← The Peter Attia Drive

#85 - Iñigo San Millán, Ph.D.: Mitochondria, exercise, and metabolic health

Dec 23, 2019 2h 53m 24 insights
<p>In this episode, Dr. Iñigo San Millán, Assistant Professor at the University of Colorado School of Medicine, explains the crucial role of mitochondrial function in everything from metabolic health to elite exercise performance. Iñigo provides a masterclass into the many different energy system pathways, the various fuel sources (including the misunderstood lactate), the six zones of exercise training, and the parameters he uses to measure metabolic health. Additionally, he highlights the power of zone 2 training in its ability to act as a powerful diagnostic tool, and perhaps more importantly as a treatment for mitochondrial and metabolic dysfunction.</p> <p>We discuss:</p> <ul dir="auto"> <li> <p dir="auto">Iñigo's background in sports and decision to focus on education [7:15];</p> </li> <li> <p dir="auto">Explaining the various energy systems and fuels used during exercise [14:45];</p> </li> <li> <p dir="auto">Iñigo qualifies energy systems into six training zones [26:00]; </p> </li> <li> <p dir="auto">Lactate is an important fuel source [33:00];</p> </li> <li> <p dir="auto">Zone 2 training—physiologic characteristics, fuel sources, lactate, and the transition into zone 3 [40:30];</p> </li> <li> <p dir="auto">Using blood lactate levels (and zone-2 threshold) to assess mitochondrial function [47:00];</p> </li> <li> <p dir="auto">Accessing mitochondrial function by looking at one's ability to utilize fat as fuel (with an RQ test) [55:00];</p> </li> <li> <p dir="auto">Athletes vs. metabolically ill patients—mitochondria, fat oxidation, muscle glycogen capacity, "fat droplets", and more [1:00:00];</p> </li> <li> <p dir="auto">Physiologic characteristics of zone 3, zone 4, and the lactate threshold [1:20:00];</p> </li> <li> <p dir="auto">Fueling exercise—dietary implications on glycolytic function [1:30:30];</p> </li> <li> <p dir="auto">Relationship between exercise and insulin sensitivity (and what we can learn from studying patients with type 1 diabetes) [1:46:30];</p> </li> <li> <p dir="auto">Metformin's impact on mitochondrial function, lactate production, and how this affects the benefits of exercise [2:04:15];</p> </li> <li> <p dir="auto">Raising awareness for risk of "double diabetes" [2:15:00];</p> </li> <li> <p dir="auto">How to dose zone 2 training, and balancing exercise with nutrition [2:18:00];</p> </li> <li> <p dir="auto">Proposed explanation of the Warburg Effect: Role of lactate in carcinogenesis [2:27:00];</p> </li> <li> <p dir="auto">Doping in cycling, and the trend towards altitude training [2:39:15] and;</p> </li> <li> <p dir="auto">More.</p> </li> </ul> <p>Learn more: <a href="https://peterattiamd.com/">https://peterattiamd.com/</a><br /> <br /> Show notes page for this episode: <a href="https://peterattiamd.com/inigosanmillan">https://peterattiamd.com/inigosanmillan</a><br /> <br /> Subscribe to receive exclusive subscriber-only content: <a href="https://peterattiamd.com/subscribe/">https://peterattiamd.com/subscribe/</a><br /> <br /> Sign up to receive Peter's email newsletter: <a href="https://peterattiamd.com/newsletter/">https://peterattiamd.com/newsletter/</a><br /> <br /> Connect with Peter on <a href="http://Facebook.com/PeterAttiaMD"><u>Faceboo</u></a><u>k</u> | <a href="http://Twitter.com/PeterAttiaMD"><u>Twitter</u></a> | <a href="http://Instagram.com/PeterAttiaMD"><u>Instagram</u></a>.</p>
Actionable Insights

1. Optimize Mitochondrial Function with Zone 2 Training

Engage in Zone 2 exercise, which is the highest intensity where you can still hold a conversation, or where lactate levels are between 1.5-2.0 millimoles. This stimulates slow-twitch muscle fibers to their fullest, maximizes fat oxidation, and significantly improves mitochondrial efficiency and lactate clearance.

2. Train Zone 2 for Metabolic Health

For individuals with pre-type 2 or type 2 diabetes, aim for 1 to 1.5 hours of Zone 2 training, 3-5 days a week, to significantly improve metabolic flexibility and potentially reverse pre-diabetes.

3. Leverage Zone 2 for Glucose Uptake

Consistent Zone 2 training enhances the non-insulin dependent glucose uptake pathway in muscles, allowing cells to take up glucose without relying on insulin. This is particularly beneficial for insulin sensitivity and glucose regulation.

4. Utilize Food and Exercise as Medicine

Recognize that food and exercise are the most potent tools for managing health and preventing disease, often surpassing the efficacy of pharmaceutical interventions.

5. Adopt Sustainable Lifestyle Changes

When implementing diet or exercise programs, prioritize changes that you can realistically maintain for the rest of your life, as unsustainable extremes often lead to eventual abandonment.

6. Identify Zone 2 by Conversation/Lactate

To find your Zone 2, aim for an exercise intensity where you can still comfortably carry on a conversation, or if using a lactate meter, maintain blood lactate levels between 1.5 and 2.0 millimoles. This ensures you are maximizing fat oxidation and stimulating mitochondrial function.

7. Prioritize Mitochondrial Conditioning Over Calories

When exercising for metabolic health and weight loss, focus on “mitochondrial conditioning” through Zone 2 training rather than simply burning calories. Training too hard can lead to burning less fat during exercise.

8. Implement Cool Down for Hyperglycemia

For individuals experiencing post-exercise hyperglycemia, especially those with diabetes, performing a cool-down period can help lower glucose levels and reduce the need for insulin correction.

9. Exercise Immediately After Meals (Type 2)

For individuals with Type 2 diabetes or insulin resistance, exercising immediately after a meal can leverage muscle contraction to facilitate glucose uptake without requiring as much insulin.

10. Monitor Heart Rate for Training Stress

Understand that a given power output (watts) does not always equate to the same physiological stress; monitor heart rate and lactate levels, as they are physiological parameters that reflect the body’s metabolic stress.

11. Assess Resting RQ for Dysfunction

If your fasting resting respiratory quotient (RQ) or respiratory exchange ratio (RER) is consistently 0.9 or higher, it’s a significant red flag for mitochondrial dysfunction, indicating an over-reliance on glucose over fat for fuel at rest.

12. Maintain Function with Consistent Zone 2

To maintain mitochondrial function and fat-burning capacity, incorporate Zone 2 training at least two days a week. Elite athletes in their off-season use this frequency for maintenance.

13. Incorporate Fasting for Metabolic Balance

Consider integrating various fasting protocols (e.g., weekly, monthly, quarterly) into your routine as a tool to maintain metabolic balance and achieve health goals sustainably.

14. Adjust Insulin Dosing for Exercise (Type 1)

Individuals with Type 1 diabetes should work with clinicians to adjust insulin doses, often reducing them before exercise, to prevent hypoglycemia due to increased insulin sensitivity.

15. Re-evaluate Metformin Use with Zone 2

If you are metabolically healthy and taking metformin, consider experimenting with reducing or timing your dose away from Zone 2 exercise, as it may blunt the benefits of mitochondrial training and elevate lactate levels. Consult your doctor.

16. Prioritize Quality of Life in Longevity

Focus on optimizing health and function in later years, not just extending lifespan, to ensure a high quality of life throughout longevity.

17. Question Endorsements for Trust

Be skeptical of product recommendations from individuals who are paid by the company, as this can compromise trust in their advocacy.

18. Advocate for Genuine Beliefs

Only advocate for products or ideas you are genuinely passionate about and believe in, as this authenticity builds trust and enthusiasm.

19. Be Aware of Statin Impact

Understand that statins can affect mitochondrial function and may increase the risk of developing diabetes, which is a long-term consideration when evaluating their use.

20. Support the Podcast for Content

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21. Avoid Carb Restriction for Elite Performance

Elite athletes should avoid acute carbohydrate restriction or ketogenic diets during competitive training and racing seasons, as the adaptation period is too long and can severely impair performance.

22. Consider Carb Restriction for Metabolic Health

For individuals not aiming for elite athletic performance, carbohydrate restriction can be a powerful tool to improve metabolic health, even if initial exercise performance is temporarily reduced.

23. Monitor Glucose During Zone 2

Track your glucose levels (e.g., with a continuous glucose monitor) during Zone 2 exercise, as a steady and consistent fall in glucose indicates effective non-insulin dependent glucose uptake and improved metabolic function.

24. Optimize Altitude Training with “Live High, Train Low”

For performance enhancement, aim to live at high altitude to increase oxygen-carrying capacity, but conduct high-intensity training at or near sea level to prevent deterioration of glycolytic capacity.