A large French study finds abnormally high lactate levels in ME/CFS even at rest…sometimes.
David Systrom seemed to call it out – his invasive CPET results suggested that mitochondrial dysfunction was present in a large subset of people with chronic fatigue syndrome (ME/CFS) – and he believed their blood lactate levels were probably elevated.
Right on the heels of that study comes a seeming stunner: a study finding elevated blood lactate levels not after exercise but at rest as well. The title of the study, “Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome”, suggested a quite troubling finding: even at rest – even when the participants’ aerobic energy production systems were not being stressed – their systems were not keeping up.
Workwell’s Staci Stevens has reported that even very light exertion causes some people with ME/CFS to exceed their aerobic capacity. If that was happening at rest in a significant proportion of patients, the French study was identifying something troubling indeed. It meant that no relief from the troubles (fatigue, pain) associated with a reliance on the toxic anaerobic energy production system was possible – even at rest.
Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome. Alaa Ghali, Carole Lacout, Maria Ghali, Aline Gury, Anne-Berengere Beucher, Pierre Lozac’h, Christian Lavigne & Geoffrey Urbanski Scientific Reports volume 9, Article number: 18817 (2019).
This very rare French ME/CFS study took place between 2011 and 2017 and grew to include 123 patients, all of whom met the International Consensus Criteria for ME.
It appears to have been very well controlled. The participants were admitted to the University hospital Angers-France the night before. Their blood was taken in the morning (following a meal after a sixteen hour fast) and then seven more times during the day. During their stay, food and activity levels were highly regulated.
The following tests were run: blood lactate, immunological assay, infectious disease screen for HIV, hepatitis B and C, Lyme disease, enterovirus, Mycoplasma pneumoniae, Chlamydia pneumoniae, serum zinc, 25-hydroxyvitamin D, plasma cortisol, testosterone, iron studies, plasma vitamin B12 and serum folate, full blood count and differential, erythrocyte sedimentation rate, electrolytes, calcium, phosphate, fasting glucose, C-reactive protein, liver function, serum protein electrophoresis, renal function, thyroid function, and creatine kinase.
Two distinct groups of ME/CFS patients were found: elevated blood lactate levels (≥2 mmol/L) were found at least once in 45% of the participants while 55% had consistently normal lactate levels (<2 mmol/L). (According to UC Davis, normal blood lactate levels at rest are 1-2 mmol/L).
A closer look at the results, though, brought some surprises. It turned out that elevated blood lactate levels at rest were not the norm at all – not even in the high lactate group. Most of the time, even their blood lactate levels were normal.
Check out the results from the first ten participants in the high lactate group. Note how much the readings jump around. High lactate levels often appear next to what appear to be abnormally low lactate levels. (Only one person in the study had abnormally high lactate levels at every time point.) While elevated lactate levels were found, normal lactate levels were the norm.
Approximately 52 of the tests showed high lactate levels but about double that number showed lactate levels that were below what is considered normal for a resting state. (Was a low lactate group present as well?)
At one time point, though – 1 hour following a meal after a 16 hour fast – blood lactate levels did appear to be consistently above normal. Something about that time point appears to have consistently tweaked a large number of people with ME/CFS.
Higher Lactate Group
There certainly was a higher lactate group. The lactate levels of the high lactate group was significantly increased at every time point relative to the normal lactate group. Even if their blood lactate levels at rest were not consistently elevated (i.e. > 2 mmol/L), they were significantly higher relative to the other group.
Plus, while the high lactate group did not experience more fatigue, they appeared to be hurting more: significantly more of the group experienced more severe PEM symptoms than in the normal lactate group.
The Blood Lactate Conundrum
With so many questions, I turned to Mark VanNess, a Workwell exercise physiologist who has participated in many ME/CFS studies. What about all the fluctuations in lactate levels, I asked. What did it mean that lactate levels at one time point, but not others, were elevated? And what about all those low lactate readings – what did those mean?
Mark couldn’t provide the answers to those questions – it turns out that no one can, but he did explain why. It’s easy to collect and measure blood lactate but accurately interpreting them is daunting. The French paper suggested that the higher blood lactate levels might reflect a mitochondrial dysfunction but other possibilities are present.
Lactate blood levels can be affected by a number of processes:
- Lactate uptake by the muscles – Because the lactate levels found in the blood present a balance between lactate production by the muscle and lactate uptake by adjacent muscle fibers, high blood lactate levels could indicate high lactate production by the muscle or reduced lactate uptake.
- Lactate uptake by the liver and other tissues – Because the liver and other tissues also take up lactate from the blood to use to produce energy (yes, lactate is used as an energy substrate), problems with liver (or other tissue) uptake of lactate could result in increased blood lactate levels.
- Damaged slow twitch muscle fibers – Fast twitch muscle fibers produce lactate while slow twitch muscle fibers actually use lactate. It’s been hypothesized that problems with energy production in ME/CFS patients’ slow-twitch muscles could be causing them to rely more on the lactate-producing fast twitch fibers – even during lower intensity physical activity.
- Altered enzyme activity in the mitochondria – Two enzymes – lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) – convert pyruvate into either lactate or acetyl-CoA. If the LDH enzyme dominates in ME/CFS, as has been conjectured, then more lactate will be produced.
- Noisy variable! – Lactate levels are dependent on so many factors that interpreting single measures is a daunting task. The best lactate study would subject patients to different levels/types of activity and then compare lactate levels.
In the end, then, any number of factors (increased lactate production, decreased clearance, altered tolerance, enhanced or impaired metabolism) could be causing elevated (or reduced) blood lactate levels. In fact, it’s possible that all are happening in one subset or the other of ME/CFS patients.
A final complication concerns the inability of sedentary people to utilize lactate as efficiently as people who exercise. The sedentariness that comes with ME/CFS could be having some effect on blood lactate levels.
This study found that intermittently increased lactate levels (particularly at one time point) occurred in a large subset (45%) of ME/CFS patients even when they were at rest. That group also consistently had higher lactate levels than the normal lactate group. Most of their resting lactate levels were, however, in the normal range.
Unfortunately, there are no easy answers. I’ve tended to associate increased blood lactate solely with mitochondrial and energy production problems, but they could also reflect problems with liver or muscle lactate uptake or slow twitch muscle issues. More study needs to be done to unravel what, if anything, is happening with this easy-to-collect but difficult-to-understand measure in ME/CFS.
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Blood lactate, it turns out, is quite a bit more complex than it seems. Health Rising found that out when we dug deeper – which is what we do as we try to get the bottom of what is going on with ME/CFS and FM. If that kind of deep dive supports you, please consider supporting us 🙂
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