Folate vs. Folic Acid for Male Fertility

By Margaret Eich, MS, RDN

Many women thinking of getting pregnant have heard of folic acid or folate, as we know that adequate amounts help prevent neural tube defects like spina bifida when taken in early pregnancy. Folate is vital for DNA synthesis and for DNA methylation. Folic acid generally refers to a synthetic form of folate that is found in many prenatal vitamins and supplements and fortified foods. Folate refers to the natural form found in food. Some supplements include folate instead of or in addition to folic acid. 

While the impact of folate on pregnancy in women gets a lot of press, the impact of folate on male fertility doesn’t get much attention. Ensuring adequate folate intake in men may have a beneficial impact on sperm quality and pregnancy. Folate is thought to be vital for sperm production due to its role in DNA synthesis and methylation. For example, in one study, men with the highest folate intake from both food and supplements had lower frequencies of aneuploidy (DNA abnormalities) in their sperm compared to men with lower folate intake.

An additional factor that may impact folate status in men is MTHFR polymorphisms. A MTHFR polymorphism is a change to the methylene tetrahydrofolate reductase enzyme rendering it less effective at producing the active form of folate called 5-methyltetrahydrofolate (5-MTHF). In men with MTHFR polymorphisms, supplying 5-MTHF directly may be more effective for improving sperm parameters and pregnancy rates based on some interesting new case series.

The impact of 5-MTHF is demonstrated in a case series of 30 couples each with a 4-year history of fertility issues with at least one partner in the couple having a MTHFR polymorphism. Most of the women were treated with high dose folic acid without success. The couples were then treated for 4 months with 600 mcg 5-MTHF, and 13 couples were able to conceive spontaneously without IUI or IVF. 

In another case report, a couple had a history of 6 failed IVF cycles. The woman was found to have an MTHFR polymorphism, and the couple underwent egg donation and had a successful pregnancy and birth. In trying to conceive a 2nd child, she started a series of failed donor egg cycles. She was then started on 5-MTHF (400 mcg) and did another donor egg cycle, which ended in miscarriage at 8.5 weeks. Her husband had normal sperm parameters, but tested positive for 2 copies of the MTHFR polymorphism and was started on 400 mcg 5-MTHF. The couple conceived spontaneously 8 weeks later and gave birth to a baby girl at 38 weeks. The authors conclude that his really underscores the importance of methylation in egg development and sperm production, and that when either the male or female has a MTHFR polymorphism, 5-MTHF if required as high dose folic acid will not allow the embryo to develop properly.

It is often the case that men don’t know if they have a MTHFR polymorphism, and if testing is unavailable, it makes sense to take a 5-MTHF supplement to ensure adequate folate in the active form is available for DNA synthesis and methylation to promote conception and a healthy pregnancy.  Learn more about how nutrition and supplements can support male fertility by meeting with our Nutrition Team and book your consult today!

References:

  • Young SS, et al. The association of folate, zinc, and antioxidant intake with sperm aneuploidy in healthy non-smoking men. Human Reproduction. 2008;23(5): 1014-1022. 
  • Servy EJ, et al. MTHFR isoform carriers. 5-MTHF (5-methyltetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genetic. 2018;35(8): 1431-1435.
  • Jacquesson-Fournols L, et al. A paternal effect of MTHFR SNPs on gametes and embryos should not be overlook: case reports. J Assist Reprod Genetic. 2019;36(7):1351-1353.

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