It is easy to check your genetic results on 23andMe or AncestryDNA for the two main MTHFR variants known as C677T and A1298C.
If you have 23andMe results (it doesn’t matter if you have the health option or not!), click on the link below to check your MTHFR gene.
If you have AncestryDNA results, you will need to download your raw data file and search for the rs id number below. (How to download AncestryDNA and Search)
Or, become a Genetic Lifehacks Member and see your data right in the articles :-)
MTHFR Genetic Variants:
Check your genetic data for rs1801133 (23andMe v4, v5; AncestryDNA):
- G/G: typical *
- A/G: one copy of MTHFR C677T allele (heterozygous), decreased by 40%
- A/A: two copies of MTHFR C677T (homozygous), decreased by 70 – 80%
Members: Your genotype for rs1801133 is —.
Check your genetic data for rs1801131 (23andMe v4, v5; AncestryDNA):
- T/T: typical *
- G/T: one copy of MTHFR A1298C (heterozygous), slightly decreased enzyme function
- G/G: two copies of MTHFR A1298C (homozygous), decreased enzyme by about 20%
Members: Your genotype for rs1801131 is —.
What does the MTHFR gene do?
The MTHFR gene codes for an enzyme that is an important part of the methylation cycle.
There is a lot of swirl on the internet about MTHFR — with people thinking the “MTHFR mutation” is the cause of everything under the sun. This seems to have caused a backlash with doctors claiming that MTHFR variants are completely unimportant.
Let’s cut through the hype, and I’ll explain the science. Research shows that the MTHFR variants do statistically increase the risk of quite a few things. But this relative risk needs to be kept in perspective and considered along with environmental factors (diet, lifestyle, etc).
At the end of the article, you will find solid, evidence-based lifestyle solutions for optimizing for the MTHFR variants.
What is the methylation cycle?
I mentioned above that the MTHFR gene codes for an enzyme that is an important part of the methylation cycle.
Methylation is the adding and removing of a methyl group (CH3) to amino acids, DNA, and other enzymes or proteins.
Most of our the molecules in our body are chains of hydrocarbons — carbons plus hydrogens. So adding a methyl group stacks on one more link in a hydrocarbon chain. Sometimes it helps me to visualize it as the molecule being made of Legos, and the methyl group is just adding another Lego component onto your creation.
Adding a methyl group – or an extra carbon plus three hydrogens – then changes the original molecule into something different.
Here’s an example:
a methyl group is added to neurotransmitter serotonin in the conversion to melatonin, an importantcircadian rhythm hormone.
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 ] 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.
What does the MTHFR enzyme do?
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.
Here is an image to explain:
What does MTHFR C677T and A1298C mean?
Let’s talk about terminology…
A mutation is the change in a gene that happens in less than 1% of the population. These are the rare changes.
A polymorphism is a change that occurs in the gene for more than 1% of the population. We all have lots of different polymorphisms — these are the small changes that make us all unique.
The MTHFR C677T variant is considered a single nucleotide polymorphism(SNP) which means that one nucleotide base pair (the As, Cs, Gs, and Ts) is different for part of the population.
Neither MTHFR C677T or A1298C variants are considered mutations. Both are commonly found in the population.
What problems can the MTHFR C677T or A1298C variants cause?
Research shows that the MTHFR genetic variants (C677T and A1298C) have been linked to a statistically increased risk of:
- high 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 does not mean that it will cause you to have that disease. It just increases the susceptibility to diseases when diet and lifestyle factors are not optimal.
More importantly, food choices or supplemental methyl folate can eliminate the problems from the MTHFR variants.
Getting specific on the MTHFR C677T variant:
The MTHFR variants cause a reduction in methylfolate levels.
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 ]
People with the rs1801133 A/A genotype have the greatest impact. They have about a 70% reduction in the enzyme function.
You may be wondering why it is described as a C to T substitution, but the bases are usually referred to as G and A. This is because the C677T variant was initially described on the opposite side of the DNA strand than is referenced in 23andMe or AncestryDNA data. You’ll notice that everything on this website explains the variants in reference to the forward or plus orientation to match with what you see on your genetic data. But if you look at research studies, especially older studies, you will see the alleles referred to as C or T. To switch between the two orientations, just know that C=G and T=A.
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.
While a MTHFR variant can play a role in different chronic diseases, it usually isn’t the absolute cause for most diseases.
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. (Side note- everyone has the MTHFR gene! It’s one of those genes you can’t live without.)
Most physicians are trained to treat diseases (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. They simply don’t have the time in a 10-minute visit to discuss the nuances of diet, genetics, toxicant exposure, etc. To be fair, most people going to a doctor with an ailment expect to get a simple answer or pill that solves the problem immediately.
Does the MTHFR variant increase the risk of heart disease?
There are extensive studies showing a link between MTHFR C677T and an increased risk of cardiovascular disease. A meta-study that combined other study results shows that the MTHFR 677 A/A genotype increases 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!
Knowing that you carry a MTHFR genetic variant can help guide your choice of foods and supplements.
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.
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, therefore food sources of betaine (beets, quinoa, and spinach) are also helpful here.
Supplemental Methyl Folate and B12:
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.
Riboflavin (vitamin B2):
The MTHFR C677T variant decreases its ability to bind to FAD, a riboflavin-dependent enzyme.[ref] If you have high homocysteine (a marker for heart disease risk), a couple of studies show that adding riboflavin lowers homocysteine levels in those with the A/A genotype. [ref][ref] Other research points to riboflavin lowering homocysteine levels only if vitamin B6 levels are adequate.[ref]
Check your homocysteine levels:
High homocysteine levels increase the risk of heart disease. Methyl folate plus B12 and B6 may help reduce your homocysteine.[ref ] Ask your doctor about getting your homocysteine checked the next time you or there for a physical. Alternatively, in the US, you can order this test online without a trip to the doctor through UltaLabs for $34 (*affiliate link) or other online testing providers.
Related Genes and Topics:
Having trouble with supplements containing methyl groups? Wondering why your neurotransmitters are out of balance? It could be due to your COMT genetic variants. This important enzyme is tasked with breaking down neurotransmitters, such as dopamine.
You may have read or heard that anyone who carries MTHFR variants should not be vaccinated. Usually, the reason given is that those with decreased MTHFR enzyme activity cannot detoxify or ‘handle’ vaccinations, often with references to mercury in the vaccines. This article reviews the published scientific studies on the topic of MTHFR and vaccinations.
If you are just getting started with researching your MTHFR polymorphisms, you may want to start with some background information. I have a list of resources on the MTHFR page that you might find helpful. MTHFR is a key gene in regulating the body’s folate metabolism and, consequently, is involved in the methylation cycle.
Histamine is a molecule that plays many roles in the body. It is involved in allergic reactions, plays a role in our immune defense system, acts as a vasodilator, and is a neurotransmitter. While most of us think of histamine only when reaching for an antihistamine during allergy season, it is a vital part of our body’s everyday functions.
MTR (methionine synthase) and MTRR (methionine synthase reductase) are two genes involved in the conversion of homocysteine to methionine, and a couple of fairly common gene variants cause the genes to work differently.
A quick post to recommend a good podcast to anyone looking into MTHFR variants. Chris Masterjohn put out a well balanced and well-researched podcast a few weeks ago titled Living with MTHFR. For those of you who don’t have two hours to listen to it, there is a transcript of the show, which is a much faster read.