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No significant difference in overall effect size was shown after removing each study using sensitivity analysis. Sensitivity analysis revealed that no single study likely affected the pooled results. Sensitivity analysis demonstrated no evidence of the impact of a single study on the results. Study location, treatment duration and type of control were detected as sources of heterogeneity following subgroup analysis (Table 2). Thus, trim and fill analysis was conducted with five imputed studies. Sensitivity analysis determined that no particular study likely affected the pooled results. The type of control and study location were identified as sources of high heterogeneity following subgroup analysis.
In this meta-analysis, compared with the control group, the viscosity, liquefaction time, and sperm volume of NAC group were significantly increased. 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). Due to the higher number of participants, this study was greatly weighted and influenced the overall results, so removing of mentioned study in sensitivity analysis changed the increasing effects of NAC on the FSH levels. Performing subgroup analysis revealed that the effects of NAC on TT levels in studies with intervention duration ≥ 8 weeks were more robust than the entire sample (Table 2).
Epigenetic and environmental changes are various in different countries, and this issue may lead to different responses to NAC supplementation(Reference Diamanti-Kandarakis, Kandarakis and Legro33). A decline in TT was reported in both studies(Reference Elnashar, Fahmy and Mansour21,Reference Chandil, Pande and Sen27) . Also, it has been shown that a longer duration of supplementation might be more effective.
Glutathione also acts as an antioxidant, neutralizing inflammatory molecules called free radicals or ROS that can damage cellular structures. Glutathione is a tripeptide composed of three amino acids, glutamate, glycine, and cysteine. NAC supports detoxification primarily through its role as a precursor to glutathione, a powerful antioxidant involved in the body's natural detoxification processes. NAC is used as a precursor for glutathione and possesses both antioxidant and mucolytic properties. 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).
The interconnected nature of the endocrine system means that changes in one hormone can have ripple effects, impacting the function of others. Despite, numerous studies suggesting NAC can protect sperm from cro-injury but similar effect was not observed in all species . Our results showed a significant decline in concentrations of MDA, a specific marker of lipid peroxidation, while TAC significantly increased after treatment with NAC. Bidmeshkipour et al. reported that TAC levels in the seminal plasma of asthenospermic men were significantly lower than those of healthy men, accordingly, the effect of NAC on MDA and TAC was investigated in the seminal plasma. NAC may benefit protamination by feeding the one-carbon metabolism, which, besides increasing GSH and antioxidant capacity of sperm, provides activated methyl groups for epigenetic DNA reprogramming . GSH is a critical intracellular antioxidant that helps limit the impact of oxidative stress and protect vital cellular components (lipids, proteins, DNA) against harmful peroxidation.
No, NAC does not directly increase testosterone production. Does NAC directly increase testosterone production? Based on available evidence, the answer to the question, does NAC decrease testosterone? Its role is primarily supportive, helping the body recover and potentially aiding in the restoration of natural testosterone production. NAC is sometimes used during post-cycle therapy (PCT) due to its antioxidant and liver-protective properties. After a cycle of anabolic steroids, individuals often experience a suppression of their natural testosterone production. It’s best to start with a lower dose and gradually increase it as needed, monitoring for any side effects.
The peripheral blood sample was taken from each patient and was immediately centrifuged for 10 min at 3000 rpm (Hettich, EBA20, UK) and serum samples stored at − 70 °C for future evaluation and analysis. Sperm count was evaluated by a sperm counting chamber and expressed as million/ml. Normal morphology was assessed by Papanicolaou staining and subjects with less than 4% normal sperm morphology were considered as teratozospermic according to WHO criteria.
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