• Nancy Mullan, MD

MTHFR C677T And The Many Forms Of Folate

Updated: Jan 23

It takes a specific form of folate to bypass an MTHFR C677T mutation. 

The folic acid in many vitamins is a synthetic form of folate. It does not bypass an MTHFR C677T mutation. Taking low dose folic acid is not toxic for people with MTHFR mutations because it is useful for other reactions in your body, but It does not aid in methyl group production.

Folic acid is more stable than the other forms of folate in your body, which is good, because folate is actually a chain of glutamate molecules. When it breaks down, it breaks down into glutamate, which is an excitatory neurotransmitter that may give you symptoms. Folic acid breaks down into fewer molecules of glutamate than other forms of folate, so it has less chance of over exciting your nervous system than other folates. 

Another frequently recommended form of folate is folinic acid. Folinic acid functions in the folate cycle at 11:00 on the way to making tetrahydrofolate at 12:00 in cycle 3 of the methylation pathway below. It is also called 5 formyl tetrahydrofolate and is the main ingredient in Leucovorin, a very high dose pharmaceutical form of folinic acid used for patients undergoing chemotherapy. It is also given to people with an MTHFR C677T mutation because it does change into the form of folate that helps make methyl groups, but it takes a number of other cofactors and biochemical reactions to make that change. I am simplifying folate biochemistry to an almost absurd degree here in order to make it understandable.



An MTHFS mutation impacts the ability of folinic acid to move along its biochemical pathways. This is a different mutation from MTHFR. If you have an MTHFS mutation, high dose folinic acid administration may increase folinic acid too far, compromise your production of tetrahydrofolate, reduce your ability to make the building blocks for DNA and RNA, and increase your glutamate to excessive levels from the breakdown of excessive folinic acid. It is better to supplement the folate pathway in a balanced fashion rather than high dose one component such as folinic acid/Leucovorin.

5 methyl tetrahydrofolate (5 MTHF) is the only form of folate that bypasses the block in methyl group formation that occurs from an MTHFR C677T mutation. 

The sticking point is at 8:00 in cycle 3 in the methylation pathway. The MTHFR enzyme is supposed to convert 5, 10 methylene THF into 5 MTHF. But 48 % of the population has a mutation in the MTHFR gene that makes a weakened enzyme. 12% of the population has two mutations at MTHFR that generates a much more weakened, unstable enzyme. And when you combine the MTHFR mutation(s) with non-optimal genetics in the other parts of the methyl group producing pathway, you are at the gateway to real health problems.

I have talked in many places about the major health impacts of methyl groups. Most recently you can find this information in my e book, The Methyl Group, What It Can Do for You. You can get this free download by clicking here.

The impacts of MTHFR mutations and related issues in the methyl group producing pathway can be serious and far reaching. Do not leave your health in the hands of someone who knows little or nothing about this issue. If you have an MTHFR mutation, you will not react normally to drugs, your immune system will be impaired, and you may have depression or other neurological issues. If your doctor is ignorant of the many impacts of this mutation, it will not go well for you.

Get an Exploratory Conversation. This is 30-minutes with me in which I will listen to your health issues, review your recent test results, and make recommendations about what I think you should do. It will clear up any confusion you have about which direction is up, which supplements you should start first, and what you can expect. 

The fee for this service is $129. It is easy to set a time for one soon, and it can save you weeks or months of doing the wrong thing, lurching around in the dark with a clinician who isn’t easy to reach or who doesn’t know that much about the genetics or biochemistry of MTHFR. Whether you have one or two mutations, you may be dealing with conditions in your body that are confusing and difficult to understand. You can cut through all of that and get clarifying input that gives you hope and moves you in the right direction.

I look forward to being able to help you, Dr. Mullan


What people like you are saying about Dr. Mullan’s work:

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Thank you so much, Dr. Mullan. Thank you so, so much for everything you do. MS

Wow! I have to tell you, this was such an uplifting session. It’s so nice to hear good news, especially about a child. Anxiety, OCD and a host of other mental/psychiatric symptoms have been a huge hurdle for me. So to hear this story of all those awful symptoms totally going away is such a bright light for me!!!! TR

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