Melatonin suppression is exquisitely sensitive to light and primarily driven by melanopsin in humans

Abstract

Introduction Light elicits a range of non‐visual responses in humans. Driven predominantly by intrinsically photosensitive retinal ganglion cells (ipRGCs), but also by rods and/or cones, these responses include melatonin suppression. A sigmoidal relationship has been established between melatonin suppression and light intensity; however, photoreceptoral involvement remains unclear. Methods and Results In this study, we first modelled the relationships between alpha‐opic illuminances and melatonin suppression using an extensive dataset by Brainard and colleagues. Our results show that (a) melatonin suppression is better predicted by melanopic illuminance compared to other alpha‐opic illuminances, (b) melatonin suppression is predicted to occur at levels as low as ~1.5 melanopic lux (melanopsin‐weighted irradiance 0.2 µW/cm2), (c) saturation occurs at 305 melanopic lux (melanopsin‐weighted irradiance 36.6 µW/cm2). We then tested this melanopsin‐weighted illuminance‐response model derived from Brainard and colleagues' data and show that it predicts equally well melatonin suppression data from our laboratory, although obtained using different intensities and exposure duration. Discussion Together, our findings suggest that melatonin suppression by monochromatic lights is predominantly driven by melanopsin and that it can be initiated at extremely low melanopic lux levels in experimental conditions. This emphasizes the concern of the non‐visual impacts of low light intensities in lighting design and light‐emitting devices.

Changing color and intensity of LED lighting across the day impacts on human circadian physiology, sleep, visual comfort and cognitive performance

“…We found 36% more attenuation of melatonin during sLED in the last sample before sleep compared to dynLED, which corroborates the results by Chellappa et al 2011 57 and fits the model proposed by Prayag et al 2019 58 well. Their findings support the assumption that melatonin suppression by light is predominantly driven by melanopsin and that it can be initiated already at low irradiances.…”

Light Modulation of Human Clocks, Wake, and Sleep

“…Effects of light intensity/irradiance Illuminance response curves for (i) subjective alertness (KSS), EEG (5-9 Hz), slow-eye movements (Cajochen et al [37]) (ii) melatonin suppression and circadian phase-shifting (Zeitzer et al [38]) (iii) melatonin suppression as a function of melanopic illuminance (Nowozin et al [39]; Prayag et al [40])…”

“…Light-dependent circadian responses are also sensitive to the intensity of the light exposure [37,38,40]. Using a 6.5 h (polychromatic white light) exposure centered 3.5 h before minimum core body temperature at a range of light intensities (3-9100 lux), Zeitzer and colleagues generated sigmoidal dose-response curves for melatonin phase-shift and melatonin suppression ( Figure 4) [38].…”

Evidence That Homeostatic Sleep Regulation Depends on Ambient Lighting Conditions during Wakefulness

“…Recent evidence shows that melanopsin and/ or rhodopsin are the main drivers for melatonin suppression in humans [26,27]. Furthermore, based on a metaanalysis on a large data set from [37], Prayag et al [38] concluded that suppression of melatonin by monochromatic lights is predominantly driven by melanopsin, and that it can be initiated at extremely low "melanopic lux" levels in experimental conditions. Here we did not calculate dose response relationships for other alpha-opic irradiances than melanopic irradiance.…”