Short answer: In the two largest US trials, no. FAZST gave 2,370 men folic acid and zinc or placebo for 6 months: live birth was 34% vs 35%, sperm counts did not improve, and sperm DNA damage was slightly higher on the supplement. MOXI gave men with abnormal semen an antioxidant mix with vitamins C and E, selenium, L-carnitine, zinc, folic acid and lycopene: semen and DNA results did not improve and live birth was 15% vs 24%.
The Folic Acid and Zinc Supplementation Trial was led by researchers at the NIH child health institute and run at four US fertility centers. Men in 2,370 couples planning infertility treatment were randomly given 5 mg of folic acid and 30 mg of zinc a day, or placebo, for 6 months. The authors chose these two because they are common in supplements marketed for male fertility.
| Outcome | Folic acid + zinc | Placebo |
|---|---|---|
| Live birth | 404 (34%) | 416 (35%) |
| Sperm count, motility, shape, volume | No significant difference | — |
| Sperm DNA fragmentation | 29.7% | 27.2% (difference 2.4 points, statistically significant) |
| Abdominal discomfort or pain | 6% | 3% |
| Nausea | 4% | 2% |
The authors concluded the results do not support folic acid and zinc for male partners as a fertility treatment. The folic acid dose used, 5 mg, is five times the 1,000 mcg adult upper limit the NIH Office of Dietary Supplements lists for folic acid from supplements and fortified foods.
The Males, Antioxidants, and Infertility trial enrolled 174 men with low sperm count, low motility, abnormal shape or high DNA fragmentation, whose partners were ovulating and had open tubes. Men took an antioxidant blend (500 mg vitamin C, 400 mg vitamin E, 0.20 mg selenium, 1,000 mg L-carnitine, 20 mg zinc, 1,000 mcg folic acid and 10 mg lycopene a day) or placebo for 3 to 6 months. Couples tried naturally for 3 months, then with clomiphene and intrauterine insemination.
After 3 months there was no significant difference in sperm shape, motility or DNA fragmentation, including in the subgroups who started with each specific problem. Cumulative live birth at 6 months was 15% on antioxidants and 24% on placebo. The authors say the study was limited by its size, and conclude antioxidants do not improve semen or DNA integrity in these men.
Both trials were placebo-controlled and run with NIH support. They did not test every ingredient sold for fertility; CoQ10 on its own, for example, was not studied. They also did not test men with a known deficiency, where correcting it is a different question.
Men on testosterone therapy face a separate issue: testosterone from outside the body can lower sperm production, which no supplement in these trials addresses. See fertility on TRT and the hCG on TRT article, and talk to the prescriber or a fertility specialist before a plan.
Both trials treated men for 3 to 6 months before measuring results. Dose Track can keep supplement start dates, any medicine changes and semen test dates in one log to share with the clinic.
Read more on Dose Track: Fertility on TRT · Zinc · Folate · Selenium · Placebo