Castell, L M, Yamamoto, T, Phoenix, J et al. · Advances in experimental medicine and biology · 1999 · DOI
This study looks at tryptophan, a building block the brain uses to make serotonin, a chemical involved in fatigue and sleep. The researchers measured tryptophan levels in ME/CFS patients and people recovering from surgery, comparing how their bodies handled tryptophan differently than healthy controls. They found that ME/CFS patients had unusually high tryptophan levels that didn't change with exercise, which might help explain why they feel persistently tired.
This research provides a potential biochemical mechanism for the persistent fatigue characteristic of ME/CFS—abnormal tryptophan metabolism leading to excessive central serotonin signaling. The findings suggest a testable hypothesis that BCAA supplementation might counteract this effect, offering a possible therapeutic avenue. Understanding these amino acid dynamics could inform treatment strategies for both ME/CFS and fatigue in other acute stress conditions.
This study does not prove that tryptophan abnormalities cause ME/CFS fatigue, only that they are associated with it; causation cannot be established from cross-sectional amino acid measurements. It does not demonstrate that BCAA supplementation will improve symptoms in ME/CFS patients—only that it has shown promise in athlete recovery. The small sample size and lack of detailed patient demographic data limit generalizability to the broader ME/CFS population.
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
Castell, L M, Yamamoto, T, Phoenix, J, & Newsholme, E A (1999). The role of tryptophan in fatigue in different conditions of stress.. Advances in experimental medicine and biology. https://doi.org/10.1007/978-1-4615-4709-9_90
BibTeX
@article{mecfsatlas-castell-1999-role-tryptophan,
author = {Castell, L M and Yamamoto, T and Phoenix, J and Newsholme, E A},
title = {The role of tryptophan in fatigue in different conditions of stress.},
journal = {Advances in experimental medicine and biology},
year = {1999},
doi = {10.1007/978-1-4615-4709-9_90},
note = {PubMed: 10721121},
url = {https://www.mecfsatlas.com/evidence/castell-1999-role-tryptophan},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/castell-1999-role-tryptophan
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