Although light is accepted as the dominant zeitgeber for entrainment of the human circadian system, there is evidence that nonphotic stimuli may play a role. This review critically assesses the current evidence in support of nonphotic entrainment in humans. Studies involving manipulations of sleep-wake schedules, exercise, mealtimes, and social stimuli are re-examined, bearing in mind the fact that the human circadian clock is sensitive to very dim light and has a free-running period very close to 24 h. Because of light confounds, the study of totally blind subjects with free-running circadian rhythms represents the ideal model to investigate the effects of nonphotic stimuli on circadian phase and period. Strong support for nonphotic entrainment in humans has already come from the study of a few blind subjects with entrained circadian rhythms. However, in these studies the nonphotic stimulus(i) responsible was not identified. The effect of appropriately timed exercise or exogenous melatonin represents the best proof to date of an effect of nonphotic stimuli on human circadian timing. Phase-response curves for both exercise and melatonin have been constructed. Given the powerful effect of feeding as a circadian zeitgeber in various nonhuman species, studies of meal timing are recommended. In conclusion, the available evidence indicates that it remains worthwhile to continue to study nonphotic effects on human circadian timing to identify treatment strategies for shift workers and transmeridian travelers as well as for the blind and possibly the elderly.
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