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

Jahangir, Eiman, Vita, Joseph A., Handy, Diane, Holbrook, Monica, Palmisano, Joseph, Beal, Ryan, Loscalzo, Joseph and Eberhardt, Robert T. (2009) The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vascular Medicine, 14 3: 239-248. doi:10.1177/1358863X08100834

Author Jahangir, Eiman
Vita, Joseph A.
Handy, Diane
Holbrook, Monica
Palmisano, Joseph
Beal, Ryan
Loscalzo, Joseph
Eberhardt, Robert T.
Title The effect of L-arginine and creatine on vascular function and homocysteine metabolism
Journal name Vascular Medicine   Check publisher's open access policy
ISSN 1358-863X
Publication date 2009-08-01
Sub-type Article (original research)
DOI 10.1177/1358863X08100834
Open Access Status Not Open Access
Volume 14
Issue 3
Start page 239
End page 248
Total pages 10
Place of publication London, United Kingdom
Publisher Sage Publications
Language eng
Formatted 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.
Keyword Creatine
Endothelial function
Nitric oxide
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
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