Supplementation
Meta-Analysis
2020
Wake up and smell the coffee: caffeine supplementation and exercise performance—an umbrella review of 21 published meta-analyses
By Jozo Grgic, Pavle Mikulic, Brad J. Schoenfeld, Craig Pickering, David J. Bishop and Zeljko Pedisic
British Journal of Sports Medicine, 54(11), pp. 681-688
<h2>Abstract</h2>
<p><a href="/terms/caffeine/" class="term-link" data-slug="caffeine" title="Caffeine">Caffeine</a> is among the most widely consumed and extensively researched ergogenic aids in sports nutrition. The present umbrella review synthesized findings from 21 published meta-analyses examining the effects of caffeine supplementation across a broad spectrum of exercise performance outcomes, including muscular strength, muscular endurance, anaerobic power, aerobic endurance, and sport-specific tasks.</p>
<p>Caffeine supplementation consistently and meaningfully improved performance across all major exercise modalities examined. For muscular strength, effect sizes in the range of small-to-moderate magnitude were observed, with upper body strength appearing somewhat more responsive than lower body strength. Anaerobic power output and high-intensity sprint performance demonstrated reliable improvements, while endurance performance showed consistent enhancements in time-to-exhaustion and time trial outcomes [1].</p>
<p>The <a href="/terms/dose-response-relationship/" class="term-link" data-slug="dose-response-relationship" title="dose-response relationship">dose-response relationship</a> indicated that 3–6 mg per kg of body mass administered 30–60 minutes prior to exercise represents the efficacious range, with minimal additional benefit observed above 6 mg/kg and greater incidence of adverse effects at higher doses. Importantly, ergogenic effects persisted even in habitual caffeine consumers, challenging earlier assumptions that tolerance fully attenuates the performance-enhancing response [2].</p>
<p>Adverse effects at recommended doses were generally mild, including tachycardia, anxiety, and gastrointestinal discomfort. The impact on post-exercise <a href="/terms/sleep-hygiene/" class="term-link" data-slug="sleep-hygiene" title="sleep quality">sleep quality</a> emerged as a particularly important consideration for athletes training or competing in the afternoon or evening. These findings confirm caffeine as an evidence-based <a href="/terms/ergogenic-aid/" class="term-link" data-slug="ergogenic-aid" title="ergogenic aid">ergogenic aid</a> warranting inclusion in evidence-informed supplementation strategies for performance-oriented individuals.</p>
<h3>References</h3>
<p>[1] Grgic J, et al. Wake up and smell the coffee: caffeine supplementation and exercise performance. <em>Br J Sports Med</em>. 2020;54(11):681–688.</p>
<p>[2] Doherty M, Smith PM. Effects of caffeine ingestion on exercise testing: a <a href="/terms/meta-analysis/" class="term-link" data-slug="meta-analysis" title="meta-analysis">meta-analysis</a>. <em>Int J Sport Nutr Exerc Metab</em>. 2004;14(6):626–646.</p>
<h2>Introduction</h2>
<p><a href="/terms/caffeine/" class="term-link" data-slug="caffeine" title="Caffeine">Caffeine</a> (1,3,7-trimethylxanthine) is a naturally occurring xanthine alkaloid found in coffee, tea, cocoa, and numerous other plant sources. It is the most widely consumed psychoactive substance in the world, with global coffee consumption alone exceeding 2 billion cups per day. In the context of sport and exercise, caffeine has been studied for over a century and is now recognized as one of the most robustly supported ergogenic aids in the sports science literature [1].</p>
<p>The primary pharmacological mechanism underlying caffeine's performance-enhancing effects is non-selective antagonism of adenosine receptors, particularly A₁ and A₂A subtypes. Adenosine is an endogenous neuromodulator whose accumulation during exercise contributes to the perception of effort and fatigue. By competitively blocking adenosine receptors in the central nervous system and peripheral tissues, caffeine attenuates the rise in perceived exertion, facilitates greater <a href="/terms/motor-unit/" class="term-link" data-slug="motor-unit" title="motor unit">motor unit</a> recruitment, and may enhance pain tolerance during high-intensity effort [2]. Secondary mechanisms include increased catecholamine release, enhanced glycogenolysis, and direct effects on contractile protein calcium kinetics, though the relative contribution of these peripheral mechanisms remains debated.</p>
<p>Caffeine was removed from the World Anti-Doping Agency (WADA) prohibited list in 2004, reflecting both its widespread dietary prevalence and the evolving scientific understanding of its <a href="/terms/dose-response-relationship/" class="term-link" data-slug="dose-response-relationship" title="dose-response">dose-response</a> characteristics. Nonetheless, WADA continues to monitor caffeine use, and concentrations exceeding 12 µg/mL in urine may warrant investigation in some governing bodies [3].</p>
<p>Despite the extensive primary literature, individual meta-analyses have varied in scope, methodology, and conclusions. An umbrella review approach, synthesizing evidence across multiple meta-analyses, provides an opportunity to generate the most comprehensive and methodologically robust synthesis of the available evidence base.</p>
<h3>References</h3>
<p>[1] Fredholm BB, et al. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. <em>Pharmacol Rev</em>. 1999;51(1):83–133.</p>
<p>[2] Davis JM, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA. Central nervous system effects of caffeine and adenosine on fatigue. <em>Am J Physiol Regul Integr Comp Physiol</em>. 2003;284(2):R399–R404.</p>
<p>[3] World Anti-Doping Agency. <em>The Prohibited List</em>. Montreal: WADA; 2021.</p>
<h2>Methods</h2>
<h3>Umbrella Review Design</h3>
<p>An umbrella review methodology was employed to systematically synthesize existing meta-analyses examining the effects of <a href="/terms/caffeine/" class="term-link" data-slug="caffeine" title="caffeine">caffeine</a> supplementation on exercise performance. This approach differs from a primary <a href="/terms/meta-analysis/" class="term-link" data-slug="meta-analysis" title="meta-analysis">meta-analysis</a> in that it synthesizes the findings of pre-existing meta-analyses rather than individual study data, enabling a higher-order synthesis of the evidence landscape across multiple performance domains [1].</p>
<h3>Search Strategy</h3>
<p>Systematic searches were conducted in PubMed, EMBASE, and SPORTDiscus from database inception through December 2019. The search strategy combined terms for caffeine and its synonyms with terms for meta-analysis, <a href="/terms/systematic-review/" class="term-link" data-slug="systematic-review" title="systematic review">systematic review</a>, and exercise or athletic performance. No language restrictions were applied, though all included meta-analyses were published in English. Reference lists of identified records were manually searched to identify additional eligible reviews.</p>
<h3>Inclusion and Exclusion Criteria</h3>
<p>Meta-analyses were eligible <a href="/terms/intermittent-fasting/" class="term-link" data-slug="intermittent-fasting" title="if">if</a> they: (1) used systematic search and pooling procedures consistent with accepted guidelines; (2) examined caffeine supplementation as the primary intervention; (3) included randomized controlled trials as the primary included study design; and (4) reported quantitative summary estimates for at least one exercise performance outcome. Reviews examining caffeine in combination with other ingredients that precluded isolation of the caffeine effect were excluded [2].</p>
<h3>Data Extraction and Quality Assessment</h3>
<p>Two investigators independently extracted data including: number of included primary studies, participant characteristics, caffeine dose and timing, exercise outcomes, and <a href="/terms/effect-size/" class="term-link" data-slug="effect-size" title="effect size">effect size</a> estimates with confidence intervals. Methodological quality of each meta-analysis was assessed using the AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) instrument, providing critical appraisal of conduct and reporting quality [3].</p>
<h3>References</h3>
<p>[1] Aromataris E, Fernandez R, Godfrey CM, Holly C, Khalil H, Tungpunkom P. Summarizing systematic reviews. <em>Int J Evid Based Healthc</em>. 2015;13(3):132–140.</p>
<p>[2] Shea BJ, et al. AMSTAR 2: a critical appraisal tool for systematic reviews. <em>BMJ</em>. 2017;358:j4008.</p>
<p>[3] Moher D, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. <em>BMJ</em>. 2009;339:b2535.</p>
<h2>Results</h2>
<h3>Characteristics of Included Meta-Analyses</h3>
<p>Twenty-one meta-analyses published between 1994 and 2019 met the inclusion criteria, collectively covering 310 primary randomized controlled trials and approximately 4,800 unique participants. The included reviews were heterogeneous in terms of the exercise domains examined, ranging from maximal strength and power to submaximal endurance, sprint performance, and sport-specific tasks. AMSTAR-2 quality ratings were moderate to high for the majority of included meta-analyses, with the primary limitations being incomplete reporting of funding sources and potential language bias in some earlier reviews [1].</p>
<h3>Muscular Strength and Power</h3>
<p>Meta-analyses examining maximal voluntary contraction strength consistently demonstrated small-to-moderate improvements with <a href="/terms/caffeine/" class="term-link" data-slug="caffeine" title="caffeine">caffeine</a> supplementation (SMD range: 0.19–0.38). Upper body strength appeared to be somewhat more responsive than lower body strength, possibly reflecting differential adenosine receptor density or <a href="/terms/motor-unit/" class="term-link" data-slug="motor-unit" title="motor unit">motor unit</a> characteristics. Peak power output in Wingate anaerobic testing showed reliable improvements of approximately 3–7% across pooled analyses [2].</p>
<h3>Endurance Performance</h3>
<p>Caffeine supplementation produced robust improvements in endurance performance across all time-to-exhaustion and time trial protocols examined. Pooled effects for cycling and running time-to-exhaustion demonstrated moderate-to-large effect sizes (SMD: 0.37–0.60), while time trial performance improvements of 2.0–4.3% were reported in analyses isolating this outcome measure.</p>
<h3>Dose, Timing, and Habituation</h3>
<p>Doses of 3–6 mg/kg body mass administered 30–60 minutes before exercise consistently produced ergogenic effects across multiple performance domains. Evidence for an additional benefit above 6 mg/kg was limited, while adverse event frequency increased. Habitual caffeine consumers showed comparable performance benefits to non-consumers in most analyses [3].</p>
<h3>References</h3>
<p>[1] Grgic J, et al. <em>Br J Sports Med</em>. 2020;54(11):681–688.</p>
<p>[2] Grgic J, Grgic I, Pickering C, et al. Wake up and smell the coffee: caffeine supplementation and strength performance. <em>Br J Sports Med</em>. 2019;54(11).</p>
<p>[3] Lara B, et al. Time course of tolerance to the performance benefits of caffeine. <em>PLoS One</em>. 2019;14(1):e0210275.</p>
<h2>Discussion</h2>
<p>The findings of this umbrella review reinforce and extend the evidence base supporting <a href="/terms/caffeine/" class="term-link" data-slug="caffeine" title="caffeine">caffeine</a> as a broad-spectrum <a href="/terms/ergogenic-aid/" class="term-link" data-slug="ergogenic-aid" title="ergogenic aid">ergogenic aid</a>. Unlike some supplements whose benefits are confined to specific exercise modalities or populations, caffeine appears to confer performance advantages across a remarkably wide range of exercise types, including strength, power, high-intensity intermittent performance, and aerobic endurance. This cross-modal efficacy is consistent with caffeine's primary mechanism of action in the central nervous system, where adenosine receptor antagonism modulates the perception of effort and fatigue in a manner that is largely independent of specific metabolic demands [1].</p>
<h3>Individual Variability and Genetic Considerations</h3>
<p>A notable limitation of population-level estimates is the substantial individual variability in response to caffeine. A meaningful proportion of individuals exhibit diminished or absent ergogenic responses, while some may experience performance decrements, particularly at higher doses. Genetic polymorphisms in the CYP1A2 gene, which encodes the primary caffeine-metabolizing enzyme, and the ADORA2A gene, encoding the A₂A adenosine receptor, have been identified as potential modulators of inter-individual response variability [2]. This genetic context may partially explain the inconsistent findings across primary studies and should be considered when translating population-level recommendations to individual athletes.</p>
<h3>Sleep and Recovery Considerations</h3>
<p>The half-life of caffeine ranges from 3 to 7 hours and is influenced by individual differences in hepatic metabolism. Athletes who train or compete in the late afternoon or evening face a genuine trade-off between acute performance benefits and potential disruption to <a href="/terms/sleep-hygiene/" class="term-link" data-slug="sleep-hygiene" title="sleep quality">sleep quality</a> and duration. Given the established importance of sleep for recovery, adaptation, and next-day performance, athletes should carefully weigh the timing of caffeine use relative to their sleep schedule [3].</p>
<h3>Practical Recommendations</h3>
<p>Evidence supports a dose of 3–6 mg/kg body mass consumed 30–60 minutes before exercise. Caffeine-naive individuals should begin at the lower end of this range and titrate upward based on tolerance and response. Anhydrous caffeine capsules and coffee appear to be equally efficacious delivery formats at equivalent doses.</p>
<h3>References</h3>
<p>[1] Pickering C, Grgic J. Caffeine and exercise: what next? <em>Sports Med</em>. 2019;49(7):1007–1030.</p>
<p>[2] Pickering C, Kiely J. Are the current guidelines on caffeine use in sport optimal for everyone? <em>Sports Med</em>. 2018;48(1):7–16.</p>
<p>[3] Drake C, Roehrs T, Shambroom J, Roth T. Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. <em>J Clin Sleep Med</em>. 2013;9(11):1195–1200.</p>