Lactic acid, lactate in ME/CFS

[Jonathan Edwards]

There seems to be something amiss with all the evidence gathered here. Reference sources indicate that a lactate above 2 mmol/L is abnormal and above 4 seriously so, to the extent of suggesting sepsis or metabolic failure. People are reporting very high values without any apparent evidence of extreme exercise, sepsis or organ failure.

My memory is that lactate levels used to be done on samples kept on ice and transported rapidly to the lab. Presumably without careful handling you can get artifactual high levels. I wonder if this is an issue. Lactate as a basis for PEM symptoms makes no sense to me at all - for reasons given by others.

 

[Dude]

Perhaps a circulation problem? If blood flow to the muscles is impaired, the muscle cells are less able to utilize oxygen and switch earlier to anaerobic metabolism, which produces lactate.

There was a thread about abnormal blood lactate after exercise:

Physiological Reports Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome by Katarina Lien et al

Abstract
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 uptake (VO2) and power output (PO) in ME/CFS. Whether this affects arterial lactate concentrations ([Laa]) is unknown.

We studied 18 female patients (18–50 years) fulfilling the Canadian Consensus Criteria for ME/CFS and 15 healthy females (18–50 years) who underwent repeated CPETs 24 h apart (CPET1 and CPET2) with [Laa] measured every 30th second. VO2 at peak exercise (VO2peak) was lower in patients than in controls on CPET1 (P < 0.001) and decreased in patients on CPET2 (P < 0.001).

However, the difference in VO2peak between CPETs did not differ significantly between groups. [Laa] per PO was higher in patients during both CPETs (Pinteraction < 0.001), but increased in patients and decreased in controls from CPET1 to CPET2 (Pinteraction < 0.001).

Patients had lower VO2 (P = 0.02) and PO (P = 0.002) at the gas exchange threshold (GET, the point where CO2production increases relative to VO2), but relative intensity (%VO2peak) and [Laa] at GET did not differ significantly from controls on CPET1. Patients had a reduction in VO2 (P = 0.02) and PO (P = 0.01) at GET on CPET2, but no significant differences in %VO2peak and [Laa] at GET between CPETs.

Controls had no significant differences in VO2, PO or %VO2peak at GET between CPETs, but [Laa] at GET was reduced on CPET2 (P = 0.008).

In conclusion, previous exercise deteriorates physical performance and increases [Laa] during exercise in patients with ME/CFS while it lowers [Laa] in healthy subjects.

 

[Jonathan Edwards]

There was a thread about abnormal blood lactate after exercise:

But exercise testing does not have much to do with normal daily activity for people with ME/CFS. If people with ME/CFS only got symptoms after going on an exercise bike there wouldn't be much of a problem.

 

[Arfmeister]

There seems to be something amiss with all the evidence gathered here. Reference sources indicate that a lactate above 2 mmol/L is abnormal and above 4 seriously so, to the extent of suggesting sepsis or metabolic failure. People are reporting very high values without any apparent evidence of extreme exercise, sepsis or organ failure.

My memory is that lactate levels used to be done on samples kept on ice and transported rapidly to the lab. Presumably without careful handling you can get artifactual high levels. I wonder if this is an issue. Lactate as a basis for PEM symptoms makes no sense to me at all - for reasons given by others.

Maybe I’m an anomaly, but I doubt it, as I’ve spoken to a few more patients with exact similar symptomalogy.
(But not as extensive testing because that’s just very rare)

These measurements were taken in an academic hospital early in the morning before even getting out of bed. Immediately brought to the hospital lab. Seeing the first result of measurement my doctor was puzzled and shocked by the high lactate level and said exactly the same thing as you: this level would suggest sepsis.

I’m talking about this one : 9 of September 2025.
(And I would expect it to be even higher in the course of the day as burning-muscle symptoms and exertion increase)

Lactate (09.09.25) – 9.0 mmol/l (range 0.5 – 1.6)

PS: I’ve taken an interest into lactate levels already since 2017 when my first measurement was high (corresponding with a crash)
Consecutive measurements have been increasingly higher corresponding with my worsening (currently bedbound)

 

[jnmaciuch]

My memory is that lactate levels used to be done on samples kept on ice and transported rapidly to the lab. Presumably without careful handling you can get artifactual high levels. I wonder if this is an issue. Lactate as a basis for PEM symptoms makes no sense to me at all - for reasons given by others.

If kept at room temperature for long enough, live cells in the sample can artificially increase lactate levels by glycolysis. There’s some additive I’m forgetting the name of that is supposed to suppress this as well. I vaguely remember from discussions a long time ago that processing time differences of ~20-30 mins didn’t make a huge difference in someone’s data, but maybe longer time periods would start to push someone’s levels into sepsis territory.

Though being consistently at those high levels when processed by different staff at different labs would come across like a real phenomenon to me.

 

[jnmaciuch]

Also I thought there wasn’t much evidence for lactate itself causing organ damage in sepsis? In which case it would just be a response to infection or one of the downstream consequences, and could be triggered under other circumstances

 

[Covidivici]

But exercise testing does not have much to do with normal daily activity for people with ME/CFS. If people with ME/CFS only got symptoms after going on an exercise bike there wouldn't be much of a problem.

I agree that the PEM triggers don’t seem to follow directly from exercise per se. Could the lactic acid be a maladaptive reaction to the muscles’ apparent inability to solicit as many proteins as healthy controls? In which case any cell needing juice to function ends up busting its budget? (I am no expert, clearly).

Also, does it matter that I’m lactate intolerant?

(I’ll see myself out)

 

[Jonathan Edwards]

Also I thought there wasn’t much evidence for lactate itself causing organ damage

It doesn't, but lactic acidaemia can occur as a result of organ failure, e.g. liver.

 

[Jonathan Edwards]

Also, does it matter that I’m lactate intolerant?

That's lactose. Lactate and lactose are both called lact- because they are found in milk but that's about it I think.

Edit: I guess lactose gets broken down to lactate by bacteria but that is probably not where the name came from.

 

[Trish]

That's lactose. Lactate and lactose are both called lact- because they are found in milk but that's about it I think.

Lactose is a sugar found in milk. The enzyme lactase breaks it down to its component parts glucose and galactose. I think lactose intolerant people lack this enzyme.

Lactate or lactic acid is an organic acid formed from glucose in anaerobic respiration.

 

[Jonathan Edwards]

Lactate or lactic acid is an organic acid formed from glucose in anaerobic respiration.

Indeed, so presumably the lactobacilli in milk turn the glucose into lactate through anaerobic respiration.

And lactate makes the taste of yoghurt?

 

[jnmaciuch]

Also, does it matter that I’m lactate intolerant?

ba dum tsss

It doesn't, but lactic acidaemia can occur as a result of organ failure, e.g. liver.

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.

 

[Jonathan Edwards]

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.

That seems pretty unlikey if people with massive immune perturbation all over, in joints, bone marrow liver and spleen and so on with RA don't have raised lactate? The cellular activity in an RA joint is enough to drop local glucose levels to zero but I have never heard of it leading to lactic acidaemia.

If it was that easy to raise lactate I think that would be widely known in intensive care medicine.

 

[jnmaciuch]

That seems pretty unlikey if people with massive immune perturbation all over, in joints, bone marrow liver and spleen and so on with RA don't have raised lactate? The cellular activity in an RA joint is enough to drop local glucose levels to zero but I have never heard of it leading to lactic acidaemia.

So perhaps not “immune perturbation” in general but a specific set of processes that overlap between ischemia, sepsis, and some cases on the more severe end of ME/CFS.

 

[Jonathan Edwards]

So perhaps not “immune perturbation” in general but a specific set of circumstances that overlap between ischemia, sepsis, and some cases on the more severe end of ME/CFS.

Hard to see what that would be?

If lactic acidaemia was a real phenomenon in ME/CFS I find it hard to believe that it has not been documented. People like David Jones and Mike Rennie at UCL studied basic metabolites in blood and muscle in ME/CFS patients and found nothing as far as I know.

 

[jnmaciuch]

If lactic acidaemia was a real phenomenon in ME/CFS I find it hard to believe that it has not been documented. People like David Jones and Mike Rennie at UCL studied basic metabolites in blood and muscle in ME/CFS patients and found nothing as far as I know.

Unless it's transient--I'm inclined to think not every report of abnormal test results here is a fluke because transient lactic acidosis would be entirely consistent with the transient "poisoned" feeling that some pwME describe.

And it's been described as the most profoundly uncomfortable state of their fluctuating ME/CFS, so it makes sense that few pwME are making it to a sample collection appointment for a study when it might be evident in their blood or muscle. There's probably lots of signaling that we don't know about because it would only be detectable in the blood during peak PEM.

Hard to see what that would be?

STING activation, perhaps? Documented in ischemia from apoptotic cell DNA, and would be triggered in sepsis both by uncontrolled infection itself and corresponding cell death.

https://www.sciencedirect.com/science/article/pii/S0753332223012568

 

[Jonathan Edwards]

Unless it's transient--I'm inclined to think not every report of abnormal test results here is a fluke because transient lactic acidosis would be entirely consistent with the transient "poisoned" feeling that some pwME describe.

As far as I am aware there is no suggestion from clinical documentation that lactic acidaemia makes people feel poisoned. If it occurs with competitive exercise I know it doesn't from personal experience. Phenformin poisoning can produce a gross lactic acidosis. I looked after a young woman who had taken an overdose and required massive bicarbonate infusion to correct the metabolic shift and she said nothing about feeling poisoned.

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

It all looks an uninterpretable mess to me. Maybe with peripheral blood pooling in people not moving about venous lactate is unreliable anyway.

Documented in ischemia from apoptotic cell DNA

Surely in ischemia cell death would be necrotic? And there clearly isn't any ischemia producing cell death in ME/CFS on a daily basis. There would be local pain and an inflammatory response. This just seems completely out of proportion.

 

[jnmaciuch]

Surely in ischemia cell death would be necrotic?

Mostly necrotic but apoptotic as well from hypoxia. Both would lead to STING activation, though only the latter would be intracellular from mtDNA ejection through the BAX pore.

And there clearly isn't any ischemia producing cell death in ME/CFS on a daily basis.

Cell death isn’t necessary for STING activation, just cytosolic DNA. Cell death would just be the source of STING activation in the specific case of ischemia, likely not in ME/CFS if it is a feature there as well.

As far as I am aware there is no suggestion from clinical documentation that lactic acidaemia makes people feel poisoned.

I’ve heard anecdotes that it can, but yes I agree it’s not something explicitly mentioned in literature, which tends to be pretty limited in what gets documented anyways. There also may be substantially different presentations for lactic acidosis from exercise vs. other causes—exercise would also mobilize lots of other metabolites and pathways, and it may matter where/how the lactate is produced.

 

[Kitty]

transient "poisoned" feeling that some pwME describe

They do, but not as transient. Some severely ill people speak of having it most of the time, others every time they get PEM. I've only had it once, but it persisted for months. It was there when I was on bed rest during that crash, and when I was starting to come out of it, and when I'd recovered enough to return to work. No relationship to activity.

 

[jnmaciuch]

Some severely ill people speak of having it most of the time, others every time they get PEM.

Those would be the least likely to end up in a study assessing blood analytes, then.

No relationship to activity.

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