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The Importance of Folate in Pregnancy

You may have heard that it’s important to get enough folate in pregnancy. Actually, it’s important even before a woman finds out she’s pregnant! Like many other nutrients, a woman’s folate needs increase in pregnancy. While some women gladly up their intake and/or take prenatal vitamins without any question, sometimes people want to know WHY this is important. It’s actually pretty cool, so let’s discuss.

Oh, and by the way, if you want a handy cheat-sheet that tells you all the important nutrients in pregnancy (including folate), how much you need, and foods to find them in, check out my  FREE Pregnancy Nutrient Cheat Sheet!

Warning: Science Ahead!

Nutrition for a healthy pregnancy includes making sure to get enough folate. This post delves into the science that explains why folate in pregnancy is important, and also talks about how to get it!

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This post might get a little more science-heavy than you’re used to, but I’ll do my best to not make it boring!

Folate vs Folic Acid

Something I should probably mention right off the bat is that folate and folic acid are NOT actually the same thing! Folate is naturally found in food sources such as egg yolks, liver, and leafy green vegetables. Folic acid is a synthetic supplement, which actually is more bioavailable than food-derived folate. (Please do not get the idea that supplemental folic acid is somehow a bad thing simply because it’s not “natural.” The opposite is actually true.)

Dietary folate from a mixed diet is estimated to be about 50% available (meaning you only actually absorb half of what you take in), while folic acid from supplements or fortified foods is 100% available. If folic acid and dietary folate are consumed together, the availability is about 85%.1 Folic acid in supplements and fortified foods is in the most stable form of the vitamin too. Folate in food is unfortunately subject to potential loss by cooking, heat, oxidation, and UV exposure.1 Thus, folic acid is a more dependable method of ensuring adequate intake.1,2

I will use the term folate throughout most of the article, for the sake of simplicity.

What does Folate do?

Folate is a B vitamin, specifically B9. It’s an essential vitamin, meaning we don’t make it in our own bodies, we MUST get it from food or supplements. It is required for lots of different metabolic and bodily processes, even when we’re not pregnant.

One of its key functions is in methylation reactions, something that is important for amino acid metabolism and the synthesis of purines and pyrimidines2 (if you’re wondering what on earth those are, they are components of DNA). Hence, folate is pretty darn important!

Most of us have heard of iron deficiency anemia, but did you know that anemia can also happen as a result of folate deficiency?

Inadequate folate leads to inadequate production of the above DNA components, which impairs the creation of DNA in the cells that make red blood cells (RBCs). Having funky RBCs means a decreased ability to transport oxygen, and subsequent anemia.1,2 Not fun!

But that’s not really pregnancy-specific is it? Sure, the potential anemia that can result from low folate is a concern when pregnant since our blood volume increases quite a bit during pregnancy. But that’s not actually the main reason folate is important.

The biggest reason folate is imperative in early pregnancy is to prevent a specific group of birth defects, known as neural tube defects, or NTDs.

If that sounds pretty scary, yes, it can be.

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A little bit of baby-growing background:

Before we can talk about these defects, I think it’s important to talk about normal development first. This is the super simplified version of what is supposed to happen:

Around the third week of early prenatal development (right about the time you might find out you’re pregnant), a group of cells within the embryo forms what is called the notochord. One of the notochord’s functions is to direct the development of the brain and spinal cord. It does this by directing the nearby cells to develop into what is called the neural plate. The edges of the neural plate, called the neural folds, start to rise up and come together, forming what’s known as the neural tube.

The formation of the tube (or closing of the neural folds) begins near the middle of the embryo and progresses outward toward the head and tail ends. (Think of a cannoli or taco shell – when you bring the edges together to form a tube, the middle parts meet first.) The cells of the resulting neural tube eventually differentiate into the brain and spinal cord3.

Neural Tube Disorders: When things go awry

NTDs result when the above process does not happen correctly and the neural tube fails to close properly. The most common NTDs are spina bifida and anencephaly.

If the end of the tube closer to the head end of the fetus does not close properly, the brain and skull do not develop correctly and anencephaly occurs.4 Since the brain is missing in these cases (anencephaly literally means “without brain”), this condition is fatal and the infant typically dies before or shortly after birth.

If the other end of the neural tube, closer to the tail end of the fetus, fails to close properly, spina bifida results. There are varying degrees of spina bifida. In all cases, the vertebral arches (bones) of the spinal column fail to close correctly. The mildest form, occult spina bifida, causes no clinical symptoms. In the more severe forms, the opening where the arches failed to close is big enough that stuff starts to protrude out and create a cyst. In the worst case, the actual spinal cord is included in the cyst, which obviously causes severe neurological dysfunction as a result of the exposed nerve tissue.4

The reason folate in pregnancy (and folic acid) is so important is because it can go a long way in preventing these devastating defects!

Now, I have to tell you that it’s still unclear exactly how or why the tube fails to close. It appears that there are both genetic AND environmental factors involved. If we don’t fully know why it fails to close, we also don’t know exactly why folate/folic acid prevents that from happening. However, we DO know that folate and/or folic acid supplementation can reduce the risk of NTD development, since it has been shown over and over again in research.

So now, further research is sort of working backwards in order to determine why this is the case. Currently, the leading hypothesis is known as the Methylation Hypothesis. Methylation appears to be important in preventing NTDs for a few reasons, one of which is related to epigenetics.

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Epi-what? What’s Epigenetics?

In a nutshell, epigenetics is an alteration of the expression of our genes, without any underlying mutation of the genes. Basically, genes can be turned “on” or “off” by various mechanisms.5 One of those mechanisms is methylation, or the attachment of a methyl group at specific locations in the DNA.

After fertilization, the DNA of the embryo quickly demethylates (methyl groups detach), and this causes the cells to have all genes potentially active. The DNA then undergoes re-methylation in certain sequences. The sequence or order by which re-methylation occurs appears to be associated with the eventual structure and function of the resulting tissues.5

Therefore, if the methylation of the embryo’s DNA gets messed up, it can negatively affect the development of the tissues.

However, impaired methylation does not appear to be solely responsible for NTD occurrence since genetic factors still appear to play a major role. “Folate-deficiency can, however, exacerbate susceptibility in embryos that carry a genetic predisposition to NTDs.”5

Three ways to be deficient in Folate:

  1. Deficient folate leads to fewer purines and pyrimidines (DNA building blocks): Fewer nucleotides means a decreased ability to synthesize DNA. That’s not a good thing when you’re building a human! We need to make sure we get enough folate/folic acid so that we’re making DNA and able to methylate DNA as well.
  2. Defective folate metabolism: There is a key enzyme, known as MTHFR (which I pronounce in my head as “mother effer”, haha! I can’t possibly be the only one who does this….), which is critical in folate and folic acid metabolism. Mutations in the gene that codes for this enzyme decrease the ability to metabolize folate/folic acid appropriately, which leads to interference in DNA methylation.2
  3. Lack of folate absorption due to deficiency or inhibition of receptors. Not being able to absorb the folate or folic acid you take in will leave you deficient in folate even if you think you’re getting enough. Two main reasons this can happen are taking folate-antagonist medications when pregnant, or having folate receptor auto-antibodies.6

*Only one of the things above is within our direct control: getting enough folate.

Things like genetic mutations that affect folate receptor antibodies or metabolism, are outside of our control and also things a woman is very unlikely to know she has. Thankfully, most women will not need to worry about them! Dealing with them is also certainly beyond the scope of this blog post. If you’re concerned about the possibility of having those issues, talk with your doctor! What we’re talking about here is focused on ensuring women get enough folate/folic acid in their diet or supplements, not differences in genetic traits.*

Getting your folate and/or folic acid:

So it’s pretty apparent by now WHY folate/folic acid is so important in pregnancy, right? Since neural development happens so early in the process, it’s important that we get adequate folate/folic acid BEFORE pregnancy as well.

The general consensus is that 50–70% of NTDs can be prevented with folic acid supplementation.7

This is why there are supplementation recommendations that have been in effect since 1992. For most women, the recommendation is 0.4mg (400micrograms) of folic acid supplementation per day.However, if a woman has already had an NTD-affected pregnancy, the recommendation is 4mg per day to prevent recurrence.

Like most nutrient recommendations though, it turns out women tend to ignore them or not even know they exist, which is why the government started mandating fortification of certain foods with folic acid back in 1996. It seems to be helping. Some estimates are as high as a 70% reduction in NTD occurrence since fortification began.7

The Recommended Dietary Allowance (RDA) for folate is done in Dietary Folate Equivalents (DFE). “One DFE is equal to 1mcg of food folate, 0.6mcg of folic acid from a supplement or fortified food consumed with a meal, or 0.5mcg of folic acid from a supplement taken without food (empty stomach).”1

For pregnant women, the RDA is 600DFE, with 400mcg coming from supplemental folic acid.

Okay, so what do I do?

If you’re thinking about becoming pregnant, start paying attention to your folate intake now. Since it is important so early in pregnancy, it is important that folate is already adequate by the time development starts. It can be difficult to ensure adequate folate (food) intake due to the losses that can occur from cooking and other factors. Thus, it is recommended that pregnant women, and women looking to become pregnant get 400mcg of folic acid, either in supplement form, or from fortified foods like breads, cereals, etc. This is in addition to naturally occurring dietary folate, and is relatively easy to get with prenatal vitamins.

If you’re super keen on getting folate primarily from food, it’s certainly possible. Some great sources include:

spinach (131mcg in ½ cup) 
broccoli (92mcg in ½ cup)
asparagus (127mcg in ½ cup)
collard greens (75mcg in ½ cup)
various beans (~130mcg in ½ cup)
lentils (160mcg in ½ cup)
Fruits like strawberries and oranges are also good sources, as well as mushrooms and brussels sprouts.1

It is difficult to actually say how much is in those sources though since cooking and storing and other factors can decrease the amount, therefore the amounts listed here are rough estimates.

If you want a handy cheat-sheet that tells you all the important nutrients in pregnancy, how much you need, and foods to find them in, check out my FREE Pregnancy Nutrient Cheat Sheet!

I hope this article was helpful in explaining why folic acid is so important before and during pregnancy. As always, discuss supplementation and family planning with your doctor!

Please share this article with women you know who are newly pregnant or thinking of becoming pregnant! And comment below to let me know what you thought of this incredibly long post. Was it too over-the-top sciencey, and made you zone out with glazed over eyes? Hopefully not, but if so, I need to know!

Sources:

1.     Gropper, Sareen A; Smith JL. Advanced Nutrition and Human Metabolism. 6th ed. (Wadsworth, ed.). Belmont, CA; 2013.

2.     Greenberg JA, Bell SJ, Guan Y, Yu Y-H. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol. 2011;4(2):52-59. doi:10.3909/riog0157.

3.     Tortora, G. J., & Derrickson B. Principles of Anatomy and Physiology. 13th ed. (John Wiley & Sons I, ed.). Hoboken, NJ; 2012.

4.     Crowley LV. An Introduction to Human Disease; Pathology and Pathophysiology Correlations. 9th ed. (Jones and Bartlett Learning L, ed.). Burlington, MA; 2013.

5.     Greene NDE, Stanier P, Moore GE. The emerging role of epigenetic mechanisms in the etiology of neural tube defects. Epigenetics. 2011;6(7):875-883. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3154428&tool=pmcentrez&rendertype=abstract. Accessed August 19, 2014.

6.     Blom HJ, Shaw GM, den Heijer M, Finnell RH. Neural tube defects and folate: case far from closed. Nat Rev Neurosci. 2006;7(9):724-731. doi:10.1038/nrn1986.

7.     Dunlap B, Shelke K, Salem SA, Keith LG. Folic acid and human reproduction-ten important issues for clinicians. J Exp Clin Assist Reprod. 2011;8:2. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3183498&tool=pmcentrez&rendertype=abstract. Accessed August 19, 2014.

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