Not all Folate is Created Equal- MTHFR Gene Mutation and Your Fertility

gene mutation model

By Dr. Chris D. Meletis

Your Genetics Can Impact Your Fertility

Fertility is a reflection of your nutritional status, your overall level of health, and your genetics. In turn, genetic risk factors can be controlled to some extent by diet and lifestyle. A clear example of the relationship between genetics and fertility is how your body metabolizes Vitamin B9, the vitamin commonly referred to as folic acid or folate. This vitamin is famous 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 folic acid. But, did you know that not everyone can utilize the synthetic folic acid that is found in vitamin supplements and fortified foods? It is estimated that between 25 and 60 percent of people have a genetic mutation that prevents them from converting folic acid, and even some of the folate that naturally occurs in foods, into the active form of folate. Given the important role that folate plays in fertility and pregnancy outcomes, if you are trying to get pregnant it may be beneficial to do some genetic testing to determine if you have the genetic mutation that prevents your body from utilizing the folic acid that you take in through your diet.

Overview of B9 and its Active Form

Vitamin B9 is typically referred to as folic acid or folate, the synthetic form found in fortified foods and many vitamin supplements or the form that naturally occurs in foods, respectively. Yet, to be utilized effectively in the body, 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). It is at this time, when MTHF is created, that “active B9” can enter cells and cross over the blood brain barrier to help nourish our tissues and brains optimally. Successful conversion from folic acid or folate to MTHF is dependent upon a converting enzyme known as MTHFR. Unfortunately, gene mutations to this enzyme are quite common, impacting between 25 and 60 percent of the population. When this converting enzyme does not function due to a genetic mutation, the conversion of folic acid and folate to the active form of vitamin B9 is inhibited, which leads to increased risk for multiple diseases, worsens certain aspects of PCOS, and negatively impacts pregnancy outcomes.

PCOS and Methylfolate

When it comes to classical ovarian challenges, the most common specific condition is polycystic ovary syndrome (PCOS), which contributes to both hormonal and metabolic imbalances, including blood sugar dysregulation. Women with PCOS often experience chronic anovulation (when ovaries do not release an oocyte during a menstrual cycle), irregular periods (oligomenorrhea), hyperandrogenism (too much testosterone) and insulin-resistance. Given this array of fertility-related symptoms, it is not surprising that PCOS is a leading cause of infertility. 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.

Frequent Miscarriages and MTHFR

The causes of miscarriage are often difficult to identify with absolute certainty. However, researchers have discovered an association between high homocysteine levels and recurrent miscarriage, which suggests that the MTHFR mutation may play a role in pregnancy loss. Here’s the connection: 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.

Take Home Message

If you are trying to conceive or if you are already pregnant, don’t underestimate the importance of naturally occurring folate for your fertility and pregnancy wellness. Mom was right – eat your veggies! All of this talk about the potential dangers of synthetic folic acid for people with MTHFR mutations shouldn't deter you from eating as much naturally occurring folate as you can. Foods high in folate, such as kale and spinach, and nuts and legumes, contain lots of vitamins and minerals that are important for your health, and the naturally occurring folate can help mitigate problems associated with getting too much synthetic folic acid. Also, consider getting your genes tested (this can be done through your health care provider or via an at-home test) to determine if you have the MTHFR genetic mutation. This will empower you with the information you need 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.

Dr. Chris Meletis

Dr. Chris MeletisDr. Chris Meletis is an educator, international author and lecturer. His personal mission is “Changing World’s Health One Person at a Time.” Dr Meletis has authored 18 books and over 200 national scientific articles in journals including Natural Health, Alternative and Complementary Therapies, Townsend Letter for Doctors and Patients, Life Extension, Natural Pharmacy, and PubMed.gov articles.

Dr. Meletis served as Dean of Naturopathic Medicine and Chief Medical Officer for 7 years for the National College of Naturopathic Medicine (now the National University of Natural Medicine). He was awarded the 2003 Physician of the Year by the American Association of Naturopathic Physician of the Year by the American Association of Naturopathic Physicians. He has a deep passion for helping the underprivileged and spearheaded the creation of 16 free natural medicine healthcare clinics in the Portland metropolitan area of Oregon.


  • 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.

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