Clinical Pharmacology of the Dietary Supplement Creatine Monohydrate

Adam M. Persky¹ and Gayle A. Brazeau²

Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida

I. Introduction
II. Creatine Synthesis and Transport
    A. Synthesis
    B. Transporters
III. Mechanisms of Action
    A. Energy Metabolism
    B. Protein Synthesis
    C. Membrane Stabilization
IV. Pharmacokinetics
    A. Dosing
    B. Absorption and Distribution
    C. Clearance
    D. Pharmacokinetic Studies
V. Therapeutic Usage
    A. Exercise Performance
    B. Gyrate Atrophy
        1. Human Studies.
    C. Diseases Affecting Mitochondria
        1. Parkinson's Disease.
            a. Animal Studies.
        2. Huntington's Disease.
            a. Animal Studies.
        3. Other Mitochondrial Pathologies.
            a. Animal Studies.
            b. Human Studies.
    D. Other Brain Pathologies
        1. Animal Studies.
        2. Human Studies.
    E. Muscular Disease
        1. Animal Studies.
        2. Human Studies.
    F. Heart Disease
        1. Animal Studies.
        2. Human Studies.
    G. Use of Creatine Analogs
VI. Side Effects
VII. Products
VIII. Conclusion
Acknowledgments
References

Creatine is a dietary supplement purported to improve exercise performance and increase fat-free mass. Recent research on creatine has demonstrated positive therapeutic results in various clinical applications. The purpose of this review is to focus on the clinical pharmacology and therapeutic application of creatine supplementation. Creatine is a naturally occurring compound obtained in humans from endogenous production and consumption through the diet. When supplemented with exogenous creatine, intramuscular and cerebral stores of creatine and its phosphorylated form, phosphocreatine, become elevated. The increase of these stores can offer therapeutic benefits by preventing ATP depletion, stimulating protein synthesis or reducing protein degradation, and stabilizing biological membranes. Evidence from the exercise literature has shown athletes benefit from supplementation by increasing muscular force and power, reducing fatigue in repeated bout activities, and increasing muscle mass. These benefits have been applied to disease models of Huntington's, Parkinson's, Duchenne muscular dystrophy, and applied clinically in patients with gyrate atrophy, various neuromuscular disorders, McArdle's disease, and congestive heart failure. This review covers the basics of creatine synthesis and transport, proposed mechanisms of action, pharmacokinetics of exogenous creatine administration, creatine use in disease models, side effects associated with use, and issues on product quality.