Creatine Supplementation Dose and Duration Are Not Associated with Increased Side Effects: A Structured Review and Study-Level Dose-Response Analysis of Randomized Controlled Trials.
Level 1 - systematic review of randomized trials
Structured review and study-level dose-response analysis of 684 randomized controlled trials
PubMed 42043069 · doi:10.3390/sports14040137
What was done
Analyzed side effect data from creatine monohydrate (CrM) and placebo arms across 684 randomized controlled trials encompassing over 12,800 participants. Total absolute CrM dose and supplementation duration were categorized into tertiles (low, moderate, high) and analyzed using chi-square tests. Multivariable logistic regression models adjusted for biological sex, age, and population categories tested dose and duration as continuous predictors of side effects.
What was found
Side effects across the 684 trials were infrequent, mild, and nonspecific. Although CrM dose and duration tertiles showed statistical associations with study-level reporting, effect sizes were uniformly small with no consistent exposure-response pattern. Adjusted logistic regression analyses found no consistent dose- or duration-dependent increase in side effect risk, with placebo groups often reporting similar or higher event rates. CrM did not increase the risk of gastrointestinal, renal, liver, or musculoskeletal side effects relative to placebo (specific numerical incidence rates and odds ratios were not provided in the abstract).
Why it matters
This large-scale synthesis indicates that neither higher doses nor longer durations of creatine monohydrate supplementation are associated with a clinically meaningful increase in adverse side effects compared to placebo.
Limits
The analysis relied on study-level aggregated data rather than individual participant data. Side effect definitions, monitoring rigor, and reporting criteria varied across the included primary trials. Specific effect sizes, confidence intervals, and event rates were omitted from the abstract.