However, no changes were observed in GR activity in the IG compared to the non-supplemented group. Overall, subjects tolerated NAC supplementation well and no moderate or severe adverse reactions to NAC were observed during the supplementation, exercise, or post-supplementation periods (Table 3). Investigators administered supplementation 1 h before the test 21,22,24,29, before lunch plus dinner 25,26,27 or plus test , during the test 31,32,33,34,36, in the morning, 1–2 h prior to test , and during main meal 23,29,35. Furthermore, five studies 31,32,33,34,36 used two consecutive doses, 125 mg/kg/h during 15 min + 25 mg/kg/h, of intravenous solution. Doses of NAC supplementation varied from 20 mg/kg to 140 mg/kg , with 1200 mg/day as the most common oral dose used 25,26,30. " indicates lack of information or uncertainty about the potential for bias; the higher the score, the greater the risk of bias.
Exercise-induced increases in the intraerythrocytic concentration of oxidised haemoglobin have been described . NAC directly increases the concentration of thiols, and therefore, seems to modulate the EPO response, while at the same time attenuating OS. The increase in the TNF-α-supplemented group could be related to muscle damage altering a transition phase between intracellular TNF-α production and release . NAC also increases the concentration of protein thiols by converting GSSH to GSH .
The patients consisted of 50 infertile men with asthenoteratozoospermia who received NAC (600 mg/d) orally for 3 months, after which they were compared with pre-treatment status. NAC plus Gly supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, and physical function . Secondly, there is a large heterogeneity of the studies in terms of outcomes, supplementation dose, and duration of intervention, which does not allow us to perform a meta-analysis. However, not all studies 21,22,24,25,26,28,30,32,34 have demonstrated performance benefits with NAC supplementation compared to CG. For example, the effects of NAC supplementation on cytokine production were controversial in the trials included in this systematic review 23,24,30,35,36.
The blinding of subjects and researchers was reported in four studies(Reference Hashim, Anwar and El-Fatah22,Reference Nasr9,Reference Chandil, Pande and Sen27,Reference Gayatri, Kumar and Kumar28) . Overall, five studies were defined as high quality(Reference Hassan, Alalfy and Hassan18,Reference Badawy, El Nashar and El Totongy20,Reference El Sharkwy and Abd El Aziz24,Reference Kose and Naziroglu26,Reference Ghomian, Khadem and Moeindarbari5) . The duration of the intervention varied from 5 d to 24 weeks among the studies. Overall, eighteen articles met the inclusion criteria and enrolled in the meta-analysis. After removing duplicate papers and screening the articles carefully by the title and abstract, thirty-five papers were included. Publication bias was determined by visual inspection of the funnel plot.
When NAC is ingested and absorbed, it undergoes deacetylation, resulting in the release of cysteine, which is then free to serve as a precursor in glutathione synthesis. Conditions such as fatty liver disease, hepatitis, and cirrhosis are often characterized by decreased glutathione levels. The liver is exposed to high levels of oxidative stress due to its metabolic functions. 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.
Naimi et al. reported that NAC alone had no significant beneficial effect on the number of ovarian follicles and the levels of hormones in adult rats. Sensitivity analysis revealed that the overall effect size did not depend on one individual study. Subgroup analysis was not performed due to the low number of studies. 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.
NAC effects on GSH rely on the presence of the free sulfyhydryl group as a ready source of reducing equivalents to quench radical species . Both exogenous and endogenous ROS can induce sperm DNA damage in vitro, confirming that ROS may play a role in the etiology of sperm DNA damage in infertile men 30, 31 . Relationship between sperm DNA fragmentation and sperm motility or abnormality.
Comparison of age, duration of infertility, weight, height, and BMI before and after treatment with NAC. Five hundred sperm per slide were evaluated under a fluorescence microscope (BX51, Olympus, Japan). Five hundred sperms per slide were assessed under a fluorescence microscope (BX51, Olympus, Japan) at 100x magnification. Seminal total antioxidant capacity (TAC) was measured using a commercially available kit (Zell Bio GmbH, Wurttemberg, Germany).

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