Unlocking the potential of antioxidant supplementation with N-acetylcysteine to improve seminal parameters and analysis of its safety: A systematic review and meta-analysis of randomized controlled trials

Introduction and objectives: N-acetyl-cysteine (NAC) is one of the oldest and most powerful antioxidants used to treat various diseases. It plays an important role in protecting cells against oxidative damage and has the potential to improve seminal parameters in male with infertility. This systematic review and meta-analysis aim to comprehensively evaluate the efficacy and safety profile of antioxidant supplementation with NAC in male with infertility or impaired semen parameters. Materials and methods: This systematic review and meta-analysis adhered to Cochrane Handbook guidelines. A literature search across PubMed, ScienceDirect, Cochrane Library and Scopus on February 21, 2024 of studies evaluating NAC supplementation for male infertility or impaired semen parameters was conducted. Study quality was assessed using Revised Cochrane's risk of bias (RoB 2.0) and RevMan 5.4 was used for meta-analysis. Results: Search yielded 1.106 articles and 5 studies were included in this meta-analysis. Our study showed that patients who received NAC had statistically significant results in improving sperm volume [MD: 0.69 (0.26-1.12), P = 0.002], sperm concentration [MD: 4.43 1.50-7.36), P = 0.003], sperm total motility [MD: 9.69 (6.61-12.77), P < 0.00001], and normal sperm morphology [MD: 1.36 (0.70-2.03), P < 0.0001] compared to control. Additionally, patients given NAC had no reported side effects based on our included studies. Conclusions: We found NAC supplementation significantly improves seminal parameters and has a favorable safety profile. These findings highlight the potential role of NAC as a safe supplementation for male with infertility or in male with impaired semen parameters.