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

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

Post by BrianR »

https://peterattiamd.com/inigosanmillan/ or APPLE PODCASTS | RSS | GOOGLE | OVERCAST | STITCHER

I thought this one was interesting.
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.
In addition to the above, they discuss mitochondrial function in diabetes patients. Note that they spend very little time discussion the brain and don't touch on AD or other types of dementia at all.
Attia-inigosanmillan.png
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xactly
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Re: Peter Attia #85 - Iñigo San Millán, Ph.D.: Mitochondria, exercise, and metabolic health

Post by xactly »

I also am finding this episode fascinating. I'm about halfway through.

I am particularly interested in the statement that lactate is an important fuel source for the body and brain. It is not, as is popularly thought, a waste product. San Millan states that lactate is actually a better fuel for the brain that beta hydroxy butyrate (BHB) because it burns more quickly.

Most of the recommendations I've seen about the benefits of exercise for preventing Alzheimer's say you need 150 minutes a week of exercise at 60% - 80% of max heart rate. However, exercise in that zone, which San Millan calls Zone 2, utilizes all of the lactate you produce locally (in the muscles). It's only when you exceed the Zone 2 threshhold (i.e., can no longer carry on a normal conversation), that lactate spills into the bloodstream and is transported elsewhere in the body, importantly to the brain.

Rhonda Patrick says that Zone 2 exercise is where the most BDNF is produced; however, exercising above the Zone 2 threshhold would seem to be beneficial for the brain as well because of the ability of high-intensity exercise to produce lactate as a brain fuel source. So, it seems the exercise recommendation for AD prevention should be a combination of low/moderate- and high-intensity exercise.
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Re: Peter Attia #85 - Iñigo San Millán, Ph.D.: Mitochondria, exercise, and metabolic health

Post by aphorist »

I went through the call and notes last night. It was pretty good. I'm going to modify my own exercise regimen around this Zone 2 conditioning framework. The explanations of how lactate works in the body (and its role in cancer) were superb. The discussion really connected a lot of metabolic pathways and concepts for me.
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Re: Peter Attia #85 - Iñigo San Millán, Ph.D.: Mitochondria, exercise, and metabolic health

Post by xactly »

aphorist wrote:I'm going to modify my own exercise regimen around this Zone 2 conditioning framework. The explanations of how lactate works in the body (and its role in cancer) were superb. The discussion really connected a lot of metabolic pathways and concepts for me.
I would also like to modify my exercise regimen to include three (or more) Zone 2 training sessions a week to achieve the benefits of improved mitochondrial density and efficiency they discussed.

I'm trying to confirm that San Millan's definition of Zone 2 is 60 - 70% of your max heart rate. Peter Attia talks about keeping track of his Zone 2 workouts by using watts and FTP, not heart rate. And San Millan talks about a Zone 6, which I have never seen before in conjunction with heart rate monitoring.
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Re: Peter Attia #85 - Iñigo San Millán, Ph.D.: Mitochondria, exercise, and metabolic health

Post by BrianR »

xactly wrote:I'm trying to confirm that San Millan's definition of Zone 2 is 60 - 70% of your max heart rate. Peter Attia talks about keeping track of his Zone 2 workouts by using watts and FTP, not heart rate. And San Millan talks about a Zone 6, which I have never seen before in conjunction with heart rate monitoring.
I don't think San Millán uses heart rate, per se, to define his zones. From this Training Peaks article [open access]
zone2-screenshot_1.png
Skeletal muscle is composed of 2 kinds of muscle fibers- Type I, also known as slow twitch, and Type II, or fast twitch. Fast twitch fibers are also divided in two subgroups called Type IIa and IIb. Muscle fiber contraction obeys a sequential recruitment pattern where Type I muscle fibers are the first ones to be recruited. As exercise intensity increases muscle contractile demands increase and Type I muscle fibers cannot sustain the necessary demand. Type IIa muscle fibers kick in and eventually as intensity keeps increasing Type IIb will finally be recruited. Simply put, slow twitch fibers are used at slower speeds and fast twitch at faster speeds. Each muscle fiber has different biochemical properties and thus different behaviors during exercise and competition. Type I muscle fibers have the highest mitochondrial density and capacity and therefore are very efficient at utilizing fat for energy purposes. Type IIa fibers have a lower mitochondrial density and a higher capacity to utilize glucose. Type IIb muscle fibers have a little mitochondrial density and a very high capacity to use glucose as well as ATP stored in these fibers for instant anaerobic energy. Therefore, each exercise intensity implies different metabolic responses and muscle fiber recruitment patterns which also corresponds to different training zones [see above]
Thus type of muscle and type of muscle metabolism seem to define the zones.

So, [from the 2018 paper Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals] here is an example showing the crossover into zone 2, defined as "the point at which their mitochondria are no longer able to meet the energy output requirement at blood lactate increases"
fig-8-inigo-753x1024.png
and in this 2015 presentation slide deck: Sports Performance testing in the Cyclist: where are we in 2015 and how does it apply to the recreational athlete?, he shows the 'Crossover Point' at which the athlete transitions from zone 2 into zone 3.
Screen Shot 2020-01-04 at 1.03.43 PM.png
In this case, a heart rate for a particular athlete is shown, but I don't think you can generalize from that.

I did find this article Training Center: Why heart rate shouldn't be ignored which suggests that, once you've developed a lactate utilization profile and correlated it with heart rates, you can use heart rate as a proxy to define your zone. And you might also be able to use disciplined time trial type tests to develop approximate zones.
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Re: Peter Attia #85 - Iñigo San Millán, Ph.D.: Mitochondria, exercise, and metabolic health

Post by xactly »

BrianR wrote: I did find this article Training Center: Why heart rate shouldn't be ignored which suggests that, once you've developed a lactate utilization profile and correlated it with heart rates, you can use heart rate as a proxy to define your zone. And you might also be able to use disciplined time trial type tests to develop approximate zones.
Thanks for this information. It looks like there are invasive and non-invasive ways of doing lactate testing, so I will do some more digging. I've been exercising to increase BDNF in plasma, and preserve muscle mass and bone density, but the idea of increasing mitchondrial density and efficiency through Zone 2 workouts is intriguing, especially if it's possible in older adults.
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