MTHF Folate vs Folic Acid in Pregnancy: What's Better for Prenatal Vitamins?

Originally published 06/14/2023. Updated for accuracy and relevancy on 04/17/2024

Learn about the distinctions between the different types of folate and how to choose which one is best for you.

By Dr. Liz Kane

What’s the Difference Between Folate, Folic Acid, and MTHF Folate?

A good prenatal vitamin should be one of the first purchases you make after you decide you want to get pregnant. One of the key ingredients in a prenatal vitamin is folate, but not all forms of folate in vitamins are equal. MTHF folate vs folic acid vs folate: these forms can be found in vitamin and dietary supplements and differ in many ways. To help you understand the differences, we're going to walk you through the important scientific details, starting with some keywords¹:

• Folate is a B vitamin. It is an umbrella term for a class of chemical compounds found naturally in foods, food folates, and ones made artificially, synthetic folates.
• Folic acid is a synthetic form of folate made in a laboratory. It’s found in vitamins, and it is also used in fortification of some processed foods.
• MTHF folate is food folate that can also be found in prenatal vitamins. It’s a bit confusing, but MTHF folate can go by many names, such as levomefolic acid, methyl folate, L-5-MTHF, L-5-methyltetrahydrofolate, (6S)-5-methyltetrahydrofolate, and (6S)-5-MTHF. They are all the same kind of folate.

The Best Form of Folate

To choose the most beneficial form of folate supplementation, you’ll want to consider how your body absorbs and utilizes MTHF folate versus folic acid. While all folates are absorbed in the intestine, there are distinctions in the processing of each type.¹

MTHF folate can be utilized immediately by your body. This means it has high bioavailability, which is a measure of how well a drug can be absorbed by the body. In fact, MTHF folate is the most common folate found in the human body.

In contrast, folic acid cannot directly be used by the body. It must be converted by two chemical reactions into another folate that your body can metabolize— specifically, MTHF folate.² That’s right, folic acid must first be converted into MTHF folate for your body to use it. Folic acid supplements also carry the risk of masking symptoms of a vitamin B12 deficiency, which can lead to anemia — one of the very risks you’re trying to prevent by taking a prenatal vitamin.

Benefits of Folate During Pregnancy

The most important role folate plays in a prenatal vitamin is the prevention of neural tube defects (NTDs) in the baby. NTDs are deformities of the neural tube, which is the embryonic precursor to the brain and spine. During a healthy pregnancy, the tube will seal itself off between three and four weeks of fetal development.³ In the case of an NTD, the tube doesn’t fully close, leading to devastating and life-threatening birth defects like spina bifida.

Research studies have shown that folate supplementation reduces the incidence of NTDs significantly.⁴ The results of these studies prompted the United States government to institute a folic acid food fortification program in 1998 so that all women of childbearing age would consume extra folate intake through their diet.⁵ Since the implementation of folate-fortified food, NTDs have decreased in the US by 35%.⁶ We don’t yet fully understand how folate supplementation lowers NTD risk, but we know that it involves decreasing levels of homocysteine, an amino acid which is also tied to a higher risk of heart disease and stroke.^7,9 

It should be noted that the studies performed by the United States government only used synthetic folic acid, and not other naturally-occurring forms such as 5-MTHF; however, as we mentioned above, folic acid is converted into MTHF folate as part of metabolism. Besides helping to prevent NTDs, folate intake is also essential for creating new DNA, proteins, and red blood cells, the cells that transport oxygen throughout the body.¹⁰

The MTHFR Gene

There’s another risk of folic acid to consider: based on your genetics, you could be impaired in your ability to convert folic acid into MTHF folate.⁸ Your body uses an enzyme (a protein that facilitates a chemical reaction) called methylenetetrahydrofolate reductase (MTHFR) in one of the steps to convert folic acid to MTHF folate.⁸ Up to 25% of the population has a variant of the MTHFR gene (MTHFR 677TT) that significantly impairs their ability to metabolize folic acid.¹⁰ Individuals with this MTHFR gene mutation are also at a higher risk of having a child with neural tube defects. The research is still preliminary, but people with this MTHFR variant would likely benefit from MTHF supplementation over folic acid as well.⁹

How Much Folate Should I Take?

When it comes to taking a folic acid supplement or increasing dietary folate intake, it's important to know just how much you should take.

Most health professionals recommend a daily intake of 400 micrograms of folate one to three months before conception and 600 micrograms of folate for the duration of pregnancy.¹¹ While it’s theoretically possible to consume this much from folate-rich foods, absorption of dietary folate is variable and not guaranteed (particularly since a significant amount of folate supplementation in food takes the less-efficient form of folic acid). Ask yourself, “Am I getting enough folate?” To ensure you reach the folate levels you need, it’s recommended that all women planning a pregnancy take a dietary supplement containing folate. Taking a prenatal vitamin with MTHF folate as soon as you even consider trying to conceive (or just as soon as you find out you’re pregnant) can provide this nutritional safety net, supporting pregnancy health and potentially preventing pregnancy complications. 

Support Your Nutrition With Natalist

We know these details and decisions feel stressful and high stakes, and that’s because they are. This is your baby’s development, and it’s normal to want to cover all your bases and do everything you can to support a healthy pregnancy. It’s a way of feeling more in control in an unpredictable, sometimes-scary time in your life. From a prenatal supplement to a folic acid supplement, there are many benefits to keeping up with your vitamins and minerals during preconception, pregnancy, and postpartum.

We encourage you, though, to try and consider your choice of prenatal vitamins as a means of pregnancy self-care to provide yourself with support for your emotional well-being, as well as your physical health. You can’t control whether or not you get severe morning sickness that keeps you from eating a balanced diet. You certainly can’t control your genes. However, choosing a prenatal vitamin with MTHF folate means optimizing the likelihood that your vitamin will support your health—and your baby’s—in the best way possible.

References:

1. Folate Fact Sheet for Health Professionals. NIH. November 2022. URL. 
2. Obeid R, Holzgreve W, Pietrzik K. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?. J Perinat Med. 2013;41(5):469-483. doi:10.1515/jpm-2012-0256
3. Greene ND, Copp AJ. Neural tube defects. Annu Rev Neurosci. 2014;37:221-242. doi:10.1146/annurev-neuro-062012-170354
4. Higdon, J. Drake, V. Delage, B. McNulty, H. Folate. Oregon State University. Updated 2014. URL. 
5. Folic Acid Fortification and Supplementation. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Centers for Disease Control and Prevention. July 13 2022. URL. 
6. CDC. Updated Estimates of Neural Tube Defects Prevented by Mandatory Folic Acid Fortification — United States, 1995–2011. MMWR Morb Mort Wkly Rep. 2015: 64(01); 1-5.
7. van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ. Folate, homocysteine and neural tube defects: an overview. Exp Biol Med (Maywood). 2001;226(4):243-270. doi:10.1177/153537020122600402
8. Refsum H, Ueland PM, Nygård O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med. 1998;49:31-62. doi:10.1146/annurev.med.49.1.31
9. Hankey GJ, Eikelboom JW. Homocysteine and stroke. Curr Opin Neurol. 2001;14(1):95-102. doi:10.1097/00019052-200102000-00015
10. de Franchis R, Buoninconti A, Mandato C, et al. The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy. J Med Genet. 1998;35(12):1009-1013. doi:10.1136/jmg.35.12.1009
11. Nutrition During Pregnancy. FAQ001. American College of Obstetricians and Gynecologists. Updated June 2023. URL.