Effect of Oral L-arginine Supplementation on Blood Pressure: a Meta-analysis of Randomized, Double-blind, Placebo-controlled Trials

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.