Elsevier

American Heart Journal

Volume 162, Issue 6, December 2011, Pages 959-965
American Heart Journal

Curriculum in Cardiology
Effect of oral l-arginine supplementation on blood pressure: A meta-analysis of randomized, double-blind, placebo-controlled trials

https://doi.org/10.1016/j.ahj.2011.09.012Get rights and content

Background

Previous studies suggest that l-arginine, an amino acid and a substrate of nitric oxide synthase, may have blood pressure (BP)-lowering effect. Because some studies were performed with limited number of patients with hypertension and therefore limited statistical power with sometimes inconsistent results, we aimed to examine the effect of oral l-arginine supplementation on BP by conducting a meta-analysis of randomized, double-blind, placebo-controlled trials.

Methods

PubMed, Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov databases were searched through June 2011 to identify randomized, double-blind, placebo-controlled trials of oral l-arginine supplementation on BP in humans. We also reviewed reference lists of obtained articles. Either a fixed-effects or, in the presence of heterogeneity, a random-effects model was used to calculate the combined treatment effect.

Results

We included 11 randomized, double-blind, placebo-controlled trials involving 387 participants with oral l-arginine intervention ranging from 4 to 24 g/d. Compared with placebo, l-arginine intervention significantly lowered systolic BP by 5.39 mm Hg (95% CI −8.54 to −2.25, P = .001) and diastolic BP by 2.66 mm Hg (95% CI −3.77 to −1.54, P < .001). Sensitivity analyses restricted to trials with a duration of 4 weeks or longer and to trials in which participants did not use antihypertensive medications yielded similar results. Meta-regression analysis suggested an inverse, though insignificant (P = .13), relation between baseline systolic BP and net change in systolic BP.

Conclusions

This meta-analysis provides further evidence that oral l-arginine supplementation significantly lowers both systolic and diastolic BP.

Section snippets

Search strategy

We attempted to follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses5 guidelines in the report of this meta-analysis. We searched PubMed, Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov databases through June 2011 for relevant studies, using terms of “arginine” and “l-arginine” in combination with “blood pressure” and “hypertension.” Our search was limited to randomized controlled trials of oral l-arginine supplementation in humans. In

Characteristics of the studies

We identified 11 studies12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 that fully met the inclusion criteria for this meta-analysis. A flow chart of literature search and study selection is presented in Figure 1. The characteristics of the selected trials are presented in Table I. The included trials were published between 1996 and 2010. The sample size varied from 12 to 79, reaching a total of 387. All trials were randomized, double-blind, and placebo-controlled, of which 9 trials were

Discussion

This meta-analysis of randomized, double-blind, placebo-controlled trials brought evidence that oral l-arginine supplementation, compared with placebo, significantly lowered systolic BP by 5.39 mm Hg (95% CI −8.54 to −2.25) and diastolic BP by 2.66 mm Hg (95% CI −3.77 to −1.54).

The magnitudes of the BP reductions in response to l-arginine supplementation in this meta-analysis are moderate but detectable. It should be noted that most participants included in these studies were normotensive, a

Disclosures

The authors have no conflicts of interest. The authors are solely responsible for the design and conduct of this study, all study analyses and drafting and editing of the manuscript and its final contents.

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