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Abstract
Over the past few decades the use of dietary creatine monohydrate has emerged as one of the most popular dietary ergogenic supplements. But some researchers have warned that such supplementation may not be entirely safe. This is based on multiple case reports that have indicated a possible link between creatine supplementation and renal dysfunction. Yet several studies have not supported a link between creatine supplementation and renal function, leaving many athletes to wonder what the risks of supplementation might be.
This review re-examines data associated with methods used to analyze renal function in individuals who supplemented with dietary creatine monohydrate. The emphasis of this review is on the various renal function marker methods [i.e., plasma creatinine [mg/dL], plasma urea [mg/dL], estimated creatinine clearance [ml/min], urinary creatinine [g/24hr], ⁵¹Cr-EDTA [ml/min], Cystatin C [mg/L], and urinary urea [g/24/hr] as well as influential factors associated with the individuals that may have the potential to impact renal function [i.e., exercise, type of exercise, medicated, diseased, daily creatine intake, and length of creatine cycle]. The combination of these data was imported into the statistical program Comprehensive Meta-Analysis [CMA]. In all, a total of 21 studies were examined, which included 1,620 control subjects and 961 subjects treated with creatine. Data were compared in a variety of ways, including the comparisons of pre- and post-treatment urinary function markers via an unpaired t-test. The results of the unpaired t-tests found that plasma creatinine and estimated creatinine clearance [eCrnCl] were different before and after creatine supplementation [p is less than 0.05], while other renal function markers did not differ. The groups assessed with plasma creatinine and estimated creatinine clearance were then evaluated individually against categorical moderators associated with exercise, medications, duration of creatine supplementation and pre-existing disease. Results indicated that the combination of exercise and consumption of high doses of creatine monohydrate for a short period of time, as well as consumption of the recommended dose for an extended period of time, had the greatest influence on levels of plasma creatinine [p is less than 0.001] and estimated creatinine clearance [p is less than 0.001].
Because both plasma creatinine and estimated creatinine clearance might change because of changes in creatine intake that are unrelated to renal function, it is recommended that additional clinical studies of creatine supplementation use either Cystatin C or ⁵¹Cr-EDTA as the measure of renal function. In this review, neither of these markers changed with creatine supplementation, and they would not be expected to be directly influenced by creatine intake. In summary, the determination of the impact of creatine supplementation on renal function may be confounded by the marker used to assess renal function, and choosing a marker that is not directly affected by creatine intake [independent of renal function] would provide the most reliable results.