Could Folic Acid, Zinc Supplementation Improve Male Infertility?

Although dietary supplements with claims to offer male fertility benefits often contain folic acid and zinc, limited prior evidence has supported their role in improving semen quality.

Now, new findings suggest that folic acid and zinc supplementation among male partners is not likely associated with improved semen quality or couples’ live birth rates compared with placebo.

Researchers arrived at their conclusion after performing the Folic Acid and Zinc Supplementation Trial–a randomized clinical trial of 2370 couples planning infertility treatment. Male partners included in the trial were aged 18 years or older, and female partners were aged 18 to 45 years. Between June 2013 and December 2017, participating couples were enrolled at 4 US reproductive endocrinology and infertility care study centers.

Men were block randomized based on study center and planned infertility treatment to receive either 5 mg folic acid and 30 mg elemental zinc (n = 1185) or placebo (n = 1185) once daily for 6 months. Treatment groups included couples who underwent in vitro fertilization, couples who underwent another treatment at a study site, and couples who underwent other treatment at an outside clinic.

Primary outcomes of the trial included:

• Live births that resulted from pregnancies occurring within 9 months of randomization
• Semen quality parameters at 6 months post-randomization, including sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count.

A total of 1773 (75%) of 2730 men who were randomized attended the final 6-month study visit. The results of the study indicated that data on live birth outcomes, which were available for all couples, were not significantly different between groups (404 [34%] in folic acid and zinc group compared with 416 [35%] in the placebo group).

A total of 1629 (69%) men had semen available for analysis at 6 months post-randomization. The results of the study showed that there were no significant differences between groups for most of the semen quality parameters. However, the researchers noted, a statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation compared with placebo (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group compared with 27.2% in the placebo group).

Also of note, gastrointestinal symptoms, including abdominal discomfort or pain, nausea, and vomiting, were more commonly observed in the folic acid and zinc group compared with the placebo group.

“These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility,” the researchers concluded.

—Christina Vogt

Reference:
Schisterman EF, Sjaarda LA, Clemons T, et al. Effect of folic acid and zinc supplementation in men on semen quality and live birth among couples undergoing infertility treatment: a randomized clinical trial. JAMA. 2020;323(1):35-48. doi:10.1001/jama.2019.18714.