July 30


What is MTHFR and Why Do I Need to Know About It?

By Sunny Brigham, MS, CNS

July 30, 2018

Methylenetetradydrafolate reductase.  I know.  That’s an eyeful and a mouthful.  For short, it’s called MTHFR.  In school, we called it the Monday Thursday Friday gene.  I call it the M&$#^&*$*&er gene…because it is.

Some of you know what MTHFR because you have it and are dealing with the symptoms.  Some of you have never heard of this before but probably are also dealing with the symptoms as well.  You see…it’s actually a pretty common genetic mutation that many have. 

There is really so much that goes into MTHFR and methylation.  You can be an overmethylator or an undermethylator.  You can have mutations that are not expressed and mutations that are expressed.  This is a very complex process and treatment is going to change from one person to the next.  Today, we are sticking just to MTHFR mutations. 

In this blog, we’ll discuss exactly what MTHFR is, affected genes, expression of those genes, symptoms associated with gene expression, and what steps you can take towards feeling better.

Myself…I’m heterozygous for one of the two MTHFR genes.  But I am much more symptomatic than most that are heterozygous because of other mutations I have.  I’ll explain more later…let’s get into it, shall we?

What is MTHFR?

MTHFR is not a gene…it’s an enzyme.  This specific enzyme provides a methyl group to various processes in the body, specifically to the methylation of folate and B12.  Folate is the food form and folic acid is the synthetic form often found in vitamins.  Folate = okay.  Folic acid = bad.  In order to use the folate in food form, we need MTHFR to methylate the vitamin.  The same goes for B12.  The food form in cyanocobalamin and the form that is found in most synthetic supplements.  The active form is methylcobalamin.  We need MTHFR to methylate B12 for use. 

We need folate for DNA synthesis, prevention and treatment of macrocytic anemia, prevention of various birth defects, prevention of mental health issues, prevention of cognitive decline, and to create energy in the body.  Without proper methylation, we can develop any of these issues rather quickly.  There are a few forms of folate, but we are focusing on methylfolate for the purpose of this blog. 

We need B12 for DNA synthesis, prevention and treatment of macrocytic anemia, proper nerve function, cognitive function, and to create energy in the body.  There are several forms of B12, but for the purpose of this blog, we are just focusing on methylcobalamin.  Without proper methylation, we will feel fatigue and usually have nerve conduction issues.


If you’ve had any genetic testing completed, you’ll be able to find what your MTFHR status is.  Many have done 23andme testing or Ancestry testing.  By downloading your raw data, you can see what your status is. 

When looking at your data, you’ll be looking for the A1298C or the C677T single nucleotide polymorphism (SNP)…aka gene.  The more prominent gene is the C677T SNP.  This means if you have this mutation, you’re at an increased risk of experiencing the effects over someone with just the A1298C mutation.  By the way…having at least one mutation is pretty common.

Let’s look at some terms to be familiar with:

Allele – one of two portions of a gene

Heterozygous – one mutated allele

Homozygous – two mutated alleles

If you haven’t had any of that done, next time you are in to see your physician for a physical and labs (annually I hope), ask to have your homocysteine levels tested.  Homocysteine is a byproduct amino acid in the body.  If it’s elevated, there’s a good chance you have an MTHFR mutation.  Some say it’s a better indication of the mutation.  This is because you can have a mutation and it not be expressed…meaning you have no symptoms of it because it’s not an active mutation.  If your homocysteine levels are elevated, you probably have a mutation that is actively being expressed.  This will require treatment. 

Symptoms of MTHFR

This is a difficult section because the symptoms of the mutation are vast.  Not only that, the conditions the mutation can cause are also vast.  So, narrowing it down to a few isn’t an easy task. 

Now, just because you have some of these symptoms, it does not mean that you have a mutation.  Many of these symptoms can be associated with many other conditions or vitamin deficiencies.  With that said, here are a few of the common things people with an expressed mutation may experience:


Tingling in the fingers or toes

Dry skin

Fatigue not relieved by better sleep or dietary changes


Exercise fatigue




Poor hair condition

Poor appetite

Poor memory

Weak nails

Grinding teeth


All of these I can relate to another condition or vitamin need.  Therefore, I don’t go after an MTHFR mutation first, even if I have a genetic report telling me someone has the mutation.  Because, again, just because you have the mutation, it doesn’t mean that mutation is being expressed. 

I will, however, treat the mutation if homocysteine levels are high.


Improving overall dietary intake is going to be a good first step.  No…that won’t “fix” the mutation, but it’s a good health move and will prevent any other unexpressed mutations from expressing. 

For most, taking an MTHFR specific supplement (there are many on the market) will be a starting point.  These supplements are typically high in methylfolate, have some methylcobalamin, and contain peripheral nutrients as well. 

Proceed with caution though...

Caution of Self Treatment 

If you recall in the beginning, I mentioned that I’m heterozygous for one MTHFR mutation (A1298C) but have more symptoms than many.  That’s because I have a few other mutations that cause me to be an undermethylator.  This means that aside from the MTHFR mutation, my methylation status is compromised.

Being an undermethylator, I exhibit many of the common symptoms:


OCD tendencies


Social isolation

Strong willed/ control

Calm demeanor with high inner tension (classic duck on a water scenario)

Terse speech

Now, here’s where self-treatment gets tricky.  If I were to treat myself for the MTHFR mutation assuming that I am expressing that mutation, I’m going to increase my methylfolate intake…as that’s the standard starting point.  The problem with that is, as an undermethylator, I have low neurotransmitter activity.  (Neurotransmitters are the cars that drive the mood stabilization hormones to the brain.)  Folate further reduces neurotransmitter activity.  I would make my mood much worse and likely increase my anxiety if I went the standard MTHFR treatment route.

Methyl trapping could also take place.  This is where, again, someone self-treats for MTHFR mutations by taking an increased about of either methylcobalamin or methylfolate in an attempt to feel better.  Often, initially they will feel better.  And then things will regress quickly.  Not knowing what happened, they may increase their dose again…making things worse.  This causes a blockage of the methylation cycle…the cycle is trapped. 

On top of that, too much methylfolate can mask a B12 deficiency causing nerve conduction or cognitive issues down the road.

Let’s not self-treat on this one, mkay?  If you suspect MTHFR issues, speak with someone educated in this aspect of genetics to help figure out the proper supplementation for you.

Wrap Up

Do you suspect that you have an MTHFR mutation?  Or do you have a confirmed mutation?  Share with me below what you’ve tried to help yourself feel better.

Don’t forget to share this blog with your friends…who knows whom it’ll help!


Brustolin, S., Giugliani, R., & Félix, T. M. (2010). Genetics of homocysteine metabolism and associated disorders. Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Medicas E Biologicas / Sociedade Brasileira de Biofisica ... [et Al.], 43(1), 1–7.

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