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.

Patient room lighting influences on sleep, appraisal and mood in hospitalized people.

Irregular 24 h light/dark cycles with night-time light exposure and a low amplitude are disruptive for sleep, mood and circadian rhythms. Nevertheless such lighting conditions are quite common in medical care facilities. A controlled clinical trial among 196 cardiology ward patients (mean age 66.5 ± 13.1 years SD) investigated how a patient room lighting intervention affects sleep, appraisal and mood across hospitalization. Patients were either assigned to a standardly-lit room or to a room with an interventional lighting system offering a dynamic 24 h light/dark cycle with low nocturnal light exposure and 2 h of bright light (1750 lux) during daytime. Measures included wrist actigraphy and questionnaires assessing alertness, sleep quality, anxiety, depression and lighting appraisal. The median length of hospitalization was 5 days in both study arms. Subjective scores on sleep, alertness, anxiety and depression did not differ between arms. Lighting appraisal in intervention rooms was better as compared to standardly-lit rooms, both in patients (P < 0.001) and staff (P < 0.005). Actigraphic sleep duration of patients improved by 5.9 min (95% CI: 0.6-11.2; P = 0.03 intervention × time effect) per hospitalization day with interventional lighting instead of standard lighting. After 5 days of hospitalization, sleep duration in the lighting intervention rooms increased by 29 min, or a relative 7.3%, as compared to standardly-lit rooms. A 24 h lighting system with enhanced daytime brightness and restricted nocturnal light exposure can improve some aspects of appraisal and objective sleep in hospital patients. More clinical research is needed to establish the best lighting strategy to promote healing and wellbeing within healthcare settings.

A revision of existing Karolinska Sleepiness Scale responses to light: A melanopic perspective.

A new photometric measure of light intensity that takes into account the relatively large contribution of the ipRGCs to the non-image forming (NIF) system was recently proposed. We set out to revise publications reporting on alertness scores as measured by the Karolinska Sleepiness Scale (KSS) under different light conditions in order to assess the extendibility of the equivalent-melanopic function to NIF responses in humans. The KSS response (-Δ KSS) to the different light conditions used on previous studies, preferably including a comparison to a dim light condition, was assessed. Based on the light descriptions of the different studies, the equivalent melanopic lux (m-illuminance) was calculated. The -Δ KSS was plotted against photopic-illuminance and m-illuminance, and fitted to a sigmoidal function already shown to described KSS responses to different light intensities. The root mean-squared error and r(2) were used as criteria to explain the best-describing light unit measurement. Studies that compared only the influence of light under otherwise same conditions and in which participants were not totally sleep deprived were included. Our results show that the effects of light on KSS are better explained by a melanopic unit measurement than by photopic lux. The present analysis allowed for the construction of a melanopic alertness response curve. This curve needs to be validated with appropriate designs. Nonetheless, it may serve as starting point for the development of hypothesis of predictions on the relative changes in KSS under a given condition due to changes in light properties.

Effects of a chronic reduction of short-wavelength light input on melatonin and sleep patterns in humans: evidence for adaptation.

Light is an important environmental stimulus for the entrainment of the circadian clock and for increasing alertness. The intrinsically photosensitive ganglion cells in the retina play an important role in transferring this light information to the circadian system and they are elicited in particular by short-wavelength light. Exposure to short wavelengths is reduced, for instance, in elderly people due to yellowing of the ocular lenses. This reduction may be involved in the disrupted circadian rhythms observed in aged subjects. Here, we tested the effects of reduced blue light exposure in young healthy subjects (n = 15) by using soft orange contact lenses (SOCL). We showed (as expected) that a reduction in the melatonin suppressing effect of light is observed when subjects wear the SOCL. However, after chronic exposure to reduced (short wavelength) light for two consecutive weeks we observed an increase in sensitivity of the melatonin suppression response. The response normalized as if it took place under a polychromatic light pulse. No differences were found in the dim light melatonin onset or in the amplitude of the melatonin rhythms after chronic reduced blue light exposure. The effects on sleep parameters were limited. Our results demonstrate that the non-visual light system of healthy young subjects is capable of adapting to changes in the spectral composition of environmental light exposure. The present results emphasize the importance of considering not only the short-term effects of changes in environmental light characteristics.

Short-wavelength attenuated polychromatic white light during work at night: limited melatonin suppression without substantial decline of alertness.

Exposure to light at night increases alertness, but light at night (especially short-wavelength light) also disrupts nocturnal physiology. Such disruption is thought to underlie medical problems for which shiftworkers have increased risk. In 33 male subjects we investigated whether short-wavelength attenuated polychromatic white light (<530 nm filtered out) at night preserves dim light melatonin levels and whether it induces similar skin temperature, alertness, and performance levels as under full-spectrum light. All 33 subjects participated in random order during three nights (at least 1 wk apart) either under dim light (3 lux), short-wavelength attenuated polychromatic white light (193 lux), or full-spectrum light (256 lux). Hourly saliva samples for melatonin analysis were collected along with continuous measurements of skin temperature. Subjective sleepiness and activation were assessed via repeated questionnaires and performance was assessed by the accuracy and speed of an addition task. Our results show that short-wavelength attenuated polychromatic white light only marginally (6%) suppressed salivary melatonin. Average distal-to-proximal skin temperature gradient (DPG) and its pattern over time remained similar under short-wavelength attenuated polychromatic white light compared with dim light. Subjects performed equally well on an addition task under short-wavelength attenuated polychromatic white light compared with full-spectrum light. Although subjective ratings of activation were lower under short-wavelength attenuated polychromatic white light compared with full-spectrum light, subjective sleepiness was not increased. Short-wavelength attenuated polychromatic white light at night has some advantages over bright light. It hardly suppresses melatonin concentrations, whereas performance is similar to the bright light condition. Yet, alertness is slightly reduced as compared with bright light, and DPG shows similarity to the dim light condition, which is a physiological sign of reduced alertness. Short-wavelength attenuated polychromatic white light might therefore not be advisable in work settings that require high levels of alertness.

Effects of artificial dawn on subjective ratings of sleep inertia and dim light melatonin onset.

The timing of work and social requirements has a negative impact on performance and well-being of a significant proportion of the population in our modern society due to a phenomenon known as social jetlag. During workdays, in the early morning, late chronotypes, in particular, suffer from a combination of a nonoptimal circadian phase and sleep deprivation. Sleep inertia, a transient period of lowered arousal after awakening, therefore, becomes more severe. In the present home study, the authors tested whether the use of an alarm clock with artificial dawn could reduce complaints of sleep inertia in people having difficulties in waking up early. The authors also examined whether these improvements were accompanied by a shift in the melatonin rhythm. Two studies were performed: Study 1: three conditions (0, 50, and 250 lux) and Study 2: two conditions (0 lux and self-selected dawn-light intensity). Each condition lasted 2 weeks. In both studies, the use of the artificial dawn resulted in a significant reduction of sleep inertia complaints. However, no significant shift in the onset of melatonin was observed after 2 weeks of using the artificial dawn of 250 lux or 50 lux compared to the control condition. A multilevel analysis revealed that only the presence of the artificial dawn, rather than shift in the dim light melatonin onset or timing of sleep offset, is related to the observed reduction of sleep inertia complaints. Mechanisms other than shift of circadian rhythms are needed to explain the positive results on sleep inertia of waking up with a dawn signal.

Effects of artificial dawn on sleep inertia, skin temperature, and the awakening cortisol response.

The effect of artificial dawn during the last 30 min of sleep on subsequent dissipation of sleep inertia was investigated, including possible involvement of cortisol and thermoregulatory processes. Sixteen healthy subjects who reported difficulty with waking up participated in random order in a control and an artificial dawn night. Sleep inertia severity was measured by subjective ratings of sleepiness and activation, and by performance on an addition and a reaction time task measured at 1, 15, 30, 45, 60, and 90 min after waking up at habitual wake up time at workdays. At all intervals, saliva samples were collected for cortisol analysis. Sleep electroencephalogram was recorded during the 30 min prior to waking up; core body temperature and skin temperatures were recorded continuously until 90 min after waking up. Subjective sleepiness was significantly decreased and subjective activation increased after waking up in the artificial dawn condition as compared with control, in which lights were turned on at waking up. These effects can be explained by effects of artificial dawn on skin temperature and amount of wakefulness during the 30 min prior to the alarm. Artificial dawn accelerated the decline in skin temperature and in the distal-to-proximal skin temperature gradient after getting up. No significant effects of artificial dawn on performance, core body temperature, and cortisol were found. These results suggest that the physiology underlying the positive effects of artificial dawn on the dissipation of sleep inertia involves light sleep and an accelerated skin temperature decline after awakening.

In vivo quantification of the retinal reflectance spectral composition in elderly subjects before and after cataract surgery: Implications for the non-visual effects of light.

Light is the signal that entrains the biological clock in humans to the 24-hour external time. Recently, it has been shown that short wavelengths play a key role in this process. In the present study, we describe a procedure to measure, objectively and in a quick way, the spectral composition of the light reaching the retina in vivo. The instruments involved are the foveal reflection analyzer (FRA) and the macular pigment reflectometer (MPR). By making use of these reflectometers, we show quantitatively that in subjects with cataracts, the light input is especially reduced in the short wavelength range. After cataract surgery during which the crystalline lens is replaced by a transparent artificial lens, the transmittance of the short wavelengths (between 420-500 nm) improved on average by a factor of 4. We conclude that this technique holds great promises for the chronobiological field because it allows for quantification of the spectral composition and light levels reaching the retina in vivo.