Effect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials.

A decade-old meta-analytic work indicated that l-arginine supplementation might have a blood pressure (BP)-lowering effect in different populations. However, several relevant investigations have emerged in the last 10 y, and an up-to-date systematic review and meta-analysis on this topic is currently lacking. Therefore, we aimed to examine the impact of l-arginine supplementation on BP by conducting a systematic review and dose-response meta-analysis of randomized placebo-controlled clinical trials (RCTs). We searched online databases using relevant keywords up to April 2021 to identify RCTs using oral l-arginine on systolic BP (SBP) and diastolic BP (DBP) in adults. Inclusion criteria were adult participants and an intervention duration ≥4 d. Exclusion criteria were the use of l-arginine infusion and acute interventions. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% CI. Twenty-two RCTs with 30 effect sizes were included in this meta-analysis. The pooled analysis demonstrated significant decreases in SBP (WMD = -6.40 mmHg; 95% CI: -8.74, -4.05; P < 0.001) and DBP (WMD = -2.64 mmHg; 95% CI: -3.94, -1.40; P < 0.001) after l-arginine supplementation. Subgroup analysis showed significant reductions in SBP and DBP regardless of baseline BP category (normotensive, hypertensive), study duration (≤24 d, >24 d), sex (female, male), health status (healthy, unhealthy), and BMI (normal, overweight, obese). No significant changes were observed with dosages >9 g/d, trial duration >24 d, or in obese individuals. l-Arginine supplementation also appears to decrease DBP more effectively in females than in males. Moreover, meta-regression analysis for DBP demonstrated a significant relation between the dose of l-arginine intake and changes in DBP (P = 0.020). In the nonlinear dose-response analysis, the effective dosage of l-arginine supplementation was detected to be ≥4 g/d for SBP (P = 0.034), independent of trial duration. Overall, l-arginine supplementation may be effective for decreasing BP. This study was registered at PROSPERO as CRD42021242772.