So you have one of the common MTHFR mutations and are not sure how to start supplementing. You went online to find out what to take and read that taking folic acid is a good idea. We are here to tell you it’s NOT. Check out our article “Using Folic Acid Supplements In Fertility Treatments” for an overview. Once you are up to speed on folic acid, take a look at where it enters the folate cycle in the graphic below.
You can see folic acid entering the folate cycle right at the beginning. It’s the first molecule setting the folate cycle in motion, but it’s not the best molecule to start the process of folate metabolism. This type requires an extra metabolic step, that is slow and inefficient, before entering the folate cycle where naturally occurring folates do.
Folic Acid Vs. Natural Folates
Folic acid is a synthetic form of folate (vitamin B9) that are made to be more chemically stable. It is made to be more stable than naturally occurring folates because they are not broken down during the manufacturing process as much. Companies can get folic acid to the shelf a lot easier than they can get naturally occurring folates. The companies want to make as much money as possible so they market and sell synthetic product over naturally occurring folates. Extracting, processing and storing naturally occurring folates is difficult and expensive. Many of the folates at the beginning of the manufacturing process end up breaking down, rendering them useless. Folic acid was the first form of folate available but in recent years the active forms are now able to be put in supplements.
Dihydrofolate Reductase (DHFR)
The dihydrofolate reductase (DHFR) enzyme breaks down folic acid and natural folates into tetrahydrofolate (THF). Taking folic acid can reduce your ability to metabolize naturally occurring folates you are getting through your diet. The graphic shows DHFR acting slowly on folic acid and fast on dietary folates. This is because it is made to be a more stable molecule compared to non-synthetic forms of folate. The chemical stability and slight change in shape of folic acid compared to natural folates, make it difficult for DHFR to use/metabolize. The reaction takes much longer to happen because the chemical structure of folic acid is resistant to metabolism by DHFR.
There are a limited number of DHFR enzymes available for metabolizing folic acid and dietary folates. When most of the folates in your diet are coming from synthetic supplementation or from foods fortified with folic acid, the DHFR enzymes are busy trying to metabolize folic acid instead of naturally occurring folates.
The DHFR enzyme itself can only metabolize 200 mcg of folic acid per day. If you are getting over 200 mcg of folic acid through supplementing and/or from fortified foods, the DHFR enzyme is going to be inhibited. This causes a build of folic acid and folates at the beginning of the folate cycle within the body. The build-up of folic acid is called un-metabolized serum folic acid or UMFA for short.
For more information about UMFA read our article Folic Acid: What Happens When You Have Too Much?
Take Aways and MTHFR
Too much folic acid in your diet from fortified foods, or taking folic acid supplements, is going to reduce your ability to metabolize folates you are getting from your diet. It is best to stay away from foods fortified with folic acid when you can and eat more food with high levels of naturally occurring folates. Since folic acid will build up in the folate cycle, there will be less folate making it through the final stage of the cycle which requires the MTHFR enzyme. If you have an MTHFR mutation, you know your MTHFR enzyme has a 20-70% loss in function when converting 5,10-methylene-THF to 5-MTHF. Including folic acid in your diet or supplement makes the entire folate cycle even less efficient! You need to avoid taking folic acid and adopt a diet full of natural folates, especially if you have an MTHFR mutation! Here you can find out the Top 20 Folate Containing Foods.
For some people, a consistent and high folate diet may be difficult. If you are worried about not getting enough folates, there are better ways to get folates through supplementation than through a synthetic method, check out our Guide To Folate Supplementation.
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