EXOGENOUS MELATONINS PHASE-SHIFTING EFFECTS ON THE ENDOGENOUS MELATONIN PROFILE IN SIGHTED HUMANS - A BRIEF REVIEW AND CRITIQUE OF THE LITERATURE

Melatonin's phase-shifting effects in humans are thought by some inves tigators to be subtle, particularly in comparison to those achieved wi th appropriately timed bright light exposure. The initial study in sig hted people was only intermittently successful in phase advancing the endogenous melatonin profile. The study of free-running blind people s howed statistically significant phase advances the day after melatonin administration. When holding the light-dark cycle constant, consisten t phase advances the day after melatonin administration in sighted peo ple were first shown in the course of describing the melatonin phase r esponse curve (PRC), which also provided the first evidence that melat onin could cause phase delays. More recent studies have replicated the PRC and shown that phase shifts can occur in response to physiologica l doses within 1 day. This article reviews this literature and attempt s to reconcile some of the results from differing studies. If the timi ng of melatonin administration is optimized according to the melatonin PRC, then consistent phase advances and delays can be achieved. If a reliable and sensitive circadian phase marker (e.g., the highly resolv ed dim Light melatonin onset) is used, then phase shifts can be demons trated consistently-even a small shift the day after a single physiolo gical dose. The present authors predict that in the near future, melat onin administration will become as useful as bright light exposure in the treatment of circadian phase disorders.