Association of <span style="font-variant: small-caps">l</span>-Arginine Supplementation with Markers of Endothelial Function in Patients with Cardiovascular or Metabolic Disorders: A Systematic Review and Meta-Analysis

• Main Authors: Josianne Rodrigues-Krause, Mauricio Krause, Ilanna Marques Gomes da Rocha, Daniel Umpierre, Ana Paula Trussardi Fayh
• Format: Article
• Language: English
• Published: MDPI AG 2018-12-01
• Series: Nutrients
• Subjects: obesity; type 2 diabetes; cardiovascular disease; nitric oxide; flow-mediated dilation; asymmetric dimethylarginine
• Online Access: https://www.mdpi.com/2072-6643/11/1/15

<span style="font-variant: small-caps;">l</span>-Arginine supplementation is a potential therapy for treating cardiovascular and metabolic diseases. However, the use of distinct <span style="font-variant: small-caps;">l</span>-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 <span style="font-variant: small-caps;">l</span>-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 <span style="font-variant: small-caps;">l</span>-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 <span style="font-variant: small-caps;">l</span>-arginine and placebo groups before and after the intervention period (standardized mean difference (SMD) = 0.30; 95% confidence intervals (CIs) = &#8722;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 <span style="font-variant: small-caps;">l</span>-arginine supplementation was not associated with improvements on selected variables in these patients (PROSPERO Registration: CRD42017077289).