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Folate or Folic Acid in Pregnancy?

Folate is a water-soluble B-vitamin that is naturally present in many foods. Your body needs folate to make DNA and other genetic material. Your body also needs folate for your cells to divide. A form of folate, called folic acid, is used in fortified foods and most dietary supplements.

Some dietary supplements also contain folate in the monoglutamyl form, 5-MTHF (also known as L-5-MTHF, 5-methyl-folate, L-methylfolate, and methylfolate).

Folate and its synthetic cousin, folic acid are vital for developing a healthy baby because it prevents neural tube defects. Since the neural tube develops within the first 28 days of pregnancy, it is recommended all women of childbearing years consume folate. Folate prevents certain heart abnormalities, cleft palate and cleft lip. It also lowers the risk of developing anemia, miscarriage, preterm delivery and low birth weight.

Folate is naturally present in:

  • Beef liver

  • Vegetables (especially asparagus, brussels sprouts, and dark green leafy vegetables such as spinach and mustard greens)

  • Fruits and fruit juices (especially oranges and orange juice)

  • Nuts, beans, and peas (such as peanuts, black-eyed peas, and kidney beans)

Folic acid is added to the following foods:

  • Enriched bread, flour, cornmeal, pasta, and rice

  • Fortified breakfast cereals

  • Fortified corn masa flour (used to make corn tortillas and tamales, for example)

Folate deficiency is rare in the United States, but some people do not get enough. Getting too little folate can result in megaloblastic anemia, a blood disorder that causes weakness, fatigue, trouble concentrating, irritability, headache, heart palpitations, and shortness of breath. Folate deficiency can also cause open sores on the tongue and inside the mouth as well as changes in the color of the skin, hair, or fingernails.

Women who don’t get enough folate are at risk of having babies with neural tube defects, such as spina bifida. Folate deficiency can also increase the likelihood of having a premature or low birth weight baby.

Groups at Risk of Folate Inadequacy

People with alcohol use disorder

Women of childbearing age

Pregnant women

People with malabsorptive disorders

People with an MTHFR polymorphism

In one study

Folate intake during pregnancy is essential for adequate fetal and placental development and for a long time health of the individual. Its deficiency may induce fetal pathologies, including neural tube disease (NTD). Therefore, several countries implemented public policies to fortify foods with folic acid (FA). Chile started the fortification of wheat flour with FA in the year 2000, decreasing a 43% the prevalence of NTD. However, despite the high consumption of bread (the main fortified food with FA) by our population, a high number of pregnant women consume FA supplements, thus, overpassing the maximal recommended FA intake.

In another study

Folate (vitamin B9) is widely accepted to protect against fetal neural tube defects. The main sources of dietary folate are folic acid-fortified foods and folic acid-containing dietary supplements. However, folic acid is inactive in the human body and must be converted by the liver into the active molecule 5-methyltetrahydrofolate (5-MTHF). 5-MTHF functions as a methyl donor in many metabolic reactions, including the conversion of homocysteine into methionine, the biosynthesis of glycine from serine, and the biosynthesis of DNA precursor molecules. Therefore, folate is fundamental for growth, especially in the embryonic and fetal stages. Prescription of folic acid to women in the preconception period and during pregnancy is a consolidated practice. However, it can pose health risks in certain conditions, such as megaloblastic anemia, where it will conceal megaloblastic anemia due to vitamin B12 deficiency and in cases of reduced hepatic transformation of folic acid. Some of these risks can be avoided by supplementation with 5-MTHF rather than folic acid. Because 5-MTHF does not require activation, it is immediately available to the mother and fetus and does not accumulate in blood like folic acid does in cases of reduced hepatic transformation.

Naturally occurring 5-MTHF has significant advantages over synthetic folic acid – it is well absorbed even when gastrointestinal pH is altered and its bioavailability is not affected by metabolic defects. Using 5-MTHF instead of folic acid reduces the potential for masking haematological symptoms of vitamin B12 deficiency, reduces interactions with drugs that inhibit dihydrofolate reductase and overcomes metabolic defects caused by methylenetetrahydrofolate reductase polymorphism. Use of 5-MTHF also prevents the potential negative effects of unconverted folic acid in the peripheral circulation.

Analysis of the recent literature reposts suggests that metafolin could be an effective and safe alternative to folic acid supplementation and could effectively prevent complications in pregnancy and serious birth defects in fetuses and newborns.

Part 2

It is estimated that between 25 and 60 percent of the population have a variation in one of their MTHFR genes that negatively impacts their ability to convert folic acid (the synthetic version of B9), and even some of the folate that naturally occurs in foods, into the active form of folate. If you are trying to get pregnant, consider getting your genes tested to determine if you have the MTHFR genetic variation. Knowledge will give you the power to make informed choices about your unique nutritional needs, including whether or not you should choose prenatal and fertility supplements that contain the active, methylfolate form of folic acid.

Vitamin B9 is found as either the synthetic form (folic acid) that appears in many vitamin supplements and fortified foods or the naturally occurring form found in foods (folate). Both the synthetic and most of the food-derived folate we consume must be converted via a natural enzyme pathway in our body to the final bioactive form called L-methylfolate (also known as 5-MTHF). Once MTHF is created, this active form of B9 can enter cells and cross over the blood-brain barrier to help nourish our tissues and brains. Successful conversion from folic acid or folate to MTHF is dependent upon a converting enzyme known as MTHFR.

MTHFR is the cause of elevated homocysteine levels tied to frequent miscarriages

Why do homocysteine levels become elevated? Methylfolate, the active form of folic acid, plays a role in converting homocysteine into methionine (a harmless amino acid), so if methylfolate is lacking due to the MTHFR mutation and subsequent inability to convert folic acid to methylfolate, homocysteine can build up to dangerous levels.

Researchers have discovered an association between high homocysteine levels and recurrent miscarriage, which suggests that the MTHFR genetic variation may play a role in pregnancy loss.

The link between MTHFR and PCOS

The most common specific condition that causes infertility in women is polycystic ovary syndrome (PCOS). Women with PCOS are prone to hormonal and metabolic imbalances, including blood sugar dysregulation, also known as insulin resistance. These metabolic issues can cause chronic anovulation (when ovaries do not release an oocyte during a menstrual cycle), oligomenorrhea (irregular periods), hyperandrogenism (too much testosterone), and insulin resistance. Given this wide range of fertility-related symptoms, it is not surprising that PCOS is a leading cause of infertility.

Many studies are being done to understand the underlying causes of PCOS. A 2014 study found a connection between PCOS and MTHFR gene mutations, with the researchers concluding that a specific MTHFR mutation increases susceptibility to PCOS. The common thread between MTHFR and PCOS once again has to do with homocysteine levels. In general, the most common cause of elevated homocysteine levels (hyperhomocysteinemia) is reduced activity of MTHFR, which results in reduced production of methylfolate. Women with PCOS typically test positive for higher homocysteine levels than other healthier women.



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