Knook, L, Kavelaars, A, Sinnema, G et al. · The Journal of clinical endocrinology and metabolism · 2000 · DOI
Researchers measured melatonin (a natural hormone that helps control sleep) in saliva samples from 13 teenagers with ME/CFS and 15 healthy teenagers. They found that ME/CFS patients had significantly higher melatonin levels during the night, yet paradoxically, all the ME/CFS patients reported their sleep felt unrefreshing and unrestorative. Based on this finding, the researchers suggested that giving melatonin supplements to teenagers with ME/CFS may not be helpful.
Sleep disturbance is a cardinal symptom of ME/CFS, and understanding the biochemical mechanisms underlying unrefreshing sleep is crucial for developing effective treatments. This study directly challenges the assumption that melatonin deficiency causes ME/CFS-related sleep problems, potentially preventing inappropriate supplementation and redirecting research toward other mechanisms of sleep dysfunction in this population.
This study does not establish that elevated melatonin causes poor sleep quality in ME/CFS—it only shows an association. It also does not rule out circadian rhythm abnormalities outside the measured window, does not examine melatonin receptor sensitivity, and cannot generalize findings to adults with ME/CFS based on an adolescent-only sample.
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
Knook, L, Kavelaars, A, Sinnema, G, Kuis, W, & Heijnen, C J (2000). High nocturnal melatonin in adolescents with chronic fatigue syndrome.. The Journal of clinical endocrinology and metabolism. https://doi.org/10.1210/jcem.85.10.6857
BibTeX
@article{mecfsatlas-knook-2000-high-nocturnal,
author = {Knook, L and Kavelaars, A and Sinnema, G and Kuis, W and Heijnen, C J},
title = {High nocturnal melatonin in adolescents with chronic fatigue syndrome.},
journal = {The Journal of clinical endocrinology and metabolism},
year = {2000},
doi = {10.1210/jcem.85.10.6857},
note = {PubMed: 11061525},
url = {https://www.mecfsatlas.com/evidence/knook-2000-high-nocturnal},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/knook-2000-high-nocturnal
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