What Does It Mean to Have an MTHFR Deficiency?

As epigenetics shows us, your genes are not your destiny. However, your genes are one of the primary determinants of your health and risk factors for certain conditions. One particular gene that’s been getting a lot of press recently is the gene that codes for methylenetetrahydrofolate reductase, commonly known as MTHFR. Curiosity around MTHFR has risen steadily as at-home genetic testing has boomed, but as with most things health-related, there are a lot of misconceptions about it. We’re here to clear them up. Read on to learn about MTHFR deficiency risks, what it actually means to have a “mutation” on this gene and common MTHFR gene mutation symptoms, the best MTHFR supplements, and more. 

You can also listen to Adrienne read this guide on The WellBe Podcast.

What Is an MTHFR Gene Mutation?

First things first, let’s clear something up: MTHFR isn’t actually a gene. It’s an enzyme that breaks down the amino acid homocysteine and converts folate into a form that’s usable for the human body. When people talk about the MTHFR gene, they’re talking about the specific gene that gives your body instructions on how to produce MTHFR. For the sake of simplicity here, we’ll be calling this gene the MTHFR gene (even though as we just explained, MTHFR itself is not a gene). 

As with every gene out there, different MTHFR genes can have different DNA codes. When part of the DNA sequence of a MTHFR gene varies from what’s expected, it’s called a variant, or a mutation. If you’ll remember from high school biology, each gene is actually a pair of two alleles, one inherited from each parent. So you could have an MTHFR gene with a mutation from just one parent (called heterozygous), from both parents (called homozygous), or from neither. Simple enough, right?

Bear with us, because it does get a bit more complicated: there are actually two locations on the MTHFR gene known to have variants. This means that it’s possible for a person to have mutations in both locations, one location, or neither, and to be heterozygous or homozygous in either. The two different mutations in question are:

• C677T: This is a mutation at position 677 on the MTHFR gene. Approximately 25% of the global population have this mutation, with those of Hispanic descent being most likely to carry it. 
• A1298C: This is a mutation at position 1298 on the MTHFR gene. Less is known about how many people have this mutation, and there’s also less known about its implications for a carrier’s health. 

There are other mutations on the MTHFR gene, as there are many potential variants for every gene. However, when you hear people talk about MTHFR gene mutations, they’re talking about these two variants. If you have either (or both) mutations, it will impact your ability to produce the MTHFR enzyme, leading to an MTHFR deficiency and MTHFR gene mutation symptoms. 

MTHFR Deficiency  & MTHFR Gene Mutation Symptoms 

There’s not one set of MTHFR gene mutation symptoms, the way there’s a list of symptoms for, say, strep throat or the flu. Rather, having one or more of the MTHFR gene mutations has the potential to impact your body’s ability to produce the MTHFR enzyme, which can cause an MTHFR deficiency, which can have health repercussions. 

With that disclaimer out of the way, let’s talk about the MTHFR gene mutation symptoms, risks, and other health complications. When your body produces MTHFR normally, you’re able to efficiently process homocysteine, an amino acid produced when proteins break down. In healthy humans, almost all homocysteine is converted into other substances that your body needs, so there is very little left in your bloodstream. When there’s an MTHFR deficiency, however, your homocysteine levels are elevated, which is concerning because high levels of homocysteine can cause blood clots and damage arteries. 

An MTHFR deficiency also impairs your body’s ability to convert the nutrient folate into the form that your body can use. In fact, when consuming the same amount of folic acid (the synthetic form of folate), people who were homozygous for the MTHFR gene mutation had a 16% lower level of folate in their blood than those without a variant. This can be a big problem, because your body needs folate to make red blood cells, produce DNA and RNA, and convert carbohydrates into energy. 

Specific MTHFR deficiency symptoms and risks include:

• An increased risk of cardiovascular issues, including heart disease, stroke, high blood pressure, and blood clots
• Homocystinuria, a disorder affecting the eyes, joints, and cognitive abilities
• Psychological and mental health issues, including mood swings, depression, anxiety, bipolar disorder, and schizophrenia
• Frequent migraines (check out our guide to natural migraine remedies that actually work)
• Birth defects, specifically neural tube defects, which are severe birth defects of the brain and spine. Studies show that women who are homozygous for the MTHFR gene mutation are twice as likely to have a child with a neural tube defect. This is because folate is essential for proper neural development — which is why it’s so important for pregnant women to take a prenatal vitamin with folate.
• Recurrent miscarriages 
• Certain cancers, like leukemia and colon cancer
• Chronic pain and fatigue

If you’re homozygous for a variant, you’re much more likely to experience MTHFR deficiency and associated health problems than if you’re heterozygous. But not everyone who has a variant will have an MTHFR deficiency and associated MTHFR gene mutation symptoms — and, of course, the conditions mentioned above can have other causes. That’s why it’s important to get tested and do some investigating to find the root cause of your health concerns.

Getting Diagnosed: The MTHFR Gene Mutation Test

Speaking of testing, let’s get into the MTHFR gene mutation test. The mutation is not something that most of us get tested for normally; in fact, many people will go through their whole lives never knowing their MTHFR mutation status, and it won’t make any difference! But sometimes, it makes sense to find out if you’re a carrier of one of the common variants.

If you’re experiencing health issues and learn that you have high homocysteine levels or low folate levels — or both — you could benefit from an MTHFR gene mutation test. However, both elevated homocysteine and folate deficiency have several other potential causes, so it’s important to try to unearth any other potential issues. For instance, high homocysteine levels could be caused by:

• Nutritional deficiencies 
• Hypothyroidism  
• Diabetes
• Physical inactivity
• Smoking 
• Obesity 
• Kidney disease
• Psoriasis
• Certain medications (specifically, certain drugs used to treat cancer and high cholesterol)

If you’ve ruled out a different underlying cause, or have a family history of MTHFR mutations, the next step is to get an MTHFR gene mutation test. The test will look for mutations in your MTHFR gene, specifically on the two locations mentioned above (C677T and A1298C). 

If you go to your doctor for the test, it will be done by drawing a blood sample. You can also opt for an at-home testing kit, like 23andME or specific MTHFR at-home tests, both of which use cheek swabs to analyze your genetic material . The results of your MTHFR gene mutation test will show whether you’re positive for a mutation. If you are, it will also show which of the two mutations you have and whether you’re homozygous or heterozygous (or double heterozygous, meaning you have one mutation on each location, or double homozygous, meaning two mutations at each location). 

We should mention here that many professional medical bodies, including the American College of Obstetricians and Gynecologists, the College of American Pathologists, the American College of Medical Genetics, and the American Heart Association recommend against getting a MTHFR gene mutation test, citing a lack of evidence backing up a need for the test, as well as a lack of utility. We agree that for most people, a MTHFR gene mutation test is unnecessary. However, in certain cases — like for those with a family history or who are experiencing health issues that could likely be MTHFR gene mutation symptoms — having some knowledge about your genetic status could be a powerful piece of information.

MTHFR Supplements & Other Preventative Tips

Having an MTHFR genetic mutation isn’t a condition in and of itself. It’s totally possible to live a healthy life and never even know that you have a mutation at all! But if you’re a carrier of one of the mutations, it does decrease your ability to produce the MTHFR enzyme, which has the potential to lead to health issues — especially if you’re homozygous. 

The good news is that these health issues can be easily prevented or reversed with some simple lifestyle changes and targeted MTHFR supplements. In terms of basic lifestyle choices, here’s what could lower your risk of developing high homocysteine levels and other problems related to an MTHFR deficiency:

• Stop smoking. If you needed one more reason why smoking is horrible for your body, here it is! Research has shown an association between smoking and high homocysteine levels in those with an MTHFR gene mutation.
• Eat folate-rich foods. An MTHFR deficiency reduces your body’s ability to process folate, so consuming a higher level of folate could help offset this issue. Folate-rich foods include lentils, chickpeas, leafy greens, berries, nuts, and seeds.
• Reduce stress. High levels of stress can exacerbate MTHFR gene mutation symptoms. Keep your stress in check by practicing meditation, getting regular exercise, and taking the time for self-care.  

Taking specific MTHFR supplements is one of the most powerful things you can do to reduce your chances of having any health problems related to an MTHFR deficiency. That’s because the MTHFR gene mutation affects your ability to break down certain micronutrients that your body needs, and taking them in supplement form often allows you to skip that step. Here’s what to look for when it comes to MTHFR supplements:

• Folate. Having an MTHFR deficiency often means you can’t properly process folate. To combat this, take a folate supplement that contains the most bioavailable form of folate, methylated folate. This can help your body absorb this crucial nutrient more easily. This is especially important for pregnant women, as folate deficiency can lead to serious birth defects.
• B vitamins. The MTHFR gene mutation is most known for affecting levels of folate (vitamin B-9), but it is also associated with other B vitamin deficiencies. To offset this, take a B-complex that contains B-12, B-6, and riboflavin (B-2).
• Choline. Research shows that the MTHFR gene mutation is also associated with low levels of the nutrient choline. Taking a choline supplement can help. 
• N-Acetyl-Cysteine (NAC). Cysteine is an amino acid that can help lower homocysteine levels. It’s found in high-protein foods like chicken, turkey, yogurt, legumes, and eggs, but those with an MTHFR mutation would be wise to up their intake by taking it in supplement form, when it’s known as NAC. 

You can take all of the above supplements separately, or you can opt to buy a specifically designed MTHFR supplement, which will contain a number of different nutrients that can help prevent MTHFR gene mutation symptoms. Either way, be sure to check out the WellBe Non-toxic Product Database for vetted, curated, medical-grade supplement brand recommendations. 

The WellBe Takeaway on the MTHFR Gene Mutation

The MTHFR gene mutation is widely misunderstood. Here’s what to remember about what it means for your health:

• MTHFR is an enzyme that converts folate into the form your body can use, and breaks down the amino acid homocysteine. What is commonly referred to as the MTHFR gene is the gene that gives your body instructions on how to produce the MTHFR enzyme.
• When part of the DNA sequence on your MTHFR gene is different from what’s expected, it’s called a mutation, or a variant. On the MTHFR gene, there are two common variants, called C677T and A1298C. Because a gene is a set of two alleles (one from each parent), it’s possible to have two mutations, one mutation, or no mutation. Having one mutation is known as being heterozygous, and having two mutations is known as being homozygous. Being homozygous increases your risk of having health issues related to the mutation. 
• Not everyone with a mutation has MTHFR gene mutation symptoms. However, because it can impact production of the MTHFR enzyme, it can lead to an MTHFR deficiency, which has the potential to cause problems associated with high levels of homocysteine and low levels of folate and other essential micronutrients. MTHFR gene mutation symptoms include psychological and mental health issues, frequent migraines, birth defects, recurrent miscarriages, certain cancers, chronic pain and fatigue, and increased risk of cardiovascular issues. 
• Most people don’t need to get an MTHFR gene mutation test. In fact, most people will go through their whole life without knowing their MTHFR status. However, if you’re experiencing health issues that you think might be related to an MTHFR mutation and tests show that you have high homocysteine levels and low levels of folate, it could be helpful to be tested. You can get a test from your doctor, or use an at-home testing kit.
• If you’re a carrier for an MTHFR gene mutation, making certain lifestyle changes can reduce your risk of having any health issues. Eating a healthy diet full of folate-rich foods, reducing stress, and quitting smoking can all help.
• MTHFR supplements can also be helpful in preventing any MTHFR gene mutation symptoms. You can take a specific MTHFR supplement with multiple different nutrients, or take individual supplements. The most important nutrients to supplement are folate, B-6, B-12, riboflavin, choline, and N-Acetyl-Cysteine. Check out the WellBe Non-toxic Product Database for vetted, curated, medical-grade supplement brand recommendations. 

Have you been tested for an MTHFR variant, or know someone who has? Let us know in the comments below!

Listen to Adrienne read this guide on The WellBe Podcast.

Citations:

1. Dean L. Methylenetetrahydrofolate Reductase Deficiency. 2012 Mar 8 [Updated 2016 Oct 27]. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-.
2. Graydon, James S et al. “Ethnogeographic prevalence and implications of the 677C>T and 1298A>C MTHFR polymorphisms in US primary care populations.” Biomarkers in medicine vol. 13,8 (2019): 649-661. 
3. Tsang BL, et al. Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies. Am J Clin Nutr. 2015 Jun;101(6):1286-94. 
4. Zaghloul, Ahmed et al. “Methylenetetrahydrofolate Reductase Polymorphism and Premature Coronary Artery Disease.” Cureus vol. 11,6 e5014. 27 Jun. 2019.
5. Rainero I, et al. Targeting MTHFR for the treatment of migraines. Expert Opin Ther Targets. 2019 Jan;23(1):29-37.