Nocturnal Urinary Melatonin Excretion Research Articles

Preterm infants produce less melatonin than term infants at 9 and 12 months of age: A randomized controlled trial

Melatonin production is known to be delayed in preterm infants up to 6 months of age. We aimed to test the profile of melatonin production in these infants at 9–12 months of age. Twenty-three term and 23 preterm infants (gestational age: 29–34 weeks) were randomly assigned. We tested nocturnal urinary melatonin excretion, within a repeated measures design, both at 9 and 12 months of age. Nocturnal urine was extracted from diapers and urinary melatonin derivate (6-sulphatoxymelatonin) excretion was analyzed by enzyme-linked immunosorbent assay assays. Preterm infants had significantly lower urinary melatonin excretion both at 9 and 12 months of age as compared to term infants. At 9 months: 8502 ± 6215 vs. 12,735 ± 10,284 ng, and at 12 months: 8623 ± 5095 vs. 14,985 ± 10,890 ng respectively, (F [1,42]=4.276), (P

Association between light exposure at night and nighttime blood pressure in the elderly independent of nocturnal urinary melatonin excretion

Circadian misalignment between internal and environmental rhythms dysregulates blood pressure (BP) variability because of disruption of the biological clock, resulting in increased nighttime BP. Although exposure to light-at-night is associated with the circadian misalignment, it remains unclear whether exposure to light-at-night in home settings is associated with nighttime BP. In this cross-sectional analysis of 528 elderly individuals (mean age: 72.8 years), we measured bedroom light intensity at 1-min intervals on two consecutive nights along with ambulatory BP, overnight urinary melatonin excretion and actigraphy. With regard to adjusted mean comparisons using analysis of covariance, the light-at-night group (average: ≥5 lux; n = 109) showed significantly higher nighttime systolic BP (SBP; adjusted mean: 120.8 vs. 116.5 mmHg, p = 0.01) and diastolic BP (70.1 vs. 67.1 mmHg, p < 0.01) compared with the Darker group (average: <5 lux; n = 419) independently of potential confounding factors including overnight urinary melatonin excretion and actigraphic sleep quality. We observed consistent associations between light-at-night and nighttime BP in different cutoff values for light-at-night intensity (i.e. 3 and 10 lux). In conclusion, exposure to light-at-night in home settings is significantly associated with increased nighttime BP in elderly individuals independently of overnight urinary melatonin excretion. A 4.3 mmHg increase in nighttime SBP is associated with a 6.1% increase in total mortality, which corresponds to approximately 10 000 annual excess deaths in Japanese 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.

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.

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.

188 Preterm-Born Infants Produce Less Melatonin Than Term-Born Infants at 9 and 12 Months of Age: A Randomized Controlled Trial

Background: Melatonin production is known to be delayed in preterm-born infants up to 6 months of age. We aimed to test the profile of melatonin production in these infants at 9-12 months of age. Methods: Twenty three term-born and 23 preterm-born infants (gestational age: 29-34 weeks) were randomly assigned. We tested nocturnal urinary melatonin excretion, within a repeated measures design, both at 9 and 12 months of age. Nocturnal urine was extracted from diapers and urinary melatonin derivate (6-sulphatoxymelatonin) excretion was analyzed by ELISA assay. Results: Preterm-born infants had significantly lower urinary melatonin excretion both at 9 and 12 months of age as compared to term-born infants. At 9 months: 8502 ± 6215 vs 12735 ±10284 ng, and at 12 months: 8623 ± 5095 vs 14985 ± 10890 ng respectively, [F (1,42)=4.276], (p < 0.05). Conclusion: At 9 and 12 months of age, the delayed maturation of melatonin production is still persistent in preterm-born infants as compared to term-born mates. The impact of persistent decreased melatonin production in preterm-born infants up to 12 months of age on their psychomotor development is to be elucidated.

Effects of pressure on the skin exerted by clothing on responses of urinary catecholamines and cortisol, heart rate and nocturnal urinary melatonin in humans.

The study investigated how the pressure exerted on the skin by clothing worn while working in the daytime affected the urinary excretion of adrenaline, noradrenaline and cortisol, heart rate, and also melatonin secretion at night. Nine young women (experiment I) and seven young women (experiment II) participated. Participants wore either a 100% cotton jacket (tight clothes, TC) or a 100% cotton T-shirt (loose clothes, LC). Loose-fitting, 100% cotton tank tops and panties were worn as underwear in both the TC and the LC groups. The main results can be summarized as follows: (1) urinary excretion of adrenaline, noradrenaline and cortisol was facilitated, and the amounts of urinary excretion were significantly higher when TC were worn. Heart rate was significantly higher in the TC group; (2) nocturnal urinary melatonin excretion was significantly greater in the TC group. These results are discussed in terms of an enhancement of diurnal sympathetic nervous system activity caused by pressure on the skin produced by tight clothing.

Disruption of nocturnal melatonin rhythm and immunological involvement in ischaemic stroke patients.

The aim of this study was to evaluate nocturnal and diurnal urinary melatonin excretion in a group of ischaemic stroke patients, and to verify if a possible impairment of this excretion could be linked with some changes of immunological and neuro-psychic status. We assessed 13 ischaemic stroke patients and five healthy controls for nocturnal urinary melatonin excretion, which was found to be impaired in stroke patients (patients, 0.05 +/- 0.01 ng/ml; controls, 30 +/- 3.0 ng/ml; P < 0.001). No differences were found between the groups with regard to diurnal excretion. Patients with impaired nocturnal melatonin excretion presented: a decreased cell-mediated immunity (assessed by a skin-test); a prevalence of anergic status (69% of patients were anergic compared with 0% of controls; P < 0.05); a slight (but not significant) enhancement of plasma cortisol levels; and some changes in lymphocyte subsets (an overall decrease in CD3 lymphocyte number). In almost all the ischaemic stroke patients there was an impairment of cortisol/melatonin ratio (a marker of depression) and an altered sleep rhythm with mood disorders. Our data suggest that ischaemic stroke patients had an impairment of nocturnal urinary melatonin excretion, which was associated with an impaired cell-mediated immunity and some changes of lymphocyte subsets. In addition, reduced melatonin excretion might be associated with neurological and psychical symptoms.

Pathophysiological aspects of menstrual migraine.

We review the role of several biochemical and hormonal factors in menstrual migraine pathogenesis: ovarian hormones, aldosterone circadian rhythm, nocturnal urinary melatonin excretion, sympathetic autonomic system, prolactin levels and dopaminergic function, endogenous opioid tonus, platelet activity and arachidonic acid metabolites. In particular, we focus on certain aspects of platelet function and prostaglandin metabolism, taking into consideration the different behavior of platelet sensitivity to prostacyclin, intraplatelet 5HT, peripheral plasma concentrations of 6-keto-PGF1alpha and PGE2 in menstrual migraine sufferers and in control subjects during the menstrual cycle. A comprehensive view of the data suggests that a complex impairment of PG and 5HT metabolism, and of platelet function, may play a significant role in the pathogenesis of menstrual migraine. However, it is not yet clear whether these alterations are primary or secondary to neuroendocrine disorders.

Urinary melatonin excretion throughout the ovarian cycle in menstrually related migraine.

Nocturnal urinary melatonin excretion was significantly decreased throughout an ovarian cycle in 12 migraine without aura patients compared to 8 healthy controls. Normal increases in urinary melatonin excretion during the luteal phase was less pronounced in the migraine patients. Melatonin excretion was further decreased during headache. The data indicate impaired pineal function in migraine.

Effect of short-term fasting on nocturnal melatonin secretion in obesity

To investigate whether the function of pinealocytes is altered in obesity, nocturnal melatonin (MT) secretion was determined in nine healthy subjects and compared with that of eight obese individuals. Serum MT levels were measured every second hour between 6:00 pm and 8:00 am, and total nocturnal MT secretion (as reflected by the MT incremental area), MT peak time, and nocturnal urinary MT excretion were determined. None of these parameters differed significantly in the two groups. The obese subjects were reinvestigated after 2 days of complete fasting. This caused a decrease in body weight and basal blood glucose levels of 2.6 ± 0.2 kg (mean ± SEM, P < .001) and 1.5 ± 0.2 mmol/L ( P < .001), respectively, whereas serum cortisol levels remained unchanged. Short-term fasting reduced nocturnal MT secretion, as evidenced by MT incremental areas, which were reduced from 2.01 ± 0.26 before fasting to 1.64 ± 0.26 nmol/L · h after fasting ( P < .02). MT secretion peaks were reached simultaneously, and urinary MT excretion values did not change significantly in fasting. To see whether glucose supplementation during short-term fasting would normalize nocturnal MT secretion, we gave an additional seven obese subjects eight small oral doses of glucose (each dose, 0.5 g/kg body weight) at regular intervals during a 2-day fast. Their body weight decreased by 2.8 ± 0.4 kg ( P < .001), but blood glucose and cortisol concentrations were similar before and after the glucose-supplemented fast, as was the nocturnal MT secretion. These findings imply that pinealocytes of fed obese patients secrete normal amounts of MT during the night, but lose secretory potential during fasting-induced hypoglycemia. Since glucose supplementation during fasting returns MT secretion to normal, it is assumed that pinealocytes of obese individuals require a certain minimal glucose delivery to function normally.

Nocturnal urinary melatonin excretion and plasma cortisol levels in children and adolescents after a single oral dose of dexamethasone.

In the present study, the possible relationship between melatonin secretion as reflected by nocturnal melatonin excretion (2000 h-0800 h) and the pituitary-adrenocortical axis was investigated. Nocturnal urinary melatonin excretion and plasma cortisol levels were determined in 41 children with weight problems before and after a single oral dose of dexamethasone. A first group of 15 individuals with normal cortisol cycle (12.2 +/- 1.4 at 0800 h and 3.1 +/- 0.5 micrograms/100 ml at 1700 h), and levels below 1.0 microgram/100 ml after dexamethasone, showed a highly significant increase in melatonin excretion during the night following dexamethasone treatment (63.5 +/- 5.5 ng/12 h vs 33.6 +/- 3.0 for the control night, P less than 0.001). This increase was observed from prepuberty to young adulthood (pubertal stages PI-PV). In a second group of 16 subjects with mean cortisol levels similar at 0800 h and 1700 h (10.7 +/- 1.3 and 9.3 +/- 1.5 micrograms/100 ml respectively), but with a normal cortisol suppression after dexamethasone administration, nocturnal melatonin excretion increased from 21.2 +/- 2.1 to 33.4 +/- 3.0 ng/12 h (P less than 0.01). A significant increase was found in prepubertal children (PI) whereas no change was observed at the end of pubertal development (stages PIV-PV). A third group of 10 patients with both low amplitude cortisol cycles (16.2 +/- 2.5 and 10.8 +/- 2.4 micrograms/100 ml) and abnormal cortisol suppression after dexamethasone administration (9.1 +/- 2.4 micrograms/100 ml), showed no increase in melatonin excretion (24.2 +/- 2.7 and 24.9 +/- 3.7 ng/12 h).(ABSTRACT TRUNCATED AT 250 WORDS)