Caffeine is America’s favorite (legal) white powder. You may know intimately the contours of its high: the jump in your step, the buzz in your brain, that jolt that renders you oh so gloriously and involuntarily alert. In a new study, researchers have quantified the effect of this potent stimulant on your circadian rhythm and explained how it works not just on your brain but also on the cells in your body.
Caffeine was already known to alter the circadian clock in red bread mold, green algae, fruit flies, and sea snails. But humans were liable to be a little different. For the first half of the study, published Wednesday in Science Translational Medicine, researchers at the University of Colorado–Boulder measured how caffeine influenced the circadian rhythms of five human caffeine consumers over 49 days.
Each participant was subjected to four phases of circadian manipulation: dim light, dim light with caffeine, bright light, and bright light with caffeine. First, participants swallowed either a rice-powder placebo or a caffeine pill—equivalent to a double espresso—three hours before bedtime. Then, they struggled to sleep. Researchers measured changes in melatonin, the primary hormone that tells the body to go nighty-night, to see whether the caffeine had shifted the circadian clock.
In short, it did: The effect was pronounced, or “physiologically meaningful,” says Kenneth Wright, a sleep and circadian physiologist at Boulder and co-author of the study. Caffeine consumers saw their clocks swing by 40 minutes, about half the magnitude of the change caused by bright light, a powerful and well-studied time cue for the circadian clock.
In the second half of the study, researchers in London looked at how caffeine works at the molecular level. They administered caffeine to a human cell line, which was primed to glow when there was activity in receptors involved with cellular timekeeping. By comparing the effect of caffeine with that of another stimulant, the researchers determined that caffeine was acting on adenosine receptors to shift each cell’s clock.
The way caffeine works on cells in the body might be different than how it works on the brain. “Your liver has clocks in it. Your muscles have clocks in them,” says Wright. “We know if you jet-lag a mouse, the brain adapts really quickly. Whereas it could take time for the other tissues to catch up. In other words, jet lag isn’t just the fact that your brain is in another time zone—it’s that your liver might be in a different time zone than your brain.”
One potential application of the research is in fact a “jet lag pill,” says Wright. Companies might be able to create the precise cocktail of caffeine and other drugs to help travelers adapt to sudden time shifts. That means that, one day, you could disembark from your flight to Sweden well-rested and well-adjusted. “Safe and targeted manipulation of the human biological clock” is the goal, says co-author and cell biologist John O’Neill of the Medical Research Council’s Laboratory of Molecular Biology in Cambridge.
Until then, you’ll have to settle for an actual cocktail.
