Critical Commentary

NAC is an ^-acetyl derivative of the naturally occurring amino acid l-cysteine [67]. Due to the antioxidant nature of NAC, it is thought that NAC supplementation may improve redox status in idiopathic male infertility and semen parameters.

Table 22.3 Quality assessment of oral iV-acetyl-cysteine supplementation

References

Study design

Cases

Dosage

Duration

Ages

Main outcome

Paradiso Galatioto et al. [65]

Randomized controlled

Safarinejad and Safarinejad [45]

Double-blind, randomized controlled

468 (116A; 118B; 116c 118D)

600 mg/d + vitamin-minerals4; Placebo®

90-d intervention + 12-m follow-up

Se (200 |ig/d)A; NAC (600 |ig/d)B; Se (200 |ig/d) + NAC (600 |ig/d)c; Placebo13

26-week intervention + 30-W treatment-free

23-36 t Count A(p = 0.009). > = 0.1) f Motile number A(p = 0.752), B(p = 0.976) t Morphology A(p = 0.926). B(p = 0.833) 25-48 t Count A(p = 0.02). B(p = 0.04). c(p = 0.01). D(p = 0.08) f Concentration A(p = 0.03). B(p = 0.04). c(p = 0.01), D(P = 0.1) t Motility A(p = 0.03). B(p = 0.07). c(p = 0.02). D(P = 0.1) t Morphology A(p = 0.03). B(p = 0.03), c(p = 0.03).

(continued)

Table 22.3 (continued)

References

Study design

Cases

Dosage

Duration

Ages

Main outcome

Randomized controlled

NAC 600 mg/dA; Placebo®

3-m intervention

33 I Concentration A(NS) t Motility A(p< 0.05) t Morphology A(NS) t Volume A(p<0.05) I Viscosity A(p<0.001) t TAC A(p<0.001) I TP A(p<0.001) _J,QSIA(p<0.001)

NAC iV-acetyl-cysteine; Se selenium; TAC total antioxidant capacity; TP total peroxide; OSI oxidative stress index; NS not significant; d day; m month

Oxidative stress is thought to cause inflammation and fibrosis leading to the entanglement of spermatozoa. This is thought to prevent proper migration of sperm through to cervical tract fluids and the site of fertilization [68]. NAC's reducing nature is thought to lower these effects of ROS activity in semen and decrease semen viscosity. Human semen samples incubated with NAC (1.0 mg/mL) at room temperature exhibited improved total sperm motility and significantly reduced ROS [69]. Ciftci et al. demonstrated that sperm volume, viscosity, liquefaction time, and motility, as well as oxidative status in the plasma were significantly improved in the NAC-treated group compared to a control group [66]. Another study confirmed the effect of NAC administration to decrease seminal oxidative stress. However, no improvement in sperm motility was seen [70] .

The safe and effective dosage of NAC has yet to be determined. An overdose of NAC has been to cause a minimal allergic reaction. No contraindications other than hypersensitivity have been demonstrated. In a study by Ciftci et al., no side effects were reported in any patients following 3 months of NAC (600 mg/day) treatment [66]. Taken together, the evidence presented suggests that NAC can act as an antioxidant to protect sperm from ROS damage by reducing the production of oxygen radicals. Nevertheless, its efficacy and clinical usefulness remain controversial. To fully understand its mechanism of action, additional studies should be performed on a molecular level. Randomized controlled trials to evaluate the safety and efficacy of NAC-combination therapy are essential to confirm its benefits and standardize therapeutic values.

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