The Peter Attia Drive

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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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