Bulbule, Sarojini, Gottschalk, Carl Gunnar, Drosen, Molly E et al. · Journal of central nervous system disease · 2024 · DOI
Researchers found that patients with ME/CFS who experience dizziness upon standing have abnormally high levels of certain molecules called biopterins in their blood. The study discovered that these molecules are produced through an unusual metabolic pathway involving the breakdown of glucose, and this pathway appears to trigger inflammation in immune cells. This finding suggests a potential biochemical explanation for some ME/CFS symptoms.
This study identifies a specific molecular mechanism that could explain both the orthostatic intolerance and inflammatory symptoms seen in some ME/CFS patients. Understanding this metabolic dysregulation opens potential avenues for biomarkers to identify ME+OI subgroups and for targeted therapeutic interventions. The findings bridge cellular metabolism, immune activation, and clinical symptoms in a way that could advance personalized medicine approaches.
This study does not establish whether elevated biopterins cause orthostatic intolerance or are merely associated with it; the direction of causality remains unclear. The in vitro cell culture findings, while suggestive, do not directly prove this pathway operates identically in living ME/CFS patients. The study also does not demonstrate that targeting this pathway would be therapeutically effective or safe.
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
Bulbule, Sarojini, Gottschalk, Carl Gunnar, Drosen, Molly E, Peterson, Daniel, Arnold, Leggy A, & Roy, Avik (2024). Dysregulation of tetrahydrobiopterin metabolism in myalgic encephalomyelitis/chronic fatigue syndrome by pentose phosphate pathway.. Journal of central nervous system disease. https://doi.org/10.1177/11795735241271675
BibTeX
@article{mecfsatlas-bulbule-2024-dysregulation-tetrahydrobiopterin,
author = {Bulbule, Sarojini and Gottschalk, Carl Gunnar and Drosen, Molly E and Peterson, Daniel and Arnold, Leggy A and Roy, Avik},
title = {Dysregulation of tetrahydrobiopterin metabolism in myalgic encephalomyelitis/chronic fatigue syndrome by pentose phosphate pathway.},
journal = {Journal of central nervous system disease},
year = {2024},
doi = {10.1177/11795735241271675},
note = {PubMed: 39161795},
url = {https://www.mecfsatlas.com/evidence/bulbule-2024-dysregulation-tetrahydrobiopterin},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/bulbule-2024-dysregulation-tetrahydrobiopterin
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