Acute phase-shifting effects of melatonin associated with suppression of core body temperature in humans

Appropriately administered melatonin is able to phase shift circadian rhythms, to induce transient sleepiness and to suppress core body temperature. The relationships between these phenomena have not been fully explored. In a double-blind, placebo-controlled crossover study, 8 healthy males maintained a regular sleep-wake cycle in a natural environment throughout. From dusk until 2400 h on days (D) 1-4 subjects were in dim artificial lighting (< 100 lux) with darkness (< 1 lux) from 2400-0800 h. Sunglasses were worn during the day when outside. At 1700 h on D3 either melatonin (5 mg) or placebo was administered. Saliva samples were collected at 30 min intervals, 1600-2400 h on D3 and D4, and subjective alertness rated at 30 min intervals from 1600-2400 h on D3 and hourly from 0800-2400 h D4. Sleep quality was rated on nights 2, 3 and 4 and core temperature was recorded throughout. Melatonin induced a significant suppression of temperature and alertness peaking 2.5 h after the dose, together with improved sleep quality on the night of D3 and a phase advance of the endogenous melatonin rhythm on D4. The degree of phase shift was related to the amount of temperature suppression in 6 of 7 subjects with detectable melatonin, suggesting that temperature suppression is an integral part of the phase-shifting mechanism.