University of California, San Francisco. In this episode, we talk about new data on Omicron, long COVID, masks, kids and schools, vaccine mandates, policy questions, and treatments. We also discuss some of the most prevalent misinformation and spend time talking about claims made by Robert Malone. We end with a conversation about our exit strategy. 

Please note: we recorded this episode on January 17, 2022, and in an effort to get it out as soon as possible, this won’t have full show notes or a video. Additionally, Monica was only able to join us for the first section of the podcast, so you’ll hear her drop off partway through.

We discuss:

• Severity of infection from Omicron—reviewing the data [5:15];
• Factors contributing to the relative mildness of Omicron infections [8:30];
• Is SARS-CoV-2 evolving to cause less severe disease? [13:00];
• Potential of Covaxin—an inactivated virus-based COVID-19 vaccine [17:45];
• How B cells and T cells work together to defend against viruses [22:00];
• Comparing COVID-19 vaccines, and the rationale for the time between doses [25:30];
• Reviewing the purpose and effectiveness of boosters for reducing severity and transmission [32:30];
• Debating vaccine mandates, and putting COVID’s mortality risk in perspective [41:00];
• Why the topic of COVID has become so polarized [1:03:15]  
• Reviewing the data on masks for protecting oneself and protecting others [1:06:30];
• The inconsistent logic used for mask mandates [1:16:00]; 
• Long COVID and the potential for vaccines to reduce risk [1:21:45];
• Risks for children and policies for schools [1:27:30];
• Reviewing the outcomes from Sweden, where the government didn't impose lockdowns [1:31:00];
• Draconian measures implemented in Canada [1:38:15]; 
• Antiviral treatments for COVID and a common-sense approach [1:42:15];
• Importance of ending tribalism and having rational discussions with humility [1:47:30];
• Treating infection with monoclonal antibodies and convalescent sera [2:01:45];
• Reviewing claims made by the controversial Dr. Robert Malone [2:11:15];
• A potential exit strategy from the current situation [2:30:30];
• Changes needed at the NIH [2:40:00];
• More.

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Episode Description:

Karl Deisseroth is a world-renowned clinical psychiatrist, neuroscientist, and author of Projections: A Story of Human Emotions. In the episode, Karl explains his unique career path that led to the development of optogenetics—a revolutionary technique that uses specialized light-sensitive ion channels to precisely control the activity of select populations of neurons. Karl provides a concise overview of how optogenetics works and how it can be used to better understand mental illness, to identify the neurons responsible for specific behaviors, and to guide development of new treatments. Karl uses his experience as a practicing psychiatrist to provide deep insights into depression, anxiety, autism, and personality disorders and explains the role of optogenetics in mapping out brain regions responsible for common mental health afflictions.

We discuss:

• Karl’s journey through medical school and interest in the brain [5:00];
• A profound medical school experience that changed Karl’s career path to psychiatry [17:30];
• Karl’s commitment to research and challenges overcome early in his career [27:00];
• The state of psychiatry and mental health therapies when Karl started his lab in 2004 [33:15];
• Neuroscience 101: fundamentals of neuroanatomy and neurophysiology [38:15];
• Traditional techniques for identifying the brain regions involved in specific behaviors [47:15];  
• Intro to optogenetics and how to get a gene into a neuron [51:15];
• How viruses helped make optogenetics possible [1:01:45];  
• How optogenetics was used to investigate the effects of dopamine neurons [1:15:45];
• Appreciating the power of optogenetics [1:22:00];
• Investigating and treating anxiety with optogenetics [1:26:45];
• Autism and autism-related anxiety, and the potential of optogenetics in treating autism [1:38:00];
• Optogenetics as a powerful tool for the discovery and creation of medical treatments [1:45:00];
• Karl’s inspiration to write his book, Projections [1:48:00];
• Mania and bipolar disorder: evolutionary basis, symptoms, and the high prevalence in North America [1:52:45];
• Depression: evolutionary basis and insights from optogenetics [2:03:15];
• The effects of trauma early in life [2:18:45]; and
• More.

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Episode Description:

Paul Conti, a returning guest on The Drive, is a practicing psychiatrist and recent author of Trauma: The Invisible Epidemic: How Trauma Works and How We Can Heal From It, in which he offers valuable insights on healing from trauma. In this episode, Paul explains how his personal experience with trauma and his many years seeing patients have shaped his understanding of trauma’s impact on the brain, its common patterns and manifestations, and how often people don't recognize the implications of trauma in their own life. He discusses major challenges in recognizing trauma, including the lack of biomarkers in psychiatry and psychology, as well as the misguidance of the mental health system in targeting symptoms as opposed to root problems. He talks about shame as the biggest impediment to healing from trauma and offers solutions to how, as a society, we can start to change the stigma of mental health and allow more people to receive help. Finally, he concludes with a discussion about the potential role of psychedelics like psilocybin and MDMA in treating trauma.

We discuss:

• Paul’s background and unique path to psychiatry [2:30];
• A personal tragedy that shaped Paul’s understanding of trauma and resulting feelings of shame and guilt [5:30];
• The current state of psychiatry training and need for improvement [20:15];
• The over-reliance on outdated metrics and lack of attention to past trauma as impediments to patient care [28:30];
• Defining trauma: various types, heterogeneity, and effects on the brain [34:30];
• Importance of finding the roots of trauma and understanding the “why” [47:00];
• The major challenge of recognizing trauma in patients [55:15];
• How shame and guilt are barriers to treatment and healing [1:06:00];
• How treating trauma compares to treating an abscess—a powerful analogy [1:11:30];
• How evolutionary survival instincts create problems in modern society [1:15:15];
• First step toward healing: overcoming the fear of talking about past trauma [1:19:00];
• Shame: the biggest impediment to healing [1:25:15];
• The antidote to shame and the need for discourse and understanding [1:34:15];
• The emotional health component of healthspan [1:41:15];
• How to reframe the conversation about mental health for a better future [1:52:00];
• The growing impact of trauma on our society and the need for compassion [1:58:45];
• Society’s antiquated way of treating manifestations of trauma rather than root issues [2:04:15];
• Potential role of psychedelics like psilocybin and MDMA in treating trauma [2:11:15];
• Parting thoughts and resources for getting help [2:16:30];
• More.

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In this episode, Peter sits down with Drs. Marty Makary and Zubin Damania (aka ZDoggMD), both previous guests on The Drive. Marty is a Johns Hopkins professor and public health researcher and ZDoggMD is a UCSF/Stanford trained internist and the founder of Turntable Health. This episode, recorded on December 27, 2021, was in part inspired by some of the shoddy science and even worse messaging coming from top officials regarding COVID-19. In this discussion, Marty and ZDoggMD discuss what is known about the omicron variant, the risks and benefits of vaccines for all age groups, and the taboo subject of natural immunity and the protection it offers against infection and severe disease. Furthermore, they discuss at length the poor messaging coming from our public officials, the justification (and lack thereof) for certain mandates and policies in light of the current evidence, and the problems caused by the highly politicized and polarized nature of the subject. Themes throughout the conversation include the difference between science and advocacy, the messaging which is sowing mistrust in science despite major progress, and a search for what a possible “end” to this situation might look like. 

NOTE: Since this episode was recorded over the holiday and published ASAP, this is an audio-only episode with limited show notes. 

We discuss:

• Comparing omicron to delta and other variants [4:15];
• Measuring immunity and protection from severe disease—circulating antibodies, B cells, and T cells [13:15];
• Policy questions: what is the end game and how does the world go back to 2019? [18:45];
• A policy-minded framework for viewing COVID and the problem of groupthink [24:00];
• The difference between science and advocacy [39:00];
• Natural immunity from COVID after infection [46:00];
• The unfortunate erosion of trust in science despite impressive progress [57:15];
• Do the current mandates and policies make sense in light of existing data? [1:02:30];
• Risks associated with vaccines, and the risk of being labeled an anti-vaxxer when questioning them [1:18:15];
• Data on incidence of myocarditis after vaccination with the Pfizer and Moderna vaccines [1:26:15];
• Outstanding questions about myocarditis as a side effect of mRNA vaccination and the benefit of boosters [1:35:00];
• The risk-reward of boosters and recommendations being ignored by policy makers in the US [1:40:30];
• Sowing distrust: lack of honesty and humility from top officials and policy makers [1:43:30];
• Thoughts on testing: does it make sense to push widespread testing for COVID? [1:52:15];
• What is the endpoint to all of this? [1:58:45];
• Downstream consequences of lockdowns and draconian policy measures [2:05:30];
• The polarized nature of COVID—tribalism, skeptics, and demonization of ideas [2:10:30];
• Looking back at past pandemics for perspective and the potential for another pandemic in the future [2:20:00];
• What parents can do if their kids are subject to unreasonable policies [2:25:00];
• Voices of reason in this space [2:28:45];
• Strong convictions, loosely held: the value in questioning your own beliefs [2:32:15];
• More.

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Today’s episode of The Drive is a rebroadcast of the conversation with Iñigo San Millán, (released on December 23rd, 2019). This episode with Iñigo was one of the most popular discussions to date and is a prelude to an upcoming follow-up discussion in 2022.

In this episode, Dr. Iñigo San Millán, Assistant Professor at the University of Colorado School of Medicine, explains the crucial role of mitochondrial function in everything from metabolic health to elite exercise performance. Iñigo provides a masterclass into the many different energy system pathways, the various fuel sources (including the misunderstood lactate), the six zones of exercise training, and the parameters he uses to measure metabolic health. Additionally, he highlights the power of zone 2 training as both an effective diagnostic tool and, perhaps more importantly, as a treatment for mitochondrial and metabolic dysfunction.

We discuss:

• Iñigo’s background in sports and decision to focus on education [3:45];
  
• The various energy systems and fuels used during exercise [11:15];
  
• Iñigo’s qualification of energy systems into six training zones [19:30];
  
• Lactate as an important fuel source [29:30];
  
• Zone 2 training—physiologic characteristics, fuel sources, lactate, and the transition into zone 3 [37:00];
  
• Using blood lactate levels (and zone-2 threshold) to assess mitochondrial function [43:30];
  
• Accessing mitochondrial function by testing one’s ability to utilize fat as fuel [51:30];
  
• Athletes vs. metabolically ill patients—mitochondria, fat oxidation, muscle glycogen capacity, “fat droplets”, and more [56:30];
  
• Physiologic characteristics of zone 3, zone 4, and the lactate threshold [1:16:30];
  
• Fueling exercise—dietary implications on glycolytic function [1:27:00];
  
• Relationship between exercise and insulin sensitivity (and what we can learn from studying patients with type 1 diabetes) [1:43:00];
  
• Metformin’s impact on mitochondrial function, lactate production, and how this affects the benefits of exercise [2:00:45];
  
• Raising awareness of the risk of “double diabetes” [2:11:30];
  
• How to dose zone 2 training, and balancing exercise with nutrition [2:14:30];
  
• Proposed explanation of the Warburg Effect: Role of lactate in carcinogenesis [2:23:30];
  
• Doping in cycling, and the trend towards altitude training [2:35:45] and;
  
• More.

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In this “Ask Me Anything” (AMA) episode, Peter and Bob dive deep into all things related to studying studies to help one sift through all the noise to find the signal. They define the various types of studies, how a study progresses from idea to execution, and how to identify study strengths and limitations. They explain how clinical trials work, as well as the potential for bias and common pitfalls to watch out for. They dig into key factors that contribute to the rigor (or lack thereof) of an experiment, and they discuss how to measure effect size, differentiate relative risk from absolute risk, and what it really means when a study is statistically significant. Finally, Peter lays out his personal process when reading through scientific papers.

If you’re not a subscriber and 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 on our website at the AMA #30 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• The ever changing landscape of scientific literature [2:15];
  
• The process for a study to progress from idea to design to execution [4:15];
  
• The various types of studies and how they differ [7:30];
  
• The different phases of a clinical trial [19:15];
  
• Observational studies and the potential for bias [26:30];
  
• Experimental studies: Randomization, blinding, and other factors that make or break a study [44:00];
  
• Power, p-values, and statistical significance [56:15];
  
• Measuring effect size: Relative risk vs. absolute risk, hazard ratios, and “Number Needed to Treat” [1:07:45];
  
• How to interpret confidence intervals [1:17:30];
  
• Why a study might be stopped before its completion [1:23:45];
  
• Why only a fraction of studies are ever published and how to combat publication bias [1:31:30];
  
• Why certain journals are more respected than others [1:40:30];
  
• Peter’s process when reading a scientific paper [1:43:45]; and
  
• More.

Sam Apple is the author of the book Ravenous: Otto Warburg, the Nazis, and the Search for the Cancer-Diet Connection, published in May 2021. In this episode, Sam describes the fascinating life story of Otto Warburg, a Nobel Prize-winning scientist who, despite being both Jewish and gay, survived Nazi Germany because of his valuable research on cellular metabolism and cancer. Sam describes Warburg’s observation that cancer cells consume large amounts of glucose anaerobically – a phenomenon subsequently known as the “Warburg Effect” – and relates how Warburg’s seminal work on this topic was largely forgotten after the discovery of oncogenes, only to regain relevance decades later within the field of cancer biology. Sam sheds light on the current debate around Warburg’s interpretation of the causes of cancer, and Peter gives his personal take on the matter. Finally, Peter and Sam tie it all together with a discussion about cancer prevention, the role of hyperinsulinemia, and the link between dietary sugar and cancer.

We discuss:

• Sam’s interest in Otto Warburg and work as a writer [2:30];
  
• Otto Warburg’s dedication to science and his complicated life in Germany [14:00];
  
• Warburg’s interest in cancer and early discoveries about cellular consumption of oxygen [23:00];
  
• The role models who fueled Warburg’s desire to make a great discovery [34:15];
  
• How Warburg described the primary and secondary causes of cancer [42:15];
  
• Warburg’s Nobel Prize in 1931 [45:45];
  
• Warburg’s life and work during WWII in Nazi Germany [46:30];
  
• Warburg’s research in hydrogen transfers and coenzymes—his best science? [59:45];
  
• Warburg’s decision to stay in Germany after WWII [1:03:30];
  
• Discovery of oncogenes in the 1970s and the decline in interest in Warburg’s ideas [1:07:30];
  
• The renaissance of Warburg’s ideas on cancer metabolism and a new explanation for the Warburg Effect [1:13:45];
  
• The argument against the Warburg Effect as a primary cause of cancer and the potential role hyperinsulinemia [1:21:15];
  
• Identifying primary and secondary causes of cancer for the purpose of prevention [1:27:00];
  
• The link between sugar, fructose, and cancer [1:35:30];
  
• Sam’s reflections on the work that went into Ravenous [1:39:45];
  
• More

Patrick Radden Keefe is an award-winning staff writer at The New Yorker and the bestselling author of Empire of Pain: The Secret History of the Sackler Dynasty. In this episode, Patrick tells the story of the Sackler family and Purdue Pharma - makers of the pain management drug OxyContin, providing the backdrop for the ensuing opioid epidemic and public health crisis. He reveals the implicit and sometimes explicit corruption of all parties involved in the development, approval, and marketing of OxyContin, leading to a cascade of unintended consequences including addiction and death. He explains the unfortunate lack of accountability for the current crisis, as well as what it all means for those with legitimate pain management needs. Finally, he examines the difficult path ahead towards finding a solution.

We discuss:

• Patrick’s investigation into distribution and use of drugs in our society [3:55];
  
• The scale of the opioid crisis [9:15];
  
• The Sackler brothers: family life, career in the pharmaceutical industry, and role in the current crisis [11:45];
  
• Purdue Pharma: origins, early years, and move towards pain management drugs [17:30];
  
• The development of OxyContin: its conception, marketing, and the controversy around the FDA approval process [25:30];
  
• Early reports of OxyContin addiction and unintended consequences and how Purdue Pharma sidestepped responsibility [40:45];
  
• The many paths to addiction and abuse of OxyContin and the ensuing downfall of Purdue Pharma [47:15];
  
• Peter’s personal experience with OxyContin [57:00];
  
• Pain—the “fifth vital sign,” how doctors are trained in pain management, and the influence of money [1:08:00];
  
• Other players that helped facilitate the eventual opioid crisis [1:16:15];
  
• Lack of accountability following the investigation and prosecution of Purdue and the Sackler family [1:23:30];
  
• Legacy of the Sackler family and their disconnect from reality [1:34:45];
  
• Patrick’s views on the regulation and use of pain management drugs [1:42:15];
  
• The difficult path forward [1:44:45]; and
  
• More.

Allan Sniderman is a highly acclaimed Professor of Cardiology and Medicine at McGill University and a foremost expert in cardiovascular disease (CVD). In this episode, Allan explains the many risk factors used to predict atherosclerosis, including triglycerides, cholesterol, and lipoproteins, and he makes the case for apoB as a superior metric that is currently being underutilized. Allan expresses his frustration with the current scientific climate and its emphasis on consensus and unanimity over encouraging multiple viewpoints, thus holding back the advancement of metrics like apoB for assessing CVD risk, treatment, and prevention strategies. Finally, Allan illuminates his research that led to his 30-year causal model of risk and explains the potentially life-saving advantages of early intervention for the prevention of future disease.

We discuss:

• Problems with the current 10-year risk assessment of cardiovascular disease (CVD) and the implications for prevention [4:30];
  
• A primer on cholesterol, apoB, and plasma lipoproteins [16:30];
  
• Pathophysiology of CVD and the impact of particle cholesterol concentration vs. number of particles [23:45];
  
• Limitations of standard blood panels [29:00];
  
• Remnant type III hyperlipoproteinemia—high cholesterol, low Apo B, high triglyceride [32:15];
  
• Using apoB to estimate risk of CVD [37:30];
  
• How Mendelian randomization is bolstering the case for ApoB as the superior metric for risk prediction [40:45];
  
• Hypertension and CVD risk [49:15];
  
• Factors influencing the decision to begin preventative intervention for CVD [58:30];
  
• Using the coronary artery calcium (CAC) score as a predictive tool [1:03:15];
  
• The challenge of motivating individuals to take early interventions [1:12:30];
  
• How medical advancement is hindered by the lack of critical thinking once a “consensus” is reached [1:15:15];
  
• PSK9 inhibitors and familial hypercholesterolemia: two examples of complex topics with differing interpretations of the science [1:20:45];
  
• Defining risk and uncertainty in the guidelines [1:26:00];
  
• Making clinical decisions in the face of uncertainty [1:31:00];
  
• How the emphasis on consensus and unanimity has become a crucial weakness for science and medicine [1:35:45];
  
• Factors holding back the advancement of apoB for assessing CVD risk, treatment, and prevention strategies [1:41:45];
  
• Advantages of a 30-year risk assessment and early intervention [1:50:30];
  
• More.

Today’s episode of The Drive is a rebroadcast of the conversation with Rick Johnson (originally released January 6th, 2020). This episode was one of the most popular discussions to-date and is a prelude to an upcoming follow-up discussion which will be coming out in February 2022 along with the release of Rick’s new book.

In this episode, Rick Johnson, professor of nephrology at the University of Colorado, explains how his research into the causes of blood pressure resulted in a change of research direction to focus more on how fructose has such profound metabolic effects. Rick begins by talking about the relationship between salt and high blood pressure, then provides a masterclass into uric acid, and then expertly reveals the mechanisms and pathways by which sugar (specifically fructose) can profoundly impact metabolic health. From there, he explains how he applies this information to real life patients as well as touches on some of the most promising ideas around pharmacotherapy that are being developed in response to the epidemics of fatty liver, insulin resistance, diabetes, and obesity. Furthermore, Rick gives his take on artificial sweeteners compared to real sugar, discusses cancer’s affinity for fructose, and much more.

We discuss:

• The connection between blood pressure and fructose that shifted Rick’s professional focus [3:00];
  
• The relationship between salt and blood pressure (and the role of sugar) [4:45];
  
• Defining fructose, glucose, and sugar [18:30];
  
• An ancient mutation in apes that explains why humans turn fructose into fat so easily [22:00];
  
• The problems with elevated uric acid levels, and what it tells us about how sugar causes disease [30:30];
  
• How sugar causes obesity—explaining the difference in glucose vs. fructose metabolism and the critical pathway induced by fructose [39:00];
  
• Why drinking sugar is worse than eating it [49:00];
  
• Unique ability of sugar to drive oxidative stress to the mitochondria, insulin resistance, and diabetes [53:00];
  
• Why cancer loves fructose [59:20];
  
• The many areas of the body that can use fructose [1:04:00];
  
• Fructokinase inhibitors—a potential blockbuster? [1:06:15];
  
• Treating high uric acid levels—Rick’s approach with patients [1:09:00];
  
• Salt intake—what advice does Rick give his patients? [1:15:30];
  
• How excess glucose (i.e., high carb diets) can cause problems even in the absence of fructose [1:20:00];
  
• Artificial sweeteners vs. real sugar—which is better? [1:28:15];
  
• Umami, MSG, alcohol, beer—do these have a role in metabolic illness? [1:32:45];
  
• Fructose consumption—Is any amount acceptable? Is fruit okay? Where does Rick draw a hard line? [1:37:45]
  
• How does Rick manage the sugar intake of his young kids? [1:42:00]; and
  
• More.
  

In this “Ask Me Anything” (AMA) episode, Peter and Bob discuss all things related to GLP-1 agonists—a class of drugs that are gaining popularity for the treatment of obesity. They cover the discovery of these peptides, their physiology, and what it is they do in their natural state. Next, Peter and Bob break down a recently published study which showed remarkable results for weight loss and other metabolic parameters using a once-weekly injection of the GLP-1 agonist drug semaglutide, also known as Ozempic, in overweight and obese patients. Finally, they compare results from the semaglutide study to results from various lifestyle interventions and give their take on the potential future of GLP-1 agonists.

If you’re not a subscriber and 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 on our website at the AMA #29 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Remarkable results of a recent study in overweight adults [2:15];
  
• Key background on insulin, glucagon and the incretin effect [4:00];
  
• What is GLP-1 and how does it work? [16:30];
  
• 2021 semaglutide study: remarkable results, side effects, and open questions [30:00];
  
• Semaglutide vs. lifestyle interventions: comparing results with semaglutide vs. lifestyle interventions alone [44:00];
  
• Closing thoughts and open questions on the therapeutic potential of semaglutide [47:30]; and
  
• More

James Clear is the author of the New York Times bestseller Atomic Habits. His extensive research into human behavior has helped him identify key components of habit formation and develop the “Four Laws of Behavioral Change.” In this episode, James provides insights into how both good and bad habits are formed, including the influence of genetics, environment, social circles, and more. He points to changes one can make to cultivate more perseverance and discipline and describes the profound impact habits can have when tying them into one’s self-identity. Finally, James breaks down his “Four Laws of Behavioral Change” and how to use them to create new habits, undo bad habits, and make meaningful changes in one’s life.

We discuss:

• Why James became deeply interested in habits [1:45];
  
• Viewing habits through an evolutionary lens [6:00];
  
• The power of immediate feedback for behavior change, and why we tend to repeat bad habits [9:15];
  
• The role of genetics and innate predispositions in determining one’s work ethic and success in a given discipline [14:30];
  
• How finding one’s passion can cultivate perseverance and discipline [23:15];
  
• Advantages of creating systems and not just setting goals [29:15];
  
• The power of habits combined with self-identity to induce change [36:30];
  
• How a big environmental change or life event can bring on radical behavioral change [50:30];
  
• The influence of one’s social environment on their habits [54:15];
  
• How and why habits are formed [1:00:30];
  
• How to make or break a habit with the “Four Laws of Behavior Change” [1:09:30];
  
• Practical tips for successful behavioral change—the best strategies when starting out [1:16:15];
  
• Self-forgiveness and getting back on track immediately after slipping up [1:30:30];
  
• Law #1: Make it obvious—strategies for identifying and creating cues to make and break habits [1:39:45];
  
• Law #2: Make it attractive—ways to make a new behavior more attractive [1:47:45];
  
• Law #3: Make it easy—the 2-minute rule [1:58:45];
  
• Law #4: Make it satisfying—rewards and reinforcement [2:03:30];
  
• Advice for helping others to make behavioral changes [2:06:00];
  
• More.

David Nutt is a psychiatrist and a neuroscientist at Downing College, Cambridge.  His research focuses on illicit drugs—their harm, classification, and potential for therapeutic use in psychiatry. In this episode, David discusses his framework for assessing the potential harm caused by common recreational drugs and explains how they are regulated, which is oftentimes misaligned with actual risk. He describes in detail the neurobiology, mechanisms of action, and addiction potential of alcohol, opiates, cocaine, and methamphetamine and contrasts those with psychedelics, which have been given a similar regulatory classification despite their relatively low risk of harm and their numerous potential therapeutic uses. Additionally, David explains the promise of psychedelics like ketamine, MDMA, and psilocybin for treating drug addiction and depression and discusses how political pressures have created roadblocks to future necessary research.

We discuss:

• David’s early interest in the brain and experience in psychiatry [2:45];
  
• David’s brief work on government drug policy in the UK [10:15];
  
• A scale for rating the relative harm of certain drugs [13:45];
  
• The contrast in regulation between cannabis vs. alcohol and why research on potential benefits of cannabis is lacking [19:15];
  
• The opiate crisis and rise of fentanyl: the cause and potential solution [25:00];
  
• The science of addiction and the potential use of psychedelics for treating drug addiction [35:00];
  
• Cocaine: mechanisms of action and risks [41:45];
  
• Methamphetamine and crystal meth: mechanisms of action and neurotoxicity [48:15];
  
• How psychedelics came to be classified as schedule I drugs despite their numerous therapeutic uses [52:45];
  
• The history of MDMA and the bad science and political forces leading to its demonization [1:08:45];
  
• History of ketamine, medical use of esketamine, and the waning effects of psychedelics with increasing usage [1:13:30];
  
• Psilocybin for depression: David’s promising research and the roadblocks to more robust experiments [1:20:15];
  More.

Robert (Bob) Gatenby is a radiologist who specializes in exploring theoretical and experimental models of evolutionary dynamics in cancer and cancer drug resistance. He has developed an adaptive therapy approach for treating cancer which has shown promise in improving survival times with less cumulative drug use. In this episode, Bob explains what brought him into medicine, his search for organizing principles from which to understand cancer, and the mathematical modeling of other complex systems that led him to model the dynamics of tumor cell changes in cancer. He discusses his pilot clinical trial treating metastatic prostate cancer, in which he used an evolutionary game theory model to analyze patient-specific tumor dynamics and determine the on/off cycling of treatment. He describes how altering chemotherapy to maximize the fitness ratio between drug-sensitive and drug-resistant cancer cells can increase patient survival and explains how treatment of metastatic cancer may be improved using adaptive therapy and strategic sequencing of different chemotherapy drugs.

We discuss:

• Bob’s unlikely path to medicine and disappointment with his medical school experience [1:45];
  
• Rethinking the approach to cancer: using first principles and applying mathematical models [12:15];
  
• Relating predator-prey models to cancer [26:30];
  
• Insights into cancer gathered from ecological models of pests and pesticides [32:15];
  
• Bob’s pilot clinical trial: the advantages of adaptive therapy compared to standard prostate cancer treatment [41:45];
  
• New avenues of cancer therapy: utilizing drug-sensitive cancer cells to control drug-resistant cancer cells [48:15];
  
• The vulnerability of small populations of cancer cells and the problem with a “single strike” treatment approach [56:00];
  
• Using a sequence of therapies to make cancer cells more susceptible to targeted treatment [1:05:00];
  
• How immunotherapy fits into the cancer treatment toolkit [1:15:30];
  
• Why cancer spreads, where it metastasizes, and the source-sync trade off [1:20:15];
  
• Defining Eco- and Evo-indices and how they can be used to make better clinical decisions [1:29:45];
  
• Advantages of early screening for cancer [1:40:15];
  
• Bob’s goals for follow-ups after the success of his prostate cancer trial [1:42:15];
  
• Treatment options for cancer patients who have “failed therapy” [1:51:15];
  
• More.
  

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In this “Ask Me Anything” (AMA) episode, Peter and Bob discuss all things related to testosterone: what happens when testosterone levels are low, and the potential benefits and risks of testosterone replacement therapy (TRT). They explain the physiology of testosterone, how it works, and how its level changes over the course of a person's life. They have a detailed discussion about existing literature, which reveals vast potential structural, functional, and metabolic benefits of testosterone replacement therapy. They also take a very close look at potential risks of this therapy, with a focus on the controversial effects on cardiovascular disease and prostate cancer.

If you’re not a subscriber and 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 on our website at the AMA #28 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• A primer on the hormone testosterone and how it influences gene expression [3:30];
  
• How the body naturally regulates testosterone levels [11:30];
  
• The defining threshold for "low testosterone," how low T impacts men, and why free testosterone is the most important metric [16:15];
  
• When it makes sense to treat low testosterone [26:00];
  
• The structural and metabolic benefits of testosterone replacement therapy [29:15];
  
• Body composition changes with TRT [45:30];
  
• Changes in bone mineral density with TRT [48:15];
  
• The metabolic impact of TRT: glucose, insulin, triglycerides, and more [52:30];
  
• A study investigating testosterone replacement therapy for prevention or reversal of type 2 diabetes [59:30];
  
• The impact of TRT on metabolic parameters and body composition—A study comparing results from continuous vs. interrupted treatment [1:07:15]
• The controversy over TRT and cardiovascular disease [1:21:45];
  
• Two flawed studies that shaped perceptions of risks associated with TRT [1:44:15];
  
• The controversy over TRT and prostate cancer [1:56:45];
  
• Other potential risks with testosterone replacement therapy [2:02:15]; and
  
• More

Jeremy Loenneke has a Ph.D. in exercise physiology, a Master’s in nutrition and exercise, and is currently the director of the Kevser Ermin Applied Physiology Laboratory at the University of Mississippi, where he focuses his research on skeletal muscle adaptations to exercise in combination with blood flow restriction (BFR). In this episode, Jeremy explains the science of BFR and the mechanisms by which BFR training can produce hypertrophy using low loads. Here, he reviews anatomy and terminology of muscle structure and discusses the evidence that increasing muscular strength may not be dependent on increasing muscle size. Additionally, Jeremy goes into depth on how one might take advantage of BFR training, including practical applications for athletes and average people, as well as the situations for which BFR training would be most advantageous.

We discuss:

• Jeremy’s interest in exercise and weightlifting and his scientific training [3:30];
  
• The microstructure and physiology of muscle [8:00];
  
• Definitions of fast-twitch and slow-twitch muscle fibers [12:45];
  
• Comparison of strength vs. hypertrophy [21:30];
  
• Blood flow restriction training and the origins of the Kaatsu system [28:30];
  
• The details and metrics related to exercise under blood flow restriction [44:45];
  
• Considerations when training with blood flow restriction: loading, pace, rest, and risks [53:00];
  
• Blood flow restriction studies and the relationship between muscle size and muscle strength [1:04:15];
  
• Evidence that increasing muscular strength is not dependent on increasing the size of the muscle [1:16:30];
  
• Practical applications of blood flow restriction training for athletes and average people [1:27:30];
  
• Situations in which blood flow restriction training is most advantageous [1:35:30];
  
• The mechanisms by which blood flow restriction training can produce so much hypertrophy at such low loads [1:39:45];
  
• Applications of “passive” blood flow restriction training [1:47:15];
  
• What experiments would Jeremy do if he had unlimited resources? [1:51:45];
  
• More.

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Lance Armstrong is a legendary figure in professional cycling having won seven consecutive Tour de France titles but also a controversial figure facing scrutiny for the use of performance enhancing drugs. In this episode, Lance takes us through his meteoric rise to one of the most famous athletes in the world and his equally accelerated fall from grace. Lance describes how he persevered through his brutal diagnosis of testicular cancer before rattling off a historic run of seven consecutive Tour de France titles all while facing tremendous scrutiny for his alleged use of performance enhancing drugs such as EPO and cortisone. Lance opens up about his decision to come clean about his use of performance enhancing drugs, the remorse for how he treated other people during that time in his life, and the personal growth that’s helped him emerge on the other end of that. Finally, Lance recounts some of favorite stories from his cycling career, reflects on his legacy, and explains how he stays fit at age 50.

We discuss:

• What everyone wants to know—yes and no questions [2:15];
  
• Lance’s childhood and beginnings of a great athlete [4:15];
  
• Lance’s realization that he had a knack for racing after his first pro race at age 15 [13:00];
  
• The move to cycling full time and a desire to compete in the Olympics [16:30];
  
• Metrics tracked early in Lance’s career and his time with Motorola team [20:00];
  
• The grueling nature of the Tour de France and the beginnings of serious drug usage in cycling [27:00];
  
• The impact of EPO on cycling performance [35:15];
  
• Testicular cancer diagnosis—denial, torturous symptoms, and treatment [38:15]
  
• Livestrong is born [50:45];
  
• Return to cycling post-cancer and a crossroad in Lance’s career [53:45]
  
• Lance’s rise to prominence in the late 90s and the growing use of EPO in the sport [1:00:00];
  
• Racing in the early 2000’s, blood transfusions, and rivalry with Jan Ulrich [1:12:00];
  
• Retirement in 2005 and a comeback in 2009 [1:22:45];
  
• Lance’s decision to come clean and tell the truth [1:27:30];
  
• Growth through downfall: learning from his mistakes and helping others after their own fall from grace [1:33:00];
  
• Moving forward: Living his life, reflecting on his legacy, the state of Livestrong [1:42:30];
  
• Turning back the clock: Advice Lance would give to his 15 year-old self [1:46:45];
  
• Keeping fit at age 50 [1:51:00];
  
• More.

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Steve Rosenberg is the Chief of Surgery at the National Cancer Institute, a position he has held continuously for the past 47 years. Steve is a pioneer in the field of immunotherapies for cancer and a recipient of nearly every major award in science. In this episode, Steve discusses his inspiration for devoting his career to cancer research and describes his keen observation of two cases of spontaneous cancer remission, driving him to learn how to harness the immune system to treat cancer. Steve’s personal story essentially serves as a roadmap for the field of immunotherapy, from the very non-specific therapies such as interleukin-2, the discovery of tumor-infiltrating lymphocytes, checkpoint inhibitors, CAR T-cells, and adoptive cell therapy. Perhaps most importantly, Steve expresses his optimism for what lies ahead, especially in the face of some of the more recent discoveries with respect to tumor antigenicity. Finally, Steve discusses the human side of cancer which helps him to never lose sight of why he chose to become a physician.

We discuss:

• Steve’s childhood and inspiration to become a physician and medical researcher [3:15];
  
• Patients that influenced Steve’s thinking about cancer and altered the course of his career [13:15];
  
• The discovery of antigen presentation, Steve’s first job, and why he knew he wanted to study cancer [19:30];
  
• Cancer treatment in the early 1970’s and Steve’s intuition to utilize lymphocytes [26:45];
  
• Cancer cells versus non-cancer cells, and why metastatic cancer is so deadly [31:45];
  
• The problem with chemotherapy and promise of immunotherapy [38:30];
  
• How the immune system works and why it seems to allow cancer to proliferate [43:15];
  
• Steve discovers how to use interleukin-2 to mediate cancer regression [52:00];
  
• The immunogenic nature of certain cancers and the role of mutations in cancer [1:03:45];
  
• The improbable story of how CAR T cell therapy was developed [1:16:30];
  
• The discovery of tumor infiltrating lymphocytes (TIL) and engineering of T cells to recognize specific antigens [1:28:00];
  
• Steve’s experience treating President Ronald Reagan’s colon cancer [1:36:00];
  
• Why Steve has turned down many tempting job offers to focus on his research at the National Cancer Institute [1:41:00];
  
• The role of checkpoint inhibitors in cancer therapy and the promise of adoptive cell therapy [1:43:00];
  
• Optimism for using immunotherapy to cure all cancers [1:48:00];
  
• The human side of cancer and the important lessons Peter learned from working with Steve [1:52:15]; and
  
• More

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In this “Ask Me Anything” (AMA) episode, Peter and Bob discuss the longevity benefits from greater cardiorespiratory fitness (CRF) and greater muscle mass and strength. Conversely, they dive deep into the literature showing a rapid increase in morbidity and mortality risk as fitness levels decline with age. They also try to tease out the relative contributions of CRF, muscle mass, and strength. Additionally, they discuss the impact of fasting on muscle mass, the potential tradeoffs to consider, and finish by discussing why it’s critical to maximize your fitness level.

If you’re not a subscriber and 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 on our website at the AMA #27 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• VO2 max and its association with cardiorespiratory fitness [2:45];
  
• Changing mortality risk based on VO2 max and cardiorespiratory fitness [7:45];
  
• The profound impact of improving cardiorespiratory fitness [15:15];
  
• Muscle mass, function, and loss with aging: how it’s defined, measured, and the cutoff points for sarcopenia [25:00];
  
• Increasing mortality risk associated with declining muscle mass and strength [40:00];
  
• Muscle size vs. strength—which has the bigger impact on mortality risk? [58:00];
  
• Evaluating the cumulative impact of cardiorespiratory fitness and muscular strength on mortality risk when put together [1:03:30];
  
• Investigating the rising incidence in deaths from falls, and what role Alzheimer’s disease might play [1:09:00];
  
• The impact of fasting on muscle mass and the potential tradeoffs to consider [1:14:30];
  
• The critical importance of working to maintain muscle mass and strength as we age [1:20:30]; and
  
• More.

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Matt Kaeberlein is globally recognized for his research on the biology of aging and is a previous guest on The Drive. In this episode, Matt defines aging, the relationship between aging, chronic inflammation, and the immune system, and talks extensively about the most exciting molecules for extending lifespan. He discusses the current state of the literature of testing rapamycin (and rapalogs) in animals and humans, including Matt’s Dog Aging Project, and provides insights into how we can improve future trials by conceptualizing risk, choosing better endpoints, and working with regulators to approve such trials. He also examines the connection between aging and periodontal disease, biomarkers of aging, and epigenetic clocks. Finally, they explore some of the biological pathways involved in aging, including mTOR and its complexes, sirtuins, NAD, and NAD precursors.

We discuss:

• The various definitions of aging [3:25];
  
• The relationship between disease and the biology of aging [16:15];
  
• Potential for lifespan extension when targeting diseases compared to targeting biological aging [22:45];
  
• Rapamycin as a longevity agent and the challenges of targeting the biology of aging with molecules [32:45];
  
• Human studies using rapalogs for enhanced immune function [39:30];
  
• The role of inflammation in functional declines and diseases of aging [50:45];
  
• Study showing rapalogs may improve the immune response to a vaccine [56:15];
  
• Roadblocks to studying gero-protective molecules in humans [1:01:30];
  
• Potential benefits of rapamycin for age-related diseases—periodontal, reproductive function, and more [1:12:15];
  
• Debating the ideal length and frequency of rapamycin treatment for various indications like inflammation and longevity [1:21:30];
  
• Biomarkers of aging and epigenetic clocks [1:29:15];
  
• Prospects of a test that could calculate biological age [1:37:45];
  
• The Dog Aging Project testing rapamycin in pet dogs [1:42:30];
  
• The role of the mTOR complexes [1:58:30];
  
• mTor inhibitor called Torin2, mitochondrial disease and other potential pathways [2:09:45];
  
• Catalytic inhibitors, sirtuins, and NAD [2:19:15];
  
• NAD precursors: help or hype? [2:28:15]; and
  
• More.
  

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Lawrence Wright is the author of The Looming Tower: Al-Qaeda and the Road to 9/11 which won the 2007 Pulitzer Prize for general nonfiction and was named one of Time's top 100 books of all time.  In this episode, released just before the 20th anniversary of the September 11th attacks, Lawrence and Peter discuss the book and the lasting impact of that day. Lawrence reflects on his personal experiences on that day and how he was first drawn into reporting on the attacks. Lawrence then discusses in detail the history that led up to 9/11 which is really composed of two parallel stories. The first story is of the growing discontent in Muslim countries, the roots of Islamic radicalism, and how two extremists, Osama bin Laden and Ayman al-Zawahiri, joined forces to create the global terrorist organization Al-Qaeda. The second story is about how interpersonal and institutional conflicts between the FBI and CIA led to a massive failure in intelligence and resulted in multiple missed opportunities to predict and prevent the attacks on September 11th, 2001. Finally, they reflect on what we should have learned from 9/11 and the future of terrorism.

We discuss:

• Lawrence and Peter recount their personal experiences on September 11th, 2001 [3:30];
• How 9/11 changed the US into a security state and affected a generation [9:45];
• Lawrence’s early coverage of 9/11 and how he knew it was going to be “the story of our lifetime” [14:45];
• Egyptian politics and the foundation of radical Islam [22:45];
• Anwar Sadat’s presidency, assassination, and the birth of the radical Islamic movement [33:00];
• Aftermath of the Sadat assassination, and establishment of Al-Qaeda in Afghanistan [50:15];
• Osama bin Laden: Upbringing, involvement in the Soviet–Afghan War, and rise to celebrity status in Saudi Arabia [56:00];
• How the Western intervention in Saudi Arabia impacted Arab nationalist’s hatred of America [1:15:30];
• Theorizing on the role of the religion in holding back Islamic states from making progress towards democracy [1:20:30];
• Bin Laden’s time in Sudan [1:32:30];
• The CIA vs. the FBI: setting the stage for the failure of US intelligence [1:37:00];
• The mistake by US intelligence of not taking the bombings of the US embassies and the USS Cole seriously [1:46:00];
• Al-Qaeda in America: Losing the planners of the 9/11 attacks from our clutches and incompetence at the FBI and CIA [1:56:00];
• Problematic policies in Europe, and a direct message warning of the 9/11 attacks [2:14:45];
• The role of political infighting and personality conflicts that helped enable the 9/11 attacks and the lack of accountability [2:22:45];
• What came of the 9/11 commission, the role of the Saudi government, and the trials of Ali Soufan [2:36:00];
• Lessons from 9/11 and the future of terrorism [2:46:30]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter and Bob answer numerous follow-up questions to recently discussed deep-dive topics such as the use of continuous glucose monitors and getting the most from zone 2 exercise. They also discuss the incredible feats of cyclists in the Tour de France through the lens of the amazing performance physiology required from these athletes. Additionally, Peter ties the conversation together by sharing his foundational framework when considering different interventions, even in the absence of data from a randomized controlled trial.

If you’re not a subscriber and 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 on our website at the AMA #26 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Peter’s foundational framework when considering different interventions [1:30];
  
• Applying Peter’s framework to the idea of using a CGM [8:00];
  
• Why certain fruits have a bigger impact on glucose, and the limitations of a CGM can tell you [16:00];
  
• Importance of paying attention to insulin, and the prospects of a continuous monitor for insulin levels [20:00];
  
• How exercise impacts glucose and peak glucose numbers to stay under [24:15];
  
• Impact of anxiety on stress on glucose, and why it’s important to calibrate your CGM [26:30];
  
• The five main tools for managing blood glucose numbers [33:45];
  
• Benefits of moving or exercising after a meal, and where ingested carbohydrates get can be stored [37:15];
  
• How to make decisions about an action or intervention in the absence of data from a rigorous, randomized controlled trial [40:30];
  
• The incredible athletic feats of Tour de France cyclists [48:30];
  
• Different modalities for doing zone 2 exercise: running, rowing, cycling, and more [1:00:15];
  
• Proxies for knowing your in zone 2 short of using a lactate monitor [1:07:30];
  
• Monitoring lactate for zone 2 exercise [1:10:00]; and
  
• More.
  

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Steve Austad is a distinguished professor of biology at the University of Alabama and director of one of the Nathan Shock Centers of Excellence in aging biology. Steve's current research seeks to understand the underlying causes of aging, specifically with a long-term goal of developing medical interventions that slow the age-related decay of human health. In this episode, Steve tells Peter about his unusual childhood and stints as a cab driver and lion tamer. He goes on to describe what led to his focus on studying aging and some of the major challenges and limitations of working with laboratory animals. Steve and Peter talk about the relationship between caloric restriction and lifespan, including some of the most important studies exploring this question. Additionally, they hypothesize what might explain the sex-related differences in longevity between men and women, explain the importance of finding longevity biomarkers, and discuss the most promising molecules as potential longevity agents.

We discuss:

• Steve’s background and unusual childhood [2:30];
  
• Steve’s adventures driving a cab in New York City [9:00];
  
• How Steve drove to LA and accidentally became a lion tamer [13:30];
  
• How Steve’s early graduate school experiences led him to study longevity [23:00];
  
• The challenges and limitations of working with lab mice [30:45];
  
• The connection between caloric restriction and lifespan [43:00];
  
• Mice vs. rats and rodent aging experiments [51:15];
  
• The impact of dietary composition and the harm of sucrose: Comparing two caloric-restriction studies in monkeys [56:00];
  
• Challenges of studying animals due to major differences in the lab animal vs. wild animals [1:10:00];
  
• Human studies of calorie restriction [1:24:45];
  
• Better dietary protocols for humans: Alternatives to long-term caloric restriction [1:33:45];
  
• The protective effect of fasting [1:38:00];
  
• Reflecting on the sex differences in human lifespan, and why women have more neurodegenerative diseases [1:45:45];
  
• The importance of identifying longevity biomarkers and which ones show the potential to change the landscape of longevity research [2:03:30];
  
• Molecules showing the most promise as longevity agents [2:14:00]; and
  
• More.

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In this “Ask Me Anything” (AMA) episode, Peter and Bob dive deep into cancer screening, including why it’s important, what you need to know about a test, and Peter’s approach with patients. They specifically discuss various screening methods, explain important terms like sensitivity and specificity, and how layering and stacking different tests in tandem can improve predictive values. They conclude with a discussion on one of the more exciting screening tools, diffusion-weighted MRI, and how it’s changing the cancer screening landscape.

If you’re not a subscriber and 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 on our website at the AMA #25 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• The importance of cancer screening [1:15];
  
• Cancer screening terms: sensitivity, specificity, false positives, and false negatives [8:25];
  
• Cancer screening terms: positive and negative predictive value [17:00];
  
• Improving predictive value by layering tests, and the predictive values of mammograms [25:45];
  
• How smoking impacts the predictive value of cancer screening [30:45];
  
• Liquid biopsies for ruling out cancer and the blind spots of common cancer screening tests [33:00];
  
• The difference between cancer originating from inside versus outside the body [41:15];
  
• How diffusion-weighted MRI is changing cancer screening [45:15];
  
• Summary of Peter’s approach to cancer screening [53:45]; and
  
• More.

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Hugh Jackman is an award-winning actor and an overall fascinating and introspective individual. In this episode, Hugh reflects upon his acting career, including how he navigated many tough decisions that led to important professional turning points for him. Peter and Hugh have an intimate discussion related to handling professional criticism, self-identity, spirituality, raising kids, and the role that past trauma often plays in extremely driven individuals. Hugh gives the inside scoop on some of his most well-known character roles and explains how he finds the energy to consistently perform. Finally, they tie the conversation together with a discussion on the importance of physical and mental health and wellbeing.

We discuss:

• Hugh’s voracious curiosity and early years of his acting career [2:15];
  
• Self-identity, overworking, and the importance of living well [9:15];
  
• Handling criticism and letting go of the desire to please everyone [18:30];
  
• Dismissing vitriol on social media, and the challenge of communicating science [28:15];
  
• Going with your gut and the value in finding the right partner [31:30];
  
• A hard decision that lead to a turning point in Hugh’s life [40:15];
  
• How driven personalities often develop from a place of trauma, and how to avoid going from productive to destructive [47:00];
  
• The effect of fame on Hugh’s family [58:45];
  
• How Hugh finds the energy to consistently perform, and the spiritual connection he feels when acting [1:07:15];
  
• Hugh’s experiences on the set of The Fountain and the meaning behind the film [1:26:30];
  
• The potential of imagination, the idea of a higher power, and thoughts on science vs. religion [1:33:45];
  
• The deep connection Hugh felt to Logan (his character in Wolverine) [1:41:45];
  
• Reflections on physical aging, emotional wellbeing, and longevity [1:55:15]; and
  
• More

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Gary Taubes is an investigative science and health journalist and a best-selling author. In this podcast, Gary explains how he developed a healthy skepticism for science as he was transitioning from being a physics major to beginning as a science journalist. He talks about how he was particularly drawn to sussing out “pathologic science,” telling the stories behind his books on the discovery of the W and Z bosons and cold fusion, emphasizing the need for researchers to perform a thorough background analysis. Gary then describes how his work came to focus on public health, nutrition, and obesity. He provides a great historic overview of obesity research and provides his explanation for why the conventional wisdom today is incorrect.
We discuss:

• Gary’s background in science and journalism, and developing a healthy skepticism for science [2:20];
  
• Gary’s boxing experience, and the challenge of appreciating behavioral risk [8:40];
  
• How Gary developed his writing skills, and what the best science writers do well [16:45];
  
• Example of how science can go wrong, and the story behind Gary’s first book, Nobel Dreams [25:15];
  
• Theoretical vs. experimental physicists: The important differentiation and the relationship between the two [36:00];
  
• Pathological science: research tainted by unconscious bias or subjective effects [40:30];
  
• Reflecting on the aftermath of writing Nobel Dreams and the legacy of Carlo Rubbia [49:45];
  
• Scientific fraud: The story of the cold fusion experiments at Georgia Tech and the subject of Gary’s book, Bad Science [53:45];
  
• Problems with epidemiology, history of the scientific method, and the conflict of public health science [1:09:00];
  
• Gary’s first foray into the bad science of nutrition [1:26:45];
  
• Research implicating insulin’s role in obesity, and the story behind what led to Gary’s book, Good Calories, Bad Calories [1:36:15]
  
• The history of obesity research, dietary fat, and fat metabolism [1:46:00]
  
• The evolving understanding of the role of fat metabolism in obesity and weight gain [1:55:15]
  
• Mutant mice experiments giving way to competing theories about obesity [2:04:00]
  
• How Gary thinks about the findings that do not support his alternative hypothesis about obesity [2:08:00]
  
• Challenges with addressing the obesity and diabetes epidemics, palatability and convenience of food, and other hypotheses [2:14:45];
  
• Challenging the energy balance hypothesis, and the difficulty of doing good nutrition studies [2:25:00]; and
  
• More.
  

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Dr. Patricia Corby is Associate Professor of Oral Medicine and Associate Dean of Translational Research at Penn Dental Medicine. Her work focuses on the importance of providing dental services alongside critical public healthcare services, like cancer treatment. In this episode, Pat provides an overview of dental anatomy, the importance of oral hygiene to overall health, and the association of poor oral health and systemic diseases like cancer and diabetes. She addresses tooth decay, oral hygiene in children, the utility of dental products, and ideal oral care regimens for different populations. She also discusses issues specific to immunocompromised patients and those with chronic illnesses as well as her own research with cancer patients undergoing radiation treatment.

We discuss:

• Anatomy of teeth and the purpose of the dental pulp—a highly vascularized and innervated region of the tooth [3:00];
• Types of teeth and the different purpose they serve [14:15];
• Anatomy of the oral cavity, bacteria in the mouth, and what a healthy mouth looks like [18:10];
• Pat’s study demonstrating the importance of flossing [23:00];
• Detrimental effects of sugar and the importance of fluoride and oral hygiene [31:45];
• Oral health challenges for cancer patients and immunocompromised people [39:45];
• Pat’s current research on cancer patients undergoing radiation treatment and the oral health risks associated with human papilloma virus (HPV) [50:00];
• Periodontal disease: caries and root canals [57:30];
• The relationship between poor oral health and systemic health diseases [1:11:00];
• Potential connection between oral hygiene and COVID-19 [1:17:45];
• Dry mouth leading to oral infections and ways to prevent it [1:22:30];
• What determines the appearance of teeth, methods of teeth whitening, and whether you should remove mercury fillings [1:27:30];
• Importance of fluoride for preventing tooth decay, and dental care for children [1:32:45];
• Useful dental products: floss, electrics toothbrushes, and more [1:39:15];
• Ideal oral care regimens [1:47:30]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter and Bob dive deep into nicotine, a complicated and interesting molecule that has effects on both the brain and the body. They analyze the results of the studies that describe nicotine’s cognitive benefits and potential for inducing weight loss. They talk about a smoking cessation technique called nicotine replacement therapy and give a full breakdown of the various routes of administration, dosing, and safety. Finally, they explore the fascinating and counterintuitive observation that cigarette smokers are less likely to get a severe case of COVID-19.

If you’re not a subscriber and 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 on our website at the AMA #23 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• How Peter first became interested in the potential benefits of nicotine [1:15];
  
• Untangling nicotine from tobacco [6:00];
  
• Nicotine replacement therapy (NRT) for quitting smoking: products, protocols, and a review of the literature [9:30];
  
• The cognitive benefits of nicotine: Overview of the literature [15:50];
  
• Where nicotine has the most positive impact on cognition [30:30];
  
• Possible mechanisms conferring the benefits of nicotine [37:00];
  
• How modafinil and other nootropics compare to nicotine [47:15];
  
• How nicotine may induce weight loss [54:00];
  
• Relationship between smoking and COVID-19: Analyzing the observation that smoking appears protective against COVID-19 [1:01:45];
  
• Breakdown of the various nicotine replacement therapies: route of administration, dosing, and safety [1:11:30];
  
• Concluding thoughts on nicotine: use cases, addictive properties, and more [1:19:45]; and
  
• More.

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Paul Offit is a pediatrician specializing in infectious diseases and an expert in virology and vaccine development. He currently serves on the FDA committee evaluating COVID-19 vaccines. In this episode, Paul’s second appearance on The Drive, he provides an update on all the SARS-CoV-2 vaccines currently deployed, explains why the concerns raised around the mRNA vaccines are not legitimate, and offers his view on the prospects and timeframe of reaching herd immunity. He also takes a deep dive into immunology, explaining the short-term and long-term immune response to both natural infection and vaccination and how these two can function together to provide durable immunity. Additionally, they discuss the theories on the origins of this virus, what impact the new COVID-19 variants might have, and the recent pausing of the J&J vaccine. Finally, they discuss how we can be better prepared for an inevitable future outbreak of a novel virus. This episode was originally recorded on April 14, 2021.

We discuss:

• Overview and current status of the SARS-CoV-2 vaccine strategies [4:10];

• Addressing concerns about mRNA vaccines [9:00];

• How the failure to make an effective HIV vaccine aided the development of a COVID-19 vaccine [16:45];

• Where SARS-CoV-2 falls on the spectrum of its ability to mutate and what that means for immunity and vaccination [21:30];

• How the combination of short-term and long-term immune response to SARS-CoV-2 work together to provide durable immunity [28:00];

• Importance of understanding relative vs. absolute risk reduction [38:15];

• Implications of pausing the J&J vaccine due to reports of blood clotting in the brain [42:45];

• What constitutes herd immunity and the concerns of rising vaccine hesitancy [47:45];

• When we might reach herd immunity, future vaccines for children, and long-term outlook for maintaining population immunity [58:45];

• Theories about the origins of SARS-CoV-2 [1:07:00];

• Preparing for the possibility of a future pandemic and how we can learn from our mistakes [1:10:40]; and

• More.

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Michael Rintala is a sports medicine chiropractor and one of only 18 international instructors teaching dynamic neuromuscular stabilization (DNS) for the Prague School of Rehabilitation. This episode focuses on understanding DNS, including the foundational principles and how it relates to human motor development. Michael also shares the most common injuries and issues he sees in patients in his practice, such as postural problems and back pain, and how the movements of a DNS program are used to avoid injury, maintain longevity, and improve sports performance.

We discuss:

• Michael’s background in chiropractic sports medicine and rehabilitation (3:15);
• The Prague School of Rehabilitation, and functional rehabilitation as the foundation of the dynamic neuromuscular stabilization (DNS) program (5:00);
• Foundational principles of DNS, and the role of the diaphragm in muscular stability (19:00);
• Types of muscle contractions (28:15);
• Human motor development through the lens of DNS, and when issues begin to arise (32:30);
• Common postural syndromes (50:00);
• Increasing functional threshold to minimize time in the functional gap (56:45);
• DNS for injuries, pain, pre-habilitation, and performance enhancement (1:03:45);
• Etiology of back pain (1:10:00);
• How a stress fracture in his back led Michael to the Prague School (1:16:00);
• The Prague School curriculum: 3 tracks for certification in DNS (1:20:45); and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter and Bob discuss all things related to insulin resistance by revisiting the important points made in the fascinating, yet quite technical, episode of The Drive with Gerald Shulman. They devote the entire discussion to understanding the condition known as insulin resistance, how it’s measured, how it manifests in the muscle and liver, and ultimately, what we can do about it.

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We discuss:

• Phil’s background in running, and training insights from a six-day race (2:30);
• The difference between being “fit” and being “healthy” (11:00);
• Defining the aerobic and anaerobic systems, and why VO2 max doesn’t predict performance (18:15);
• Defining maximum aerobic function (MAF), determining your MAF heart rate with Phil’s 180 Formula, and why a strong aerobic system is crucial to health and performance (24:00);
• Using the MAF test to track and improve your aerobic fitness (37:30);
• How increasing your sub-max pace at a given heart rate can increase your maximum pace (40:00);
• The impact of nutrition on one’s ability to use fat as fuel while exercising (43:00);
• Phil’s nutritional approach with patients, the concept of “carbohydrate intolerance” (51:45);
• Assessing the impact of a low-carb diet on high intensity exercise and anaerobic performance (58:00);
• Extracting insights from world-class marathoners (1:04:45);
• How being “overfat” affects health and performance, and ways to decrease excess body fat (1:13:30); and
• More.

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Robert Abbott is a six-time Emmy award winner and the director of “The Last Days of Knight,” the behind-the-scenes documentary of legendary coach Bobby Knight, and the events that led to his termination from Indiana University. In this episode, Robert takes us through his investigative journey, which revealed cautionary tales of a winning at all costs environment—how pain often gets left in the wake of unchecked anger, ego, and perfectionism. Robert reflects on Knight’s legacy and extracts lessons in self-awareness and accountability that can be applied to ensure history doesn’t repeat itself.

We discuss:

• Robert’s career covering sports and interesting athletes (2:30);
• Robert’s early impression of Bobby Knight’s controversial persona (10:15);
• The journalistic work that uniquely prepared Robert for his Bobby Knight story (13:30);
• The cost of excellence in sports—cautionary tales of ‘greatness at any cost’ (19:15);
• Knight’s coaching style, waning success in the 90s, and what put him on Robert’s radar (25:30);
• Three alarming accounts from a former player (Neil Reed) that launched Robert’s investigation into Bobby Knight (35:15);
• The “win-first” environment at Indiana that provided cover for Knight’s toxic behavior (44:45);
• Knight’s ego swells—a shift from team-first to “I” and “me” (53:00);
• How patience, honesty, and gaining trust with his sources paid off in his reporting on Bobby Knight (1:01:30);
• The vicious cycle and anger and shame, and why Bobby Knight is so interesting to Peter (1:08:00);
• Releasing the choking tape—Breaking open the Knight story, vindicating his earlier reporting, and the most powerful moment Robert has ever witnessed in his journalistic career (1:20:00);
• The bittersweet story of Neil Reed—triumph, PTSD, and breaking the cycle of pain (1:43:15);
• Examining Bobby Knight's legacy, and how society can avoid a repeat of similar devastating situations (1:57:30);
• Final thoughts on Bobby Knight and the pain left in his wake (2:08:00); and
• More.

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James O’Keefe is a preventative cardiologist and bestselling author of The Forever Young Diet and Lifestyle. In this episode, James discusses cardiac physiology and what makes the human heart susceptible to disease. He provides evidence for what supports his approach to exercise--elucidating both positive and negative kinds of exercise for heart health. He also discusses the role of nutrition, specific nutrients, and pharmacological interventions to support heart and brain longevity.

In this “Ask Me Anything” (AMA) episode, Peter and Bob explore the quality of evidence for hot and cold therapy. In the discussion, they evaluate the safety, efficacy, and opportunity costs of various hot and cold therapy protocols, and Peter ultimately considers the addition of dry sauna to his longevity toolkit. Once again, Bob Kaplan, Peter’s head of research, will be asking the questions. If you’re not a subscriber and 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 on our website at the AMA #16 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• How stress can show up as physical pain, and tips for changing time zones [1:45];
• Literature overview of heat and cold therapy [7:15];
• Cold therapy for delayed onset muscle soreness (DOMS) [12:00];
• Quality of evidence for cold therapy for depression or immune enhancement [19:30];
• Cold therapy and brown adipose tissue (BAT) [21:15];
• Weighing the safety, efficacy, and opportunity cost of cold therapy [28:45];
• An overview of heat therapy benefits [40:00];
• Longevity benefits of sauna—reviewing the studies [41:30];
• Limitations in the sauna literature—Where might we be fooled? [54:30];
• Possible mechanisms conferring the longevity benefits of sauna, and how it compares to exercise [1:02:15];
• Parting thoughts on sauna, opportunity costs, and Bob’s personal regimen [1:06:30]; and
• More.

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Beth Lewis is a former professional dancer and a self-described “educator of movement” who has an unmatched ability to assimilate information and customize training plans from multiple training systems. In this episode, Beth takes us through how she identifies problematic movement patterns and postures to help individuals relieve pain, avoid injury, and move better within all types of exercise. She explains how movement is in fact a trainable skill and provides suggestions for what people can add to their exercise routine to benefit their health and longevity.

We discuss:

• Beth’s “way of no way” training philosophy [4:45]
• Beth’s background in dancing and how she ended up in New York City [7:30]
• Beth’s transition to fitness coaching and how her training philosophy has evolved [12:45];
• Functional Range Conditioning and scapular mobility [21:50];
• An overview of Postural Restoration Institute and Peter’s squat assessment [35:30];
• The important connection between the ribs and breathing [39:45];
• The role of sitting and external stress in chronic muscular tension [42:30];
• The important role of your toes, minimalist footwear, and toe yoga [44:30];
• Dynamic Neuromuscular Stabilization (DNS) [48:30];
• A different view on knee valgus [52:45];
• Is there such a thing as “bad posture”? [56:30];
• How Beth identifies an issue, addresses it, and keeps clients motivated [58:45];
• Lifting weights, the Centenarian Olympics, and dancing into old age [1:11:00];
• The importance of the hamstrings versus abs [1:21:15];
• Benefits of rowing, and why everyone should add it to their exercise regimen [1:27:15]
• Different roles of concentric versus eccentric strength [1:35:15];
• Flexibility and high-intensity interval training (HIIT) [1:39:40];
• Training versus playing sports, and the best type of activity for kids [1:43:00]; and
• More.

Renowned social psychologists Carol Tavris and Elliot Aronson are the co-authors of Mistakes Were Made (But Not By Me), a book which explores the science of cognitive biases and discusses how the human brain is wired for self-justification. In this episode, Carol and Elliot discuss how our desire to reconcile mental conflicts adversely affects many aspects of society. The two give real-world examples to demonstrate the pitfalls in attempts to reduce mental conflict, or dissonance. The examples reveal that no one is immune to dissonance reduction behavior, how intellectual honesty can be trained and lastly, how to think critically in order to avoid engaging in harmful dissonant behaviors.

We discuss:

• Carol and Elliot’s respective background, collaboration history, and their decision to write Mistakes Were Made (But Not By Me) [4:00];
• The theory of cognitive dissonance, and real examples of dissonance reduction in action [11:15];
• How Elliot advanced the theory of cognitive dissonance [23:00];
• The evolutionary reason for dissonance reduction, and cultural differences in what causes cognitive dissonance [30:30];
• The great danger of smart, powerful people engaging in dissonance reduction [35:15];
• Two case studies of cognitive dissonance in criminal justice [39:30];
• The McMartin preschool case study—The danger in making judgements before knowing all the information [43:30];
• How ideology distorts science and public opinion [56:30];
• How time distorts memories [58:30];
• The downside of certainty [1:05:30];
• Are we all doomed to cognitive dissonance?—How two people with similar beliefs can diverge [1:09:00];
• Cognitive dissonance in the police force [1:21:00];
• A toolkit for overcoming cognitive dissonance [1:27:30];
• Importance of separating identity from beliefs, thinking critically, & and the difficulty posed by political polarity [1:30:30];
• How to impart the lessons from their work into future generations [1:48:00]; and
• More.

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World-renowned lipidologist Tom Dayspring returns to give an update on the current thinking in lipidology as a follow-up to his 2018 five-part podcast series. In this episode, Tom discusses the growing consensus that atherogenic lipoproteins are essential drivers of atherosclerotic vascular disease. Tom further emphasizes apolipoprotein B (apoB) and lipoprotein(a) (Lp(a)). He provides insights into risk assessment, including which lab metrics to use, how to interpret them, and the appropriate therapeutic targets. Additionally, Tom discusses the most recent developments in lipid-lowering drug therapies—from the continued evolution of PCSK9 inhibitors, to the latest understanding of EPA and DHA, and the most recent addition of bempedoic acid to the list of therapeutic agents.

We discuss:

• The latest in the field of lipidology and cardiovascular disease [3:45];
• Apolipoproteins—the key to understanding lipid biology [9:30];
• ApoB as a preferred metric over LDL-P [16:30];
• Therapeutic goals for apoB concentration [21:45];
• Drivers of atherosclerosis [34:15];
• Overview and current thinking on high density lipoproteins (HDLs)—Is it a useful metric? [37:00];
• Lipoprotein(a)—the most dangerous particle you’ve never heard of [55:00];
• Are low density lipoprotein triglycerides (LDL-TGs) a useful metric? [1:13:15];
• Tom’s preferred lab measurements [1:17:45];
• The latest in lipid-lowering therapies [1:21:30];
• The different pathways among various lipid-lowering drugs [1:30:45];
• The latest on EPA and DHA [1:38:15];
• Fibrates—an underappreciated treatment for hypercholesterolemia [1:49:45] and;
• More.

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Irene Davis is the founding Director of the Spaulding National Running Center at the Harvard Medical School. In this episode, Irene describes how her research of biomechanics and clinical work with running injuries, as well as research by others, has shaped her views on maintaining body alignment and foot health. Irene discusses her argument for the role of modern footwear in running-related injuries and how minimalist footwear helps resolve the subsequent biomechanical issues.

We discuss:

• Irene’s path to her Ph.D., her entry into physical therapy, and her interest in biomechanics [3:20];
• How Irene’s thinking about the use of orthotics has changed [7:15];
• The evolution of the human foot and the transition from walking to running [10:30];
• The evolution of shoes and its impact on running injuries [17:30];
• An overview of running injuries [26:00];
• Cushioned running shoes, heel striking and impact forces [29:30];
• Shin splints [33:45];
• How heel strike patterns promotes knee stress through rate of loading [35:30];
• The critical importance of exercise [42:15];
• Impact forces and injury potential [45:45];
• How shoe cushioning alters impact forces despite forefoot striking [49:00];
• An overview of minimalist shoes [52:30];
• Irene’s protocol for transitioning people out of orthotics [58:45];
• Transitioning to minimalist shoes and a forefoot strike [1:05:30];
• Foot muscle volume, minimalist shoes, and orthotics [1:07:00];
• The recognition of the importance of foot strength in podiatry [1:09:45];
• Minimalist shoes across the lifespan—from children to adults [1:12:30];
• Why learning to forefoot strike on soft surfaces is not the best approach [1:20:00];
• Knee valgus and factors related to knee injury [1:21:45];
• IT band syndrome [1:28:30];
• Physics and ground reaction forces [1:33:15];
• Irene’s approach to retraining a runner’s gait [1:36:00];
• Case study—How the transition to minimalist shoes decreased injury and improved performance [1:42:15];
• Importance of proper movement patterns and the negative influence of our modern environment [1:45:30]; and
• More.

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In this special episode, Matthew Walker returns for his third AMA episode to provide his expert insight into numerous sleep-related questions directly from listeners. He explains how he adjusted his hypotheses on topics like blue light and caffeine, and why he is more bullish on the importance of REM sleep. Matt also answers questions about sleep wearables, how fasting affects sleep, how sleep deprivation impacts gut health, and magnesium as a sleep aid. Finally, Matt reveals what he believes is the next evolution in sleep science and technology. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or on our website on the show notes page.

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John Arnold is widely regarded as the greatest natural gas trader of all time, but in his late 30’s he walked away from it all and turned full-time philanthropist. He and his wife have committed to strategically give away most of their vast fortune in their lifetime and are already doing so at a staggering pace of nearly a half billion dollars a year. In this episode, John explains his quest to address the most challenging social programs plaguing the country, including criminal justice, health care policy, and K-12 education. John also shares self-identified attributes that contributed to his success in natural gas trading and how those same traits have translated to his philanthropic aspirations.

We discuss:

• John’s background, upbringing, and early entrepreneurial tendencies [3:50];
• John’s time and rise at Enron [16:45];
• Characteristics that made John an exceptional natural gas trader and how they translate to his philanthropic work [27:30];
• The collapse of Enron [35:00];
• The success of John’s hedge fund, and his early interest in philanthropy [40:30];
• The infamous 2006 trade that brought down Amaranth Advisors [55:45];
• John’s analytical prowess and emphasis on fundamentals [1:02:15];
• The decision to become a full-time philanthropist and the founding of Arnold Ventures [1:09:00];
• Education—John’s quest to fundamentally change K-12 education [1:18:45];
• Strategic philanthropy—preventing problems by attacking root causes and creating structural change [1:24:30];
• The criminal justice system—structural changes needed to address mass incarceration, policing practices, and recidivism [1:31:45];
• Re-imagining prisons to reduce recidivism [1:49:00];
• US health care policy—John’s focus on drug prices, and the severe consequences of not making system changes [1:56:15];
• Climate change—the bipartisan role of John’s foundation [2:13:45];
• Advice for young adults interested in philanthropy [2:17:45]; and
• More

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In this episode, Joan and Nir discuss their extensive research into rapamycin (including the category of analogs to rapamycin known as rapalogs) and metformin, respectively. Based on his work with metformin, Nir shares how he believes it could be a pro-longevity drug and the clinical trial he’s leading to test this belief. Joan discusses her work with rapalogs, their ability to suppress the immune system as well as provide immune-enhancement, and the clinical trials she has led that inform her insights. We also talk about the potential beneficial roles of both metformin and rapamycin in reducing mortality from COVID-19, reducing the risk of neurodegenerative diseases, and delaying aging as well as its related diseases.

We discuss:

• Joan’s career, interest in aging, and work with rapamycin analogs [3:45];
• When Nir became convinced metformin could be a pro-longevity agent [15:00];
• How metformin and rapamycin impact the hallmarks of aging and extend lifespan [24:15];
• Enhancing the immune system with rapalogs and metformin [34:15];
• Potential of metformin and rapamycin in reducing mortality from COVID-19 [41:30];
• Insights from Joan’s studies investigating the immune-enhancing effects of rapalogs [59:30];
• Vaccines and treatments strategies for COVID-19, and the likelihood of long-term immunity [1:08:15];
• The potential role of rapalogs and metformin in neurodegenerative disease [1:14:30];
• Nir’s TAME trial—primary objectives and latest updates [1:18:00];
• Potential synergistic effect when combining metformin with rapamycin [1:25:45];
• Why Peter stopped taking metformin and started taking rapamycin [1:27:30];
• Story from Nir’s book that demonstrates the challenge of doing good scientific studies [1:37:30];
• The biology of aging—epigenetic clocks, proteomics, and Nir’s centenarian data [1:42:00];
• Joan’s dream experiment to test immune-enhancing effect of RTB101 [1:57:15];
• Concluding thoughts on COVID-19 [1:59:45]; and
• More.