#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
#373 – Thyroid function and hypothyroidism: why current diagnosis and treatment fall short for many, and how new approaches are transforming care | Antonio Bianco, M.D., Ph.D.
The Peter Attia Drive
Antonio Bianco is a world-renowned physician-scientist and expert in thyroid physiology and metabolism. In this episode, Antonio explores the complex biology of thyroid hormone production, conversion, and regulation—highlighting how deiodinase enzymes modulate hormone activity at the tissue level and why that matters for interpreting lab results. He discusses the shortcomings of relying solely on TSH as a marker of thyroid function, the ongoing debate around combination therapy with T3 and T4 versus standard T4 treatment, and how genetics, tissue sensitivity, and individual variability...
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#372 - AMA #77: Dietary fiber and health outcomes: real benefits, overhyped claims, and practical applications
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter breaks down the science of dietary fiber, moving beyond the blanket advice to “eat more fiber” to uncover what it actually does in the body and where its benefits are truly supported by evidence. He explains how different types of fiber—soluble, insoluble, viscous, and fermentable—affect digestion, satiety, weight management, and glycemic control, and compares their impact to other, more potent metabolic tools. Peter also examines how certain fibers influence lipid metabolism and cardiovascular risk, evaluates the strength of...
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#371 – Women’s sexual health: desire, arousal, and orgasms, navigating perimenopause, and enhancing satisfaction | Sally Greenwald, M.D., M.P.H.
The Peter Attia Drive
Sally Greenwald is an OB-GYN who specializes in women’s sexual health from a hormonal and physiologic perspective, with expertise spanning desire, arousal, pelvic floor function, contraception, and menopause care. In this episode, she explains why sexual health is a vital component of overall well-being, exploring topics such as the drivers of desire, the anatomy of sexual function, myths and realities around orgasm, and the role of hormones in perimenopause and menopause. She also covers vaginal and pelvic health, pain with sex, evidence-based therapies for low desire and arousal, how...
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Longevity 101: a foundational guide to Peter’s frameworks for longevity, and understanding CVD, cancer, neurodegenerative disease, nutrition, exercise, sleep, and more (re-broadcast)
The Peter Attia Drive
In this special episode, Peter provides a comprehensive introduction to longevity, perfect for newcomers or those looking to refresh their knowledge. He lays out the foundational concepts of lifespan, healthspan, and the marginal decade. Additionally, Peter discusses the four main causes of death and their prevention, as well as detailing the five key strategies in his longevity toolkit to improve lifespan and healthspan. Detailed show notes provide links for deeper exploration of these topics, making it an ideal starting point for anyone interested in understanding and improving their...
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#370 - AMA #76: Peter evaluates longevity drugs, aspirin for CVD, and strategies to improve muscle mass — proven, promising, fuzzy, noise, or nonsense?
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter revisits the “proven, promising, fuzzy, noise, nonsense” scale and applies it to a variety of popular topics. He begins with a refresher on what each category represents before classifying a range of interventions based on the strength of their supporting evidence. The conversation spans three main areas: drugs for geroprotection (including GLP-1 receptor agonists, SGLT2 inhibitors, methylene blue, and telomere-lengthening supplements), the use of low-dose aspirin for cardiovascular disease prevention, and strategies to improve muscle...
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#369 ‒ Rethinking protein needs for performance, muscle preservation, and longevity, and the mental and physical benefits of creatine supplementation and sauna use | Rhonda Patrick, Ph.D.
The Peter Attia Drive
Rhonda Patrick is a scientist, health educator, and host of the FoundMyFitness podcast whose work explores the intersection of nutrition, aging, and disease prevention. In this episode, Rhonda joins Peter for part two of his deep dive on protein, continuing last week’s discussion with David Allison and expanding the conversation to include creatine supplementation and sauna use. She discusses why the current RDA for protein is insufficient, how much more is needed to maintain muscle mass and prevent frailty, how activity level and aging influence protein requirements through mechanisms...
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#368 ‒ The protein debate: optimal intake, limitations of the RDA, whether high-protein intake is harmful, and how to think about processed foods | David Allison, Ph.D.
The Peter Attia Drive
David Allison is a world-renowned scientist and award-winning scientific writer who has spent more than two decades at the forefront of obesity research. In this episode, David joins for his third appearance on The Drive to bring clarity to one of the most contentious topics in modern nutrition—protein. He explores the historical pattern of demonizing macronutrients, the origins and limitations of the RDA for protein, and what the evidence really says about higher protein intake, muscle protein synthesis, and whether concerns about harm are supported by actual data. He also discusses the...
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#367 - Tylenol, pregnancy, and autism: What recent studies show and how to interpret the data
The Peter Attia Drive
In this special episode of The Drive, Peter addresses the recent headlines linking acetaminophen (Tylenol) use during pregnancy to autism in exposed children. Recognizing the confusion these claims have sparked among patients, listeners, and the broader public, Peter uses this episode to provide a framework for thinking critically about complex conditions and the research related to them. He highlights the dramatic rise in autism diagnoses over recent decades, noting that multifactorial conditions rarely have a single cause, and emphasizes the importance of resisting oversimplified...
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#366 ‒ Transforming education with AI and an individualized, mastery-based education model | Joe Liemandt
The Peter Attia Drive
Joe Liemandt is a software entrepreneur turned education reformer who left Stanford in 1989 to found Trilogy, a highly profitable private software company, before pivoting to transforming K-12 learning. In this episode, Joe shares how he transitioned from leading a global software enterprise to becoming principal of Alpha School, where his focus is building a mastery-based, individualized education model that leverages AI as the missing infrastructure for large-scale change. He details the shortcomings of traditional K-12 education, explains how Alpha replaces conventional seat time with...
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#365 ‒ Training for longevity: A roundtable on building strength, preventing injury, meeting protein needs, guidance for women and youth athletes, and more | Gabrielle Lyon, Mike Boyle, Jeff Cavaliere
The Peter Attia Drive
In this special episode of The Drive, Peter hosts a strength and conditioning roundtable with three experts in the field—Gabrielle Lyon, Jeff Cavaliere, and Mike Boyle. Together they explore why maintaining muscle mass, strength, and power is essential for healthspan and longevity, and examine how resistance training supports metabolic resilience and injury prevention across the lifespan. The conversation covers practical strategies for getting started and staying consistent, the importance of a protein-centered diet tailored to age and activity level, and approaches to resistance...
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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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