Association of l-Arginine Supplementation with Markers of Endothelial Function in Patients with Cardiovascular or Metabolic Disorders: A Systematic Review and Meta-Analysis
What this study found
Overall, oral L-arginine did not improve endothelial function versus placebo across the pooled trials. In the main meta-analysis, blood flow showed no overall benefit (SMD 0.30; 95% CI -0.85 to 1.46; N = 469; p = 0.60), and neither NOx (mean difference 4.41 µmol/L; 95% CI -0.50 to 9.32; N = 336; p = 0.08) nor ADMA (mean difference -0.04 µmol/L; 95% CI -0.15 to 0.08; N = 290; p = 0.53) changed significantly. Sensitivity analyses suggested a possible positive blood flow effect after removing highly heterogeneous studies (SMD 0.59; 95% CI 0.10 to 1.08; N = 323), and NOx improved in obese/type 2…
- Study & population
- Systematic review and meta-analysis of 13 randomized controlled trials in adults with cardiovascular disease, obesity, impaired glucose tolerance/metabolic syndrome, and/or type 2 diabetes.
- Intervention
- Oral L-arginine supplementation was tested across 13 randomized placebo-controlled trials in doses ranging from 3 g/day to 15 g/day, using tablets, capsules, powder, bars, or effervescent tablets; treatment durations ranged from 3 days to 18 months.
- Key limitation
- The evidence base was small and highly heterogeneous, with substantial variation in dose, duration, formulation, and patient population.
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Open PDFOriginal abstract
l-Arginine supplementation is a potential therapy for treating cardiovascular and metabolic diseases. However, the use of distinct l-arginine sources, intervened populations, and treatment regimens may have yielded confusion about their efficacy. This research constitutes a systematic review and meta-analysis summarizing the effects of l-arginine supplementation compared to placebo in individuals with cardiovascular disease (CVD), obesity, or diabetes. Eligibility criteria included randomized clinical trials and interventions based on oral supplementation of l-arginine with a minimum duration of three days; comparison groups consisted of individuals with the same disease condition receiving an oral placebo substance. The primary outcome was flow-mediated dilation, and secondary outcomes were nitrite/nitrate (NOx) rate and asymmetric dimethylarginine (ADMA). Statistical heterogeneity among studies included in the meta-analyses was assessed using the inconsistency index (I2). Fifty-four full-text articles from 3761 retrieved references were assessed for eligibility. After exclusions, 13 studies were included for data extraction. There was no difference in blood flow after post-ischemic hyperemia between the supplementation of l-arginine and placebo groups before and after the intervention period (standardized mean difference (SMD) = 0.30; 95% confidence intervals (CIs) = −0.85 to 1.46; I2 = 96%). Sensitivity analysis showed decreased heterogeneity when the studies that most favor arginine and placebo were removed, and positive results in favor of arginine supplementation were found (SMD = 0.59; 95% CIs = 0.10 to 1.08; I2 = 75%). No difference was found in meta-analytical estimates of NOx and ADMA responses between arginine or placebo treatments. Overall, the results indicated that oral l-arginine supplementation was not associated with improvements on selected variables in these patients (PROSPERO Registration: CRD42017077289).