#255 ‒ Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease and CVD, familial hypercholesterolemia, and more | John Kastelein, M.D., Ph.D.
Release Date: 05/22/2023
#364 – AMA #75: Diets: how to evaluate and implement any diet including keto, carnivore, vegan, Mediterranean, and more
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter explores how to determine the right diet for yourself rather than searching for a universal “best” diet. He begins by laying out five non-negotiable criteria that any sustainable eating pattern must meet—energy balance, metabolic health, adequate protein, micronutrient sufficiency, and long-term adherence—before introducing a practical rubric for evaluating different diets. Using this framework, Peter walks through the ketogenic, carnivore, vegan, and Mediterranean diets, highlighting their strengths, ideal candidates for each, and...
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#363 ‒ A new frontier in neurosurgery: restoring brain function with brain-computer interfaces, advancing glioblastoma care, and new hope for devastating brain diseases | Edward Chang, M.D.
The Peter Attia Drive
Edward Chang is a neurosurgeon, scientist, and a pioneering leader in functional neurosurgery and brain-computer interface technology, whose work spans the operating room, the research lab, and the engineering bench to restore speech and movement for patients who have lost these capabilities. In this episode, Edward explains the evolution of modern neurosurgery and its dramatic reduction in collateral damage, the experience of awake brain surgery, real-time mapping to protect critical functions, and the split-second decisions surgeons make. He also discusses breakthroughs in brain-computer...
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Lower back pain: causes, treatment, and prevention of lower back injuries and pain | Stuart McGill, Ph.D. (#287 rebroadcast)
The Peter Attia Drive
Stuart McGill is a distinguished professor emeritus at the University of Waterloo and the chief scientific officer at Backfitpro where he specializes in evaluating complex cases of lower back pain from across the globe. In this episode, Stuart engages in a deep exploration of lower back pain, starting with the anatomy of the lower back, the workings of the spine, the pathophysiology of back pain, and areas of vulnerability. He challenges the concept of nonspecific back pain, emphasizing the importance of finding a causal relationship between injury and pain. Stuart highlights compelling...
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#362 ‒ Understanding anxiety: defining, assessing, and treating health anxiety, OCD, and the spectrum of anxiety disorders | Josh Spitalnick, Ph.D., A.B.P.P.
The Peter Attia Drive
Josh Spitalnick is a clinical and research psychologist with expertise in treating a variety of anxiety conditions with cognitive-behavioral therapy (CBT) and other evidence-based approaches. In this episode, Josh unpacks the four layers of anxiety—psychological, emotional, cognitive, and behavioral—highlighting why avoidance is the key feature that transforms ordinary worry into disorder. He explains why he continues to treat OCD and PTSD as anxiety conditions despite their DSM-5 reclassification, and he draws important distinctions between worries versus worrying and thoughts versus...
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#361 - AMA #74: Sugar and sugar substitutes: weight control, metabolic effects, and health trade-offs
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter explains how to evaluate sugar and its substitutes in the context of health. Peter explores the role of sweeteners in three common use-cases – beverages, protein supplements, and sweet treats – and breaks down how our evolutionary craving for sweetness now clashes with today’s food environment. He examines whether sugar is uniquely fattening, the hormonal effects of sugar consumption, and the significance of timing in sugar intake. The episode compares natural versus refined sugars, sugar in beverages versus in solid foods, and the...
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#360 ‒ How to change your habits: why they form and how to build or break them | Charles Duhigg, M.B.A
The Peter Attia Drive
Charles Duhigg is a Pulitzer Prize-winning journalist and best-selling author known for distilling complex neuroscience and psychology into practical strategies for behavior change, performance, and decision-making. In this episode, Charles explores the neuroscience behind habit formation, including how cue-routine-reward loops drive nearly half of our daily actions and why positive reinforcement is far more effective than punishment. He explains how institutions like the military and Alcoholics Anonymous engineer environments to change behavior at scale, as well as discussing the limits of...
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#359 ‒ How metabolic and immune system dysfunction drive the aging process, the role of NAD, promising interventions, aging clocks, and more | Eric Verdin, M.D.
The Peter Attia Drive
Eric Verdin is a physician-scientist and the CEO of the Buck Institute for Research on Aging whose career has centered on understanding how epigenetics, metabolism, and the immune system influence the aging process. In this episode, Eric traces his scientific journey from studying viruses and histone deacetylases (HDACs) to leading aging research at the Buck Institute, offering insights into how aging impairs immune and nervous system function—including thymic shrinkage, chronic inflammation, and reduced vaccine response—and how these changes impact lifespan. He explores the metabolic...
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#358 ‒ Peter’s takeaways on navigating HRT, rejuvenating the face, understanding the biology of aging, optimizing fertility, and learning to live well from the dying | Quarterly Podcast Summary #6
The Peter Attia Drive
In this quarterly podcast summary (QPS) episode, Peter summarizes his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from his discussions with Paul Turek and Paula Amato on male and female fertility; Rachel Rubin on menopause and hormone replacement therapy; Brian Kennedy on the biology of aging; Tanuj Nakra and Suzan Obagi on facial aging and skin rejuvenation; and BJ Miller and Bridget Sumser on lessons we can learn from the dying about how to live. Peter highlights the most important insights from each episode and any behavioral...
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#357 ‒ A new era of longevity science: models of aging, human trials of rapamycin, biological clocks, promising compounds, and lifestyle interventions | Brian Kennedy, Ph.D.
The Peter Attia Drive
Brian Kennedy is a renowned biologist, leader in aging research, and director of the Center for Healthy Longevity at the National University of Singapore. In this episode, Brian shares insights from ongoing human aging studies, including clinical trials of rapamycin and how dosing strategies, timing, and exercise may influence outcomes. He presents two key models of aging—one as a linear accumulation of biological decline and the other as an exponential rise in mortality risk—and explains why traditional models of aging fall short. He also explains why most current aging biomarkers lack...
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#356 - AMA #73: Preserving brain health, optimizing exercise programming, improving body composition, and more
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter addresses frequently requested topics, including brain health, exercise programming, and body composition. He explores the factors that influence dementia risk—including metabolic health, fitness, sleep, hearing, cholesterol levels, and more. He explains how to implement zone 2 training and VO₂ max intervals for cardiovascular fitness and also covers how to combine cardio modalities, how to stay in zone 2, and special considerations for women. Peter highlights the benefits of light movement after meals and offers strength training tips...
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John Kastelein is a renowned expert in lipoprotein metabolism and atherosclerotic cardiovascular disease (ASCVD) research. In this discussion, John delves deep into familial hypercholesterolemia (FH), a genetic disorder characterized by high levels of LDL cholesterol in the blood that increases the risk of developing heart disease. He covers its definition, genetic underpinnings, and clinical identification. He then explores the therapeutic options available for the prevention and treatment of cardiovascular disease, including the captivating history of CETP inhibitors. He explains the past shortcomings of previous CETP inhibitors before underscoring the compelling potential of the latest iterations, not only for cardiovascular disease but also for conditions like Alzheimer's disease and type 2 diabetes. Moreover, he unveils the intricate role of APOE, shedding light on why the APOE4 isoform codes for a protein that significantly increases the risk of Alzheimer's disease and cardiovascular disease. Concluding the discussion, John shares a profound sense of optimism, envisioning the possibility of targeted therapeutic interventions for high-risk patients in the near future.
We discuss:
- Familial hypercholesterolemia (FH): a genetic condition [4:30];
- Differentiating between phenotype and genotype when it comes to FH [9:45];
- The pathophysiology related to mutations of FH [15:30];
- Clinical presentations, physical manifestations, and diagnosis of FH [22:00];
- Why a small fraction of people with FH do not develop premature ASCVD [34:15];
- Treatment and prevention for those with FH [39:45];
- Addressing the assertion by some that elevated LDL is not casual in cardiovascular disease [52:45];
- The history of CETP inhibitors, and the role of the CETP protein [55:45];
- The thrifty gene hypothesis and why genes underlying FH may have been preserved [1:09:00];
- The compelling potential of the latest CETP inhibitor (obicetrapib) [1:13:00];
- Promising results from phase 3 trials exploring obicetrapib [1:27:45];
- Why the APOE4 allele increases the risk of Alzheimer’s disease, and the connection to blood lipids [1:41:30];
- The role of APOE in cardiovascular disease [1:51:45];
- Takeaways and looking ahead [1:57:00]; and
- More.
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