Caffeine Use in Sport: A Systematic Review and Meta-analysis of Acute Side Effects and Implications for Athlete Health and Safety

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Abstract
Given the widespread use of caffeine among athletes, this meta-analysis quantifies the incidence of acute side effects associated with caffeine supplementation. Despite its well-established performance benefits, evidence on caffeine's side effects remains fragmented, as these outcomes are often reported only as secondary findings. To address this gap, we systematically reviewed and meta-analyzed evidence from randomized controlled trials on acute caffeine-related side effects in athletes. Following PRISMA guidelines, we searched five databases (MEDLINE, Scopus, Web of Science, Embase, Google Scholar) up to July 2025. Eligible studies were randomized controlled trials in athletes aged ≥ 15 years examining acute caffeine ingestion versus placebo with reported side effects. Risk of bias was assessed using PEDro and Cochrane criteria. Data on frequency and magnitude of side effects were pooled using random-effects meta-analyses, with subgroup and dose-response analyses. A total of 48 studies (940 athletes; 63% male, 37% female) were included in the systematic review, of which 38 were eligible for meta-analysis. The mean caffeine dose was 4.9 ± 2.4 mg/kg (range 1.3-12 mg/kg), commonly ingested as capsules or beverages. Compared with placebo, athletes who ingested caffeine self-reported significantly higher odds of headache (Log OR = 0.74, p < 0.001), abdominal discomfort (Log OR = 1.12, p < 0.001), increased feelings of vigor/activeness (classified in this review as a side effect for methodological consistency, although it may also reflect an ergogenic benefit; Log OR = 1.14, p < 0.001), tachycardia (Log OR = 1.47, p < 0.001; > fourfold higher odds compared with placebo), insomnia (Log OR = 1.20, p < 0.001), increased urine output (Log OR = 1.04, p < 0.001), anxiety (Log OR = 1.29, p < 0.001), and nervousness (Log OR = 0.82, p < 0.001). Meta-regression of dose-response effects showed a significant association between caffeine dose and tachycardia (slope = 0.31, p < 0.001), headache (slope = 0.23, p < 0.001), abdominal discomfort (slope = 0.29, p < 0.001), vigor/activeness (slope = 0.18, p < 0.001), increased urine output (slope = 0.28, p < 0.001), and anxiety (slope = 0.37, p < 0.001). Caffeine intake in athletes increases the likelihood of side effects in a dose-dependent manner, with tachycardia, insomnia, abdominal discomfort, and anxiety being the most consistent. Evidence suggests that, compared with high doses (> 6 mg/kg), low to moderate doses (≤ 6 mg/kg) of caffeine may reduce the risk of side effects.

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