Proal, Amy D, Albert, Paul J, Marshall, Trevor G et al. · Immunologic research · 2013 · DOI
This study suggests that ME/CFS may be caused by multiple germs (bacteria, viruses, and fungi) working together in the body, rather than a single pathogen. The researchers proposed that these microbes interfere with how our genes are expressed, and developed an immunostimulatory treatment that showed promise in improving both how patients feel and measurable health markers.
This research offers a novel explanation for why decades of searching for a single cause of ME/CFS have been unsuccessful, suggesting instead a complex polymicrobial model. If validated, this approach could redirect treatment strategies toward targeting multiple organisms and immune dysregulation patterns rather than single-pathogen interventions.
This study does not establish causation—it presents a mechanistic model without demonstrating that VDR dysregulation directly causes ME/CFS or that the proposed treatment is effective in rigorous controlled trials. The findings are preliminary and do not prove the immunostimulatory therapy is superior to existing treatments or placebo, as controlled trial data are not presented.
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
Proal, Amy D, Albert, Paul J, Marshall, Trevor G, Blaney, Greg P, & Lindseth, Inge A (2013). Immunostimulation in the treatment for chronic fatigue syndrome/myalgic encephalomyelitis.. Immunologic research. https://doi.org/10.1007/s12026-013-8413-z
BibTeX
@article{mecfsatlas-proal-2013-immunostimulation-treatment,
author = {Proal, Amy D and Albert, Paul J and Marshall, Trevor G and Blaney, Greg P and Lindseth, Inge A},
title = {Immunostimulation in the treatment for chronic fatigue syndrome/myalgic encephalomyelitis.},
journal = {Immunologic research},
year = {2013},
doi = {10.1007/s12026-013-8413-z},
note = {PubMed: 23576059},
url = {https://www.mecfsatlas.com/evidence/proal-2013-immunostimulation-treatment},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/proal-2013-immunostimulation-treatment
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