Little is known about long-term side effects of creatine, but no consistent toxicity has been reported in studies of creatine supplementation. In a study of side effects of creatine, diarrhea was the most commonly reported adverse effect of creatine supplementation, followed by muscle cramping.¹¹ Some reports showed that kidney, liver, and blood functions were not affected by short-term higher amounts^{12, 13} or long-term lower amounts ^{14, 15} of creatine supplementation in healthy young adults. In a small study of people taking 5–30 grams per day, no change in kidney function appeared after up to five years of supplementation.¹⁶ However, interstitial nephritis, a serious kidney condition, developed in an otherwise healthy young man, supplementing with 20 grams of creatine per day.¹⁷ Improvement in kidney function followed avoidance of creatine. Details of this case strongly suggest that creatine supplementation triggered this case of kidney disease. Creatine supplementation may also be dangerous for people with existing kidney disease. In one report, a patient with nephrotic syndrome (a kidney disorder) developed glomerulosclerosis (another serious kidney condition) while taking creatine. when the creatine was discontinued, the glomerulosclerosis resolved.¹⁸

Muscle cramping after creatine supplementation has been anecdotally reported in three studies.^{19, 20, 21}