Cerebrospinal fluid metabolomics, lipidomics and serine pathway dysfunction in [ME/CFS], 2025, Baraniuk

Abstract:
We proposed that cerebrospinal fluid would provide objective evidence for disrupted brain metabolism in myalgic encephalomyelitis/chronic fatigue syndroome (ME/CFS). The concept of postexertional malaise (PEM) with disabling symptom exacerbation after limited exertion that does not respond to rest is a diagnostic criterion for ME/CFS. We proposed that submaximal exercise provocation would cause additional metabolic perturbations. The metabolomic and lipidomic constituents of cerebrospinal fluid from separate nonexercise and postexercise cohorts of ME/CFS and sedentary control subjects were contrasted using targeted mass spectrometry (Biocrates) and frequentist multivariate general linear regression analysis with diagnosis, exercise, gender, age and body mass index as independent variables.

ME/CFS diagnosis was associated with elevated serine but reduced 5-methyltetrahydrofolate (5MTHF). One carbon pathways were disrupted. Methylation of glycine led to elevated sarcosine but further methylation to dimethylglycine and choline was decreased. Creatine and purine intermediates were elevated. Transaconitate from the tricarboxylic acid cycle was elevated in ME/CFS along with essential aromatic amino acids, lysine, purine, pyrimidine and microbiome metabolites. Serine is a precursor of phospholipids and sphingomyelins that were also elevated in ME/CFS. Exercise led to consumption of lipids in ME/CFS and controls while metabolites were consumed in ME/CFS but generated in controls.

The findings differ from prior hypometabolic findings in ME/CFS plasma. The novel findings generate new hypotheses regarding serine-folate-glycine one carbon and serine-phospholipid metabolism, elevation of end products of catabolic pathways, shifts in folate, thiamine and other vitamins with exercise, and changes in sphingomyelins that may indicate myelin and white matter dysfunction in ME/CFS.

Link | PDF (Nature Scientific Reports, March 2025, open access)

 

This seems like a duplicate of Exertional Exhaustion Post-Exertional Malaise, PEM Evaluated by the Effects of Exercise on Cerebrospinal Fluid Metabolomics–Lipidomics and Serine Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (2025, International Journal of Molecular Sciences)

 

Serine had interest maybe three decades ago, transaconitate sounds like something I might have discussed two and a half decades ago; purines have always been high with me, leading to a wrong diagnosis of gout. I am not sure what they mean by metabolites consumed in exercise, guess I will have to read the paper. Take my mind off the cyclone that may hit my area in a day or three. [cyclone discussion moved here]

If we have broken energy metabolism then the cell finds other pathways and metabolites. However most tissues might have trouble consuming lactate, which means the liver has to consume it all, and it does so slowly.

 

Indeed, the data and figures look the same.

Strange situation. Normally journals forbid submitting the same manuscript elsewhere.

 

Hmm good spot. Papers are extremely similar.

 

Not to sound pedantic, but a typo in the first sentence of a paper published in Nature Sci Reports? "syndroome"

 

Not to sound pedantic, but he uses “we” in the abstract for a single author paper.

Also getting red flags for a single author paper with so much data

 

Isn’t ‘we’ even for a single author research paper standard practice. Had it been an opinion piece that would have been different.

 

I think it is.

 

Scientific Reports, despite being published by Nature [Publishing Group], is not a quality journal, but this fact isn't really appreciated outside of academia. They accept a large percentage of submitted papers, very often publish trash, and the journal has been implicated in numerous scientific fraud cases.