Zone 2 training: impact on longevity and mitochondrial function, how to dose frequency and duration, and more | Iñigo San-Millán, Ph.D. (#201 rebroadcast)
Release Date: 07/08/2024
#390 ‒ AMA #84: Family health history, preventing heart disease, metabolic health, strength training efficiency, dementia risk reduction, NAD supplements, and hydration
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter answers listener questions across a wide range of topics, focusing on how to think through real-world trade-offs and apply scientific evidence in practice. He explores how to build and interpret a meaningful family health history, how individual risk tolerance influences decisions around testing and treatment, and why heart disease remains poorly prevented despite available tools. He also examines whether it’s possible to carry excess body fat while remaining metabolically healthy, outlines the minimum effective dose for strength training...
info_outline
#389 - Thinking scientifically: why it's hard, why it matters, and a practical toolkit
The Peter Attia Drive
In this episode, Peter explores one of the most foundational topics underlying nearly everything discussed on the podcast: how to think scientifically. Framed as an introspective deep dive, he examines why scientific thinking is inherently difficult for humans, the cognitive biases and tendencies that make it challenging to separate belief from evidence, and why these challenges are even more consequential in today’s environment saturated with misinformation. He also offers a framework for improving our ability to evaluate claims, question assumptions, and identify a personal panel of...
info_outline
#388 — Prostate cancer screening: why current PSA guidelines are failing men and how modern tools improve early detection and save lives
The Peter Attia Drive
In this episode, Peter takes a deep dive into prostate cancer screening, explaining why advanced and metastatic diagnoses continue to rise despite the availability of screening tools, and what can be done to reverse this trend. He breaks down what PSA actually measures and why it is far more informative when tracked over time rather than interpreted as a single value, and he explores how tools like MRI, PSA density, PSA velocity, and improved biopsy techniques can both reduce unnecessary procedures and improve the detection of aggressive cancers. Peter also discusses the role of active...
info_outline
#387 - AMA #83: Peptides—evaluating the science, safety, and hype in a rapidly growing field
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter explores the topic of gray-market peptides, one of the most requested and most confusing topics he’s covered on The Drive. Peptides sit at the intersection of biological plausibility, clinical promise, and aggressive commercialization, and are often marketed as cutting-edge therapies for everything from muscle repair and longevity to cosmetic enhancement. Rather than promoting or dismissing peptides wholesale, Peter lays out a clear, repeatable framework for evaluating any peptide or drug—covering mechanism, intended effects, safety,...
info_outline
#386 - Aging clocks—what they measure, how they work, and their clinical and real-world relevance
The Peter Attia Drive
In this episode, Peter takes a deep dive into the science and application of aging clocks, unpacking what they are, the differences between chronological age, biological age, and the pace of aging, and what epigenetic clocks may actually be measuring. He explores key research in the field, including a randomized controlled trial that tested simple lifestyle interventions against several commonly used aging clocks, as well as a study using brain MRI to assess the pace of aging and its relationship to dementia risk and mortality. Throughout the episode, Peter highlights the promises and...
info_outline
#385 - AMA #82: Applying the tools of longevity in the real world: disease prevention, DEXA scans, artificial sweeteners, injury recovery, stability training, habit formation, protein intake and mTOR activation, and more
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter answers listener questions across a wide range of topics, focusing on practical decision-making and real-world application. He explores how health priorities and strategies should evolve across different decades of life, which chronic diseases are most challenging to manage and how to think about risk hierarchies, and which emerging interventions—beyond exercise—show the most promise for dementia prevention. Peter also breaks down the utility of wearables and explains how to use and interpret DEXA scans effectively. He discusses the...
info_outline
#384 - Special episode — Obicetrapib: The CETP inhibitor with cardiovascular benefits and potential Alzheimer's prevention
The Peter Attia Drive
In this special episode, Peter takes a deep dive into obicetrapib, an investigational drug that has captured his attention and renewed interest in an entire class of therapies known as CETP inhibitors. He explains what obicetrapib is and how it works, revisits the history of CETP inhibitors and why earlier versions of these drugs failed—sometimes dramatically—and breaks down the key clinical trials designed to evaluate their impact on cardiovascular risk. Peter examines how obicetrapib influences major lipid biomarkers, including LDL cholesterol and lipoprotein(a) [Lp(a)], and discusses...
info_outline
#380 ‒ The seed oil debate: are they uniquely harmful relative to other dietary fats? | Layne Norton, Ph.D.
The Peter Attia Drive
Layne Norton is a nutrition scientist and accomplished power athlete,who returns to The Drive for a conversation that departs from the show’s usual format. In this episode, Layne presents the evidence-based case that seed oils are not uniquely harmful under isocaloric conditions, while Peter steelmans the strongest versions of the opposing argument that seed oils are inherently harmful. They examine how scientific bias and evidence are evaluated, revisit the historical randomized controlled trials that shaped the seed oil controversy, and explore the mechanistic biology underlying LDL...
info_outline
#379 - AMA #79: A guide to cardiorespiratory training at any fitness level to improve healthspan, lifespan, and long-term independence
The Peter Attia Drive
In this “Ask Me Anything” (AMA) episode, Peter brings together his most up-to-date thinking on cardiorespiratory fitness into a single, practical guide designed to help listeners structure training for maximal impact on healthspan, lifespan, and long-term independence. He explains why cardiorespiratory fitness is one of the strongest modifiable predictors of longevity, clarifies what zone 2 training actually represents and how it differs from higher-intensity work, and addresses persistent confusion around exercise volume, intensity, and time constraints. The discussion covers how to...
info_outline
#378 ‒ Women’s health and performance: how training, nutrition, and hormones interact across life stages | Abbie Smith-Ryan, Ph.D.
The Peter Attia Drive
Abbie Smith-Ryan is a leading researcher in exercise physiology whose work focuses on how training and nutrition influence body composition, metabolism, cardiovascular health, and women’s health across the lifespan, with particular attention on perimenopause and post-menopause. In this episode, Abbie explains how early exercise and play help build the foundation for bone health, muscle development, and cardiorespiratory fitness in girls, as well as how puberty and menstruation shape athletic performance, motivation, and recovery. She also explores how women can tailor training and...
info_outlineView the Show Notes Page for This Episode
Become a Member to Receive Exclusive Content
Sign Up to Receive Peter’s Weekly Newsletter
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 [2:00];
- Metrics for assessing athletic performance in cyclists and how that impacts race strategy [7:30];
- The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [16:15];
- Tadej Pogačar’s race strategy and mindset at the Tour de France [23:15];
- Defining Zone 2, fat oxidation, and how they are measured [26:00];
- Using fat and carbohydrate utilization to calculate the mitochondrial function and metabolic flexibility [35:00];
- Lactate levels and fat oxidation as it relates to Zone 2 exercise [39:15];
- How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:00];
- Bioenergetics of the cell and what is different in elite athletes [56:30];
- How the level of carbohydrate in the diet and ketogenic diets affects fuel utilization and power output during exercise [1:07:45];
- Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:14:15];
- How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:20:15];
- Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:24:00];
- Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:40:30];
- How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:50:30];
- Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:00];
- The effects of metformin, NAD, and supplements on mitochondrial function [2:04:30];
- The role of lactate and exercise in cancer [2:12:45];
- How assessing metabolic parameters in long COVID patients provides insights into this disease [2:18:30];
- The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise [2:25:00];
- Metabolomics reveals how cellular metabolism is altered in sedentary individuals [2:33:00];
- Cellular changes in the metabolism of people with diabetes and metabolic syndrome [2:38:30]; and
- More.
Connect With Peter on Twitter, Instagram, Facebook and YouTube