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

Am J Clin Nutr. 2009 Jan;89(1):77-84. doi: 10.3945/ajcn.2008.26544. Epub 2008 Dec 3.


Background: Previous 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.

Objective: The 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).

Design: We 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.

Results: Thirteen 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).

Conclusion: Short-term oral l-arginine is effective at improving the fasting vascular endothelial function when the baseline FMD is low.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Arginine / pharmacology*
  • Brachial Artery / drug effects*
  • Brachial Artery / physiology
  • Cardiovascular Diseases / prevention & control*
  • Child
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology*
  • Fasting
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulsatile Flow / drug effects
  • Randomized Controlled Trials as Topic
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Time Factors
  • Vascular Resistance / drug effects
  • Vasodilation / drug effects
  • Young Adult


  • Arginine