Testing for MTHFR Mutations

The first step in treating MTHFR mutations is to accurately test for all MTHFR mutations, as well as other related single-nucleotide polymorphisms (SNPs). Genetic testing is the only reliable method to test for MTHFR mutations. Thankfully, genetic testing is now very affordable and convenient via home saliva testing. The easiest way to test for MTHFR mutations is by using the genetic testing services of
23andMe ($99) combined with methylation analysis provided by Genetic Genie (free). The 23andMe test provides the raw genetic data for you to connect with Genetic Genie and obtain in-depth methylation analysis.

Genetic Testing

Step 1: Purchase DNA test from
23andMe ($99).
Step 2: Connect your 23andMe results with
Genetic Genie (this is a free service, but donations are suggested).

Your methylation analysis from Genetic Genie will include an extensive methylation report. It is important that you carefully read and understand your results before proceeding with MTHFR treatment.

Your results will indicate whether your are homozygous or heterozygous for any mutations. Homozygous mutations are more severe than heterozygous mutations and often require additional treatment. If you see a +/+ for any mutation, this means you are homozygous for that mutation. If you see +/- for a mutation, this means you are heterozygous for that mutation. A -/- means you do not have that mutation.

Overview of MTHFR Mutations

The two most common MTHFR mutations are C677T and A1298C. Treatment options for both are similar, but it is important to know the subtle differences between each type of mutation in order to most effectively address each mutation. Here is a brief overview of each type of mutation:


If you are either heterozygous or homozygous for the MTHFR C677T mutations, your body has trouble converting folic acid into the active form of folate in the body. The nutritional implications of this are twofold. First, you do not tolerate folic acid well. Consuming large amounts of foods fortified with folic acid or supplements containing folic acid may cause adverse reactions. Long-term, excessive folic acid in someone with MTHFR C677T may increase risk of cancer. Second, you are more likely to be folate deficient. This means you should make sure you regularly eat foods containing natural folate, such as leafy green vegetables. Furthermore, a MTHFR C677T mutation may cause elevated levels of homocysteine in the body. Homocysteine contributes to oxidative stress and increases risk of heart disease when elevated.


MTHFR A1298C mutations affect conversion of methylfolate into BH4, or tetrahydrobiopterin. BH4 plays an important role in neurotransmitter production, which is why MTHFR A1298C mutations are often associated with psychological disorders. The particular neurotransmitters affected include serotonin, dopamine, epinephrine, and norepinephrine. MTHFR A1298C mutations may also affect melatonin production, which often leads to sleep disturbances. Additionally, BH4 is important for heart health and deficiency may play a role in the development of cardiovascular disease.

MTHFR Treatment

The treatment of MTHFR mutations is often a two-pronged approach. First, supplemental methylfolate and methylcobalamin directly address dysfunction in methylation pathways. Second, it is important to adopt appropriate lifestyle habits to down-regulate epigenetic expression of MTHFR mutations.


The two most common supplements used to treat MTHFR mutations are methylfolate and methylcobalamin, both of which are methylated forms of B vitamins. The forms of these B vitamins found in typical multivitamins and supplements are not methylated. It is important to choose methylated forms to ensure adequate absorption and utilization.


As more and more research emerges on treating MTHFR mutations, the benefits of methylfolate supplementation becomes increasingly obvious. Methylfolate is the most active form of folate in the body. By taking methylfolate, the body is able to bypass any methylation defects affecting folate metabolism. This means the negative health effects of MTHFR mutations are lessened. If you have MTHFR mutations, you should strongly consider taking methylfolate supplements.

Dosing requirements for methylfolate vary from person to person. Homozygous mutations often increase methylfolate requirements compared with heterozygous mutations. A good strategy is to start with a modest dose and monitor how you feel as you increase the dose every few days.

It is also important to consider the form of methylfolate you take, as some forms are much more bioavailable than others. Metafolin and Extrafolate-S are two highly bioavailable forms. That’s not to say other forms won’t work, but you may need to take at least twice as much of other forms to have the same benefit. Here are a few options that contain either Metafolin or Extrafolate-S:

Solgar Folate (as Metafolin), 800 mcg

Thorne Research 5-MTHF (as Extrafolate-S), 1 mg

Thorne Research 5-MTHF(as Extrafolate-S), 5 mg


Methylcobalamin, or methyl-B12, is an important complement to methylfolate. This is due to vitamin B12 acting as a cofactor for folate in the body. Taking the methylated form of both vitamins allows them to act in a synergistic manner. This will also help to ensure you have a balance of these two important vitamins. When choosing a methylcobalamin supplement, the main thing to look out for are artificial colors, flavorings, and sweeteners. Here are two good options from Jarrow that contain only natural flavoring, no added coloring, and are naturally sweetened with xylitol:

Jarrow Formulas Methyl B-12, 1,000 mcg

Jarrow Formulas Methyl B-12, 5,000 mcg


While methylfolate and methylcobalamin play a big role in MTHFR treatment, they are not the only pieces to the puzzle. It is also important to understand the role of epigenetics. Epigenetics looks at how environmental factors influence gene expression. In other words, if you lead a healthy lifestyle, you can minimize the expression of MTHFR mutations. Two good resources for learning how to lead a healthy lifestyle are
Cold Dark Keto: Winter Simulation for Optimal Health by Steven Thomas and The Primal Blueprint by Mark Sisson.


The treatment of MTHFR mutations is multifaceted. The first step is to correctly identify which mutations are present. Once the mutations are identified, utilization of methylated forms of folate and vitamin B12 are primary treatment options. Dosing requirements will vary from person to person, so careful monitoring of supplementation response is important. Finally, addressing epigenetic problems may alleviate symptoms by down-regulating MTHFR gene expression.

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Disclaimer: The information on this website is for educational purposes only. It is not intended to be used in place of treatment or advice from a medical professional, nor is it intended to diagnose, treat, or prevent any disease or condition. Always seek the advice of your physician or other qualified healthcare provider before making any significant lifestyle changes or taking any supplements.