Healthy Hormones

What is MTHFR?

What is MTHFR?  Is that a curse word?

Science and medicine are in the early stages of understanding genes and gene mutations and the potential of gene therapy to treat disease.

The MTHFR gene mutations are probably the best known of the gene mutations, but relatively little is truly known about them by most people.

Having one of these gene mutations may increase your risk of developing heart disease, stroke, depression, neurological disorders, birth defects, developmental disorders, and possibly even cancer.

In this article, I will discuss the MTHFR gene mutation, explain how you can be tested for it, and show what it may mean if you are positive for one of its common variants.

Here we go...


What is a Gene?

Even though this is not a hormone issue, I am frequently asked about MTHFR in my practice.  Since is could potentially impact your health it deserves a blog post in order to help you stay informed.

In order to understand MTHFR and the concept of a gene mutation, we need to do a quick primer on genetics.  

Every person in the world has the same approximately 20,000 genes (NOT jeans for you shopaholics reading this!).

The differences between us come from the slight variations in those genes.

Almost every cell in your body contains the complete set of instructions on how to make you.  These instructions are coded in your DNA.

Deoxyribonucleic acid (DNA) is a long, ladder-shaped molecule.  Each rung of that ladder is made up of a pair of bases called units. Those units are either adenine (A), thymine (T),  guanine (G) or cytosine (C).  A and T are always paired together, and G and C are always paired together.

The DNA strands are then organized into larger pieces called chromosomes.  Humans have 23 pairs of chromosomes for a total of 46.  Other animals and plants have a different number of chromosomes. 

For example, a dog has 39 chromosomes, a rice plant 12, and a fruit fly only 4.

Chromosomes are further organized into short segments of DNA called genes.  A gene has a set of instructions that tells your cells how to function and what traits to express.

The cells use the instructions given by the genes to make proteins.  Proteins do much of the work in the cells of your body.  Some give the cell its shape and structure, while other proteins help the cells carry out certain biological processes, such as carrying oxygen to the body.

Proteins can be further organized into larger molecules called enzymes.  Enzymes serve as catalysts to bring about certain biochemical reactions.

In the situation we are discussing in this article, an enzyme causes a reaction that allows nutrients from food that were eaten to be metabolized so that they can be used by the body.

The body typically metabolizes substances by triggering an enzymatic reaction that attaches a molecule to the substance.

If an oxygen molecule is attached in the reaction, it's called oxidation.  If a sulfate group is attached, it's called sulfation.  If a methyl group is attached, it's called methylation. And so on.

So if every cell contains all of the same DNA, how does one cell know to make a finger while another makes a heart?  The answer lies in the intricate system of genetic switches.  

Master genes turn other genes on and off, ensuring that the right proteins are produced at the right time in the right cells.

I hope I haven't overwhelmed you.

Now that you have an overview, let's get into the specific situation of MTHFR...

What is MTHFR?

The MTHFR gene is found on the short arm of chromosome 1.

MTHFR stands for methylenetetrahydrofolate reductase.  The MTHFR gene contains instructions for making the MTHFR enzyme.

The MTHFR enzyme has 2 primary functions:

1.  It metabolizes folic acid (also called folate or vitamin B9) by converting it to methylfolate.  Remember, it adds a methyl group to it.

2.  It helps to keep homocysteine levels low because methylfolate converts homocysteine back into methionine, which is then recycled.

Methionine is used to make other important proteins in the body.  These include SamE, which plays a major role in serotonin production, and glutathione, which helps with detoxification of heavy metals and environmental toxins.

Up to 60% of the population has been shown to have a defect in the MTHFR gene (also called a polymorphism or SNP).  The defects can impair the ability of the MTHFR enzyme to methylate folic acid and convert homocysteine to methionine.

Remember, you have 2 copies of every gene in your body (one from mom, one from dad).

If only one of the two genes contains the defect, it is called a heterozygous defect.  If both genes have the defect, it is called a homozygous defect.  "Hetero" means different, "Homo" mean the same.

If the defect is on both genes (homozygous), it results in a more severe impairment of the function of the enzyme compared to a heterozygous defect.

With the MTHFR gene, the defect usually occurs in 2 locations - C677T and A1298C.

People can also be heterozygous for both - meaning they have a defect at the C677T location on one gene and a defect at the A1298C location on the other gene.  This is called compound heterozygous.

Studies have shown that the above genetic defects may impair the efficiency of the MTHFR enzyme by the following percentages:

  • Homozygous  C677T - up to 70% impairment
  • Heterozygous C677T - up to 35% impairment
  • Homozygous A1298C - up to 35% impairment
  • Heterozygous A1298C - Minimal impairment
  • Compound Heterozygous - Possibly >70% impairment

Symptoms of an MTHFR Mutation

The gene mutations themselves do not directly cause any health problems.  However, they may cause an exaggerated response to a poor diet or poor lifestyle choices.

Any signs or symptoms caused by the MTHFR gene mutation will be the result of having an elevated homocysteine level, a low folic acid level, or low SamE and glutathione levels.

Central Nervous System -

These include

- depression

- fatigue


- memory loss


bipolar disorder


These conditions seem to be more common with the A1298C mutation.

Studies have shown that using methylfolate is as effective as traditional anti-depressant drugs in the treatment of depression, even in patients that did not respond to the anti-depressant drugs.

This probably occurs because the methylfolate increases levels of SamE which then raises serotonin levels.

Cardiovascular System -

MTHFR gene mutations, particularly the homozygous C677T and compound heterozygous mutations, have been shown to be a risk factor for the following:  

- heart disease


- blood clots

- peripheral neuropathy

- recurrent miscarriages

- congenital birth defects

The increase in incidence is most likely due to the elevation of homocysteine levels caused by the gene defect.

Toxic Exposures -

With the MTHFR defect, less methionine is produced which results in lower levels of glutathione.

Glutathione is one of the primary detox molecules in our body.  It helps to clear heavy metals, BPA, and other environmental toxins from our body.

Symptoms that can occur if we have an excess of these toxins can include nausea, diarrhea, abdominal pain, asthma, hair loss, rashes, and others.

Other Systems -

An MTHFR mutation has been possibly linked to autism, fibromyalgia, chronic fatigue syndrome and chronic lyme disease.

In one study, there was a 3-fold increase in the risk of autism in children with the C677T defect.  If they also had the A1298C defect, their risk rose by 8-fold.

In another study, mothers with an MTHFR mutation who didn't take folic acid during their pregnancy were found to be 7 times more likely to have a child with autism.

Folic acid and B12 supplementation has been shown to reduce the symptoms of fibromyalgia.

MTHFR mutations have also been possibly linked to colon and gastric cancers.

Pregnancy -

MTHFR mutations have been linked to an increase risk of premature delivery as well as birth defects.

Diagnosing an MTHFR Defect

There is a blood test available to test for an MTHFR defect.  It can also be tested through buccal (cheek) swabs.

Testing for MTHFR is not routinely ordered in most doctors offices unless the patient has an elevated homocysteine level or a positive family history of having an MTHFR defect.

In fact, there are many experts that believe there is not enough data to support or recommend routine testing at all for the defects.

If you want to have it tested "just so you will know," then there is a strong possibility that your insurance will not cover it and it could cost a few hundred dollars.

A cheaper option may be to order a home testing kit from an online source such as Most cost about $150.  Another option would be to get a full genetic testing kit through

If you have a family history of an MTHFR defect, and/or if you have a personal or family history of an elevated homocysteine level, I would recommend that you get tested.  This is especially true if there is also a strong family history of heart disease, stroke, or one of the other conditions that have been linked to a genetic defect in the MTHFR gene.

Some experts recommend also testing for S-adenosylhomocysteine and methymalomic acid (MMA) if you are positive for a homozygous MTHFR mutation or compound heterozygous.  S-adenosylhomocysteine appears to be a more sensitive indicator of cardiovascular disease than homocysteine.

Treatment of an MTHFR Gene Defect

Since the core issue with an MTHFR gene defect is inadequate methylation of B vitamins (particularly foic acid), taking a B complex vitamin that has methylated forms of folic acid, B12 and B6 is a mainstay of treatment.

It is important to stay away from vitamins that have synthetic folic acid and synthetic B12 (cyanocobalamin) if you have an MTHFR defect. Since your ability to methylate it is already impaired, it could actually make things worse.

You can buy my methylated B vitamin of choice by clicking here.

There is inadequate data at this time that eating a diet low in folic acid has any significant impact.

Helping your body to detox naturally is also key.  This includes:

  • Eat a diet of whole, natural, unprocessed foods
  • Sweat! - regular exercise, sauna, etc.
  • Avoid environmental toxins - Avoid cleansers, pesticides, plastic bottles
  • Maintain good gut health - Regular, consistent BMs, take a daily probiotic
  • Stress Management - Yoga, good sleep, meditation

On a personal note, my homocysteine level was 16.3 on labwork from a year ago.  Further testing showed that I was heterozygous for one of the MTHFR mutations.  Since cleaning up my diet, detoxing better, and taking a methylated B vitamin, my most recent labwork showed my homocysteine level at 4.5!


The MTHFR gene carries the instructions for making the MTHFR enzyme.  That enzyme is responsible for methylating folic acid which allows it to be metabolized in the body.

There are several known genetic defects in the MTHFR gene that can reduce its ability to methylate.

The lack of methylation can lead to low levels of folic acid and high levels of homocysteine, which can increase cardiovascular risk and multiple other medical conditions.

This can be managed by taking a methylated B vitamin, eating a whole, natural food diet, managing stress, and detoxing adequately.

Now it's your turn...

Have you or someone you know been diagnosed with an MTHFR defect?

If so, how are you managing it?

Leave any questions or comments below.

About the Author Dr. Jeff Whelchel

Dr. Whelchel is a family physician who specializes in functional medicine, especially hormone optimization. He has over 20 years experience in private practice managing patients with various medical issues. His passion is helping patients reach their full potential of wellness and quality of life. He grew up in the Texas Panhandle where he currently lives. He is married and has 3 awesome children.

Leave a Comment:

Terry Jones says February 5, 2018

Very interesting!

    George Graves says March 7, 2018

    Very helpful article. Thanks! Would enjoying some follow up with you on this. I too am a Family Physician.

      Dr. Jeff Whelchel says March 11, 2018

      Hello George. I would be happy to talk with you anytime. Send me an email and we can connect.

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