If you have a history of recurrent miscarriage or failed IVF cycles, there is a good chance that a genetic variant in the MTHFR gene is one contributing factor. The MTHFR gene encodes an enzyme that converts other forms of folate to the biologically active methylfolate. If you have one of several common variants in this gene, you may not be able to efficiently convert folate from food or supplements into methylfolate, creating a deficiency in this important vitamin.
Researchers have known for many years that MTHFR mutations are a common culprit in women with recurrent miscarriage. A study published in May 2016 also found that MTHFR mutations are much more common in women with failed IVF cycles and chromosomally abnormal embryos. (To find out whether you have one or more variants, your Doctor can order an MTHFR blood test or you can order DNA analysis yourself through 23andme and have the data analyzed through the free website Genetic Genie.)
How Do MTHFR Mutations Contribute to Infertility and Miscarriage?
Folate plays an essential role in the production of DNA and in detoxification. Both functions are absolutely critical to early embryo formation. If you have a genetic variant that compromises your ability to produce methyl-folate when needed, toxins such as homocysteine can accumulate. High homocysteine and low folate appears to increase the risk of chromosomal abnormalities in embryos. These abnormalities are the primary cause of early miscarriage and failed IVF cycles (read more on miscarriage and chromosomal abnormalities here). High homocysteine may also contribute to miscarriages by raising the risk of blood clots, although this is more controversial and some studies have found no effect.
To solve these problems, the first step is to supplement with more folate, in order to support DNA production and the detoxification of homocysteine.
Folate Supplements for MTHFR Mutations
In years past, those with MTHFR mutations and either a history of miscarriage or neural tube defects were advised to take 4000 micrograms of synthetic folic acid to get around impaired folate metabolism. It is now clear that a better approach is to supplement directly with methylfolate. Those with MTHFR mutations typically need at least 800 mcg per day of methylfolate.
Troubleshooting Methylfolate Supplements & Side Effects
The only problem with supplementing directly with methylfolate is that it can sometimes cause side effects such as mood changes and joint pain, particularly when taken in higher doses and if vitamin B12 is low.
If you are taking a prenatal that contains 800 mcg or more of methylfolate and find that it bothers you, consider switching to a multivitamin that contains 400 micrograms of methylfolate (such as Thorne Basic Nutrients 2/day), and then add 400 to 1200 micrograms of folinic acid and perhaps some additional vitamin b12.
Folinic acid is another form of folate that is naturally found in foods. It is more readily converted to methylfolate than synthetic folic acid. I recommend Seeking Healthy Folinic Acid Lozenges, which come in two versions: one with hydroxo B12 and one that is folinic acid alone. Another good quality product is Kirkman Labs Folinic Acid
The Bottom Line
Most people will not have any problems with a prenatal containing 800-1000mcg of methyl-folate, and chances are if you have an MTHFR variant, you may actually start to feel much better overall. You will also be taking an important step towards getting pregnant more quickly and preventing miscarriage.
Recommended prenatals containing methylfolate include:
There are of course many other strategies to further improve fertility and reduce the risk of miscarriage for those with MTHFR mutations, as I explain in It Starts with the Egg.
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