Effectof L-ArginineSupplementationonBlood PressureinAdults:ASystematicReviewand Dose–ResponseMeta-analysisofRandomized ClinicalTrials

Abstract

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 thistopiciscurrentlylacking.Therefore,weaimedtoexaminetheimpactof L-argininesupplementationonBPbyconductingasystematicreview anddose–responsemeta-analysisofrandomizedplacebo-controlledclinicaltrials(RCTs).Wesearchedonlinedatabasesusingrelevantkeywordsup toApril2021toidentifyRCTsusingoral L-arginineonsystolicBP(SBP)anddiastolicBP(DBP)inadults.Inclusioncriteriawereadultparticipantsand an intervention duration≥4 d. Exclusion criteriawere the use of L-arginine infusionand 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. LArginine supplementation also appears to decrease DBP more effectively in females than in males. Moreover, meta-regression analysis for DBP demonstratedasignificantrelationbetweenthedoseofL-arginineintakeandchangesinDBP(P=0.020).Inthenonlineardose–responseanalysis, theeffectivedosageofL-argininesupplementationwasdetectedtobe≥4g/dforSBP(P=0.034),independentoftrialduration.Overall,L-arginine supplementationmaybeeffectivefordecreasingBP.ThisstudywasregisteredatPROSPEROasCRD42021242772