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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)
This study was conducted as a randomized, blinded clinical trial. Comhaire et al. also found that NAC improved sperm concentration and acrosome reaction while reducing ROS and oxidation of sperm DNA . At the same time, antioxidants, which protect the cell from excessive ROS-induced lipid peroxidation, are also present in the ejaculate . Spermatozoa are susceptible to oxidative damage because their plasma membranes are rich in polyunsaturated fatty acids and have low concentrations of scavenging enzymes . In infertile men’s semen, leukocytes and immature or abnormal spermatozoa are often the two main sources of ROS . Therefore, scavenging excess ROS is essential for normal spermatogenesis and fertilization . Increased pathological ROS generation leads to sperm dysfunction (lipid peroxidation), decreased semen quality and sperm DNA damage .
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.
The direct antioxidant activity of NAC is due to the ability of its free thiol group to react with ROS, but the direct antioxidant activity of NAC is usually lower than that of other antioxidant supplements . TAC is considered to be a reliable indicator of antioxidant content, which would measure the antioxidant capacity of the organism and therefore evaluate the efficacy of antioxidant supplements . The number and severity of these side effects are proportional to the dose, with a maximum tolerated dose of 70 mg/kg and a minimum effective dose of 9 mg/kg , since toxic effects in both adults and children only occur at doses of 6 g/kg when orally taken . In addition, researchers have reported the occurrence of adverse effects such as flatulence, abdominal discomfort, nausea, pruritus, or erythema at doses higher than 20 mg/kg 29,32,33. NAC supplementation was administered by oral capsules 21,22,23,24,25,28,29,35, solution , or powder 26,27,30 and intravenous 31,32,33,34,36. However, NAC supplementation did not induce immune alterations (NK or Lymphocytes) .
Two RCTs including 139 patients were included in the analysis. Two RCTs including 86 patients were included in the analysis. Three RCTs including 431 patients were included in the analysis. Four RCTs including 190 patients were included in the analysis. All included studies were randomized controlled design with specific randomized protocols, and three study described the calculation of sample size. The meta-analysis was performed to access efficacy of L-carnitine/L-acetyl-carnitine (LC/LAC) and N-acetyl-cysteine (NAC) in men with idiopathic asthenozoospermia. Overall, this study supports the efficacy and favourable effects of NAC supplementation on improvement of reproductive system function.