There are several different available forms of creatine: creatine anhydrous which is creatine with the water molecule removed in order to increase the concentration of creatine to a greater amount than that found in CM. Creatine has been manufactured in salt form: creatine pyruvate, creatine citrate, creatine malate, creatine phosphate, magnesium creatine, creatine oroate, Kre Alkalyn (creatine with baking soda). Creatine can also be manufactured in an ester form. Creatine ethyl ester (hydrochloride) is an example of this, as is creatine gluconate which is creatine bound to glucose. Another form is creatine effervescent which is creatine citrate or CM with citric acid and bicarbonate. The citric acid and bicarbonate react to produce an effervescent effect. When mixed with water the creatine separates from its carrier leaving a neutrally charged creatine, allowing it to dissolve to a higher degree in water. Manufacturers claim that creatine effervescent has a longer and more stable life in solution. When di-creatine citrate effervescent was studied [59
] for stability in solution it was found that the di-creatine citrate dissociates to citric acid and creatine in aqueous solutions which in turn forms CM and eventually crystallises out of the solution due to its low solubility. Some of the creatine may also convert to creatinine.
Jager et al [60
] observed 1.17 and 1.29 greater peak plasma creatine concentration 1 hour after ingesting creatine pyruvate compared to isomolar amount of CM and creatine citrate respectively. However time to peak concentration, and velocity constants of absorption and elimination, was the same for all three forms of creatine. Although not measured in this study it is questionable that these small differences in plasma creatine concentrations would have any effect on the increase of muscle creatine uptake. Jäger et al [61
] investigated the effects of 28-days of creatine pyruvate and citrate supplementation on endurance capacity and power measured during an intermittent handgrip (15 s effort per 45s rest) exercise in healthy young athletes. The authors used a daily dose protocol with the intention to slowly saturate muscle creatine stores. Both forms of creatine showed slightly different effects on plasma creatine absorption and kinetics. The two creatine salts significantly increased mean power but only pyruvate forms showed significant effects for increasing force and attenuating fatigability during all intervals. These effects can be attributed to an enhanced contraction and relaxation velocity as well as a higher blood flow and muscle oxygen uptake. On the other hand, the power performance measured with the citrate forms decreases with time and improvements were not significant during the later intervals. In spite of these positive trends further research is required about the effects of these forms of creatine as there is little or no evidence for their safety and efficacy. Furthermore the regularity status of the novel forms of creatine vary from country to country and are often found to be unclear when compared to that of CM [62
In summary, creatine salts have been show to be less stable than CM. However the addition of carbohydrates could increase their stability [62
]. The potential advantages of creatine salts over CM include enhanced aqueous solubility and bioavailability which would reduce their possible gastrointestinal adverse effects [63
]. The possibility for new additional formulation such as tablets or capsules is interesting for its therapeutic application due to its attributed better dissolution kinetics and oral absorption compared to CM [63
]. However more complete in vivo pharmaceutical analysis of creatine salts are required to fully elucidate their potential advantages/disadvantages over the currently available supplement formulations.
Creatine is a hydrophilic polar molecule that consists of a negatively charged carboxyl group and a positively charged functional group [64
]. The hydrophilic nature of creatine limits its bioavailability [65
]. In an attempt to increase creatines bioavailability creatine has been esterified to reduce the hydrophilicity; this product is known as creatine ethyl ester. Manufacturers of creatine ethyl ester promote their product as being able to by-pass the creatine transporter due to improved sarcolemmal permeability toward creatine [65
]. Spillane et al [65
] analyzed the effects of a 5 days loading protocol (0.30 g/kg lean mass) followed by a 42 days maintenance phase (0.075 g/kg lean mass) of CM or ethyl ester both combined with a resistance training program in 30 novice males with no previous resistance training experience. The results of this study [65
] showed that ethyl ester was not as effective as CM to enhance serum and muscle creatine stores. Furthermore creatine ethyl ester offered no additional benefit for improving body composition, muscle mass, strength, and power. This research did not support the claims of the creatine ethyl ester manufacturers.
Polyethylene glycol is a non-toxic, water-soluble polymer that is capable of enhancing the absorption of creatine and various other substances [66
]. Polyethylene glycol can be bound with CM to form polyethylene glycosylated creatine. One study [67
] found that 5 g/d for 28 days of polyethylene glycosylated creatine was capable of increasing 1RM bench press in 22 untrained young men but not for lower body strength or muscular power. Body weight also did not significantly change in the creatine group which may be of particular interest to athletes in weight categories that require upper body strength. Herda et al [68
] analyzed the effects of 5 g of CM and two smaller doses of polyethylene glycosylated creatine (containing 1.25 g and 2.5 g of creatine) administered over 30 days on muscular strength, endurance, and power output in fifty-eight healthy men. CM produced a significantly greater improvement in mean power and body weight meanwhile both CM and polyethylene glycosylated form showed a significantly (p
0.05) greater improvement for strength when compared with control group. These strength increases were similar even though the dose of creatine in the polyethylene glycosylated creatine groups was up to 75% less than that of CM. These results seem to indicate that the addition of polyethylene glycol could increase the absorption efficiency of creatine but further research is needed before a definitive recommendation can be reached.