Zone 2 training: impact on longevity and mitochondrial function, how to dose frequency and duration, and more | Iñigo San-Millán, Ph.D. (#201 rebroadcast)
Jul 8, 2024
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In this podcast, Physiologist Iñigo San-Millán discusses the potential of elite athletes and Zone 2 training on longevity and mitochondrial function. Topics include lactate levels, fat oxidation, carbohydrate impact on lactate, optimal exercise dosage, high intensity training benefits, metformin/NAD for mitochondria, and insights from studying ICU long COVID patients' mitochondria.
Zone 2 training boosts mitochondrial function and impacts longevity.
Efficient lactate utilization crucial for delaying muscle fatigue and optimizing performance.
Boosting NAD levels with supplements may impact mitochondrial health and longevity.
Metformin's effect on mitochondrial function raises questions about its use in training.
Balancing high-intensity training with lower-intensity training is key for overall health.
Understanding mitochondrial function essential for promoting healthy aging and overall well-being.
Deep dives
Impact of Genetic Versus Training on Physiological Adaptations
The podcast delves into the significance of genetic predisposition and training in elite athletes like Bogacar. It highlights the role of multiple factors, including genetic make-up, epigenetics, and tailored training programs in enhancing physiological adaptations. The discussion emphasizes how elite athletes like Bogacar possess a high number of MCT1 transporters on their outer mitochondrial membranes, enabling efficient lactate oxidation and explaining lower lactate levels at similar work levels compared to others.
Fat Oxidation and Lactate Dynamics in Athletes
The summary elaborates on the intricate relationship between fat oxidation and lactate dynamics in athletes. It explains how exercise intensity impacts glucose utilization, leading to the production of lactate. The correlation between lactate levels and fat oxidation signifies metabolic efficiency and determines the ability to transition between energy sources. The discussion sheds light on the physiological mechanisms that underlie optimized energy utilization during high-intensity exercises.
Role of MCT Transporters in Metabolic Adaptation
The episode explores the function of MCT transporters in facilitating metabolic adaptations in muscle fibers. It details the process where lactate produced from glucose utilization is shuttled to adjacent slow-twitch muscle fibers for oxidation. The presence of MCT1 transporters enables lactate to be converted back to pyruvate in mitochondria, contributing to sustained energy production. The conversation underlines the importance of efficient lactate utilization in delaying muscle fatigue and optimizing athletic performance.
Interplay Between Glucose Metabolism and Energy Production
The summary outlines the metabolic interplay between glucose metabolism and energy production in different muscle fiber types during exercise. It illustrates how lactate generated from glucose breakdown serves as a vital energy substrate in maintaining muscle function. The explanation clarifies the diverse roles of MCT transporters in regulating lactate utilization and mitochondrial activity, emphasizing their pivotal role in sustaining energy levels and delaying fatigue during intense physical exertion.
Impact of NAD on Mitochondrial Function and Longevity
Boosting NAD levels with supplements like NR or NMN is touted as beneficial for mitochondrial health and longevity. However, the clinical relevance and actual impact on mitochondrial function remain debated. While these supplements are NAD precursors, it's unclear if they significantly boost cellular NAD levels. There is a need for more research to understand the true effects of NAD supplements on mitochondria.
Metformin and Mitochondrial Function
Metformin, a common medication for diabetes, can inhibit complex one in the electron transport chain, affecting mitochondrial function. Elevated lactate levels observed in patients on metformin raise questions about mitochondrial health. Studies are ongoing to determine if metformin impairs mitochondrial function or if it's an artifact, posing challenges in interpreting zone two data in patients taking metformin.
Potential Risks of High NAD Levels
There is a theoretical risk that excessively boosting NAD levels could be harmful, especially in certain populations like cancer patients. Studies have shown that increased NAD levels may favor tumor metabolism, promoting tumor growth. Research in mice has demonstrated a 15% increase in tumor growth with NAD supplementation, highlighting the need for caution in using NAD-boosting supplements.
Longevity and the Compound Effects of Supplements
While supplements like NAD precursors are marketed for longevity, it's essential to recognize that longevity is influenced by a combination of factors, not just one supplement. Understanding the complexities of cellular and mitochondrial health, along with lifestyle factors, is crucial for comprehensive approaches to health and longevity.
Balancing High-Intensity Training and Mitochondrial Health
Balancing high-intensity training like intervals with zone two training is crucial for optimal mitochondrial health. While high-intensity training offers metabolic benefits, long-term sustainability and balance with lower-intensity training are key for overall health and mitochondrial function. An individualized approach that combines various training intensities can promote mitochondrial efficiency and overall wellness.
Fundamental Concepts of Mitochondrial Function and Health
Mitochondrial function plays a critical role in overall health and longevity. Understanding the impact of supplements like NAD precursors and medications like metformin on mitochondrial function requires further research. Balancing training intensities, addressing potential risks of NAD supplementation, and considering individual metabolic responses are essential in promoting mitochondrial health and overall well-being.
Mitochondrial Health and Aging
Mitochondrial health impacted by factors like supplements, medications, and training intensities plays a significant role in aging and longevity. Research into the effects of NAD precursors and metformin on mitochondrial function can shed light on their potential risks and benefits. Maintaining a balance in training regimens and dietary interventions is crucial for preserving mitochondrial function and promoting healthy aging.
Exercise Impact on Cancer Cell Growth and Proliferation
High glycolytic rate in cancer cells leads to lactate production, an onco-metabolite that drives cell growth. By blocking lactate production, cancer growth stops within hours. Exercise increases lactate clearance, impacting cancer patients' net response to exercise.
Mitochondrial Function and Metabolic Dysregulation in Sedentary Individuals
Sedentary individuals display significant dysregulation in mitochondrial function, impacting glucose and fat metabolism. Their mitochondria show decreased capacity for oxidation and reduced substrate transporters. The study highlights alterations in the mitochondrial pyruvate carrier and fat oxidation transporters as potential early indicators of metabolic dysfunction prior to clinical symptoms.
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
