Creatine is one of the most extensively researched nutritional supplements used to enhance athletic performance. Recent research, however, has raised some concerns about potential side effects of creatine.
A study from a South African university found that 3 weeks of creatine raised the blood levels of dihydrotestosterone among young rugby players, without changing levels of testosterone. Dihydrotestosterone is a metabolite of testosterone that is more active than testosterone. The study’s authors voiced concern about long-term safety of this effect.
Another study, from Boston University School of Medicine, found that 3 weeks of creatine supplementation raised blood levels of homocysteine by 10-20%. Homocysteine is an amino acid that is toxic to blood vessels. The authors of this study believed that the increase in homocysteine with creatine was due to impairment of kidney function.
Reference and Abstracts:
Clin J Sport Med. 2009 Sep;19(5):399-404.Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players.van der Merwe J, Brooks NE, Myburgh KH.Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
OBJECTIVE: This study investigated resting concentrations of selected androgens after 3 weeks of creatine supplementation in male rugby players. It was hypothesized that the ratio of dihydrotestosterone (DHT, a biologically more active androgen) to testosterone (T) would change with creatine supplementation. DESIGN: Double-blind placebo-controlled crossover study with a 6-week washout period. SETTING: Rugby Institute in South Africa. PARTICIPANTS: College-aged rugby players (n = 20) volunteered for the study, which took place during the competitive season. INTERVENTIONS: Subjects loaded with creatine (25 g/day creatine with 25 g/day glucose) or placebo (50 g/day glucose) for 7 days followed by 14 days of maintenance (5 g/day creatine with 25 g/day glucose or 30 g/day glucose placebo). MAIN OUTCOME MEASURES: Serum T and DHT were measured and ratio calculated at baseline and after 7 days and 21 days of creatine supplementation (or placebo). Body composition measurements were taken at each time point. RESULTS: After 7 days of creatine loading, or a further 14 days of creatine maintenance dose, serum T levels did not change. However, levels of DHT increased by 56% after 7 days of creatine loading and remained 40% above baseline after 14 days maintenance (P < 0.001). The ratio of DHT:T also increased by 36% after 7 days creatine supplementation and remained elevated by 22% after the maintenance dose (P < 0.01).
CONCLUSIONS: Creatine supplementation may, in part, act through an increased rate of conversion of T to DHT. Further investigation is warranted as a result of the high frequency of individuals using creatine supplementation and the long-term safety of alterations in circulating androgen composition.
STATEMENT OF CLINICAL RELEVANCE: Although creatine is a widely used ergogenic aid, the mechanisms of action are incompletely understood, particularly in relation to dihydrotestosterone, and therefore the long-term clinical safety cannot be guaranteed.
Vasc Med. 2009 Aug;14(3):239-48. The effect of L-arginine and creatine on vascular function and homocysteine metabolism.Jahangir E, Vita JA, Handy D, Holbrook M, Palmisano J, Beal R, Loscalzo J, Eberhardt RT.Boston University School of Medicine, Boston, MA 02118, USA.
Studies with L-arginine supplementation have shown inconsistent effects on endothelial function. The generation of guanidinoacetate (GAA) from L-arginine with subsequent formation of creatine and homocysteine and consumption of methionine may reduce the pool of L-arginine available for nitric oxide generation. Experimental studies suggest that creatine supplementation might block this pathway. We sought to determine the effects of L-arginine, creatine, or the combination on endothelium-dependent vasodilation and homocysteine metabolism in patients with coronary artery disease. Patients with coronary artery disease were randomized to L-arginine (9 g/day), creatine (21 g/day), L-arginine plus creatine, or placebo for 4 days (n = 26-29/group). Brachial artery flow-mediated dilation and plasma levels of L-arginine, creatine, homocysteine, methionine, and GAA were measured at baseline and follow-up. L-arginine and creatine supplementation had no effects on vascular function. L-arginine alone increased GAA (p < 0.01) and the ratio of homocysteine to methionine (p < 0.01), suggesting increased methylation demand. The combination of creatinine and L-arginine did not suppress GAA production or prevent the increase in homocysteine-to-methionine ratio. Unexpectedly, creatine supplementation (alone or in combination with L-arginine) was associated with an 11-20% increase in homocysteine concentration (p < 0.05), which was not attributable to worsened renal function, providing evidence against an effect of creatine on decreasing methylation demand. In conclusion, the present study provides no evidence that L-arginine supplementation improves endothelial function and suggests that l-arginine may increase methylation demand. Creatine supplementation failed to alter the actions of L-arginine on vascular function or suppress methylation demand. The unexpected increase in homocysteine levels following creatine supplementation could have adverse effects and merits further study, since creatine is a commonly used dietary supplement.