Abstract We compared the effects of bedroom-intensity light from a standard fluorescent and a blue- (i.e., short-wavelength) depleted LED source on melatonin suppression, alertness, and sleep. ...Sixteen healthy participants (8 females) completed a 4-day inpatient study. Participants were exposed to blue-depleted circadian-sensitive (C-LED) light and a standard fluorescent light (FL, 4100 K) of equal illuminance (50 lx) for 8 h prior to a fixed bedtime on two separate days in a within-subject, randomized, cross-over design. Each light exposure day was preceded by a dim light (< 3 lx) control at the same time 24 h earlier. Compared to the FL condition, control-adjusted melatonin suppression was significantly reduced. Although subjective sleepiness was not different between the two light conditions, auditory reaction times were significantly slower under C-LED conditions compared to FL 30 min prior to bedtime. EEG-based correlates of alertness corroborated the reduced alertness under C-LED conditions as shown by significantly increased EEG spectral power in the delta-theta (0.5–8.0 Hz) bands under C-LED as compared to FL exposure. There was no significant difference in total sleep time (TST), sleep efficiency (SE%), and slow-wave activity (SWA) between the two conditions. Unlike melatonin suppression and alertness, a significant order effect was observed on all three sleep variables, however. Individuals who received C-LED first and then FL had increased TST, SE% and SWA averaged across both nights compared to individuals who received FL first and then C-LED. These data show that the spectral characteristics of light can be fine-tuned to attenuate non-visual responses to light in humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Studies suggest that female reproductive hormones are under circadian regulation, although methodological differences have led to inconsistent findings.
To determine whether circulating levels of ...reproductive hormones exhibit circadian rhythms.
Blood samples were collected across ∼90 consecutive hours, including 2 baseline days under a standard sleep-wake schedule and ∼50 hours of extended wake under constant routine (CR) conditions.
Intensive Physiological Monitoring Unit, Brigham and Women's Hospital.
Seventeen healthy premenopausal women (22.8 ± 2.6 years; nine follicular; eight luteal).
Fifty-hour CR.
Plasma estradiol (E2), progesterone (P4), LH, FSH, SHBG, melatonin, and core body temperature.
All hormones exhibited significant 24-hour rhythms under both standard sleep-wake and CR conditions during the follicular phase (P < 0.05). In contrast, only FSH and SHBG were significantly rhythmic during the luteal phase. Rhythm acrophases and amplitudes were similar between standard sleep-wake and CR conditions. The acrophase occurred in the morning for P4; in the afternoon for FSH, LH, and SHBG; and during the night for E2.
Our results confirm previous reports of ∼24-hour rhythms in many female reproductive hormones in humans under ambulatory conditions but demonstrate that these hormones are under endogenous circadian regulation, defined as persisting in the absence of external time cues. These results may have important implications for the effects of circadian disruption on reproductive function.
Previous studies have demonstrated short-wavelength sensitivity for the acute alerting response to nocturnal light exposure. We assessed daytime spectral sensitivity in alertness, performance, and ...waking electroencephalogram (EEG).
Between-subjects (n = 8 per group).
Inpatient intensive physiologic monitoring unit.
Sixteen healthy young adults (mean age ± standard deviation = 23.8 ± 2.7 y).
Equal photon density exposure (2.8 × 10(13) photons/cm(2)/s) to monochromatic 460 nm (blue) or 555 nm (green) light for 6.5 h centered in the middle of the 16-h episode of wakefulness during the biological day. Results were compared retrospectively to 16 individuals who were administered the same light exposure during the night.
Daytime and nighttime 460-nm light exposure significantly improved auditory reaction time (P < 0.01 and P < 0.05, respectively) and reduced attentional lapses (P < 0.05), and improved EEG correlates of alertness compared to 555-nm exposure. Whereas subjective sleepiness ratings did not differ between the two spectral conditions during the daytime (P > 0.05), 460-nm light exposure at night significantly reduced subjective sleepiness compared to 555-nm light exposure at night (P < 0.05). Moreover, nighttime 460-nm exposure improved alertness to near-daytime levels.
The alerting effects of short-wavelength 460-nm light are mediated by counteracting both the circadian drive for sleepiness and homeostatic sleep pressure at night, but only via reducing the effects of homeostatic sleep pressure during the day.
Abstract
This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring ...together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep–wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.
Abstract
Context
Dyslipidemia and cardiovascular disease are common in shift workers and eating at night may contribute to this pathophysiology.
Objective
To examine the effects of eating at ...different times of day on lipid profiles.
Design
Two 24-hour baseline days with 8 hours of sleep, 3 meals (breakfast, lunch, dinner) and a snack, followed by a 40-hour constant routine (CR) with hourly isocaloric meals.
Setting
Intensive Physiological Monitoring Unit, Brigham and Women’s Hospital.
Participants
Twenty-one healthy adults 23.4 ± 2.7 years, 5F
Intervention
Forty-hour CR.
Main Outcome Measures
A standard clinical lipid panel, consisting of total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), was assayed in blood samples collected 4-hourly across ~4 days.
Results
When participants ate at night, levels of TG were similar to eating during the day, however, these levels at night were reached with consuming approximately half the calories. Additionally, 24-hour levels of TG were 10% higher when meals were consumed hourly across 24 hours compared to consuming a typical 3-meal schedule while awake during the day and sleeping at night. The endogenous circadian rhythms of TG, which peaked at night, were shifted earlier by ~10 hours under baseline conditions, whereas the rhythms in total cholesterol, HDL-C, and LDL-C remained unchanged and peaked in the afternoon.
Conclusions
The time-of-day dependency on postprandial lipid metabolism, which leads to hypersensitivity in TG responses when eating at night, may underlie the dyslipidemia and elevated cardiovascular disease risk observed in shift workers.
While studies suggest that light and feeding patterns can reset circadian rhythms in various metabolites, whether these shifts follow a predictable pattern is unknown. We describe the first phase ...response curves (PRC) for lipids and hepatic proteins in response to combined light and food stimuli. The timing of plasma rhythms was assessed by constant routine before and after exposure to a combined 6.5-hour blue light exposure and standard meal schedule, which was systematically varied by ~20° between in0000dividuals. We find that the rhythms shift according to a PRC, with generally greater shifts for lipids and liver proteins than for melatonin. PRC timing varies relative to the stimulus, with albumin and triglyceride PRCs peaking at a time similar to melatonin whereas the cholesterol and high-density lipoprotein PRCs are offset by ~12 h. These data have important implications for treating circadian misalignment in shiftworkers who consume meals and are exposed to light around the clock.
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Intermittent light (IML) pulses are more efficient per minute of exposure than continuous exposure in resetting the phase of the human circadian pacemaker. We assessed the spectral ...sensitivity in phase resetting, melatonin suppression and alertness induced by IML pulses. Twelve healthy young adults (6 females; mean age ± SD = 25.4 ± 3.6 years) were exposed to six monochromatic light pulses (2.8 × 1013 photons/cm2/s) over a 6.5 h window during the biological night. Six participants (3F) received 6 × 15-minute 460 nm (blue) pulses and six participants received 6 × 2-minute 555 nm (green) light pulses. Results were compared to historical data in 16 individuals who received continuous 460 nm (n = 8) or 555 nm (n = 8) light exposure using an identical protocol. As expected, long duration continuous 460 nm light exposure induced the largest total phase delay shifts, but intermittent 555 nm light induced the largest phase delay shifts per minute of the photic stimulus. Melatonin suppression was significantly higher under continuous light exposure compared to intermittent exposure patterns, and for 460 nm versus 555 nm exposure (under both light patterns). These data extend prior work showing a non-linear relationship between light exposure duration and phase resetting responses and illustrate the potential role of light wavelength, and therefore photoreceptor recruitment, in mediating these responses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Human circadian, neuroendocrine, and neurobehavioral responses to light are mediated primarily by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs) but they also ...receive input from visual photoreceptors. Relative photoreceptor contributions are irradiance- and duration-dependent but results for long-duration light exposures are limited. We constructed irradiance-response curves and action spectra for melatonin suppression and circadian resetting responses in participants exposed to 6.5-h monochromatic 420, 460, 480, 507, 555, or 620 nm light exposures initiated near the onset of nocturnal melatonin secretion. Melatonin suppression and phase resetting action spectra were best fit by a single-opsin template with lambda
at 481 and 483 nm, respectively. Linear combinations of melanopsin (ipRGC), short-wavelength (S) cone, and combined long- and medium-wavelength (L+M) cone functions were also fit and compared. For melatonin suppression, lambda
was 441 nm in the first quarter of the 6.5-h exposure with a second peak at 550 nm, suggesting strong initial S and L+M cone contribution. This contribution decayed over time; lambda
was 485 nm in the final quarter of light exposure, consistent with a predominant melanopsin contribution. Similarly, for circadian resetting, lambda
ranged from 445 nm (all three functions) to 487 nm (L+M-cone and melanopsin functions only), suggesting significant S-cone contribution, consistent with recent model findings that the first few minutes of a light exposure drive the majority of the phase resetting response. These findings suggest a possible initial strong cone contribution in driving melatonin suppression and phase resetting, followed by a dominant melanopsin contribution over longer duration light exposures.
Although evidence exists for a daily rhythm in bone metabolism, the contribution of factors such as melatonin levels, the light–dark cycle, and the sleep–wake cycle is difficult to differentiate ...given their highly correlated time courses. To examine these influences on bone resorption, we collected 48-h sequential urine samples under both ambulatory (8-h sleep:16-h wake) and constant routine (CR) (constant wake, posture, nutrition and dim light) conditions from 20 healthy premenopausal women. Urinary 6-sulphatoxymelatonin (aMT6s; ng/h) and the bone resorption marker amino-terminal cross-linked collagen I telopeptide (NTx; bone collagen equivalents nM/h) were assayed and fit by cosinor models to determine significant 24-h rhythms and acrophase. Most participants had significant 24-h aMT6s rhythms during both ambulatory and CR conditions (95 and 85%, respectively), but fewer had significant 24-h NTx rhythms (70 and 70%, respectively). Among individuals with significant rhythms, mean (± SD) aMT6s acrophase times were 3:57 ± 1:50 and 3:43 ± 1:25 h under ambulatory and CR conditions, respectively, and 23:44 ± 5:55 and 3:06 ± 5:15 h, respectively, for NTx. Mean 24-h levels of both aMT6s and NTx were significantly higher during CR compared with ambulatory conditions (
p
< 0.0001 and
p
= 0.03, respectively). Menstrual phase (follicular versus luteal) had no impact on aMT6s or NTx timing or 24-h levels. This study confirms an endogenous circadian rhythm in NTx with a night-time peak when measured under CR conditions, but also confirms that environmental factors such as the sleep–wake or light–dark cycles, posture or meal timing affects overall concentrations and peak timing under ambulatory conditions, the significance of which remains unclear.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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