van de Luit, L, van der Meulen, J, Cleophas, T J et al. · Angiology · 1998 · DOI
This study found that people with ME/CFS have unusually large swings in heart rate and blood pressure throughout the day and night, even though the overall pattern matches healthy controls. Importantly, their nighttime blood pressure drops too low (below 100 mm Hg systolic), which may contribute to fatigue and other symptoms. When treated with a heart-strengthening medication called inopamil, nighttime blood pressure improved, but melatonin actually made it worse.
This is one of the first quantitative characterizations of circadian rhythm abnormalities in ME/CFS, providing objective physiological evidence linking disturbed autonomic function to fatigue. The finding that nighttime hypotension may be correctable with specific medications offers a potential therapeutic target and suggests ME/CFS involves treatable cardiovascular regulation dysfunction.
This study does not prove that amplified circadian rhythms cause ME/CFS fatigue, only that the association exists. The small 4-week pilot treatment trial cannot establish efficacy or optimal dosing of inopamil or definitively rule out melatonin, and open-label design means results are vulnerable to placebo effects. Causality between nighttime hypotension and symptoms remains unestablished.
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
van de Luit, L, van der Meulen, J, Cleophas, T J, & Zwinderman, A H (1998). Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin.. Angiology. https://doi.org/10.1177/000331979804901105
BibTeX
@article{mecfsatlas-van-de-luit-1998-amplified-amplitudes,
author = {van de Luit, L and van der Meulen, J and Cleophas, T J and Zwinderman, A H},
title = {Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin.},
journal = {Angiology},
year = {1998},
doi = {10.1177/000331979804901105},
note = {PubMed: 9822046},
url = {https://www.mecfsatlas.com/evidence/van-de-luit-1998-amplified-amplitudes},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/van-de-luit-1998-amplified-amplitudes
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