MTHFR Mutation: How to check your genetic data

The MTHFR gene codes for a key enzyme that your body needs in order to use folate in the methylation cycle. The methylation pathway is a central biochemical process that impacts all of our cells.

It is easy to check your genetic results for the two main MTHFR variants:

Check your genetic data for rs1801133 (23andMe v4, v5; AncestryDNA):

  • G/G: normal (wildtype)
  • A/G: one copy of MTHFR C677T allele (heterozygous), decreased by 40%
  • A/A: two copies of MTHFR C677T (homozygous), decreased by 70 – 80%

Check your genetic data for rs1801131 (23andMe v4, v5; AncestryDNA):

  • T/T: normal (wildtype)
  • G/T: one copy of MTHFR A1298C (heterozygous),  decreased enzyme
  • G/G: two copies of MTHFR A1298C (homozygous), decreased enzyme

 Here is what the MTHFR gene does:

There is a lot of swirl on the internet about MTHFR with people thinking it is the cause of everything under the sun. This seems to have caused a bit of a backlash with doctors claiming that MTHFR variants are completely unimportant.

Let’s take a look at a bit of the science:

Methylation is the adding and removing of a methyl group (CH3) to amino acids, DNA, and other enzymes or proteins. Most of our biological molecules are chains of hydrocarbons — carbons plus hydrogens. So adding a methyl group stacks on one more link in a hydrocarbon chain.

Adding a methyl group – or an extra carbon plus three hydrogens – then changes the original molecule into something different. For example, a methyl group is added to serotonin in the conversion to melatonin.

Methylation can turn on and off genes, maintain and repair your DNA, and alter proteins. It is important in the nervous system in the production and breakdown of neurotransmitters and in the detoxification of some environmental toxicants.

The methylation cycle is also intimately involved in heart health. It controls the level of homocysteine, an important marker of heart disease risk. It is also involved in cholesterol levels[ref], and genetic variants in the methylation pathway have been linked to heart disease in many studies. Additionally, the pathway is involved in regulating hormones, such as estrogen, as well as playing a role in histamine levels.

Genetic variants can change how well a piece of the methylation pathway works. Knowing where you have genetic variations can help you understand what you need to do to get around the slow-downs in the methylation pathway.

MTHFR is a central gene in the methylation cycle and is a limiting factor for producing methyl groups from folate. Common genetic variants in the coding of this gene affect more than half the population.

Specifically, the MTHFR (methylenetetrahydrofolate reductase) gene codes for an enzyme that turns folate into the active form, 5-methyltetrahydrofolate, that your body uses. This, along with the active form of vitamin B-12  (methylcobalamin) drives an important portion of the methylation cycle.

The MTHFR genetic variants (C677T and A1298C) have been linked to an increased risk of:

  • higher homocysteine levels and heart disease [ref][ref][ref]
  • neural tube defects (spina bifida) [ref]
  • stroke [ref]
  • preeclampsia and hypertension in pregnancy [ref][ref]
  • miscarriage [ref][ref]
  • mood disorders.[ref][ref] [ref][ref][ref]

Carrying an MTHFR variant is statistically associated with an increase in the risk of the above diseases (and others!), but this doesn’t mean that it will cause you to have that disease.  The increase in risk is usually small, and diet or supplementation can offset the increase in risk.

The MTHFR variants cause a reduction in methylfolate levels, with the 677 T/T genotype having the greatest impact.

Why exactly does the MTHFR C677T variant do? 
The MTHFR C677T is a change in one nucleotide base (a “T” instead of a “C”) at one spot in the gene. The variant slightly changes the protein structure. This change causes the enzyme to break down faster at normal body temperature, thus reducing the amount of enzyme available. [ref][ref][ref]

Why do some doctors think that MTHFR variants are unimportant?
The very extensive research (it’s one of the most researched genes) shows that MTHFR variants are linked to an increased risk for the disorders listed above, as well as a bunch of other diseases.

But while the MTHFR variants could play a role in different chronic diseases, they aren’t usually a huge smoking-gun, absolute cause for most diseases. So when patients are flooding into the doctor’s office to demand treatment for ”having the MTHFR gene”, the automatic backlash is to say that MTHFR variants aren’t important.

Most physicians are trained to treat a disease (or the symptoms of a disease) rather than to hunt down all of the various aspects of lifestyle, diet, and environment that could be contributing to the disease. To be fair, most people, when they go to a doctor with an ailment, expect to get a pill that solves the problem immediately.

While your general physician may not think that the MTHFR variants are causing your  (fill in the blank)   illness, cardiologists may take it more seriously. There is an extensive number of studies showing a link to an increased risk of cardiovascular disease. A meta-study that combined other study results showed that the MTHFR 677T/T genotype increased the risk of heart disease by 38%.[ref] With heart disease being the number one killer in most countries, a 38% increase in risk is important.

Overall, optimizing your methylation cycle can be important to your health (especially heart health). It is definitely a foundational first step; perhaps it will keep you from getting an illness that sends you to the doctor’s office.


What should you do about an MTHFR mutation?  First off, start reading and educate yourself! There is a lot more to the methylation cycle than just the MTHFR gene.

Increasing your intake of folate from foods will help mitigate some of the risks from the MTHFR variant.  Foods containing folate include leafy greens, lentils, asparagus, and broccoli.  Note that when you are looking at folate content, you need to make sure it isn’t folic acid (synthetic form in processed foods) if you have methylation cycle variations. Here is a good list of food sources of folate.

If you aren’t getting enough folate from foods, you could try a low-dose methyl folate supplement. Vitamin B12 is also important in the methylation cycle, so you need to ensure you are getting enough B12 either through diet or supplements.

Go and get your homocysteine level checked.  High homocysteine levels have been linked to an increased risk of heart disease.  Methyl folate plus B12 and B6 may help reduce your homocysteine.[ref]  In the US, you can order this online without a trip to the doctor through Walk-In Labs or other online testing providers.

Choline can help your body bypass a lack of folate in the methylation cycle. [ref][ref] Good sources of choline include egg yolks, beef liver, and wheat germ. A metabolite of choline, betaine, is actually what is working through the methylation cycle, so food sources of betaine (beets, quinoa, and spinach) are also helpful here.

Recap: If you carry one of the MTHFR genetic variants, eating a healthy diet with green veggies and legumes (or liver) is important to you. Some people can get away with eating junk food all the time — you are not one of those people.

More to read about methylation cycle variants:

General MTHFR and Methylation cycle information:

updated 12/2017