E3 PreliminaryPreliminaryPEM unclearCross-SectionalPeer-reviewedReviewed
Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome.
Regland, B, Andersson, M, Abrahamsson, L et al. · Scandinavian journal of rheumatology · 1997 · DOI
Quick Summary
Researchers tested the spinal fluid of 12 women who had both fibromyalgia and ME/CFS and found unusually high levels of a molecule called homocysteine in their brains and spinal cords. They also noticed that patients with lower vitamin B12 levels in their spinal fluid reported more severe fatigue. This suggests that a vitamin B12 deficiency might prevent the body from properly breaking down homocysteine, which could contribute to symptoms like exhaustion.
Why It Matters
This study provides early evidence of a specific biochemical abnormality in the central nervous system of ME/CFS patients, moving beyond symptoms to identify potential underlying mechanisms. If replicated, elevated CSF homocysteine could become a biomarker for disease and vitamin B12 supplementation could be explored as a therapeutic target.
Observed Findings
- Elevated cerebrospinal fluid homocysteine levels detected in all 12 patients studied
- Positive correlation between CSF homocysteine levels and reported fatiguability
- Positive correlation between CSF vitamin B12 levels and fatigue severity (CPRS-15)
- Blood laboratory values remained generally normal despite CSF abnormalities
Inferred Conclusions
- Vitamin B12 deficiency impairs the remethylation of homocysteine, leading to its accumulation in the central nervous system
- Increased homocysteine in the CSF is a characteristic biochemical marker in patients with both fibromyalgia and ME/CFS
- Central nervous system metabolic dysfunction, rather than systemic disease, may be primary in these conditions
Remaining Questions
- How does CSF homocysteine elevation relate to specific ME/CFS symptoms beyond fatigue (cognitive dysfunction, post-exertional malaise, etc.)?
- Would vitamin B12 supplementation normalize CSF homocysteine levels and improve clinical outcomes?
- Are elevated homocysteine levels present in ME/CFS patients without fibromyalgia, and are they present in healthy controls?
What This Study Does Not Prove
This study does not prove that homocysteine elevation *causes* ME/CFS or fibromyalgia—it only shows a correlation. The small sample size, lack of control group, and female-only population limit generalizability. The study does not establish whether B12 supplementation would reduce homocysteine or improve fatigue.
Tags
Symptom:PainFatigue
Biomarker:MetabolomicsBlood Biomarker
Method Flag:PEM Not DefinedNo ControlsSmall SampleMixed CohortWeak Case DefinitionExploratory Only
Metadata
- DOI
- 10.3109/03009749709105320
- PMID
- 9310111
- Review status
- Editor reviewed
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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