What is the MTHFR Mutation?

The MTHFR Mutation is found throughout the population in the United States. However, many people are asymptomatic (without symptoms). If you suffer from depression, anxiety, difficulty focusing, or poor memory, you may be one of the people that are symptomatic from this enzyme mutation. Also, if you have high levels of inflammation or homocysteine (hyperhomocysteinemia), you may need to supplement L-methylfolate. The MTHFR enzyme is found throughout your body, and its functions include:


  • Anti-inflammation / anti-oxidation
  • Detoxification of heavy metals
  • Production of neurotransmitters in your brain

Why should I take L-methylfolate?

The MTHFR Enzyme converts folic acid, or folate, into its active counterpart L-methylfolate. If you have a mutation in the enzyme, you are not able to produce as much L-methylfolate as your body needs. By taking activated folic acid as L-methylfolate, you bypass the MTHFR Mutation (see graphic to the left). L-methylfolate is used to create neurotransmitters which may improve your depression, anxiety, or focus problems. It probably will not “cure” you and allow you to stop your medications. However, you may notice that you can take less medicine for depression or ADD. You may notice that you have less mood swings, irritability, flares, or the severity of illness will decrease. You may notice that you have more energy now that your brain is not struggling to create neurotransmitters. When your brain is depleted of neurotransmitters, you are more likely to develop low energy levels because you require more effort to perform your normal daily functions. With the MTHFR Mutation, you will not be able to detoxify mercury or other heavy metals as well. The Glutathione pathway which detoxifies heavy metals requires adequate L-methylfolate in order to regenerate its ability to detoxify. In other words, glutathione can detoxify 1 atom of mercury, but it requires a reset to detoxify more atoms. Without L-methyfolate, it cannot reset the pathway thus allowing mercury to build up.

Why should I avoid Folic Acid (folate) in my supplements?

If your MTHFR enzyme is mutated, and you have the MTHFR deficiency, you will want to avoid folic acid (aka folate) in your dietary supplements. Folic acid competes with L-methylfolate to gain entrance into the brain. The blood brain barrier is an important barrier that prevents toxins and bacteria from entering the brain. It also regulates which nutrients and vitamins get into the brain. There is only one transporter for both folate and L-methylfolate. The 2 nutrients compete for access into the brain. If you take extra folic acid, then your brain cannot adequately absorb the L-methylfolate since it is being blocked by the extra folic acid.

You should look at all of your vitamins and supplements (especially your multivitamins) in order to look for folic acid. You want to avoid folic acid supplementation because it may make your symptoms worse. We have a multivitamin with methylated folic acid available in our office from PURE. The multivitamin is called O.N.E. Please see our supplement list for pricing

If possible, you should also avoid folic acid reducing medicines like Methotrexate, Birth control, and antacids (like omeprazole, zantac, tums, Rolaids).

Many foods contain folic acid, but you only need to avoid foods that are fortified with folic acid, or folate. You do NOT need to avoid foods naturally containing folic acid. The dosage in food is not high enough to affect the absorption across the blood brain barrier.

What are the differences between the mutations?

Each mutation to the MTHFR enzyme has different severities. You get 1 gene (or allele) from each of your biological parents. Getting 1 bad and 1 good allele is not as severe as 2 bad alleles. If you have 1 of each allele, you are a heterozygote for the mutation. However, if you have 2 bad alleles, then you are a homozygote for the mutation. Being a homozygote is the most severe mutation. We grade mutation severity by the amount of L-methylfolate that they produce.

What dose of L-methylfolate should I take?

You should take whichever dose of L-methylfolate was suggested to you by your healthcare provider. There are some general recommendations below if you do not remember which dose was suggested for you. If you are currently taking the over the counter supplement and want to try the prescription, please call or come by the office. Sometimes we have samples available for you.

Heterozygotes without symptoms (C/T or A/C):

If you are a heterozygote (see above) and do not have any of the symptoms mentioned above, then you should take the over the counter supplement of L-methylfolate. The dosage we recommend is 1mg (or 1,000mcg) daily. We have this supplement available for purchase in our office. Please visit our supplement page for pricing. You can also get this over the counter at most drug and nutrition stores. Please do not buy low quality, cheap supplements as these will contain less active ingredient and more “filler” that is not the actual active ingredient.

Heterozygotes with symptoms (C/T or A/C): If you are a heterozygote and have symptoms of inflammation, fatigue, depression, anxiety, or difficulty focusing, then you should take the prescription strength L-methylfolate which is called Deplin. As a heterozygote with symptoms, you are in the same category as Homozygotes. Please read the Homozygotes section for more details below.

Homozygotes (T/T or C/C): If you have 2 bad alleles, you will need to take the prescription strength methylated folate (or L-methylfolate) which is brand named Deplin. You should take Deplin 15mg one tab per day for 3 months in order to rebuild your neurotransmitter stores. After 3 months, you can decrease your dose to 7.5mg daily. You can decrease your dose to 7.5mg daily in 3 different ways:

1. Ask for a prescription of Deplin 7.5mg capsules.

2. Cut your Deplin 15mg tablets in half. (Note: Deplin now comes in capsules, and you cannot cut capsules in half)

3. You can take Deplin 15mg every other day. This method is not as effective, but it is a good way to save on cost.

People who are homozygotes need to avoid folic acid in foods more than heterozygotes. 

How long do I need to take L-methylfolate?

Since the MTHFR Mutation is a genetic mutation and you cannot change your DNA, you will need to take this medicine for the rest of your life if it is benefitting you.

How much does L-methylfolate cost?

There are different doses of L-methylfolate and each dose costs different amounts.

Over the Counter L-methylfolate: The over the counter dosage of 1mg or less will depend where you get the supplement.  We have this supplement available for purchase in our office.  Please visit our supplement page for pricing. 

Deplin or Prescription Strength L-methylfolate: Deplin is usually more expensive at local pharmacies, so we have shopped around for the cheapest price for you. Currently, we are suggesting that you get Deplin from Brand Direct Health which is a mail order pharmacy in Mandeville, Louisiana (see contact information below). We will send your prescription to them electronically, and they will call you to get your insurance and payment information. If you get a call from a 985 area code, it is probably them.

Brand Direct Pharmacy 
68397 Tammany Trace Drive
Mandeville, La 70471
Phone: 1-866-331-6440 Fax: 1-866-227-5928
Email: [email protected]

Where can I get L-methylfolate? 

As discussed in the above question, you can get L-methylfolate from us at Austin Family Medicine Associates, many drug and nutrition stores, but you can only get prescription strength from pharmacies. Also please contact us if you have any questions about the MTHFR Mutation.

Read our latest MTHFR blogs here.