The effects of skin pressure by clothing on circadian rhythms of core temperature and salivary melatonin

The present experiment investigated the effects of skin pressure by foundation garments (girdle and brassiere) on the circadian rhythms of core temperature and salivary melatonin. Ten healthy females (18-23 years) maintained regular sleep-wake cycles for a week prior to participation in the experiment. The experiments were performed from June to August 1999 using a bioclimatic chamber controlled at 26.5 degrees C +/- 0.2 degrees C and 62% +/- 3% RH. Ambient light intensity was controlled at 500 lux from 07:30 to 17:30, 100 lux from 17:30 to 19:30, 20 lux from 19:30 to 23:30; there was total darkness from 23:30 to 07:30. The experiment lasted for 58h over three nights. The participants arose at 07:30 on the first full day and retired at 23:30, adhering to a set schedule for 24h, but without wearing foundation garments. For the final 24h of the second full day, the subjects wore foundation garments. Rectal and leg skin temperatures were measured continuously throughout the experiment. Saliva and urine were collected every 4h for the analysis of melatonin and catecholamines, respectively. Skin pressure applied by the foundation garments was in the range 11-17 gf/cm2 at the regions of the abdomen, hip, chest, and back. The main results were as follows: (1) Rectal temperatures were significantly higher throughout the day and night when wearing foundation garments. (2) The nocturnal level of salivary melatonin measured at 03:30 was 115.2 +/- 40.4 pg/mL (mean +/- SEM, N = 10) without and 51.3 +/- 18.4 pg/mL (mean +/- SEM, N = 10) with foundation garments. (3) Mean urinary noradrenaline excretion was significantly lower throughout the day and night when wearing foundation garments (p < .05), but mean urinary adrenaline excretion was not different. The results suggest that skin pressure by clothing could markedly suppress the nocturnal elevation of salivary melatonin, resulting in an increase of rectal temperature.     

Circadian Rhythms of Core Body Temperature and Urinary Noradrenaline Secretion under the Influence of Skin Pressure due to Foundation Garments Worn during Wakefulness

The present experiment investigated the effects of skin pressure by foundation garments (brassiere plus girdle) worn during wakefulness on the circadian rhythms of core temperature and endocrine secretion. Eight healthy females (18–23 yrs) maintaining regular sleep-wake cycles for a week prior to participation in the experiment served as participants. The experiments were performed from June to August, 1999, using a bioclimatic chamber controlled at 26.5 ± 0.2°C and 62 ± 3% RH. Ambient light intensity was controlled at 500 lx from 07:30 h to 17:30 h, 100 lx from 17:30 h to 19:30 h, 20 lx from 19:30 h to 23:30 h and there was total darkness from 23:30 h to 07:30 h. The experiment lasted for 58?h over 3 nights. The participant rose at 07:30?h in the morning of the first day and retired at 23:30 h, adhering to a set schedule for 24 h but without wearing foundation garments. From 07:30 h to 23:30 h of the second day the participant wore foundation garments but did not wear foundation garments during the sleep. Rectal and leg skin temperatures were continuously measured throughout the experiment. Urine was collected every 4 h for the analysis of catecholamines. Skin pressure applied by the foundation garments was in the range 11–17 gf/cm² at the regions of abdomen, hip, chest and back. The main results were as follows: Rectal temperature was significantly higher (p < 0.01) during wakefulness, but significantly lower (p < 0.01) during sleep with than without foundation garments. Furthermore, the amplitude of rectal temperature was larger with than without foundation garments (p < 0.033). Urinary noradrenaline was mostly lower with foundation garments throughout the day and night. The results suggest that skin pressure by foundation garments worn during wakefulness could influence the level of core body temperature and noradrenaline secretion not only during wakefulness, but also during sleep.     

Timing Light Treatment for Eastward and Westward Travel Preparation

Jet lag degrades performance and operational readiness of recently deployed military personnel and other travelers. The objective of the studies reported here was to determine, using a narrow bandwidth light tower (500 nm), the optimum timing of light treatment to hasten adaptive circadian phase advance and delay. Three counterbalanced treatment order, repeated measures studies were conducted to compare melatonin suppression and phase shift across multiple light treatment timings. In Experiment 1, 14 normal healthy volunteers (8 men/6 women) aged 34.9±8.2 yrs (mean±SD) underwent light treatment at the following times: A) 06:00 to 07:00 h, B) 05:30 to 07:30 h, and C) 09:00 to 10:00 h (active control). In Experiment 2, 13 normal healthy subjects (7 men/6 women) aged 35.6±6.9 yrs, underwent light treatment at each of the following times: A) 06:00 to 07:00 h, B) 07:00 to 08:00 h, C) 08:00 to 09:00 h, and a no-light control session (D) from 07:00 to 08:00 h. In Experiment 3, 10 normal healthy subjects (6 men/4 women) aged 37.0±7.7 yrs underwent light treatment at the following times: A) 02:00 to 03:00 h, B) 02:30 to 03:30 h, and C) 03:00 to 04:00 h, with a no-light control (D) from 02:30 to 03:30 h. Dim light melatonin onset (DLMO) was established by two methods: when salivary melatonin levels exceeded a 1.0 pg/ml threshold, and when salivary melatonin levels exceeded three times the 0.9 pg/ml sensitivity of the radioimmunoasssy. Using the 1.0 pg/ml DLMO, significant phase advances were found in Experiment 1 for conditions A (p?<?.028) and B (p?<?0.004). Experiment 2 showed significant phase advances in conditions A (p?<?0.018) and B (p?<?0.003) but not C (p?<?0.23), relative to condition D. In Experiment 3, only condition B (p?<?0.035) provided a significant phase delay relative to condition D. Similar but generally smaller phase shifts were found with the 2.7 pg/ml DLMO method. This threshold was used to analyze phase shifts against circadian time of the start of light treatment for all three experiments. The best fit curve applied to these data (R²?=?0.94) provided a partial phase-response curve with maximum advance at approximately 9–11 h and maximum delay at approximately 5–6 h following DLMO. These data suggest largest phase advances will result when light treatment is started between 06:00 and 08:00 h, and greatest phase delays will result from light treatment started between 02:00 to 03:00 h in entrained subjects with a regular sleep wake cycle (23:00 to 07:00 h).     

Less Exposure to Daily Ambient Light in Winter Increases Sensitivity of Melatonin to Light Suppression

This study was carried out to examine the seasonal difference in the magnitude of the suppression of melatonin secretion induced by exposure to light in the late evening. The study was carried out in Akita (39° North, 140° East), in the northern part of Japan, where the duration of sunshine in winter is the shortest. Ten healthy male university students (mean age: 21.9±1.2 yrs) volunteered to participate twice in the study in winter (from January to February) and summer (from June to July) 2004. According to Japanese meteorological data, the duration of sunshine in Akita in the winter (50.5 h/month) is approximately one‐third of that in summer (159.7 h/month). Beginning one week prior to the start of the experiment, the level of daily ambient light to which each subject was exposed was recorded every minute using a small light sensor that was attached to the subject's wrist. In the first experiment, saliva samples were collected every hour over a period of 24 h in a dark experimental room (<15 lux) to determine peak salivary melatonin concentration. The second experiment was conducted after the first experiment to determine the percentage of melatonin suppression induced by exposure to light. The starting time of exposure to light was set 2 h before the time of peak salivary melatonin concentration detected in the first experiment. The subjects were exposed to light (1000 lux) for 2 h using white fluorescent lamps (4200 K). The percentage of suppression of melatonin by light was calculated on the basis of the melatonin concentration determined before the start of exposure to light. The percentage of suppression of melatonin 2 h after the start of exposure to light was significantly greater in winter (66.6±18.4%) than summer (37.2±33.2%), p<0.01). The integrated level of daily ambient light from rising time to bedtime in summer was approximately twice that in winter. The results suggest that the increase in suppression of melatonin by light in winter is caused by less exposure to daily ambient light.     

Circadian Phase,Sleepiness, and Light Exposure Assessment in Night Workers With and Without Shift Work Disorder

Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean?±?SD] age: 39.2?±?12.5 yrs; mean yrs on shift?=?9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6?±?8.6 yrs; mean years on shift?=?8.4) participated. All participants were admitted to the sleep center at 16:00?h, where they stayed in a dim light (<10 lux) private room for the study period of 25 consecutive hours. Saliva samples for melatonin assessment were collected at 30-min intervals. Circadian phase was determined from circadian rhythms of salivary melatonin onset (dim light melatonin onset, DLMO) calculated for each individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00?h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42?±?3.25?h, whereas in the SWD group it was 20:42?±?2.21?h (z = 2.4; p?<?.05). Sleep did not differ between groups, except the SWD group showed an earlier bedtime on off days from work relative to that in ANW group. The MSLT corresponding to night work time (01:00–09:00?h) was significantly shorter (3.6?±?.90?min: [M?±?SEM]) in the SWD group compared with that in ANW group (6.8?±?.93?min). DLMO was significantly correlated with insomnia severity (r = ?.68; p < .03), indicating that the workers with more severe insomnia symptoms had an earlier timing of DLMO. Finally, SWD subjects were exposed to more morning light (between 05:00 and 11:00?h) as than ANW ones (798 vs. 180 lux [M?±?SD], respectively z?=??1.7; p?<?.05). These data provide evidence of an internal physiological delay of the circadian pacemaker in asymptomatic night-shift workers. In contrast, individuals with SWD maintain a circadian phase position similar to day workers, leading to a mismatch/conflict between their endogenous rhythms and their sleep-wake schedule. (Author correspondence: vgumeny1@hfhs.org)     

A Compromise Phase Position for Permanent Night Shift Workers: Circadian Phase after Two Night Shifts with Scheduled Sleep and Light/Dark Exposure

Night shift work is associated with a myriad of health and safety risks. Phase‐shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a “snapshot” of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (～3500 lux; ～1100 µW/cm²) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths—especially short wavelengths (“blue‐blockers”)—while traveling home after the shifts, and sleep in the dark (08:30–15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (T_min), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The T_min of the experimental subjects (n=11) was 04:24±0.8 h (mean±SD) at baseline and 7:36±1.4 h after the night shifts. Thus, after two night shifts, the T_min had not yet delayed into the daytime sleep period, which began at 08:30 h. The T_min of the control subjects (n=12) was 04:00±1.2 h at baseline and drifted to 4:36±1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

Bright Light Exposure During the Daytime Affects Circadian Rhythms of Urinary Melatonin and Salivary Immunoglobulin A

The effects of bright light exposure during the daytime on circadian urinary melatonin and salivary immunoglobulin A (IgA) rhythms were investigated in an environmental chamber controlled at a global temperature of 27°C ± 0.2°C and a relative humidity of 60% ± 5%. Seven diurnally active healthy females were studied twice, in bright and dim light conditions. Bright light of 5000 lux was provided by placing fluorescent lamps about 1 meter in front of the subjects during the daytime exposure (06:30-19:30) from 06:30 on day 1 to 10:30 on day 3. Dim light was controlled at 200 lux, and the subjects were allowed to sleep from 22:30 to 06:30 under both light exposure conditions. Urine and saliva were collected at 4h intervals for assessing melatonin and IgA. Melatonin excretion in the urine was significantly greater during the nighttime (i.e., at 06:30 on day 1 and at 02:30 on day 2) after the bright light condition than during the dim light condition. Furthermore, the concentration and the amount of salivary IgA tended to be higher in the bright light than in the dim light condition, especially during the nighttime. Also, salivary IgA concentration and the total amount secreted in the saliva were significantly positively correlated with urinary melatonin. These results are consistent with the hypothesis that bright light exposure during the daytime enhances the nocturnal melatonin increase and activates the mucosal immune response.     

Human Retinal Light Sensitivity and Melatonin Rhythms Following Four Days in Near Darkness

The rods in the retina are responsible for night vision, whereas the cone system enables day vision. We studied whether rod function in humans exhibits an endogenous circadian rhythm and if changes occur in conditions of prolonged darkness. Seven healthy subjects (mean age±SD: 25.6±12.3 yr) completed a 4.5‐day protocol during which they were kept in complete darkness (days 1 and 4) and near darkness (<0.1 lux red light, days 2 and 3). Electroretinography (ERG) and saliva collections were done at intervals of at least 3 h for 27 h on days 1 and 4. Full‐field ERGs were recorded over 10 low‐intensity green light flashes known to test predominantly rod function. As a circadian marker, salivary melatonin concentration was measured by radioimmunoassay. The ERG data showed that rod responsiveness to light progressively diminished in darkness (significantly lower a‐ and b‐wave amplitudes, longer b‐wave implicit time). The decrease in amplitude (b‐wave) from day 1 to day 4 averaged 22±14%. After correction for the darkness‐related linear trend, the circadian variations in ERG indices were weak and usually non‐significant, with slightly higher responsiveness to light during the day than night. Rod sensitivity (by K index) tended to decrease. Strikingly, the overall amount of melatonin secretion (area under 24 h curve) also decreased from day 1 to day 4 by 33.1±18.9% (p=.017). The drift of the melatonin rhythm phase was within the normal range, less than 56 min over three days. There was no significant correlation between the changes in ERG responses and melatonin. In conclusion, scotopic retinal response to (low‐intensity) light and the amount of melatonin secreted are diminished when humans are kept in continuous darkness. Both processes may have a common underlying mechanism implicating a variety of neurochemicals known to be involved in the regulation of both photoreceptor and pineal gland function.     

Diurnal variations of heart rate,urine flow and catecholamine excretion in subjects wearing clothing that provides different thermal insulation

This study investigated the effects of clothing providing different Clo values upon the circadian rhythm of sympathetic nervous activity, as inferred from urinary catecholamine excretion and heart rate, in a thermoneutral environment. Seven health female subjects were studied for 37.5 h, from 21:00 h on the first day to 10:30 h on the third day, in an isolated climatic chamber controlled at 23.8?±?0.2 °C and 60?±?5% RH. Light intensity was 500 lux from 06:30 to 19:30 h, 100 lux from 19:30 to 22:30 h and 0 lux from 22:30 to 06:30 h. Subjects were tested while wearing two different types of clothing: Type L, offering 1.048 Clo of thermal insulation and with the subjects’ extremities covered; and Type H, 0.744 Clo of thermal insulation and the subjects’ extremities exposed. Urine samples were collected every 4 h, their volumes were measured and they were later assayed for their contents of adrenaline and noradrenaline; the mean heart rate for each of these 4-h periods was also calculated. The daily profiles of the variables were assessed by ANOVA, which indicated that the amplitudes and phases of the daily rhythms differed between the clothing types. This result was examined in more detail by assessing the profiles by single and group cosinor analysis (period = 24 h). All four physiological variables showed clear and statistically significant group cosinor rhythms with both types of clothing. The mean amplitudes of urine flow, the excretion rate of urinary adrenaline and heart rate were greater when wearing Type H rather than Type L clothing (p = 0.01 for urine flow and heart rate; p = 0.072 for rate of excretion of adrenaline). Also, the acrophase of the rate of urinary adrenaline excretion was earlier in all subjects wearing Type H rather than Type L clothing (p = 0.048), and the acrophases of urine flow and urinary noradrenaline excretion rate were earlier in six and five of the subjects, respectively. These results show that clothing which is worn in an environment of moderate temperature (23.8 °C) and which offers a lower Clo value (especially if the distal extremities are exposed) might induce an increase in amplitude and/or an advance of acrophase in circadian rhythms of urine flow, excretion of urinary catecholamines and heart rate. It is suggested that these rhythmic changes, which imply changes in the daily profile of sympathetic nervous system activity, might be important when daily thermoregulation and comfort in response to the type of clothing being worn in daily life are considered.     

Dim Light Melatonin Onset in Alcohol-Dependent Men and Women Compared with Healthy Controls

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean?±?SD age: 36.0?±?11.0 yrs of age, 10 women) who were 3–12 wks since their last drink (abstinence: 57.9?±?19.3 d) and 19 age- and sex-matched HCs (34.4?±?10.6 yrs, 5 women). Following a 23:00–06:00?h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00?h bedtime) during which salivary melatonin samples were collected every 30?min beginning at 19:30?h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02?±?00:41?h, than in HC, 20:44?±?00:21?h (t?=??2.4, p?=?.02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18?min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats. (Author correspondence: daconroy@med.umich.edu)     

The Circadian Body Temperature Rhythm in the Elderly: Effect of Single Daily Melatonin Dosing

The present study is part of a more extensive investigation dedicated to the study and treatment of age‐dependent changes/disturbances in the circadian system in humans. It was performed in the Tyumen Elderly Veteran House and included 97 subjects of both genders, ranging from 63 to 91 yrs of age. They lived a self‐chosen sleep‐wake regimen to suit their personal convenience. The experiment lasted 3 wks. After 1 control week, part of the group (n=63) received 1.5 mg melatonin (Melaxen?) daily at 22:30 h for 2 wks. The other 34 subjects were given placebo. Axillary temperature was measured using calibrated mercury thermometers at 03:00, 08:00, 11:00, 14:00, 17:00, and 23:00 h each of the first and third week. Specially trained personnel took the measurements, avoiding disturbing the sleep of the subjects. To evaluate age‐dependent changes, data obtained under similar conditions on 58 young adults (both genders, 17 to 39 yrs of age) were used. Rhythm characteristics were estimated by means of cosinor analyses, and intra‐ and inter‐individual variability by analysis of variance (ANOVA). In both age groups, the body temperature underwent daily changes. The MESOR (36.38±0.19°C vs. 36.17±0.21°C) and circadian amplitude (0.33±0.01°C vs. 0.26±0.01°C) were slightly decreased in the elderly compared to the young adult subjects (p<0.001). The mean circadian acrophase was similar in both age groups (17.19±1.66 vs. 16.93±3.08 h). However, the inter‐individual differences were higher in the older group, with individual values varying between 10:00 and 23:00 h. It was mainly this phase variability that caused a decrease in the inter‐daily rhythm stability and lower group amplitude. With melatonin treatment, the MESOR was lower by 0.1°C and the amplitude increased to 0.34±0.01°C, a similar value to that found in young adults. This was probably due to the increase of the inter‐daily rhythm stability. The mean acrophase did not change (16.93 vs. 16.75 h), although the inter‐individual variability decreased considerably. The corresponding standard deviations (SD) of the group acrophases were 3.08 and 1.51 h (p<0.01). A highly significant correlation between the acrophase before treatment and the phase change under melatonin treatment indicates that this is due to a synchronizing effect of melatonin. Apart from the difference in MESOR, the body temperature rhythm in the elderly subjects undergoing melatonin treatment was not significantly different from that of young adults. The data clearly show that age‐dependent changes mainly concern rhythm stability and synchronization with the 24 h day. A single daily melatonin dose stabilizes/synchronizes the body temperature rhythm, most probably via hypothermic and sleep‐improving effects.     

Opuntia ficus-indica juice supplementation: what role it plays on diurnal variation of short-term maximal exercise?

The aim of this study was to investigate the effect of natural Opuntia ficus-indica juice (OFIJ) supplementation on anaerobic performance at two times of day. Twenty-two healthy male subjects (20.91 ± 1.22; 21.00 ± 0.84 years) divided into two groups: Experimental group (EG: n = 11) and a control group (CG: n = 11) performed two tests-sessions (30-s of Wingate test (i.e. Peak power (PP), Mean power (MP)), Sargent jump test (SJT), sprint 10 m), before and after natural OFIJ supplementation at 07:00 h and 17:00 h. T-test showed that the OFIJ has a potent antioxidant capacity for capturing free radicals following the 22-diphenyl-1-picrylhydrazyl (DPPH^●) test (p < 0.05). Likewise, the ANOVA revealed that anaerobic performances were significantly higher at 17:00 h compared to 07:00 h around the peak of the temperature (p < 0.05) in both EG and CG before supplementation. Moreover, OFIJ lead an improvement of performances with (+2.09% at 07:00 h vs.+9.36% 17:00 h) for PP, (+11.29% at 07:00 h vs.+11.77% 17:00 h) for MP, (+9.42% at 07:00 h vs.+7.63% 17:00 h) for SJT in EG. The RPE scores on response to the Wingate test decrease after OFIJ supplementation (p < 0.01). For the sprint values, a significant improvement was after OFIJ (?7.10% at 07:00 h vs. ?6.45% 17:00 h). However, no change was observed for CG after supplementation. In conclusion, the natural OFIJ supplementation for two weeks appears to ameliorate the performance upon two times of day with great improvement observed in the evening during short-term maximal exercise given the higher muscle damage, inflammatory, and oxidative responses at this time of day. Thus, it’s necessary that athletes, coaches, and medical staff consider the positive effects of Opuntia ficus-indica to improve anaerobic performance.     

Entrainment of Circadian Programs

Circadian rhythms were recently proposed as a measure of physiological state and prognosis in disorders of consciousness (DOC). So far, melatonin regulation was never assessed in vegetative state (VS). Aim of our research was to investigate the nocturnal melatonin levels and light-induced melatonin suppression in a cohort of VS patients. We assessed six consecutive patients (four men, age 33.3?±?9.3 years) with post-traumatic VS and nine age-matched healthy volunteers (five men, age 34.3?±?8.9 years) on two consecutive nights: one baseline and one light exposure night. During baseline, night subjects were in bed in a dim (<5?lux) room from 10?pm to 8?am. Blood samples were collected hourly 00:30–3:30?am (00:30?=?MLT1; 1:30?=?MLT2; 2:30?=?MLT3; and 3:30?=?MLT4). Identical setting was used for melatonin suppression test night, except for the exposure to monochromatic (470?nm) light from 1:30 to 3:30?am. Plasma melatonin levels were evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by melatonin suppression score (caMSS) and suppression rate. We searched for group differences in melatonin levels, differences between repeated samples melatonin concentrations during baseline night and light exposure night, and light-induced suppression of melatonin secretion. During baseline night, controls showed an increase of melatonin (MLT4 vs MLT1, p?=?0.037), while no significant changes were observed in VS melatonin levels (p?=?0.172). Baseline night MLT4 was significantly lower in VS vs controls (p?=?0.036). During light-exposure night, controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2, p?=?0.016 and 0.002, respectively), while VS patients displayed no significant changes. The magnitude of light-induced suppression of melatonin levels was statistically different between groups considering control adjusted caMSS (p?=?0.000), suppression rate (p?=?0.002) and absolute percentage difference (p?=?0.012). These results demonstrate for the first time that VS patients present an alteration in night melatonin secretion and reduced light-induced melatonin suppression. These findings confirm previous studies demonstrating a disruption of the circadian system in DOC and suggest a possible benefit from melatonin supplementation in VS.     

FAILURE OF EXTRAOCULAR LIGHT TO FACILITATE CIRCADIAN RHYTHM REENTRAINMENT IN HUMANS

Although extraocular light can entrain the circadian rhythms of invertebrates and nonmammalian vertebrates, almost all studies show that the mammalian circadian system can only be affected by light to the eyes. The exception is a recent study by Campbell and Murphy that reported phase shifts in humans to bright light applied with fiber-optic pads behind the knees (popliteal region). We tested whether this extraocular light stimulus could accelerate the entrainment of circadian rhythms to a shift of the sleep schedule, as occurs in shift work or jet lag. In experiment 1, the sleep/dark episodes were delayed 8h from baseline for 2 days, and 3h light exposures were timed to occur before the temperature minimum to help delay circadian rhythms. There were three groups: (1) bright (about 13,000 lux) extraocular light from fiber-optic pads, (2) control (dim light, 10–20 lux), and (3) medium-intensity (about 1000 lux) ocular light from light boxes. In experiment 2, the sleep/dark episodes were inverted, and extraocular light was applied either before the temperature minimum to help delay circadian rhythms or after the temperature minimum to help advance rhythms. Circadian phase markers were the salivary dim light melatonin onset (DLMO) and the rectal temperature minimum. There was no evidence that the popliteal extraocular light had a phase-shifting effect in either experiment. Possible reasons for phase shifts in the Campbell and Murphy study and not the current study include the many differences between the protocols. In the current study, there was substantial sleep deprivation before the extraocular light was applied. There was a large shift in the sleep/dark schedule, rather than allowing subjects to sleep each day from midnight to noon, as in the Campbell and Murphy study. Also, when extraocular light was applied in the current protocol, subjects did not experience a change from sleeping to awake, a change in posture (from lying in bed to sitting in a chair), or a change in ocular light (from dark to dim light). Further research is necessary to determine the conditions under which extraocular light might produce phase shifts in human circadian rhythms. (Chronobiology International, 17(6), 807–826, 2000).     

Effects of different light intensities in the morning on dim light melatonin onset

The present study evaluated the effects of exposure to light intensity in the morning on dim light melatonin onset (DLMO). The tested light intensities were 750 lux, 150 lux, 3000 lux, 6000 lux and 12,000 lux (horizontal illuminance at cornea), using commercial 5000 K fluorescent lamps. Eleven healthy males aged 21-31 participated in 2-day experiments for each light condition. On the first experimental day (day 1), subjects were exposed to dim light (<30 lux) for 3 h in the morning (09:00-12:00). On the same day, saliva samples were taken in dim light (<30 lux) every 30 min from 21:00 to 01:00 to determine the DLMO phase. The subjects were allowed to sleep from 01:00 to 08:00. On the second experimental day (day 2), the subjects were exposed to experimental light conditions for 3 h in the morning. The experimental schedule after light exposure was the same as on day 1. On comparing day 2 with day 1, significant phase advances of DLMO were obtained at 3000 lux, 6000 lux and 12,000 lux. These findings indicate that exposure to a necessary intensity from an ordinary light source, such as a fluorescent lamp, in the morning within one day affects melatonin secretion.     

BLUE LIGHT Exposure Reduces Objective Measures of Sleepiness during Prolonged Nighttime Performance Testing

This study examined the effects of nocturnal exposure to dim, narrowband blue light (460 nm, ～1 lux, 2 µW/cm²), compared to dim broad spectrum (white) ambient light (～0.2 lux, 0.5 µW/cm²), on subjective and objective indices of sleepiness during prolonged nighttime performance testing. Participants were also exposed to a red light (640 nm, ～1 lux, 0.7µW/cm²) placebo condition. Outcome measures were driving simulator and psychomotor vigilance task (PVT) performance, subjective sleepiness, salivary melatonin, and electroencephalographic (EEG) activity. The study had a repeated-measures design, with three counterbalanced light conditions and a four-week washout period between each condition. Participants (n?=?8) maintained a regular sleep-wake schedule for 14 days prior to the ～14 h laboratory study, which consisted of habituation to light conditions followed by neurobehavioral performance testing from 21:00 to 08:30 h under modified constant-routine conditions. A neurobehavioral test battery (2.5 h) was presented four times between 21:00 and 08:30 h, with a 30 min break between each. From 23:30 to 05:30 h, participants were exposed to blue or red light, or remained in ambient conditions. Compared to ambient light exposure, blue light exposure suppressed EEG slow wave delta (1.0–4.5 Hz) and theta (4.5–8 Hz) activity and reduced the incidence of slow eye movements. PVT reaction times were significantly faster in the blue light condition, but driving simulator measures, subjective sleepiness, and salivary melatonin levels were not significantly affected by blue light. Red light exposure, as compared to ambient light exposure, reduced the incidence of slow eye movements. The results demonstrate that low-intensity, blue light exposure can promote alertness, as measured by some of the objective indices used in this study, during prolonged nighttime performance testing. Low intensity, blue light exposure has the potential to be applied to situations where it is desirable to increase alertness but not practical or appropriate to use bright light, such as certain occupational settings.     

The Effect on Body Temperature and Melatonin of A 39-H Constant Routine with Two Different Light Levels at Nighttime

Eight healthy subjects were studied during 39-h spans (from 07:00 on one day until 22:00 the second) in which they remained awake. During one experiment, subjects were exposed to 100 lux of light between 18:00 and 8:00, and during a second experiment, they were exposed to 1000 lux during the same time span. Throughout the daytime period, they were exposed to normal daylight (1500 lux or more). The nighttime 1000-lux light treatment suppressed the melatonin metabolite aMT6s, while the 100 lux treatment did not. On the treatment day, the 1000 lux, in comparison to the 100 lux, light treatment resulted in both an elevated temperature minimum and a delay in its clock-time occurrence overnight. No real circadian phase shift in the temperature, urinary melatonin, or Cortisol rhythms was detected after light treatment. This study confirmed that nocturnal exposure to lower light intensities is capable of modifying circadian variables more than previously estimated. The immediate effects of all-night light treatment are essentially not different from those of evening light. This may be important if bright light is used to improve alertness of night workers. Whether subsequent daytime alertness and sleep recovery are affected by the protocol used in our study remains to be determined.     

THERMOREGULATORY EFFECT IN HUMANS OF SUPPRESSED ENDOGENOUS MELATONIN BY PRE-SLEEP BRIGHT-LIGHT EXPOSURE IN A COLD ENVIRONMENT

This study investigated the physiological function of suppressed melatonin through thermoregulation in a cold environment. Interactions between thermoregulation directly affected by exposure to a cold environment and indirectly affected by endogenous melatonin suppression by bright-light exposure were examined. Ten male subjects were exposed to two different illumination intensities (30 and 5000 lux) for 4.5?h, and two different ambient temperatures (15 and 27°C) for 2?h before sleep under dark and thermoneutral conditions. Salivary melatonin level was suppressed by bright light (p?<?0.001), although the ambient temperature condition had no significant effect on melatonin. During sleep, significant effects of pre-sleep exposure to a cold ambient temperature (p?<?0.001) and bright light (p?<?0.01) on rectal temperature (T_re) were observed. Pre-sleep, bright-light exposure led to an attenuated fall in T_re during sleep. Moreover, T_re dropped more precipitously after cold exposure than thermoneutral conditions (cold: ?0.54?±?0.07°C/h; thermoneutral: ?0.16?±?0.03°C/h; p?<?0.001). Pre-sleep, bright-light exposure delayed the nadir time of T_re under thermoneutral conditions (p?<?0.05), while cold exposure masked the circadian rhythm with a precipitous decrease in T_re. A significant correlation between the T_re nadir and melatonin level (r?=??0.774, p?<?0.05) indicated that inter-individual differences with higher melatonin levels lead to a reduction in T_re after cold exposure. These results suggest that suppressed endogenous melatonin inhibits the downregulation of the body temperature set-point during sleep. (Author correspondence: ishibasi@design.kyushu-u.ac.jp)     

Bright-light exposure during daytime sleeping affects nocturnal melatonin secretion after simulated night work

The guidelines for night and shift workers recommend that after night work, they should sleep in a dark environment during the daytime. However, staying in a dark environment during the daytime reduces nocturnal melatonin secretion and delays its onset. Daytime bright-light exposure after night work is important for melatonin synthesis the subsequent night and for maintaining the circadian rhythms. However, it is not clear whether daytime sleeping after night work should be in a dim- or a bright-light environment for maintaining melatonin secretion. The aim of this study, therefore, was to evaluate the effect of bright-light exposure during daytime sleeping on nocturnal melatonin secretion after simulated night work. Twelve healthy male subjects, aged 24.8 ± 4.6 (mean ± SD), participated in 3-day sessions under two experimental conditions, bright light or dim light, in a random order. On the first day, the subjects entered the experimental room at 16:00 and saliva samples were collected every hour between 18:00 and 00:00 under dim-light conditions. Between 00:00 and 08:00, they participated in tasks that simulated night work. At 10:00 the next morning, they slept for 6 hours under either a bright-light condition (>3000 lx) or a dim-light condition (<50 lx). In the evening, saliva samples were collected as on the first day. The saliva samples were analyzed for melatonin concentration. Activity and sleep times were recorded by a wrist device worn throughout the experiment. In the statistical analysis, the time courses of melatonin concentration were compared between the two conditions by three-way repeated measurements ANOVA (light condition, day and time of day). The change in dim light melatonin onset (ΔDLMO) between the first and second days, and daytime and nocturnal sleep parameters after the simulated night work were compared between the light conditions using paired t-tests. The ANOVA results indicated a significant interaction (light condition and3 day) (p = .006). Post hoc tests indicated that in the dim-light condition, the melatonin concentration was significantly lower on the second day than on the first day (p = .046); however, in the bright-light condition, there was no significant difference in the melatonin concentration between the days (p = .560). There was a significant difference in ΔDLMO between the conditions (p = .015): DLMO after sleeping was advanced by 11.1 ± 17.4 min under bright-light conditions but delayed for 7.2 ± 13.6 min after sleeping under dim-light conditions. No significant differences were found in any sleep parameter. Our study demonstrated that daytime sleeping under bright-light conditions after night work could not reduce late evening melatonin secretion until midnight or delay the phase of melatonin secretion without decreasing the quality of the daytime sleeping. Thus, these results suggested that, to enhance melatonin secretion and to maintain their conventional sleep–wake cycle, after night work, shift workers should sleep during the daytime under bright-light conditions rather than dim-light conditions.     

Differences in circadian phase and weekday/weekend sleep patterns in a sample of middle-aged morning types and evening types

Factors contributing to sleep timing and sleep restriction in daily life include chronotype and less flexibility in times available for sleep on scheduled days versus free days. There is some evidence that these two factors interact, with morning types and evening types reporting similar sleep need, but evening types being more likely to accumulate a sleep debt during the week and to have greater sleep extension on weekend nights. The aim of the present study was to evaluate the independent contributions of circadian phase and weekend-to-weekday variability to sleep timing in daily life. The study included 14 morning types and 14 evening types recruited from a community-based sample of New Zealand adults (mean age 41.1 ± 4.7 years). On days 1–15, the participants followed their usual routines in their own homes and daily sleep start, midpoint and end times were determined by actigraphy and sleep diaries. Days 16–17 involved a 17 h modified constant routine protocol in the laboratory (17:00 to 10:00, <20 lux) with half-hourly saliva samples assayed for melatonin. Mixed model ANCOVAs for repeated measures were used to investigate the independent relationships between sleep start and end times (separate models) and age (30–39 years versus 40–49 years), circadian phase [time of the dim light melatonin onset (DLMO)] and weekday/weekend schedules (Sunday–Thursday nights versus Friday–Saturday nights). As expected on weekdays, evening types had later sleep start times (mean = 23:47 versus 22:37, p < .0001) and end times (mean = 07:14 versus 05:56, p < .0001) than morning types. Similarly on weekend days, evening types had later sleep start times (mean = 00:14 versus 23:07, p = .0032) and end times (mean = 08:56 versus 07:04, p < .0001) than morning types. Evening types also had later DLMO (22:06 versus 20:46, p = .0002) than morning types (mean difference = 80.4 min, SE = 18.6 min). The ANCOVA models found that later sleep start times were associated with later DLMO (p = .0172) and weekend-to-weekday sleep timing variability (p < .0001), after controlling for age, while later sleep end times were associated with later DLMO (p = .0038), younger age (p = .0190) and weekend days (p < .0001). Sleep end times showed stronger association with DLMO (for every 30 min delay in DLMO, estimated mean sleep end time occurred 14.0 min later versus 10.19 min later for sleep start times). Sleep end times also showed greater delays on weekends versus weekdays (estimated mean delay for sleep end time = 84 min, for sleep start time = 28 min). Comparing morning types and evening types, the estimated contributions of the DLMO to the mean observed differences in sleep timing were on weekdays, 39% for sleep start times and 49% for sleep end times; and on weekends, 41% for sleep start times and 34% of sleep end times. We conclude that differences in sleep timing between morning types and evening types were much greater than would be predicted on the basis of the independent contribution of the difference in DLMO on both weekdays and weekend days. The timing of sleep in daily life involves complex interactions between physiological and psychosocial factors, which may be moderated by age in adults aged 30–49 years.