December 23, 2019

Exercise & Physical Health

#85 – Iñigo San Millán, Ph.D.: Zone 2 Training and Metabolic Health

“What I have been seeing for 25 years, working with elite athletes, is that [zone 2] is the exercise intensity where I see the biggest improvement in fat burning and the biggest improvement in lactic clearance capacity. Therefore, that means that the mitochondria is where you see the biggest improvement.” —Iñigo  San Millán, Ph.D.

Read Time 28 minutes

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

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.


We discuss:

  • Iñigo’s background in sports and decision to focus on education [7:15];
  • Explaining the various energy systems and fuels used during exercise [14:45];
  • Iñigo qualifies energy systems into six training zones [23:00]; 
  • Lactate is an important fuel source [33:00];
  • Zone 2 training—physiologic characteristics, fuel sources, lactate, and the transition into zone 3 [40:30];
  • Using blood lactate levels (and zone-2 threshold) to assess mitochondrial function [47:00];
  • Accessing mitochondrial function by looking at one’s ability to utilize fat as fuel (with an RQ test) [55:00];
  • Athletes vs. metabolically ill patients—mitochondria, fat oxidation, muscle glycogen capacity, “fat droplets”, and more [1:00:00];
  • Physiologic characteristics of zone 3, zone 4, and the lactate threshold [1:20:00];
  • Fueling exercise—dietary implications on glycolytic function [1:30:30];
  • Relationship between exercise and insulin sensitivity (and what we can learn from studying patients with type 1 diabetes) [1:46:30];
  • Metformin’s impact on mitochondrial function, lactate production, and how this affects the benefits of exercise [2:04:15];
  • Raising awareness for risk of “double diabetes” [2:15:00];
  • How to dose zone 2 training, and balancing exercise with nutrition [2:18:00];
  • Proposed explanation of the Warburg Effect: Role of lactate in carcinogenesis [2:27:00];
  • Doping in cycling, and the trend towards altitude training [2:39:15] and;
  • More.


Iñigo’s background in sports and decision to focus on education [7:15]

  • He works with elite and recreational athletes in his clinical and research work and he was an athlete himself 
  • Grew up in spain, played fútbol for Real Madrid Academy for six years
  • At 16, he discovered cycling and changed sports – racing professionally for six years
  • He became very familiar with everything the sport involves at an elite level 
  • The distinction between ability of top caliber cyclists is not subtle 
    • Decreasing categories represent higher ability levels with category 1 being the immediate step below professional level
    •  even between category one collegiate athletes 
    • At a professional level there is a step between a domestic and European pro and moreover, between a European pro and a major team
  • Iñigo left racing behind when he decided to focus on his studies – did an internship at a sports medicine clinic in Spain where Platelet Rich Plasma Therapy (PRP) was developed  
  • Has been at the University of Colorado for 11 years
  • Works with professional cycling teams and has developed a protocol for zone 2 training as a way to improve and test mitochondrial function 


Explaining the various energy systems and fuels used during exercise [14:45]

  • Defines metabolic training zones by type of muscle fiber recruitment and whether energy demand is aerobic and anaerobic 
  • Outside of sprinting, we do the majority of activity in an aerobic state
  • Fuel type utilized used to produce energy is what changes
  • Peter refers to aerobic and anaerobic energy systems in a previous blog post 

“The immense majority of activity that we do is aerobic. We tend to believe that any hard effort is anaerobic, and therefore the concept of anaerobic threshold. But actually, even what we call the anaerobic threshold is aerobic activity. The majority of the efforts that we do are in an aerobic environment except for when you do a sprint…or a one minute maximal.” – Iñigo San Millán, Ph.D.

Muscle Fiber Type

  • Depending on the energy system (training zone) different muscle fibers are recruited 
    • “Slow” and “fast” twitch fibers require different force 
    • The speed refers to how quickly the fibers fatigue 
  • Type I muscle fibers are used during low intensity exercises 
    • Don’t need to contract as forcefully 
    • Have a high oxidative and low glycolytic capacity
  • Speed refers to how quickly they fatigue
  • type 2 fiber divided into 2A and 2B
    • IIA have high oxidative and  glycolytic capacity and fatigue relatively slowly 
    • IIB have low oxidative and high glycolytic capacity and fatigue quickly (recruited for anaerobic sprint – short time duration under stress)
  • Fatigue faster because metabolically more stressed 

Cellular Fuels

  • Main fuels: fatty acids and glucose 
  • Fatty acids are the cellular fuel source for lower intensity activities…

{end of show notes preview}

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Iñigo San Millán, Ph.D.

Iñigo San Millán, Ph.D. is an Assistant Professor at the University of Colorado School of Medicine, where his areas of research, clinical work, and interests include exercise metabolism, nutrition, sports performance, overtraining, diabetes, cancer, and critical care.  He’s internationally renowned applied physiologist having worked for the past 20 years for many professional teams and elite athletes worldwide across multiple sports like running, football, soccer, basketball, rowing, triathlon, swimming, Olympics and cycling, including eight Pro Cycling Teams. Iñigo has also been a consultant in exercise physiology and sports medicine to international organizations like the US Olympic Committee and the International Cycling Union. He has been a pioneer in developing new methodologies for monitoring athletes at the metabolic and physiological level including a novel method to measure mitochondrial function and metabolic flexibility as well as the invention of the first method to measure skeletal muscle glycogen in a non-invasive way using high frequency ultrasound. Previously, Inigo was a competitive athlete and played soccer for 6 years for Real Madrid soccer academy team as well as raced as a professional cyclist for 2 years. He also returns to Spain every summer to run with the bulls. []

Twitter: @doctorinigo

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  1. Hey!

    I was listening and you really struck a cord when you mentioned people who are endurance athletes with extremely high SHBG that basically have no insulin.

    I’m a healthy male who has suffered from extremely elevated SHBG while also being an endurance athlete NOT on a ketogenic diet an NOT at a low level of body fat (12-15%). Are there any resources discussing this more than you have read? I really want to get to the bottom of all this! Thanks for being an outstanding individual.

    • Bumping this comment, would love to hear a deeper discussion of the SHBG-insulin relationship.

    • Bumping this comment again. I have the same questions about SHBG!

      Would love to hear Peter’s opinion.

  2. You mentioned that elite athletes fail races without sugar. I believe that 1500 calories can come from MCT oil. The secret is to emulsify it. Emulsified, it’s spread over the entire surface of the intestine, so there is no GI distress.

    Try this recipe: in a small container, add 1 egg yolk per 2 tablespoons of MCT oil, and an equal amount of water as oil; shake vigorously until emulsified; enjoy in coffee or whatever. There is zero egg taste.

    I have got up to 100 grams at once.

    • I emulsify MCT oil basically the same way, but I use sunflower liquid lecithin rather than egg yolk.

    • The point that is made in the podcast (and in any exercise physiology textbook) is that the fuel REQUIRED for sprinting is ONLY glucose. Glycolysis is the only way to supply ATP fast enough to support the highest intensity associated with winning and losing races.

    • I am a hobbyist level endurance athlete (fondos, competing with my friends on strava segments) and nerd. As an athlete/nerd, the mitochondrion is by far my favorite science topic because it is so important to endurance performance.

      This episode is probably #1 all time if measured on the “best for endurance nerd” scale. I really love all the other mitochondrion focused episodes too (e.g. Navdeep Chandel recently, but there are several others)

  3. Regarding measuring fat oxidation.. are there any recommended consumer devices to either directly measure RQ (blood) or indirectly RER (breath)? Is this the power meter mentioned / FTP? What about measuring lactate during exercise.. or is heart rate a close enough proxy?

  4. Thank you for all this great info. Ok, ok, you’ve sold me on the benefits of zone 2 training! But how do you know your zone 2? This sent me searching how to calculate, but there seems to be no real consensus besides taking a VO2 Max test to find your lactate threshold (based on some of the links in the above notes). Then I remembered that you guys had a AMA episode that talked about it, .
    Any particular reason to calculate zone 2 based on HR max vs. the anaerobic threshold (e.g. 20 min avg HR from a 30 minute time trial)? Or am I just splitting hairs at this point?

    Another question that came up when you guys were talking about fat adapted professional cyclist. At this years tour there was a bunch of news about how the Jumbo-Visma team was “doping/cheating” by using ketones. (the comments are hilarious in a face-palm kind of way).
    Curious to know your thoughts about how these cyclist are using ketones and how using ketones affect zone training.

    Thanks again for all your work.

    • <>

      I too want to know the answer to this question. A more precise wording might be “what is the best way to determine my zone 2 training zone” where “best” includes “affordable” and “most accurate for my budget”. Sure, we COULD sign up for a performance camp at Fast Labs ( but that is outside my budget …

      I’m guessing that an RER test is the test we need to determine fatmax. On the topic of RER testing, PNOE looks interesting. I would love to hear 3rd party assessments of how accurate/useful PNOE is in helping me calculate my training zone 2.

      TANGENT: the Fast Talk podcast episodes 51, 54 and 75 ( feature Dr Stephen Seiler — another expert on endurance training and advocate of 80/20 training.

      • Exactly my question as well (how to determine my Zone 2)… Various programs are estimating it – (Wahoo App based on FTP value) but not sure it is accurate.
        Also, nearly every cycling coach (with much less of a scientific background) seems to suggest ‘sweet spot’ training is better/more efficient then Zone 2 – but that is not what I heard here. Curious to hear what the recommendation is for non-pro cyclists (the majority of cyclists listening to the podcast) …. Lots of Zone 2 of Sweet Spot (Zone 3.5ish)???
        Thanks – just awesome listening!

  5. To learn about the powerful new way to control blood glucose for people with Type 1 who wear a CGM, catch up with pediatric endocrinologist, Dr Stephen Ponder, MD, FAAP, CDE. He has type 1 himself and has developed what he calls “dynamic diabetes management” or “sugar surfing”. Here’s a 30 minute video in which he explains the underlying principles:
    It’s the wave of the future for BG management.

  6. One of the best podcasts on this subject . Looking at this whole thing from a practical standpoint based on years of experience with training athletes really made this come to life. The discussion of why Zone 2 is so important was very good – the understanding of the use of fat as fuel in slow twitch muscles finally made me understand what this was about. A lot of this was hard to follow for the lay person but I appreciate the rigorous interrogative approach. As a woman it would be great to understand whether the same protocols affect both sexes differently.

  7. Props to your team on these show notes…there’s so much good content here.

    An interesting (currently debatable) topic is the causal role of lactic acid as root cause of acidosis during extreme physical exertion (re. the “In the context of physical exertion, lactate has been largely misunderstood…” section). In Brooks paper (that I’m grateful is linked here) he makes the case that the acidosis during muscle exertion is possibly caused/influenced by many other metabolic processes (and not just the lactic acid generated by glycolysis (which is even a debate whether lactate vs lactic acid is what is actually generated!). Interesting paradoxes pointed out in that paper.

    I guess my point is, there could be a few more bullets in the “misunderstood” section to further elucidate the ongoing research and hypotheses.


  8. First, I really enjoyed this podcast. One of my favorites so far.

    Second, I would appreciate it if you could provide or link to additional material on how to design a zone 2 training program with the resources many will have at hand (HR monitor and gym-based exercise equipment).

    Finally, should a zone 2 program that is not sport-specific rotate through different modes of exercise (row, bike, walk/run, etc?) in order to recruit the mitochondria changes from a larger percentage of the body’s muscle mass?

    Kind regards,


  9. At some point lactate strips were mentioned. Can you buy equipment to measure lactate levels?

    • Yes, there is definitely equipment available. I am not sure of the specifics that Dr. Attia uses but he has definitely mentioned them as purchasable by anybody, but that the strips are extremely expensive (the meter is not cheap either, but the strips get ya).

  10. Excellent points. But how does the layman can establish what zone 2 is for the specific individual in question? Peter always said: a pace at which you can go on forever-talk easily to someone. Is that still accurate?

  11. I am curious about how you can ascertain or differentiate between diabetics type 2 having high RQ because their mitochondria are defective vs hyperglycemia and hence high insulin pushing glucose into muscle, and also inhibiting hormone sensitive lipase and so shutting down free fatty acid production?

  12. Super informative podcast! A lot of jumping points for me to research and learn about. If there is a follow up Q&A with him I would love to hear if he has any experience with looking at mitochondrial function of people with PCOS? Or perhaps if there is someone out there doing this please have them on!

  13. Great information, I would love a printer friendly version. For now I have to copy the pages to MS-Word then edit for about 20 minutes then print in a usable format.

  14. Hi Dr. Attia,

    I hope you and your family are safe and well.

    I bought a Lactate Plus meter for my 18 year old son, who is a competitive rower. He wants to train in Zone 2.

    Unfortunately, his lactate readings are all over the map, even at the same pace. He does a deep puncture, wipes blood, gets another drop, and puts it on the test strip.

    Do you have suggestions to improve accuracy?

    Thanks and Best Regards,

    • I recently listened to AMA #19 and Dr. Attia mentions that his protocol for taking a lactate reading involves washing his hands with soap and water (alcohol not sufficient) quickly before taking the reading and that he uses the third drop of blood. I’m not sure if this will solve your problems but may help.

  15. I am just starting my road to longevity at 37. Had 40% body fat up until 7 months ago. Low carb made me loose 10kgs of fat. I just tried ciclying at 250w after this talk to understand what it would do to me and couldn’t hold it for 1 min . I am fasted and my glucose rose from 85 to 145 after this try and 15 more min at 160w. Kicked me out of ketosis (0.3 mmol)I am going to listen to everything again with a completely different perspective. Thank you

  16. Dear Peter,
    Thanks a lot for this. Amazing episode!

    As I always have said, it is time for you to get in touch with Longo. He always said: be careful of Metformin and Rapalogs, those may have more than the already known side effects. Now we see that his advise seems to be very wise! Longo is working on a project of fasting and exercise in Italy. It would be great if you can ask him about it and the so many interesting things you always ask. From all the Gurus, you are still missing Longo an Panda. Why? I hope you can find some time to chat with them (they are your neighbours!).

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