Evidence map›Paper›PMID 26378246›Full record

Trial reportScience translational medicine2015

Effects of caffeine on the human circadian clock in vivo and in vitro.

Tina M Burke, Rachel R Markwald, Andrew W McHill, Evan D Chinoy, Jesse A Snider, Sara C Bessman, Christopher M Jung, John S O'Neill, Kenneth P Wright

Open access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed, 2 pooled it
10.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 268 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Social jetlag in a longitudinal Chinese wearable cohort: weekly variation, solar-time mismatch, and sleep-activity associations.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2026
    Article
  6. Work-Influenced Circadian Disruption Connected to Disease Risk but Not Microbiomes in a Cohort of Philadelphia Nurses.American journal of human biology : the official journal of the Human Biology Council · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

58 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Tina M BurkeSleep and Chronobiology Laboratory, Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA.
Rachel R MarkwaldSleep and Chronobiology Laboratory, Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA.
Andrew W McHillSleep and Chronobiology Laboratory, Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA.
Evan D ChinoySleep and Chronobiology Laboratory, Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA.
Jesse A SniderSleep and Chronobiology Laboratory, Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA.
Sara C BessmanSleep and Chronobiology Laboratory, Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA.
Christopher M JungSleep and Chronobiology Laboratory, Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA.
John S O'NeillMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. kenneth.wright@colorado.edu oneillj@mrc-lmb.cam.ac.uk.
Kenneth P WrightSleep and Chronobiology Laboratory, Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309-0354, USA. kenneth.wright@colorado.edu oneillj@mrc-lmb.cam.ac.uk.
MRC Laboratory of Molecular Biology · GB

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Circadian Integration of Photic and Non-photic StimuliR01HL081761 · NHLBI · UNIVERSITY OF COLORADO · PI WRIGHT, KENNETH P · 2006 to 2009
$1.1M
Howard Hughes Medical InstituteMedical Research Council MC_UP_1201/4NCATS NIH HHS UL1 TR001082NHLBI NIH HHS R01 HL081761Wellcome Trust 093734Wellcome Trust 093734/Z/10/Z
6 · The paper itself

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.

Indexed as

AdultAnalysis of VarianceBiosensing TechniquesCaffeineCell Line, TumorCircadian ClocksCircadian RhythmCyclic AMPDose-Response Relationship, DrugDouble-Blind MethodFemaleHealthy VolunteersHumansLuminescenceMaleMelatoninCaffeineCyclic AMPMelatoninRNA, Small Interfering

Identifiers

PMID26378246
PMCPMC4657156
OpenAlexW1899622156

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.