Combination of light and melatonin time cues for phase advancing the human circadian clock

Sleep. 2013 Nov 1;36(11):1617-24. doi: 10.5665/sleep.3110.


Study objectives: Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure.

Design: Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time.

Setting: Sleep and chronobiology laboratory environment free of time cues.

Participants: Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD).

Results: Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances.

Conclusion: Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.

Keywords: Light response; phase shift; zeitgeber.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Circadian Clocks / drug effects
  • Circadian Clocks / physiology*
  • Circadian Clocks / radiation effects
  • Cues
  • Double-Blind Method
  • Female
  • Humans
  • Light
  • Male
  • Melatonin / administration & dosage
  • Melatonin / analysis
  • Melatonin / pharmacology*
  • Photic Stimulation*
  • Saliva / chemistry
  • Young Adult


  • Melatonin