Dose–response effects of light therapy on sleepiness and circadian phase shift in shift workers: a meta-analysis and moderator analysis

Light therapy has been considered to be effective in mitigating sleepiness and regulating circadian phase shift in shift workers. However, the effective treatment dose of light therapy remains undetermined. We performed a meta-analysis of randomized experimental studies to determine the effect of light therapy doses on sleepiness and circadian phase shift in shift workers. An article search was performed in 10 electronic databases from inception to June 2020. Two raters independently screened and extracted data and reached consensus. Twenty-one eligible studies were included. Analyses were performed using random-effects models. Light therapy exerted significantly small to medium effects on sleepiness and large treatment effects on circadian phase shift. Moderator analyses performed with subgroup and metaregression analyses revealed that medium-intensity light therapy for a shorter duration more effectively reduced sleepiness at night, whereas higher-intensity light therapy more effectively induced phase shifting, but the required treatment duration remained inconclusive. This study provides evidence regarding the effect of light therapy in reducing sleepiness and shifting circadian phase in shift workers. Exposure to medium-intensity light for a short duration at night reduced sleepiness, whereas exposure to high-intensity light improved sleep by shifting their circadian phase.

Comment Concerning the Effects of Light Intensity on Melatonin Suppression in the Review “Light Modulation of Human Clocks, Wake, and Sleep” by A. Prayag et al.

Dose-response curves for circadian phase shift and melatonin suppression in relation to white or monochromatic nighttime illumination can be scaled to melanopic weighed illumination for normally constricted pupils, which makes them easier to interpret and compare. This is helpful for a practical applications.

Integration of brief light flashes varying in intensity and duration by the human circadian system

The human circadian system is exquisitely sensitive to light, through a pathway connecting the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) to the hypothalamic suprachiasmatic nuclei (SCN). ipRGCs are characterised by a delayed off-time following cessation of light exposure; we exploited this unusual physiologic property and examined how a sequence of flashes of bright light differing in intensity or duration presented in the biological night could delay the human circadian clock in vivo in healthy young participants (n=54). To understand the mechanism underlying circadian photoreception, we probed temporal integration by manipulating flash intensity and duration independently. In a 34-hour in-laboratory between-subjects design, we examined variable-intensity (3, 30, 95, 300, 950, 3000, or 9500 photopic lux; n=28 participants) flashes at fixed duration (2 ms), and variable-duration (10 μs, 100 μs, 1 ms, 10 ms, 100 ms, 1 sec, 10 sec) flashes at fixed intensity (2000 photopic lux; n=31 participants). We measured the phase shift of dim-light melatonin onset on the subsequent evening, and acute melatonin suppression and alertness during the flash sequence. In the variable-intensity study, we find a clear sigmoidal dose-response relationship for flash intensity and the induced circadian phase shift. In the variable-duration study, we find no parametric relationship between flash duration and induced circadian phase shift, indicating a relative insensitivity of the circadian system to flashes varying in duration. As the intermittent periods of darkness in our stimulation paradigm supports the recovery of extrinsic rod-cone signalling into the ipRGCs, our results strongly suggest rod-cone contributions into circadian photoreception.