Kunz Dieter, Mahlberg Richard, Müller Cordula, Tilmann Amely, Bes Frederik
Department of Psychiatry and Psychotherapy, Charité Campus Mitte-Universitätsmedizin Berlin, 10117 Berlin, Germany.
J Clin Endocrinol Metab. 2004 Jan;89(1):128-34. doi: 10.1210/jc.2002-021057.
Recent data suggest that melatonin may influence human physiology, including the sleep-wake cycle, in a time-dependent manner via the body's internal clock. Rapid-eye-movement (REM) sleep expression is strongly circadian modulated, and the impact of REM sleep on primary brain functions, metabolic processes, and immune system function has become increasingly clear over the past decade. In our study, we evaluated the effects of exogenous melatonin on disturbed REM sleep in humans. Fourteen consecutive outpatients (five women, nine men; mean age, 50 yr) with unselected neuropsychiatric sleep disorders and reduced REM sleep duration (25% or more below age norm according to diagnostic polysomnography) were included in two consecutive, randomized, double-blind, placebo-controlled, parallel design clinical trials. Patients received 3 mg melatonin daily, administered between 2200 and 2300 h for 4 wk. The results of the study show that melatonin was significantly more effective than placebo: patients on melatonin experienced significant increases in REM sleep percentage (baseline/melatonin, 14.7/17.8 vs. baseline/placebo, 14.3/12.0) and improvements in subjective measures of daytime dysfunction as well as clinical global impression score. Melatonin did not shift circadian phase or suppress temperature but did increase REM sleep continuity and promote decline in rectal temperature during sleep. These results were confirmed in patients who received melatonin in the second study (REM sleep percentage baseline/placebo/melatonin, 14.3/12.0/17.9). In patients who received melatonin in the first study and placebo in the second, the above mentioned effects outlasted the period of melatonin administration and diminished only slowly over time (REM sleep percentage baseline/melatonin/placebo, 14.7/17.8/16.2). Our findings show that exogenous melatonin, when administered at the appropriate time, seems to normalize circadian variation in human physiology. It may, therefore, have a strong impact on general health, especially in the elderly and in shift workers.
近期数据表明，褪黑素可能通过人体内部生物钟以时间依赖的方式影响人体生理机能，包括睡眠-清醒周期。快速眼动（REM）睡眠的表现受到强烈的昼夜节律调节，在过去十年中，REM睡眠对大脑主要功能、代谢过程和免疫系统功能的影响越来越清晰。在我们的研究中，我们评估了外源性褪黑素对人类REM睡眠紊乱的影响。连续纳入14名门诊患者（5名女性，9名男性；平均年龄50岁），这些患者患有未经筛选的神经精神性睡眠障碍且REM睡眠时间缩短（根据诊断性多导睡眠图，低于年龄正常范围25%或更多），参与了两项连续的、随机的、双盲的、安慰剂对照的平行设计临床试验。患者每天在22:00至23:00之间服用3毫克褪黑素，持续4周。研究结果表明，褪黑素比安慰剂显著更有效：服用褪黑素的患者REM睡眠百分比显著增加（基线/褪黑素，14.7/17.8 vs. 基线/安慰剂，14.3/12.0），白天功能障碍的主观测量指标以及临床总体印象评分也有所改善。褪黑素并未改变昼夜节律相位或抑制体温，但确实增加了REM睡眠的连续性，并促进了睡眠期间直肠温度的下降。这些结果在第二项研究中接受褪黑素治疗的患者中得到了证实（REM睡眠百分比基线/安慰剂/褪黑素，14.3/12.0/17.9）。在第一项研究中接受褪黑素治疗而在第二项研究中接受安慰剂治疗的患者中，上述效果在褪黑素给药期之后仍然存在，并且随着时间的推移仅缓慢减弱（REM睡眠百分比基线/褪黑素/安慰剂，14.7/17.8/16.2）。我们的研究结果表明，外源性褪黑素在适当时间给药时，似乎可以使人体生理机能的昼夜变化正常化。因此，它可能对总体健康有很大影响，尤其是对老年人和轮班工作者。
