The effect of l-arginine and creatine on vascular function and homocysteine metabolism

Abstract

AbstractStudies 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.