Saturday, September 24, 2022
Mitochondrial Health

201 – Deep dive back into Zone 2 Training | Iñigo San-Millán, Ph.D. & Peter Attia, M.D.



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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:
0:00:00 – Intro
0:00:10 – The amazing potential of cyclist Tadej Pogačar
0:06:54 – Metrics for assessing athletic performance in cyclists and how that impacts race strategy
0:17:20 – The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition
0:26:06 – Tadej Pogačar’s race strategy and mindset at the Tour de France
0:29:58 – Defining Zone 2, fat oxidation, and how they are measured
0:40:04 – Using fat and carbohydrate utilization to calculate the mitochondrial function and metabolic flexibility
0:44:30 – Lactate levels and fat oxidation as it relates to Zone 2 exercise
0:59:54 – How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance
1:06:27 – Bioenergetics of the cell and what is different in elite athletes
1:19:19 – How the level of carbohydrate in the diet and ketogenic diets affects fuel utilization and power output during exercise
1:27:27 – Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients
1:34:27 – How exercise mobilizes glucose transporters—an important factor in diabetic patients
1:39:00 – Metrics for finding Zone 2 threshold—lactate, heart rate, and more
1:58:27 – Optimal Zone 2 training: dose, frequency, duration, and type of exercise
2:10:22 – How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness
2:23:25 – Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age
2:27:57 – The effects of metformin, NAD, and supplements on mitochondrial function
2:37:45 – The role of lactate and exercise in cancer
2:44:42 – How assessing metabolic parameters in long COVID patients provides insights into this disease
2:52:57 – The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise
3:02:30 – Metabolomics reveals how cellular metabolism is altered in sedentary individuals
3:08:49 – Cellular changes in the metabolism of people with diabetes and metabolic syndrome

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About:

The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 40 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.

Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life).

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43 thoughts on “201 – Deep dive back into Zone 2 Training | Iñigo San-Millán, Ph.D. & Peter Attia, M.D.
  1. In this episode, we discuss:

    0:00:00 – Intro

    0:00:10 – The amazing potential of cyclist Tadej Pogačar

    0:06:54 – Metrics for assessing athletic performance in cyclists and how that impacts race strategy

    0:17:20 – The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition

    0:26:06 – Tadej Pogačar’s race strategy and mindset at the Tour de France

    0:29:58 – Defining Zone 2, fat oxidation, and how they are measured

    0:40:04 – Using fat and carbohydrate utilization to calculate the mitochondrial function and metabolic flexibility

    0:44:30 – Lactate levels and fat oxidation as it relates to Zone 2 exercise

    0:59:54 – How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance

    1:06:27 – Bioenergetics of the cell and what is different in elite athletes

    1:19:19 – How the level of carbohydrate in the diet and ketogenic diets affects fuel utilization and power output during exercise

    1:27:27 – Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients

    1:34:27 – How exercise mobilizes glucose transporters—an important factor in diabetic patients

    1:39:00 – Metrics for finding Zone 2 threshold—lactate, heart rate, and more

    1:58:27 – Optimal Zone 2 training: dose, frequency, duration, and type of exercise

    2:10:22 – How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness

    2:23:25 – Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age

    2:27:57 – The effects of metformin, NAD, and supplements on mitochondrial function

    2:37:45 – The role of lactate and exercise in cancer

    2:44:42 – How assessing metabolic parameters in long COVID patients provides insights into this disease

    2:52:57 – The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise

    3:02:30 – Metabolomics reveals how cellular metabolism is altered in sedentary individuals

    3:08:49 – Cellular changes in the metabolism of people with diabetes and metabolic syndrome

  2. Thanks Peter and Inigo. Your conversation has reinforced my understanding and as an intermediate age grouper, (55-59) who's been following a predominantly Z2 TP program for around 5mths now, I'm starting to notice those small incremental improvements. I have for a great many years now believed that you can treat most things through diet, exercise and strength training. Building that Z2 base just continues to reap benefits for me. 🙏

  3. Very nice and informative interview Peter. Still not convinced you are in Z2 though 😉 And I think Inigol was too polite to challenge your definition of LT1 as 2mml/l.

  4. Another great episode. One question I’m still unsure on is what happens when intensity drifts into the tempo (Coggan L3) zone? The TSS will be higher per unit time obviously but do the higher lactate levels actually inhibit mitochondria biogenesis?

    Also I’m interested to know whether Peter’s seen any impact from Rapamycin on Z2 performance?

  5. I’m listening to this when I can… started at 1:39:00 and drinking all this great information in. Interesting experiment Dr. Attia did with Propranolol. My HR was extra high today (by 10-15 bpm) doing zone 2 after a cup of coffee. Increased the duration from 45 mins to an hour. Not having a lactate meter, I felt reassured to use perceived exertion as described by Dr. Attia and Dr. San Millan. Can’t wait to listen to more.
    People often use the phrase life-changing for things that really aren’t. It’s no exaggeration to say this and so many other things we’ve learned from this podcast are truly life-changing and I am so thankful that Dr. Attia shares his brilliance and expertise with others so we can all have better lives.

  6. 2:25:20 "You can make relatively quick changes in your glycolytic efficiency. You can take an untrained person with a vo2 max of 20 and you could take them to 30 in a period of months with the right amount of training. A 50% improvement in a few months. It's very difficult to see a 50% improvement in mitochondrial function in a few months. It speaks to why this level of training should be thought of in the same way that you think of accumulating wealth: which is it's day-in and day-out small compounded gains over years and years. "

    Powerful. I gotta get on it!

  7. Great podcast guys. Q re Metformin effect on mitochondria: how about recruit subjects with Z2 threshold of say 2.5-3w/kg and introduce metformin dose for 1-3 months? This cohort are clearly active and a good reference group

  8. does mitochondrial efficiency or adaptations occur systematically or at the working muscles post-exercise. For example, when cycling or running we are primarily using the leg muscles. The pectoral muscles or triceps are not even close to the same level of exertion.

  9. Is this zone 2 in a 3, 5 or 7 zone model? How is it defined in function of FTP? As most of us have power meters and heart rate monitors available, but no equipement to measure lactate.

  10. It takes (or used to take) several years to build up endurance in order to win road races. But the new generation of riders (Pogačar, Van Aert, MvdP,, etc) don't seem to care. How do they do it?

  11. On March 29, 2022, Dr. Sarah Hallberg passed away.

    Dear Dr. Attia, Inigo, and everyone else watching this.

    There is no more chance for salvation after death no matter how physically healthy you are.

    If Dr. Sarah Hallberg did not put her faith in Jesus Christ and have him wash away her sins, she will be in hell when everyone is resurrected regardless of how many people she has helped with her dietary advice and all her accomplishments would have meant nothing.

    Hell is a terrible place. The pain is both physical as well as spiritual. The fires will not be put out, the worms will not die, and people will live and suffer in hell forever.

    There will be no sexual intercourse or childbearing in heaven or the desire for them, but there won't be these things in hell either.

    Matthew 16:26
    26 For what is a man profited, if he shall gain the whole world, and lose his own soul? or what shall a man give in exchange for his soul?

    Matthew 10:28
    28 And fear not them which kill the body, but are not able to kill the soul: but rather fear him which is able to destroy both soul and body in hell.

    Mark 9:48-49
    48 Where their worm dieth not, and the fire is not quenched.

    49 For every one shall be salted with fire, and every sacrifice shall be salted with salt.

    Revelation 14:11
    11 And the smoke of their torment ascendeth up for ever and ever: and they have no rest day nor night, who worship the beast and his image, and whosoever receiveth the mark of his name.

    Hebrews 9:27-28
    27 And as it is appointed unto men once to die, but after this the judgment:

    28 So Christ was once offered to bear the sins of many; and unto them that look for him shall he appear the second time without sin unto salvation.

  12. One of your best episodes, Peter. Outstanding physiology information and love the deep dives regarding zone 2 training. As a cyclist, this is what makes this podcast special. Keep it coming.

  13. Thank you both for sharing so many important elements that intuitively I was already aware of, but now being backed up by research and studies will make my life easier with the athletes I train and my family members affected with cancer and obesity/sedentarism

  14. Really really want to know if you can do weight training immediately after a zone 2 session! Will it negate the effects of zone 2?

  15. Great shows thanks . I’m wondering how he would this Zone 2 training into a training plan for a good agegroupe/pro triathlete and if he understand zone 2 training only has the high part of the endurance zone ( so until around 75% of if we we want do use this as a way of defining the question) or if it can be the endurance part with lower watts ( let’s say 60-65% of ftp. Thanks

  16. h 2:36: so early retirement is the answer 🙂 thank you both for a fascinating episode. As an age grouper, this gives me extra ammunition to convince my group (and coach…) to emphasize Z2 over HIIT intervals!

  17. I'm one of the lucky ones hit with Long Covid. Prior to Covid infection I was a fulltime endurance athlete. I'm 11 months now and slowly getting back to exercise. I could barely walk for 4 months. But starting light bikes rides and skiing from month 5 to now. I'm planning to bike Zone 2 for 5 days a week for an hour to hopefully restore my mitochondria. At this point in the journey, activity seems to help, which supports his theory. I've seen some other endurance types recover from LC using a very slow build up in activity; it seems to take about 12-18 months for them to get back to normal activity levels.

  18. does fat and pyruvate compete for oxygen to form acetyl coa? is the amount of acetyl coa directly correlated to vo2max? or are you just producing more acetyl coa as you become better at fat oxidation?

  19. I am a long time listener and admirer of Attia, and an elite competitive masters cyclist. This is a thoroughly comprehensive interview. Outstanding information!👏 Watch it repeatedly! Internalizing it! Be confident in its application! Then go do epic shit! 🚴‍♂️🧠

  20. + Peter Attia MD Due to this podcast I've decided to start doing zone 2 training and am really enjoying it. Coming back from a run and still feeling fresh is a pleasant change. HOWEVER…I replayed this podcast today and at 1:46:45 you say that zone 2 was 70 to 80% percent of MAX heart rate. I thought zone 2 was 60 to 70% MHR. Am I wasting my time at 60 to 70? 70 to 80 percent is what I've normally been doing in the past for an easy day run.

  21. Ironman athlete here who went through 6 months of long covid. Was dreadful, lost everything fitness wise. Heart problems, total mitochondrial breakdown — couldnt keep up with my 8 year old on a bike for 10 minutes. Full recovery a year later. Great episode and nice to hear you touch on the subject.

  22. Great podcast! One question. You have mentioned type 2 diabetes as per reference to metabolic syndrome. Can we draw the same conclusions to diabetic type 1 patients?

  23. Really great stuff – Thank you Peter Attia!
    Question about zone 5 (and zone 2). Based on PAs "Q&A, 21. apr. 2021", at 51:50): PA says he is within 2 beats of his max hr, at the end of the 1-minute hard effort! How can that be? Most people require a much longer effort, before reaching (within 2 beats of) max hr!(?) Im curious: does PA have a higher max hr than he thinks – or is he unbelievably good at increasing hr (in one minute (biking!))? If his max hr is higher than he thinks, that would suggest that we should be lower than 78-81 % of hr (in zone 2). And it looks like many people believe they should be lower than 80 % of max hr (for zone 2). Personally, Im sure about my max hr (200), and I need a lot more time and effort to reach that kind of heart rate (195-200) while running (would be even more difficult, for me, on a bike). I also suspect that my zone 2 is more likely to be between 75 and 80 % of max hr (than 78-81). I know that (% of max) hr is not the most accurate, but i found PAs statement at 51:50 to be very strange. Would love to hear him explain/elaborate. Link to episode https://www.youtube.com/watch?v=txLrNhv8GW0 (51:40 –> )

  24. Is gundry's mitochondrial "polyphenol" theory relevant here (or true)..

    The theory that polyphenols increase the abilities of mitochondria to burn energy. He quotes a lot of studies and has genuine expertise. But of course a second opinion is essential.

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