Kashi, Alex A, Davis, Ronald W, Phair, Robert D · Diagnostics (Basel, Switzerland) · 2019 · DOI
This study proposes a new theory about what might cause ME/CFS based on how the body processes an amino acid called tryptophan. The researchers suggest that if two proteins involved in tryptophan processing don't work properly together, the body could get stuck in a harmful state that causes ME/CFS symptoms. According to their mathematical model, if we could find a way to reset tryptophan levels back to normal, patients might recover.
This hypothesis provides one of the first mechanistic explanations for ME/CFS pathogenesis, moving beyond symptom-based treatment approaches. If validated experimentally, it could identify specific biomarkers for diagnosis and suggest targeted interventions to reset tryptophan metabolism. The model also explains why ME/CFS can appear in clusters and suggests the condition may be reversible under the right conditions.
This study presents a mathematical model and does not provide experimental evidence from ME/CFS patient samples or cell cultures. The hypothesis has not been tested with labeled tryptophan or validated in any cell type. The model does not prove that tryptophan metabolism abnormalities actually cause ME/CFS in real patients, nor does it identify what exogenous perturbation might reset the system.
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 →
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Primary citation
Kashi, Alex A, Davis, Ronald W, & Phair, Robert D (2019). The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS.. Diagnostics (Basel, Switzerland). https://doi.org/10.3390/diagnostics9030082
BibTeX
@article{mecfsatlas-kashi-2019-ido-metabolic,
author = {Kashi, Alex A and Davis, Ronald W and Phair, Robert D},
title = {The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS.},
journal = {Diagnostics (Basel, Switzerland)},
year = {2019},
doi = {10.3390/diagnostics9030082},
note = {PubMed: 31357483},
url = {https://www.mecfsatlas.com/evidence/kashi-2019-ido-metabolic},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/kashi-2019-ido-metabolic
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