Light-induced Melatonin Suppression Research Articles

Effect of Diurnal Light Conditions on Electroretinogram Responses to Red and Blue Flickering Light.

Bright light impacts the human circadian system such that exposure to bright light at night can suppress melatonin secretion, and exposure to bright light in the morning prevents light-induced melatonin suppression at night. The preventive effect of morning light may attenuate the prior history of light sensitivity of intrinsically photosensitive retinal ganglion cells (ipRGCs) that regulate the circadian system. In this study, we evaluated electroretinogram (ERG) responses to red and blue flickering lights following dim and bright daylight conditions. Eleven healthy females underwent ERG measurements during exposure to 33Hz flickering red or blue light under dim and bright daytime conditions. We averaged ERG waves for 50 flickering light pulses of the trigger signal data. We obtained the amplitude of the signal-averaged ERG by calculating the difference between the waves' peaks and bottoms. Although there was no significant dim and bright light difference in the amplitude of ERG waves, the ERG amplitude to flickering blue light under the bright light condition was significantly lower than to flickering blue light under the dim light condition. In this study, blue light stimulated mainly ipRGCs and S-cones. Since S-cones may contribute minimally to the light-adapted 33Hz flicker ERG results, our findings suggest that bright light during the daytime attenuates the sensitivity of human ipRGCs.

Greater sensitivity of the circadian system of women to bright light, but not dim-to-moderate light.

Women typically sleep and wake earlier than men and have been shown to have earlier circadian timing relative to the light/dark cycle that synchronizes the clock. A potential mechanism for earlier timing in women is an altered response of the circadian system to evening light. We characterized individual-level dose-response curves for light-induced melatonin suppression using a within-subjects protocol. Fifty-six participants (29 women, 27 men; aged 18-30 years) were exposed to a range of light illuminances (10, 30, 50, 100, 200, 400, and 2000 lux) using melatonin suppression relative to a dim control (<1 lux) as a marker of light sensitivity. Women were free from hormonal contraception. To examine the potential influence of sex hormones, estradiol and progesterone was examined in women and testosterone was examined in a subset of men. Menstrual phase was monitored using self-reports and estradiol and progesterone levels. Women exhibited significantly greater melatonin suppression than men under the 400-lux and 2000-lux conditions, but not under lower light conditions (10-200 lux). Light sensitivity did not differ by menstrual phase, nor was it associated with levels of estradiol, progesterone, or testosterone, suggesting the sex differences in light sensitivity were not acutely driven by circulating levels of sex hormones. These results suggest that sex differences in circadian timing are not due to differences in the response to dim/moderate light exposures typically experienced in the evening. The finding of increased bright light sensitivity in women suggests that sex differences in circadian timing could plausibly instead be driven by a greater sensitivity to phase-advancing effects of bright morning light.

Melatonin suppression by light involves different retinal photoreceptors in young and older adults.

Age-related sleep and circadian rhythm disturbances may be due to altered nonvisual photoreception. Here, we investigated the temporal dynamics of light-induced melatonin suppression in young and older individuals. In a within-subject design study, young and older participants were exposed for 60 min (0030-0130 at night) to nine narrow-band lights (range: 420-620 nm). Plasma melatonin suppression was calculated at 15, 30, 45, and 60 min time intervals. Individual spectral sensitivity of melatonin suppression and photoreceptor contribution were predicted for each interval and age group. In young participants, melanopsin solely drove melatonin suppression at all time intervals, with a peak sensitivity at 485.3 nm established only after 15 min of light exposure. Conversely, in older participants, spectral light-driven melatonin suppression was best explained by a more complex model combining melanopsin, S-cone, and M-cone functions, with a stable peak (~500 nm) at 30, 45, and 60 min of light exposure. Aging is associated with a distinct photoreceptor contribution to melatonin suppression by light. While in young adults melanopsin-only photoreception is a reliable predictor of melatonin suppression, in older individuals this process is jointly driven by melanopsin, S-cone, and M-cone functions. These findings offer new prospects for customizing light therapy for older individuals.

A pilot study of light exposure as a countermeasure for menstrual phase-dependent neurobehavioral performance impairment in women

ObjectiveTo examine effects of menstrual phase and nighttime light exposure on subjective sleepiness and auditory Psychomotor Vigilance Task performance. MethodsTwenty-nine premenopausal women (12 =Follicular; 17 =Luteal) completed a 6.5-hour nighttime monochromatic light exposure with varying wavelengths (420-620 nm) and irradiances (1.03-14.12 µW/cm2). Subjective sleepiness, reaction time, and attentional lapses were compared between menstrual phases in women with minimal (<33%) or substantial (≥33%) light-induced melatonin suppression. ResultsWhen melatonin was not suppressed, women in the follicular phase had significantly worse reaction time (mean difference=145.1 ms, 95% CI 51.8-238.3, p < .001, Cohen’s D=1.9) and lapses (mean difference=12.9 lapses, 95% CI 4.37-21.41, p < .001, Cohen’s D=1.7) compared to women in the luteal phase. When melatonin was suppressed, women in the follicular phase had significantly better reaction time (mean difference=152.1 ms, 95% CI 43.88-260.3, p < .001, Cohen’s D=1.7) and lapses (mean difference=12.3 lapses, 95% CI 1.14-25.6, p < .01, Cohen’s D=1.6) compared to when melatonin was not suppressed, such that their performance was not different (p > .9) from women in the luteal phase. Subjective sleepiness did not differ by menstrual phase (mean difference=0.6, p > .08) or melatonin suppression (mean difference=0.2, p > .4). ConclusionsNighttime light exposure sufficient to suppress melatonin can also mitigate neurobehavioral performance deficits associated with the follicular phase. Despite the relatively small sample size, these data suggest that nighttime light may be a valuable strategy to help reduce errors and accidents in female shift workers.

α-opic flux models based on the five fundus photoreceptors for prediction of light-induced melatonin suppression

Light is effective to suppress the melatonin and affects the non-visual responses. The relationship between light conditions and melatonin suppression is significant when designing light environments. Based on the α-opic illuminances of five fundus photoreceptors, various previous models are built to fit and predict the experimental melatonin suppression. In this study, we present models based on α-opic fluxes, which are products of α-opic illuminances and pupil areas, to improve the fitting results of the experimental melatonin suppression. For 30- and 90-min light exposures, the α-opic flux models present higher adjusted R-squared and lower root mean square of error (RMSE) when fitting the experimental melatonin suppression, regardless of pupil dilation or not. The α-opic flux models also explain the spectral opponency on melatonin suppression. According to the residuals between predicable and experimental melatonin suppression, the effects of pupil dilation, type of light source, and subject's age are further discussed. The subject's age has little effect on the melatonin suppression. The α-opic flux models decrease the fitting residuals under different conditions, improving the applicability of the fitting models on melatonin suppression.

Unanticipated daytime melatonin secretion on a simulated night shift schedule generates a distinctive 24-h melatonin rhythm with antiphasic daytime and nighttime peaks.

The daily rhythm of plasma melatonin concentrations is typically unimodal, with one broad peak during the circadian night and near-undetectable levels during the circadian day. Light at night acutely suppresses melatonin secretion and phase shifts its endogenous circadian rhythm. In contrast, exposure to darkness during the circadian day has not generally been reported to increase circulating melatonin concentrations acutely. Here, in a highly-controlled simulated night shift protocol with 12-h inverted behavioral/environmental cycles, we unexpectedly found that circulating melatonin levels were significantly increased during daytime sleep (p < .0001). This resulted in a secondary melatonin peak during the circadian day in addition to the primary peak during the circadian night, when sleep occurred during the circadian day following an overnight shift. This distinctive diurnal melatonin rhythm with antiphasic peaks could not be readily anticipated from the behavioral/environmental factors in the protocol (e.g., light exposure, posture, diet, activity) or from current mathematical model simulations of circadian pacemaker output. The observation, therefore, challenges our current understanding of underlying physiological mechanisms that regulate melatonin secretion. Interestingly, the increase in melatonin concentration observed during daytime sleep was positively correlated with the change in timing of melatonin nighttime peak (p = .002), but not with the degree of light-induced melatonin suppression during nighttime wakefulness (p = .92). Both the increase in daytime melatonin concentrations and the change in the timing of the nighttime peak became larger after repeated exposure to simulated night shifts (p = .002 and p = .006, respectively). Furthermore, we found that melatonin secretion during daytime sleep was positively associated with an increase in 24-h glucose and insulin levels during the night shift protocol (p = .014 and p = .027, respectively). Future studies are needed to elucidate the key factor(s) driving the unexpected daytime melatonin secretion and the melatonin rhythm with antiphasic peaks during shifted sleep/wake schedules, the underlying mechanisms of their relationship with glucose metabolism, and the relevance for diabetes risk among shift workers.

Predicting melatonin suppression by light in humans: Unifying photoreceptor-based equivalent daylight illuminances, spectral composition, timing and duration of light exposure.

Light‐induced melatonin suppression data from 29 peer‐reviewed publications was analysed by means of a machine‐learning approach to establish which light exposure characteristics (ie photopic illuminance, five α‐opic equivalent daylight illuminances [EDIs], duration and timing of the light exposure, and the dichotomous variables pharmacological pupil dilation and narrowband light source) are the main determinants of melatonin suppression. Melatonin suppression in the data set was dominated by four light exposure characteristics: (1) melanopic EDI, (2) light exposure duration, (3) pupil dilation and (4) S‐cone‐opic EDI. A logistic model was used to evaluate the influence of each of these parameters on the melatonin suppression response. The final logistic model was only based on the first three parameters, since melanopic EDI was the best single (photoreceptor) predictor that was only outperformed by S‐cone‐opic EDI for (photopic) illuminances below 21 lux. This confirms and extends findings on the importance of the metric melanopic EDI for predicting biological effects of light in integrative (human‐centric) lighting applications. The model provides initial and general guidance to lighting practitioners on how to combine spectrum, duration and amount of light exposure when controlling non‐visual responses to light, especially melatonin suppression. The model is a starting tool for developing hypotheses on photoreceptors’ contributions to light's non‐visual responses and helps identifying areas where more data are needed, like on the S‐cone contribution at low illuminances.

Effects of 2-hour nighttime nap on melatonin concentration and alertness during 12-hour simulated night work.

A nighttime nap is expected to mitigate melatonin suppression during night work by blocking light input to the retina, but it is unclear. In the present study, we investigated the effects of a nap break on melatonin level, subjective sleepiness, and vigilance performance during simulated night work. Eleven healthy young males (mean ± SD age: 22.2 ± 4.1 years) participated in counterbalanced crossover design experiments with two conditions (nap vs. no nap). The subjects performed 12-hour simulated night work from 21:00 to 09:00 h (illuminance: ∼500 lx). Subjects with a nap condition took a nap for 2 hours in a dark room from 03:00, while subjects with a no nap condition continued the simulated night work. The results showed that immediately after the 2-h nap break, the melatonin level at 05:00 h temporarily recovered from light-induced melatonin suppression during the simulated night work but significantly suppressed again at 07:00 and 09:00 h. Subjective alertness and vigilance performance were impaired immediately after the nap break but subsequently enhanced. The results suggest that a single nap break for 2 hours could be a strategy to enhance alertness during the last part of night shift but inadequate for mitigating melatonin suppression.

Salivary melatonin suppression under 100-Hz flickering blue light and non-flickering blue light conditions

Bright light at night has been known to suppress melatonin secretion. Photoreceptors, known as intrinsically photosensitive retinal ganglion cells (ipRGCs), project dark/bright information into the superchiasmatic nucleus, which regulates the circadian system. Electroretinograms of ipRGCs show fluctuation that is synchronized with light ON-OFF stimulation. This finding suggests that the flickering condition of light may have an impact on our circadian system. In this study, we evaluate light-induced melatonin suppression under flickering and non-flickering light conditions. Fifteen male subjects between the ages of 20 and 23 years (mean ± SD, 21.9 ± 1.9) were exposed to three light conditions (dim, 100-Hz flickering and non-flickering light) from 1:00 a.m. to 2:30 a.m. Saliva samples were taken just before 1:00 and at 1:15, 1:30, 2:00, and 2:30 a.m. Repeated-measure t-test with Bonferroni correction showed a significant decrease in melatonin levels under both 100-Hz and non-flickering light conditions compared to dim light conditions after 2:00 a.m. Moreover, at 2:30 a.m., the rate of change in melatonin level under 100 Hz of flickering light was significantly lower than that under non-flickering light. Our present findings suggest that 100-Hz flickering light may suppress melatonin secretion more than non-flickering light.

Light-induced melatonin suppression in 3-4 year-old children

Light-induced melatonin suppression in 3-4 year-old children

Reduced melatonin synthesis in pregnant night workers: Metabolic implications for offspring

Several novel animal studies have shown that intrauterine metabolic programming can be modified in the event of reduced melatonin synthesis during pregnancy, leading to glucose intolerance and insulin resistance in the offspring. It is therefore postulated that female night workers when pregnant may expose the offspring to unwanted health threats. This may be explained by the fact that melatonin is essential for regulating energy metabolism and can influence reproductive activity. Moreover, the circadian misalignment caused by shift work affects fertility and the fetus, increasing the risk of miscarriage, premature birth and low birth weight, phenomena observed in night workers. Thus, we hypothesize that light-induced melatonin suppression as a result of night work may alter intrauterine metabolic programming in pregnant women, potentially leading to metabolic disorders in their offspring.

High sensitivity and interindividual variability in the response of the human circadian system to evening light

Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light-stimuli at extreme ends of the circadian system's dose-response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30-300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose-response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18-30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10-2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock's role in human health and disease.

Melatonin profiles during the third trimester of pregnancy and health status in the offspring among day and night workers: A case series

Successful pregnancy requires adaptation in maternal physiology. During intrauterine life the mother's circadian timing system supports successful birth and postnatal development. Maternal melatonin is important to transmit circadian timing and day length to the fetus. This study aims to describe the third trimester of pregnancy among day (n = 5) and night (n = 3) workers by assessing their melatonin levels in a natural environment. Additionally, we describe the worker's metabolic profiles and compare the health status of the newborns between groups of day and night working mothers. Our results indicate an occurrence of assisted delivery (cesarean and forceps) among night workers. Moreover, the newborns of night workers showed lower Apgar index and breastfeeding difficulty indicating a worse condition to deal with the immediate outside the womb environment. Additionally, there was lower night-time melatonin production among pregnant night workers compared to day workers. These findings may be related to light-induced suppression of melatonin that occurs during night work. We conclude that night work and consequent exposure to light at unconventional times might compromise the success of pregnancy and the health of the newborn. Further studies need to be carried out to monitor pregnancy and newborn health in pregnant night workers.

Suppression of salivary melatonin secretion under 100-Hz flickering and non-flickering blue light

BackgroundBright light at night is known to suppress melatonin secretion. Novel photoreceptors named intrinsically photosensitive retinal ganglion cells (ipRGCs) are mainly responsible for projecting dark/bright information to the suprachiasmatic nucleus and thus regulating the circadian system. However, it has been shown that the amplitude of the electroretinogram of ipRGCs is considerably lower under flickering light at 100 Hz than at 1–5 Hz, suggesting that flickering light may also affect the circadian system. Therefore, in this study, we evaluated light-induced melatonin suppression under flickering and non-flickering light.MethodsTwelve male participants between the ages of 20 and 23 years (mean ± S.D. = 21.6 ± 1.5 years) were exposed to three light conditions (dim, 100-Hz flickering, and non-flickering blue light) from 1:00 A.M. to 2:30 A.M., and saliva samples were obtained just before 1:00 A.M. and at 1:15, 1:30, 2:00, and 2:30 A.M.ResultsA repeated measures t test with Bonferroni correction showed that at 1:15 A.M., melatonin concentrations were significantly lower following exposure to non-flickering light compared with dim light, whereas there was no significant difference between the dim and 100-Hz flickering light conditions. By contrast, after 1:30 A.M., the mean melatonin concentrations were significantly lower under both 100-Hz flickering and non-flickering light than under dim light.ConclusionAlthough melatonin suppression rate tended to be lower under 100-Hz flickering light than under non-flickering light at the initial 15 min of the light exposure, the present study suggests that 100-Hz flickering light may have the same impact on melatonin secretion as non-flickering light.

P101. The influence of sex and age on melatonin suppression by warm-white light (K 2883 K)

Introduction In the past, the suppression of the pineal hormone melatonin by light has been investigated in several studies, frequently using small samples and only male subjects. Whereas the nocturnal melatonin production is thought to decrease with age, our knowledge about the extent of the light-induced melatonin suppression depending on sex and age is only limited. Our study addressed this issue in more details. Methods Subjects for this study were pre-screened for the onset of melatonin production in the evening hours. In total, 94 healthy subjects between 18 and 73 years were enrolled (42 men/52 women). All of them had a regular sleep-wake schedule and were morning or intermediate types according to the Ostberg-Horne-Ostberg morningness-eveningness questionnaire (scores: 41–73). They completed 4 evening laboratory sessions (19:00–23:00 h) predominantly in a weekly interval. The light protocol for each session consisted of a 2-h dim light ( Results After 2 h of dim-light condition all enrolled study participants showed an increase in melatonin production versus baseline of different magnitude. One hour of warm-white light at 500 lx (0.264 W/m2) caused very variable suppression of melatonin which did not exceed about 64% in both sexes. The average melatonin suppression over all subjects was 30.2% with sex related differences in the frequency of strong suppression, being higher in men. The inter-individual variability in melatonin suppression by warm-weight light was not related to the age of study participants. We also proved the impact of physical activity. Men with low physical activity showed relatively small plasma melatonin concentrations after 2 h dim-light condition, but a high sensitivity to the warm-white light applicated. Conclusions The obvious individual variability in the sensitivity of melatonin production for artificial light in the evening with possible sex but not clear and simple age related differences could be a critical factor in our understanding of light effects. Levels of physical activity in the leisure time could be a masking factor which should be adequately controlled in similar studies.

Suppression of Melatonin Secretion in Totally Visually Blind People by Ocular Exposure to White Light: Clinical Characteristics

Although most totally visually blind individuals exhibit nonentrained circadian rhythms due to an inability of light to entrain the circadian pacemaker, a small proportion retain photic circadian entrainment, melatonin suppression, and other nonimage-forming responses to light. It is thought that these responses to light persist because of the survival of melanospin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), which project primarily to the circadian pacemaker and are functionally distinct from the rod and cone photoreceptors that mediate vision. We aimed to assess the integrity of nonimage-forming photoreception in totally visually blind patients with a range of ocular disorders. Within-subject, dark-controlled design. A total of 18 totally visually blind individuals (7 females; mean age ± standard deviation=49.8±11.0 years) with various causes of blindness, including 3 bilaterally enucleated controls. Melatonin concentrations were compared during exposure to a 6.5-hour bright white light (∼7000 lux) with melatonin concentrations measured 24 hours earlier at the corresponding clock times under dim-light (4lux) conditions. Area under the curve (AUC) for melatonin concentration. Melatonin concentrations were significantly suppressed (defined as ≥33% suppression) during the bright-light condition compared with the dim-light condition in 5 of 15 participants with eyes (retinitis pigmentosa, n= 2; retinopathy of prematurity [ROP], n= 2; bilateral retinal detachments, n= 1). Melatonin concentrations remained unchanged in response to light in the remaining 10 participants with eyes (ROP, n= 3; optic neuritis/neuropathy, n= 2; retinopathy unknown, n= 2; congenital glaucoma, n= 1; congenital rubella syndrome, n= 1; measles retinopathy, n= 1) and in all 3 bilaterally enucleated participants. These data confirm that light-induced suppression of melatonin remains functionally intact in a minority of totally visually blind individuals with eyes. None of the bilaterally enucleated individuals or those with phthisis bulbi was responsive to light; of the remainder, half were responsive to light. Although inner retinal damage is associated with a high likelihood that nonimage-forming photoreception is absent, the impact of outer retinal damage is more ambiguous, and therefore the assessment of the presence, attenuation, or absence of nonimage-forming light responses in totally blind patients requires careful individual confirmation and cannot simply be assumed from the type of blindness.

Preventive Effect of Morning Bluish LED Light on Light-induced Melatonin Suppression at Night

Preventive Effect of Morning Bluish LED Light on Light-induced Melatonin Suppression at Night

Impact of sex and age on light-induced melatonin suppression in the evening

Impact of sex and age on light-induced melatonin suppression in the evening

An ancestral haplotype of the human PERIOD2 gene associates with reduced sensitivity to light-induced melatonin suppression.

Humans show various responses to the environmental stimulus in individual levels as “physiological variations.” However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05). The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05), and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.

Light-induced melatonin suppression at night after exposure to different wavelength composition of morning light

Bright nocturnal light has been shown to suppress melatonin secretion. However, bright light exposure during the day might reduce light-induced melatonin suppression at night. The human circadian system is sensitive to short wavelength light. This study evaluated the preventive effect of different wavelengths of daytime light on light-induced melatonin suppression at night. Twelve male subjects were exposed to various light conditions (dim, white, and bluish white light) between the hours of 09:00 and 10:30 (daytime light conditions). They were then exposed to light (300lx) again between 01:00 and 02:30 (night-time light exposure). Subjects provided saliva samples before (00:55) and after night-time light exposure (02:30). A two-tailed paired t-test yielded significant decrements in melatonin concentrations after night-time light exposure under daytime dim and white light conditions. No significant differences were found in melatonin concentrations between pre- and post-night-time light exposure with bluish-white light. Present findings suggest that daytime blue light exposure has an acute preventive impact on light-induced melatonin suppression in individuals with a general life rhythm (sleep/wake schedule). These findings may be useful for implementing artificial light environments for humans in, for example, hospitals and underground shopping malls to reduce health risks.