A new study provides further evidence of mitochondrial dysfunction and abnormal lactic acid production in ME/CFS.
By Godlewska, B.R., Sylvester, A.L., Emir, U.E. et al., Molecular Psychiatry
Summary
- The study used magnetic resonance spectroscopy (MRS) to explore the brain and muscle chemistry in people with ME/CFS and Long Covid, compared to healthy controls, and found the following:
- In people with ME/CFS:
- They had more lactate (a chemical linked to energy use) in two brain areas.
- This suggests that their brains might be under energy stress or that their mitochondria (energy factories in cells) aren't working properly.
- In people with long COVID:
- They had less choline (a chemical important for brain function) in one brain area.
- This might be linked to problems with blood flow or tiny blood clots in the brain, which could explain their brain fog.
- In muscles:
- There were no major differences in energy-related chemicals in the muscles of any group.
- But there was a small trend showing people with ME/CFS might have less carnosine, a chemical that helps muscles work properly. This could add to feelings of muscle tiredness.
- In people with ME/CFS:
On the 12th July, 2025, a new paper titled: ‘Brain and muscle chemistry in myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and long COVID: a 7T magnetic resonance spectroscopy study,' was published in Molecular Psychiatry, Nature.
Extracts
Abstract:
Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a common debilitating medical condition, whose main symptoms – fatigue, post-exertional malaise and cognitive dysfunction – are also present in many cases of long COVID.
Magnetic resonance spectroscopy (MRS) allows the insight into their pathophysiology through exploration of a range of biochemicals putatively relevant to aetiological processes, in particular mitochondrial dysfunction and energy metabolism.
24 patients with ME/CFS, 25 patients with long COVID and 24 healthy controls (HC) underwent brain (pregenual and dorsal anterior cingulate cortex, respectively, pgACC and dACC) and calf muscle MRS scanning at 7 Tesla, followed by a computerised cognitive assessment.
Compared to HC, ME/CFS patients had elevated levels of lactate in both pgACC and dACC, while long COVID patients had lowered levels of total choline in dACC. By contrast, skeletal muscle metabolites at rest did not significantly differ between the groups. The changes in lactate in ME/CFS are consistent with the presence of energetic stress and mitochondrial dysfunction.
A reduction in total choline in long COVID is of interest in the context of the recently reported association between blood clots and ‘brain fog’, and earlier animal studies showing that choline might prevent intravascular coagulation.
Importantly, differences in findings between ME/CFS and long COVID suggest that the underlying neurobiological mechanisms, while leading to similar clinical presentations, may differ. An important implication is that patients with ME/CFS and those with fatigue in the course of long COVID should not be studied as a single group, at least until the mechanisms are better understood.
MEA Comment:
Some important new research from a group in Oxford that the MEA is linked to.
The results provide further strong evidence of mitochondrial dysfunction (mitochondria are battery like structures that create energy at a cellular level) and abnormal lactic acid production in ME/CFS resulting in a defective energy production – all of which may well be related to activity induced fatigue and post exertional malaise in ME/CFS.
It is now over 40 years since I was involved with very similar MRS and muscle biopsy muscle research in Oxford (Prof George Radda) and Glasgow (Professors Peter and Mina Behan) and using my own skeletal muscle. This research demonstrated an early and excessive lactic acidosis following exercise. We published this research in The Lancet back in 1984.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
