March 28, 2022

Aerobic & Zone 2 Training

#201 – Deep dive back into Zone 2 | Iñigo San-Millán, Ph.D. (Pt. 2)

You can accomplish very important mitochondrial adaptations and very important metabolic adaptations by exercising one hour.” —Iñigo San-Millán

Read Time 48 minutes

Check out more content with expert, Iñigo San Millán, Ph.D.:

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 [3:00];
  • Metrics for assessing athletic performance in cyclists and how that impacts race strategy [8:30];
  • The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [17:00];
  • Tadej Pogačar’s race strategy and mindset at the Tour de France [24:00];
  • Defining Zone 2, fat oxidation, and how they are measured [26:45];
  • Using fat and carbohydrate utilization to calculate the mitochondrial function and metabolic flexibility [35:45];
  • Lactate levels and fat oxidation as it relates to Zone 2 exercise [40:00];
  • How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:45];
  • Bioenergetics of the cell and what is different in elite athletes [57:30];
  • How the level of carbohydrate in the diet and ketogenic diets affects fuel utilization and power output during exercise [1:08:30];
  • Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:15:00];
  • How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:21:00];
  • Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:25:00]; 
  • Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:41:15];
  • How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:51:15];
  • Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:45];
  • The effects of metformin, NAD, and supplements on mitochondrial function [2:05:15]; 
  • The role of lactate and exercise in cancer [2:13:30];
  • How assessing metabolic parameters in long COVID patients provides insights into this disease [2:19:00];
  • The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise [2:25:45];
  • Metabolomics reveals how cellular metabolism is altered in sedentary individuals [2:33:45];
  • Cellular changes in the metabolism of people with diabetes and metabolic syndrome [2:39:15]; and
  • More.


The amazing potential of cyclist Tadej Pogačar [3:00]

Tadej Pogačar

  • No one knew who Tadej Pogačar was 2.5 years ago but now he may potentially go down as the greatest Tour de France cyclist of all time
    • To win the tour at such a young age (21)
    • Not just win the yellow Jersey, but the white Jersey, and the polka-dot Jersey repeatedly, he looks like something of a different species almost

Iñigo’s work with Tadej Pogačar

  • Iñigo began working with Tadej Pogačar in late 2018 when he signed up for the the UAE team
    • Pogačar had just turned 19 
    • Iñigo recognized right away his potential
  • Physiological testing of Pogačar  revealed his amazing capabilities
    • His ability to clear lactate and put out a great amount of power for long periods of time
    • Iñigo measured his blood lactate levels at a given power output
      • He’s been doing this testing for 20 years with professional athletes, professional cyclists
      • This allows him to categorize people
    • Pogačar was at a different category in his first year as a pro cyclist
    • He could sustain a high amount of power with very low lactate compared to the rest 
  • Iñigo uses TrainingPeaks software to track his ability to sustain a given power output for the whole day or a specific glycolytic effort
  • Iñigo saw his trainability, how easy he would get the concepts, how easy he would be comfortable with the training, how easy he would recover
  • Iñigo would talk to him once, twice a day using the WhatsApp
    • He would know when Pogačar had a hard week and Pogačar would often tell him he was good and recovering well
      • Where as other cyclists would have to take it easy after that week


Metrics for assessing athletic performance in cyclists and how that impacts race strategy [8:30]

  • Around this time, Iñigo began developing a platform for metabolomics with colleagues at the university, Angelo D’Alessandro and Travis Nemkov
  • They can look at hundreds, if not thousands of metabolites in the human body
  • They did this in the Tour of California in 2019, which was around April; Pogačar won
    • So he has the analysis of all of Pogačar’s metabolites
    • Prior to this, they ran this analysis at the training camp in January, 2018

Wow, this guy has different metabolites at the glycolytic level, acidic level, recovery level…. this guy is different”— Iñigo San-Millán

  • One of the most telling data points for a cyclist is lactate production (y-axis) versus watts per kilo (x-axis)
    • A normal climbing tempo in the Tour de France is about 5 watts
    • Someone at that intensity might have already six millimoles (mmol) of lactate, where it would be 1 mmol at resting levels
    • This can predict how taxing the work is and really predicts performance
  • In the first training camp of the year for the team they do physiological testing and he gets this data 
    • This allows him to rank the cyclists
    • They test this with different racing simulations; this measurement is very predictive
  • Peter notes this is one thing he loves about cycling— knowing where the athletes stand before the race based on their FTP (functional threshold power) in watts per kilo
  • Peter interviewed Lance Armstrong last year and Lance revealed when he was off EPO he could hold 450 watts for 30 minutes
    • So that would be slightly above FTP
    • He was around 70 to 75 kilos
    • This was in the ballpark of 6 watts per kilo
    • But on EPO it was 7.1 watts per kilo, a huge difference
  • Only the GC contenders could do that, ride at 6 watts per kilo
    • But there relatively few moments in the tour when one needs to sustain that level
    • These moments occur at the most important strategic times; this is where the race is won and lost
      • Because races are won and lost by minutes
      •  It takes about 4-5 hours per day for 23 days to complete the Tour de France; it’s about 100 hours in all
      • Yet the difference between the 1st, 2nd, 3rd guy will be, in some cases seconds, in some cases a few minutes
      • For someone to win by 5 minutes is considered a blowout
  • Iñigo uses this metric a lot
  • Knowing the power output a ricker can sustain for specific times and climbed tells alot about his capabilities 

{end of show notes preview}

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Iñigo San-Millán, Ph.D.

Iñigo San-Millán earned his doctorate at the University of the Basque Country School of Medicine.  He did his postdoctoral research at the Harvard Medical School Cancer Research Program.  Currently he is an Assistant professor in the School of Medicine at the University of Colorado School – Colorado Springs.  His research and clinical work focuses on: exercise metabolism, cancer metabolism, metabolic health, nutrition, sports performance, diabetes, and critical care.

Dr. San-Millán has worked for the past 25 years with many professional teams and elite athletes worldwide across multiple sports, this includes: soccer, cycling, football, basketball, track and field, rowing, triathlon, swimming, and Olympic training. He has been a consultant in exercise physiology and sports medicine to international organizations such as the US Olympic Committee.  He has pioneered the development of new methodologies for monitoring athletes at the metabolic and physiological level.  He developed the first method to indirectly measure mitochondrial function and metabolic flexibility/  He co-developed the first methodology to deploy metabolomics assessment to professional sports as well as the first method to indirectly measure skeletal muscle glycogen in a non-invasive manner using high frequency ultrasound.  Currently, he is the Director of Performance for Team UAE Emirates cycling team and the personal physiologist and coach of 2020 and 2021 Tour de France winner Tadej Pogacar. 

Although now a recreational athlete, he used to be a competitive athlete.  He played soccer for 6 years for the developmental academy of Real Madrid soccer team.  He also raced as a low-key, professional cyclist for 2 years.  [Dr. San-Millan’s Website]

Twitter: @doctorIñigo

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  1. In the last interview, it was recommended that 45 minute seasons 4 times a week were necessary to improve mitochondrial function with zone 2 training. In this interview it was stated that 60 minute session, 4 times a week were necessary. Has the science changed or is that just, “off the top of my head”, numbers?

  2. Peter,
    This is one of your most significant submissions! I am a retired Family Physician, very interested in evolution of the Academy of Lifestyle Medicine (6 Pillars: exercise, sleep, community, nutrition, <stress, substance avoidance). I am curious about the relevance of this whole discussion to sarcopenia in elderly adults, and what physiology and spin off (^lactate, inactivity, glutamate robbing promoting atrophy, the mitochondrial biochemistry, etc)
    Your and Dr. San-Millan's discussion are so relevant to essential benefits of exercise, but the opposite the detriments of our propensity to 'slothiness'. The biochemical physiology details, charts, post ICU states, possible long Covid associations, and Warburg/Lactate/cancer physiology discussion were much appreciated. Your quest as to how to best dose this non-pharmaceutical 'elixir' of exercise/locomotion/resistance training is huge! Is is possible to send a copy (via copy and paste) of this show notes to a couple of exercise physiology associates and Cardilogist's who might have interest?
    Boyd Myers

  3. Tremendous podcast. The one aspect that left me wondering was that men and women have different capacities of fat oxidation, with it being greater in the latter for submaximal intensities. That fat oxidation is also higher during the luteal phase? How might this affect the focus on zone 2 exercise for mitochondrial health, is there a greater or lesser need in women? Thank you.

  4. Really interesting podcast. I pulled up the paper the figures came from to get the whole story and had some other thoughts and questions, in case you ever do another one.
    1. The podcast discussed plotting watts/kg on the X-axis, which would be interesting. I understand it didn’t go into the paper because of reviewers, but it would be interesting to show in the notes here. Would it be worthwhile to normalize the X-axis by estimating FTP from the test, then making the X-axis percentage of FTP (going over 100% at the right end)? Then it might be possible to more easily see if, for example, the MA group has a similar shape as the PA group, but shifted when plotted on absolute power.
    2. Some endurance coaches emphasize looking at the size of the gap between aerobic threshold and lactate threshold and trying to make it smaller. A relative power plot might show to what extent the PA group achieve that.
    3. In retrospect, would it be better to have a protocol that starts below 100 watts, and goes up in smaller increments, at least for the MA and MtS groups, to see if their curves have any of the shape characteristic of the PA curve, but shifted?
    4. With regard to the recommendations on zone 2 duration and frequency, to really validate those would require a long study with a bunch of people that I imagine would be unaffordable. Has there been any consideration given to partnering with groups that have extensive data on a large number of people’s training (like Peloton, Strava, or Training Peaks)? Perhaps use databases like that to solicit volunteers who fit a specific training profile (e.g. X hours per peak of training measured as Zone Y) to be metabolically tested? Obviously it is not an RCT, but it would be somewhat like this study, albeit with the possibility of forming MA-like groups with more fine-grained control on what training they’ve been doing.
    5. I’d be really curious to see the curves for a group of PA level people who pursue mainly high-intensity training. Maybe international level sprinters or Crossfit Games qualifiers.

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