A comparative study between N-acetylcysteine and L-carnitine in the management of male infertility (placebo-controlled trial)

Background. Male infertility is a globally recognised health condition, which is mainly reported in the age range of 35–39 years. Males from at least three in six couples are impacted by infertility on a global scale. Research evidence reveals the therapeutic benefits of L-carnitine and N-acetylcysteine for infertile males; however, the current evidence is limited by high heterogeneity in contemporary studies. Therefore, this study aimed to investigate the influence of these treatments on sperm parameters and the semen’s malondialdehyde level and total antioxidant capacity. Materials and methods. This randomised placebo-controlled clinical trial deployed 180 male patients with normal female factor and idiopathic oligoasthenoteratozoospermia from January 2021 to December 2024. The patients in the age group of 25–40 years were randomised into L-carnitine (1000 mg oral dose), N-acetylcysteine (oral dose), and placebo (sugar sachets) treatments. The baseline data included the patient’s age and sperm parameters (including sperm motility, sperm concentration, sperm morphology, and semen volume). The semen parameters in the study groups were re-investigated after six months of the study intervention. Additionally, total antioxidant capacity and malondialdehyde levels in the semen were evaluated before and after the treatment administration. Results. The six-monthly analysis revealed that the sperm parameters, including sperm motility (38 and 38 vs. 4 %), morphology (30 vs. 29 vs. 7 %), and concentration (25 and 24 vs. 2 %), significantly improved with the administration of N-acetylcysteine and L-carnitine, respectively, in comparison to the placebo. However, semen volume (6 and 5 vs. 4 %) was not impacted by either treatment and did not differ significantly from the placebo group (p > 0.05). Compared to pretreatment, N-acetylcysteine monotherapy improved the total antioxidant capacity (1.92 ± 0.12 vs. 2.61 ± 0.12; p = 0.01) and reduced the level of malondialdehyde (2.46 ± 0.11 vs. 1.85 ± 0.10; p = 0.01) in the semen. However, in comparison to the placebo, these improvements were not observed with L-carnitine monotherapy. Conclusions. The oral L-carnitine and N-acetylcysteine treatments effectively improved sperm concentration, morphology, and motility in male patients with infertility. However, as a single-agent therapy, no statistically significant differences were observed between the outcomes of N-acetylcysteine and L-carnitine. In addition, N-acetylcysteine appeared superior to L-carnitine in reducing the oxidative stress and malondialdehyde levels in the seminal plasma. Prospective studies should identify the mechanisms underlying the efficacy of L-carnitine/N-acetylcysteine and evaluate the safety and effectiveness of combination antioxidant treatments against male infertility.