Clinical reviewCoffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials
Introduction
Caffeine is the most widely consumed psychoactive substance in the world, which is reflected in the estimated 85% of the US population drinking at least one caffeinated beverage each day [1]. It is a xanthine alkaloid and is found in a variety of foods and beverages, such as chocolate, coffee, and tea. Coffee is the primary dietary caffeine source in Western Europe and the United States [2], although among adolescents, soda appears to have emerged as the caffeinated beverage of choice [3] and energy drinks are growing in popularity [4], [5]. Caffeine is used to treat apnea of prematurity [6] and is found in several over-the-counter medications against headache or to suppress appetite [7]. Caffeine is also used to enhance performance among university athletes [8] and as a fatigue countermeasure, for example by truck drivers [9] and shift workers [10], as well as by airline pilots [11].
It is generally accepted that caffeine promotes wakefulness by antagonizing adenosine A1 and A2A receptors in the brain [7]. A role for adenosine in sleep and arousal regulation has been established by studies in humans and in animals [12]. Adenosine receptor agonists generally promote sleep. Caffeine is metabolized in the liver almost entirely by the cytochrome P450 iso-enzyme 1A2 (CYP1A2) [13].
The word “caffeine” is derived literally from the German word for coffee, “Kaffee,” and was coined in 1819 upon its chemical identification by Friedlieb Ferdinand Runge [14] at the encouragement of his contemporary, Johann Wolfgang von Goethe, who supplied him with the coffee beans for the experiments [15].
According to legend [7], the wake-promoting qualities of caffeine were once cleverly exploited by the abbot of a Yemenite monastery, who proscribed coffee to his monks to facilitate their nighttime prayers. The effects of caffeine on human sleep have been the focus of serious scientific inquiry since at least 1912, when Hollingworth [16] published a report on a series of his experiments involving ‘‘caffein’’ [sic] and subjective sleep quality in a sample of 16 adult men and women. Subsequent research in the century since Hollingworth's writing has confirmed and extended his findings, which relate to dose- and timing-response relationships, as well as individual differences in caffeine sensitivity that mediate its disruptive effects on sleep. These subjective findings have been reproduced using objective measures, such as electroencephalography (EEG) and actigraphy, and genetic studies are beginning to uncover potential genetic substrates underlying individual differences in caffeine sensitivity and sleep disruption.
Despite their widespread and increasing use, and the general consensus that coffee and caffeine may interfere with the quality of sleep, there exists presently no comprehensive review of the effects of coffee and caffeine on sleep. The aim of this study was to produce one, and in doing so, address the major open questions relating to coffee, caffeine and human sleep. To this end, a systematic review of all pertinent literature published in peer-reviewed journals was conducted. In the interest of maximizing the utility and applicability of the review, an effort was made to be as inclusive as possible, and both epidemiological as well as controlled clinical trials were examined.
Section snippets
Study selection
A computerized literature search was conducted with the Web-of-Science and MEDLINE (PubMed) electronic databases that have a comprehensive catalogue of scientific articles in the fields of psychology and medicine. Three search terms were used: ‘‘coffee,’’ ‘‘caffeine,’’ and ‘‘sleep.’’ The search was conducted on all citations published until August 2014. The computerized search was then complemented by manual search through the references of the selected studies.
Articles chosen for review met
Studies associating caffeine with variables of sleep quality in infants
The currently available evidence suggests that caffeine hardly influences variables related to sleep quality in infants (Table S1, supplementary information). The children of 177 high caffeine-consuming mothers (≥300 mg/d) did not awaken more frequently than those of low-consuming mothers during pregnancy, as well as three months postpartum [18]. Similarly, no significant differences in heart rate and sleep duration estimated from heart rate were observed in breast-fed infants from mothers
Discussion
An influence of caffeine on human sleep has been the focus of a considerable body of scientific research in the past century. In healthy adults, changes in sleep are well characterized, and experiments utilizing healthy adult samples yield reliable results. Other age groups have received less attention. This is unfortunate, because age may represent a mitigating factor in response to caffeine. The fewest studies were dedicated to infants, and no studies investigated young children.
Caffeine
Conclusions
This review presented reliable associations between altered sleep quality and dietary caffeine intake, which were reported in epidemiological studies. These observations were supported by studies conducting experiments in controlled laboratory settings. By blocking the adenosine neuromodulator and receptor system, which contributes importantly to sleep–wake regulation, caffeine impairs nighttime sleep, at least in vulnerable individuals. The equivalent of caffeine contained in one or two
Conflicts of interest
IC reported no conflict of interest. Some of HPL's research has been supported by Novartis Foundation for Medical-Biological Research.
Acknowledgements
HPL's research has been supported by Swiss National Science Foundation, Zürich Center for interdisciplinary Sleep Research, Clinical Research Priority Program “Sleep & Health” of the University of Zürich, Zürich Center for Integrative Human Physiology, and Neuroscience Center Zürich.
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