Urinary Melatonin Research Articles

Abstract B37: Urinary melatonin levels and risk of breast cancer in the Nurses' Health Study II

Abstract Shift work has been hypothesized to increase breast cancer risk as two recent meta-analyses suggest a 21- 51% increased risk of breast cancer in women reporting night shift work. Melatonin, a hormone produced by the pineal gland that follows a circadian rhythm with highest levels observed at night, is frequently referenced as the biological mechanism through which shift work may increase breast cancer risk. While decreased urinary melatonin levels are associated with an increased risk of breast cancer in postmenopausal women, only three studies have evaluated the association between melatonin levels and breast cancer in premenopausal women with inconsistent findings. Therefore, we investigated this relationship in predominantly premenopausal women by conducting a nested case-control study in the prospective Nurses' Health Study II cohort. From 1996 to 1999, first morning urine was collected from 29,613 cancer-free participants who were followed through June 2007. Incident breast cancer was confirmed through review of medical records and pathology reports, and potential confounders were reported on biennial questionnaires and a questionnaire administered at urine collection. Concentrations of 6-sulfatoxymelatonin (aMT6s), the major metabolite of melatonin, were available for 603 cases and 798 controls matched for age, menopausal status, ethnicity, fasting status, luteal day of menstrual cycle, and month, year, day, and time of urine collection. We used multivariable conditional logistic regression models to estimate the risk of breast cancer by quartile of urinary aMT6s concentrations, with cutpoints based on values of control participants. We did not observe an association between melatonin levels and risk of breast cancer (odds ratio for highest versus lowest aMT6s quartile: 0.87, 95% confidence interval: 0.57-1.35). Our results were largely unchanged when we examined the relationship between urinary melatonin levels and invasive breast cancer (n=443 cases, odds ratio for highest versus lowest aMT6s quartile: 0.91, 95% CI: 0.54-1.56), in situ breast cancer (n=160 cases, odds ratio for highest versus lowest aMT6s quartile: 1.23, 95% CI: 0.45-3.35), and among women with ER+ tumors (n=398 cases, odds ratio for highest versus lowest aMT6s quartile: 0.77, 95% CI: 0.44-1.34). These prospective data do not provide strong support for a significant association between urinary melatonin levels and breast cancer risk in predominantly premenopausal women. Citation Format: Susan Boyer Brown, Susan E. Hankinson, Eva S. Schernhammer. Urinary melatonin levels and risk of breast cancer in the Nurses' Health Study II. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B37.

Changing the Direction of Sleep Medicine: Business can Boom, but it is Not as Usual

Changing the Direction of Sleep Medicine: Business can Boom, but it is Not as Usual

Exposure to light at night and risk of depression in the elderly

BackgroundRecent advances in understanding the fundamental links between chronobiology and depressive disorders have enabled exploring novel risk factors for depression in the field of biological rhythms. Increased exposure to light at night (LAN) is common in modern life, and LAN exposure is associated with circadian misalignment. However, whether LAN exposure in home settings is associated with depression remains unclear. MethodsWe measured the intensities of nighttime bedroom light and ambulatory daytime light along with overnight urinary melatonin excretion (UME) in 516 elderly individuals (mean age, 72.8). Depressive symptoms were assessed using the Geriatric Depression Scale. ResultsThe median nighttime light intensity was 0.8lx (interquartile range, 0.2–3.3). The depressed group (n=101) revealed significantly higher prevalence of LAN exposure (average intensity, ≥5lx) compared with that of the nondepressed group (n=415) using a multivariate logistic regression model adjusted for daytime light exposure, insomnia, hypertension, sleep duration, and physical activity [adjusted odds ratio (OR): 1.89; 95% confidence interval (CI), 1.10–3.25; P=0.02]. Consistently, another parameter of LAN exposure (duration of intensity ≥10lx, ≥30min) was significantly more prevalent in the depressed than in the nondepressed group (adjusted OR: 1.71; 95% CI, 1.01–2.89; P=0.046). In contrast, UME was not significantly associated with depressive symptoms. LimitationCross-sectional analysis. ConclusionThese results suggested that LAN exposure in home settings is significantly associated with depressive symptoms in the general elderly population. The risk of depression may be reduced by keeping nighttime bedroom dark.

The influence of vitamin D supplementation on melatonin status in patients with multiple sclerosis

Multiple sclerosis (MS) incidence is higher in geographic regions with less sunlight exposure. Both vitamin D and melatonin are essential mediators of the effect of sunlight in health, and as such are candidates to play a key role in MS. We hypothesized that vitamin D and melatonin may have related influences in patients with MS. In a randomized, double blind study of 40 IFN-β treated MS patients, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 19 patients received 4,370 IU vitamin D3 per day (high dose) for one year. Serum 25-hydroxy-vitamin-D (25-OH-D) and nighttime urine melatonin metabolite, 6-sulphatoxy-melatonin (6-SMT), were measured at baseline, 3 months and 1 year from enrolment. After 3 months supplementation, 25-OH-D levels increased and nighttime melatonin secretion decreased significantly in the high dose group, but not in the low dose group. After 1 year, a decrease in 25-OH-D levels, accompanied by an increase of urine nighttime 6-SMT were observed in the high dose group. Percent change in serum 25-OH-D was significantly and negatively correlated with percent change in urine 6-SMT after 3 months and between 3 months to 1 year. 25-OH-D levels by the end of the study were significantly and negatively correlated to BMI. Melatonin secretion is negatively correlated with alterations in serum 25-OH-D in IFN-β treated patients with MS. The finding suggests that melatonin should be considered as a potential mediator of vitamin D neuro-immunomodulatory effects in patients with MS.

Nocturnal urinary melatonin excretion is associated with non-dipper pattern in elderly hypertensives

Although oral melatonin administration may enhance a nocturnal blood pressure fall, it remains unclear whether endogenous melatonin, which is present at considerably lower levels than pharmacological melatonin, is associated with the non-dipper pattern. The present cross-sectional study aimed to determine the association between urinary melatonin excretion, an index of endogenous melatonin, and the non-dipper pattern. We measured the following variables in 141 elderly hypertensives: overnight urinary melatonin excretion, ambulatory blood pressure and actigraphic physical activity. We defined a non-dipper pattern as a <10% fall in sleep systolic blood pressure compared with awake systolic blood pressure. When participants were divided into two groups (high and low melatonin groups) by the cutoff value for identifying the top tertile, the characteristics, except for age, did not significantly differ between the two groups. Crude logistic regression analysis showed significant associations of the non-dipper pattern with age, diabetes, higher urinary melatonin excretion (high vs. low) and daytime activity. In a multivariate analysis after adjustment for age, diabetes and daytime activity, the odds ratio for the non-dipper pattern in the high melatonin group was significantly lower than that in the low melatonin group (odds ratio: 0.39, 95% confidence interval (CI): 0.17-0.91, P=0.03). Moreover, the mean percentage systolic blood pressure nocturnal fall, adjusted for the former covariates, was significantly higher in the high melatonin group than the low melatonin group (difference 3.5%, 95% CI: 0.0-7.0%, P=0.048). Among elderly hypertensive individuals, nocturnal urinary melatonin excretion is significantly and inversely associated with the non-dipper pattern.

Optical sensing of urinary melatonin with molecularly imprinted poly(ethylene-co-vinyl alcohol) coated zinc oxide nanorod arrays

In this work, aligned zinc oxide (ZnO) nanorods were selectively hydrothermally grown on acetate-seeded spots on a gold substrate; the nanorods had an average length and diameter of 1.7μm and 240nm, respectively. Melatonin was imprinted into poly(ethylene-co-vinyl alcohol), EVAL, which was coated onto ZnO nanorod arrays. The ZnO nanorods not only increased the surface area for sensing target molecules, but also constituted an optical sensing element, as the ZnO fluorescence decreases when targets bind to the imprinted EVAL film; the fluorescence decrease, as a function of melatonin concentration, is well fit by a Langmuir adsorption isotherm. Poly(ethylene-co-vinyl alcohol) with 44mol% ethylene showed the best imprinting effectiveness (ratio of the fluorescence decrease on binding melatonin to imprinted vs. non-imprinted EVAL-coated ZnO nanorod arrays) among the several compositions studied. In real urine analysis, the MIP films responded linearly to added (exogenous) melatonin, even in the presence of many possible interfering compounds in urine. This demonstrates the feasibility of using these MIPs as part of a total urinalysis MIP system.

Poor sleep in PCOS; is melatonin the culprit?

Are daily cycles in urinary melatonin and oxidative stress marker levels (8-hydroxydeoxyguanosine) altered in PCOS, and is this associated with changes in sleep quality? There is an association between elevated nighttime melatonin and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and poor sleep quality in our PCOS study group. Women with PCOS are known to have poorer sleep. However, there have been few studies examining the possible association between melatonin levels and sleep quality in women with polycystic ovarian syndrome (PCOS). This is a case-control study of PCOS (n = 26) and non-PCOS control (n = 26) subjects recruited from a tertiary gynaecological centre. The participants were requested to complete sleep questionnaires for a month. In a subgroup from these cohorts (PCOS, n = 15; controls, n = 18), urine samples were also collected at various time points over a 24-h period. In addition, their sleep patterns and lighting environment were monitored for 3 consecutive days and nights using a wrist-mounted Actiwatch device. PCOS women had significantly elevated night-time urinary levels of the melatonin metabolite 6-sulfatoxymelatonin (aMT6s) and of 8-OHdG (both at P < 0.05), as well as significantly reduced sleep quality (P < 0.05), compared with the controls. Due to the small sample size of the study, further studies will be required to confirm our findings. Our preliminary work provides a possible new insight into the interactions between melatonin, increased oxidative stress and sleep in women with PCOS. The study was funded by the Faculty of Medicine, University of Southampton.

Large neutral amino acid supplementation increases melatonin synthesis in phenylketonuria: a new biomarker.

To determine whether levels of melatonin in blood and urine can serve as a peripheral biomarker to reflect brain serotonin synthesis in individuals with phenylketonuria (PKU). We measured the levels of melatonin, a serotonin metabolite in the pinealocytes, in the blood and urine of individuals with PKU in a randomized double-blind placebo controlled crossover study consisting of three 3-week phases in 10 adults with PKU: phase 1 (washout), phase 2 (supplementation of large neutral amino acid [LNAA] tablets or placebo), and phase 3 (alternate supplementation). An overnight protocol to measure blood melatonin and urine 6-sulfatoxymelatonin and dopamine in first void urine specimens was conducted after each phase for subjects with PKU and once in 10 controls. Significantly lower concentrations of these neurotransmitter metabolites were observed in subjects with PKU after phase 1 compared with controls (serum melatonin P = .008, urine melatonin P = .0043, urine dopamine P < .0001), with significant increases after LNAA supplementation compared with the placebo phase (serum melatonin P = .0008, urine melatonin P = .0008, urine dopamine P = .0005). The mean tryptophan/LNAA and tyrosine/LNAA ratios were markedly lower in subjects with PKU compared with controls, and these ratios were significantly increased in the LNAA phase compared with the placebo phase (P = .016, P = .0003, respectively). Blood phenylalanine levels in subjects with PKU were not significantly different between placebo and LNAA phases (P = .74). Blood and urine melatonin levels may serve as biomarkers reflecting brain serotonin synthesis in subjects with PKU. Because this cannot be evaluated using blood phenylalanine levels, it may provide information on neurotransmitter metabolism for optimal dietary management.

Abstract B90: Variation in circadian rhythm genes and risk of prostate cancer in the AGES-Reykjavik cohort

Abstract Background: Disruption of sleep duration or circadian rhythms has been associated with an increased risk of prostate cancer. Studies have suggested that circadian genes may be involved in regulating cancer-related pathways, such as cell proliferation, DNA damage response and apoptosis. As such, we hypothesized that genetic susceptibility to prostate cancer may be in part due to common variation in the core circadian rhythm genes. We assessed the association of genetic variation in core circadian rhythm genes with risk of prostate cancer and with urinary levels of melatonin among men in the prospective Age, Gene/Environment Susceptibility (AGES)-Reykjavik study. Methods: The study population was 1,352 men in the AGES-Reykjavik cohort with data from a previous genome wide association study. We examined 96 single-nucleotide polymorphisms (SNPs) across twelve genes chosen to represent common variation in genes that control the circadian rhythm (CLOCK, neuronal PAS domain protein 2 (NPAS2), aryl hydrocarbon receptor nuclear translocator-like (ARNTL), cryptochrome 1(CRY1), cryptochrome 2 (CRY2), period 1 (PER1), period 2 (PER2), period 3 (PER3), casein kinase 1-epsilon (CSNK1E)), two melatonin receptor genes (MTNR1A and MTNR1B), and the Timeless (TIM) gene. Melatonin levels were determined from first morning void urine samples using an ELISA assay. Prostate cancer (N = 138) was identified from hospital records using ICD codes; death from prostate cancer (N = 24) was determined from nationwide death records. We used unconditional logistic regression to evaluate the association between each SNP and overall and lethal prostate cancer. Linear regression was used to assess the association between each SNP and log-transformed melatonin levels. Finally, to test whether multimarker SNP-sets in the pathway were associated with prostate cancer or melatonin levels, we used a kernel machine test. Results: None of the 96 SNPs evaluated were significantly associated with prostate cancer overall. The variant allele in two SNPs in CRY1 (rs7297614 and rs1921126) and one in PER1 (rs2289591) were nominally (p-value &amp;lt;0.05 without adjusting for multiple testing) associated with an elevated risk of lethal prostate cancer, while SNPs in NPAS2 (rs3754674), ARNTL (rs969485) and PER2 (rs10462023) were nominally associated with a reduced risk of lethal disease. Among men without cancer, 4 SNPs in TIM and 6 in NPAS2 were nominally associated with lower levels of urinary melatonin; 2 SNPs in PER3 and 1 in CSNK1E were associated with higher levels of urinary melatonin. Pathway analyses showed that variability across the individual genes CRY1 and PER2 were nominally associated with lethal prostate cancer (p-value 0.01 and 0.05, respectively). For melatonin levels, the set of SNPs across all 12 genes and TIM was nominally associated with urinary melatonin levels (p-value 0.05 and 0.02, respectively). Conclusion: Variation in circadian genes, such as PER1, CRY1, and CRY2, has been previously associated with increased prostate cancer risk; variation in NPAS2 has been associated with reduced prostate cancer risk. Similar to previously reported literature, we observed several suggestive associations between variation in genes that regulate the circadian rhythm and lethal prostate cancer risk as well as urinary melatonin levels. Our findings provide further support for a role of circadian disruption in prostate cancer progression. Citation Format: Sarah Coseo Markt, Unnur A. Valdimarsdottir, Lara G. Sigurdardottir, Irene M. Shui, Jennifer R. Rider, Julie L. Kasperzyk, Steven W. Lockley, Charles A. Czeisler, Meir J. Stampfer, Thor Aspelund, Albert Vernon Smith, Vilmundur Gudnason, Lorelei A. Mucci. Variation in circadian rhythm genes and risk of prostate cancer in the AGES-Reykjavik cohort. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B90.

Exposure to Light at Night, Nocturnal Urinary Melatonin Excretion, and Obesity/Dyslipidemia in the Elderly: A Cross-Sectional Analysis of the HEIJO-KYO Study

Obesity and exposure to light at night (LAN) have increased globally. Although LAN suppresses melatonin secretion and disturbs body mass regulation in experimental settings, its associations with melatonin secretion, obesity, and other metabolic consequences in uncontrolled home settings remain unclear. The aim of this study was to determine the association of exposure to LAN in an uncontrolled home setting with melatonin secretion, obesity, dyslipidemia, and diabetes. A cross-sectional study was performed in 528 elderly individuals (mean age, 72.8 yr). The intensity of LAN in the bedroom was measured at 1-min intervals during two consecutive nights, along with overnight urinary melatonin excretion and metabolic parameters. Compared with the Dim group (average <3 lux; n = 383), the LAN group (average ≥3 lux; n = 145) showed significantly higher body weight (adjusted mean, 58.8 vs. 56.6 kg; P = 0.01), body mass index (23.3 vs. 22.7 kg/m(2); P = 0.04), waist circumference (84.9 vs. 82.8 cm; P = 0.01), triglyceride levels (119.7 vs. 99.5 mg/dl; P < 0.01), and low-density lipoprotein cholesterol levels (128.6 vs. 122.2 mg/dl; P = 0.04), and showed significantly lower high-density lipoprotein cholesterol levels (57.4 vs. 61.3 mg/dl; P = 0.02). These associations were independent of numerous potential confounders, including urinary melatonin excretion. Furthermore, LAN exposure is associated with higher odds ratios (ORs) for obesity (body mass index: OR, 1.89; P = 0.02; abdominal: OR, 1.62; P = 0.04) and dyslipidemia (OR, 1.72; P = 0.02) independent of demographic and socioeconomic parameters. In contrast, urinary melatonin excretion and glucose parameters did not show significant differences between the two groups. Exposure to LAN in an uncontrolled home setting is associated with impaired obese and lipid parameters independent of nocturnal urinary melatonin excretion in elderly individuals. Moreover, LAN exposure is associated with higher ORs for obesity and dyslipidemia independent of demographic and socioeconomic parameters.

Differential effects of light at night and shift rotation pattern on the circadian system in night workers.

1556 Background: Light at night as in shift work suppresses nocturnal secretion of melatonin, a pineal hormone with oncostatic properties. Several studies have associated night shift work with higher risk of cancer, leading WHO in 2007 to classify rotating night shift work as “probably carcinogenic”. We conducted one of the most comprehensive studies, to date, to evaluate the effects of light and night shift work on melatonin measurements in the field. Methods: Study participants were 130 active nurses (84 current rotating night shift workers and 46 day shift workers) participating in NHS2. Each nurse wore a head-mounted light- and accelerometer for a 3-day study period, during which each spontaneous urine was collected for repeated urinary 6-sulfatoxymelatonin (melatonin) measurements. In addition, nurses were asked to fill out paper questionnaires and diaries. We used mixed models to evaluate the influence of light, activity and night shift work on urinary melatonin level adjusting, for age, lifestyle, and occupational history. We log-transformed main variables and report geometric means (GM [standard deviation]). Results: Greater levels of light were associated with lower melatonin (P &lt; 0.0001), independent of activity level. An increase in light intensity from 10 to 100 lux was associated with a 12% decrease in geometric mean of melatonin level; however, this inverse association was only significant at night (Ptrend = 0.01). At night, each hour increase in exposure to ≥ 20 lux light lowered melatonin level by 5.7% (Ptrend &lt; 0.0001). A single night shift affected the circadian system by lowering melatonin peak by 22% (day shift: GM = 17.57 [2.73]; night shift: GM = 13.64 [2.54]) and induced a phase shift (PS) of 0.9 hours, -changes that reset to normal by the next day. Two consecutive night shifts had a similar effect as a single shift. However, the effect was worse after three consecutive night shifts (GM = 10.11 [2.77]; PS = 2.2 hours). Conclusions: We found significant inverse associations of intensity and duration of exposure to light at night with urinary melatonin, independent of activity level. Three consecutive night shifts affected the circadian system more strongly than two consecutive, or a single night shift.

Biological and physiological markers of tactile sensorial processing in healthy newborns.

The main objective of this review is to provide a descriptive analysis of the biological and physiological markers of tactile sensorial processing in healthy, full-term newborns. Research articles were selected according to the following study design criteria: (a) tactile stimulation for touch sense as an independent variable; (b) having at least one biological or physiological variable as a dependent variable; and (c) the group of participants were characterized as full-term and healthy newborns; a mixed group of full-term newborns and preterm newborns; or premature newborns with appropriate-weight-for-gestational age and without clinical differences or considered to have a normal, healthy somatosensory system. Studies were then grouped according to the dependent variable type, and only those that met the aforementioned three major criteria were described. Cortisol level, growth measures, and urinary catecholamine, serotonin, and melatonin levels were reported as biological-marker candidates for tactile sensorial processing. Heart rate, body temperature, skin-conductance activity, and vagal reactivity were described as neurovegetative-marker candidates. Somatosensory evoked potentials, somatosensory evoked magnetic fields, and functional neuroimaging data also were included.

Sleep duration and endometrial cancer risk

Recent data indicate that night shift work is associated with increased endometrial cancer risk, perhaps through a pathway involving lower melatonin production. Melatonin is an antiestrogenic hormone, with production in a circadian pattern that is dependent on presence of dark at night. Sleep duration is positively associated with melatonin production and may be an indicator of melatonin levels in epidemiologic studies. We evaluated associations between self-reported sleep duration and endometrial cancer risk using publicly available prospective data on 48,725 participants in the Women's Health Initiative Observational Study, among whom 452 adjudicated incident cases of endometrial cancer were diagnosed over approximately 7.5 years of follow-up. Sleep duration was self-reported at baseline. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for endometrial cancer risk with adjustment for potential confounders. Most women reported sleeping ≤ 6 (33.3%) or 7 (38.5%) h each night; fewer reported sleeping 8 (23.4%) or ≥ 9 (4.8%) h each night. In adjusted analyses, there was an indication of reduced risk associated with longer sleep duration, though no statistically significant association was observed. Women who slept ≥ 9 h had a nonsignificant reduced risk of endometrial cancer compared with women who slept ≤ 6 h (HR = 0.87; 95% CI = 0.51-1.46). We found weak evidence of an association between sleep duration and endometrial cancer risk. Self-reported sleep duration may not adequately represent melatonin levels, thus further studies utilizing urinary melatonin levels are necessary to establish the mechanism by which night shift work increases endometrial cancer risk.

Neuroimmune endocrine effects of antidepressants

Antidepressant pharmacotherapy is to date the most often used treatment for depression, but the exact mechanism of action underlying its therapeutic effect is still unclear. Many theories have been put forward to account for depression, as well as antidepressant activity, but none of them is exhaustive. Neuroimmune endocrine impairment is found in depressed patients; high levels of circulating corticosteroids along with hyperactivation of the immune system, high levels of proinflammatory cytokines, low levels of melatonin in plasma and urine, and disentrainment of circadian rhythms have been demonstrated. Moreover, antidepressant treatment seems to correct or at least to interfere with these alterations. In this review, we summarize the complex neuroimmune endocrine and chronobiological alterations found in patients with depression and how these systems interact with each other. We also explain how antidepressant therapy can modify these systems, along with some possible mechanisms of action shown in animal and human models.

Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality

Tart Montmorency cherries have been reported to contain high levels of phytochemicals including melatonin, a molecule critical in regulating the sleep-wake cycle in humans. The aim of our investigation was to ascertain whether ingestion of a tart cherry juice concentrate would increase the urinary melatonin levels in healthy adults and improve sleep quality. In a randomised, double-blind, placebo-controlled, crossover design, 20 volunteers consumed either a placebo or tart cherry juice concentrate for 7 days. Measures of sleep quality recorded by actigraphy and subjective sleep questionnaires were completed. Sequential urine samples over 48 h were collected and urinary 6-sulfatoxymelatonin (major metabolite of melatonin) determined; cosinor analysis was used to determine melatonin circadian rhythm (mesor, acrophase and amplitude). In addition, total urinary melatonin content was determined over the sampled period. Trial differences were determined using a repeated measures ANOVA. Total melatonin content was significantly elevated (P < 0.05) in the cherry juice group, whilst no differences were shown between baseline and placebo trials. There were significant increases in time in bed, total sleep time and sleep efficiency total (P < 0.05) with cherry juice supplementation. Although there was no difference in timing of the melatonin circardian rhythm, there was a trend to a higher mesor and amplitude. These data suggest that consumption of a tart cherry juice concentrate provides an increase in exogenous melatonin that is beneficial in improving sleep duration and quality in healthy men and women and might be of benefit in managing disturbed sleep.

Moderate Alcohol Consumption and 24-Hour Urinary Levels of Melatonin in Postmenopausal Women

Low overnight urinary melatonin metabolite concentrations have been associated with increased risk for breast cancer among postmenopausal women. The Postmenopausal Women's Alcohol Study was a controlled feeding study to test the effects of low to moderate alcohol intake on potential risk factors for breast cancer including serum and urinary levels of hormones and other biomarkers. Previously, we observed significant increases in concentrations of serum estrone sulfate and dehydroepiandrosterone sulfate in participants after consumption of 15 or 30 g (one or two drinks) of alcohol per day. In the present analysis, we evaluated the relationship of alcohol consumption with 24-h urinary 6-sulfatoxymelatonin (6-SMT) concentration (micrograms per 24 h). Healthy postmenopausal women (n = 51) consumed a controlled diet plus each of three treatments (a nonalcoholic placebo beverage or 15 or 30 g alcohol/d) during three 8-wk periods in random order under conditions of weight maintenance. 6-SMT was measured in 24-h urine samples that were collected at entry into the study (baseline) and at the midpoint (4 wk) and end (8 wk) of each of the three diet periods. Concentration of 6-SMT was not significantly modified by the alcohol treatment after adjustment for body mass index, hours of sleep, daylight hours, and baseline level of 6-SMT. These results suggest that low to moderate daily alcohol consumption does not significantly affect 24-h urinary levels of melatonin among healthy postmenopausal women.

Associations of urinary 6-sulfatoxymelatonin with biomarkers related to cardiovascular disease in Japanese women

Melatonin's potential preventive effect against cardiovascular disease (CVD) remains hypothetical. No study has evaluated the relationships between endogenous melatonin and the established blood biomarkers related to CVD. The objective of the present study is to examine the association between the endogenous melatonin level and various established blood biomarkers of risk of CVD, including white blood cell (WBC) count and plasma concentrations of lipids, homocysteine, uric acid (UA), and high-sensitivity C-reactive protein (hs-CRP). This cross-sectional study included 181 Japanese women who attended a health checkup program provided by a general hospital between March 2005 and March 2006. All study subjects responded to a self-administered questionnaire and were measured for weight, height, and blood pressure. Venous fasting blood and first-void morning urine were obtained from all subjects. Statistically significant inverse correlations were observed between urinary 6-sulfatoxymelatonin (aMT6s), the major metabolite of melatonin in urine, and WBC count, UA, and hs-CRP after controlling for age, body mass index, menopausal status, smoking status, diet, sleeping habits, and exercise ( r = −0.19, −0.21, and −0.24, respectively). There were no significant correlations between urinary aMT6s and plasma lipids and homocysteine. These data suggested that the urinary aMT6s level was inversely associated with established independent risk factors for CVD, such as WBC, UA, and hs-CRP. Endogenous melatonin may have implications for the risk of CVD.

Physical Activity, Sedentary Behavior, and Melatonin Among Rotating Shift Nurses

To determine the effect of physical activity and sedentary behavior on melatonin levels in a group of rotating shift nurses. Physical activity and sedentary behaviors for 118 nurses were recorded during both a day shift and a night shift using activity diaries, and concentrations of urinary 6-sulfatoxymelatonin were analyzed for each shift. During the day shift, energy expended in moderate- and vigorous-intensity physical activity between 3 PM and 7 AM was negatively associated with melatonin levels (P = 0.024). During the night shift, energy expended in sedentary behaviors was negatively associated with melatonin levels (P = 0.008). Physical activity and energy expended in sedentary behavior are inversely associated with morning urinary melatonin concentrations. Nevertheless, energy expenditure explains a relatively small amount of melatonin variation, perhaps suggesting that peak melatonin is minimally affected by these patterns of physical activity.

The effect of sleep restriction and psychological load on the diurnal metabolic changes in tryptamine-related compounds in human urine

The effect of a severely stressful situation (sleep restriction and psychological load) on the diurnal changes in novel tryptamine-related compounds (hydroxydiacetyltryptamine, sulphatoxymelatonin, and dihydromelatonin) was evaluated in human subjects for 16days. The subjects were allowed to sleep for 5h on days three through 12 and for 8h on the other days. On days three through 12, the subjects were asked to perform a psychological task. The first two and the last 4days were viewed as control days. A performance test was administered to evaluate the extent of the subjects' fatigue. Total urine was sampled by collecting it into bottles three times a day [(1) during the sleeping period, (2) in the morning, and (3) in the afternoon]. Seven tryptamine-related compounds in urine were assayed using HPLC-fluorometry. The urine melatonin level was high at night and low during the day. In contrast, urinary levels of hydroxydiacetyltryptamine and sulphatoxydiacetyltryptamine were low at night and high during the day. Dihydromelatonin was undetectable in urine during the sleeping period. Sleep restriction and psychological load did not affect diurnal changes in urinary melatonin, hydroxydiacetyltryptamine, sulphatoxydiacetyltryptamine, or N-acetylserotonin levels. The concentrations of hydroxymelatonin and sulphatoxymelatonin in urine did not show diurnal changes and decreased gradually during the experimental days. A principal component analysis confirmed the diurnal changes and suggested two novel metabolic pathways: (1) N-acetylserotonin to sulphtoxydiacetyltryptamine via hydroxydiacetyltryptamine, and (2) melatonin to dihydromelatonin. Severely stressful situations did not affect diurnal changes in melatonin, hydroxydiacetyltryptamine, sulphatoxydiacetyltryptamine, or N-acetylserotonin levels in urine.

A circadian rhythm sleep disorder: melatonin resets the biological clock

Circadian rhythm sleep disorders are poorly understood and often misdiagnosed. They are all related to the timing of sleep within the 24-hour day. This paper describes a patient with a long history of sleep disturbance whom we diagnosed as having delayed sleep phase syndrome by history and measurement of urinary melatonin metabolite excretion. Literature on the characteristics, diagnosis and management of this syndrome are briefly reviewed. In addition, the relation of the neurohormone melatonin to circadian rhythm and its other physiological roles are described.