July 8, 2024 • 2hr 46min
Zone 2 training: impact on longevity and mitochondrial function, how to dose frequency and duration, and more | Iñigo San-Millán, Ph.D. (#201 rebroadcast)
The Peter Attia Drive
Key Takeaways
- Zone 2 training is critical for improving mitochondrial function and metabolic health. It involves exercising at an intensity that maximizes fat oxidation and lactate clearance.
- Elite athletes like Tadej Pogačar have an incredible ability to clear lactate and sustain high power outputs due to highly developed mitochondrial function.
- Measuring zone 2 can be done through lactate testing, indirect calorimetry to measure fat oxidation, or perceived exertion. A good rule of thumb is being able to talk but with some strain.
- Optimal zone 2 training involves 3-5 sessions per week of 60-90 minutes each. Consistency and frequency are key for mitochondrial adaptations.
- High intensity training is still important to include, but should be a smaller portion of overall training volume compared to zone 2.
- Mitochondrial function declines with age and sedentary behavior, but can be improved at any age through proper training.
- Long COVID patients show significant mitochondrial dysfunction, highlighting the importance of metabolic health.
- Exercise is likely the most potent tool we have for improving longevity, working through multiple mechanisms to enhance metabolic and mitochondrial health.
Introduction
In this episode, Dr. Peter Attia interviews Dr. Iñigo San-Millán, an internationally renowned applied physiologist and researcher focused on exercise metabolism, metabolic health, and mitochondrial function. They discuss the science behind zone 2 training, insights from elite athletes, how to properly implement this type of training, and its implications for health and longevity.
Topics Discussed
Insights from Elite Cyclists (2:00)
Dr. San-Millán discusses his work with Tour de France champion Tadej Pogačar and what makes him physiologically exceptional:
- Ability to clear lactate and sustain high power outputs
- Extremely low lactate levels at given power outputs compared to other athletes
- Highly developed fat oxidation capacity
- Superior recovery between hard efforts
"He has a much higher level to oxidize lactate. So there's a genetic component, no doubt about it. There's also an epigenetic component." - Dr. Iñigo San-Millán
Defining Zone 2 and Fat Oxidation (26:00)
The discussion turns to defining zone 2 exercise and how it relates to fat oxidation:
- Zone 2 is the exercise intensity that maximally stresses mitochondria and oxidative capacity
- It recruits mainly type 1 muscle fibers and mobilizes the highest amount of fat
- Stimulates oxidative phosphorylation in mitochondria
- Develops lactate clearance capacity through MCT1 transporters
"This is where you're recruiting mainly type one muscle fibers. This is where you are mobilizing the highest amount of fat, both from lipolysis, from adipose tissue, as well from fat oxidation inside the mitochondria." - Dr. Iñigo San-Millán
Measuring Zone 2 and Fat Oxidation (31:54)
They discuss different methods for measuring and estimating zone 2 intensity:
- Indirect calorimetry to measure fat oxidation
- Lactate testing (typically around 1.7-2.0 mmol/L for zone 2)
- Heart rate (roughly 70-80% of max heart rate)
- Perceived exertion - able to talk but with some strain
"If you can exercise, whatever the exercise you do and maintain a conversation like you and I are doing, you're way too easy. You're probably zone one. If you can talk, but it's some form of strain, you can talk for 2 hours, but we're talking a little bit like that...you're just at that threshold." - Dr. Iñigo San-Millán
Optimal Zone 2 Training Protocol (1:40:30)
Dr. San-Millán outlines his recommendations for zone 2 training:
- Frequency: 3-5 sessions per week
- Duration: 60-90 minutes per session
- Intensity: Guided by lactate, fat oxidation, or perceived exertion
- Can start with shorter durations (20-30 min) and build up over time
- Consistency is key for mitochondrial adaptations
"Four days a week is ideal. That's the first principle. The second principle is the duration. Going back to where I was saying with 1 hour, maybe Pogačar needs 4 hours, 5 hours to keep increasing those huge mitochondria for a long time. But a more mortal, especially someone who might be prediabetes or might be out of fitness or has an exercise in a long time...1 hour if you walk or if you run might be very, very good for you." - Dr. Iñigo San-Millán
Incorporating High Intensity Training (1:50:30)
They discuss the role of high intensity training in addition to zone 2:
- Still important to include to stimulate glycolytic capacity
- Can be done as separate sessions or at the end of zone 2 workouts
- Helps improve VO2 max and peak aerobic capacity
- Should be a smaller portion of overall training volume
"I think is necessary because we also lose glycolytic capacity as we age. And it's important to stimulate it." - Dr. Iñigo San-Millán
Compounding Benefits of Zone 2 Exercise (2:01:00)
Dr. San-Millán emphasizes the long-term benefits of consistent zone 2 training:
- Can maintain or improve metabolic health parameters into older age
- Seen dramatic improvements in people starting in their 60s and 70s
- Benefits compound over years of consistent training
- More impactful for longevity than short-term high intensity programs
"I've seen people in their seventies with the metabolic parameters of people active, morally active, in their thirties...This is incredibly inspiring. Then I think that we're rewriting what's been taught to us in the books." - Dr. Iñigo San-Millán
Metformin, NAD, and Mitochondrial Function (2:04:30)
They discuss the effects of metformin and NAD precursors on mitochondrial health:
- Metformin may impair mitochondrial function by inhibiting complex 1
- Unclear if long-term metformin use impacts longevity
- NAD precursors like NR and NMN have unclear benefits
- Pilot study showed NAD precursors may accelerate tumor growth
"We need a lot of research on that, I think, to understand this better. Definitely. It seems to work in many patients. Obviously, for those ones in the pre diabetic first stage diabetes, it's a very good medication that's been used for a long time with good results. But how about the long term results?" - Dr. Iñigo San-Millán on metformin
Lactate and Exercise in Cancer (2:12:45)
Dr. San-Millán discusses his research on lactate's role in cancer:
- Lactate acts as an oncometabolite, regulating gene expression in cancer cells
- Blocking lactate production stops cancer growth in studies
- Exercise may help counteract cancer's lactate effects
- Muscle-derived exosomes may have anti-cancer properties
"We are showing that it's an onco metabolite. So if you have a high glycolytic rate in a cell, you're going to produce a lot of lactate you cannot clear that lactate, it's going to drive cell growth and proliferation, as we're seeing, and in fact, we're now blocking lactate production both through genetic engineering as well as DCA, for example. And we're seeing that cancer growth and proliferation completely stops within hours." - Dr. Iñigo San-Millán
Metabolic Dysfunction in Long COVID Patients (2:18:30)
They discuss Dr. San-Millán's research on long COVID patients:
- Patients show significant mitochondrial dysfunction
- Fat oxidation and lactate clearance severely impaired
- Metabolic parameters worse than type 2 diabetes patients
- May be due to virus hijacking mitochondria
- Exercise could potentially help but more research needed
"We suspect from this data, which, again, is indirect, from the indirect calorimetry and the lactate that it points out towards mitochondrial dysfunction. So that's what we need to do now, biopsies, to understand this at a better detail. What the heck is going on?" - Dr. Iñigo San-Millán
Conclusion
This wide-ranging discussion highlights the critical importance of mitochondrial and metabolic health for overall wellbeing and longevity. Zone 2 training emerges as a powerful tool for improving these parameters, with benefits that compound over time. The insights from elite athletes demonstrate the remarkable capacity of human physiology when optimized. At the same time, the metabolic dysfunction seen in sedentary individuals and long COVID patients underscores how quickly these systems can decline without proper stimulation. Overall, the conversation reinforces exercise, particularly zone 2 training, as perhaps the most potent intervention available for enhancing healthspan and lifespan.