If you’re trying to find a prenatal vitamin, you won’t have to look very far. There are probably hundreds of different vitamin formulations all claiming to be the most “complete” with the best combination of vitamins and minerals for optimal mom and baby health.
Taking a prenatal vitamin certainly is important. Both times I’ve called my OB office to schedule a first-trimester appointment, they’ve asked me when my last menstrual period was and whether I’m taking a daily prenatal vitamin. Prenatal nutrition is definitely high on the priority list!
But, what are the most important things to consider when actually choosing a vitamin? Specifically, there’s a lot of buzz about methylated forms of certain vitamins, including folate. Is this something that we should be considering now when choosing a prenatal?
What is folate?
We’ve written before about how your nutrient needs dramatically increase during pregnancy. While a “food first” approach is always recommended, pregnancy is one of those times when nearly all women can benefit from added nutrients in the form of a multivitamin supplement.
One of the most important nutrients needed during pregnancy right from the start is folate, which is responsible for preventing neural tube defects in the developing embryo. Folate is one of the B vitamins that’s water-soluble (which means any excess is removed by your body through your urine). In vitamins and supplements, you’ll often see folate in its synthetic form, folic acid (For a list of food sources naturally high in folate, see this resource).
Neural tube defects
Neural tube defects (NTDs) include a class of developmental defects to the brain and spinal cord. They typically occur very early in the developing embryo, often before week four of pregnancy. In pregnancy dating, that’s usually the time a woman “misses” her period, so most women are only taking their first pregnancy test by this time.
The neural tube is a narrow channel that needs to fold and close properly to eventually form the brain and spinal cord. One of the most common NTDs you may have heard about is spina bifida, a disorder in which the part of the neural tube that didn’t close becomes a part of the backbone that doesn’t close over and protect the spine.
The biggest thing to keep in mind about NTDs is that by the time you know you’re pregnant, they may have already occurred. This is where the importance of folic acid before conception comes in.
Folic acid recommendations
Because of the timing of your baby’s neural tube formation, doctors typically recommend that any woman of childbearing age take a daily multivitamin containing at least 400 micrograms of folic acid. If you are actively trying to conceive, you may benefit from even higher amounts of folic acid. But while you may be reading this article because you’re trying to prepare for a very desired baby, not all pregnancies are planned—which, again, is why it’s recommended that all women of childbearing age supplement with folic acid.
In the U.S. (and depending on the study), up to 45% of pregnancies may be unplanned. This means many women get pregnant unintentionally, and when a woman isn’t expecting to get pregnant, she probably isn’t paying as much attention to her diet or vitamins. And she may not take a pregnancy test as early as possible.
History of folic acid supplementation in food and vitamins
So what about women who aren’t taking a prenatal vitamin? Do their babies have a higher risk of neural tube defects? This is exactly what doctors observed as early as the 1960s when they saw folic acid supplementation reduce NTDs in women, particularly those who had a previous birth of a baby with any NTD [1, 2, 3]. Several randomized clinical trials followed in the 1990s, in which scientists tested whether folic acid supplementation directly impacted the rate of NTDs [4].
It took until 1991 for the Centers for Disease Control and Prevention (CDC) to recommend 4,000 micrograms of folic acid for women with prior NTDs, and it took until 1992 for the U.S Public Health Service to initiate the consensus recommendation of 400 microgram folic acid supplementation for all women. In 1998, it became mandatory to fortify grain and cereal products with folic acid (called “enriched wheat” in the ingredients) to ensure women were getting adequate folic acid even if they didn’t take a multivitamin. Nearly all major health organizations continue to affirm the enormous benefit of folic acid supplementation in early pregnancy [5].
Methylated folate vs. folic acid
With all the evidence regarding folic acid in reducing the incidence of NTDs, you might be wondering what could possibly be controversial about adding it to more foods (for example, California Governor Gavin Newsom recently made headlines by signing into law AB 1830, which required the addition of folic acid to corn masa flour—the basis for tortillas). The answer lies in how folic acid is metabolized, or used up, in your body.
Remember, folic acid is the synthetic form of the B vitamin, folate. In your body, folic acid is converted to L-methylfolate (also called 5-MTHF) by enzymes, and this is the active form of the vitamin that gets to work in your body.
One of the most important enzymes in the folic acid conversion process is the MTHFR enzyme, and in some people, the gene that encodes this enzyme has variants that reduce the enzyme’s efficiency in converting folic acid to its active form. Hypothetically, this means if you have one of these gene variants, you would have less bioavailable, or active, folate in your body—and therefore higher levels of unmetabolized folic acid. The only way to know if you have the MTHFR gene variant is through genetic testing.
Some prenatal vitamins use a methylated form of folate instead of the synthetic folic acid, to bypass the conversion step your body has to do. They claim this means their vitamin has “more bioavailable” folate, or that it might be better absorbed, especially by women with a MTHFR variant.
Folic acid vs. methylated folate: What clinical trials have shown us
Folic acid is the only form of folate that has been clinically studied to reduce the occurrence of NTDs. The obvious next step would be to perform the same studies with methylated folate [6]. Since we have clear and consistent evidence of the overwhelming benefit of folic acid supplementation in pregnancy, there are several considerations to take into account for future studies.
In clinical trial design, you can never design a trial that would subject a person to known harm, or remove something of known benefit to them. This is the case with folic acid—there could never be an ethical randomized clinical trial in which some women receive synthetic folic acid while others receive methylated folate, because this design removes folic acid from half the study participants. The only way a trial like this would be feasible is if the participants were voluntarily taking methylated folate (and this would not be a randomized control trial, and would come with its own slew of confounders).
Furthermore, we don’t actually know the mechanism through which folic acid reduces NTDs. Shannon M. Clark, MD, known as Babies After 35 on Instagram, regularly shares about the recommendations for prenatal vitamins based on evidence. While we know folic acid is converted to methylated folate in the body, and that this is the active form, we don’t know whether the methylated folate is directly acting on neural tube formation. There could be an entirely unknown mechanism through which folic acid works that we just haven’t discovered yet! And, one study showed that the folate status (or how much folate a woman has) was not necessarily correlated with babies having NTDs [7].
Thus far, there hasn’t been any evidence of harm due to supplementing with methylated folate compared to folic acid. In other words, we haven’t seen an increase in NTDs among women who only take methylated folate compared to women taking folic acid. This suggests that the overall folate levels in the mother’s body do contribute to protection against NTDs to some extent, although we do not have the direct evidence that methylated folate performs equally to folic acid in preventing NTDs. Still, for women with the MTHFR who may be concerned about the potential harms of high levels of unmetabolized folic acid, methylated folate may be a good choice [8], as discussed in this Natural Womanhood article on prenatal vitamins.
The bottom line
Folic acid remains the gold standard in any multivitamin supplement for women of childbearing age. It’s safe, stable, and inexpensive to prevent NTDs. Methylated forms of folate are also safe and stable, but are more expensive, and current evidence does not suggest they are any better at preventing NTDs.
Any woman with a history of babies born with any NTD or even a family history of NTDs is recommended by the CDC, American College of Obstetrics and Gynecology (ACOG), and the World Health Organization to consume between 4,000 to 5,000 micrograms of synthetic folic acid (not folate!) daily for at least one month before conception. While there are some women with the MTHFR gene variant who may need to weigh the decision to supplement with synthetic folic acid or methylated folate more heavily, most women would do well to focus on the clinical evidence for standard folic acid supplements.
