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).
Highlights
IntroductionCardiovascular (CVD) and metabolic diseases (such as obesity, insulin resistance, and diabetes) are major health problems worldwide
Cardiovascular (CVD) and metabolic diseases are major health problems worldwide
41 articles were excluded due to the following reasons: type of patient, comparison group, non-specific outcomes or methods of assessment, type of intervention, study design, language, multiple publications, and lack of author responses
Summary
Cardiovascular (CVD) and metabolic diseases (such as obesity, insulin resistance, and diabetes) are major health problems worldwide Such conditions are physiologically related through mechanisms that involve endocrine, nervous, and immune system cross-talk [1]. CVD and diabetes impose large economic burdens on the individual patient and on national healthcare systems For this reason, the search for complementary and alternative therapies is of major interest. One of the major connections between these diseases is the availability of nitric oxide (NO), a nitrogen free radical that is continuously produced from the semi-essential amino acid, L-arginine [10] This molecule participates in several regulatory processes such as relaxation and proliferation of vascular smooth muscle cells, angiogenesis, immune response, insulin secretion and signaling, and cell communication [1]
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