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

Boston University School of Medicine

Joseph A Vita

Boston University School of Medicine

Diane Handy

Harvard Medical School

Monica Holbrook

Boston University School of Medicine

Joseph Palmisano

Boston University School of Medicine

Ryan Beal

Boston University School of Medicine

Joseph Loscalzo

Harvard Medical School

Robert T Eberhardt

Boston University School of Medicinerobert.eberhardt{at}bmc.org

Abstract

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.

Key Words: creatine • endothelial function • homocysteine • l-arginine • methylation • nitric oxide

Vascular Medicine, Vol. 14, No. 3, 239-248 (2009)
DOI: 10.1177/1358863X08100834


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