Male Factor Fertility & MTHFR

Updated: Nov 19, 2019

MTHFR (Methylentetrahydrofolate Reductase) is a gene that codes for an enzyme responsible for critical biochemical pathways in our bodies. Having a variation in the way this enzyme works (also called a polymorphism or single nucleotide polymorphism, SNP) can influence the health of DNA repair, production and methylation. Methylation is basically the process of adding a methyl group to a molecule, most often “turning on” or “turning off” the function of a cell.


Now, back to 6th grade science - we know that making a human (conception) is heavily dependent on healthy DNA. Remember: egg + sperm carry the DNA coding that will multiply rapidly in those first few days to begin creating a human. Pretty cool stuff.


So, when an enzyme that is critically responsible for DNA function works sub-optimally there can be direct impacts on health. It is estimated that 50% of infertility among couples is due to a male factor. Numerous research articles have proven a direct correlation of male factor infertility from abnormal sperm correlated to males with MTHFR variants. One particular meta-analysis of 26 research studies measuring 5,575 cases showed a significant association of MTHFR C677T variants on infertility risk.


How do I know if I have a MTHFR variant?

You can do a blood test with a medical provider or a full genetic panel (often our recommendation) to better understand what polymorphisms your genes have. Two types of MTHFR variants are titled:

  • C6777T

  • A1298C

Most research has found more deleterious fertility outcomes in males with a C677T variant, especially if they are homozygous. A homozygous variant means they have 2 varied copies of the gene, one copy was inherited from mom and another inherited from dad.


What can we do about this?

  1. The very first recommendation we often make when talking with someone about how to optimize their genetic function with regard to fertility is to avoid folic acid. Folic acid is the synthetic version of folate, used in enriched flour and many nutritional supplements or multivitamins. Research has shown that supplementing with synthetic folic acid, especially if someone has a homozygous variant of MTHFR C677T, has opposite effects on sperm health. Meaning, folic acid supplementation in someone with MTHFR resulted in a worsening of sperm parameters. The better option will always be active folate, either from a supplement or, more preferred, from whole foods.

  2. Our second recommendation is usually for folks to get a more comprehensive genetic report. If there is a variant in MTHFR (and even if not), there is likely other genetic polymorphisms that could be impacting methylation and thus, DNA production.

Best food sources of folate include:

Dark leafy green vegetables, legumes, nuts, seeds, asparagus, eggs, beets, edamame, peas, liver.


Foods that often have folic acid (avoid these):

Any enriched or fortified flour, often found in pastas, cereals, breads, baked goods, cookies, muffins, bread crumbs, even some alternative milks. Check labels. If “folic acid” is listed anywhere, search for an alternative.

A better flour alternative would be whole wheat, whole grain or non-enriched.


Lastly, here is a little more information on why MTHFR function is so important for DNA health and overall body function. MTHFR is the enzyme responsible for activating folate. Folate is an essential nutrient for DNA synthesis, repair and methylation. If methylation of DNA is impaired, there are direct negative impacts on sperm maturation. Nutrients that are essential for DNA methylation include folate, vitamin B6, vitamin B12 and choline. Folate deficiency can also lead to hyperhomocysteinemia (an elevation of homocysteine which causes cardiovascular and neurological inflammation), which is another finding associated with male factor infertility. Folate combines with vitamin B12 to make SAMe. SAMe is basically the key that turns on (or off) dozens of other biochemical pathways in our body. Pathways that regulate sleep, mood, anxiety, depression, detox and overall nutrient function. Healthy levels of vitamin B12 and folate are essential for, not only the health of our bodies, but also the health of our DNA to make future babies.


Remember, 50% of infertility among couples trying to get pregnant comes from a male factor. Working to improve genetic expression can directly improve sperm parameters, especially if the sperm is coming from someone with an impaired MTHFR enzyme.


Resources:

  1. Gong M, Dong W, He T, et al. MTHFR 677C>T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies. PLoS One. 2015;10(3):e0121147. Published 2015 Mar 20. doi:10.1371/journal.pone.0121147

  2. Aarabi M, Christensen KE, Chan D, et al. Testicular MTHFR deficiency may explain sperm DNA hypomethylation associated with high dose folic acid supplementation. Hum Mol Genet. 2018;27(7):1123–1135. doi:10.1093/hmg/ddy021

  3. Aarabi M, San Gabriel MC, Chan D, et al. High-dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Hum Mol Genet. 2015;24(22):6301–6313. doi:10.1093/hmg/ddv338