Advancing human circadian rhythms with afternoon melatonin and morning intermittent bright light

J Clin Endocrinol Metab. 2006 Jan;91(1):54-9. doi: 10.1210/jc.2005-1009. Epub 2005 Nov 1.


Context: Both light and melatonin can be used to phase shift the human circadian clock, but the phase-advancing effect of the combination has not been extensively investigated.

Objective: The objective of the study was to determine whether phase advances induced by morning intermittent bright light and a gradually advancing sleep schedule could be increased with afternoon melatonin.

Participants: Healthy adults (25 males, 19 females, between the ages of 19 and 45 yr) participated in the study.

Design: There were 3 d of a gradually advancing sleep/dark period (wake time 1 h earlier each morning), bright light on awakening [four 30-min bright-light pulses (approximately 5000 lux) alternating with 30 min room light < 60 lux] and afternoon melatonin, either 0.5 or 3.0 mg melatonin timed to induce maximal phase advances, or matching placebo. The dim light melatonin onset was measured before and after the treatment to determine the phase advance.

Results: There were significantly larger phase advances with 0.5 mg (2.5 h, n = 16) and 3.0 mg melatonin (2.6 h, n = 13), compared with placebo (1.7 h, n = 15), but there was no difference between the two melatonin doses. Subjects did not experience jet lag-type symptoms during the 3-d treatment

Conclusions: Afternoon melatonin, morning intermittent bright light, and a gradually advancing sleep schedule advanced circadian rhythms almost 1 h/d and thus produced very little circadian misalignment. This treatment could be used in any situation in which people need to phase advance their circadian clock, such as before eastward jet travel or for delayed sleep phase syndrome.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antioxidants / pharmacology*
  • Circadian Rhythm / drug effects*
  • Circadian Rhythm / radiation effects*
  • Female
  • Humans
  • Jet Lag Syndrome / psychology
  • Light*
  • Male
  • Melatonin / pharmacology*
  • Middle Aged
  • Patient Compliance
  • Sleep / drug effects
  • Sleep / radiation effects
  • Surveys and Questionnaires


  • Antioxidants
  • Melatonin