Related Experiment Video
Updated: Apr 27, 2026

Caffeine Extraction, Enzymatic Activity and Gene Expression of Caffeine Synthase from Plant Cell Suspensions
Published on: October 2, 2018
Caffeine Use in Sport: A Systematic Review and Meta-analysis of Acute Side Effects and Implications for Athlete
Raoof Negaresh1, Shihab Aldin Ahmad Al-Riyami2, Majid Mardaniyan Ghahfarrokhi3
1Department of Physical Education, Farhangian University, Tehran, Iran.
Background:
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.
Objective:
To address this gap, we systematically reviewed and meta-analyzed evidence from randomized controlled trials on acute caffeine-related side effects in athletes.
Methods:
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.
Results:
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).
Conclusions:
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.
More Related Videos
Related Concept Videos
Stimulants
Cocaine can be administered via snorting, injection, or smoking. It primarily functions by blocking the reuptake of dopamine, resulting in a euphoric high characterized by an intense sensation of happiness and...
Substance Use Disorders Affecting Sleep
Understanding the concepts of physical dependence,...
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Exercise and Cardiovascular Response
Light to moderate physical activity initiates a series of interconnected responses in the body. The heart rate modestly increases in anticipation of the workout, followed by widespread vasodilation as oxygen consumption by skeletal muscles increases. This results in decreased peripheral resistance, increased capillary blood flow, and accelerated...
CNS Stimulants: Cocaine, Amphetamines and Cannabinoids
Insufficient Sleep and Sleep Deprivation
Sleep deprivation is a more severe form of sleep loss...

