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Likewise, we show here that supplementation of infertile individuals with 600 mg/day of NAC significantly reduces DNA fragmentation from 19.34 ± 0.47 before treatment to 15.14 ± 0.46 after treatment and also improves sperm protamine content. Most of such clinical studies have evaluated men with high levels of sperm DNA damage. N-acetylcysteine (NAC) is a thiol-based antioxidant that plays an important role in the protection of cellular constituents against oxidative damage.
NAC appears to be a more appropriate supplement than GSH or CySH administration to modulate OS induced by drugs (paracetamol) or diseases that occur with low GSH levels, such as chronic obstructive pulmonary disease (COPD), by increasing intra-tissue GSH 47,48. GSH is the most abundant non-protein thiol in the body and one of the major antioxidants against ROS, and GSH is a cofactor of GPx . The reduction in lipid peroxidation occurs as with other antioxidant supplements, such as vitamin C and/or E, and prevents OS 43,44. This is in line with Yalçin et al. who reported that oral supplementation with 100 mg/day of NAC blocked lipid peroxidation in chronic blepharitis. Exercise stimulates an increase in peroxidation that damages cell membranes, alters lipoproteins, and breaks down structures containing lipid conjugates . The concentration of NAC is considered to be a limiting factor in its direct antioxidant activity .
The antioxidant, glutathione homeostasis, anti-inflammatory, haematological, and regulatory mechanisms make NAC the right supplement for athletes seeking to improve their athletic performance, but more evidence is needed to confirm these findings. In this sense, Kumar et al. recently described that the effects of NAC supplementation can be enhanced by adding glycine (Gly). This research could be of interest to sports physicians, nutritionists, and trainers who want to improve exercise performance, antioxidant capacity, and post-exercise glutathione homeostasis in their athletes.
However, if the body experiences a deficiency in these precursor amino acids, cysteine becomes essential and must be obtained through dietary sources. This designation implies that the body can synthesize cysteine from two other amino acids, namely serine and methionine. Oxidative stress may lead to dysfunction in endocrine glands, contributing to hormone imbalances (13, 27). Excessive production of reactive oxygen species (ROS) can damage cells and impair the intricate signaling pathways that regulate hormone synthesis, secretion, and receptor binding.
The blinding of subjects and researchers was reported in four studies(Reference Hashim, Anwar and El-Fatah22,Reference Nasr9,Reference Chandil, Pande and Sen27,Reference Gayatri, Kumar and Kumar28) . Overall, five studies were defined as high quality(Reference Hassan, Alalfy and Hassan18,Reference Badawy, El Nashar and El Totongy20,Reference El Sharkwy and Abd El Aziz24,Reference Kose and Naziroglu26,Reference Ghomian, Khadem and Moeindarbari5) . The duration of the intervention varied from 5 d to 24 weeks among the studies. Overall, eighteen articles met the inclusion criteria and enrolled in the meta-analysis. After removing duplicate papers and screening the articles carefully by the title and abstract, thirty-five papers were included. Publication bias was determined by visual inspection of the funnel plot.
We utilised a random-effects model to get the overall effect size if the amount of between-study heterogeneity was significant. If the trial had ‘low risk’ for all domains, a high-quality study was considered a low risk of bias. The Cochrane Collaboration’s risk of bias tool was employed to assess the risk of bias for each study(Reference Higgins, Altman and Gøtzsche19). Then, relevant studies were assessed to ensure the suitability of a study for full-text assessment. Numerous studies have indicated that NAC is effective for the induction of ovulation and pregnancy rates in PCOS patients.
N-acetylcysteine (NAC) is used as a sports supplement for its ability to modulate exercise-induced oxidative damage through its antioxidant actions and maintenance of glutathione homeostasis, positioning NAC as a strategy to improve physical performance. The meta-analysis was performed to access the role of N-acetyl-cysteine (NAC) orally daily on the sperm parameters and serum hormones in idiopathic infertile men. However, the studies included in this study are all RCTs, which increases the strength of the research results. Many studies have reported that their effects on sperm epididymal maturation and energy metabolism are an intracellular mechanism, and their effects on testicular epididymal microenvironment are an indirect antioxidant effect (Lenzi et al., 1992). For the analysis of serum hormones, NAC had no obvious differences in improving the serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin compared with the placebo group. High levels of LC in epididymal fluid plays an important role in sperm cell metabolism (Enomoto et al., 2002), and some studies report that the onset of sperm motility is related to the increase of LC in epididymal cavity and the concentration of L-acetyl-carnitine (LAC) in sperm cells (Radigue et al., 1996). For the analysis of serum hormones, NAC had no obvious differences in improving the serum testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin compared with non-treatment group.

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