Plasma melatonin rhythm in humans was investigated: its stability, relationship to the sleep-wake rhythm, and response to light. The so-called day-to-day variation of reference phases of plasma melatonin rhythm was within 1.4 h when blood was sampled at 1-hour intervals. Therefore, a change in phase beyond this value is regarded as a phase shift of melatonin rhythm in individuals. Plasma melatonin rhythm was spontaneously desynchronized from the sleep-wake rhythm and probably regulated by the common circadian pacemaker which drives the rhythm in rectal temperature. When a bright-light pulse was applied, the melatonin rhythm produced a phase shift, but the amount of phase shift seems to be different for the ascending and descending phases of nocturnal melatonin rise. Finally, a partial entrainment was observed in a subject who developed a non-24-hour sleep-wake syndrome later, in which the plasma melatonin rhythm was free-running whereas the sleep-wake rhythm was apparently entrained by a 24-hour day-night alternation. It is concluded that the plasma melatonin rhythm is the best marker of the human circadian pacemaker so far available.
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Honma et al. (1997) studied this question.