Melatonin entrains free-running blind people according to a physiological dose-response curve

Alfred J. Lewy, Jonathan S. Emens, Bryan J. Lefler, Krista Yuhas, Angela R. Jackman

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


The specific circadian role proposed for endogenous melatonin production was based on a study of sighted people who took low pharmacological doses (500 μg) of this chemical signal for the "biological night": the magnitude and direction of the induced phase shifts were dependent on what time of day exogenous melatonin was administered and were described by a phase-response curve that turned out to be the opposite of that for light. We now report that lower (physiological) doses of up to 300 μg can entrain (synchronize) free-running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day. The resulting log-linear dose-response curve in the physiological range adds support for a circadian function of endogenous melatonin in humans. Efficacy of exogenous doses in the physiological range are of clinical significance for totally blind people who will need to take melatonin daily over their entire lifetimes in order to remain entrained to the 24 h day. Left untreated, their free-running endocrine, metabolic, behavioral, and sleep/wake cycles can be almost as burdensome as not having vision.

Original languageEnglish (US)
Pages (from-to)1093-1106
Number of pages14
JournalChronobiology International
Issue number6
StatePublished - Nov 2005


  • Blindness
  • Endogenous circadian period (tau)
  • Free-running circadian rhythms
  • Melatonin
  • Melatonin entrainment dose-response curve

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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