#42

How is your endurance exercise routine?

#43

Misunderstanding. The “it” that clearly impairs adaptation is metformin, not lactate.

1 Like
#44

Have you done prolonged comparison of exercise response on and off of the Metformin?

#45

High levels of lactic acid are associated with sepsis, shock, ischemia, and a few more Code Blue conditions. In sepsis, “dysfunction in the microcirculation (where oxygen is exchanged) leads to lactate production.”

The following paper is not a paper but an excerpt from a nurse’s blog. It’s fantastic.

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#46

This should say VERY HIGH levels of lactate are associated with sepsis, shock, ischemia…

Lactate increases and deceases all the time as a normal part of physiology. Higher lactate in the blood usually means you are exercising at a level of intensity higher than can be sustained by only aerobic metabolism (mitochondria burning fat & glucose with oxygen). My simplified understanding is that the lactate created with anaerobic (without oxygen) metabolism is a fuel that can be used by mitochondria in the muscle (and elsewhere), but as lactate production continues to rise, there is eventually too much lactate so it starts being exported to the blood to be used by other organs as fuel. Lactate is a good thing but you can have too much when the body is unwell. You cannot realistically get “too much” lactate from exercise because your brain will make you want to stop exercising (you won’t feel well) when you have high lactate in your blood. In addition, the production of lactate is accompanied by the production of hydrogen ions which increase the acidity of the muscles which make it harder and harder for the muscle to function. You can train to tolerate higher lactate…the best athletes can handle a lot of lactate.

But after you throw up, you’ll be fine…in my personal experience.

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#47

There are tons of different adaptions to exercise. Just because metformin can partially inhibit one of them in some people doesn’t mean they don’t still get lots of benefits from exercise.

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#48

As Peter Attia has stated, measuring lactate levels can give you a reading on mitochondrial health, and therefor may function as a longevity biomarker. I’m happy to finally see a continuous lactate monitor on the market at the consumer level. @John_Hemming , I would think that you would be interested in this. I’m certainly considering it.

https://mmabrasil.localizer.co/t/new-wearable-measures-cholesterol-and-lactate/15829/5?u=ng0rge

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#49

Even the blood lactate measurements are not very accurate, especially regarding the timing. Continuous lactate monitoring would likely be delayed and less accurate, introducing more noise.

#50

What you are interested in is the time, during exercise, that it takes to reach “lactate threshold”. Through repeated testing, the goal is to increase this time which indicates better mitochondrial function. This is considered reliable where it is primarily used - by competitive athletes. Some links:

https://run.outsideonline.com/training/getting-started/do-it-yourself-lactate-threshold-testing/

Peter Attia on lactate testing…from 5min to 10min mark.

https://www.youtube.com/watch?v=7-gUBEOH1Ls&t=300s

Some very good info on lactate levels and mitichondrial health here:

https://www.youtube.com/watch?v=-6PDBVRkCKc&t=9312s

And 2 of my previous posts on lactate and mitochondria.
https://mmabrasil.localizer.co/t/how-is-dunedinpace-rate-of-aging-calculated-how-is-physiological-aging-quantified-how-is-it-affected-by-rapamycin-usage/5943/15?u=ng0rge

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#51

New article in the NYT about mitochondrial adaptations.

Is ‘Zone 2’ the Magic Effort Level for Exercise?

https://www.nytimes.com/2025/02/19/well/move/zone-2-exercise-benefits.html

It’s well established that having more mitochondria is associated with positive outcomes like better insulin sensitivity and athletic performance. But Dr. San Millan, along with a growing cohort of other scientists, believes they also function as a sensitive predictor of future metabolic problems: the first place that signs of trouble appear on the long road to chronic conditions like type 2 diabetes, heart disease and even Alzheimer’s disease.

In their theory, the prescription for warding off such ailments is to exercise at Zone 2, which forces the mitochondria to adapt and grow.

But when researchers perform muscle biopsies to directly measure how much mitochondria is present, Zone 2 doesn’t fare as well, according to Kristi Storoschuk, a doctoral candidate in muscle physiology at Queen’s University who is one of the few researchers in the world currently studying the topic. Instead, intense exercise well above Zone 2 produces the biggest effects on mitochondria. That’s also the conclusion of a newly published systematic review by scientists in Norway and Denmark, and it’s a perspective shared by many scientists in the field.

If the interest in Zone 2 leads people to assume that easier is always better, Ms. Storoschuk warned, they might end up exercising at such a low intensity that their mitochondria don’t benefit at all.

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#52

Yes, Zone 2 is only based on San Millan’s experience in training his athletes like Tadej Pogačar in what improves it the most.

But I wonder about the amount of time you can spend in each zone, athletes train most of the time around that intensity for a reason, otherwise someone with a better approach would win.

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#53

The efficiency of mitochondria is key rather than necessarily the quantity (which the body can easily resolve).

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#54

John, wouldn’t a continuous lactate monitor to measure the change in your lactate threshold be a good indicator of both? or overall mitochondrial health in general?

I keep searching for feedback on the Onasport Continuous Lactate Monitor that I posted -

https://tri-excellence.com/products/onasport-glucose-ready

But, I haven’t turned up anything. Guess I should ask Dr. San Millan. Unfortunately, I’m banned on X for unknown reasons, with no response.

#55

Lactate is more of an oxygen shortage thing than an ATP/O efficiency thing. I would accept that it is possible that ATP/O effiency has a minor effect on driving lactate production, but I would not rely on lactate measurements as guide to Mitochondrial Membrane Potential.

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#56

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So, VO2 Max is a reasonable measure of Oxygen Consumption Rate (OCR)?

What would be the best measure of Mitochondrial health (at the consumer level) if not VO2 Max or Lactate Threshold levels?

#57

If that were to be a response to my comment I would ask where the word lactate appears,

#58

It doesn’t. Lactate threshold, I’m taking from Peter Attia and Dr San Millan.

I consider mitochondrial health a super-important biomarker for longevity…thus my interest in the best ways to monitor it.

#59

Another driver of lactate is the need for more muscle power which forces the usage of fast twitch muscle fibers which do not have many mitochondria and burn mostly glucose via glycolysis producing (eventually) lactate which get exported to slow twitch fiber to use as fuel (with mitochondria). As lactate production overwhelms the muscle ability to use the lactate, the excess lactate gets exported to the blood stream to be used elsewhere in the body (and can be measured via a blood test).

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#60

Searching around, I just found this…

https://www.religendx.com/neurology/mitoswab-test/

MitoSwabTM : A Simple Test for Mitochondrial Health

The MitoSwabTM test offers a non-invasive way to evaluate mitochondrial function. This innovative test utilizes a painless cheek swab to collect cells from your inner cheek lining (buccal mucosa). The collected cells are then analyzed to measure the activity of specific enzymes within the mitochondria.

I discovered MitoSwab in this very interesting PrePrint:

https://www.medrxiv.org/content/10.1101/2025.01.13.25320480v2.full

A Mitochondrial Supplement Improves Function and Mitochondrial Activity in Autism: A double-blind placebo-controlled cross-over trial

Mitochondrial targeted nutritional supplements have been studied in general ASD who did not specifically have mitochondrial dysfunction. Controlled studies have examined carnitine.9–12 Open label and observational studies have examined carnitine13 NAD and ribose,14 ubiquinol,15 ubiquinone16 and thiamine tetrahydrofurfuryl disulfide.17 Only one open-label trial treated 11 children with ASD and mitochondrial dysfunction with carnitine, coenzyme Q10 and alpha-lipoic acid.18 Three months of treatment improved mitochondrial function and behavior including the social withdrawal and inappropriate speech subscales from the Aberrant Behavior Checklist (ABC). The ABC and mitochondrial function worsened three months after withdrawal of the treatment. No blinded controlled trials have examined a mitochondrial targeted supplement on individuals with ASD who specifically have mitochondrial dysfunction.

Thus, we aim to determine whether a mitochondrial-targeted dietary supplement affects mitochondrial activity and ASD symptoms. Previous treatment studies were either open-label or did not measure mitochondrial activity. The primary aim of the study was to determine if the treatment normalizes ETC activity as measured by the MitoSwab (Plymouth Meeting, PA) and increases mitochondrial resilience as measured by PBMC respiration.

#61

Personally i measure mitochondrial function through somatic function. Vo2 max wont measure it. Acid base balance is most likely to measure it. As it varies from cell to cell measuring individual cells has an inbuilt uncertainty

1 Like