Study Deep Dive: Creatine is SAFE | Episode 13

Creatine is SAFE, the verdict is in!

After decades of people claiming that creatine will wreck your kidneys, liver, & various other claims, a new study has put these myths to bed. 

In my latest episode of the Dr. Layne Norton Podcast, I go DEEP on the most comprehensive dataset to date: a brand new meta-analysis by Kreider et al. (2025) which reviewed 250+ studies, covering over 26,000 participants, some lasting more than a decade, and examined nearly 50 potential side effects.

The verdict? Absolutely no evidence of harm.

I broke down the full paper, the methods, and what this means for athletes and everyday lifters in the latest episode of the podcast.

🧬 Study: Safety of creatine supplementation: analysis of the prevalence of reported side effects in clinical trials and adverse event reports

Introduction

Creatine is a naturally occurring amino acid derivative synthesized endogenously from arginine, glycine, and methionine, that is involved in the production of energy. 1 Creatine is combined with a phosphate ion to form phosphocreatine which is a high energy phosphate donor that can be used to replenish adenosine tri-phosphate (ATP) that has been degraded to adenosine di-phosphate (ADP) during intense work. 2

While the human body can make creatine endogenously, typically the endogenous production is not sufficient to maximize intracellular phosphocreatine stores, therefore supplementation with a dose of 0.3-0.6g/kg/d has been demonstrated to maximize phosphocreatine stores. 3 Creatine is one of the, if not the most effective ergogenic supplements on the market. It has been demonstrated to:

• Increase lean mass. 4
• Increase strength. 5
• Improved power output and sprint speed. 6
• Improve cognition (attention time, processing speed, & memory. 7
• Improve symptoms of depression and anxiety. 8
• May protect against injury, severity of concussions, & traumatic brain injury.  9
• May also improve immune function, cardiovascular health, & brain health 10 11 12 13

When examining total creatine intake from diet & supplements, there are interesting associations

• Lower than recommended creatine intake in children (<1.5g/day) is associated with lower weights & height, less lean mass, bone mineral content, & higher fat mass than those who consumed greater amounts of creatine. 14 15
• Women over the age of 12 who consume low amounts of creatine (<13mg/kg) had increased risk for fetal macrosomia, infections, hysterectomy, oophorectomy, and receiving hormone replacement therapy, while those consuming diets higher in creatine had lower risks of irregular menstrual periods, obstetric conditions, and pelvic pathology.  16
• In older (>60 years old) low creatine intake (<0.95g/day) was associated with poorer cognitive function, increased risk of angina pectoris, & liver problems.  17 18
• In adults, low creatine intake is associated with increased risk of cancer incidence and depression. 19

Based on these data, it is clear that creatine supplementation is an effective ergogenic supplement that may also have wide reaching benefits for overall health including cognition. To date, hundreds, if not thousands of clinical trials to evaluate the effectiveness and safety of creatine have been performed. Still, questions about the safety of creatine supplementation have persisted since it’s introduction to the supplement market ~30 years ago, despite creatine monohydrate being generally recognized as safe (GRAS) by the FDA. The purpose of this meta-analysis was to critically examine the safety of creatine supplementation from human randomized control trials compared to placebo. This meta-analysis examined:

• The presence of reported side effects in trials involving creatine supplementation
• The frequency of these reported side effects in these trials from people supplementing with creatine compared to those receiving a placebo
• The presence of adverse event reporting (AERs) in this trial
• The side effects reported in trials compared to claims made about creatine on the internet

Methods

Inclusion criteria for studies included in this meta-analysis:

• Any trial that included supplementation with creatine (685 trials included) 
• Any trials that included a placebo compared to creatine (652 of the 685 trials)
• The researchers then created a data table including any reported side effects from these trials 
• The table separated side effects reported for creatine & side effects reported for placebo
• They also examined the frequency of the reported side effects in the people receiving creatine vs. the frequency in people who received a placebo
• Reported the number of adverse events reported (AERs)
• The researchers also performed a ‘sentiment analysis’ using an analysis of online comments on YouTube and X social media platforms to determine what the sentiment towards creatine is

Results

• The average study had ~20 participants & were ~30 years old, who were approx 75kg body weight, & on average ingested creatine for 65 days at an average of 0.17g/kg/d or about 12.5g/day
• Longest study was 14 years long
• Oldest population was 77 years old
• Study with the most participants had 874 subjects
• 35 side effects were reported
• 13.2% of subjects taking placebo reported side effects whereas 13.7% of subjects taking creatine reported side effects with no significant difference between the 2 in number of total side effects reports
• The only 2 side effects that were reported more frequently in the creatine supplemented group vs. the placebo group were GI distress (4.9% in supplement groups vs. 4.3% in the placebo groups) and muscle cramps (2.9% in supplement groups vs. 0.9% in placebo groups). However, when the number of participants reporting side effects was considered from all studies, no significant differences were observed in the frequency of GI issues or any of the other side effects
• No differences in kidney or liver function and markers of kidney and liver health
• There were no difference between the frequency of the other 33 reported side effects between placebo & creatine supplemented groups. The other 33 side effects included vertigo, hypertension, headache, dizziness, lightheadedness, nausea, diarrhea, impaired concentration, sleep disturbances, poor appetite, fatigue, excessive sweating, edema, palpations, thromboembolic events, kidney-related issues, elevated liver enzymes, pregnancy, and other complaints
• This data set included a 8 year clinical trial in Parkinson’s patients providing 10g/day of creatine. They reported the incidences of neoplasm, nerve & muscle complaints, nervous system issues, infections and infestations, renal/urinary issues, psychiatric disorders, respiratory complaints, vascular issues, bone and joint problems, metabolism and nutrition issues, skin complications, cardiac conditions, eye disorders, and reproductive issues. There were no differences between placebo & creatine supplemented groups for any of these issues that were assessed. 20
• There were no differences between frequency of side effects when groups were separated based on sex, age, and healthy vs. clinical based populations
• 203 AERs were reported out of 28.4 million total AERs reported to the database
• Overall online sentiment was more positive than negative for creatine supplementation

Discussion

This study demonstrated that creatine supplementation is safe and effective with no more frequent reporting of side effects in the subjects who supplemented with creatine vs. those that received placebo. This data demonstrates that despite decades of concerns about creatine safety, there is overwhelming evidence that it is the single safest & most effective supplement on the market. It should also be noted that there is NO EVIDENCE that other forms of creatine like HCl, ethyl ester, or buffered creatine have less side effects or are more effective than creatine monohydrate.