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The Effects of Low-Dose 0.5-mg Melatonin on the Free-Running Circadian Rhythms of Blind Subjects

Centre for Chronobiology, School of Biomedical and Life Sciences, University of Surrey, Guildford, GU2 7XH, UK

Steven W. Lockley

Centre for Chronobiology, School of Biomedical and Life Sciences, University of Surrey, Guildford, GU2 7XH, UK

Josephine Arendt

Centre for Chronobiology, School of Biomedical and Life Sciences, University of Surrey, Guildford, GU2 7XH, UK

Debra J. Skene

Centre for Chronobiology, School of Biomedical and Life Sciences, University of Surrey, Guildford, GU2 7XH, UK, d.skene{at}surrey.ac.uk

Exogenous melatonin (0.5-10 mg) has been shown to entrain the free-running circadian rhythms of some blind subjects. The aim of this study was to assess further the entraining effects of a daily dose of 0.5 mg melatonin on the cortisol rhythm and its acute effects on subjective sleep in blind subjects with free-running 6-sulphatoxymelatonin (aMT6s) rhythms (circadian period [] 24.23-24.95 h). Ten subjects (9 males) were studied, aged 32 to 65 years, with no conscious light perception (NPL). In a placebo-controlled, single-blind design, subjects received 0.5 mg melatonin or placebo p.o. daily at 2100 h (treatment duration 26-81 days depending on individuals' circadian period). Subjective sleep was assessed from daily sleep and nap diaries. Urinary cortisol and aMT6s were assessed for 24 to 48 h weekly and measured by radioimmunoassay. Seven subjects exhibited an entrained or shortened cortisol period during melatonin treatment. Of these, 4 subjects entrained with a period indistinguishable from 24 h, 2 subjects continued to run for up to 25 days during melatonin treatment before their cortisol rhythm became entrained, and 1 subject appeared to exhibit a shortened cortisol period throughout melatonin treatment. The subjects who entrained within 7 days did so when melatonin treatment commenced in the phase advance portion of the melatonin PRC (CT6-18). When melatonin treatment ceased, cortisol and aMT6s rhythms free ran at a similar period to before treatment. Three subjects failed to entrain with initial melatonin treatment commencing in the phase delay portion of the PRC. During melatonin treatment, there was a of free significant increase in nighttime sleep duration and a reduction in the number and duration of daytime naps. The positive effect of melatonin on sleep may be partly due to its acute soporific properties. The findings demonstrate that a daily dose of 0.5 mg melatonin is effective at entraining the free-running circa-dian systems in most of the blind subjects studied, and that circadian time (CT) of administration Optimal melatonin may be important entrains to melatonin treatment. 24-h sleep disorder should p.o. in determining whether a subject disorder the sleep-wake cycle) in addition to improving sleep acutely. correct treatment with melatonin for the underlying circadian this (to non-entrain

Key Words: melatonin • circadian rhythms • blindness • cortisol • sleep • napping

Journal of Biological Rhythms, Vol. 18, No. 5, 420-429 (2003)
DOI: 10.1177/0748730403256796


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