High Sensitivity of Human Melatonin, Alertness, Thermoregulation, and Heart Rate to Short Wavelength Light

Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate (ϳ2. T HE HUMAN CIRCADIAN timing system is sensitive to ocular light exposure. The effects of light depend on the circadian phase at which light is administered: light given after the core body temperature (CBT) nadir advances the phase of circadian rhythms, whereas light given before the CBT nadir induces delays. This can be quantified by a so-called "human phase-response curve to light" (1, 2). Besides the timing of exposure, the intensity of light (i.e. irradiance) also plays a crucial role in human circadianphase resetting (3, 4). The irradiance dose-response function to a single episode of light in the phase-delay region can be characterized by a logistic function with high sensitivity, such that half of the maximal resetting response achieved in response to bright light (9100 lux) is obtained with just 1% of this light (dim room light of ϳ100 lux; see Ref. 4). Recent results indicate that very low intensity monochromatic light in the short-wave range (460 nm) also affects the human circadian timing system and is capable of inducing a significantly greater phase shift than monochromatic light at 555 nm (the peak of the three-cone photopic visual system) (5). Furthermore, short wavelength light between 436 and 456 nm induced a phase advance similar to that for polychromatic light (i.e. white light) containing 185-fold more photons (6). These studies clearly demonstrate that the human circadian timing system is highly sensitive to ocular light exposure, particularly in the short wavelength range. Besides circadian phase shifts, light also elicits acute physiological effects in humans such as a rapid suppression of melatonin at night (for review, see Ref. 7), an increase in CBT (8 -11) and heart rate (12), and an immediate dose-dependent alerting response, measured subjectively and objectively via the electroencephalogram (10). Brainard et al. (13, The acute effects of light, as well as the circadian effects, seem to be mediated by the eyes. Thus, acute elevation of body temperature and suppression of melatonin are not observed when the eyes are covered (11, 16) or when light is administered to the skin in the popliteal region (17-19). There is mounting evidence that nonrod and noncone photoreceptors might form the basis of this nonimageforming photoreceptive pathway mediating both the circadian and direct effects of light in rodents (20, 21) (for review, see Ref. 22). Therefore, we hypothesized that the acute effect of light on melatonin, alertness, thermoregulation, and heart rate is blue-shifted, such that short wavelength light at 460 nm induces a greater melatoninsuppressing, alerting, hyperthermic, and tachycardic effect than light at 550 nm