The Potential Role of NO-pathway-related Supplements on Erectile Dysfunction: a Systemic Review and Meta-Analysis

Introduction The efficacy and safety of arginine supplements in erectile dysfunction (ED) remain debatable. Aim To assess the potential role of arginine supplements on ED as alternatives to phosphodiesterase inhibitors. Methods Studies published up to April 2018 that evaluated the efficacy of arginine supplements were identified from multiple databases (Google Scholar, PubMed, Medline, Embase, Kiss, DBpia, and Cochrane databases). Studies comparing arginine supplements with placebo or no treatment; focusing only on patients with mild to moderate severity of ED; and presenting outcomes such as improvement rate, International Index of Erectile Function (IIEF) score, and adverse effects were included. Subgroup analysis for arginine alone and arginine in combination with other substances was further conducted to increase interpretability. Main Outcome Measure The strength of the association between arginine supplements and ED was assessed using relative odds ratios and weighted mean differences with 95% CI. Results In total, 10 randomized controlled trials met the inclusion criteria, reporting the outcomes of 540 patients with ED. The analysis demonstrated that arginine supplements with dosage ranging from 1,500 to 5,000 mg significantly improved ED compared with placebo or no treatment (odds ratios, 3.37 [1.29, 8.77], P = .01, I2 = 44). Arginine supplements also caused significant improvements in the IIEF subdomain scores of overall satisfaction, intercourse satisfaction, orgasmic function, and erectile function, whereas the IIEF sexual desire score remain unchanged. The adverse effect rate in the arginine-treated group was 8.3%, and that in the placebo group was 2.3%, none of which were severe. Clinical Implications Arginine supplements can be recommended to patients with mild to moderate ED. Strength & Limitations The strength of this study is that it is the first meta-analysis to assess the potential role of arginine supplements in ED compared with placebo or no treatment. A limitation is that the treatment dosage and duration varied among studies, which may have contributed to study heterogeneity. Conclusion The results of our systematic review and meta-analysis provide evidence on the effectiveness of arginine supplements for mild to moderate ED.