Melatonin Does Not Shift the Circadian Clock, But Promotes Sleep at Bedtime

Contrary to popular belief, melatonin does not shift circadian rhythms when taken for conditions like jet lag, but it can promote sleep if taken in the evening, a study by Yale researchers has found.

Circadian rhythms are 24-hour rhythms generated by a biological clock in the brain and include an individual’s 24-hour sleep/wake schedule. Melatonin is a hormone produced and secreted by the pineal gland at the base of the brain during the sleep phase of the circadian cycle.

Disruption in the relationship of circadian rhythms with the light-dark cycle can be caused by travel to different time zones or working a night shift in a job. This can result in sleep difficulties, reduced alertness, and impaired job performance. The popular belief is that melatonin can rapidly reset the biological clock and restore the circadian equilibrium. But the Yale study published in the Journal of Clinical Endocrinology and Metabolism presented a contrary finding.

“We have found under rigorous conditions very difficult to achieve in clinical studies that there is no evidence melatonin shifts the circadian clock, although it can induce sleepiness when taken in the evening,” said Scott Rivkees, associate professor in the Section of Pediatric Endocrinology at Yale School of Medicine.

Rivkees and his co-researcher, Haiping Hao, a postdoctoral associate in pediatrics, studied the effects of melatonin on circadian phase in primates that have sleep/wake cycles similar to humans.

Baseline circadian phase was measured over a two-week period. Melatonin was administered in varying doses at different times of day and changes in the circadian phase were assessed.

“Surprisingly, at all doses and times tested, melatonin did not shift the circadian phase,” Rivkees said. “But, although melatonin did not shift rhythms at any of the doses tested, it acutely reduced activity levels and induced sleep.” These effects only occurred when the doses were administered in the evening.

“The effects we saw, which we call hypnotic effects, were time of day dependent,” Rivkees said. “The same dose of melatonin given during midday or morning did not induce sleep.”

A separate recent study published in the New England Journal of Medicine showed that melatonin administered to blind individuals at the same time each day kept the subjects’ circadian clocks from drifting.

“We looked at something different,” Rivkees said. “We wanted to know if giving melatonin could actually cause the clock to shift and reset. We found that melatonin, given as is currently prescribed for conditions such as jet lag, does not shift the circadian clock. These observations raise the possibility that the beneficial effects of melatonin seen in the treatment of jet lag or other circadian disorders are not due to phase-shifting effects of this commonly used pineal hormone, but may be due to its well recognized hypnotic properties.”