The 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 years, 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 (SBP) and diastolic BP (DBP) in adults. Inclusion criteria were adult participants and an intervention duration >= 4 days. 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% confidence (CI). Twenty-two RCTs with 30 effect sizes were included in this meta-analytic work. 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. Sub-group analysis showed significant reductions in SBP and DBP regardless of baseline BP category (normotensive, hypertensive), study duration (<= 24 days, >24 days), sex (female, male), health status (healthy, unhealthy), and body mass index (normal, overweight, obese). No significant changes were observed with dosages >9 g/day, trial duration >24 days, 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 relationship 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/day for SBP (P = 0.034) independent of trial duration. Overall, L-arginine supplementation may be effective for decreasing BP.