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Pharmacokinetics of the Dietary Supplement Creatine

Clinical Pharmacokinetics volume 42, pages 557–574 (2003)Cite this article

Abstract

Creatine is a nonessential dietary component that, when supplemented in the diet, has shown physiological benefits in athletes, in animal-based models of disease and in patients with various muscle, neurological and neuromuscular disease. The clinical relevance of creatine supplementation is based primarily on its role in ATP generation, and cells may be able to better handle rapidly changing energy demands with supplementation.

Although the pharmacological outcome measures of creatine have been investigated, the behaviour of creatine in the blood and muscle is still not fully understood. Creatine is most probably actively absorbed from the gastrointestinal tract in a similar way to amino acids and peptides. The distribution of creatine throughout the body is largely determined by the presence of creatine transporters. These transporters not only serve to distribute creatine but serve as a clearance mechanism because of creatine ‘trapping’ by skeletal muscle. Besides the pseudo-irreversible uptake by skeletal muscle, creatine clearance also depends on renal elimination and degradation to creatinine.

Evidence suggests that creatine pharmacokinetics are nonlinear with respect to dose size and frequency. Skeletal muscle, the largest depot of creatine, has a finite capacity to store creatine. As such, when these stores are saturated, both volume of distribution and clearance can decrease, thus leading to complex pharmacokinetic situations. Additionally, other dietary components such as caffeine and carbohydrate can potentially affect pharmacokinetics by their influence on the creatine transporter. Disease and age may also affect the pharmacokinetics, but more information is needed.

Overall, there are very limited pharmacokinetic data available for creatine, and further studies are needed to define absorption characteristics, clearance kinetics and the effect of multiple doses. Additionally, the relationship between plasma creatine and muscle creatine needs to be elucidated to optimise administration regimens.

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Notes

  1. Since the time of writing this review, Persky et al., published results from a clinical study that supports many of the hypotheses from this review.

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Acknowledgements

The authors would like to thank Mrs. Patricia Kahn for her help in preparation of the manuscript. Preparation of this manuscript was supported, in part, by The Experimental and Applied Science (EAS) Research Grant on Nutrition and Human Performance from the American College of Sport Medicine Foundation.There are no conflicts of interest relevant to the content of this review.

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  1. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, USA

    Adam M. Persky & Günther Hochhaus

  2. Department of Pharmacy Practice and Pharmaceutics, State University of New York at Buffalo, Amherst, New York, USA

    Gayle A. Brazeau

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Correspondence to Adam M. Persky.

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Persky, A.M., Brazeau, G.A. & Hochhaus, G. Pharmacokinetics of the Dietary Supplement Creatine. Clin Pharmacokinet 42, 557–574 (2003). https://doi.org/10.2165/00003088-200342060-00005

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