Increase in fasting vascular endothelial function after short-term oral l-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials

Yongyi Bai,Lan Sun,Tao Yang,Kai Sun,Jingzhou Chen,Rutai Hui

doi:10.3945/ajcn.2008.26544

Abstract

BackgroundPrevious trials suggest that oral l-arginine administration affects endothelial function. However, most of these studies were small, the conclusions were inconsistent, and the precise effects are therefore debatable. ObjectiveThe objective was to assess the effect of oral l-arginine supplementation on endothelial function, as measured with the use of fasting flow-mediated dilation (FMD). DesignWe conducted a meta-analysis of randomized, placebo-controlled l-arginine supplementation trials that evaluated endothelial function. Trials were identified in PubMed, Cochrane Library, Embase, reviews, and reference lists of relevant papers. The weighted mean difference (WMD) was calculated for net changes in FMD by using random-effect models. Previously defined subgroup analyses and meta-regression analyses were performed to explore the influence of study characteristics. ResultsThirteen trials were included and evaluated. Because there was only one long-term study, we focused on short-term effects of l-arginine (12 studies, 492 participants). In an overall pooled estimate, l-arginine significantly increased FMD (WMD: 1.98%; 95% CI: 0.47, 3.48; P = 0.01). Meta-regression analysis indicated that the baseline FMD was inversely related to effect size (regression coefficient = −0.55; 95% CI: −1.00, −0.1; P = 0.016). A subgroup analysis suggested that l-arginine supplementation significantly increased FMD when the baseline FMD levels were <7% (WMD: 2.56%; 95% CI: 0.87, 4.25; P = 0.003), but had no effect on FMD when baseline FMD was >7% (WMD: −0.27%; 95% CI: −1.52, 0.97; P = 0.67). ConclusionShort-term oral l-arginine is effective at improving the fasting vascular endothelial function when the baseline FMD is low.

Highlights

Cardiovascular disease (CVD), the biggest burden and dominant chronic disease in many parts of the world, has been predicted to be the main cause of disability and death worldwide in the 21st century [1]
flow-mediated dilation (FMD) levels were significantly higher in the L-arginine–supplemented subjects than in the placebo-treated subjects (13 comparisons, 493 participants; weighted mean difference (WMD): 1.98%; 95% CI: 0.47, 3.48; P 1⁄4 0.01) (Figure 2)
Meta-regression analysis of the data showed that the baseline FMD was negatively related to effect size, which largely explained the heterogeneity of the effect

Summary

INTRODUCTION

Cardiovascular disease (CVD), the biggest burden and dominant chronic disease in many parts of the world, has been predicted to be the main cause of disability and death worldwide in the 21st century [1]. Endothelial function has been shown to be influenced by several vascular risk factors. The semiessential amino acid L-arginine is the only substrate for NO synthesis in vascular endothelial cells This amino acid has the potential to improve endothelial function and is expected to play a role in the prevention or treatment of CVD and other vascular disorders [7]. The precise effects of arginine administration are still under debate In most of these studies, endothelial function was measured by fasting flow-mediated dilation (FMD), which represents the ability of the brachial artery to dilate in response to ischemiainduced hyperemia and reflects the local bioavailability of NO under a physiologic stimulation [38].

Literature search

Findings

DISCUSSION