Lactic acid, lactate in ME/CFS

[Arfmeister]

Yes, I don’t think there necessarily has to be any relationship to “anerobic threshold”.

Why not ?

• Is this not part of what frequently is happening with PEM
• Exertion above certain aerobic threshold ⇒ glycolysis outpaces aerobic metabolism ⇒ forcing pyruvate ⇒ causing lactate accumulation
• I presume my main energy production in my muscle cells is impeded because of an impaired oxygen uptake from the blood into the cells or mitochondriaI resume

And these lactate levels do not seem to relate to transient episodes after exercise. They are reported without reference to that.

1) I’m one of those very severe bedbound that have constant burning muscles and muscle pain, worsened by the minimal exertion
- mostly in my arms as those are most used
- but also often jaw muscles after eating / talking
- and my legs explode after my max 2 steps a day.

And IF it’s really bad, I go to sleep with it, and wake up with burning muscles + including poisoned feeling (horrible)
- This poisoned feeling feels very similar to how I used to feel when I ran 10 K ; but in this case, this feeling never drops
- While after high exercise - when healthy - it used to drop in less than 5 minutes


2) in my experience there’s a clear correlation between
Overexertion - and - PEM / poisoned feeling / high lactate
- Correlating with anaerobic glycolysis

But currently it happens even in the morning from the get-go by just moving my arms on the iPad


3) my high lactate measurements
As my doctor and myself have taken an interest in this, my lactate levels have been measured at regular time points since 2017
- consistently the height of the L-lactate in blood corresponds with how bad I feel - including all my symptoms e.g poisonous feeling

Since 2017 consistent high measurements* > 2 mmol/L at rest - while typically is <1.5 mmol/L at rest

• 2017
• 2018 (4x above)
• 2019
• 2024
• 2025 (7x above)

*Some as high as 9 mmol/L
⇒ Measurements >4 are typical of sepsis and will lead to hospitalization and aggressive treatment !!

 

[Arfmeister]

“Some severely ill people speak of having it most of the time, others every time they get PEM.”
- Those severe would be the least likely to end up in a study assessing blood analytes, then.

Yes. 100%
My conviction is that it does not show up more because when this phenomenon happens, you’re in no state to go to a hospital / participate at a trial

 

[Amw66]

ba dum tsss


Right, where it’s usually assumed to be a byproduct of insufficient oxygen supply or lactate clearance in a damaged organ. But we don’t fully know what it is about the organ damage that leads to elevated lactate levels—ischemia nearly always co-occurs with macrophage polarization and lactate production from them as well, for example.

So I don’t think it’s out of the question that you can have something like immune perturbation in tissue (maybe even somehow triggered by low levels of exertion, without necessarily being a result of passing “anerobic threshold”) and end up with elevated lactate. Which in the absence of an actual infection doesn’t necessarily implicate irreversible organ damage.

ischemic cardiomyopathy - impacts mitochondrial activity too ?

 

[Jonathan Edwards]

Why not ?

• Is this not part of what frequently is happening with PEM
• Exertion above certain aerobic threshold ⇒ glycolysis outpaces aerobic metabolism ⇒ forcing pyruvate ⇒ causing lactate accumulation
• I presume my main energy production in my muscle cells is impeded because of an impaired oxygen uptake from the blood into the cells

The idea that anaerobic threshold is important in ME/CFS has been put about by some of the physiology reearchers but I don't see any good evidence for it. Lots of things happen in a muscle when exercised and any one of those might send signals that lead on to PEM. Moreover PEM does not seem to be limited to the muscle used so it seems likely that the signals are systemic or neural.

Lactate does not seem to me to be a plausible source of PEM symptoms because the timing is wrong.

 

[Arfmeister]

The idea that anaerobic threshold is important in ME/CFS has been put about by some of the physiology reearchers but I don't see any good evidence for it. Lots of things happen in a muscle when exercised and any one of those might send signals that lead on to PEM.

Would it make a difference for you if it said : exerting above a certain threshold causes PEM ?

Moreover PEM does not seem to be limited to the muscle used so it seems likely that the signals are systemic or neural.

Yes, brain fog / neural symptoms is (probably) not explained by exercising beyond an anaerobic threshold
- although I’ve read a study about lactate levels in the brain.
(I will post this one in another post)

Lactate does not seem to me to be a plausible source of PEM symptoms because the timing is wrong.

Can you elaborate that?
“What do you exactly mean with the *timing is wrong*?”

In my case the correlation seems to be perfect : lactate = PEM

I’m actually NOT implying that Lactate = cause PEM, but it corresponds

• there are either upstream processes that cause glycolysis and lactate in group of (more severe) patients
• OR feedback loops that enforce these difference forms of PEM (brain fog, tachycardia, nausea, etc.)

 

[Arfmeister]

but I don't see any good evidence for it.

With regards to evidence for lactate in ME CFS or with PEM - there are 2 Research publications

1) Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with ME CFS

From abstract : The study included 123 patients.
- Elevated (n = 55; 44.7%) and normal (n = 68; 55.3%)
- lactate groups were comparable except for PEM, which was more severe in the elevated lactate group after adjusting
- ME/CFS patients with elevated blood lactate at rest may be at higher risk for more severe PEM

*I have checked the data and it seems that:
- research required 3 days with 8 consecutive measurements - which probably excludes the more severe patients with rolling PEM
- which is exactly the group that have consistent high lactate
- No extreme levels measurements like my 9 mmol : most around 2 mmol, one patient with various measurements close to 4 mmol

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2) Abnormal blood lactate accumulation during repeated exercise testing in ME CFS

Abnormal lactate levels are also shown in the 2 day CPET
- mind you ME CFS patients that can do 2 day CPET are not severe, but Mild - maybe Moderate

Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome - PMC

Post‐exertional malaise and delayed recovery are hallmark symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Studies on repeated cardiopulmonary exercise testing (CPET) show that previous exercise negatively affects oxygen ...

pmc.ncbi.nlm.nih.gov

 

[jnmaciuch]

ischemic cardiomyopathy - impacts mitochondrial activity too ?

Sure, but my point is that it’s possible to get lactate spikes from various causes, and macrophages have been identified as one such source

 

[Jonathan Edwards]

Would it make a difference for you if it said : exerting above a certain threshold causes PEM ?

People with ME/CFS report that doing more than a certain amount induces PEM.We can speculate that there is some 'threshold' but I am not sure that tells us any more. The thing that makes me worried about a simple concept of a threshold is that it seems to matter a lot how long people are active for. So the threshold involves some integral over time rather than just a value above some specific level at a point in time. From what people say, quite low level activity over an hour or two can be a major problem in a way that five minutes would not.

I find it hard to explain that on any metabolic basis.

 

[Jonathan Edwards]

1) Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with ME CFS

I am not sure how that would relate to going above an anaerobic threshold - I don't see how lactate levels at rest would reflect that.

2) Abnormal blood lactate accumulation during repeated exercise testing in ME CFS

Abnormal lactate levels are also shown in the 2 day CPET
- mind you ME CFS patients that can do 2 day CPET are not severe, but Mild - maybe Moderate

There might well be a correlation between lactate and reduced cardiopulmonary performance on day 2 but that doesn't mean that PEM is specifically linked to anaerobic threshold as far as I can see.
And, as you say, if these people were really in PEM they would not be doing a second test.

 

[Turtle]

I am not sure how that would relate to going above an anaerobic threshold - I don't see how lactate levels at rest would reflect that.


There might well be a correlation between lactate and reduced cardiopulmonary performance on day 2 but that doesn't mean that PEM is specifically linked to anaerobic threshold as far as I can see.
And, as you say, if these people were really in PEM they would not be doing a second test.

Maybe I would be the perfect test case because my AT was extremely low at 1 28 min. Only one CPET.
After doing groceries I always have a day after, off day.
When I know I should postpone my shopping because getting ready to go takes too long, chance of PEM is greater.
Muscle aches in both cases are the same, but cognitive PEM is way worse.
Lactic acid has only been tested once 14.11 and pyruvic acid 0.07 in 24 hour urine sample.

 

[Ferry]

Lactate does not seem to me to be a plausible source of PEM symptoms because the timing is wrong.

But could it be a plausible explanation for intense burning muscle pain that is quickly triggered during routine activities and that forces me to pause or abandon the activity? (Thank you, by the way, for your sustained interest in ME/CFS.)

 

[jnmaciuch]

But could it be a plausible explanation for intense burning muscle pain that is quickly triggered during routine activities and that forces me to pause or abandon the activity? (Thank you, by the way, for your sustained interest in ME/CFS.)

No, that’s been disproven pretty comprehensively. What we know is that lactic acid tends to correlate with the burning feeling during exercise in healthy subjects but does not appear to be the cause (though it likely has a modifying effect on peripheral nerves mediating muscle fatigue more specifically)

 

[Utsikt]

My muscles start burning without me using the as well, so presumably it can happen without having to do with activity.

 

[Arfmeister]

I am not sure how that would relate to going above an anaerobic threshold - I don't see how lactate levels at rest would reflect that.

I’m not so bothered about the anaerobic threshold. I’m interested in the correlation MECFS / PEM and lactate levels.

From that n=123 paper : 45% patients had lactate values around 2 mmol (or sometimes higher) at complete rest:
- “ resting conditions in hospital bed for at least 30  minutes and without preceding exercise “

Also, an important notion is the definition of rest IMO:
- What a healthy person or doctor might consider rest is actually not ‘rest’ for a severe / moderate / even mild ME patient
(I’m bedridden, was an athlete, but I’ve never 24/7 exercised as much as I do now).

What do you think explains these higher lactate levels at rest from that paper?
- I know it’s not the causation, but I’m looking for what explains the correlation (in about 45% of the patients)

 

[tuha]

Are we sure that in this hypothesis we accumulate lactic acid? Cannot it be something else?
I feel every day especially in my calfs something simillar to lactic acid but I think it's different what I felt after overexertion when I was healthy.
So I think lactic acid in a healthy person is different compare to "lactic acid" in ME/CFS.
Or is it a completly different thing? What do you think?
Also what is strange that after walking I feel this "lactic acid" only in my calfs and not in the upper legs. Do you have the same experiences?

 

[Arfmeister]

“Lactic acid” and “lactate” are often used interchangeably, but physiologically they are not the same.

At normal body pH (~7.4), lactic acid (which has a pKa of ~3.9) is almost completely dissociated, meaning it exists as lactate (the negatively charged ion) plus a hydrogen ion (H⁺). As a result, free lactic acid essentially does not exist in the body under physiological conditions; what is actually produced and measured in blood and muscle is lactate.

The distinction matters because lactate itself is not the cause of muscle burning or acidosis.
Lactate is a normal, useful metabolic intermediate that can be shuttled to other tissues and oxidized for energy. The acidic effect comes from the accompanying hydrogen ions (H⁺) generated during rapid ATP turnover, not from lactate. Clinically and scientifically, blood tests measure lactate, even when reports loosely say “lactic acid,” and elevated lactate reflects altered metabolism or stress rather than the presence of an acid poisoning the tissues.

I feel every day especially in my calfs something simillar to lactic acid but I think it's different what I felt after overexertion when I was healthy.
So I think lactic acid in a healthy person is different compare to "lactic acid" in ME/CFS.
Or is it a completly different thing? What do you think?

You can only measure lactate in blood as far as I know, so that’s the data where we have to go from.

Apart from the publication, I posted, I know quite a few patients that tested high for lactate (many through self tested lactate meters /devices)
Also, the burning muscle is a common thing. I started to really suffer from it 10 years into my illness.

For me, it’s very similar to my healthy person experience, with the big difference is that it doesn’t go away and it’s way more intense.

 

[tuha]

Also, the burning muscle is a common thing. I started to really suffer from it 10 years into my illness.

For me, it’s very similar to my healthy person experience, with the big difference is that it doesn’t go away and it’s way more intense.

in my case those feelings are also constant, it doesnt go away even if I walk the same distance every day, it's nothing extreme and my muscles should be use to it.
What I cannot describe good is the feelings in my calfs. It doesnt hurt (only if I get muscle cramps which I can provoke easily by myself) like after overexertion when I was healthy. Also I wouldnt say that it's like burning muscle. I feel it like something very disagreable is accumulating in my calfs and I cannot get out of it. It's also disagreable when someone touch my calfs just a modest touch is disagreable.

 

[Jonathan Edwards]

What do you think explains these higher lactate levels at rest from that paper?
- I know it’s not the causation, but I’m looking for what explains the correlation (in about 45% of the patients)

It is a very peculiar study done retrospectively with PEM judged from old records. Moreover, the lactate levels all look fairly normal and mostly vary with food intake. I don't thin it means much.

 

[Jonathan Edwards]

I think people use 'lactic acid' as a lay term for lactate. When glucose is oxidised one of the hydrogen atoms becomes dissociable, so strictly speaking I think what is produced is lactic acid, but since the pH is clamped at 7.5 all we see is an increase in lactate ion (and probably some conversion of bicarbonate to CO2?).

 

[Arfmeister]

This wearable lactate monitor will be launched in 2026
- monitor working on the same principle as the glucose meter under skin / same principle as the glucose meter in skin
- linked to a smartwatch, as far as I understand

PKvitality’s SkinTaste® micro-sensor technology,

K’Track Athlete is the second wearable to tap PKvitality’s proprietary SkinTaste technology. But unlike the K’Track Glucose, it’s got a fitness bent: Instead of measuring blood sugar, it measures lactate.

The watch uses PKvitality’s SkinTaste® micro-sensor technology, which samples interstitial fluid through tiny micropoints — painlessly and continuously — to monitor biochemical markers like lactate.

“Lactic acid is a key performance indicator for the body and a guide to how well muscles react to long-term exertion and recovery,” PKvitality says. Mostly, it’s about avoiding the Lactic Threshold, or the point at which lactate begins to accumulate in the blood at a faster rate than it can be removed. That buildup triggers fatigue, which in turn affects the body’s ability to perform optimally at activities like long-distance running, rowing, swimming, and cycling.

PKvitality's SkinTaste sensor painlessly penetrates your skin to measure glucose

PKvitality's new SkinTaste biosensor uses microneedles to measure glucose and lactic acid levels in real time. The company has unveiled two wearables, the K-Track Glucose and K-Track Athlete, that use the technology.

www.digitaltrends.com