To address these concerns, a team of leading creatine researchers conducted a review of 684 randomized clinical trials involving more than 12,800 participants across a range of populations who supplemented with creatine monohydrate at various doses and durations.
“Based on the current evidence, creatine is one of the most well-studied and well-tolerated dietary supplements,” they wrote in the journal Sport, reaffirming previous findings on the overall safety of creatine monohydrate.
“No consistent or clinically meaningful dose-dependent increases in side-effect reporting were observed across models. Even at higher doses and prolonged durations, reporting remained low and largely comparable to placebo at the study level.”
Why are there misconceptions around creatine safety?
Creatine entered the mainstream in the 1990s after The Times reported that gold medal winners Linford Christie and Sally Gunnell were using creatine monohydrate prior to their participation in the 1992 Barcelona Olympics.
At the time, creatine was somewhat of an experimental ingredient, pioneered by Dr. Roger Harris, who published his seminal paper in September 1992 demonstrating that creatine supplementation increased creatine content in the muscles.
Subsequent research from the Harris lab demonstrated that creatine supplementation improved anaerobic power and strength and the ability to generate force under fatigue. Investigations of the underlying mechanisms suggested that it works by increasing intramuscular phosphocreatine stores, boosting cellular energy and enabling faster resynthesis of ATP, the body’s primary energy-carrying molecule.
However, safety concerns began to arise in the late 1990s after creatine was suspected to have contributed to the deaths of three college wrestlers. This was later disproven, but several papers were published suggesting that creatine use was associated with renal (kidney) dysfunction.
Dr. Scott Forbes, a certified sport nutritionist and co-author of the Sports paper, said this misconception arose from a misunderstanding of creatine metabolism and a misinterpretation of creatinine.
“Creatine is non-enzymatically degraded to creatinine,” he explained. “Creatinine in the blood has been used as a marker of kidney function, and if creatinine begins to rise, this would indicate that your kidneys are not filtering properly. However, if you are taking creatine, you will have more creatine in your body and this will be broken down to creatinine, thereby elevating blood creatinine levels. This elevation has nothing to do with kidney function but is often misinterpreted as such.”
More recently, legislative efforts have attempted to limit the availability of creatine in dietary supplements to certain populations, such as children and adolescents, due to concerns about product purity, body image and a lack of long-term safety data in young people. New York became the first state to restrict the sale of muscle-building supplements to minors in April 2024.
In response, the International Society of Sports Nutrition issued a letter affirming the safety and efficacy of creatine, urging policymakers not to restrict its access. The letter states that creatine is a naturally occurring compound found in every cell in the human body and is essential to promote normal energy metabolism and healthy growth and maturation in children and adolescents.
Indeed, hundreds of clinical trials have been conducted on creatine monohydrate, involving populations from infants to elderly adults. The research consistently shows that creatine monohydrate is safe and effective, improving strength, power output and the ability to handle higher training volumes over time.
In the latest analysis, the researchers observed a slight increase in the likelihood of adverse events among individuals with higher creatine exposure; however, this did not indicate any serious safety concerns.
Of the 684 randomized clinical trials, 86.4% reported no side effects in the creatine groups. Adverse effects involving the kidneys, liver, heart, lungs and mental health were very rare, occurring in fewer than 1% of studies.
Even in the high-dose category, the symptoms reported were primarily mild and nonspecific, such as minor gastrointestinal distress. In fact, placebo groups often reported side effects at similar or even higher frequencies than the creatine groups.
The researchers suggested that the slight increase in reported events in longer or higher-dose studies is likely due to increased reporting opportunities rather than a threshold for toxicity.
What is the safe limit for creatine consumption?
Despite decades of scientific research, there is currently no established Tolerable Upper Intake Level (UL) for creatine.
In the U.S., for example, the FDA has granted creatine monohydrate generally recognized as safe (GRAS) status, but there is no government-mandated UL. However, scientific consensus and industry standards widely consider a daily maintenance dose of 3 to 5 g to be safe and effective. Canada has similar guidelines, while EFSA, the scientific risk assessment body for the European Union, has concluded that long-term daily supplementation of 3 g of high-purity creatine monohydrate is safe for healthy adults. Dr. Forbes noted that the safe dose could be up to 10 times higher, citing studies which have used up to 30 g per day without safety concerns.
One of the key reasons for using high doses is to rapidly saturate muscle stores with creatine during what is commonly referred to as a “loading phase”, a period which typically lasts about one week and allows users to experience the benefits of creatine more quickly.
Other reasons include cognitive enhancement, a relatively new research area that has only recently begun to gain recognition. While research is still in its early stages, emerging evidence suggests that doses of 10 to 20 g per day may be needed to increase brain creatine content.
“High doses of creatine (20 g per day or more) might be needed to cross the blood–brain barrier and elicit brain-related benefits in individuals facing metabolic stress, increased demands or inadequate cerebral synthesis of creatine—but not in all people,” said Sergej Ostojic, a creatine researcher and professor in the Department of Nutritional Sciences at Texas Tech University. “Whether high doses are effective is still a matter of debate, since several studies have shown a lack of effects in many brain conditions.”
Given the unknowns, he explained that alternative routes of administration and specific dosing protocols may need to be developed to effectively and safely deliver creatine to the brain. Some studies suggest that even low doses can be beneficial in some cohorts, such as perimenopausal women. This is particularly important, he noted, given that higher doses can increase the risks of certain side effects.
“Mild gastrointestinal adverse events, such as bloating or diarrhea, are more likely if single doses are too large (e.g., ≥ 10 grams), hydration is inadequate, or creatine is used alongside certain drugs it may interact with (e.g., pemetrexed and entecavir),” Dr. Ostojic said. “Overall, the consensus is that creatine has a wide safety margin, with risk largely driven by misuse rather than intrinsic toxicity.”
Alternative creatine forms and optimal cognitive dosing: Future avenues of research
Other forms of creatine, such as creatine HCl, ethyl ester and buffered creatine, have limited long-term safety data. This is not to say they are unsafe, but rather they are less validated compared to creatine monohydrate.
With preliminary data suggesting that creatine HCl might lead to fewer gastrointestinal effects and less weight gain, Dr. Ostojic noted that this represents an intriguing area for future study, alongside research to determine the optimal dose of creatine monohydrate for cognitive benefits.
Meanwhile, Dr. Forbes and colleagues recommend that future investigations focus on developing standardized frameworks for adverse event reporting in order to address the significant inconsistency and heterogeneity in how side effects are currently documented across clinical trials.
“A limitation of this research is that unless specifically asked by the researcher, participants often do not disclose side effects,” he said. “It is important for researchers to have a standardized way of asking participants to report side effects. Often, researchers did not ask participants and then note in the manuscript that there were no reported side effects. We need to interpret this with caution.”
Source: Sports. doi: 10.3390/sports14040137. “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." Authors: D. E. Gonzalez, et al.
