Analysis of the efficacy, safety, and regulatory status of novel forms of creatine

Abstract

Creatine has become one of the most popular dietary supplements in the sports nutrition market. The form of creatine that has been most extensively studied and commonly used in dietary supplements is creatine monohydrate (CM). Studies have consistently indicated that CM supplementation increases muscle creatine and phosphocreatine concentrations by approximately 15-40%, enhances anaerobic exercise capacity, and increases training volume leading to greater gains in strength, power, and muscle mass. A number of potential therapeutic benefits have also been suggested in various clinical populations. Studies have indicated that CM is not degraded during normal digestion and that nearly 99% of orally ingested CM is either taken up by muscle or excreted in urine. Further, no medically significant side effects have been reported in literature. Nevertheless, supplement manufacturers have continually introduced newer forms of creatine into the marketplace. These newer forms have been purported to have better physical and chemical properties, bioavailability, efficacy, and/or safety profiles than CM. However, there is little to no evidence that any of the newer forms of creatine are more effective and/or safer than CM whether ingested alone and/or in combination with other nutrients. In addition, whereas the safety, efficacy, and regulatory status of CM is clearly defined in almost all global markets; the safety, efficacy, and regulatory status of other forms of creatine present in today's marketplace as a dietary or food supplement is less clear.

Fig. 1

Creatine salts

Fig. 2

Chemical structure of creatine and creatine derivatives

Fig. 3

Stability of creatine monohydrate powder. Adapted from Jäger (2003)

Fig. 4

Degradation of creatine to creatinine

Fig. 5

Effect of pH on creatine stability in solution. Adapted from Howard and Harris (1999)

Fig. 6

Very low pH prevents creatine degradation

Fig. 7

Degradation of creatine and creatine ester

Fig. 8

Comparison of blood plasma levels of different forms of creatine. Adapted from Jäger et al. (2007)

Fig. 9

Percentage of creatine retained during a 3-day loading period (20 g/day). Adapted from Greenwood et al. (2003)

Fig. 10

Change in muscle-free creatine content in response to 5 days of low or high-dose creatine serum and placebo ingestion compared to CM. Adapted from Kreider et al. (2003b)

Fig. 11

Changes in total muscle creatine content in response to placebo (PLA), creatine monohydrate (CRT), and creatine ethyl ester (CEE) supplementation (Spillane et al. 2009). ^†Significantly different from PLA group. *Significant difference from baseline. Reprinted with permission

Fig. 12

Change in whole body creatine retention in response to 5 days of placebo, creatine monohydrate (CM), low-dose d-pinitol (P) and CM, and high-dose P and CM supplementation. Adapted from Kerksick et al. (2007)

Fig. 13

Influence of Russian tarragon on creatine absorption. Adapted from Jäger et al. (2008a)