Effect of Oral L-arginine Supplementation on Blood Pressure

A Meta-analysis of Randomized, Double-blind, Placebo-controlled Trials

Jia-Yi Dong, BSc; Li-Qiang Qin, MD, PhD; Zengli Zhang, MD, PhD; Youyou Zhao, PhD; Junkuan Wang, PhD; Fabrizio Arigoni, PhD; Weiguo Zhang, MD, PhD


Am Heart J. 2011;162(6):959-965. 

In This Article

Abstract and Introduction


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.


Hypertension is a huge public health burden, affecting approximately one billion individuals worldwide.[1] It has been widely believed that lifestyle and dietary factors play an important role in the development of hypertension. This view has been reinforced by studies such as the DASH which demonstrates that a diet rich in vegetables, fruits, and low-fat dairy foods and low in saturated and total fat can substantially lower blood pressure (BP).[2] Moreover, the DASH diet contains more protein than the control diet,[2] and arginine-rich protein has been hypothesized to contribute to the BP-lowering effect of this diet.

L-Arginine, a semi-essential amino acid, is the natural substrate for nitric oxide (NO) synthase and responsible for the production of the endothelium-derived relaxing factor NO, which is involved in a wide variety of regulatory mechanisms of the cardiovascular system.[3] This property led to the hypothesis that L-arginine may have BP-lowering effect. It is attractive to lower BP and prevent hypertension through effective lifestyle modification, particularly dietary supplements in persons with prehypertension, given the lack of evidence that antihypertensive drugs reduce cardiovascular morbidity and mortality in this population.[4] During the past decades, a number of clinical trials have been carried out to evaluate the role of L-arginine in BP regulation. However, the sample size of these trials was small, the quality varied from low to high, and the results were inconsistent. We therefore aimed to examine the effect of oral L-arginine supplementation on BP by conducting a meta-analysis of randomized, double-blind, placebo-controlled trials.


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