Zone 2 training: impact on longevity and mitochondrial function, how to dose frequency and duration, and more | Iñigo San-Millán, Ph.D.

Peter Attia

Jul 8, 2024

Episode description

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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 durin

Episode description

View 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 durin

Mindsip insights from this episode:

Use talk test to gauge Zone 2 exercise intensity

A reliable way to gauge Zone 2 intensity is to exercise at a level where you can hold a conversation, but the person on the other end can tell you are exercising.

Utilize resting lactate as a biomarker for metabolic health

People with metabolic syndrome can have a resting lactate level of almost 2.0 mmol, suggesting it could be a valuable biomarker for metabolic health, similar to resting glucose.

Address mitochondrial dysregulation in sedentary individuals to prevent metabolic disease

New research shows that even healthy sedentary individuals have significant mitochondrial dysregulation, which may be a precursor to metabolic disease years before clinical symptoms appear.

Rely on lactate as a marker for ketogenic diet metabolic tests

Being on a ketogenic diet can create an artifact in metabolic tests that artificially inflates fat oxidation numbers, making lactate a potentially more reliable marker in those cases.

Stack workouts by performing Zone 2 followed by high-intensity intervals

To train both mitochondrial efficiency and glycolytic power in one session, perform your Zone 2 workout first and then add a short, high-intensity interval at the very end.

Address mitochondrial dysfunction in long COVID patients

Some long COVID patients, even previously healthy athletes, show severe mitochondrial dysfunction with fat oxidation and lactate profiles worse than those of type 2 diabetics.

Exercise caution with NAD supplements due to tumor growth risk

A pilot study in mice showed that the NAD precursor Nicotinamide Riboside (NR) was associated with a 15% increase in tumor growth, suggesting caution for its use as a longevity supplement.

Prioritize frequent, shorter Zone 2 sessions for optimal adaptation

For optimal mitochondrial adaptation, it is more beneficial to do frequent, shorter Zone 2 sessions, such as four 60-minute workouts per week, than fewer, longer sessions.

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