It is easy to check your 23andMe results for the two main MTHFR variants:

Check your 23andMe results for rs1801133 for the MTHFR C677T:

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

 

Check your 23andMe results for rs1801131 for the MTHFR A1298C:

  • T/T: normal (wildtype)
  • G/T: one copy of A1298C allele (heterozygous), MTHFR efficiency slightly reduced
  • G/G: two copies of A1298C (homozygous), MTHFR efficiency reduced

 


 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:

The methylation pathway is a central biochemical process that impacts all of our cells. 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.

Methylation turns on and off genes, maintains and repairs your DNA, and alters proteins. It is important in the nervous system in the production and breakdown of neurotransmitters. For example, to turn serotonin into melatonin, your body uses a methyl group.

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.


Lifehacks

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

17 Comments

Alexander Hawkins · April 8, 2018 at 4:30 am

I contacted 23andme with some questions and now they deny tracking MTHFR genes any longer. If this is in response to MTHFR’s interest I’m not sure… I suppose it could just be customer service not knowing what they’re talking about. From what you know about their process can you verify? Would they just stop tracking certain genes or not? From their website, they only give a handful of terribly brief reports now and not the detailed genetic details this website seems to imply.
Any light you could shine on this would be greatly appreciated.

    Debbie Moon · April 9, 2018 at 5:01 pm

    Hi,
    As far as I know, the raw data file still contains the data for the two most looked at MTHFR variants. 23andMe doesn’t include MTHFR in their health reports, which could be what the customer support response meant. I’ve found that getting answers from their customer support is sometimes difficult in that they send answers that seem scripted.
    The health reports on the 23andMe website are ones that the FDA has approved for them to present to their customers. What most people look at – from 23andMe, AncestryDNA, etc – is the raw data file (contains about 600,000 SNPs).
    Debbie

    park bear · May 22, 2018 at 6:06 pm

    log in and then: https://you.23andme.com/tools/data/?query=MTHFR&filter_by_platforms=false

Alexander Hawkins · April 12, 2018 at 2:05 am

Thanks Debbie. It seems they try to move everyone through the “Browse Raw Data” feature, which contains a limited number of SNPs, but your explanation and from what I’m able to see about the raw data file, which is still available, makes sense and is what I’m looking for. Thanks again!

Becky · May 3, 2018 at 6:07 am

There’s a lot more to methylation than 1 gene, and the majority of the population, I believe it’s 80% or so have one variant in the two listed. Although these genes are important, they work synergistically with MANY other genes, some that could be wayyy more important in the long run. For most, if not all, there are many gene variants at need to be worked out prior to MTHFR. If the others aren’t functioning than of course you will have an issue with methylation and your varied MTHFR.
I know you mentioned that there is a lot more to it but I commented because this issue is SO vital for people to understand. 5 or so years ago when I found out I was heterozygous for both MTHFR genes mentioned I thought that was the end all be all and I just needed to supplement—and so did every practitioner under the sun. BIG MISTAKE!! I cringe when I see suggestions that say to try certain supplements with such little information, because it can cause devastating consequences. Coming from someone who had a habit of playing her own doctor over here! Please please PLEASE educate yourselves people, and start working with a Doctor well versed in methylgenetic nutrition. An MD or ND that knows more than the bare minimum—which can actually be somewhat hard to find. Best of luck~ and more so education, perseverance and dedication to all who read this!
In health,
Becky :)

    Debbie Moon · May 3, 2018 at 10:34 am

    I completely agree that there is more just MTHFR to learn about, and I would add that there is a lot more than just methylation cycle genes. So much more that I’ve written 100+ articles on this website about other genetic variants that impact our lives :-) I encourage you, and everyone else, to keep reading and keep learning.
    Debbie

Marc · June 21, 2018 at 4:18 am

Hi Debbie,

While it does seem pretty clear that being homozygous for MTHFR C677T causes a number of issues, what about being heterozygous for same ? I’ve repeatedly read that someone who’s heterozygous for C677T (and having wild type A1298C) whose gene efficiency is reduced by ~ 40 % may not have any overt health issues.

    Debbie Moon · June 21, 2018 at 8:04 pm

    Hi Marc,
    Good questions.
    Research studies usually show statistical effects (e.g. increased risk of heart disease, increased risk of miscarriage) in those who are homozygous rather than heterozygous. But everyone is different, and other genetic variants (as well as environmental factors) can play a role. For me (I’m heterozygous), I could tell a difference when adding in methyl folate and methylcobalamin at first. That prompted me to eat better and add in more dietary folate, so I don’t supplement daily anymore – just when I’m not eating a lot of greens.
    A good percentage of the population carries the MTHFR C677T variant, which leads people to think that it can’t be making a huge difference. On the other hand, there is a large portion of the population that just doesn’t feel well – fatigue, brain fog, etc. So the difference for someone who is heterozygous may be the difference between just making through the day vs. really being optimal.

Marc · June 21, 2018 at 4:40 am

I should’ve added that in addition to being heterozygous for C677T, I’m also homozygous for MTHFD1. Though this last hasn’t been studied extensively, it seems to worsen any existing MTHFR SNPs. What isn’t clear, is how much worse can it make my existing C677T SNP ?

Elise Colton · December 31, 2018 at 4:13 pm

Hi There, please forgive my ignorance if the answer to my question is obvious, I’m just beginning to try to investigate some of my issues. I followed your link to my 23andme results and they came right up. My question is, should I be looking at what is listed as “genotype” or “variants” when comparing to your chart?

    Debbie Moon · December 31, 2018 at 11:32 pm

    Hi Elise –
    You need to look at the “Your Genotype” column :-)
    Good luck as you get started on learning more about your genes and your health!
    Debbie

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