Urinary 6-sulfatoxymelatonin Excretion Research Articles

Disruption of the circadian rhythm of melatonin: A biomarker of critical illness severity

Circadian dysrhythmias occur commonly in critically ill patients reflecting variable effects of underlying illness, ICU environment, and treatments. We retrospectively analyzed the relationship between clinical outcomes and 24-h urinary 6-sulfatoxymelatonin (aMT6s) excretion profiles in 37 critically ill patients with shock and/or respiratory failure. Nonlinear regression was used to fit a 24-h cosine curve to each patient's aMT6s profile, with rhythmicity determined by the zero-amplitude test. From these curves we determined acrophase, amplitude, phase, and night/day ratio. After assessing unadjusted relationships, we identified the optimal multivariate models for hospital survival and for discharge to home (vs. death or transfer to another facility). Normalized aMT6s rhythm amplitude was greater (p = 0.005) in patients discharged home than in those who were not, while both groups exhibited a phase delay. Patients with rhythmic aMT6s excretion were more likely to survive (OR 5.25) and be discharged home (OR 8.89; p < 0.05 for both) than patients with arrhythmic profiles, associations that persisted in multivariate modelling. In critically ill patients with shock and/or respiratory failure, arrhythmic and/or low amplitude 24-h aMT6s rhythms were associated with worse clinical outcomes, suggesting a role for the melatonin-based rhythm as a novel biomarker of critical illness severity.

SEX-RELATED DIFFERENCES IN THE LEVELS OF URINE 6-SULFATOXYMELATONIN IN VERY LOW BIRTH WEIGHT INFANTS

Background. The sex-related differences of the urinary 6-sulfatoxymelatonin have not been studied in premature infants yet. The purpose of the work was to measure the daily urinary 6-sulfatoxymelatonin in premature infants with a very low birth weight. Materials and Methods. Fifty premature infants (28 males and 22 females) with gestational age less than 33 weeks and body weight from 999 g to 1499 g were involved in the study. Urine 6-sulfatoxymelatonin was assessed using urine collection on the 1st day and on the 10th‒14th days of life. Results. The level of urine 6-sulfatoxymelatonin on the 1st day of life showed a significant increase in its excretion in females compared to males. The median values in males were 202.0 (95% CI 77.1–390.9) pg/ml and in females 437.0 (279.6–501.0) pg/ml, p=0.0103. Its level on the 10th–14th days of life significantly decreased both in males 57.0 (95 % СІ 45,0–99.7) pg/ml, p=0.0028 and in females 90.0 (51.9–160.7) pg/ml, p=0.0021 without differences in sex-related distribution, p=0.3940. Conclusions. The melatonin metabolite as urinary 6-sulfatoxymelatonin in premature infants with a very low birth weight demonstrates sex-related differences with significant increase in females compared to males on the 1st day of life and no sex-related difference on the 10th–14th days of life. The trend of reduced pineal function is a key point in understanding the neuroendocrine reactivity in male preterms. Future investigation of sex-related aspects of urinary 6-sulfatoxymelatonin excretion in children, especially premature infants, is required.

Short-wavelength light exposure at night and sleep disturbances accompanied by decreased melatonin secretion in real-life settings: a cross-sectional study of the HEIJO-KYO cohort

ObjectivesTo determine the association between short-wavelength light exposure at night (LAN) power and sleep quality or melatonin levels in real-life settings. MethodsIn this cross-sectional study of 580 older adults (mean age, 71.0 years), we measured short-wavelength LAN power at cornea level using an originally developed light loggers over two nights. Sleep quality and physiological melatonin levels were measured using the Pittsburgh sleep quality index (PSQI) questionnaire and overnight urinary 6-sulfatoxymelatonin excretion (UME), respectively. ResultsThe first and second tertile short-wavelength LAN power values obtained were 0.77 × 10−2 μW/cm2 and 7.0 × 10−2 μW/cm2, respectively, and the overall prevalence of sleep disturbances was 34.7%. The mean UME was 1.88 ± 0.70 log μg. The mean global PSQI score and the prevalence of sleep disturbances significantly increased (P = 0.004 and 0.006, respectively) with increasing tertile groups of short-wavelength LAN power. In multivariable analysis adjusted for potential confounders, the odds ratio (OR) for sleep disturbances was significantly higher in the highest tertile group of short-wavelength LAN power compared with that in the lowest tertile group (adjusted OR, 1.90; 95% confidence interval [CI]: 1.20, 3.00; P = 0.006). In addition, UME was significantly lower in the highest tertile group of short-wavelength LAN power than that in the lowest tertile group (adjusted mean difference, −0.14 log μg; 95% CI: −0.28, −0.007; P = 0.039). ConclusionsAlthough short-wavelength LAN power measured at cornea level in real-life settings seemed to be significantly low, our findings suggest that short-wavelength LAN power is significantly associated with both melatonin levels and sleep disturbance.

Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances.

Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autism spectrum disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6-sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in 20 controls and 20 ASD participants, as well as correlating these measures with sleep disturbances. Although 60% of ASD participants showed a significant night-time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (P<.05). The remaining 40% of ASD individuals showed no significant increase in nocturnal aMT6s. ASD individuals showed higher nocturnal levels of saliva TNF, but not IL-6. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night-time aMT6s excretion (r=-.28, P<.05). Dysfunction in sleep breathing was inversely correlated with aMT6s (r=-.31, P<.05) and positively associated with TNF level (r=.42, P<.01). Overall such data indicate immune-pineal axis activation, with elevated TNF but not IL-6 levels associated with disrupted pineal melatonin release and sleep dysfunction in ASD. It is proposed that circadian dysregulation in ASD is intimately linked to heightened immune-inflammatory activity. Such two-way interactions of the immune-pineal axis may underpin many aspects of ASD pathophysiology, including sleep disturbances, as well as cognitive and behavioral alterations.

Melatonin secretion in patients with Parkinson's disease receiving different-dose levodopa therapy

ObjectiveMelatonin is involved in the regulation of sleep and circadian biological rhythmicity; decreased melatonin secretion has been associated with circadian disruptions. Previous studies evaluating melatonin levels between patients with Parkinson's disease (PD) and controls without PD have found conflicting results; however, large-scale studies have not been performed. Our aim is to compare endogenous melatonin levels between patients with Parkinson's disease (PD) and non-PD older adults. MethodsIn this cross-sectional study on 201 outpatients with PD and 380 community-dwelling older Japanese adults (controls), urinary 6-sulfatoxymelatonin excretion was measured to estimate endogenous melatonin levels. ResultsUrinary 6-sulfatoxymelatonin excretion (UME) did not significantly differ overall between PD patients and non-PD controls, even after adjusting for age, gender, medications, sleep habits, and seasons. Among PD patients, a clear and robust dose–response association was found between levodopa equivalent dose and UME, independent of potential confounding factors, including Parkinson's disease severity. Compared with the lowest levodopa equivalent dose quartile group (mean levodopa equivalent dose, 132 mg/day), the highest group (mean levodopa equivalent dose, 973 mg/day) exhibited a 68% increase in UME (17.8 vs. 30.0 ng/mg cre, respectively). In addition, compared with the non-PD controls, PD patients receiving a lower levodopa equivalent dose displayed decreased UME and those receiving higher levodopa equivalent dose displayed increased UME. ConclusionOur study suggests that melatonin levels in PD patients receiving average levodopa doses are comparable with those in older adults, even after considering confounding factors. This association was modulated by daily levodopa dose in PD patients.

Gender differences in the association between melatonin secretion and diabetes in elderly: The HEIJO-KYO cohort.

Reportedly, melatonin protects the pancreatic islets and decreases insulin resistance; thus, it may contribute to preventing diabetes. Epidemiological data suggested that lower melatonin secretion is associated with higher incidence of diabetes in female nurses. Such associations are unknown in the general population. We evaluated the association between melatonin secretion and diabetes in a general population, including both genders. Cross-sectional study. A total of 1096 community-based elderly males (n=519) and females (n=577) (mean age, 71.8years) were enrolled. Overnight urinary 6-sulfatoxymelatonin excretion (UME) and diabetes prevalence were measured. The median UME was 6.7μg (interquartile range, 4.0-10.5); the prevalence of diabetes was 17.5% in males and 10.7% in females. The prevalence of diabetes decreased with increasing UME quartiles among males (P for trend=0.009) but not among females (P for trend=0.96). In a multivariable logistic regression analysis adjusting for potential confounding factors, such as age, smoking and drinking habits, economic status, caloric intake, and physical activity, the odds ratio (OR) for diabetes was significantly lower in the highest UME quartile group compared with the lowest quartile group among males (OR, 0.35; 95% CI, 0.17-0.70; P=0.003) but not females (OR, 0.94; 95% CI, 0.45-1.95; P=0.87). Consistent results were observed in the analysis after adjusting for clinical parameters or using continuous UME data. Melatonin secretion was significantly and inversely associated with diabetes in males but not in females. This association was independent of several important confounding factors.

The effect of long-term melatonin supplementation on psychosomatic disorders in postmenopausal women.

Different psychosomatic disorders are observed in postmenopausal women. The decrease of estrogen production is believed to be the main cause of their severity. It is nowadays evident that the decreased melatonin release in women at this age who suffer from postmenopausal disorders might also contribute to the severity of the symptoms. The aim of the study was to evaluate the effect of melatonin supplementation on female hormones release and the alteration in climacteric symptoms. The study included 60 postmenopausal women, aged 51 - 64 years, who were randomly allotted into two equal groups. Group I was recommended placebo (2 x 1 tablet) and Group II - melatonin (3 mg in the morning and 5 mg at bedtime) for 12 months. Serum levels of 17β-estradiol, follicle-stimulating hormone (FSH), melatonin and urinary 6-sulfatoxymelatonin (aMT6s) excretion as well as Kupperman Index (KI) and body mass index (BMI) were determined before the start and at 12 months after placebo or melatonin administration. In Group I only the value of KI slightly decreased (28.4 ± 2.9 versus 25.6 ± 3.8 points, P = 0,0619). In Group II - KI decreased from 29.1 ± 2.9 to 19.7 ± 3.1 points (P < 0.001) and BMI from 30.9 ± 2.9 to 28.1 ± 2.3 kg/m2 (P < 0.05). Melatonin supplementation failed to change significantly the serum concentration of female reproductive hormones 17β-estradiol and FSH. We conclude that melatonin supplementation therapy exerts a positive effect on psychosomatic symptoms in postmenopausal women and can be recommended as the useful adjuvant therapeutic option in treatment of these disorders.

Clinical Considerations Derived From the Administration of Melatonin to Children With Sleep Disorders

Background and ObjectivesDespite the numerous investigations carried out in relation to melatonin, there is a lack of knowledge about the specific melatonin secretion patterns in the diverse primary sleep disturbances. The objective of this study was to analyze the plasma melatonin concentrations in children with primary sleep disorders and the effects of melatonin therapy on their serum levels and their actigraphic sleep parameters. MethodsFourteen participants (nine girls; seven to 14 years old) diagnosed with diverse primary sleep disorders were recruited. Four different melatonin secretion patterns were identified: low plasma melatonin levels, absence of a circadian rhythm, advanced acrophase, and delayed acrophase. A placebo (one week) was administered followed by three months of melatonin therapy (3 mg/night). Urinary 6-sulfatoxymelatonin levels, 24-hour plasma melatonin concentrations, and a seven-day actigraphic record were collected after both treatments. ResultsAfter melatonin therapy, a significant increase (P < 0.001) of urinary 6-sulfatoxymelatonin excretion with a clear circadian variation was observed. Plasma melatonin concentrations were also significantly higher with a recovery in the circadian rhythm. Actual sleep time was significantly longer, with a substantial reduction in the sleep onset latency and night awakenings. No severe side effects were reported. ConclusionsThe main clinical implication of this study is to demonstrate the efficacy of melatonin in three main circumstances: an insufficient hormone production, a disturbed circadian rhythm, and an advanced or delayed acrophase. As ongoing work, we are exploring the effect of different doses of melatonin on the regulation of its concentrations and of its secretion rhythm.

Serotonin and melatonin secretion in postmenopausal women with eating disorders.

Postmenopausal women manifest emotional disorders associated with an increase in appetite. The aim of the study was to assess the serotonin and melatonin secretion and metabolism in postmenopausal women in relation to eating disorders. Sixty postmenopausal women and 30 women without hormonal disturbances were enrolled into the study and divided into three groups: group I (control) - women without menstrual disorders, group II - postmenopausal women without appetite disorders and change in body weight, and group III - postmenopausal women with increased appetite and weight gain. Serum melatonin, serotonin, urinary 6-sulfatoxymelatonin (aMT6s), and 5-hydroxyindoleacetic acid (5-HIAA) excretion were measured. Serum serotonin and melatonin levels in groups II and III were lower compared to group I. Urinary 5-HIAA and aMT6s excretion was lower in overweight women. In group III the correlation between the serum level of serotonin, melatonin, and BMI was negative; a high statistical significance was found between BMI and urinary aMT6s excretion. Melatonin supplementation and use of drugs modulating the serotonin homeostasis together with female hormones have a beneficial effect in complex treatment of disorders of eating in postmenopausal women. (Endokrynol Pol 2016; 67 (3): 299-304).

Melatonin Secretion and Muscle Strength in Elderly Individuals: A Cross-Sectional Study of the HEIJO-KYO Cohort.

Decreased muscle strength is associated with functional limitation and disability and is a predictor of cardiovascular and all-cause mortality. Recently, oxidative stress and inflammation have been shown to contribute to the loss of muscle strength, and although melatonin has antioxidative and anti-inflammatory properties, the association between melatonin secretion and muscle strength remains unclear. In this cross-sectional study of 760 community-based elderly individuals (mean age, 71.0 years), we measured overnight urinary 6-sulfatoxymelatonin excretion (UME) and grip strength and quadriceps strength. Median UME was 7.0 μg (interquartile range, 4.2-11.1), and mean grip and quadriceps strength were 27.5±8.4kg and 162.6±80.1 Nm, respectively. On dividing participants into quartiles by their UME level (lowest-highest UME, Q1-Q4), higher quartiles were significantly associated with increased grip strength and quadriceps strength (p for trend < .001, both). Multivariable analyses adjusted for potential confounders (age, gender, body mass index, smoking and drinking statuses, renal function, hypertension, diabetes, physical activity, depressed mood, cognitive impairment, bedtime, sleep duration, and day length) revealed that both grip and quadriceps strength were significantly increased in Q4 compared with that in Q1 (adjusted mean difference, Q4 - Q1: grip strength, 1.5kg; 95% confidence interval [CI], 0.4-2.6kg; p = .006; quadriceps strength, 14.2 Nm; 95% CI, 1.3-27.1 Nm; p = .031). Melatonin secretion was significantly associated with muscle strength in this elderly population. Further longitudinal studies are needed to ascertain the effect of melatonin levels on muscle strength.

Physiological Levels of Melatonin Relate to Cognitive Function and Depressive Symptoms: The HEIJO-KYO Cohort.

In contrast with randomized controlled trials, observational studies have suggested that physiological levels of melatonin are reduced in patients with dementia or depression, but the relationship has not been evaluated in large populations. The objective was to determine the relationships between physiological levels of melatonin and cognitive function and depressive symptoms. A cohort of 1105 community-dwelling elderly individuals was enrolled in this cross-sectional study (mean age, 71.8 ± 7.1 y). Urinary 6-sulfatoxymelatonin excretion (UME) and Mini-Mental State Examination (MMSE; n = 935) and Geriatric Depression Scale (GDS; n = 1097) scores were measured as indices of physiological melatonin levels, cognitive function, and depressive symptoms, respectively. With increases in UME quartiles, the prevalence of cognitive impairment (MMSE score ≤ 26) and depressed mood (GDS score ≥ 6) significantly decreased (P for trend = .003 and .012, respectively). In multivariate logistic regression models, after adjusting for confounders such as age, gender, socioeconomic status, physical activity, and sleep/wake cycles, higher UME levels were significantly associated with lower odds ratios (ORs) for cognitive impairment and depressed mood (ORs: Q1 = 1.00; Q2 = 0.88 and 0.76; Q3 = 0.66 and 0.85; Q4 = 0.67 and 0.53; P for trend = .023 and .033, respectively). In addition, the highest UME group showed a significantly lower OR for depressed mood than the lowest UME group (Q4 vs Q1: OR, 0.53; 95% confidence interval, 0.32-0.89; P = .033). UME levels above the median value were significantly associated with a lower OR for cognitive impairment, even after further adjustment for depressive symptoms (OR = 0.74; 95% confidence interval, 0.55-0.99; P = .043). Significant associations of higher physiological melatonin levels with lower prevalence of cognitive impairment and depressed mood were revealed in a large general elderly population. The association between physiological melatonin levels and cognitive function was independent of depressive symptoms.

Higher melatonin secretion is associated with lower leukocyte and platelet counts in the general elderly population: the HEIJO-KYO cohort.

Circulating white blood cell (WBC) and platelet (PLT) counts are widely available and inexpensive cellular biomarkers of systemic inflammation and have been associated with a risk of cardiovascular disease, cancer, and mortality. Melatonin may reduce systemic inflammation through its direct and indirect antioxidative effect; however, the associations of melatonin secretion with systemic inflammation remain unclear. In this cross-sectional study on 1088 elderly individuals (mean age, 71.8years), we measured overnight urinary 6-sulfatoxymelatonin excretion (UME) and WBC and PLT counts as indices of melatonin secretion and systemic inflammation, respectively. UME was naturally log-transformed for linear regression models because of skewed distribution (median, 6.8μg; interquartile range, 4.1-10.6μg). Univariate models revealed that higher log-transformed UME levels were significantly associated with lower WBC and PLT counts (P=0.046 and 0.018). After adjusting for potential confounding factors significantly associated with WBC or PLT counts, higher log-transformed UME levels were significantly associated with lower WBC and PLT counts (WBC: β, -0.143; 95% confidence interval, -0.267 to -0.020; P=0.023; PLT: β, -6.786; 95% confidence interval, -12.047 to -1.525; P=0.012). Furthermore, the adjusted mean differences in WBC and PLT counts between the lowest and highest UME tertile groups were 0.225×10(9) /L and 9.480×10(9) /L, respectively. In conclusion, melatonin secretion was significantly and inversely associated with WBC and PLT counts in the general elderly population. The associations were independent of several major causes of systemic inflammation, including aging, obesity, smoking, hypertension, diabetes, and physical inactivity.

Comparisons of Objective Sleep Quality Between Elderly Individuals With and Without Cataract Surgery: A Cross-Sectional Study of the HEIJO-KYO Cohort

BackgroundCataract surgery (CS) drastically increases the capacity for light reception to the retina. Several previous studies have suggested the beneficial effect of CS on subjectively measured sleep quality; however, the association between CS and objectively measured sleep quality remains uncertain.MethodsTo evaluate the association between CS and objectively measured sleep quality in home settings, we conducted a cross-sectional study in 1037 elderly individuals (mean age, 71.9 years). We evaluated actigraphically measured sleep quality, urinary 6-sulfatoxymelatonin excretion, and ambulatory light levels, in addition to CS status.ResultsThe CS group (n = 174) showed significantly higher sleep efficiency and shorter wake after sleep onset than the no CS group (n = 863), even after adjustment for age, gender, body mass index, current smoking status, alcohol consumption, hypertension, diabetes, sleep medication, bedtime, rising time, daytime physical activity, daytime and nighttime light exposure, and urinary 6-sulfatoxymelatonin excretion (sleep efficiency: 85.8% in the CS group vs 84.4% in the no CS group, P = 0.042; wake after sleep onset: 45.7 min vs 50.6 min, respectively, P = 0.033). In contrast, urinary 6-sulfatoxymelatonin excretion, sleep onset latency, total sleep time, and sleep-mid time did not differ significantly between the CS and no CS groups.ConclusionsAmong a community-dwelling elderly population, CS is significantly associated with objectively measured sleep quality, but urinary levels of melatonin metabolite do not differ between individuals with and without CS. These associations are independent of daily light exposure profiles.

Lower melatonin secretion in older females: gender differences independent of light exposure profiles.

BackgroundMelatonin is associated with a variety of diseases in advanced age, including insomnia, depression, and dementia, and its secretion is influenced by light exposure. Although studies in young and middle-aged subjects have shown that females tend to have higher melatonin levels than males, gender differences in melatonin levels among older people remain unclear.MethodsTo determine the gender differences in melatonin levels among older people in home settings, we conducted a cross-sectional study in 528 older people. We measured overnight urinary 6-sulfatoxymelatonin excretion (UME; an index of melatonin secretion), and ambulatory light intensity.ResultsThe mean age of females was 1.8 years younger, and average intensity of daytime light exposure was half that in males (P < 0.01). In a univariate comparison, UME was significantly lower in females than in males (P < 0.01). A multivariate model using analysis of covariance showed that log-transformed UME remained significantly lower in females after adjustment for potential confounding factors, including age and daytime and nighttime light exposure profiles (males vs. females: 1.90 vs. 1.73 log µg; adjusted mean difference 0.17 log µg [95% confidence interval [CI] 0.02–0.32]; P = 0.02). This result indicates that older females have 18.4% (95% CI, 2.2–37.4%) lower UME than older males.ConclusionsOlder females have significantly lower UME than older males, an association which is independent of light exposure profiles in home settings. Our findings may be useful as basic data for further research to investigate gender differences in several diseases associated with melatonin in the elderly.

Relationship between urinary 6-sulfatoxymelatonin excretion and cancer antigen 125 in women with endometriosis

Abstract Objective Pelvic endometriosis was found to be associated with oxidative stress in the peritoneal cavity. Endogenous melatonin was known for its antioxidative activities, and oral melatonin had been studied as a treatment option for endometriosis. However, the association between endogenous melatonin and endometriosis has not yet been determined. Materials and methods A cross-sectional case-control study was implemented. Blood and urine samples from women with surgically confirmed ovarian endometriomas, benign adnexal tumors other than endometriomas, and healthy volunteers were collected and tested for cancer antigen 125 (CA125) as well as urinary 6-sulfatoxymelatonin (aMT6s), a surrogate for average serum melatonin level. Results A total of 97 patients with endometriomas, 59 with benign ovarian tumors other than endometriomas, and 80 women without adnexal lesion were recruited. Elevated serum CA125 and decreased body mass index were found in patients with ovarian endometriosis (both p p = 0.88). A statistically nonsignificant negative correlation between urinary creatinine-adjusted aMT6s and CA125 ( p = 0.16) in patients with ovarian endometriosis was found. Conclusion Endogenous melatonin might not be a major determinant for the occurrence of endometriosis. A potential negative correlation between endogenous melatonin and the severity of endometriosis merits further investigations.

Association between light exposure at night and insomnia in the general elderly population: The HEIJO-KYO cohort

Chronic circadian misalignment between the internal and environmental rhythms, which is typically related to night-shift work and clock-gene variants, is associated with disruption of suprachiasmatic nucleus function and increased risk of insomnia. Under controlled laboratory conditions, light at night (LAN) suppresses melatonin secretion, delays the internal biological rhythm, and reduces sleepiness. Therefore, LAN exposure may cause circadian misalignment and insomnia, though it remains unclear in real-life situations whether LAN exposure is associated with insomnia. To evaluate an association between LAN exposure and sleep quality in home settings, we conducted a cross-sectional community-based study in 857 elderly individuals (mean age, 72.2 years). We evaluated bedroom light intensity using a light meter and subjectively and objectively measured sleep quality using the Pittsburgh Sleep Quality Index and an actigraph, respectively, along with urinary 6-sulfatoxymelatonin excretion. Compared with the lowest quartile group of LAN intensity, the highest quartile group revealed a significantly higher odds ratio (OR) for subjective insomnia in a multivariate model adjusted for age, gender, body mass index, daytime physical activity, urinary 6-sulfatoxymelatonin excretion, bedtime, rising time, and day length (adjusted OR, 1.61, 95% confidence interval, 1.05–2.45, p = 0.029). In addition, higher OR for subjective insomnia was significantly associated with the increase in quartiles of LAN intensity (ptrend = 0.043). Consistently, we observed significant association trends between the increase in quartiles of LAN intensity and poorer actigraphic sleep quality, including decreased sleep efficiency, prolonged sleep-onset latency, increased wake-after-sleep onset, shortened total sleep time, and delayed sleep-mid time in multivariate models adjusted for the covariates mentioned above (all ptrend < 0.001). In conclusion, we demonstrated that LAN exposure in home settings is significantly associated with both subjectively and objectively measured sleep quality in a community-based elderly population.

Association between urinary 6-sulfatoxymelatonin excretion and arterial stiffness in the general elderly population: the HEIJO-KYO cohort.

Melatonin may have a preventive effect on atherosclerosis by regulating sleep quality and circadian biological rhythmicity. However, whether endogenous melatonin is associated with arterial stiffness, a marker reflecting atherosclerosis, is unclear. The objective of the study was to determine the association between endogenous melatonin and arterial stiffness. A total of 641 community-based elderly individuals were enrolled in this cross-sectional study (mean age 71.4 y). We measured overnight urinary 6-sulfatoxymelatonin excretion (UME) and cardioankle vascular index (CAVI) as indices of melatonin secretion and arterial stiffness, respectively. The median UME was 6.8 μg (interquartile range 4.1-10.5) and the mean value of CAVI was 9.1 ± 1.1. High CAVI (ie, ≥ 9.0) was observed in 334 participants (52.1%). Univariate logistic regression models revealed marginal to significant associations between high CAVI and age, gender, body mass index, hypertension, diabetes, estimated glomerular filtration rate, log-transformed UME, bedtime, duration in bed, daytime physical activity, and log-transformed nighttime physical activity. In the multivariate logistic regression model, simultaneously adjusted for the former independent variables, higher log-transformed UME was significantly associated with a lower odds ratio (OR) for high CAVI (adjusted OR 0.708; 95% confidence interval 0.536-0.935; P = .015). This inverse association between log-transformed UME and high CAVI indicated that an increase in log-transformed UME by 1 SD was associated with an 18.1% (95% confidence interval 1.4-31.9) decrease in high CAVI prevalence. UME is significantly and inversely associated with arterial stiffness in the general elderly population. The association was independent of several major causes of atherosclerosis.

Asymmetric dimethylarginine attenuates the association of melatonin secretion with night-time blood pressure and dipping in elderly individuals.

Melatonin decreases night-time blood pressure (BP) by increasing nitric oxide (NO) in endothelial cells. Whether serum asymmetric dimethylarginine (ADMA), a major endogenous competitive inhibitor of endothelial NO synthase, attenuates the association of melatonin with night-time BP and dipping in humans is unclear. METHODS AND RESULTS: In this cross-sectional study of 852 community-based elderly individuals, serum ADMA, overnight urinary 6-sulfatoxymelatonin excretion (UME), and ambulatory BP were measured. Mean ADMA was 0.46±0.06 μmol/L. In the low-ADMA group (n=451), crude OR for nocturnal hypertension (NH) and non-dipper significantly decreased with a quartile increase in UME (P=0.023 and 0.001, respectively), but these associations were not observed in the high-ADMA group (n=401). Higher UME was significantly and inversely associated with adjusted OR for NH and non-dipper in the low-ADMA group (Q1, 1.00 and 1.00; Q2, 0.92 and 0.74; Q3, 0.57 and 0.51; Q4, 0.48 and 0.40; P=0.004 and 0.002, respectively) but not in the high-ADMA group (P=0.75 and 0.12, respectively). These association trends were also observed on continuous variable analysis (low ADMA, P=0.031 and 0.003; high ADMA, P=0.52 and 0.13; respectively). ADMA attenuates the association of endogenous melatonin with night-time BP and dipping in the general elderly population.

Association between Melatonin Secretion and Nocturia in Elderly Individuals: a Cross-Sectional Study of the HEIJO-KYO Cohort

Nocturnal voids are regulated by circadian biological rhythms, including decreased urine production and increased bladder storage capacity at night. A previous experimental study suggested that exogenous melatonin decreases urine production and increases bladder capacity in rats. However, little is known about whether melatonin secretion, which is considerably lower than exogenous melatonin, is associated with nocturia in humans. We evaluated the association between melatonin secretion and nocturia. In this cross-sectional study we examined 861 community based elderly individuals with a mean age of 72.1 years. We measured nocturnal void frequency and overnight urinary 6-sulfatoxymelatonin excretion as an index of melatonin secretion. Nocturia was defined as 2 or more nocturnal voids. Univariate comparisons between the 261 and 600 study participants with and without nocturia, respectively, showed marginal to significant associations of nocturia with age, gender, body mass index, estimated glomerular filtration rate, calcium channel blockers, benign prostatic hyperplasia, total voided urine volume, urinary 6-sulfatoxymelatonin, duration in bed, day length, and daytime and nighttime physical activity. The multivariate logistic regression model adjusted for the former confounding factors revealed that higher urinary 6-sulfatoxymelatonin was significantly associated with a lower nocturia OR (adjusted OR 0.73, 95% CI 0.56-0.96, p=0.023). After adjustment for age, gender and duration in bed the mean volume of a single voided urine significantly increased with tertiles of increasing urinary 6-sulfatoxymelatonin (p for trend=0.022). Melatonin secretion is significantly and inversely associated with nocturia in a general elderly population.

Independent associations of exposure to evening light and nocturnal urinary melatonin excretion with diabetes in the elderly

Circadian misalignment between internal and environmental rhythms dysregulates glucose homeostasis because of disruption of the biological clock, and increases risk of diabetes. Although exposure to evening light and decreased melatonin secretion are both associated with the circadian misalignment, it remains unclear whether they are associated with diabetes. In this cross-sectional study on 513 elderly individuals (mean age, 72.7 years), we measured ambulatory light intensity during the 4 h prior to bedtime at 1-min intervals during two consecutive days and overnight urinary 6-sulfatoxymelatonin excretion (UME) along with glucose metabolism. The median average intensity of evening light exposure and UME were 25.4 lux (interquartile range 17.5–37.6) and 6.6 μg (interquartile range 3.9–9.7), respectively. Both log-transformed average intensity of evening light exposure and log-transformed UME were significantly associated with diabetes in a multivariate logistic regression model adjusted for covariates, including gender, body mass index, duration in bed, and night-time light exposure [adjusted odds ratio (OR), 1.72; 95% confidence interval (CI), 1.12–2.64; p = 0.01; and adjusted OR, 0.66; 95% CI, 0.44–0.97; p = 0.04; respectively]. An increase in evening light exposure from 17.5 to 37.6 lux (25–75th percentiles) was associated with a 51.2% (95% CI, 8.2–111.4%) increase in prevalent diabetes, and an increase in UME from 3.9 to 9.7 μg (25–75th percentiles) was associated with a 32.0% (95% CI, 1.9–52.8%) decrease in prevalent diabetes. In conclusion, this study in elderly individuals demonstrated that evening light exposure in home settings and UME were significantly and independently associated with diabetes.