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In this meta-analysis, compared with the control group, the viscosity, liquefaction time, and sperm volume of NAC group were significantly increased. They researched PubMed, EMBASE, and Cochrane Library databases and references of the included studies; Medical Subject Headings (MeSH) terms were "L-carnitine, L-acetyl-carnitine, N-acetyl-cysteine, NAC, LC, LAC, infertile, idiopathic, idiopathic infertile, men, male, idiopathic asthenozoospermia." Pooled analysis of eighteen randomised clinical trials with a total population of 3161 in the current study revealed that NAC supplementation had significant increasing and decreasing effects on FSH and TT levels, respectively. Therefore, the present meta-analysis aimed to evaluate the effects of NAC supplementation on infertility parameters such as ovulation biomarkers and serum levels of sex hormones in women with PCOS. The present study assessed the effects of NAC supplementation on semen parameters and antioxidant status in asthenoteratozoospermic men partners of infertile couples. Based on the above, the present study was conducted to investigate the effects of daily oral NAC supplementation on the quality of semen parameters, chromatin integrity and reproductive hormones in asthenoteratozoospermic men.
All authors were responsible for data collection, data analysis and data interpretation in the manuscript. The authors would like to thank the Clinical Research Development Unit of Baqiyatallah Hospital, for all their support and guidance during carrying out this study. However, its impact was neutralised by performing trim and fill analysis.
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.
Join healthcare leaders for live online sessions and Q&A — delivering evidence-based strategies to guide patients toward lasting longevity. Lifestyle changes, such as regular exercise and stress management, further support hormone balance. NAC's role in detoxification processes, particularly in supporting glutathione synthesis, aligns with efforts to minimize exposure to such toxins. Avoiding toxins and endocrine-disrupting chemicals is another important practice to support detoxification systems and hormone balance.
Second, all possible subgroup and bias-controlling analyses were performed to obtain reliable results on the effects of NAC on the reproductive biomarkers. First, to our knowledge, current study is the first comprehensive systematic review and meta-analysis addressing this issue, so far. Therefore, future studies must focus on the proper design to diminish the possible sources of bias. Participants of included studies in seventeen of eighteen studies had PCOS. On the other hand, the hormone status and other metabolites levels, such as serum 25(OH)D in women younger than 30 years, are lower than that in women 30 years and older(Reference Nakamura, Nashimoto and Matsuyama45).
The hypothetical action of NAC originates from its ability to stimulate and sustain intracellular levels of reduced glutathione and also to detoxify ROS . Based on our findings and other studies 19, 22, medical therapy with oral antioxidants can improve the quality of semen parameters. Correlation between sperm parameters and chromatin status with total antioxidant capacity (TAC) and malondialdehid (MAD)
Oestrogen levels also were increased after correcting publication bias. As well, NAC supplementation increased levels of GSH in individuals with low GSH levels and improved redox homoeostasis(Reference Paschalis, Theodorou and Margaritelis48). The risk of bias in one included study was low, in two was moderate and other included studies had a higher risk of bias. 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. Rinaldi et al. showed that intake of alcohol increased serum levels of dehydroepiandrosterone sulphate, testosterone, androstenedione and oestrone compared with non-consumers women(Reference Rinaldi, Peeters and Bezemer36,Reference Shafrir, Zhang and Poole37) . 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).
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