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Older people typically exhibit poor sleep efficiency and reduced nocturnal plasma melatonin levels. The daytime administration of oral melatonin to younger people, in doses that raise their plasma melatonin levels to the nocturnal range, can accelerate sleep onset. We examined the ability of similar, physiological doses to restore nighttime melatonin levels and sleep efficiency in insomniac subjects over 50 yr old. In a double-blind, placebo-controlled study, subjects who slept normally (n = 15) or exhibited actigraphically confirmed decreases in sleep efficiency (n = 15) received, in randomized order, a placebo and three melatonin doses (0.1, 0.3, and 3.0 mg) orally 30 min before bedtime for a week. Treatments were separated by 1-wk washout periods. Sleep data were obtained by polysomnography on the last three nights of each treatment period. The physiologic melatonin dose (0.3 mg) restored sleep efficiency (P < 0.0001), acting principally in the midthird of the night; it also elevated plasma melatonin levels (P < 0.0008) to normal. The pharmacologic dose (3.0 mg), like the lowest dose (0.1 mg), also improved sleep; however, it induced hypothermia and caused plasma melatonin to remain elevated into the daylight hours. Although control subjects, like insomniacs, had low melatonin levels, their sleep was unaffected by any melatonin dose.

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The circadian dynamics of responses to cyclic guanosine 3',5'-monophosphate (cGMP) in in vitro experiments and the stimulating effects of the pineal hormone melatonin on cGMP levels both in vitro and in vivo provoked an investigation into the diurnal pattern of occurrence of this second messenger in human plasma and its correlation with plasma melatonin levels. Plasma cGMP levels were measured in 9 normal human subjects who were over 50 years of age. Samples were obtained hourly through a 20-h period (11 a.m. to 7 a.m.) that included the subjects' habitual hours of nocturnal sleep; physical activity was kept to a minimum during the daylight hours. The area under the time-plasma cGMP concentration curve showed a significant increase during the period of nocturnal sleep compared to that observed during the period of daytime wakefulness. The individual temporal pattern of the nocturnal rise in plasma cGMP differed among the subjects; however, the initial increase typically was observed soon after bedtime. No significant correlation was observed between individual nocturnal plasma melatonin levels and cGMP levels.