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.

2025-03-24
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica 97(1)
- Syarif Syarif
- Moh Anfasa Giffari Makkaraka
- Ahmad Taufik Fadillah Zainal
- Ponco Birowo
- Widi Atmoko

PubMed: 40126496
DOI: 10.4081/aiua.2025.13750

Study Design

Type: Meta-Analysis
Population: male with infertility or impaired semen parameters
Methods: systematic review and meta-analysis of studies evaluating NAC supplementation; literature search on February 21, 2024; study quality assessed using Revised Cochrane's risk of bias (RoB 2.0); meta-analysis using RevMan 5.4

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.

Research Insights

N-Acetyl Cysteine→Improved Sperm Concentration
patients who received NAC had statistically significant results in improving ... sperm concentration [MD: 4.43 1.50-7.36), P = 0.003]
Effect
Beneficial
Effect size
Moderate
N-Acetyl Cysteine→Improved Sperm Morphology
patients who received NAC had statistically significant results in improving ... normal sperm morphology [MD: 1.36 (0.70-2.03), P < 0.0001]
Effect
Beneficial
Effect size
Moderate
N-Acetyl Cysteine→Improved Sperm Total Motility
patients who received NAC had statistically significant results in improving ... sperm total motility [MD: 9.69 (6.61-12.77), P < 0.00001]
Effect
Beneficial
Effect size
Large
N-Acetyl Cysteine→Improved Sperm Volume
patients who received NAC had statistically significant results in improving sperm volume [MD: 0.69 (0.26-1.12), P = 0.002]
Effect
Beneficial
Effect size
Moderate

Adverse Events Reported

N-Acetyl Cysteine→Overall tolerability
Additionally, patients given NAC had no reported side effects based on our included studies.
Finding
Reported