• Folic Acid/Zinc Supplements Fail to Boost Fertility in Men

    January 23, 2020 04:37 pm News Staff – Family physicians play a crucial role in providing infertility services to both men and women. Although the U.S. Preventive Services Task Force has for years recommended that women who are planning a pregnancy or are capable of becoming pregnant take supplements containing folic acid to prevent neural tube defects, the evidence regarding combined folic acid and zinc supplementation to improve fertility in men is less clear. This is an important consideration given that male factors are responsible for as much as 30%of all instances of infertility in couples.

    The marketing of male fertility supplements containing folic acid and zinc appears to be based in part on limited information that suggests these substances, in combination, may increase semen quality and sperm count. To test that theory, researchers at four sites in the United States conducted a double-blind, placebo-controlled clinical trial involving 2,370 couples planning infertility treatments. Their findings, published in the Jan. 7 issue of JAMA, revealed no significant differences in semen quality or live birth rates among male partners in the supplement group compared with those in the placebo group.

    "Our study is one of the first randomized, placebo-controlled trials to assess whether folic acid and zinc supplements help to improve male fertility," said Enrique Schisterman, Ph.D., senior investigator and chief of the Epidemiology Branch in the Division of Intramural Population Health Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the study's lead author, in a news release. "Our results suggest that these dietary supplements have little to no effect on fertility and may even cause mild gastrointestinal symptoms."

    Tablet with the chemical formula of Folic Acid

    Study Design

    In the trial, 2,370 adult men (mean age 33) were randomized into two study groups. One group received daily supplements containing 5 mg of folic acid and 30 mg of elemental zinc for six months; the other group received an identical-looking placebo.

    Men in both study groups completed in-person study visits, including semen collection, at baseline and at two, four and six months after randomization. Researchers administered questionnaires about adverse events and treatment adherence at each visit to assess relevant symptoms and frequency of skipped doses.

    Women in both study groups were followed for nine months after randomization and up to nine additional months based on pregnancy status. During this period, they completed monthly questionnaires regarding infertility treatments, pregnancy status and pregnancy outcomes and were asked to report any positive urine home pregnancy tests or human chorionic gonadotropin blood tests.

    Story Highlights


    Comparison of live birth rates (based on pregnancies occurring within nine months of randomization) revealed no significant differences between couples in which men took the supplement versus those who took a placebo. In fact, live birth rates were slightly higher in the placebo group (35.1%) than in the folic acid/zinc group (34.1%).

    Regarding semen quality, there were no significant differences between study groups in terms of sperm concentration, motility, morphology, volume and total sperm count after six months.

    There was a statistically significant difference in one measurement, however. Men who took the supplement had a significantly higher sperm DNA fragmentation index than men who took a placebo. This finding was noteworthy given previous research that has suggested a link between DNA fragmentation and decreased clinical pregnancy rates.

    Moreover, men who took folic acid and zinc were more likely to experience minor gastrointestinal adverse effects and skin conditions. Men in the supplement group all had higher rates of abdominal discomfort, nausea, vomiting, erythema and skin rashes than men in the placebo group.

    "Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates," the study authors concluded. "These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility."

    More From AAFP
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    Familydoctor.org: Infertility

    Preconception Care (Position Paper)