The Bottom Line

Folic acid is one of the few vitamins where diet alone is not enough to cover what is needed during pregnancy and supplementation is necessary for the prevention of neural tube defects (NTDs). Folic acid may also play a role in successful implantation and placental development.

Recommended doses by numerous organizations vary from at least 400 to up to 1,000 micrograms (mcg)/day for two to three months prior to pregnancy, and at least through 14 weeks of pregnancy.

However, there are documented potential benefits of taking folic acid the entire pregnancy, and links between a lack of folate and preterm birth, preeclampsia, fetal growth restriction, seizure disorders, and autism are currently being studied.

It is generally recommended that women not take more than 1,000 mcg/day unless their pregnancy is at a high risk for NTDs, which may require up to 5,000 mcg/day. A woman’s health care provider (HCP) will make the determination whether the pregnancy is considered high risk.

If a woman has a genetic variant or malabsorption/gastrointestinal disorder that hinders her ability to absorb folic acid, an HCP can recommend different supplements that may also be effective at preventing NTDs.

Women should avoid taking more than 400 mcg/day of folic acid without speaking to their HCP first.

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Background

Folate is an essential B vitamin required by every cell in the body for normal growth and development.

Folate is a naturally occurring nutrient found in foods.

Folic acid is present in supplements and fortified/enriched foods (man-made).

Demands for folate increase during pregnancy. Folate is required:

For the overall growth and development of the fetus (DNA replication, central nervous system) – specifically the prevention of neural tube defects (NTD), congenital heart defects, and oral clefts.

To make extra blood; folate helps the body make red blood cells that carry oxygen from the lungs to the entire body. This process is increased during pregnancy. Without adequate folate/folic acid intake, a pregnant women has less red blood cells and can become anemic (this can also occur with iron, vitamin B6, and vitamin B12 deficiency).

Red blood cell production increases during pregnancy.

In the general population, 2 to 3 million red blood cells (RBCs) are produced every second in the bone marrow and released into the circulation (RBCs have a lifespan of about 120 days) (Dean, 2005).

Women will make even more red blood cells during pregnancy, estimated at an additional 18%; if women do not have enough iron, folate, vitamin B6, or vitamin B12 for this extra production, anemia may result, and women can feel shortness of breath and fatigue. Read more.

Neural Tube Defects

Fetal growth causes a dramatic increase in the total number of rapidly dividing cells, which requires folate. Correctly dividing cells are required to create, form, and close the neural tube.

The link between folate deficiency and NTDs was suspected as early as 1964; in the United States (U.S.), NTDs affect 3,000 pregnancies annually, and 700 to 900 in the United Kingdom (U.K). See full, detailed page on NTDs here.

The fortification of grain products with folic acid has been mandatory in the U.S. and Canada since 1998, which significantly reduced the incidence of NTDs. The voluntary fortification of several foods has been permitted in Australia since June 1995, with fortified flour (for non-organic bread) in 2009. The U.K. began considering the implementation of mandatory fortification of flour in early 2019.

Women should begin taking folic acid even before becoming pregnant.

Supplementation is recommended prior to pregnancy because even with 4,000 mcg/day, it may take 4 to 5 months to reach folate levels between 1,050 and 1,340 nmol/L in the blood, which is most optimal for the reduction of NTDs. (It is generally recommended that women only take 400 to 1,000 mcg/day unless a HCP recommends a higher amount).

However, supplementation of folic acid only works to prevent NTDs before and during the first few weeks of pregnancy (the neural tube closes around day 28 after fertilization, or 6 weeks of pregnancy).

Folic acid supplementation does not prevent all NTDs because they are caused by numerous factors; it is estimated, however, that folic acid helps prevent up to 70% of NTDs.

Photo by Tanaya Sadhukhan from Pexels
updated

Other Potential Benefits

Folic acid supplementation may assist several other functions during pregnancy:

Folate is important for normal immune function, which is required for implantation. Because folate has been shown to regulate parts of this process, it is possible that a lack of folate could interfere with the early stages of fetal/placental development leading to complications. However, research regarding low folate levels and miscarriage is inconsistent.

Additional research has shown that that folic acid supplementation could prevent seizure disorders or fetal growth restriction in the fetus, and possibly preeclampsia in the mother (based on abnormal placental development, described above).

A potential link between decreased autism risk and folic acid supplementation is of current research interest. It is believed that supplementation may have the largest effect on preventing autism when folic acid is taken as early as possible prior to pregnancy, and through at least the first trimester.

However, some research indicates that folic acid should be taken throughout the entire pregnancy:

Preterm birth (of single babies) prior to 32 weeks has been associated with low folate levels and a lack of folic acid supplementation during pregnancy.

A study published in March 2021 that followed up a prior randomized controlled trial examined the effect of folic acid supplementation in the second and third trimesters and determined that continued supplementation (400 mcg/day) throughout pregnancy can influence cognitive performance and brain function of the child up to 11 years of age.

Supplementation

Diet alone is not enough to increase folate levels during pregnancy and supplementation is necessary.

The worldwide recommendation of folic acid supplementation is 400 to 1,000 mcg/day for all women planning to have a baby and those currently pregnant, and 4,000 to 5,000 mcg/day (4 to 5 milligrams) for women who have had a baby with an NTD, or are at high risk for having a baby with an NTD (see NTD page for risk factors).

It is generally recommended that the higher dosage of 4,000 to 5,000 mcg should be prescribed and monitored by an HCP. For women on higher doses, an HCP will also check vitamin B12 levels, as high folic acid intake can "hide" a B12 deficiency.

Women pregnant with multiples may be required to take more than the recommended 400 to 1,000 mcg/day dose, depending on their HCP's advice.
Photo by Fallon Michael on Unsplash

Women carrying twins may be advised take 1,000 mcg throughout pregnancy, as anemia due to folate deficiency is eight times more common in twins compared to women pregnant with one baby.

Women who are taking anti-epileptic medication may also need higher doses of folic acid may not be metabolized very well with these medications.

Smoking decreases the amount of folate available in the body, and pregnant women who smoke may need additional folic acid supplementation during pregnancy.

Women should not take more folic acid than what is recommended or prescribed. The maximum dosage recommend is 1,000 mcg/day for pregnant women who are not considered high risk (determined by an HCP). Women should speak to their HCP prior to taking or increasing their folic acid intake for any reason during pregnancy.

Although concerns exist regarding high excess folic acid intake and cancer, cardiovascular disease, depression, and cognitive impairment, folic acid is considered to be a safe supplement, and has been studied across a wide range of dosages in different populations of individuals.

For some women, 5-MTHF may be a possible folic acid alternative in the future.

Preliminary research suggests supplementation with 5-MTHF (l-methylfolate/5-methyltetrahydrofolate) rather than folic acid may mitigate concerns over excess folic acid intake.

5-MTHF is also less likely to mask a severe vitamin B12 deficiency, may be an alternative for those with MTHFR mutations, and may be as effective or more effective than folic acid on red blood cell folate levels. Research is still new and ongoing regarding this possibility.

Note: Preliminary research conducted in pregnant animals has indicated that excess folic acid (10 times the recommended dose) caused adverse brain structure changes in embryos. Although this needs to be investigated further, it is important that women only take the amount recommended by their HCP.

Food Sources

Folate is water-soluble and is broken down by cooking. The best way to obtain folate is through raw, clean, and thoroughly washed vegetables.

Photo by Ryan Quintal on Unsplash

The best sources of folate are broccoli, asparagus, brussels sprouts, cabbage, cauliflower, spinach, green beans, lettuce, mushrooms, parsnip, sweet corn, zucchini, avocado, grapefruit, oranges, chickpeas, lima beans, kidney beans, eggs, nuts, poultry, white rice, and citrus fruits and juices, and fortified breads and cereals.

Actions

Women should speak to their HCP prior to taking or increasing their folic acid intake for any reason during pregnancy.

Women should not take multiple doses of a multi- or prenatal vitamin to get extra folic acid, as this could result in an excess of other nutrients (such as vitamin A). Women who wish or feel they need to take additional folic acid during pregnancy need to talk to their HCP.

Women who smoke should aim to quit as early as possible during pregnancy. Further, women who smoke need to inform their HCP, as additional supplementation may be necessary.

Women who are on anti-epileptic medications should call their HCP as soon as they decide to try to get pregnant or as soon as they learn they are pregnant. Their HCPs may need to adjust their medications, to include a possible increase in folic acid.

Resources

Folic Acid (Centers for Disease Control and Prevention)

Folic Acid Fact Sheet (U.S. National Institutes of Health)

References

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