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Human circadian rhythms: physiological and therapeutic relevance of light and melatonin

Ocular light plays a key role in human physiology by transmitting time of day information. The production of the pineal gland hormone melatonin is under the control of the light-dark cycle. Its profile of secretion defines biological night and it has been called the 'darkness hormone'. Light mediates a number of non-visual responses, such as phase shifting the internal circadian clock, increasing alertness, heart rate and pupil constriction. Both exogenous melatonin and light, if appropriately timed, can phase shift the human circadian system. These 'chronobiotic' effects of light and melatonin have been used successfully to alleviate and correct circadian rhythm disorders, such as those experienced following travel across time zones, in night shift work and in circadian sleep disorders. The effectiveness of melatonin and light are currently being optimized in terms of time of administration, light intensity, duration and wavelength, and melatonin dose and formulation. The aim of this review is not to replicate information that has been reported in a number of reviews of the human circadian timing system and the role of melatonin and light, but rather to extract findings relevant to the field of clinical biochemistry.