Published in the Journal of the International Society of Sports Nutrition in 2017, this position stand authored by Richard Kreider and colleagues represented the most comprehensive review of creatine research ever conducted, examining over 500 peer-reviewed studies.

The ISSN concluded that both short-term and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals when used within recommended guidelines. The review found no clinically significant adverse effects on kidney function, liver function, or other organ systems in any population studied, including infants with inborn errors of creatine synthesis, children, adolescents, adults, and elderly individuals.

The position stand also noted that creatine has potential therapeutic applications beyond athletic performance, including neuroprotection, recovery from traumatic brain injury, and management of neurodegenerative diseases. This represented the strongest consensus statement on creatine safety from a major sports science organization.

Published in the Journal of the International Society of Sports Nutrition in 2025, Kreider and colleagues conducted the most comprehensive safety analysis to date, examining reported side effects across 685 human clinical trials of creatine supplementation.

Side effects were reported by 4.21% of participants receiving placebo compared to 4.60% of participants receiving creatine, a difference that was not statistically significant. No clinical adverse events (serious medical outcomes requiring intervention) were reported in any of the 685 trials. The most common minor side effects in both groups were gastrointestinal discomfort and headache.

The researchers also searched the FDA Adverse Event Reporting System and found only 203 adverse event reports mentioning creatine among 28.4 million total global reports (0.00072%). This extremely low reporting rate, combined with the trial data showing no difference from placebo, provides strong evidence that creatine at recommended doses does not cause meaningful side effects.

Published in BMC Nephrology in 2025, researchers conducted a systematic review of 21 studies and meta-analysis of 12 studies (440 total participants) specifically examining creatine supplementation and kidney function markers.

The meta-analysis found a statistically insignificant increase in serum creatinine of 0.07 umol/L in supplemented groups, but no significant changes in glomerular filtration rate (GFR), the gold-standard measure of actual kidney function. The small creatinine increase was attributed to increased metabolic turnover of creatine to creatinine (a normal breakdown product) rather than any impairment in kidney filtration capacity.

This distinction is important because creatine is converted to creatinine in the body, so taking creatine naturally raises creatinine levels in blood and urine without necessarily indicating kidney damage. Measuring GFR directly (rather than estimating it from creatinine) confirms that the kidneys continue to function normally despite the elevated creatinine readings.

Published in Medicine and Science in Sports and Exercise in 1999, Belgian researchers Jacques Poortmans and Marc Francaux studied competitive athletes who had been using creatine monohydrate for periods ranging from 10 months to 5 years at doses of 20 g/day for loading (5 days) followed by up to 10 g/day for maintenance.

None of the kidney function parameters differed significantly between the creatine users and matched non-supplementing athlete controls: creatinine clearance, glomerular filtration rate, tubular resorption rate, and glomerular membrane permeability were all within normal ranges and statistically indistinguishable between groups.

The study concluded that neither short-term, medium-term, nor long-term oral creatine supplementation impairs renal function in healthy athletes who maintain adequate hydration. At the time of publication, this was the longest-duration human study of creatine and kidney function, providing reassurance about multi-year supplementation patterns common among competitive athletes.

Published in the European Journal of Applied Physiology in 2011, Brazilian researchers conducted a randomized, double-blind, placebo-controlled trial specifically designed to test creatine safety in people with type 2 diabetes, who are at elevated risk of kidney disease.

Participants received 20 g/day of creatine for 1 week (loading) followed by 5 g/day for 11 weeks, or matching placebo. Kidney function was measured using the gold-standard 51Cr-EDTA clearance method (not estimated from creatinine levels). There were no significant differences between groups in measured GFR, creatinine clearance, serum urea, electrolytes, proteinuria, or albuminuria.

This trial is particularly important because it tested creatine in a vulnerable population. If creatine posed kidney risks, those risks would be most likely to manifest in people with diabetes-related kidney vulnerability. Finding no harm even in this at-risk group significantly strengthens the safety case for healthy populations.

In 2020, the U.S. Food and Drug Administration accepted GRAS Notice No. 931 for creatine monohydrate (specifically the Creapure brand manufactured by AlzChem), determining that the substance is Generally Recognized As Safe under its intended conditions of use as a food ingredient.

The GRAS determination required submission of comprehensive toxicological data, manufacturing specifications, and safety evidence. Specifications require 99% or greater purity by HPLC analysis. Creatine monohydrate is the only form of creatine that has received this level of regulatory acceptance across major markets including the United States, Canada, Europe, Australia, Japan, South Korea, and China.

GRAS status is a significant regulatory milestone because it means that qualified experts have concluded, based on publicly available scientific evidence, that the substance is safe for its intended use. This is a higher bar than simply being legal to sell as a dietary supplement.

Published in the Journal of the International Society of Sports Nutrition in 2007, this position stand by Buford, Kreider, Stout, and colleagues represented the first major professional organization to issue a comprehensive safety endorsement of creatine.

The ISSN concluded that creatine monohydrate supplementation is not only safe but possibly beneficial for preventing injury and managing certain medical conditions. They stated it is the most effective ergogenic (performance-enhancing) nutritional supplement currently available to athletes for increasing high-intensity exercise capacity and lean body mass.

The position stand specifically addressed and dismissed common safety concerns: claims that creatine causes dehydration, muscle cramps, kidney damage, or gastrointestinal distress were not supported by the scientific evidence reviewed. The ISSN recommended that athletes consider creatine supplementation as part of evidence-based sports nutrition practices.

Published in the Journal of the International Society of Sports Nutrition in 2021, Kreider and Stout systematically addressed 12 widely believed misconceptions about creatine supplementation using the available scientific evidence.

Each misconception was evaluated against the body of peer-reviewed research. The review found no evidence that creatine causes dehydration or muscle cramping (some studies suggest it may actually reduce cramp incidence), no evidence of kidney damage in healthy individuals at recommended doses, no evidence of liver damage, and no consistent evidence of significant gastrointestinal distress.

The authors noted that many misconceptions originated from early case reports, media sensationalism, or confusion between creatine and anabolic steroids. They emphasized that creatine has maintained FDA GRAS status, is naturally present in meat and fish at approximately 1-2 grams per pound, and is endogenously synthesized by the human body at approximately 1 gram per day.

Published in the European Journal of Nutrition in 2023, Serbian researchers analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 to examine whether dietary creatine intake is associated with liver disease markers.

Participants consuming 2 or more grams per day of creatine (from both food and supplements) showed no significantly increased risk of liver fibrosis, cirrhosis, or hepatic steatosis (fatty liver disease) compared to those consuming less than 1 gram daily. The analysis adjusted for age, gender, BMI, total energy intake, and alcohol consumption.

This population-level analysis provides reassurance about liver safety across a nationally representative sample of Americans. While it cannot establish causation, the absence of any dose-dependent association between creatine intake and liver pathology markers in over 4,000 participants suggests that typical supplementation doses do not contribute to liver disease risk.