Rahman, A F M Towheedur, Benko, Anna, Bulbule, Sarojini et al. · Biomolecules · 2025 · DOI
This review article examines a molecule called tetrahydrobiopterin (BH4) and its possible role in ME/CFS, particularly in patients who experience orthostatic intolerance (dizziness or fainting when standing up). The researchers found that BH4 metabolism—the way the body processes this molecule—is not working properly in ME/CFS patients with these symptoms. By understanding how BH4 goes wrong, scientists hope to explain why ME/CFS patients have problems with blood flow to the brain.
Understanding what goes wrong with BH4 metabolism could help explain why some ME/CFS patients experience orthostatic intolerance and reduced blood flow to the brain—symptoms that severely limit their ability to function. If BH4 dysregulation is confirmed as a key mechanism, it could eventually lead to new treatments targeting this pathway to improve these debilitating symptoms.
This review does not prove that BH4 dysregulation causes orthostatic intolerance in ME/CFS; it proposes a mechanism based on existing evidence. The study does not present new patient data or clinical trials, so it cannot demonstrate whether correcting BH4 would improve symptoms. The review is hypothesis-generating rather than hypothesis-confirming.
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
Rahman, A F M Towheedur, Benko, Anna, Bulbule, Sarojini, Gottschalk, Carl Gunnar, Arnold, Leggy A, & Roy, Avik (2025). Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?. Biomolecules. https://doi.org/10.3390/biom15010102
BibTeX
@article{mecfsatlas-rahman-2025-tetrahydrobiopterin-myalgic,
author = {Rahman, A F M Towheedur and Benko, Anna and Bulbule, Sarojini and Gottschalk, Carl Gunnar and Arnold, Leggy A and Roy, Avik},
title = {Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?},
journal = {Biomolecules},
year = {2025},
doi = {10.3390/biom15010102},
note = {PubMed: 39858496},
url = {https://www.mecfsatlas.com/evidence/rahman-2025-tetrahydrobiopterin-myalgic},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/rahman-2025-tetrahydrobiopterin-myalgic
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