The Peter Attia Drive

Hussein Yassine is a physician and researcher who studies brain lipid utilization in the context of finding preventative measures for cognitive impairment, specifically Alzheimer's disease (AD). In my conversation with Hussein, we begin with a fundamental coursework in brain biology—including its architecture and energy systems. We go on to discuss what these systems look like when something goes wrong and cognitive decline ensues. We talk about the evolutionary origins of the ApoE genotype, with specific attention to the ApoE4 allele and its association with AD. We spend time discussing ApoE4 implications for the brain's fuel utilization, notably omega-3 fatty acids: EPA and DHA. We briefly pivot to the implications of recent omega-3 trials for cardiovascular disease and return to what we currently understand about EPA/DHA and brain health; we contemplate potential dietary interventions across the lifespan to preserve and prolong cognitive function.

We discuss:

• Hussein's Background and introduction to brain composition (3:00);
• The blood-brain barrier and brain filtration (8:00);
• Lipids and brain function (13:00);
• How the brain utilizes energy (18:00);
• Apolipoprotein E (ApoE) structure and function in the periphery (27:30);
• ApoE function in the brain (38:15);
• Evolutionary origins of ApoE isoforms (43:45);
• ApoE4 variant and Alzheimer's disease (AD) risk (53:30);
• Dietary fuel preference with the ApoE4 allele (1:03:00);
• The role of omega-3 fatty acids in the brain (1:13:30);
• Comparing findings from the REDUCE-IT and STRENGTH trial (1:21:45):
• The relationship between dietary omega-3 intake and brain health (1:34:15);
• Preventing cognitive decline: A critical window for DHA in ApoE4 carriers? (1:42:30);
• Hussein's ongoing research and recommendations for E4 carriers (1:54:00); and
• More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/HusseinYassine Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

Guy Winch is a psychologist, author, and co-host of the Dear Therapist podcast. In this episode, Guy speaks to the commonality of the human condition with relatable stories from his decades of therapy sessions as well as his own experience with incessant rumination in the early days of his private practice. He shares insights on what he sees as an epidemic of rumination that leads to career burnout, the consequences of social comparison heightened by social media, and the psychological impact of not recognizing success. He emphasizes the need for a "psychological medicine cabinet" and provides concrete and practical tools for treating emotional injuries. He concludes with a discussion about the widespread impact of the coronavirus pandemic on emotional health and how we can use experienced psychologists in a time when it's especially needed.

We discuss:

• The unique format and impetus for Guy's podcast with Lori Gottlieb (3:00);
• How Guy pieced together the many different schools of thought in psychology to develop his own unique approach (7:45);
• The most important component of successful therapy, and why it sometimes makes sense to "break the rules" (19:30);
• Insights extracted from Guy's own battle with extreme stress and anxiety around finishing his education and starting his private practice (28:15);
• The epidemic of rumination, burnout, and the inability to psychologically leave work (34:15);
• Antidotes to incessant rumination, and tips for transitioning from work to home to avoid burnout (41:15);
• The psychology of complaining: The hidden cost of complaining incorrectly and benefits of learning how and when to complain (52:30);
• The consequences of social comparison, and the impact of "failure" on emotional health (1:02:15);
• How Guy helps people who struggle to acknowledge any level of success (1:07:30);
• Emotional first aid: The importance of a psychological medicine cabinet for treating emotional injuries (1:19:00);
• The role of therapists in normalizing the discussion of emotional injuries and illuminating the commonality of feelings (1:27:45);
• The widespread impact of the coronavirus pandemic on emotional health (1:35:15);
• How to properly use affirmations—a tool for treating psychological injuries (1:42:00);
• The importance of nuanced language and the stories we tell ourselves (1:47:30);
• Peter's favorite episode of the Dear Therapist Podcast (1:53:15); and
• More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/guywinch Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

In this "Ask Me Anything" (AMA) episode, Peter and Bob take a deep dive into zone 2 training. They begin with a detailed definition of zone 2 and continue by discussing the importance of adding it to your exercise regimen. They talk about how to program zone 2 training, including intensity, frequency, and duration, and metrics for tracking improvement. Additionally, they provide a detailed overview of all things related to magnesium supplementation. The two conclude with insights about how to effectively engage with your doctor in the pursuit of getting your questions answered and considerations for finding a physician that's right for you.

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

We discuss:

• Defining zone 2 exercise (3:30);
• The most effective ways to engage in zone 2 exercise (14:00);
• The process of training a deconditioned individual with zone 2: Dosage, frequency, and metrics to watch (19:45);
• Training for health vs. performance, and the importance dedicating training time solely to zone 2 (25:00);
• Why Peter does his zone 2 training in a fasted state (31:30);
• Improving mitochondrial density and function with zone 2 training (34:00);
• Metrics to monitor improving fitness levels from zone 2 training (36:30);
• Advice for choosing a bicycle for zone 2 exercise at home (42:30);
• Comparing the various equipment options for aerobic training: Rowing machine, treadmill, stairmaster, and more [48:15];
• Back pain and exercise, and Peter's stability issues as a consequence of previous surgeries (51:45);
• A deep dive into magnesium supplementation, and Peter's personal protocol (55:30);
• Advice for engaging with and questioning your doctor (1:03:15); and
• More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/ama19 Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

Phil Maffetone is an author, health practitioner, and coach with decades of experience helping everyone from amateurs to world-class athletes optimize their health and performance. In this episode, Phil explains the importance of developing the aerobic system, defines maximum aerobic function (MAF), and explains how to determine your MAF heart rate. He then demonstrates how to integrate that into a training protocol which is designed to help people move faster at a sub maximum heart rate and increase fat utilization as the primary source of fuel—emphasizing the importance of nutrition on one's capacity to oxidize fat. Phil also extracts training insights from the amazing feats of world-class marathoners, explores the impact of a low-carb diet on one's capacity for high intensity exercise and anaerobic performance, and explains the downstream effects of being "overfat."

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.

Learn more: https://peterattiamd.com/ Show notes page for this episode: http://peterattiamd.com/PhilMaffetone Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

John Ioannidis is a physician, scientist, writer, and a Stanford University professor who studies scientific research itself, a process known as meta-research. In this episode, John discusses his staggering finding that the majority of published research is actually incorrect. Using nutritional epidemiology as the poster child for irreproducible findings, John describes at length the factors that play into these false positive results and offers numerous insights into how science can course correct. We discuss:

• John's background, and the synergy of mathematics, science, and medicine (2:40);
• Why most published research findings are false (10:00);
• The bending of data to reach 'statistical significance,' and the how bias impacts results (19:30);
• The problem of power: How over- and under-powered studies lead to false positives (26:00);
• Contrasting nutritional epidemiology with genetics research (31:00);
• How to improve nutritional epidemiology and get more answers on efficacy (38:45);
• How pre-existing beliefs impact science (52:30);
• The antidote to questionable research practices infected with bias and bad incentive structures (1:03:45);
• The different roles of public, private, and philanthropic sectors in funding high-risk research that asks the important questions (1:12:00);
• Case studies demonstrating the challenge of epidemiology and how even the best studies can have major flaws (1:21:30);
• Results of John's study looking at the seroprevalence of SARS-CoV-2, and the resulting vitriol revealing the challenge of doing science in a hyper-politicized environment (1:31:00);
• John's excitement about the future (1:47:45); and
• More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/JohnIoannidis Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

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.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/RobertAbbott Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

In this "Ask Me Anything" (AMA) episode, Peter and Bob talk all about sugar and sugar substitutes and provide a way to think about sugar consumption. The conversation begins by defining the various forms of sugar, delineating between added sugar and naturally occurring sugar, and describing the important variables that determine the potential for metabolic damage from consumption. They then take a dive deep into three main categories of sugar substitutes—non-nutritive sweeteners, alcohol sugars, and leaving allulose, in a class by itself—including the safety profile of each, impact on blood sugar and insulin, side-effects, taste preferences, 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 #18 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Delineating the various forms of "sugar" (2:00);
• Added sugar vs. naturally occurring sugar (12:30);
• Important variables related to sugar consumption: Density, volume, and velocity (17:00);
• Alternatives to sugar: Non-nutritive sweeteners (22:30);
• Alternatives to sugar: Alcohol sugars (34:15);
• Alternatives to sugar: Allulose (39:00);
• Contextualizing risk when it comes to sugar substitutes (45:00);
• Why some people report feeling better when eliminating non-nutritive sweeteners from their diet (46:30);
• The impact of sweetness—Cephalic insulin response and the metabolic drive to eat more (49:45); and
• More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/ama18/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

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

We discuss:

• Gerald's background and interest in metabolism and insulin resistance (4:30);
• Insulin resistance as a root cause of chronic disease (8:30);
• How Gerald uses NMR to see inside cells (12:00);
• Defining and diagnosing insulin resistance and type 2 diabetes (19:15);
• The role of lipids in insulin resistance (31:15);
• Confirmation of glucose transport as the root problem in lipid-induced insulin resistance (40:15);
• The role of exercise in protecting against insulin resistance and fatty liver (50:00);
• Insulin resistance in the liver (1:07:00);
• The evolutionary explanation for insulin resistance—an important tool for surviving starvation (1:17:15);
• The critical role of gluconeogenesis, and how it's regulated by insulin (1:22:30);
• Inflammation and body fat as contributing factors to insulin resistance (1:32:15);
• Treatment approaches for fatty liver and insulin resistance, and an exciting new pharmacological approach (1:41:15);
• Metformin's mechanism of action and its suitability as a longevity agent (1:58:15);
• More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/geraldshulman Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

Kristin Neff is a Professor of Educational Psychology at the University of Texas, author, and a leading expert on mindful self-compassion. In this episode, she shares how developing a self-compassion and mindfulness practice was the most effective tool for relieving her own suffering, and provides strategies and tactics to improve self-compassion and well-being.

We discuss:

• The life crisis that turned Kristin to mindfulness and self-compassion (3:30);
• How mindful self-compassion relieved Kristin's feelings of self-judgement, and the psychology that says we all have the capacity for self-compassion (9:45);
• Peter's history of self-criticism and his personal practice of self-compassion (17:15);
• The problem with prioritizing self-esteem over self-compassion, and how self-compassion produces a more stable version of self-worth (20:15);
• An argument for self-compassion over self-criticism for optimizing performance (26:15);
• How and when to introduce self-compassion to children (31:45);
• Learning her son had autism—a personal story of how Kristin used mindfulness and self-compassion (36:45);
• Self-compassion for cases of childhood trauma, PTSD, and overcoming a "fear of compassion" (44:00);
• The relationship between self-compassion and physical health (49:30);
• Distinguishing between self-compassion and self-pity, and the three necessary components self-compassion (52:30);
• Why self-criticism comes from a desire to be safe, the circular pattern of self-judgment, and self-compassion as the ultimate motivator (55:45);
• Potential role of a self-compassion practice for addiction and other maladaptive behaviors (58:45);
• Clinical applications and practical uses of self-compassion (1:01:30);
• Why you don't need to meditate to learn mindfulness and self-compassion (1:04:45);
• Kristin's personal meditation practice (1:08:40);
• Resources for learning self-compassion (1:11:45); and
• More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/kristinneff Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

Peter is joined by writer, director, actress, and founder of HFC, Lauren Miller Rogen, and previous podcast guest and director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine and New York-Presbyterian, Dr. Richard Isaacson. In this episode, Lauren tells the heartbreaking story of watching members of her family succumb to Alzheimer's disease (AD) which motivated her to proactively address her own risk with Richard's guidance. Richard discusses the various genetic and lifestyle factors that influence the risk of AD and uses Lauren's unique situation to explain how he diagnoses patients and personalizes care. They go through Lauren's protocol of preventative measures that have already produced marked results, and end with the uplifting message that one's genetic predisposition does not seal one's fate.

We discuss:

• Lauren's deep family history of Alzheimer's disease (3:10);
• The influence of genetics, epigenetics, and lifestyle on Alzheimer's disease risk (13:45);
• Lauren's mother's disease progression and the enormous stress it causes for family members (24:30);
• The various manifestations of Alzheimer's disease depending on the location of pathology (29:30);
• The three stages of Alzheimer's disease (34:45);
• Richard's deep exploration into Lauren's family history revealing clues about a diagnosis and a roadmap to successful disease mitigation (39:15);
• How exercise reduces Alzheimer's disease risk, and the different risk between males and females (58:00);
• Why knowing your APOE status is important, and whether certain people should be wearier of head trauma (1:08:00);
• How Richard uses genetic testing to personalize care (1:14:45);
• The "ABCs" of Alzheimer's prevention, lifestyle interventions, and Lauren's personal protocol for reducing her risk (1:21:45);
• Unique treatment for people with the ApoE4 variant (1:36:30);
• Richard's mixed opinion on CBD and THC as a tool for disease prevention (1:40:00);
• Cognitive testing procedures, and how Lauren's tests furthered her commitment to her disease prevention protocol (1:41:45);
• The relevance of sense of smell and hearing in Alzheimer's disease risk and prevention (1:50:00);
• The emotional benefit of knowing you have control over your mental and physical health (1:57:30);
• HFC—a charitable organization founded by Lauren and Seth (2:00:15); and
• More.

Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/laurenmillerrogen-richardisaacson/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.