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Women all over the world get folic acid supplements in early pregnancy to prevent birth defects. But are they getting the right forms of the vitamin they need?

Eighty years ago scientists thought that folic acid, also known as vitamin B9, just might be a miracle drug. For about a decade, some researchers had thought that anemia and folic acid deficiency were the same disease. That wasn't quite right, but in 1931, researcher Lucy Wills discovered that folate (the form of vitamin B9 found in food) could reverse anemia in pregnancy [1]. In 1941, a group of scientists was able to extract vitamin B9 from spinach leaves ("foliage," giving the compound the name folic acid) [2]. In the 1960's scientists concluded that folic acid was essential for preventing neural tube defects (such as spina bifida) and cleft palate in newborns (although it's not just a deficiency of folic acid that causes these problems), and governments all over the world started requiring folic acid to be added to food.

In 2017, there is a long list of countries that require addition of folic acid to at least one form of grain: Antigua and Barbuda, Argentina, Australia, Bahamas, Bahrain, Barbados, Belize, Benin, Bolivia, Brazil, Burkina Faso, Cameroon, Canada, Chile, Colombia, Costa Rica, Cote d'Ivoire, Cuba, Dominica, Dominican Republic, Ecuador, Egypt, El Salvador, Fiji, Ghana, Grenada, Guatemala, Guinea, Guyana, Haiti, Honduras, Indonesia, Iran, Iraq, Jamaica, Jordan, Kazakhstan, Kenya, Kosovo, Kuwait, Kyrgyzstan, Liberia, Mali, Mauritania, Mexico, Morocco, Nepal, Nicaragua, Niger, Nigeria, Oman, Palestine, Panama, Papua New Guinea, Paraguay, Peru, Republic of Moldova, Rwanda, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Saudi Arabia, Senegal, Sierra Leone, Solomon Islands, South Africa, Suriname, Tanzania (United Republic of), Togo, Trinidad and Tobago, Turkmenistan, Uganda, United Kingdom, United States of America, Uruguay, Uzbekistan, and Yemen [3]. However, if you live in Russia, or in China, or in Japan, or in the European Union (other than the UK), there isn't any artificial folic acid added to your food. Why does that make a difference?

It turns out that folic acid, the form of the vitamin that is added to food, can't be metabolized very well by women who have something called an MTHFR mutation.  Whether or not they know they have it it by having an MTHFR gene test, these women don't really benefit from the folic acid that gets dumped into food. They need a different form of the vitamin called methylfolate for baby's optimal health. [4]

Why Should You Avoid Vitamin-fortified Foods If You Have MTHFR Mutation

Don't be horrified if you haven't been taking folic acid. Things will probably still turn out alright. But start taking methylfolate and avoiding vitamin-fortified foods as soon as you can. Here's why:

  • Your body can't use folic acid (the synthetic compound) or folate (the form of the vitamin found in food) without first converting it into an activated form called methylfolate. This requires an enzyme called methylenetetrahydrofolate reductase, or MTHFR. Many women (and men) carry one or both of two mutations that cause a tiny change in the structure of the enzyme so that it doesn't work efficiently. [5] For them, just taking any old vitamin supplement doesn't do a lot of good.
  • What scientists know is that more methylfolate goes into cells than folic acid [6]. In women who have the MTHFR mutation, folic acid gets "parked" outside cells because they can't absorb it, so it stays in the bloodstream. You'll get a better lab test (higher folic acid numbers) [7], but a smaller benefit.
  • At least one study has found that methyfolate is likely to prevent miscarriage [8].
  • Scientists also know that women who get methylfolate instead of folic acid during pregnancy are less likely to have anemia after they give birth [9]. There was a time, when diets were generally poorer for women all over the world, that many new mothers died from anemia not long after having their babies.

Is Methylfolate Better At Preventing Birth Defects Than Dolic Acid? 

Scientists aren't quite as sure that the vitamin supplement methylfolate does a better job of preventing birth defects than folic acid.

That's because it's not a "folic acid deficiency" that is the culprit in birth defects such as spina bifida and cleft palate.

The trigger for these birth defects is the accumulation of homocysteine, a natural substance that becomes inflammatory when it accumulates to high levels.

To regulate homocysteine, your body needs activated folic acid, but also activated pyridoxine (vitamin B6) and methylcobalamin (vitamin B12).

No research team is going to run experiments depriving women of selected vitamins just to see if one is more important than another, so the best guess is that methylfolate probably does a better job of preventing birth defects than folic acid.

But one thing methylfolate does that ordinary folic acid cannot is it allows a vitamin B12 deficiency (which can also cause birth defects and anemia) to be spotted sooner [10].

Advice to take home 

It's not hard to get the prenatal vitamins a mother really needs. Folic acid is extremely cheap, but methylfolate won't break the bank. A month's supply costs less than US $10.

Simply start taking methylfolate and avoid "fortified" grains and flours and bakery goods.

It doesn't hurt to take the "right" forms of vitamins B6, usually labeled PLP (pyridoxal 5'-phosphate, which distinguishes it from pyridoxamine, pyridoxal and pyridoxine and their phosphate esters), and B12 (methylcobalamin), too. They just might make the critical difference that protects your baby from birth defects. And you may feel a lot better that you otherwise would after your baby is born.