The, Gerard K H, Verkes, Robbert J, Fekkes, Durk et al. · BMC research notes · 2014 · DOI
Researchers tested whether reducing tryptophan (a protein building block that helps make serotonin, a brain chemical) would improve ME/CFS symptoms. Five women with ME/CFS received either a special amino acid drink designed to lower tryptophan or placebo, one week apart. The drink successfully reduced tryptophan levels by 96%, but it did not change fatigue, mood, or concentration compared to placebo.
Understanding the neurochemical basis of ME/CFS fatigue is crucial for developing effective treatments, as current interventions are limited and recovery without treatment is rare. This study directly tested a specific hypothesis about serotonin dysregulation that had support from genetic and imaging data, providing important mechanistic insight. The negative result, while modest in scope, contributes to the evidence base needed to refine biological theories of ME/CFS.
This small pilot study does not rule out serotonin involvement in ME/CFS—it only shows that acute tryptophan depletion did not produce symptom changes in five patients, which may reflect inadequate sample size, patient selection, or insufficient biological sensitivity of the intervention. The study does not establish whether chronic serotonin dysregulation (rather than acute manipulation) contributes to ME/CFS symptoms. Negative findings in a pilot cannot exclude a hypothesis without larger, adequately powered replication.
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
The, Gerard K H, Verkes, Robbert J, Fekkes, Durk, Bleijenberg, Gijs, van der Meer, Jos W M, & Buitelaar, Jan K (2014). Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study.. BMC research notes. https://doi.org/10.1186/1756-0500-7-650
BibTeX
@article{mecfsatlas-the-2014-tryptophan-depletion,
author = {The, Gerard K H and Verkes, Robbert J and Fekkes, Durk and Bleijenberg, Gijs and van der Meer, Jos W M and Buitelaar, Jan K},
title = {Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study.},
journal = {BMC research notes},
year = {2014},
doi = {10.1186/1756-0500-7-650},
note = {PubMed: 25227994},
url = {https://www.mecfsatlas.com/evidence/the-2014-tryptophan-depletion},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/the-2014-tryptophan-depletion
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