Methyfolate and Folic Acid in Pregnancy: Differences and Which Is Best

From the moment of conception, the development of a new being begins. However, we know that from the very first moment the environment the body provides can influence the future of the embryo. Therefore, it is essential that a woman planning to become pregnant carefully prepares and creates a good nutritional state for the baby who will grow inside her body. If you are pregnant or trying to conceive, you’ve certainly heard of folic acid, also called folate (or vitamin B9), a fundamental component for a healthy pregnancy. It has many benefits: it helps prevent anemia, premature birth, and postpartum depression in the mother, and aids in the formation of the baby’s spinal cord and brain.

To give you an idea, this nutrient is so important that since the enrichment of wheat and corn flours with iron and folic acid became mandatory in Brazil, through the National Health Surveillance Agency (Anvisa), the prevalence of neural tube defects in babies dropped by 30% in the country.

This information was obtained by comparing birth records from the period before (2001-2004) and after mandatory flour enrichment (2005-2014). In the pre-enrichment period, there were 0.79 cases of neural tube defects per thousand live births, while in the post-enrichment period, there were 0.55 cases per thousand live births.

The fact is, all pregnant women need a higher intake of this substance (between 0.4 mg and 0.8 mg per day), but it’s rarely possible to obtain the ideal amount solely from food, which makes supplementation necessary. Nowadays, in addition to folic acid (the synthetic form of the vitamin), the product is also found on the market as methylfolate (the active form of the vitamin). In this article, we will cover this topic in detail, including why folate is found in most multivitamins and why supplementation with methylfolate is now considered the most beneficial way to obtain this powerful nutrient.

1. How vitamin B9 works during pregnancy
2. Differences between folic acid and methylfolate: which is better?
3. Why folate supplementation is essential

How vitamin B9 works during pregnancy

Since the early 1990s, specialists have agreed that vitamin B9 is extremely valuable both before and once pregnancy begins. Its importance stems from the protective effect this vitamin has against neural tube malformations during fetal development. As the neural tube develops in the first 28 days of pregnancy, the general recommendation is that all women of childbearing age consume folate. More specifically, the most appropriate time to begin supplementation is three months before becoming pregnant, continuing throughout the first trimester of pregnancy. The neural tube develops in the spinal column, and malformation occurs when, during the first four weeks of pregnancy, the brain and skull and/or the spine and spinal column do not develop properly. After numerous studies, strong evidence has been found that increased intake of vitamin B9 can reduce the risk of these malformations, the most common of which are:

• Spina bifida – this is an irregular formation of the spinal vertebrae bones, when the neural tube does not close completely and the dorsal column (in the middle of the back) is exposed or protrudes, leaving a gap. As a result, the spinal nerves (which connect to the spinal cord) do not develop fully, possibly leading to total or partial paralysis;
• Anencephaly – this is a malformation of the central nervous system where there is a partial absence of the brain and the cranial vault. In some cases, brain tissue may be exposed. It is more frequent in girls. This condition causes stillbirth or early death shortly after birth;
• Encephalocele – this is when the meninges and/or brain tissue protrude through a gap in the skull. For this to happen, there is always an associated “bone defect” (that is, a “hole in the skull bone” through which this protrusion occurs). It is usually covered with skin and looks like a “sac” attached to the child’s head.

This is the least common of the malformations and, when it occurs, results in a small proportion of stillbirths. Most deaths occur within the first year of life, however, some babies survive longer, presenting complications similar to those seen with spina bifida.

Vitamin B9 is found naturally in:

• Broccoli;
• Spinach;
• Kale;
• Arugula;
• Yeast extract;
• Legumes;
• Oranges;
• Breads and cereals fortified with folate;
• Lentils;
• Spaghetti;
• Rice;
• Beans;
• Spinach;
• Peas;
• Nuts;
• Lemon;
• Banana;
• Melon;
• Eggs;
• Milk and dairy products;
• Red meats.

In addition, during pregnancy, folate prevents certain heart defects, as well as cleft palate and cleft lip. It also reduces the risk of premature birth and low birth weight. Folate requirements also increase in pregnancy due to the rapid cell division in the fetus. Among other things, this substance is also essential for the production of red and white blood cells, as well as for the production of heme, an iron-rich molecule attached to red blood cells. This is why a deficiency in folate can lead to anemia.

Folate is also known for helping to convert a compound called “homocysteine” into an essential amino acid known as “methionine.” Without sufficient folate, homocysteine levels rise, and high levels have been associated with infertility and recurrent miscarriages in some studies. In fact, research data shows high homocysteine levels were found in 25% of women with unexplained spontaneous miscarriages.

Differences between folic acid and methylfolate: which is better?

How does folate work in the body? It acts as a coenzyme, which means it assists other enzymes in the body to perform important functions. But let’s get to the point: the major advantage of a methylfolate supplement is that it is vitamin B9 in its active form, meaning the substance does not need to be metabolized by the body. On the other hand, folic acid is the synthetic version of the vitamin.

In other words, when we take a methylfolate supplement, it starts working immediately. When we take the vitamin in folic acid form, however, the substance first needs to be converted into methylfolate by enzymes in the body before being distributed. It’s as if we need “middlemen” to finish the job.

It is estimated that when taken in its active form—that is, as methylfolate—the absorption rate by the body is 26% higher compared to folic acid. Another benefit of consuming this form is that it reduces the possibility of interaction with medications that interfere with the vitamin’s metabolism.

A major drawback of folic acid is that up to 60% of the population has a genetic mutation (called MTHFR) that prevents the conversion of folic acid into methylfolate. Women with this mutation may have a higher risk of migraines, infertility, and neural tube defects during pregnancy. The problem is most of these women don’t know if they have this mutation, i.e., they lack the valuable information about whether they fall within this significant percentage. For this reason, doctors now always prescribe methylfolate, because this guarantees it will act immediately in the expectant mother’s body. So, by taking a methylfolate supplement instead of folic acid, you do not allow this mutation to interfere.

In a comparative study between pregnant women supplemented with folic acid versus methylfolate during pregnancy and up to term (that is, the stage when the baby is ready to be born), it was found that those supplemented with methylfolate had much higher hemoglobin levels at the end of the 2nd trimester and at term. Based on this study, there appears to be a lower incidence of anemia if supplementation is done with methylfolate.

Also, in order for the body to convert folic acid into methylfolate, aside from the genetic factor, other variables such as age and individual metabolism play a role, impairing the vitamin’s bioavailability in the body.

In general terms, the word bioavailability is defined as the proportion of the micronutrient ingested that is absorbed and utilized by the body.

Why folate supplementation is essential

During pregnancy, it’s as if the body makes a kind of “contract” with the fetus. In this fascinating natural agreement made between the two, body and fetus aligned in service to life, physiological and metabolic adaptations arise in the mother. It really seems that the body thinks of everything, because these adjustments are what allow the increased demands of the pregnant woman’s body to be balanced with proper fetal growth, while ensuring the creation of the energy reserves needed during childbirth and postpartum. It’s important to remember that, from a metabolic perspective, pregnancy is divided into two phases:

• Maternal phase – anabolic, during which energy reserves are built up to be used in the second phase;
• Fetal phase – catabolic, during which most fetal growth occurs.

In this context, it’s clear how essential it is for the body to be well-adjusted and healthy in both phases: they are completely interdependent, which is why there are so many recommendations for supplementing certain compounds, both before conception, during pregnancy, and also after childbirth.

Within this perfect system, even the metabolism of nutrients changes so that the fetus can make the most of what is consumed.

Another point to note is that even with this well-established “silent contract” between body and fetus, pregnancy brings a burden to the mother’s body and a significant increase in nutrient requirements. Practically speaking, it’s not always possible to reach the ideal levels of certain substances, like folate, which can be another cause of anxiety during pregnancy.

On the other hand, studies have already shown that the folate present in certain foods loses much of its chemical activity during harvesting, storage, and food preparation, resulting in low bioavailability. For these reasons, diet may not be the best way to prevent neural tube defects. In this sense, various organizations that work with this topic, such as the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo), recommend that folate should be supplemented as soon as pregnancy is being planned, about three to four months in advance, or immediately upon learning of the pregnancy. The idea behind making this type of specific nutritional recommendation for pregnant women is precisely to positively influence the course of pregnancy and the future nutritional health of both the fetus and the mother herself.

Folate is universally recognized, but even with all the popularity about it and its qualities, approximately one in every 700 Brazilian children has conditions related to a deficiency of this substance during pregnancy, such as paralysis and mental problems.