Although melatonin treatment has been shown to phase shift human circadian rhythms, it still remains ambiguous as to whether exogenous melatonin can entrain a free-running circadian system. We have studied seven blind male subjects with no light perception who exhibited free-running urinary 6-sulphatoxymelatonin (aMT6s) and cortisol rhythms.In a single-blind design, five subjects received placebo or 5 mg melatonin p.o. daily at 2100 h for a full circadian cycle (35-71 days). The remaining two subjects also received melatonin (35-62 days) but not placebo. Urinary aMT6s and cortisol (n=7) and core body temperature (n=1) were used as phase markers to assess the effects of melatonin on the circadian system. During melatonin treatment, four of the seven free-running subjects exhibited a shortening of their cortisol circadian period (tau). Three of these had taus which were statistically indistinguishable from entrainment. In contrast, the remaining three subjects continued to free-run during the melatonin treatment at a similar tau as prior to and following treatment. The efficacy of melatonin to entrain the free-running cortisol rhythms appeared to be dependent on the circadian phase at which the melatonin treatment commenced.These results show for the first time that daily melatonin administration can entrain free-running circadian rhythms in some blind subjects assessed using reliable physiological markers of the circadian system.

The effect of photoperiod on melatonin content and the activity of the melatonin-synthesizing enzymes, namely, serotonin N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase, were investigated in the pineal gland and retina of turkeys. The birds were adapted to 3 different lighting conditions: 16L:8D (long photoperiod), 12L:12D (regular photoperiod), and 8L:16D (short photoperiod). Pineal, retinal, and plasma melatonin concentrations oscillated with a robust diurnal rhythm, with high values during darkness. The duration of elevated nocturnal melatonin levels in the turkey pineal gland, retina, and plasma changed markedly in response to the length of the dark phase, being longest during the short photoperiod with 16 h of darkness. These photoperiodic variations in melatonin synthesis appear to be driven by AANAT, because changes in the activity of this enzyme were closely correlated with changes in melatonin. By contrast, pineal and retinal hydroxyindole-O-methyltransferase activities failed to exhibit any significant 24-h variation in the different photoperiods. A marked effect of photoperiod on the level of melatonin production was also observed. Peak values of melatonin and AANAT activity in the pineal gland (but not in the retina) were highest during the long photoperiod. During the light phase, mean melatonin concentrations in the pineal gland and retina of turkeys kept under the long photoperiod were significantly higher compared with those from birds maintained under the regular and short photoperiods. In addition, mean circulating melatonin levels were lowest in the short photoperiod. Finally, the magnitude of the light-evoked suppression of nighttime pineal AANAT activity was also influenced by photoperiod, with suppression being smallest under the long photoperiod. These findings show that in the turkey, photoperiod plays an important role in regulating the melatonin signal.

Vitamin D status has been associated in recent years with an increasing variety of chronic diseases. Indeed, evidence is emerging that it may play a role in a wide range of diseases such as cancer, heart disease, autoimmune disease, dementia and diabetes (1) . Recent preliminary analysis of the 2005-2006 N-HANES (National Health and Nutrition Examination Survey) data in the US suggests vitamin D deficiency may be associated with shorter sleep duration (2) . However, to the authors' knowledge this result has not been re-tested in other datasets, or in other ethnic groups. Therefore, the aim of this study was to investigate whether there is an association between vitamin D status and self-reported sleep quality using data obtained from the D-FINES (vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England) study. In summer 2006, n 375 South Asian (A) and Caucasian (C) premenopausal (PRM) and post-menopausal (POM) women were assessed for vitamin D status (serum 25(OH)D) as well as relevant anthropometric and lifestyle information. A subset of the original participants (n 33A and n 80C) were re-assessed again in summer 2010 and also self-completed the PSQI (Pittsburgh Sleep Quality Index), which is a validated method for assessing self-reported sleep quality (3) .Partial correlations were run using PASW 18.0 to examine associations between 25(OH)D status (Summer 2006 results were used as Summer 2010 results were not yet available) and overall PSQI score, as well as between 25(OH)D and the subscales of the PSQI. The analysis controlled for the potential confounders of social deprivation index, age, physical activity and BMI. 25(OH)D and PSQI scores were skewed so were log transformed prior to analysis. Correlations were run with all participants pooled together, and also in separate ethnic and menopausal subgroups (see Table). No significant association (P ‡ 0.05) was found between 25(OH)D and total PSQI score for any of the participant subgroups. Also, no significant association was found between 25(OH)D and any of the PSQI subscales in any of the subgroups (data not shown), except for sleep duration, which in all participants together was statistically significant (r = -0.261, P = 0.01, df = 92) and of borderline significance for PRM women (r = -0.402, P = 0.07, df = 19). Also, a statistically significant result was found between 25(OH)D and habitual sleep efficiency in PRM women only (r = -0.455, P = 0.04, df = 19).Partial correlations between vitamin D status and total PSQI score by participant subgroups ALL POM

Light can induce an acute suppression and/or circadian phase shift of plasma melatonin levels in subjects with normal color vision. It is not known whether this photic suppression requires an integrated response from all photoreceptors or from a specialized subset of photoreceptors. To determine whether normal cone photoreceptor systems are necessary for light-induced melatonin suppression, we tested whether color vision-dificient human subjects experience light-induced melatonin suppression. In 1 study, 14 red-green color vision-deficient subjects and 7 normal controls were exposed to a 90-min, 200-lux, white light stimulus from 0200-0330 h. Melatonin suppression was observed in the controls (t = -7.04; P < 0.001), all color vision-deficient subjects (t = -4.76; P < 0.001), protanopic observers (t = -6.23; P < 0.005), and deuteranopic observers (t = -3.48; P < 0.05), with no significant difference in the magnitude of suppression between groups. In a second study, 6 red/green color vision-deficient males and 6 controls were exposed to a broad band green light stimulus (120 nm with lambda max 507 nm; mean +/- SEM, 305 +/- 10 lux) or darkness from 0030-0100 h. Hourly melatonin profiles (2000-1000 h) were not significantly different in onset, offset, or duration between the two groups. Melatonin suppression was also observed after exposure to the green light source at 0100 h (color vision deficient: t = -2.3; df = 5; P < 0.05; controls: t = -3.61; df = 5; P < 0.01) and 0115 h (color vision deficient: t = -2.74; df = 5; P < 0.05; controls: t = -3.57; df = 5; P < 0.01). These findings suggest that a normal trichromatic visual system is not necessary for light-mediated neuroendocrine regulation.

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