Lundell, Kathleen, Qazi, Sanjive, Eddy, Linda et al. · Arzneimittel-Forschung · 2006 · DOI
This study looked at 58 ME/CFS patients and found that most had weakened immune systems with low levels of a type of immune cell called B-lymphocytes, and most also had reactivated Epstein-Barr virus (EBV) infection. When researchers gave patients folinic acid (a form of vitamin B), about 81% reported feeling better. The findings suggest that folinic acid might help some ME/CFS patients and that immune problems may play a role in the illness.
This study provides an early mechanistic link between immune dysfunction (B-cell depletion) and ME/CFS, and identifies folinic acid as a potentially accessible intervention with a high reported response rate. For patients, it offers a low-risk, low-cost option worth discussing with their healthcare provider; for researchers, it suggests immune profiling and B-cell function deserve further investigation as therapeutic targets.
This study does not prove that folinic acid cures or universally treats ME/CFS, as it lacks a placebo control group and relies on subjective patient reports rather than objective biomarkers of improvement. It does not establish that EBV reactivation or B-cell depletion directly causes ME/CFS, only that these conditions frequently occur together. The mechanism by which folinic acid might improve symptoms remains unexplained.
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 →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Lundell, Kathleen, Qazi, Sanjive, Eddy, Linda, & Uckun, Fatih M (2006). Clinical activity of folinic acid in patients with chronic fatigue syndrome.. Arzneimittel-Forschung. https://doi.org/10.1055/s-0031-1296741
BibTeX
@article{mecfsatlas-lundell-2006-clinical-activity,
author = {Lundell, Kathleen and Qazi, Sanjive and Eddy, Linda and Uckun, Fatih M},
title = {Clinical activity of folinic acid in patients with chronic fatigue syndrome.},
journal = {Arzneimittel-Forschung},
year = {2006},
doi = {10.1055/s-0031-1296741},
note = {PubMed: 16889122},
url = {https://www.mecfsatlas.com/evidence/lundell-2006-clinical-activity},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/lundell-2006-clinical-activity
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