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Folate, Folic Acid and Methylfolate: Why the Difference Matters

Ovaterra

Last updated: January 3, 2023

Methylfolate, folate and folic acid are all different forms of Vitamin B9. The terms are often used interchangeably, and they play a crucial role in the baby's brain development in utero. A sufficient folate level helps prevent neural tube defects, a group of common birth defects. However, there are some important differences between the three forms of folate. In honor of the National Birth Defects Awareness Month, we do a deep dive into this key prenatal nutrient. Let's start with the differences between methylfolate, folate and folic acid.

 

Folic acid is a synthetic form of folate

Folate is the generic name for various natural forms of Vitamin B9. Folate is found in foods like green leafy vegetables, beans and legumes. Folic acid, on the other hand, is a synthetic form of Vitamin B9.

Manufactured through chemical processes, folic acid is added to various foods, including pasta, bread and cereal in order to help prevent neural tube defects in general population. Many countries, including the US, mandate folic acid fortification of these foods to reduce Vitamin B9 deficiency. Folic acid has its merits, which we outlined in this post.

 

Methylfolate is the active form of folate

There is another important difference in the different forms of Vitamin B9: Active vs. inactive. Methylated form of folate, called methylfolate, is considered the “active” form of Vitamin B9. This is the natural folate that does all the crucial work in the body (which we’ll get to shortly).

Folic acid from fortified foods and many supplements, as well as food-derived natural folate, need to be converted in the body first into methylfolate before it can support the baby's brain development.

 

Folate drives DNA and protein synthesis

Folate is a coenzyme in a few key metabolic processes.

In one, folate works with Vitamins B6 and B12 to produce proteins, which in turn reduces the amount of homocysteine in the body. There is some evidence, found in mostly small studies, that homocysteine levels may impact reproductive health in both men and women. For example, a lower level of homocysteine is a favorable factor in egg maturity and embryo quality and may be associated with a better chance of pregnancy.

Another important role of folate involves the synthesis of DNA and RNA, crucial during cell division, including maturation of eggs and sperm.

 

 

Folate supports baby’s brain development in the first trimester

Folate is extremely important during the early stages of pregnancy: Along with a few other nutrients that supports the baby's brain health, folate drives the brain development of the growing baby. A healthy level of this B vitamin helps prevent neural tube defects, which are some of the most common, preventable types of birth defects.

Though results a still inconclusive, several studies have also suggested a correlation between maternal folate level and cognitive functions of the baby after birth. 

The baby’s brain starts developing very early in the pregnancy and the mom’s need for folate jumps by 50% during this period. Because this happens before many women realize that they are pregnant, doctors recommend that women start taking prenatal vitamins with folate 3 months before they start trying.

 

So, is folate better than folic acid?

While most fortified food items use folic acid, some prenatal vitamins use methylfolate, the active and natural form of folate. Should you choose prenatal vitamins with methylfolate over folic acid? Not all doctors agree on this question, but the answer may depend on your genetics.

We noted earlier that folic acid needs to be converted by the body into methylfolate to work. Women with some generic variations of a gene called MTHFR (methylenetetrahydrofolate reductase) have a hard time with this conversion process. This means two things:

  • Women with these MTHFR gene variants may not get enough methylfolate to support egg development and baby’s brain health, even when they take prenatal vitamins with folic acid that meets the generic daily values (DV).
  • They can also end up with more than the normal amount of folic acid accumulating in the blood. There have been some reports of adverse effects of excess folic acid. While study results are mixed and causal relation hasn’t been established, it may be a concern for women with the MTHFR variants that affect folic acid metabolism. 

It's important to note here that most studies on neural tube defects have been done on folic acid, and studies comparing the birth outcomes between folic acid and folate are scarce. Because of that, some doctors and government bodies (including the CDC) simply recommend folic acid to all women, regardless of the MTHFR status.

However, taking prenatal vitamins with methylfolate does let you circumvent the folic acid conversion process and helps you avoid folate insufficiency, whether you are affected by an MTHFR gene variant.

 

Up to 25% of women have two copies of MTHFR gene variant

The most prevalent MTHFR gene variant, called C677T, is very common. In the US, up to 25% of Hispanic women have two copies of this variant. The rate is lower for Caucasian women at 10-15% and African American women at 6%. More women – 40 to 60% by some estimates – have one copy of this variant, where the effects on folic acid conversion is less severe.

 

Should I take a MTHFR test to decide methylfolate vs. folic acid?

To know whether you have a MTHFR genetic variant, you’ll need a genetic test. However, since the consequence of folate insufficiency during pregnancy – your baby at an elevated risk of neural tube defects – is significant, and the gene variants are relatively common, you may decide to go for methylfolate without taking a genetic test. If you do want to know first, your doctor can order one. You also have the option of taking an at-home MTHFR gene test.

 

The takeaway on folate vs. folic acid

  • Taking prenatal vitamins with 800-1,000 mcg of methylfolate will help you maintain an adequate level of folate to support the baby’s brain development, regardless of your MTHFR gene status. If you take folic acid instead, also aim for 800-1,000 mcg per day.
  • However, prenatal vitamins that use methylfolate tend to be more expensive than those that use folic acid – partly because prenatals that use methylfolate also use other higher-quality ingredients.
  • So, if cost is a concern, you may want to take a MTHFR gene test, then decide which form of folate to add to your preconception and prenatal supplement routine.
  • Also, make sure your choline intake is sufficient (450 mg/day when pregnant and 550 mg/day when nursing). 90-95% of women are deficient on choline, and it’s another key nutrient for the baby’s brain development. More on choline’s role in baby’s brain health here, and there are a few other prenatal vitamins and minerals not to miss for the baby's brain development.

 Please reach out with any questions. We are with you.

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