If you’ve “stepped foot” inside the health world recently, you’ve probably heard some buzz about MTHFR. But what is it, and how does it impact fertility? Could it be contributing to miscarriage? What can we do about it? Should you be taking a special prenatal? Read on to see what the potential risks are and how to mitigate them.


Let’s start with the some basics. MTHFR is an abbreviation for an enzyme produced in the human body. The full term is methylenetetrahydrofolate reductase. The -ase at the end lets you know it’s an enzyme.


This enzyme has a big role in the body of breaking down the amino acid homocysteine in the blood. When the blood levels of homocysteine get too high, things are ripe from some health complications such as cardiovascular issues, stroke, Alzheimer’s, osteoporosis, and more. This enzyme also helps repair DNA and converts Vitamin B9 (folate or folic acid) into an active form that can be used in the body.


So this enzyme is pretty important. And we have MTHFR genes which influence how efficient the enzymes we produce are.


The real impact comes when the MTHFR gene lowers the ability of the MTHFR enzyme to do it’s thing.


Genetic Variations

Genetic mutations or variations occur often and on a variety of genes. These are a part of us the moment we are conceived in our mother’s womb, written into our DNA. These are inherited, just like the genes for your eye color or being a carrier for cystic fibrosis for example.


Genetic variations don’t always mean doom or gloom though. Some variations seem to have no detectable impact on our health and are just a benign part of the variety in human genetic code. Others can impact health, but that can be mitigated well by certain nutritional and lifestyle factors (which we’ll discuss below in regards to MTHFR). These variations are also referred to as SNPs (“snips”) because they are a single nucleotide polymorphism. Or simply, a change to a single nucleotide on the gene, with a nucleotide being a building block of our DNA.


There are many MTHFR variations, but there are two that are the most well known and studied: C677T and A1298C.


In DNA, there are four bases: Adenine, Thymine, Guanine, and Cytosine. They are represented by the letters A, T, G, and C. The location of the gene in the genetic code is listed as a number so C677T describes the bases and location of this gene.


For a “normal” MTHFR gene, the sequence should be C677C with two cytosines. The C677T variation means that a thymine has replaced the cytosine instead.


We inherit one copy of our DNA from our mother and one copy from our father, so it’s possible to have two types of MTHFR SNPs. You can either have heterozygous variation which means you got one mutated copy from only one parent. OR you can have two mutated copies, which means BOTH of your parents also carried the variation and gave it to you, when egg met sperm in the womb.


Homozygous variations on the 677 location actually would be T677T so thymine is in both spots now, but it’s typically referred to as just Homozygous C677T. Heterozygous C677T is less severe in it’s impact on the MTHFR enzyme in the body.


It’s also possible to be compound heterozygous, meaning you have both C677T+ A1298C. Research shows this also impacts homocysteine levels making them higher.


Order of Severity

The potential negative impact on your health is determined by which type of variation you have.


No variation shows best homocysteine levels: C677C and A1298A.

Being heterozygous A1298C shows minor changes.

Heterozygous C677T can impact health and has been shows to reduce folate metabolism by up to 35%.

Homozygous A1298C (your DNA sequence would be C1298C) is more serious and seems to have a greater impact

Homozygous C677T (your DNA sequence would be T677T) is also more serious and seems to have a greater impact

Compound heterozygous A1298C and C677T also has been shown to have adverse impacts


Which one you have can dictate what amount of folate would be best for you to consume through diet and supplementation daily as well as how vigilant you may need to be about nutrition and lifestyle to maintain the same health as someone who does not have these variations.


Signs and Symptoms of MTHFR Gene Mutation

Because of the role that MTHFR has in the body on many functions, there can be immediate and more “downstream effects”. Here are some signs and symptoms (although not comprehensive) that might be happening for you:

    • Folate deficiency on blood work
    • Elevated Homocysteine levels on blood work
    • Anemia
    • Cracked Lips
    • Premature Graying Hair
    • Anxiety
    • Poor Memory
    • Fatigue
    • Blood Clots
    • Depression
    • Neural tube defects in past pregnancies (spina bifida, anencephaly, etc.)
    • Infertility
    • Miscarriage


Impact on Fertility and Miscarriage

So can MTHFR gene mutations impact fertility and miscarriage? Let’s break down some ways they can possibly become an issue.


Studies are somewhat mixed on whether having the gene mutation increase risks of miscarriage or other risks, with some saying it does and others saying it’s not clear. But we have to remember that some mutations are “worse” than others, and some people with the mutation may never have negative health impacts because their nutrition and lifestyle already mitigates those. Thus research may show mixed results.


Remember, most research on pregnant women and their babies is observational and not a randomized control trial (the gold standard in research) since that is largely unethical in pregnancy for most interventions being studied.


1. Impairing conversion of folic acid from diet and supplements into active folate.


The MTHFR enzymes plays a role in the absorption and use of Vitamin B9 or folate. Folic acid is the synthetic version of the natural folate. Folic acid must first be converted in our body into an active folate form before it can be utilized in metabolic processes. Since this process relies on the MTHFR enzyme, if the enzyme can’t do it, we can end up with lots of essentially useless folic acid in the body that’s not doing what we need it to do.


When an egg has been fertilized by sperm, the cells begin to rapidly divide and form your embryo baby even before it travels down the fallopian tube and nestles into the uterine wall. This rapid division relies on folate. As baby continues to grow and their neural tube is formed, this also relies on lots of folate to form properly.


So if there is a deficiency, such as lack of folic acid and folate from diet it can cause problems in this development. A deficiency can also occur for someone who gets adequate folic acid, but their body can’t process it into the active folate form to be utilized in the body (ie those with certain MTHFR variations).


2. Causing elevated homocysteine levels in the blood.


The MTHFR enzyme also uses this active folate to help break down homocysteine, which is an amino acid that is created in the body during some switcharoos in our protein synthesizing.


Our body takes methionine (an amino acid) and turns it into cysteine (another amino acid) and in the middle of that homocysteine is made as an intermediary step.


This process relies on B vitamins including folate. When that conversion to cysteine isn’t happening, we end up with too much homocysteine in the blood. This is what has been linked to recurrent miscarriage. This is thought to be due in part to the negative impact high homocysteine in pregnancy has on the functions of the placenta. The placenta is the life giving organ that keeps your baby alive and nourished, so disrupting that can lead to pregnancy loss and other complications.


High homocysteine levels are also linked to uterine contractions. High levels of homocysteine contribute to hypercoagulability which means that blood clots more easily than it should. During pregnancy, when blood clots at the wrong place, wrong time, it can essentially leave your baby without a source of nutrients and oxygen, which can be fatal. This can happen earlier or later in pregnancy, which will influence if your baby is lost to miscarriage or stillbirth, due to the definition of when these occur in pregnancy.


It’s not just avoiding miscarriage or stillbirth either–women with elevated homocysteine levels can be at an increased risk for other pregnancy complications such as preeclampsia and preterm labor and delivery.


Men, MTHFR and Fertility

Men aren’t off the hook though when it comes to their role in fertility. Men with MTHFR gene variations saw marked increases in sperm count, just by supplementing with folinic acid for 3 months. And a study found that men being evaluated for infertility were TWICE as likely to have homozygous MTHFR variation than those in the control group who were not seeking fertility evaluation.


Testing for MTHFR

In the context of fertility or dealing with miscarriage, there is usually one approach that is beneficial. In that regard, testing might not be essential and if money is a concern, testing can be foregone and the money spent elsewhere.


However, knowing your MTHFR status can be interesting and can help with the emotional aspect of finding a “why” in grieving a miscarriage or understanding health challenges. Testing your partner as well can also help guide supplementation and nutritional therapy if they have had abnormal semen analyses in the past.


Side not: Testing for MTHFR variations in your children may also help guide you in making health decisions for them as well as guide your priorities in nutritionally supporting them in childhood, but it’s not completely necessary and depends on your family’s priorities.


You can test for homocysteine levels directly, which can indicate a MTHFR SNP if they are high. You can also have the gene tested directly by asking your doctor or using a genetic test like MaxGen Labs Functional Panel, StrateGene, or other MTHFR specific testing available online.


Testing MTHFR can also be helpful in understanding other health risks beyond fertility or even understanding if you could pass it onto your child and how that could affect their health. If you just like info and don’t mind paying the money, then definitely feel free to get it tested! In the meantime though, I still recommend following a plan as if you have MTHFR.


The bottom line is you can test it if you want, but if we’re dealing with fertility challenges and/or miscarriage, let’s live like you do, and make some diet and lifestyle changes to limit the negative impact.


What to Do? 

Whether you tested for MTHFR or were just trying to be proactive, the plan is very similar:


  1. Avoid folic acid. Since this is the synthetic version of folate, it’s found in many prenatals, multivitamins, and in fortified foods. It was discovered in the 1900s that there was a link between folic acid and neural tube defects, so the US government began adding folic acid to things such as fortified breads, flours, cornmeal, rice, pasta, and some other grain products. Today, not all of these foods contain folic acid but you can check the labels to make sure they’re not fortified.
  2. Consume whole foods that are good sources of folate such as leafy greens, avocado, some beans, asparagus, beets, and even citrus fruit.
  3. Take active forms of folate in supplements, especially in a prenatal when preparing to conceive and pregnant. The active forms include L-methylfolate, folinic acid, metafolin, and 5-MTHF.
  4. Supplement appropriately with Vitamin B12, B6 and Folate to avoid deficiency in any one and achieve optimal levels.
  5. Be mindful that certain medications deplete folate in the body, like birth control. If you’re planning a pregnancy and suspect or know you have MTHFR mutations, be sure to use alternate forms of birth control or spend adequate time restoring any depletions after coming off birth control before trying to conceive.
  6. Focus on improving gut health as gut health determines absorption of vitamins and nutrients from diet and supplementation.
  7. Find ways to sweat on a regular basis such as exercise, sauna, epsom salt bath, etc. This encourages the natural detoxification processes of our body. If you are already pregnant, follow pregnancy safe guidelines for heat tolerance.
  8. Focus on Omega-3s in the diet to promote less risk of blood clotting. Be careful of taking Omega-3s if your doctor has you on blood thinning medications already.


Whether MTHFR gene mutations are definitively linked to miscarriage or not, the above list is a healthy part of any preconception, fertility, and pregnancy plan so you can’t go wrong making these conscious choices a part of your everyday living.


A Note: There are other genetic mutations that can impact methylation and folate pathways and thus impact the risk of miscarriage and/or fertility challenges. MTHFR may one be one piece of your unique genetic code that when not nurtured appropriately with nutrition and lifestyle, can manifest in problematic ways for our health.


Disclaimer: Always consult your doctor before making any nutrition, lifestyle, and supplement changes. This post is for educational purposes only and is not medical advice. See full website disclaimer here.