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

Original release date: 12/23/2019
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.
Show notes page: peterattiamd.c...
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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 30 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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[@jamesnorris837]

Amazing discussion! I was recently diagnosed type 2. I started wearing a continuous glucose monitor and experimenting with dietary and exercise interventions. I stumbled upon Stan efferding's rant on 10-minute walks being Superior to metformin for controlling blood sugar. Experimentation with my blood sugar utilizing 10 min walks and other forms of post-meal exercise ( cycling, rowing, swimming, weight training) lineup with everything I heard in this discussion. Now I understand why. 10-minute brisk walks consistently bring my post-meal blood sugar back down to 90 +/- 5. No other intervention produces this significant or consistent of a result and high-intensity exercise would raise my blood sugar. Sounds like I could have accomplished the same thing with cycling or rowing. I just wasn't getting Zone 2 right.

[@richardwburrill9247]

ty 4 hitting , reminding me, of key point, hiit raises blood sugar

[@etxeberre1]

Hi, would you say that a complete session of zone 2 after a meal is ideal? Cheers

[@durianriders]

do my protocols bro and you wont have insulin resistance aka T2D anymore. 1000%.

[@dyrth1]

Thank you for the info! Very interesting.

[@haimco1]

Great insight! good luck with your journey.

[@martinirving3824]

Listening to the discussion around 1:55:00 - Skeletal muscle contraction can activate glut4 transporter independent of insulin to facilitate glucose uptake. I had always been a skeptic of the idea of walking for 10 minutes after a meal ( I didn't imagine hunter-gatherers did such things) but clearly the reasoning appears to be to transport glucose into cells with less insulin requirement. Seems like a smart thing in the modern world with high levels of refined foods; particularly carbohydrates.

[@etxeberre1]

Yes this was also a surprise for me. Would you still say that a level 2 exercise after a meal rather than before is optimal? I am new to Peter so I don't know if this statement still holds up. Cheers

[@durianriders]

refined carbs DONT block the insulin receptor sites bro. Only fat can do that thus ONLY fat can cause insulin resistance. Look how lean I am at age 44 on 10g of fat a day and unlimited sugars.

[@mattcarrelo]

No, zone 2 exercise before food and then go for a walk after food@@etxeberre1

[@elvay6847]

As a long distance runner and human physiology nerd, I feel "enlightened" after listening. So much information... I will be re-listening to this several times. Thank you Dr Attia and Dr San Millán for such incredible content!

[@tarighd]

Love this. As a Personal Fitness Trainer, Pilates Teacher and Funcional Range Conditioning coach. This is invaluable to my own training and the way i train my students.

[@XX-is7ps]

Such an amazing extended format interview. I’ve listened to interviews with Inigo previously on podcasts such as the Scientific Triathlon podcast but whilst good they are heavily restricted by the short format. The lack of time pressure on this interview and the range of topics it allows to be covered in extensive and clear detail is just so appreciated, thank you

[@ericwarmath1091]

Great interview. So much good discussion. Peter you know how to keep an interview focused and circle back and leave no lose ends.

[@TheKiwNo1]

One of my favorite podcasts. So much amazing information in this one, thank you.

[@bevillenz]

This discussion is amazing. Thank you Peter for making me aware of Iñigo San Millán.

[@lklencho]

This video in terms the average workout individual could understand would really be awesome. Great content

[@miggyruru]

I would recommend taking an Exercise Physiology course on line. I took a basic course on Coursera and it addressed all the very basic information on this subject and many others, , which would help you immensely in grasping the information delivered in this discussion and others like it.

[@dannyiskandar]

@@miggyruru which one you take? science of exercise from colorado boulder?

[@miggyruru]

@@dannyiskandar McMasters University - Dr. Stuart Phillips (Hacking Exercise for Health).

[@umeshchhikara]

Great discussion and it is fascinating to learn so much on lactate. On the fat oxidation & elite athletes point: I agree that any sport where you require endurance and continuous max intensity; they would need high carb diet to refill their glycogen stores. However, with regard to other sports like badminton, tennis, hockey, basketball, cricket, baseball - 90% of the sports; it does seem that one would use more fat than carbs provided they have trained well at zone 2 level and enhanced the mitochondrial capacity. Would it be right to say that most sports are covered in Zone 2 & 3 ? Here is my understanding: 1) When I worked with cricketers, hockey, or tennis players; I always worked in zone 2. Back in the day I couldn't relate it with fat loss but after listening to this podcast; I now understand why my athletes always lost weight (who needed to) and those who were lean stayed on the same weight but became a lot faster and quicker. 2) With enhanced mitochondrial capacity and better metabolism, these athletes could not only keep their glycogen stores full but also use it for energy wherever needed. Since most sports in my opinion shuttle btw zone 2/3; it makes perfect sense to train players in these zones. Now my question to you is this: I am an athlete playing one of the above sport. I don't need a high carb diet to enhance my zone 2 capacity. I can keep my glycogen stores full. I can use my glycogen stored fuel optimally while migrating from zone 2 to zone 3 for few seconds whenever I have to speed up, swing harder, smash, or serve. I shift back to fat/zone 2 flawlessly since I am well trained for the zone. Ques 1: It does seem that if I can adapt to high fat diet (have options around) then I don't need to go on high carb just for sporting reasons? Ques 2: Secondly, doesn't this all make a perfect case for a mixed diet because the player doesn't have to worry about what he can or cant eat? There is always fat to burn in our body and all we need is good fat oxidation? My experience and hypothesis: I follow the latter. Although in my case I am keeping 40% fat in my diet but I don't force it on my athletes. And instead I allow them a mixed diet which is what we all have grown up eating. The results have always been very good and in some cases exceptional. Whereas, I can lift heavy these days with 40% fat in my diet; I think it all comes down to two: a) the mitochondrial capacity/health b) our ability to store glycogen and then the ability to optimally use it If we can keep these two in check then we can be eating everything and anything as long as it is has the desired nutritional value. Of course, this doesn't apply on endurance sports like cycling where athletes would need constant refilling of their glycogen stores. Excellent...thank you. Loved it. Warm regards, Umesh

[@taplubambhos2869]

Maybe worthwhile to note that zone 2 and 3 use carbs and fat both so it may be worth while to keep those carbs in albeit to a limited amount.

[@les0nick]

Great podcast. Noticed in few Peter's podcasts when talks about statins going wrong direction he tries to change the topic. He didn't let the guest to explain how strains impact mitochondria performance.

[@lt2339]

Stations are big pharma

[@raju-bitter]

Thanks, Peter and Iñigo. One of the podcast highlights of my life. Amazing content!

[@phantomopera5525]

Very proud of Dr. San Millán as a fellow Basque! Except for the playing for Real Madrid part ;-)

[@benphartine]

They kept talking about glucosamine but there study did not include it to be tested as an alternative fuel source, which it is. Point being, glucose can be controlled by fasting and or a ketogenic diet. But our body produces glucosamine just like it produces lactate. There are medications that can stop glucosamine production. No glucose and no glucosamine can cause the cancer cells to starve from a lack of fermentable fuel.

[@mattbrown5949]

I plan to listen to this multiple times. Fascinating talk

[@WalrusRiderEntertainment]

Total relate to 1:45:00. I was cycling 400km minimum a week then dropped to 2,000km a year

[@SGCric]

Peter, thanks for the fascinating discussion ... just curious if you were able to do the muscle biopsis.

[@janplenkers]

Great discussion, so much interesting scientific input. Thank you very much for this!

[@jeffreyharrison4045]

Loved this episode.I’m an ultra runner. I don’t recall hearing Dr San Millan views on fasted Zone 2. Will fasted increase mitochondrial function and genesis. Thanks so much!

[@mariwooldridge1421]

I cant wait to hear more about the metformin experiments. I am fit 64 5'3 l05 lbs. I went on metformin 10 years ago when diagnosed advanced stage ovarian cancer. 10 years later no reoccurrence. Functional medicine dr testing showed my biological age as 38. Started doing more zone 2 training and wonder if time to go off .

[@Unsensitive]

Wish I had this testing when I was a younger athlete. I'd always been a sprinter. The longer the race was, the worse I was. In running, I'd almost guarantee a muscle pull if I did a full out sprint. During one swim workout I was doing back to back sprints, with no break except maybe a second or 2, for 30 minutes straight. Checking my heart rate when finished was ~210. I'd be curious if I was very adept at and lactate elimination, or of there is another explanation.

[@WalrusRiderEntertainment]

I always take notice of both my resting and “at the door” HR. If it is higher than normal it tells me I not fully recovered or sick and my power numbers will be lower

[@redbull9554]

54 yr old male. Testosterone 200mg peer week(many years) Metformin 500 mg twice daily. Thyroxine 10mcg day. Lost 15 lbs kept my muscle (weights many years). Now doing zone 2 as well. I’m getting better on metformin!

[@DurianriderCyclingTips]

just cut your fat intake under 10g a day bro and you wont need that metformin rubbish lol.

[@anthonylawrence5842]

For glutaminolysis, glutamine is transported into the mitochondrial matrix through the SLC1A5 variant and subsequently converted to glutamate by GLS. Next, GLUD1 or several aminotransferases catalyze the deamidation of glutamate, producing α-KG. How does this fit into the Zone 2 model of fat and glucose synthesis?

[@fencserx9423]

God these people are talking at a level that takes me at least 5 minuets to catch up after every topic

[@Longevity-gu1ut]

How does the metabolic flexibility mentioned at 53:10 relate to metabolic flexibility gained by practicing different regimes of fasting, intermittent fasting, ketogenic diet and such? In other words, can intermittent fasting improve the metabolic flexibility mentioned at 53:10?

[@j.b8728]

Thank you for providing info. I will be glad to support. Take care

[@adapa360]

Thanks for this! Is the 7th time listening the whole thing 🙂 solid

[@dchiffy]

This is a great discussion thanks for all the info. I think that Dr. Stephan Finney and Dr. Timothy Noakes have a lot of information on the subject as well

[@AlexanderMoen]

I'd appreciate if you recorded video alongside your podcast. For some reason, video just connects better mentally, as if I'm in the room and part of a conversation. Great info overall, though. Keep it up and thanks for your efforts.

[@jellybeanvinkler4878]

I agree! Seeing their faces as they speak increases ease of understanding.

[@eugeniebreida1583]

Absolutely agree!

[@falstmusic]

Peter is amazing, what an interesting topic!

[@CrankyDanky]

Thanks for rebroadcasting 👍🏿👍🏿

[@ivanzhovannik5419]

Amazing discussion! Thanks Iñigo! Thanks Peter for the deep dive podcasts!

[@kirbymegorden8820]

47:00 transitioning to zone 3, 55:10 interpreting of RER, Indicator of bi-products & fuel source 57:00 high RER at rest, the importance of tests that control metabolic stress, tests show us 'metabolic flexibility' 59:40 baselines, 1:55:00 - Skeletal muscle contraction can activate glut4 transporter independent of insulin to facilitate glucose uptake 1:22:00 Thresholds, ACSM 1:55:00 Glut4 2:24:00 “training” for fat loss

[@anissweb]

Thank you guys !

[@Ballistichydrant]

Welcome back. We missed you

[@jamesgordon8867]

Thank you for this discussion.😊

[@manicpanic9]

2:48:18 wonder if he's talking about Pogacar? makes a lot of sense in retrospect...

[@SennaMadeF1]

Must be! A special, special athlete with so much success still to come

[@1pittmanj]

Peter I have a question for you both. When speaking about dosing in zone 2 and let’s assume you already do that 3 times a week for 60 mins, which is more important increasing the length of training time per season or the frequency? While listing to this, it almost sounds like it would be more beneficial to increase time and not frequency. Any thoughts?

[@pjetrs]

I'm just going to share my own experience, so nothing scientific here. But what I notice is that its more effective to have longer trainings, such as 2x 3 hours than 6x 1hour a week. I also see that cycling pro's also try to make long days on the bike in zone 2. If you're training to race and race to win, you need to simulate racing conditions, such as long days on the bike. And if you're able to ride 3 hours in Z2, a one hour treshold effort is going to feel easier. You also train your metabolism and your nutritient uptake capacity. But I'm interesed in the scientific answer as well

[@ColdBloodCSS]

Would like to know this aswell

[@jamesc6137]

how does the percentage of maximum heart rate typically compare to zone 2 lactate threshold? What heart rate percentage range do y’all typically see that seems to correlate to zone 2 training in most athletes?…surely there has to be a range.

[@zagreb2012]

Most important podcast on web for endurance..

[@addormitus]

At about the 50 minute mark the two of you are discussing Z2+ and the increase in blood lactate levels as a functional inability to clear it. Have you considered the possibility it could be a homeostatic mechanism to send lactate to other organ systems as a glucose substitute in order for the stressed skeletal muscles to receive more quantities of glucose?

[@etxeberre1]

I have a question. If you are not type 1 or 2 diabetic. Should you eat before or after exercise? Thank you in advance.

[@WalrusRiderEntertainment]

I love the numbers too ☺️

[@etxeberre1]

Hi, I have a question. Why do Peter emphasize the border for the lactate levels? Does going up to level 3 have a negative effect on the mitochondria training? Wouldn't it be better to at least hit low level 3 to make sure you push your mithocondria? Thank you in advance.

[@Northwindbreeze]

nope. also lactate accumulation isn't desired when it comes to mitochondrial training.

[@ErrantChordier]

@@Northwindbreeze Correct, in a different interview with Dr. San Millan he says that lactate inhibits fat oxidation so you don't want to generate much of it for too long. He does also say that all zones have SOME benefit on metabolic health, but it is BEST at what he finds to be zone 2. Going to zone 3 won't totally stop your progress but it won't be as good as it would have been in zone 2. So it's not a "negative" effect in making you worse, it's just negative in that you missed out on better progress.

[@andreis6034]

Incredible, so informative !

[@dustyfeller]

Who can I see to measure my RQ (or RAR, RER?), the respiratory test that measures metabolic flexibility, discussed at the 55:00 mark? (ie the ratio = (produced CO2 / oxygen consumed). I’m fairly certain the neither my regular cardiologist nor pulmonologist does this test. I’m trying to solve a vexing health condition, and I have a hunch that measuring my RQ will be very useful.

[@terrancephillips5798]

Glad to see you back eh.

[@LilianaGrueber]

Awesome! Great tips! Great discussion.

[@irismatamoros7870]

Thanks for this content, it is so much quality! 🙌🙌

[@javierr.c.6626]

Great Conversation!!! Could you upload english subtitles, please? Thank you

[@markt4281]

Speak on Elmhurst. I dont find ZDogg's video overwhelmingly convincing. He said she said... Be courageous and give us your opinion - regardless of the side. Please.

[@jacksoneglise1657]

Lance Armstrong had testicular cancer and was said that he produced low lactate? Might be an avenue to correlate cancer rates with the research in lactate metabolism.

[@americanmambi]

Thanks again Peter

[@ernst_42]

at 41:21 You talk about the metabolic map in the show notes. There is no metabolic map in the show notes. Where can i find it ?

[@ErrantChordier]

You have to be a paid subscriber to get the show notes

[@susigan]

What the book he (Peter) mentions in the beggining of podcast?

[@liutasx]

Thanks!!!

[@jamesgordon8867]

I don't understand why you didn't try Berberine instead of metformin

[@dinomiles7999]

Amazing upload . I'm lost .

[@MrXrisd01]

Subscribed! Good stuff 👊👍

[@mikeysc3310]

Damn, this was good. I’m sure it will accumulate a few more listens after stage 20 :-)

[@robroberts1473]

Yay!

[@annetessari1004]

fantastic discussion

[@timoringlein]

great conversation !

[@jayw900]

Actual content starts at 6:35

[@anonymousanonymous7304]

I wonder if that's why I got that unbelievable power burst when I ate homemade ice cream on bike rides.

[@hans471]

I learned more from the clear questions than from the answers 😂

[@KJBtheMosFett]

You are blowing my god damned mind right now. Pyruvate dehydrogenase becomes insulin resistant in TBI partients? I've been slacking. I love Attia equating things to principals in engineering. Yal might just save my brain.

[@naveenpaul8541]

Peter, maybe its just me.. could you maybe interrupt or interject less often. It’s difficult to follow a thread of thought from Inigo for 2-3 continuous minutes..

[@durianriders]

All this proof that sugar is needed and Peter STILL in denial and pushing keto nonsense hehe.

[@rui-9-cs315]

💕💕💕

[@cosbro5389]

💪💪💪😇

[@dinomiles7999]

Who cares , im never going to bike race . I just want a long disease free life . Blah blah blah ... Thank you

[@dinomiles7999]

I just want to have energy efficiency and total body health to live forever . I'm I asking for to much ? . RAW green power for over 20 YRS. I'm just say n. Eyes mind heart and soul wide open no fear....

[@DurianriderCyclingTips]

How is peter SO ignorant on the cause of insulin resistance? No wonder he has insulin resistance despite decades of 'healthy eating' and exercise lol. He loves his fatty foods too much to give them up.