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MTHFR Gene Variants and Your Reproductive Health

Ovaterra

The MTHFR gene drives methylation, a key biochemical process responsible for a wide variety of functions in the body. A significant portion of us have variants of this gene that slows down the folate cycle, a process involved in methylation, with potential impact on reproductive and prenatal health. Let's take a look at how the gene variants affect reproductive processes and baby's development - and what you can do to support you and the baby if you are one of the many women who have a MTHFR gene variant.

     

    What does MTHFR gene do?

    “MTHFR” in MTHFR gene stands for methylenetetrahydrofolate reductase. One of the most studied genes in the field of nutrigenomics, the MTHFR gene is responsible for producing an enzyme called the MTHFR enzyme. This enzyme drives a biochemical cycle called the folate cycle, which turns folic acid into methylfolate – the active form of folate that your body uses.

    The folate cycle – along with the adjacent methionine cycle – drive an important process in the body, methylation. A reaction that happens millions of times each day, methylation is the process of a molecule (called a “methyl donor”) giving one methyl to another molecule to drive many different functions throughout the body.

    In the context of methylation, folate is an important methyl donor. Other methyl donors include B vitamins (B2, B6 and B12) and choline, among others.

     

    Why is methylation important in reproductive health?

    Methylation is key to many biological processes, some of which are particularly relevant for reproductive health. The major ones include:

     

    MTHFR gene variants are common

    Some people have variations of the MTHFR gene that can impact the efficiency of the folate cycle. The most immediate result is the potentially reduced ability of the body to convert folic acid from prenatal vitamins and other dietary supplements into its bioactive form, methylfolate.

    Studies have found that women with one of the most common MTHFR gene variants (C677T) have the efficiency of their MTHFR enzyme reduced by up to 70%. This may be why women with MTHFR gene variants tend to have low folate levels, even when they take prenatal vitamins with folic acid, as well as high homocysteine levels.

    MTHFR gene variants are quite common, and your likelihood of carrying one or two copies of a variant changes depending on your ethnicity. Up to 25% of Hispanic women have two copy of the C677T variant, while Caucasian women have a 10-15% chance and African American women a 6% chance. Additionally, according to some studies, 40-60% of the population may have one copy of this variant. (When you have both alleles affected, your conversion efficiency is likely more impacted, than when you have a single allele affected.)

     

    Reproductive health impact of MTHFR gene variants

    Because the MTHFR gene drives the multi-functional methylation process, variants in this gene that introduce inefficiency can affect multiple aspects of our health, including reproductive and prenatal health.

     

    How do you know you have MTHFR gene variants?

    The MTHFR gene variants, especially when you have mutations on both alleles, can sometimes manifest as noticeable symptoms, including chronic fatigue, cognitive and mental health challenges, hormonal issues and more. Though these symptoms can be difficult to pin down and can be caused by other conditions, they can give you the hint that you may want to consult a doctor about some testing to investigate. 

    Several blood tests can indicate where you stand on the MTHFR gene and its impact: 

    • Folate levels: People with the MTHFR gene variants tend to have low blood folate levels, because of the inefficiency these variants introduce into the folate production cycle. This blood test is also a good way to periodically monitor your health if you know you have a MTHFR gene variant.
    • Homocysteine levels: The inefficiency in the folate cycle affects the adjoining methionine cycle. Because of its impact on the methionine cycle, women with the MTHFR gene variants often have higher homocysteine levels. High homocysteine levels can also be a sign of low folate, Vitamin B6 or Vitamin B12, in the absence of any MTHFR variants. Other conditions can cause high homocysteine levels, too.
    • Genetic testing for the MTHFR gene: The most direct way to know if you have a MTHFR gene variation is the genetic test. Although a MTHFR gene testing is relatively routine in functional medicine, many OBGYN doctors don’t recommend MTHFR genetic testing, because the evidence is mixed on whether having this information is clinically helpful, particularly in the context of the baby’s brain development.

     

    How to support your preconception and prenatal periods

    Many women with a MTHFR gene variant wonder if they should be taking folate, rather than folic acid, during their preconception and prenatal periods, since the variant may affect how much of the folic acid can be converted into folate, to be used to support the baby’s brain development.

    Most studies on baby’s brain health and folate have been done on folic acid. Because of this, the official recommendations are still exclusively on folic acid, regardless of the MTHFR gene status.

    There are several things you can do to support your – and your baby’s – health when you have one of the MTHFR gene variants:

     

    1. Check your prenatal vitamins

    As mentioned, women with MTHFR gene variants can have a difficult time using folic acid in prenatal vitamins. To make sure you get enough folate to support the baby’s healthy brain development and help prevent neural tube defects, check your prenatal vitamins. You’d want to see methylfolate. An active, ready-to-use form of folate, methylfolate doesn’t need to go through the methylation process to be useful to the body.

     

    2. Make sure you get enough B vitamins

    We saw earlier that many B vitamins are methyl donors in the methylation process. Make sure your diet – and your prenatal vitamins – contain a good amount of these B vitamins: Riboflavin (B2), Vitamin B6 and methylcobalamin (B12), in addition to folate (which is also a B vitamin, B9, to be specific).

    Look for the B vitamins in these foods: 

    • B2: Fortified cereals, oats, milk and yogurt, beef, almonds
    • B6: Chickpeas, tuna, salmon, chicken breast, fortified cereals, banana
    • B12: Beef liver, clams, tuna, salmon, milk and yogurt, fortified cereals
    • Folate (B9): Beef liver, spinach, fortified cereals, asparagus, Brussels sprouts and other dark green, leafy vegetables

     

    3. Get plenty of choline

    Choline is another methyl donor in the methionine cycle of the methylation process. To help the methionine cycle remove homocysteine, make sure you have plenty of choline in your diet - at least 450 mg during pregnancy and 550 mg when nursing.

    Choline is also a crucial nutrient during the prenatal period. Just like folate, it supports the baby’s healthy brain development and helps prevent neural tube defects. An important component of a neurotransmitter called acetylcholine, choline has been suggested as key for the baby’s cognitive development even after birth.

     

    4. Avoid alcohol, smoking and other things that also slow methylation

    Alcohol and smoking are known to slow down methylation. Not something you want to add to the already burdened methylation efficiency, potentially limited by MTHFR gene variants.

     

    5. Take steps to stay emotionally healthy

    Studies have found that excessive stress may exacerbate high homocysteine levels from MTHFR gene mutations. The mom’s stress levels during pregnancy have also been linked to several aspects of the baby’s health via the methylation process. For instance, a study suggested that prenatal stress levels of the mom may affect how the baby themselves responds to stress.

    It's not possible to completely eliminate stress, of course, but take steps to manage it and stay emotionally healthy, if you have MTHFR gene variants.

     

    6. Talk to your doctor about your MTHFR variant

    Discuss with your doctor the implications of your particular MTHFR gene variant, and what you can do to manage its impact on your reproductive - and overall - health. Some doctors are more versed in the science of MTHFR than others, so you may need to ask around.

     

    The takeaway on MTHFR gene and reproductive health

    1. Up to 40-60% of the US population carry MTHFR gene variants that can slow down the methylation process, which impacts usability of key prenatal nutrients like folate and Vitamin B12 for the body.
    2. Through the methylation process, MTHFR gene variants can also impact DNA functions, hormone balance and many other aspects of reproductive health.
    3. If you have a MTHFR gene variant that affects methylation, support your systemic and reproductive health by focusing on the B vitamins as well as choline, avoiding methylation-unfriendly activities and taking steps to manage your stress.

    Please reach out if you have any questions about MTHFR and your prenatal health. We are with you.

     

     

     

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