What is the Role of Folate and Folic Acid in Pregnancy?
Vitamin B9, also known as folic acid and folate, plays a key role in fertility, pregnancy and the health of the baby.has been well-studied for its ability to help prevent neural tube defects, which is why all women of childbearing age are encouraged to ensure that they consume a sufficient amount of Vitamin B9 whether they are TTC or not. Genetics can determine how well your body can metabolize Vitamin B9.
It is estimated that between 25 and 60 percent of the population have a variation in one of their MTHFR genes that negatively impacts their ability to convert folic acid (the synthetic version of B9), and even some of the folate that naturally occurs in foods, into the active form of folate. If you are trying to get pregnant, consider getting your genes tested to determine if you have the MTHFR genetic variation.
What’s the difference between Folic Acid and Folate?
MTHFR Converts Synthetic to Bioactive Vitamin B9
Vitamin B9 is found as either the synthetic form (folic acid) that appears in many vitamin supplements and fortified foods or the naturally occurring form found in foods (folate). Both the synthetic and most of the food-derived folate we consume must be converted via a natural enzyme pathway in our body to the final bioactive form called L-methylfolate (also known as 5-MTHF). Once MTHF is created, this active form of B9 can enter cells and cross over the blood brain barrier to help nourish our tissues and brains. Successful conversion from folic acid or folate to MTHF is dependent upon a converting enzyme known as MTHFR.
Unfortunately, gene variations to this enzyme are quite common, impacting between 25 to 60 percent of the population. When this converting enzyme does not function optimally due to a genetic mutation, the conversion of folic acid and folate to the active form of vitamin B9 is inhibited. Inadequate levels of Vitamin B9 can lead to increased risk not only for the neural tube birth defect described above, but also for miscarriage and infertility.
MTHFR is the cause of elevated homocysteine levels tied to frequent miscarriges
Homocysteine is a naturally occurring amino acid produced when proteins are broken down in the body. It is not harmful at low levels, but when present in high concentrations it can lead to a condition called hypercoagulability, in which your blood tends to clot more easily than it should. Women with elevated homocysteine levels are believed to be at higher risk for miscarriage, preeclampsia and even preterm labor – most likely due to the increased clotting caused by the elevated homocysteine levels.
Why do homocysteine levels become elevated? Methylfolate, the active form of folic acid, plays a role in converting homocysteine into methionine (a harmless amino acid), so if methylfolate is lacking due to the MTHFR mutation and subsequent inability to convert folic acid to methylfolate, homocysteine can build up to dangerous levels.
Researchers have discovered an association between high homocysteine levels and recurrent miscarriage, which suggests that the MTHFR genetic variation may play a role in pregnancy loss.
The link between MTHFR and PCOS
The most common specific condition that causes infertility in women is polycystic ovary syndrome (PCOS). Women with PCOS are prone to hormonal and metabolic imbalances, including blood sugar dysregulation, also known as insulin resistance. These metabolic issues can cause chronic anovulation (when ovaries do not release an oocyte during a menstrual cycle), oligomenorrhea (irregular periods), hyperandrogenism (too much testosterone) and insulin-resistance. Given this wide range of fertility-related symptoms, it is not surprising that PCOS is a leading cause of infertility.
Many studies are being done to understand the underlying causes of PCOS. A 2014 study found a connection between PCOS and MTHFR gene mutations, with the researchers concluding that a specific MTHFR mutation increases susceptibility to PCOS. The common thread between MTHFR and PCOS once again has to do with homocysteine levels. In general, the most common cause of elevated homocysteine levels (hyperhomocysteinemia) is reduced activity of MTHFR, which results in reduced production of methylfolate. Women with PCOS typically test positive for higher homocysteine levels than other healthier women. Many more studies are currently underway to determine the exact relationship between MTHFR and PCOS.
Methylfolate is the key to conception, pregnancy and a healthy baby
If you are trying to conceive or if you are already pregnant, don’t underestimate the importance of folate for your fertility and pregnancy wellness. Some dark green leafy vegetables such as kale and spinach, and some fermented foods such as kefir and miso, actually provide natural methylfolate, the active form of folate that does not require the converting enzyme to be utilized by your cells. And, consider getting your genes tested. Knowledge will give you the power to make informed choices about your unique nutritional needs, including whether or not you should choose prenatal and fertility supplements that contain the active, methylfolate form of folic acid.
By Dr. Chris D. Meletis
Want to Know More?
- Infertiity 101: What You Need to Know First
- Male Infertility
- Female Infertility
- Infertility Medications
- Effects of myo-inositol, gymnemic acid, and L-methylfolate in polycystic ovary syndrome patients. Gynecol Endocrinol. 2017 Dec 21:1-7.
- Maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of recurrent pregnancy loss. J Dev Orig Health Dis. 2012 Oct;3(5):327-32.
- Association of methylenetetrahydrofolate reductase gene C677T polymorphism with polycystic ovary syndrome risk: a systematic review and meta-analysis update. Eur J Obstet Gynecol Reprod Biol. 2014 Jan;172:56-61.
- MTHFR C6777T polymorphism is associated with hyperlipidemia in women with polycystic ovary syndrome. J Hum Reprod Sci. 2012 Jan-Apr; 591):52-56.
- Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: evidence from 25 case-control studies. PLoS One 2012:7(10):e41689.