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Exposure to Room Light before Bedtime Suppresses Melatonin Onset and Shortens Melatonin Duration in Humans - pdf attached
 
 
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J Clin Endocrin Metab. First published ahead of print December 30, 2010
 
from Jules: Studies in the early days of HIV, the 90s, report HIV+ individuals have disrupted sleep patterns and more recent studies show sleep deprivation is associated with increased risk for developing diseases, so here is a study discussing melatonin and sleep and the developing of metabolic diseases and cancer, and finding that exposure to electrical room light before bedtime disrupts melatonin signaling.
 
" melatonin levels were strongly suppressed by room light (by about 70%) before bedtime and during the usual hours of sleep (Figs. 2- 4). .....These findings suggest that exposure to electrical room light before bedtime and during the normal hours of sleep (e.g. during shift work) may impact physiological processes regulated by melatonin signaling, such as sleepiness, thermoregulation, blood pressure, and perhaps even glucose homeostasis.....Given that melatonin receptor genes have recently been linked to the pathogenesis of type 2 diabetes (18-20, 51), it is possible that disruption of melatonin signaling by exposure to light at night could contribute to the increased risk for developing metabolic syndrome and type 2 diabetes in shift workers."
 
"Because the onset of melatonin secretion is associated with an increase in sleep propensity, and exogenous administration of melatonin can facilitate sleep (9 -12), melatonin has long been hypothesized as a sleep-promoting factor in humans.....These findings suggest that exposure to room light before bedtime, a common practice in modern society, may inhibit melatonin production and, as a result, alter physiological processes regulated by melatonin signaling...... the physiological consequences of chronically inhibiting melatonin synthesis are unknown. Recent stud- ies have shown that indoor room light (i.e. <500 lux) can elicit strong melatonin suppression and phase shift responses (23-25), suggesting that individuals who habitually expose themselves to light during nighttime hours could have reduced melatonin levels and perturbed rhythms......Also, illumination levels that people are exposed to during the daytime could potentially modulate melatonin suppression responses to electrical light at night (e.g. by sensitizing or desensitizing melatonin suppression responses). Previously, we showed that the suppressive effect of room light on melatonin synthesis was reduced by about 15% when participants were exposed to room light, instead of dim light, during the daytime (28). In the present study, participants were also exposed to room light during the day, which may have decreased melatonin suppression sensitivity at night; nonetheless, melatonin levels were strongly suppressed by room light (by about 70%) before bedtime and during the usual hours of sleep (Figs. 2- 4).......The effects of exogenous melatonin on human physiology suggest that this hormone plays a role in regulating body temperature, blood pressure, and sleepiness.....In conclusion, our findings demonstrate that melatonin levels are remarkably sensitive to room light levels, with exposure before bedtime resulting in strong suppression of melatonin synthesis. As a result, exposure to room light into the late evening has the effect of shortening melatonin duration, thereby truncating the body's internal representation of solar night. With growing evidence that melato- nin receptor signaling plays an important role in regulating human physiology, in future studies, it will be important to determine the impact of chronic nighttime exposure to electrical lighting on melatonin suppression and morbidity.....it is possible that disruption of melatonin signaling by exposure to light at night could contribute to the increased risk for developing metabolic syndrome and type 2 diabetes in shift workers......raises the possibility that chronic light suppression of melatonin may increase the relative risk for some types of cancer"

 
Joshua J. Gooley*, Kyle Chamberlain, Kurt A. Smith, Sat Bir S. Khalsa, Shantha M. W. Rajaratnam, Eliza Van Reen, Jamie M. Zeitzer, Charles A. Czeisler, and Steven W. Lockley Division of Sleep Medicine (J.J.G., K.A.S., S.B.S.K., S.M.W.R., E.V.R., J.M.Z., C.A.C., S.W.L.), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and Faculty of Health and Medical Sciences (K.C.), University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom
 
* To whom correspondence should be addressed. E-mail: gmsjjg@nus.edu.
 
Context: Millions of individuals habitually expose themselves to room light in the hours before bedtime, yet the effects of this behavior on melatonin signaling are not well recognized.
 
Objective: We tested the hypothesis that exposure to room light in the late evening suppresses the onset of melatonin synthesis and shortens the duration of melatonin production.
 
Design: In a retrospective analysis, we compared daily melatonin profiles in individuals living in room light (<200 lux) vs. dim light (<3 lux).
 
Patients: Healthy volunteers (n = 116, 18-30 yr) were recruited from the general population to participate in one of two studies.
 
Setting: Participants lived in a General Clinical Research Center for at least five consecutive days.
 
Intervention: Individuals were exposed to room light or dim light in the 8 h preceding bedtime.
 
Outcome Measures: Melatonin duration, onset and offset, suppression, and phase angle of entrainment were determined.
 
Results: Compared with dim light, exposure to room light before bedtime suppressed melatonin, resulting in a later melatonin onset in 99.0% of individuals and shortening melatonin duration by about 90 min. Also, exposure to room light during the usual hours of sleep suppressed melatonin by greater than 50% in most (85%) trials.
 
Conclusions: These findings indicate that room light exerts a profound suppressive effect on melatonin levels and shortens the body's internal representation of night duration. Hence, chronically exposing oneself to electrical lighting in the late evening disrupts melatonin signaling and could therefore potentially impact sleep, thermoregulation, blood pressure, and glucose homeostasis.
 
INTRODUCTION
 
The pineal gland hormone melatonin is released during the biological night and provides the body's internal biological signal of darkness. Exposure to light both resets the circadian rhythm of melatonin and acutely inhibits melatonin synthesis (1, 2). In some mammals, light regulation of melatonin gives rise to photoperiodic responses including patterns of seasonal breeding and changes in pelage (3, 4). The duration of nocturnal melatonin secretion in humans is likewise dependent on photoperiod (5), but effects on the reproductive system remain controversial. Several groups have shown seasonality in births, but few studies have examined the potential link between melatonin duration and reproductive hormones that deter- mine the likelihood of conception (6-8).
 
Because the onset of melatonin secretion is associated with an increase in sleep propensity, and exogenous ad- ministration of melatonin can facilitate sleep (9 -12), melatonin has long been hypothesized as a sleep-promoting factor in humans. Melatonin treatment reduces sleep onset latency when endogenous levels of melatonin are low during the biological daytime (12). Melatonin receptors are located on circadian clock neurons in the suprachiasmatic nucleus in the anterior hypothalamus (13), suggesting that feedback regulation by melatonin signaling may contribute to circadian regulation, including the timing of sleep. Consistent with this hypothesis, daily ingestion of melatonin has been shown to synchronize circadian rhythms of behavior and physiology in blind individuals (14, 15). In addition to its hypnotic and circadian phase resetting effects, exogenous melatonin has been shown to lower blood pressure and body temperature (16, 17), and recent genome-wide association studies have established a putative link between signaling at the melatonin 1B receptor and risk for type 2 diabetes (18 -20). With melatonin receptors located in several sites of the central nervous sys- tem and in peripheral tissues including the heart, kidney, pancreatic islets, adrenal glands, stomach, and gonads (21), melatonin has been explored as a treatment option for various human disease states including insomnia, hypertension, and cancer (22).
 
Despite the potential therapeutic benefits of melatonin treatment, the physiological consequences of chronically inhibiting melatonin synthesis are unknown. Recent studies have shown that indoor room light (i.e. <500 lux) can elicit strong melatonin suppression and phase shift responses (23-25), suggesting that individuals who habitually expose themselves to light during nighttime hours could have reduced melatonin levels and perturbed rhythms. In a study that examined the dose response for melatonin suppression and phase resetting responses to white light given at night, half-maximal responses were observed at about 100 lux (25), which is substantially dimmer than recommended office lighting (about350-500 lux) (26). In that study, however, participants were kept in relatively dim light (<15 lux) for 3 d preceding the light stimulus, which may have sensitized the circadian system to light (27, 28). Nonetheless, in other studies, exposure to room light suppressed the onset of melatonin secretion even when preceded by room light levels during the day- time (24, 28). Appropriately timed exposure to indoor light (about380 lux) has also been shown to accelerate entrainment to a rapid 5-h advance of the sleep-wake cycle (29). Taken together, these studies indicate that melatonin suppression and phase shift responses are sensitive to ordinary room light levels regardless of previous light history.
 
These findings suggest that exposure to room light before bedtime, a common practice in modern society, may inhibit melatonin production and, as a result, alter physiological processes regulated by melatonin signaling. To address this possibility, we examined melatonin responses to room light vs. dim light in 116 research volunteers studied in the laboratory under a fixed sleep-wake schedule (8 h asleep, 16 h awake). Here, we report that exposure to electrical light between dusk and bedtime strongly suppresses melatonin levels, leading to an artificially shortened melatonin duration and disruption of the body's biological signal of night.
 
Discussion
 
Our results demonstrate that the melatonin profile is truncated by exposure to room light before bedtime. Specifically, we show that exposure to room light (<200 lux) in the late evening suppresses the onset of melatonin synthesis, thereby shortening melatonin duration by about 90 min compared with exposure to dim light (<3 lux). As a result of this exposure to electrical light between dusk and bedtime, presleep levels of melatonin were reduced by 71.4% and total daily levels of melatonin were reduced by about 12.5%. When room light exposure continues for the entire night, total daily melatonin is suppressed by more than 50% in most individuals, with median suppression of 73.7%. These findings suggest that exposure to electrical room light before bedtime and during the normal hours of sleep (e.g. during shift work) may impact physiological processes regulated by melatonin signaling, such as sleepiness, thermoregulation, blood pressure, and perhaps even glucose homeostasis.
 
Room light suppresses melatonin and shortens melatonin duration

 
We hypothesize that the later melatonin onset we observed during exposure to room light in the evening was due primarily to melatonin suppression, rather than phase shifting of the circadian system. In study 1, the earlier melatonin onset we observed on d 3 could be attributed, in part, to a net phase advance of the circadian system, because participants were exposed to room light in the morning and early afternoon and dim light in the late afternoon and evening. Hence, individuals were exposed to higher light levels during the predicted phase-advance region of the phase-response curve, compared with the phase-delay region (30) (Fig. 1A). If phase shifting were principally responsible for the change in melatonin onset, we would expect a comparable shift in the timing of melatonin offset in the same direction. Rather, our results show that the timing of melatonin offset was unchanged. To examine this question in greater detail, we examined results from an additional set of 58 participants who completed a similar research protocol under different lighting conditions (see Supplemental Data). In that study, volunteers were exposed to room light until the end of the third baseline day, after which time the circadian system was released into constant conditions. Whereas 70.7% of individuals showed a later melatonin offset (41 of 58 participants) in dim light, consistent with drift of the circadian pacemaker (34), 86.2% individuals showed an earlier melatonin onset (50 of 58) when exposed to dim light (<15 lux) on d 4, vs. room light on d 3 (Supplemental Figs. 2 and 3). These data suggest that the underlying circadian phase of melatonin onset on d 3 was masked by light exposure, presumably due to photic melatonin suppression. Consistent with this interpretation, in study 2, we observed that exposure to room light during the usual hours of sleep resulted in strong melatonin suppression in 84.6% of trials (Fig. 4). Some participants showed partial recovery from melatonin suppression during room light exposure, whereas others showed complete suppression of melatonin such that melatonin onset or offset could not be measured. By comparison, two participants showed weak melatonin suppression responses to room light. This inter-individual variability in melatonin suppression sensitivity is consistent with the dose-response function for melatonin suppression reported previously; room light (100 -500 lux) falls on the steep linear part of the dose-response curve, such that small differences in corneal illuminance can result in large differences in melatonin suppression magnitude (25, 32).
 
A limitation of the present study is that the dim light and room light conditions were not balanced for order of presentation. We obtained similar results in a previous study, however, in which the order of light conditions was re- versed, such that participants were exposed to dim light on d 1 (<3 lux), followed by 2 d in room light (<200 lux). In that study, melatonin onset also occurred substantially later in room light compared with dim light (by about 90 min), suggesting that the order of room light vs. dim light in the present study did not affect the primary outcomes (35). Another limitation of our study is that participants were exposed to long durations of room light or dim light (16 or 8 h) before sleep, whereas in the real world, individuals often choose to turn on, or turn off, electrical lights closer to bedtime. Also, illumination levels that people are exposed to during the daytime could potentially modulate melatonin suppression responses to electrical light at night (e.g. by sensitizing or desensitizing melatonin suppression responses). Previously, we showed that the suppressive effect of room light on melatonin synthesis was reduced by about 15% when participants were exposed to room light, instead of dim light, during the daytime (28). In the present study, participants were also exposed to room light during the day, which may have decreased melatonin suppression sensitivity at night; nonetheless, melatonin levels were strongly suppressed by room light (by about 70%) before bedtime and during the usual hours of sleep (Figs. 2- 4).
 
Potential implications of melatonin suppression by electrical lighting

 
In modern society, people are routinely exposed to electrical lighting during evening hours, after the onset of melatonin production, to partake in work, recreational, and social activities. Our results demonstrate that this indoor room light profoundly alters the timing, duration, and amount of melatonin syn- thesis, the health consequences of which are unknown. Melatonin is the body's internal representation of night duration, or scotoperiod, and is sensitive to changes in season in humans (5, 36). Chronic exposure to evening electrical lighting extends the photoperiod and shortens the scotoperiod, which is equivalent to placing modern humans in a continual biological summer. This could, in turn, have effects on metabolic function via alteration of melatonin se- cretion directly (18-20) or indirectly via altered sleep duration (37).
 
The effects of exogenous melatonin on human physiology suggest that this hormone plays a role in regulating body temperature, blood pressure, and sleepiness (12, 17, 38). Given the ability of melatonin to inhibit linoleic acid up- take, melatonin has also been proposed as a treatment option for inhibiting cancer progression (39). In an animal model for human cancer in which nude rats were implanted with breast cancer xenografts, perfusion with blood taken from women exposed to dim light at night, when melatonin is released, reduced tumor growth markedly (40). In contrast, blood taken from women who had been exposed to bright light at night, which drastically reduced levels of plasma melatonin, did not affect growth rate of xenografts. Rates of instead of dim light, during the daytime (28). In the present study, participants were also exposed to room light during the day, which may have decreased melatonin suppression sensitivity at night; nonetheless, melatonin levels were breast cancer are especially high in chronic shift workers (41-43), most of whom are exposed to light that is of sufficient intensity to suppress nighttime melatonin levels.
 
This, coupled with the finding that the rate of breast cancer is lower in blind women without light perception (44 - 46), raises the possibility that chronic light suppression of melatonin may increase the relative risk for some types of cancer (47), an idea that was proposed nearly 25 yr ago by Richard Stevens as part of his light-at-night theory (48, 49). Chronically exposing oneself to light at night could also increase cancer risk by disrupting circadian clock function; continuous exposure to light disrupts behavioral rhythms and increases tumor malignity in C57BL/6 mice, even though these animals do not secrete melatonin (50).
 
If further research substantiates melatonin suppression as a significant risk factor for breast cancer, our results demonstrating strong suppression of melatonin with evening room light could have important health implications. Moreover, in future studies, it will be important to determine whether small, chronic changes in sleep, melatonin, and circadian phase, as experienced every day in many nonshift workers, might present a health risk in vulnerable individuals (49). Given that melatonin receptor genes have recently been linked to the pathogenesis of type 2 diabetes (18-20, 51), it is possible that disruption of melatonin signaling by exposure to light at night could contribute to the increased risk for developing metabolic syndrome and type 2 diabetes in shift workers. Hence, future work should focus on determining the mechanisms by which melatonin regulates glucose metabolism and the consequences of inhibiting melatonin receptor signaling on blood glucose and insulin levels (51, 52).
 
In conclusion, our findings demonstrate that melatonin levels are remarkably sensitive to room light levels, with exposure before bedtime resulting in strong suppression of melatonin synthesis. As a result, exposure to room light into the late evening has the effect of shortening melatonin duration, thereby truncating the body's internal representation of solar night. With growing evidence that melatonin receptor signaling plays an important role in regulating human physiology, in future studies, it will be important to determine the impact of chronic nighttime exposure to electrical lighting on melatonin suppression and morbidity.
 
 
 
 
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