Nevertheless, our systematic approach followed the PRISMA method , the search was conducted using three databases, PubMed, SCOPUS, and WOS, and included grey literature. Therefore, the type and duration of supplementation, or the modality and duration of exercise, could influence the effect of NAC on the response and adaptations to exercise, making it difficult to make a clear judgement on the ergogenic potential of NAC as a sports supplement. This could suggest that NAC was effective when exercise was performed, and that NAC supplementation would have a sports-ergogenic effect. These researchers reported that vitamin C plus vitamin E supplementation did not reduce soreness in endurance runners . The increase in plasma thiol concentration induced by NAC acts as a stabiliser of the structural degradation of muscle proteins and provides an optimal/better state of skeletal muscle . Badawy et al. reported that NAC induced ovulation in PCOS patients through increasing insulin sensitivity(Reference Badawy, State and Abdelgawad13). It must be noted that the GSH levels might be effective in the relationship between NAC and reproductive biomarkers(Reference Atkuri, Mantovani and Herzenberg50). Therefore, NAC, through decreasing lipid peroxidation, could have beneficial effects on reproductive biomarkers. Regarding TT, studies with shorter duration had smaller sample sizes than studies with longer duration studies. In other investigated variables, extending supplementation duration was ineffective in the overall results. NAC supplementation for ≥ 8 weeks led to a significant decrease in TT. Among them, 44% of infertile men had no known disease that could explain infertility and these patients were assigned as idiopathic male infertility (Pierik et al., 2000). Conclusively, LC/LAC and NAC showed a greater improvement in sperm motility and normal morphology. Finally, seven articles including 621 patients were analyzed. We researched PubMed, EMBASE, and Cochrane Library databases and references to related articles. They may offer similar benefits in some cases but should not replace prescribed treatment without medical guidance. Overlapping mechanisms can increase the risk of hypoglycemia. Two studies 32,33 showed mild adverse reactions, such as erythema, vomiting, sweating, flushing, rashes, coughing, and itchy skin, and one study conducted by Ferreira et al. noted mild to severe side effects such as gas, an upset stomach, nausea, and drowsiness. In the studies included in the systematic review, no changes were reported in enzymatic activities such as CAT , SOD , and XO , and in MDA metabolite in the IG compared to the non-supplemented group. Studies included in the systematic review of the effect of N-Acetylcysteine supplementation on health biomarkers. Results of the risk of bias assessment of included studies—Cochrane Bias Methods Group . The main biases found in the studies included in the systematic review were items 1 and 4 (Table 2). Supplementation with antioxidants in conjunction with physical activity would potentially reduce the harmful effects of exercise-induced OS, enhance the antioxidant defence system, and increase the beneficial effects of physical activity by improving exercise performance . The references of included studies were also searched. Also, publication bias could change the effects of NAC on E2 levels and endometrial thickness. A comparison of two meta-analyses with the subjects of NAC and l-carnitine supplementation on inflammatory and oxidative stress biomarkers revealed that NAC had better effects than l-carnitine(Reference Faghfouri, Zarezadeh and Tavakoli-Rouzbehani6,Reference Fathizadeh, Milajerdi and Reiner44) . Other mechanisms proposed for the effects of l-carnitine on FSH and LH levels could be attributed to the regulation of lipid peroxidation and activity of antioxidant enzymes(Reference Rezaei, Mardanshahi and Shafaroudi43). Therefore, a definite interpretation of more decreasing effects of NAC on E2 levels than metformin needs more studies. 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. 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.