Nutrient Supplementation

Improving Male Fertility Fourfold

Cesar Mora-Esteves, MD; David Shin, MD


Semin Reprod Med. 2013;31(4):293-300. 

In This Article

Glutathione and N-acetylcysteine

Glutathione (GSH) is the most abundant reducing agent found in the body, protecting lipids, proteins, and nucleic acids against oxidative damage. GSH combines with vitamin E and Se to form glutathione peroxidase. In a placebo-controlled, double-blind, crossover trial, administration of 600 mg for 2 months by intramuscular injection in 20 infertile men significantly increased sperm motion characteristics and specifically improved forward progression.[74] GSH deficiency may render the midpiece unstable, resulting in defective morphology and motility.[75,76] N-acetylcysteine (NAC) is a derivative of the naturally occurring amino acid l-cysteine, and it exhibits antioxidant properties. Since it is a precursor of GSH, NAC works to increase the concentration of this endogenous reducing agent while also directly alleviating OS by scavenging free radicals.[77] In vitro NAC actions in the human seminiferous tubules have been observed to play an important role in germ cell survival.[78] Oeda et al found that incubating semen samples with NAC for 20 minutes significantly decreased ROS levels and led to improved sperm motility.[79] An uncontrolled study found that NAC improved sperm concentration and acrosome reaction, while reducing ROS and oxidation of sperm DNA. However, it did not appear to have an effect on motility and morphology.[80]

Further studies have been conducted to test the efficacy of NAC in combined antioxidant regimen. Safarinejad and Safarinejad[81] reported that NAC with Se has additive beneficial effects on mean sperm concentration and normal morphology percentage in a randomized, controlled trial. By the end of a 26-week treatment period, motility increased significantly in the combined treatment group and in those patients receiving Se alone, compared with placebo. Combination treatment led to significantly better sperm parameters than treatment with only Se.[81]