Nutrient Supplementation

Improving Male Fertility Fourfold

Cesar Mora-Esteves, MD; David Shin, MD


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

In This Article

Trace Metals and Folic Acid

Zinc and copper intake are needed to maintain the optimal functioning level of antioxidant enzymes, such as superoxide dismutase. The average daily intake in the United States is 12.3 mg of zinc and 900 mg of copper per person. Studies have shown that seminal plasma zinc concentrations differ significantly between fertile and subfertile men.[89] Zinc may promote male fertility by conferring protection to sperm structure. Zinc deficiency has been associated with abnormal flagella showing hypertrophy and hyperplasia of the fibrous sheath, axonemal disruption, and defects of the inner dynein arms of microtubular doublets, with distorted inner axonemal structure and a poorly formed or absent midpiece.[90] Prospective studies show an improvement of sperm concentration,[91–93] progressive motility, sperm integrity, and pregnancy rates in subfertile males after zinc supplementation. Omu et al showed in a recent randomized, controlled trial that zinc therapy yields various benefits in infertile men.[90] These benefits include reduction in apoptotic markers, enhancement of antioxidant capacity, decreased DNA fragmentation, and increased expression of anti-inflammatory cytokines. Zinc therapy led to improved sperm parameters, although the improvements were not statistically significant. In recent clinical trial by Atig et al, zinc was found to be statistically significantly higher in fertile men compared with both oligoasthenoteratozoospermic and asthenozoospermic patients.[94] This evidence suggests that zinc may be useful in reducing OS and the associated sperm membrane and DNA damage.

Zinc and folic acid are both essential for transfer RNA and DNA synthesis. However, the underlying mechanisms by which they affect spermatogenesis are not known.[95] According to Ebisch et al, a combination of zinc and folic acid led to an increase in sperm concentration, having an endocrine-independent mechanism, as evidenced by an unchanged follicle-stimulating hormone, testosterone, and inhibin.[96] Other studies have failed to demonstrate any significant difference in concentrations of zinc and folic acid between fertile and subfertile males.[97,98] Landau et al reported that daily supplementation with folic acid had no beneficial effect on sperm concentration in normospermic or oligoasthenozoospermic men.[99] Animal in vivo and in vitro studies have shown that zinc deficiency alters the absorption and metabolism of dietary folate.[100,101,102] In a recent double-blind, randomized, controlled trial, folic acid was given at a daily dose of 5 mg, and zinc sulfate was given at a daily dose of 66 mg. Subfertile men demonstrated a significant 74% increase in total normal sperm count and a minor increase of 4% in abnormal spermatozoa.[103] A similar finding was seen in fertile men. These findings were not correlated with pregnancy rates. Further studies are needed to address efficacy and safety of these substances.