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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.

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Lori Gottlieb is a psychotherapist and the bestselling author of Maybe You Should Talk to Someone. In this episode, Lori extracts important lessons from her experiences as both a therapist and a patient. The stories Lori shares has provided her the material for insights into living a more fulfilling life. In our conversation, Lori also dispels some misconceptions about therapy, explains the process of big therapeutic breakthroughs, and reveals the most important steps for enduring emotional health.

We discuss:

In part 2 of this special AMA episode, ketosis expert Dom D’Agostino once again joins Bob Kaplan, Peter’s Head of Research, to discuss the impact of ketosis on various chronic diseases as well as the latest research on the metabolic management of cancer. Dom also discusses the numerous applications of hyperbaric oxygen therapy, provides insights into the application of ketosis on female health and performance, and much 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 the website show notes page.

We discuss:

• Update on Dom’s Press-pulse therapeutic strategy for the metabolic management of cancer [2:05];
• Potential role for vitamin C in cancer treatment [12:45];
• Glutamine targeting in cancer therapy—evidence that the mitochondria in cancer are damaged? [17:45];
• Can a ketogenic diet lessen the toxicity of cancer therapies? [24:45];
• 3BP—a promising agent in cancer therapy [26:45];
• The relationship between cancer and ketogenic diets [29:30];
• Hyperbaric oxygen therapy (HBOT)—primer, protocols, and therapeutic uses [33:30];
• Is there a potential role for HBOT in treating COVID-19 patients? [44:15];
• Non-cancer applications of HBOT [47:30];
• The inverse relationship between glucose and ketones [50:30];
• Is a ketogenic diet appropriate for type 1 diabetics? [54:00];
• How ketosis may reduce the risk for Alzheimer’s disease and Parkinson’s disease [1:00:30];
• Ketosis for females—considerations, fertility, performance, and the latest research [1:11:00];
• Low-carb diets during pregnancy and postpartum [1:17:00];
• A high-protein diet to counteract common hormonal issues associated with the ketogenic diet [1:21:15];
• Nutritional tips for remaining metabolically flexible [1:22:45];
• What is one belief Dom has changed his mind about? [1:26:45];
• In utero experiments, and other interesting questions Dom wants to explore [1:29:45];
• The anti-catabolic effect of ketones, cancer cachexia, and nutritional interventions for cancer patients [1:38:30];
• What is the one interesting experiment Dom would do if money and time were not a barrier? [1:46:25]; and
• More.

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Terry Real, a renowned family therapist and best-selling author, helps people create the connections they desire in their relationships. In this episode, Terry describes how his upbringing with an abusive father forged his path to become a therapist, develop his Relational Life Therapy (RLT) framework, and write I Don't Want to Talk About It—a book that reveals the hidden legacy of male depression. Terry discusses the link between childhood trauma and the deep-rooted shame, anger, and depression, which can result in feeling disconnected. Using real-life examples, Terry explains how he implements RLT to confront trauma, discover its origin, and teach the skills to break the cycle of pain, in order to live a satisfying life.

• Terry’s upbringing with a depressed and abusive father [3:15];
• The importance of the repair process, after relational disharmony, to break the trauma cycle [15:15];
• The impact of a patriarchal society, and relational growth as the next step for feminism [19:00];
• Origins of deep-rooted shame, and the difference between feeling ashamed and feeling guilty [27:15];
• Preventing the propagation of trauma without over-coddling kids [35:30];
• The one-up/one-down cycle from grandiosity to shame [37:30];
• Covert depression—Steps to fixing the secret legacy of male depression [40:00];
• Three forms of false self-esteem [50:00];
• Narcissism—A misunderstood concept [51:45];
• The interplay of shame, anger, and grandiosity, and how to break the cycle [54:15];
• The Relational Life Therapy framework [1:06:30];
• How the adaptive child becomes the maladaptive adult [1:15:30];
• Speaking the language of social relationships [1:21:45];
• When does it make sense for a couple to separate? [1:26:30];
• Witness abuse—Consequences of screaming at your partner in the presence of children [1:28:15];
• Cases of instantaneous change, and other behavioral changes that may take more time [1:30:45];
• Reconciling with his father—Terry’s final conversation with his dad [1:33:45]; and
• More.

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Back by very popular demand for a special AMA episode, ketosis expert Dom D’Agostino joins Bob Kaplan, Peter’s Head of Research, to address many lingering questions about the ketogenic diet, exogenous ketones, and exercise for overall health. Dom also shares valuable insights from his personal experience with training, supplements, intermittent fasting, and other nutritional strategies to optimize his own health and performance. 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 the website show notes page.

We discuss:

• Dom’s recent and ongoing projects [3:00];
• Benefits of a ketogenic diet for an otherwise healthy person [7:00];
• Book recommendations to become more knowledgeable about a ketogenic diet [11:30];
• Best devices for measuring ketones [13:45];
• Genetic factors that influence how someone responds to the ketogenic diet [24:45];
• Ketogenic diet for those with the APOE e4 allele [28:15];
• Impact of long-term ketogenic diets on thyroid function [34:25];
• Low-carb and ketogenic diets for appetite control and weight management [39:00];
• Ketogenic diet and the microbiome [43:00];
• Comparing monounsaturated fat versus saturated fat on the ketogenic diet [45:55];
• Implications of long-term genetic and epigenetic adaptations to a ketogenic diet [47:45];
• Why some people see a rise in LDL-C and LDL-P when on a ketogenic diet and what they can do about it [50:15];
• Should someone with familial hypercholesterolemia consider a ketogenic diet? [55:00];
• Exogenous ketones—benefits, therapeutic uses, and ketone supplements that Dom has tested [56:45];
• Ketogenic protocols for management of traumatic brain injuries [1:06:00];
• Comparing the benefits and therapeutic uses of various medium-chain fatty acids—caprylic acid (C8), capric acid (C10), MCT oil, and coconut oil [1:08:45];
• Nootropics, caffeine, and other stimulants [1:16:15];
• Supplemental use of testosterone, DHEA, and creatine for muscle growth and performance [1:23:45];
• Impact of fasted-state training on strength and performance [1:30:15];
• Stacking exogenous ketones with MCTs for optimal effectiveness [1:33:30];
• BCAA supplements during a fast for muscle preservation [1:35:45];
• What app is Dom using to track his macros? [1:42:00];
• Getting enough micronutrients while on a ketogenic diet [1:47:15];
• Ideal macros and getting enough protein for strength training in ketosis [1:48:15];
• Pros, cons, and ideal macros of one meal a day [1:51:15];
• Dom’s take on “carb backloading” [1:54:45];
• Dom’s take on “carb up” days for ketogenic dieters [2:01:00];
• Dom’s thoughts on the carnivore diet and the paleolithic ketogenic diet [2:05:30];
• Advantages of the ketogenic diet for extreme endurance athletes [2:10:30];
• Impact on strength, power, and performance during the adaptation period of the ketogenic diet [2:14:00];
• Fasted-state elevation in growth hormone and its impact on training [2:17:45];
• Is it possible to build muscle on a ketogenic diet? [2:23:30];
• Why Dom took a year off from weight training [2:28:00];
• What does Dom do for cardio exercise? [2:30:45];
• Protocols for hard training recovery [2:33:15];
• Dom’s personal approach to fasting, time-restricted eating, and sleep [2:35:45];
• People, books, and other resources that shaped Dom’s training and nutrition [2:38:45]; and
• More.

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In this episode, David Watkins, professor of pathology at George Washington University, shares how insights from his HIV and Zika virus research could apply to SARS-CoV-2 protection strategies. David introduces monoclonal antibodies as an intervention to prevent and treat COVID-19 infection, and also discusses how they could be used as a hedge to vaccine development. Additionally, David’s immunology tutorial explains the innate and adaptive immune systems and their differentiated responses to viral infection.

We discuss:

• Background and current interest in immunology [4:30];
• Immunology 101—The innate and adaptive immune system [10:15];
• Defining antibodies, importance of neutralizing antibodies, and serology testing for COVID-19 [19:00];
• B cells—How they fight viruses, create antibodies, and fit into the vaccine strategy [25:00];
• T cells—Role in the adaptive immune system and ability to kill infected cells to prevent viral spread [36:15];
• Valuable lessons from HIV applied to SARS-CoV-2 [51:00];
• Lessons taken from the hepatitis C success story [1:01:30];
• Monoclonal antibodies, vaccines, and the most promising strategies for preventing and treating COVID-19 infection [1:04:45];
• COVID-19 vaccines in development [1:19:00];
• How David’s work with Zika virus informs his thinking on SARS-CoV-2 [1:25:20];
• Why a vaccine for COVID-19 doesn’t need to be perfect to be effective [1:27:45]; and
• More.

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Ned David is the co-founder of Unity Biotechnology, a company developing senolytic medicines—molecules that target and destroy senescent cells in the human body. In this episode, Ned explains the science of cellular senescence and how it impacts the aging process. Ned discusses how senolytics may delay, prevent, treat, or even reverse age-related diseases, including cancer, cardiovascular disease, and neurodegenerative disease. As a serial entrepreneur, Ned also provides advice on how to transform a simple idea into the creation of a company.

We discuss:

• Defining longevity and the principles of aging [2:50];
• The control knobs of aging and how we can turn them [15:10];
• Role of cellular senescence in aging and cancer [27:00];
• History of senescence in scientific study [40:30];
• The cellular senescence paradox [46:00];
• Developing medicines that target cellular senescence [52:15];
• Ned’s lessons on risk analysis in business [1:05:15];
• The search for a molecule that could eliminate senescent cells [1:15:15];
• Senescent cell elimination example in osteoarthritic knees [1:30:30];
• Extending lifespan by removing senescent cells [1:45:00];
• Senolytic molecule example in macular degeneration reversal [1:52:30];
• The future of senescent cell targeting [1:58:30];
• The role of cellular senescence and metabolic syndrome [2:01:30];
• The role of cellular senescence and brain health [2:03:30]
• What prepared Ned to start Unity Biotechnology [2:05:45];
• Advice for someone deciding between business and academics [2:08:50]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter explains his framework for understanding what lab tests can (and cannot) inform us as it pertains to overall longevity, with a specific focus on atherosclerosis, cancer, Alzheimer’s disease, and the physical body. Additionally, Peter shares details into two patient case studies around cardiovascular disease, including how the lab results influenced his diagnosis and treatment plan for the patients. 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 #14 show notes page.

In this episode, Lew Cantley, Professor of cancer biology and Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medical College in NYC, walks us through his amazing discovery of phosphoinositide 3-kinase (PI3K) and the implications for the care of patients with cancer. He explains various combinations of therapies being tested and used, including the possibility of pairing prescriptive nutritional therapies to increase the efficacy of drugs like PI3K inhibitors. Lew also explains the metabolic nature of cancer through the lens of his research into the connection between sugar consumption, insulin resistance, and tumor growth. Additionally, Lew provides some details about his exciting new clinical trial that is just now enrolling patients with stage 4 breast cancer and endometrial cancer.

We discuss:

• Teaching science through the lens of discovery—A better approach to learning science [5:15];
• The metabolic nature of cancer, mitochondria, and a more nuanced explanation of the Warburg Effect [8:30];
• The observation that convinced Lew to stop eating sugar [20:15];
• The connection between obesity, insulin resistance, and cancer [25:30];
• Sugar consumption and tumor growth—What did Lew’s 2019 paper find? [32:00];
• Natural sugar vs. HFCS, fruit vs. fruit juice, insulin response and cancer growth [43:00];
• Increasing efficacy of PI3K inhibitors with ketogenic diets, SGLT2 inhibitors, and metformin [53:30];
• Lew’s clinical trial enrolling stage 4 breast cancer and endometrial cancer patients [1:07:30];
• Pairing diet with drug could be the future of cancer treatment [1:09:30];
• PI3K inhibitors on the market, alpha vs. delta isoform, and the possibility of pairing them with a food prescription [1:16:15];
• What questions will Lew be focused on in the next chapter of his career? [1:22:15];
• Lew's early work that ultimately led to the discovery of PI3K [1:27:30];
• Studying the mechanism by which mitochondria make ATP [1:30:45];
• How understanding the mechanism by which insulin drove glucose uptake into a cell got Lew closer to finding PI3K [1:38:15];
• How Lew knew PI3K was important in driving the growth of cancer cells [1:55:00];
• Lew’s unlikely observation of phosphorylation at the 3' position of the inositol ring resulting in the formation of phosphatidylinositol-3-phosphate [1:59:00]; and
• More.

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In this episode, infectious disease and pandemic preparedness expert, Amesh Adalja, M.D., puts the current pandemic into context against previous coronaviruses as well as past influenza pandemics. Amesh also provides his interpretation of the evolving metrics which have contributed to big variations in modeling predictions, whether this will be a seasonally recurring virus, and perhaps most importantly—how we can be better prepared for the inevitable future novel virus. Finally, Amesh explains where he sees positive trends which give him reasons for optimism.

We discuss:

• Amesh’s background in infectious disease [2:40];
  
• When did the virus actually reach the US? And when did Amesh realize it would pose a real threat to the US? [4:00];
  
• Comparing and contrasting COVID-19 to previous pandemics like the Asian flu of 1958 and the Spanish flu of 1918 [8:00];
  
• Will COVID-19 be a recurring seasonal virus every year? [14:00];
  
• Will a future vaccine be specific to this COVID-19 or will it also cover previous coronaviruses as well? [15:15];
  
• What does Amesh think might be the true case fatality rate of SARS-CoV-2? [16:15];
  
• Why did early models over predict infections and deaths by order of millions? [18:30];
  
• Role of government—How does Amesh view the role of local versus central government in dealing with a future pandemic? [21:50];
  
• What went wrong with testing and how could we have utilized it more effectively? [25:15];
  
• Future pandemic preparedness—why Amesh is cautiously optimistic [27:30];
  
• Should there be different policies and restrictions for places like New York City compared to less populated and less affected places across the US? [30:15];
  
• Why mass gatherings might be disproportionately driving the spread of the virus [32:30];
  
• Learning from HKU1, a lesser-known novel coronavirus from 2005 [34:00];
  
• Thoughts on Sweden’s herd immunity approach [36:10];
  
• The efficacy of masks being worn in public and what role they will play as restrictions are slowly lifted [37:20];
  
• What are some positive trends and signs of optimism? [39:15]; and
  
• More.

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In this episode, psychiatrist Paul Conti, M.D. discusses the impact of the fear and uncertainty surrounding the COVID-19 pandemic and the resulting stress, anxiety, and trauma it may impart on the population. Paul examines how this situation has highlighted the challenges we face at the societal level as well as the individual level, and stresses the importance of seeking absolute truth above personal truth and taking action as individuals as a means to combat many of these pervasive problems.

We discuss:

• Paul’s personal experience with a presumptive case of COVID-19 [2:15];
  
• Through the lens of trauma, Paul’s overall take on the lasting effects of this pandemic on society [4:30];
  
• The imperative to unite as a species given the isolating and suspicious nature of an invisible enemy [8:15];
  
• The indigent population and the affluent population—The commonalities and differences in how both populations have been affected [16:15];
  
• The prevailing feeling of demoralization spanning the population [25:30];
  
• Health care workers—What lingering psychological effects might they suffer from this? [35:00];
  
• Could this pandemic be a catalyst for changing the way people think about science, truth, and logic? [46:30];
  
• How our inability to deal with uncertainty exacerbates the problem, and the need for humility [58:00];
  
• What has been Paul’s recipe for self care during this time? [1:06:45];
  
• The forthcoming challenge of reintegrating back into the world when the quarantines lift [1:14:45];
  
• An urgent need for change which must come through individuals seeking absolute truth and taking action [1:19:15]; and
  
• More.

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In this episode, Peter sits down with his daughter to answer questions from her and other kids about COVID-19.

We discuss:

• What is a virus? [1:45];
• How did this version of coronavirus (SARS-CoV-2) start? [4:30];
• How does COVID-19 compare to SARS and MERS (previous coronaviruses)? [6:00];
• Will COVID-19 come back again after we resolve the current issue? [7:15];
• When will kids go back to school? [7:45];
• How has the US surpassed China in total cases, and how could we have been better prepared for this? [8:30];
• Should have we started to quarantine sooner than we actually did? [11:45];
• What about herd immunity? Would it be easier if we all just got the virus so we could be immune? [13:45];
• Which age groups are the least and most at risk for getting a deadly version of the virus? [15:00];
• Why do we have to wipe down packages that are delivered to our homes? [16:30];
• How a lack of preparation and discipline led to this troubling situation [18:45];
• Is China to blame for all of this? [24:15];
• What did Olivia think when her parents pulled her out of school before it was mandated? [26:30];
• What's been the hardest part of this for Olivia? [27:50];
• What does Olivia appreciate now that she probably didn't appreciate in the past? [28:50];
• How are Olivia’s zone 2 workouts going? [30:00]; and
• More

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In this episode, originally recorded to be the 100th episode of The Drive, Peter discusses topics that he has changed his mind about since starting the podcast as a result of preparing for interviews as well as from the actual conversations. Peter also reviews some of his favorite moments from the first 99 episodes, shares what books he’s currently reading, and much more. Initially scheduled to be released as episode 100, this was delayed due to recent podcasts covering COVID-19.

We discuss:

• Definition of “strong convictions loosely held,” and the value in trying to shoot down your own hypotheses [2:20];
• Metformin—How Peter’s strong convictions have changed since 2018 [8:00];
  
• Getting a dog—Why Peter caved and how it’s going so far [15:45];
  
• Rapamycin—How Peter’s feelings have evolved, and the questions still needing to be answered [20:45];
  
• Archery, the joy of pursuing mastery, and the importance of stillness [26:50];
  
• Zone 2 training—Why Peter has made it a big component of his exercise regimen [37:30];
  
• Deadlifts—Why Peter now believes it’s extremely beneficial to longevity when done properly [41:45];
  
• Read any good books lately? [50:00];
  
• Baby aspirin for preventing blood clotting—Why Peter no longer takes it, and a few alternative options [53:15];
  
• Generic drugs—How and why Peter’s mind has shifted on generic drugs [55:45];
  
• Omega-3 fatty acids, EPA and DHA—How Peter’s long-held views have changed [58:15];
  
• How Peter got better at saying “no” [1:02:30];
  
• Does Peter have any favorite episodes of The Drive? [1:07:15]; and
  
• More.
  

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In this episode, Michael Osterholm, Director of the Center for Infectious Disease Research and Policy at the University of Minnesota and author of Deadliest Enemy: Our War Against Killer Germs, provides an overview on the COVID-19 pandemic in regards to what has happened to date, what we’ve learned about how the disease spreads, and his optimism and pessimism about what potentially lies ahead. Michael gives his take on the true case fatality rate, why it differs around the world, and which underlying conditions, such as obesity, impact risk of severe illness and death. We also discuss the outlook regarding vaccines, repurposed drugs/antivirals for treatment, and Michael’s growing concern about supply chain limitations with respect to drugs, vaccines, n95 masks, and testing kits.

We discuss:

• Recapping the brief history of COVID-19 and what potentially lies ahead [2:15];
  
• Some positive news about immunity and reinfection [10:45];
  
• Case fatality rate—The challenge in finding the true rate, difference by country, and the impact of age, underlying conditions, and obesity [13:00];
  
• What has to be true for less than 100,000 Americans to die from COVID-19? [24:30];
  
• How do we best protect healthcare workers? [29:45];
  
• Concerns about testing capability—Reagent shortfall and a supply chain problem [39:30];
  
• Vaccines and antivirals—The outlook, timing, and challenges [47:45];
  
• Long term health of survivors of COVID-19 [56:45];
  
• The impact of comorbidities—Diabetes, obesity, and immunosuppressed patients [59:30];
  
• Understanding R0 and how the disease spreads [1:01:30];
  
• The challenge of forecasting with so many unknown [1:08:00];
  
• What explains the difference in cases and fatalities in different parts of the world? [1:14:30];
  
• Repurposed drugs/antivirals being considered for treatment options—any optimism? [1:16:45];
  
• A parting message from Michael about what lies ahead [1:18:30]; and
  
• More.

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Ryan Holiday, bestselling author and author of Daily Stoic, discusses practical ways to find stillness and apply the insights of stoic philosophy in the midst of COVID-19 chaos. Ryan discusses the importance of taking back a feeling of control, the benefits of structure and routine, and the idea of being prepared for anything.

We discuss:

• Using times of adversity to evaluate and reflect how you’ve set up and prioritized your life [2:30];
  
• What insights might the famous stoics provide amidst this COVID-19 pandemic? [8:15];
  
• The possible consequences of the socially isolating nature of a pandemic (and why we need good leaders) [13:00];
  
• Stoicism—what it means and how to apply it [18:45];
  
• Lessons taken from the life of Winston Churchill—stillness, structure, routine, hobbies, empathy, forward thinking, and more [23:30];
  
• Alive time vs. dead time—taking control of your time and making it count [38:45];
  
• Auditing how the world (and its leaders) are handling the COVID-19 pandemic through the lens of stoic philosophy [44:15];
  
• Asserting control and using routine to find stillness in an environment not conducive for it [52:15];
  
• Why you should find a way to exercise, especially now [58:30];
  
• How to find purpose during this time—goal setting, having a project to work on, and the benefits of keeping a journal [1:02:00];
  
• What is Ryan most optimistic about and what is he most concerned about over the next few months? [1:08:45];
  
• How can you follow Ryan’s work and messages about stoicism and stillness? [1:17:45].
• And more.

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In this episode, Sam Harris, neuroscientist, author, and host of the Making Sense Podcast, joins Peter to discuss this unprecedented coronavirus (COVID-19) crisis. The discussion includes the important distinction between COVID-19 and influenza, the impact on the economy, the dire situation in New York, and the challenge of creating a safe and effective vaccine. Additionally, Sam brings insights from his extensive meditation practice to help those struggling with stress, anxiety, and fear in this extraordinary situation.

We discuss:

• A time unlike any other—why many people don’t seem to fully grasp the magnitude of this situation [2:00];
  
• Why comparing COVID-19 to influenza is a bad analogy [10:45]
  
• The impact on the economy of measures like shelter-in-place—Is the “cure” worse than the disease? [16:45];
  
• Why are some places, like New York, getting hit so much worse? [24:45];
  
• The trickle down effect of an overrun healthcare system on non-COVID-19 related health issues [34:45];
  
• How to calm our minds and manage our emotions during this craziness [38:00];
  
• Talking to kids about this situation without burdening them with undue stress [50:15];
  
• Insights from meditation practice—Recognize and unhook yourself from a heightened emotional state [52:00];
  
• How to make the most of a situation where you let your emotions get the best of you [59:15];
  
• What are some potential positive things that Sam hopes could be learned from this crisis and applied to the future? [1:09:30];
  
• The unfortunate politics being layered on top of this crisis [1:15:30];
  
• The challenge of creating a safe and effective vaccine for COVID-19 [1:20:00]; and
  
• More.

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In this episode, Dr. Peter Hotez M.D., Ph.D., Dean for the National School of Tropical Medicine Baylor College of Medicine, returns to continue the conversation on COVID-19. Dr. Hotez informs us on how we can gauge the number of infected people, behaviors to reduce the probability of becoming infected, and the inconsistency of hospitalizations among young adults between different countries.  Dr. Hotez underscores the continued uncertainty in many virus-related developments, but ends with some points of optimism.

Disclaimer: This is information accurate as of March 19, 2020, when it was recorded.

We discuss:

• • How to gauge true number of infected people [5:45]
    
  • Reducing the probability of getting infected [22:45]
    
  • Inconsistency by country in infected young people [27:15]
    
  • Conferred immunity, seasonality, and repurposed therapeutics [30:30]
    
  • Vaccine development [39:30]
    
  • Practical behaviors to reduce risk of transmission [46:00]
    
  • Mental Health resource and funding [51:00]
    
  • Points of optimism [56:00]; and
    
  • More.
    

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Today's episode of The Qualys is from podcast #47 – Matthew Walker, Ph.D., on sleep – Part I of III: Dangers of poor sleep, Alzheimer’s risk, mental health, memory consolidation, and more.

The Qualys is a subscriber-exclusive podcast, released Tuesday through Friday, and published exclusively on our private, subscriber-only podcast feed. Qualys is short-hand for “qualifying round,” which are typically the fastest laps driven in a race car—done before the race to determine starting position on the grid for race day. The Qualys are short (i.e., “fast”), typically less than ten minutes, and highlight the best questions, topics, and tactics discussed on The Drive.

Occasionally, we will also release an episode on the main podcast feed for non-subscribers, which is what you are listening to now.

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In this episode, Dr. Peter Hotez M.D., Ph.D., Dean for the National School of Tropical Medicine Baylor College of Medicine, shares his expertise on viral disease and how it applies specifically to the coronavirus disease (COVID-19) and the virus that causes it (SARS-CoV-2). Dr. Hotez informs us about the current state of disease progression, which has many unknowns, but has thus far been greatly determined by the delayed response time and lack of testing. Moreover, we discuss what we can do on a country, state, community, and individual level in order to collectively slow transmission of the disease. He shares with us a potential hope in convalescent plasma therapy and underscores the need for US federal involvement - particularly in the creation of a specialty task force to address areas of concern and unknowns.

Disclaimer: This is information accurate as of March 13, 2020, when it was recorded.

We discuss:

• The disease and the virus: transmissibility and lethality [04:30];
  
• Disease transmission: US playing catch-up [12:00];
  
• Convalescent plasma coronavirus therapy [16:00];
  
• Remdesivir drug treatment and vaccination challenges [19:45];
  
• Disease mechanism and reported pathology [27:45];
  
• Most concerning geographic regions in the US [39:00];
  
• Risk reduction [46:30]; and
  
• More.

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Today's episode of The Qualys is from podcast #37 – Zubin Damania, M.D.: Revolutionizing healthcare one hilariously inspiring video at a time.