Effects of caffeine on the human circadian clock in vivo and in vitro
Burke TM, Markwald RR, McHill AW, Chinoy ED, Snider JA, Bessman SC, Jung CM, O'Neill JS, Wright KP
Science translational medicine · 195 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People, plus animal or lab work
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Howard Hughes Medical Institute
- Nonprofit
- Wellcome Trust
- Government
- National Institutes of Health
- Government
- Medical Research Council
- Government
- National Heart, Lung, and Blood Institute
- Government
- National Center for Advancing Translational Sciences
- Government
- NCATS NIH HHS
- Government
- NIH
- Government
- NHLBI NIH HHS
- Government
- NIH/National Center for Advancing Translational Sciences Colorado Clinical and Translational Science Award
- Grants
- National Center for Advancing Translational Sciences (UL 1 TR001082); National Heart, Lung, and Blood Institute (R01-HL081761); Wellcome Trust (093734); Wellcome Trust (093734/Z/10/Z); National Institutes of Health (R01 HL081761); Medical Research Council (MC_UP_1201/4)
Based on 10 listed funder(s).
Publication
- Published
- 2015-09-16 · Sci Transl Med · vol. 7 · issue 305 · p. 305ra146
- Publisher
- American Association for the Advancement of Science
- Cited
- 283 citations · more than 99% of similar papers · 9.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 48 works
- Access
- Open access (repository copy)
- Research areas
- Circadian rhythm and melatonin · Sleep and related disorders · Coffee research and impacts
- Keywords
- Circadian clock, Circadian rhythm, Caffeine, In vivo, In vitro, Biological clock, Biology, Pharmacology, Cell biology, Chemistry, Neuroscience, Genetics, Endocrinology
- MeSH
- cell line, tumor, humans, melatonin, caffeine, rna, small interfering, cyclic amp, analysis of variance, double-blind method, biosensing techniques, circadian rhythm, dose-response relationship, drug, adult, female, male, luminescence, young adult, circadian clocks, healthy volunteers
9 authors
From US, GB
- Tina M. BurkeUniversity of Colorado Boulder
- Rachel R. MarkwaldUniversity of Colorado Boulder
- Andrew W. McHillUniversity of Colorado Boulder
- Evan D. ChinoyUniversity of Colorado Boulder
- Jesse A. SniderUniversity of Colorado Boulder
- Sara C. BessmanUniversity of Colorado Boulder
Abstract
Caffeine's wakefulness-promoting and sleep-disrupting effects are well established, yet whether caffeine affects human circadian timing is unknown. We show that evening caffeine consumption delays the human circadian melatonin rhythm in vivo and that chronic application of caffeine lengthens the circadian period of molecular oscillations in vitro, primarily with an adenosine receptor/cyclic adenosine monophosphate (AMP)-dependent mechanism. In a double-blind, placebo-controlled, ~49-day long, within-subject study, we found that consumption of a caffeine dose equivalent to that in a double espresso 3 hours before habitual bedtime induced a ~40-min phase delay of the circadian melatonin rhythm in humans. This magnitude of delay was nearly half of the magnitude of the phase-delaying response induced by exposure to 3 hours of evening bright light (~3000 lux, ~7 W/m(2)) that began at habitual bedtime. Furthermore, using human osteosarcoma U2OS cells expressing clock gene luciferase reporters, we found a dose-dependent lengthening of the circadian period by caffeine. By pharmacological dissection and small interfering RNA knockdown, we established that perturbation of adenosine receptor signaling, but not ryanodine receptor or phosphodiesterase activity, was sufficient to account for caffeine's effects on cellular timekeeping. We also used a cyclic AMP biosensor to show that caffeine increased cyclic AMP levels, indicating that caffeine influenced a core component of the cellular circadian clock. Together, our findings demonstrate that caffeine influences human circadian timing, showing one way that the world's most widely consumed psychoactive drug affects human physiology.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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