Regland, Björn, Forsmark, Sara, Halaouate, Lena et al. · PloS one · 2015 · DOI
This study looked at 38 ME/CFS patients who were receiving vitamin B12 injections and oral folic acid to see how well this treatment worked for them. Patients who improved the most received more frequent injections at higher doses, took more folic acid, and were less likely to use strong pain medications like opioids. The researchers found that this treatment combination showed real benefits for some patients, particularly when carefully matched to individual needs.
This study provides clinical evidence that B12/folic acid therapy may benefit some ME/CFS patients and identifies potentially important modifying factors like MTHFR genotype status, thyroid function, and concurrent medication use. These findings could inform more personalized treatment approaches and highlight the need for controlled trials that account for drug interactions and individual methylation capacity.
This observational study cannot establish causation or optimal dosing protocols—it only describes associations in a small, self-selected group who remained on treatment. The lack of a control group means improvements could reflect placebo effect, natural history, lifestyle changes, or selection bias favoring responders. The finding that analgesic use correlates with poor response does not prove analgesics caused worse outcomes; patients in greater pain may simply have worse underlying disease.
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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