Human Phase Response Curves to Three Days of Daily Melatonin: 0.5 mg Versus 3.0 mg
Open accessAbstract
CONTEXT: Phase response curves (PRCs) to melatonin exist, but none compare different doses of melatonin using the same protocol. OBJECTIVE: The aim was to generate a PRC to 0.5 mg of oral melatonin and compare it to our previously published 3.0 mg PRC generated using the same protocol. DESIGN AND SETTING: The study included two 5-d sessions in the laboratory, each preceded by 7-9 d of fixed sleep times. Each session started and ended with a phase assessment to measure the dim light melatonin onset (DLMO). In between were 3 d in an ultradian dim light (<150 lux)/dark cycle (light:dark, 2.5:1.5). PARTICIPANTS: Healthy adults (16 men, 18 women) between the ages of 18 and 42 yr participated in the study. INTERVENTIONS: During the ultradian days of the laboratory sessions, each participant took one pill per day at the same clock time (0.5 mg melatonin or placebo, double blind, counterbalanced). MAIN OUTCOME MEASURE: Phase shifts to melatonin were derived by subtracting the phase shift to placebo. A PRC with time of pill administration relative to baseline DLMO and a PRC relative to midpoint of home sleep were generated. RESULTS: Maximum advances occurred when 0.5 mg melatonin was taken in the afternoon, 2-4 h before the DLMO, or 9-11 h before sleep midpoint. The time for maximum phase delays was not as distinct, but a fitted curve peaked soon after wake time. CONCLUSIONS: The optimal administration time for advances and delays is later for the lower dose of melatonin. When each dose of melatonin is given at its optimal time, both yield similarly sized advances and delays.
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The melatonin phase response curve specifies how exogenous melatonin will shift the individuals' body clock when given at various times in relation to their sleep midpoint.
“The melatonin phase response curve specifies how exogenous melatonin will shift the individuals’ body clock when given at various times in relation to their sleep midpoint [65].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [65]
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- Authors
- Burgess, H. J., Revell, V. L., Molina, T. A., & Eastman, C. I.
- Affiliations
- Rush University Medical Center (US)
- University of Surrey (GB)
- Corresponding author
- Burgess, Helen J.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2010-07-01
- Volume
- 95
- Issue
- 7
- Pages
- 3325-3331
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2928909
- OpenAlex
- W2071478700
- Cited by
- 221
- References
- 26
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 12 · 2023: 11 · 2022: 18 · 2021: 16 · 2020: 24 · 2019: 15 · 2018: 11 · 2017: 10 · 2016: 13 · 2015: 17 · 2014: 11 · 2013: 10 · 2012: 8
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Research (University of Surrey) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- Rush University
- University of Surrey
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL086934)
- National Institute of Nursing Research (R01NR007677)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- melatonin, phase response curve, dim light melatonin onset, circadian rhythm, phase advance, phase lag, sleep timing
- MeSH terms
- Adolescent, Adult, Circadian Rhythm, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Melatonin, Sleep, Photoperiod, Area Under Curve
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