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After reviewing the full text and assessing potential records from databases, registries, and other sources, 16 21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36 studies were included in the systematic review (Figure 1). The literature search yielded 777 studies, 763 from the electronic databases WOS, SCOPUS, and PubMed, and 14 from other sources such as ResearchGate and reference lists of relevant studies. These parameters were included as outcomes because they are commonly investigated in health biomarker studies and sports science.
The reviewers searched 219 studies in three databases. Two reviewers searched dependently for all randomized controlled trials (RCTs) published until August 31, 2020, involving the efficacy of LC/LAC and NAC in men with idiopathic asthenozoospermia. This meta-analysis strictly followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) list (Moher et al., 2010). Compared with placebo, NAC orally daily can significantly improve sperm motility (Safarinejad & Safarinejad, 2009). As the pathogenesis of this disease is not completely clear, there is no evidence-based treatment for idiopathic male infertility, and most treatments depend on clinical experience (Dohle et al., 2012).
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) .
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. These results align with a previous study that reported improved serum testosterone after supplementation with NAC . 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. The association between sperm DNA damage and ROS is the basis for the use of antioxidants in the hope of reducing sperm DNA damage.
Clinical trials on the effects of N-acetylcysteine (NAC) supplementation on ovulation and sex hormones profile in women with PCOS have been controversial. Its ability to boost glutathione levels and support antioxidant processes encourages optimal hormone balance and detoxification. Taken together, this correlation analysis emphasizes the role of oxidative stress and anti-oxidant capacity in the quality of sperm benefiting from NAC supplementation . There are a few reports on the effects of dietary antioxidant supplementation on sperm DNA integrity. Mean of TAC significantly increased after treatment with NAC compared to before treatment. Significant reduction of serum LH, FSH and, significant increase of serum testosterone levels was observed after treatment with NAC compared to before treatment NAC oral supplementation may improve sperm parameters and oxidative/antioxidant status in infertile males.
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