It’s no secret that slugging down caffeinated drinks in the evening can disrupt sleep. 
 
 But a new study led by the University of Colorado Boulder and the Medical Research Council’s Laboratory of Molecular Biology in Cambridge, England shows for the first time that evening caffeine delays the internal circadian clock that tells us when to get ready for sleep and when to prepare to wake up. The research team showed the amount of caffeine in a double espresso or its equivalent three hours before bedtime induced a 40-minute phase delay in the roughly 24-hour human biological clock. 
 
 The study also showed for the first time how caffeine affects “cellular timekeeping” in the human body, said CU-Boulder Professor Kenneth Wright, who co-led the study with John O’Neill of the Medical Research Council’s Laboratory of Molecular Biology (LMB) in Cambridge. While it has been known that caffeine influences circadian clocks of even primitive creatures like algae and fruit flies, the new study shows that the internal clocks in human cells can be impacted by caffeine intake. 
 
 “This is the first study to show that caffeine, the mostly widely used psychoactive drug in the world, has an influence on the human circadian clock,” said Wright, a professor in CU-Boulder’s Department of Integrative Physiology. “It also provides new and exciting insights into the effects of caffeine on human physiology.” 
 
 A paper on the subject led by Wright and O’Neill is being published online in the Sept 16 issue of Science Translational Medicine. 
 
 For the study the team recruited five human subjects, three females and two males, who went though a double-blind, placebo-controlled 49-day protocol through CU-Boulder’s Sleep and Chronobiology Laboratory, which is directed by Wright. The subjects were tested under four conditions: low light and a placebo pill; low light and the equivalent of a 200-milligram caffeine pill dependent on the subject’s weight; bright light and a placebo pill; and bright light and the caffeine pill. 
 
 Saliva samples of each participant were tested periodically during the study for levels of the hormone melatonin, which is produced naturally by the pineal gland when directed to do so by the brain’s “master clock.” The master clock is re-set by exposure to light and coordinates cellular clocks throughout the human body. Melatonin levels in the blood increase to signal the onset of biological nighttime during each 24-hour period and decrease at the start of biological daytime, said Wright. 
 
 Those who took the caffeine pill under low-light conditions were found to have a roughly 40-minute delay in their nightly circadian rhythm compared to those who took the placebo pill under low light conditions, said Wright. The magnitude of delay from the caffeine dose was about half that of the delay induced in test subjects by a three-hour exposure to bright, overhead light that began at each person’s normal bedtime. 
 
 The study also showed that bright light alone and bright light combined with caffeine induced circadian phase delays in the test subjects of about 85 minutes and 105 minutes respectively. There were no significant differences between the dim light/caffeine combination and the bright light/placebo combination. Nor were there significant differences between the bright light/placebo and bright light/caffeine combinations. The results may indicate a “ceiling” was reached in the phase delay of the human circadian clock due to the external factors, Wright said. 
 
 In addition, researchers at O’Neill’s lab at the LMB in Cambridge used “reporter” genes that made cells glow when the clock genes were expressed to measure changes caused by caffeine. O’Neill’s group showed that caffeine can block cell receptors of the neurotransmitter adenosine, which normally promotes sleep and suppresses arousal. 
 
 The results may help to explain why caffeine-drinking “night owls” go to bed later and wake up later and may have implications for the treatment of some circadian sleep-wake disorders, said Wright. 
 
 The new results could benefit travelers. Properly timed caffeine use could help shift the circadian clocks of those flying west over multiple time zones, said Wright. 
 
 In a 2013 study, Wright and his research team showed one week of camping in the Rocky Mountains with no artificial light, not even flashlights, synchronized the circadian clocks of the eight study subjects with the timing of sunrise and sunset. 
 
 Other co-authors on the new paper included former CU-Boulder students and researchers Tina Burke, Rachel Markwald, Andrew McHill, Evan Chinoy, Jesse Snider, Sara Bessman and Christopher Jung. Markwald and Bessman are now at the Naval Health Research Center in San Diego, while Jung is at the University of Alaska Anchorage, and McHill and Chinoy are at Brigham and Women’s Hospital and Division of Sleep Medicine at Harvard Medical School. 
 
 The study was funded by the National Institutes of Health, including NIH’s National Center for Advancing Translational Science, as well as the Howard Hughes Medical Institute in collaboration with CU-Boulder’s Biological Sciences Initiative and its Undergraduate Research Opportunity Program. The Medical Research Council and the Wellcome Trust also helped to fund the study. 
 
 Contact: 
 
 Kenneth Wright, 303-735-6409 
 
 kenneth.wright@colorado.edu 
 
 John O’Neill, MRC Laboratory of Molecular Biology, 011-44 122-326-7037 
 
 oneillj@mrc-lmb.cam.ac.uk 
 
 Jim Scott, CU-Boulder media relations, 303-492-3114 
 
 jim.scott@colorado.edu ||||| Your daily drug resets your clock 
 
 Your morning cup of coffee may be shifting your circadian clock. Burke et al. show that caffeine—widely available, legal, and psychoactive—inserts a delay into the ~24-hour metabolic rhythm that keeps your body running in time with the world. 
 
 In a sensitive, within-subject experimental design, five people were kept under highly controlled conditions for 49 days. Before bedtime, they were given various treatments: either a double-espresso caffeine dose, exposure to bright or dim light, or a placebo. The caffeine delayed their internal clock by 40 min, a shift about half as long as bright light, a stimulus known to robustly lengthen the circadian phase. 
 
 The authors used cultured cells to determine that the drug acted directly on the adenosine receptor, which increases the intracellular messenger molecule cyclic AMP. The fact that cyclic AMP forms a key cog in the inner workings of the clock links caffeine’s biochemical effects to its delay of the circadian rhythm. 
 
 Not only do these results reinforce the common advice to avoid caffeine in the evening, but they also raise the intriguing possibility that caffeine may be useful for resetting the circadian clock to treat jet lag induced by international time zone travel. ||||| Caffeine At Night Resets Your Inner Clock 
 
 Everyone knows that caffeine can keep you awake, but a new study shows that the world's most popular drug can actually interfere with your body's internal sense of time. 
 
 "The circadian clock is way beyond 'sleep and wake,' " says Kenneth Wright, a sleep and circadian physiologist at the University of Colorado, Boulder. "The circadian clock is present in cells throughout our entire body. It's in your fat cells; it's in your muscle cells. It's in your liver, for example, as well as in your brain." 
 
 And irregularities in the circadian clock have been linked to everything from obesity to cancer. 
 
 Scientists have had hints that caffeine could alter cellular timekeeping, from studies in bread mold, green algae and sea snails. But Wright wanted to know if it did the same thing in people. 
 
 "To our surprise, no one had really tested this question," he says. 
 
 He and his colleagues got volunteers to do a 49-day sleep study that involved testing saliva for melatonin, a sleep hormone that typically surges at night. 
 
 The study showed that the amount of caffeine found in a double espresso, if taken three hours before bedtime, delayed the melatonin surge by about 40 minutes, according to a report published online Wednesday in the journal Science Translational Medicine. 
 
 "We found that caffeine did indeed, in the evening, shift your clock later," Wright says. It was about half the effect the scientists noticed when they instead exposed the volunteers to bright light. 
 
 "What we're seeing here now," Wright says, "is another way that caffeine impacts our physiology that we didn't know about before in humans." 
 
 That kind of circadian shift could be enough to make people really struggle to get up at the right time the next day, says John O'Neill, a cell biologist at the Medical Research Council's laboratory of molecular biology, in Cambridge, U.K. 
 
 Still, it's unclear whether drinking caffeine earlier in the day would mess up your internal clock in a similar way. 
 
 "I think you could probably make a reasonable guess that caffeine consumed more than about five or six hours before habitual bedtime would not have this effect; but clearly it would need to be tested," says O'Neill. That's the kind of question the researchers hope to answer next. 
 
 In general, he says, people really need to think about how and when they're using caffeine. "Leading a lifestyle where you're consistently not getting enough sleep, or where your body clock is continually out of sync with the natural world, is bad for you."
– It's no news flash that consuming caffeine close to bedtime can interfere with sleep. But scientists at the University of Colorado Boulder report in the journal Science Translational Medicine that caffeine has another physiological impact on sleep by delaying the body's natural surge in the production of the sleep hormone melatonin, which in turn pushes back the body's circadian clock. "To our surprise, no one had really tested this question," one of the researchers tells NPR. "What we're seeing here now is another way that caffeine impacts our physiology that we didn't know about before in humans." The problem in this case is that the circadian clock is "present in cells throughout our entire body," says the researcher. "It's in your fat cells; it's in your muscle cells." Messing with it appears to play a role in a wide range of health problems, from obesity to cancer. Many studies have recently suggested that bright light at night, especially the blue light emanating from our screens, impedes melatonin production. Caffeine's effect is about half what scientists found when exposing volunteers to bright light alone; volunteers who drank a double espresso three hours before bedtime experienced a 40-minute delay of the melatonin surge. Now the researchers plan to study whether caffeine consumption five or six hours before bedtime produces a similar effect. (Still want to watch TV at night? Orange glasses should do the trick.)