Effects of Caffeine on the Human Circadian Clock in Vivo and in Vitro

This paper outlines the effect of caffeine on the human circadian clock, and verifies previously assumed yet unproven interactions between the drug and sleep timing. Using human subjects the authors determined that caffeine (a timed double shot of espresso) indeed delays the circadian phase (delays sleep onset), but more saliently perhaps, the authors demonstrate that bright light (3000 lux [about 1/3 of light on a sunny day] for 3 hours around the normal bed-time hour) was associated with an increased magnitude of delayed circadian phase. Using a human U2OS bmal:luc in vitro system the authors then show that the caffeine prolongs the circadian period through a adenosine receptor/cAMP pathway. This work is the first to mechanistically tie the widely used drug caffeine to delayed circadian phase in humans but understatedly also calls attention to the significant effect of light on circadian rhythm, which has implications for both hospital recovery environments and optimal bed-time routines for the population at large.