Abstract: 

Folate is a B vitamin critical during periods of rapid growth and development, such as pregnancy. There are a lot of great food sources of folate, but because folate deficiencies can be very harmful to your baby’s development, supplementing with folate is highly recommended. Make sure your prenatal vitamin contains methyl folate rather than folic acid to ensure enough of the vitamin gets absorbed and utilized by the body! 

What is Folate? What Are the Benefits During Pregnancy? 

Folate is important. Vitamin B9 is a critical component of several molecular pathways involved in cellular replication and maintenance. It is involved in gene expression, DNA repair, and the generation of healthy red blood cells. It is critical to health maintenance and disease prevention, including cancer. 

But why is it so critical for women? And especially pregnant women or those trying to conceive? This water-soluble (hard to get too much of) B vitamin is needed to help our cells grow and multiply, making it a key vitamin in periods of rapid growth and development, such as pregnancy. 

• Increases fertility by helping the ovaries respond to follicle-stimulating hormone (FSH) and by assisting eggs to mature before ovulation
• Is needed to absorb Vitamin B12 and other amino acids, preventing anemia during pregnancy
• Prevents miscarriage
• Protects against preeclampsia, a condition marked by high blood pressure during pregnancy
• Is important for the baby's neural development and prevents defects
• Ensures overall reproductive health

The neural tube is an embryonic structure that eventually forms the baby's brain, skull, spine, and spinal cord. This tube forms and subsequently closes very early in pregnancy, at approximately 4-6 weeks pregnant. Thus, adequate folate intake is critically important prior to conception and during the first trimester of pregnancy to help prevent neural tube defects, including spina bifida. 

What Form of Supplementation is Best? 

Food is always the ideal way to obtain essential vitamins and minerals. However, the National Institute of Health, Dietary Guidelines of America, and the United States Preventive Services Task Force all agree that women of childbearing age should supplement with folate in addition to a healthy diet. When supplementing with folate, it is important to know the various forms that vitamin brands utilize. 

Folate vs. Folic Acid: Are They The Same? 

Folate, such as methyltetrahydrofolate (5-methyl-THF) and calcium folinic acid, are naturally occurring forms of folate found in food. These forms of folate do not need to be converted by the body to be used and can be found in some supplements. 

Folic acid is the synthetic version of folate, created to fortify foods and used in standard supplements. This version of folate is promoted by some health practitioners because it is accessible, easily absorbed by the body, and affordable. 

It is also essential to understand how proper folate intake, absorption, and utilization are all necessary to nourish the body and see desired health outcomes. The vitamin must successfully complete all three steps to protect the body from harmful deficiencies.

Intake vs. Absorption vs. Utilization 

Intake:

Food, fortified food, and supplementation can ensure the body gets the proper amount of folate.

Absorption:

A healthy gut is needed to absorb the folate you are consuming. The folic acid form of folate is absorbed quite easily in the GI tract. Nearly 100% of folic acid supplementation is bioavailable when consumed without food. Methyl-folate is also absorbed easily by the body, but more is needed to get the same absorption rate as folic acid. 

Utilization:

If the body does not metabolize folate, it will not be helpful in building a strong, properly functioning neural tube for the baby. Folic acid needs to be converted to methyltetrahydrofolate in the body to be used. Natural sources of folate, methyltetrahydrofolate and calcium folinic acid, do not need to be converted to be used by the body. 

It doesn't matter that folic acid is easier for the body to absorb if it cannot properly convert folic acid into a usable form. Metabolizing folate properly is influenced by our MTHFR gene, which regulates folate and methionine metabolism. This is where personalized healthcare and intimately knowing our bodies and genetic makeup can be incredibly beneficial. The MTHFR gene creates enzymes that break down folic acid and convert it into an utilized form.

However, a specific polymorphism of the MTHFR gene is associated with raised homocysteine concentrations and lower enzyme concentrations. This common MTHFR gene mutation creates problems for metabolizing folic acid and non-methylated B vitamins into more easily utilized forms. Even without the mutation, a less efficient MTHFR gene cannot produce enough MTHFR, causing low folate levels, despite proper amounts of folate being consumed and absorbed. 

Lastly, it is simply harder to metabolize folic acid regardless of MTHFR status. This causes quantities of folic acid from supplementation to circulate throughout the body in its unusable form. Evidence-based research has documented that circulating unmetabolized folic acid is harmful, decreasing the activity of natural killer cells that support the immune system during pregnancy and potentially masking vitamin B12 deficiencies. 

Furthermore, research suggests that high-dose folic acid supplementation may promote insulin resistance and dyslipidemia and disrupt glucose metabolism. That's why, to avoid these folic acid complications, methyl folate is the best form for supplementation, ensuring enough folate is being consumed, absorbed, and utilized by the body. 

How Much Folate Do You Need During Pregnancy?

Governing bodies (the National Institute of Health, the National Academy of Medicine, and the United States Preventive Services Task Force) recommend folate supplementation to all women planning to become pregnant or capable of becoming pregnant. They say that women of childbearing age should take 400-800 mcg DFE/day of folic acid from dietary supplements and/or fortified foods in addition to the folate provided by a varied diet. 

Officially, the RDA for pregnant women is 600 mcg DFE/day of folate. That is the recommended dietary allowance that is scientifically calculated to meet the nutritional needs of nearly all healthy persons. 

However, these are all folic acid recommendations. The FDA allows manufacturers to use a conversion factor of 1.7 to compare methyl folate to folic acid when determining appropriate amounts of methyl folate to use within supplementation. For example, 600 mcg of folic acid would compute to 1,020 mcg of methyl-folate to look for in a supplement. 

Specific individuals may have a higher need for folate, specifically those with impaired absorption, such as individuals with celiac disease, irritable bowel syndrome, or chronic alcohol abuse. 

Lastly, everyday use items that deplete folate stores include antacids, anti-inflammatories, inhalers, topical skin treatments, antibiotics, and hormonal birth control. If these are used daily, slightly increased amounts of supplemented folate may be smart. 

Am I Getting it From Food?

Some naturally occurring folate-rich food sources include: 

• Dark Green Leafy Vegetables: spinach, asparagus, Brussels sprouts
• Legumes: beans, peas, lentils, and peanuts 
• Nuts: almonds
• Citrus: oranges and grapefruit. 
• Other: beef liver, oatmeal and avocados 

Nice to know: High intakes of naturally-occurring folate from food sources, or methyl folate, have not been reported to cause adverse effects. Folate is a water-soluble vitamin that will be excreted in excess. Eat up! 

How Can I Tell If I Am Getting Enough Folate? 

The best way to measure your folate status is to run labs with your healthcare practitioner. Specifically, you should ask for a red blood cell (RBC) folate test. A plasma/serum folate test reflects recent intakes and is a temporary measure of levels, which is not a reliable marker of actual status. Because folic acid is readily absorbed in the intestines, it will show up in plasma levels, making them appear normal. However, absorption does not always equate with utilization, so testing specifically for RBC levels will reveal any functional deficiencies. 

Additionally, the elevated blood concentration of homocysteine indicates poor folate status and is associated with an increased risk of neural tube defects. 

Prenatal Vitamin Brands: What's the Folate Amount and Type in Popular Prenatal Brands?

Prenatal Analysis

Most specialized prenatal brands, as shown above, have voted for naturally occurring folate forms in their supplements. These brands utilize the natural usable versions of folate, methyltetrahydrofolate and calcium folinate. These folate types do not need to be successfully converted in the body before they can be used effectively and thus, are better forms for anyone with a MTHFR gene mutation or a less efficient methylation process. They are also protective against any harmful buildup in the body of un-metabolized folic acid.

Resources: 

1. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020. Available at DietaryGuidelines.gov.

2. Folate: foods, functions, how much do you need & more. Accessed February 1, 2022. https://www.eufic.org/en/vitamins-and-minerals/article/folate-foods-functions-how-much-do-you-need-more

3. FullWell. 8 Key Nutrients for Neural Tube Defect Prevention. Published January 20, 2022. Accessed January 31, 2022. https://fullwellfertility.com/blogs/blog/8-key-nutrients-for-neural-tube-defect-prevention

4. Morakinyo AO, Samuel TA, Awobajo FO, Oludare GO, Mofolorunso A. High-Dose Perinatal Folic-Acid Supplementation Alters Insulin Sensitivity in Sprague-Dawley Rats and Diminishes the Expression of Adiponectin. J Diet Suppl. 2019;16(1):14-26. doi:10.1080/19390211.2018.1426076

5. Romm AJ. Hormone Intelligence: The Complete Guide to Calming the Chaos and Restoring Your Body’s Natural Blueprint for Wellbeing. First edition. HarperOne; 2021.

6. David SS, Blakeway J. Making Babies: A Proven 3-Month Program for Maximum Fertility. 1st ed. Little, Brown; 2009.

Office of Dietary Supplements - Folate. Accessed February 1, 2022. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

7. Weschler T. Taking Charge of Your Fertility: The Definitive Guide to Natural Birth Control, Pregnancy Achievement, and Reproductive Health. 20th Anniversary Edition. William Morrow; 2015.

8. Murkoff HE, Mazel S. What to Expect When You’re Expecting. Fifth edition. Workman Publishing; 2016.