Pregnancy: here's how folic acid fights malformations, gestosis, and postpartum depression

Pregnancy folic acid: here's how it fights malformations, gestosis, and postpartum depression

Following a diet rich in folate during the pre-conception period, pregnancy and breastfeeding is very important for the health of the woman and her baby. However, a proper diet is often not enough to ensure the proper intake of these substances. That's why taking supplements containing the active form of folic acid (L-methylfolate) can help mothers-to-be avert the risk of gestosis, or serious malformations for the baby such as Spina Bifida.

What is folic acid?

Folic acid is a vitamin (vitamin B9) and as such performs essential functions in the human body. It was the American Mitchell, in the 1940s, who was the first to use the word "folic acid" (from the Latin folium, leaf) to refer to certain substances extracted from spinach leaves that can counteract particular types of anemia. Currently, the term folic acid denotes the synthetic chemical molecule found in vitamin supplements or used in the food industry to enrich certain foods. 

The term folate denotes a group of folic acid-like substances found in certain foods, and thus representing the "natural" form of vitamin B9. Although the terms "folates" and "folic acid," therefore, refer to molecules with similar structure and nutritional properties, they should not be confused. In addition to the chemical formula, folates and folic acid also differ in the ability with which they are absorbed (bioavailability) and utilized by the body. More precisely, folic acid has a higher bioavailability than the natural forms of the vitamin. Both folic acid and folates are biologically inactive, so once ingested they must both be transformed in the body into the metabolically active form: methyltetrahydrofolate (or 5-MTHF) or L-methylfolate.

In what foods are folates found?

Folate must necessarily be introduced through the diet as our body cannot produce it. The intestinal bacterial flora can form a small amount of folate but absolutely not enough to cover the needs of the human body. Folate is mainly found in green leafy vegetables and citrus fruits, but also in other foods such as offal, legumes, cereals and eggs. Foods commonly used in our diet that contain folate, in rather varying amounts, include the following:

• asparagus
• broccoli
• artichokes
• cauliflowers
• oranges, clementines, tangerines
• kiwi
• walnuts, almonds, hazelnuts
• chard
• beans, chickpeas, lentils, peas
• endive
• lettuce
• whole grain bread and pasta
• spinach
• liver and offal
• eggs

In addition to including folate-rich foods in your diet, it is important to cook them using methods, such as steaming, that do not disperse their content too much. In fact, folates are very sensitive to high temperatures and light and can be lost in the cooking liquid during preparation.

What is folic acid used for?

Within our bodies, folic acid performs several important functions, in particular it is involved in DNA synthesis, a key step in ensuring proper cell division. Folic acid is therefore essential for all those cells that undergo rapid division processes and are constantly renewing themselves, such as those of the skin, hair, nails, and blood. There are also particular stages of life characterized by a high rate of cell division, such as occurs in rapidly growing tissues in infants, children, and adolescents or in pregnancy, when organs develop and form during the formation of the embryo. At this stage of development in the womb , themother's diet alone is insufficient to provide the right amount of folic acid, and such insufficiency can be dangerous to the fetus. Folate deficiency in pregnant women is common and is a risk factor for the occurrence of malformations in the unborn child, such as Spina Bifida.

The importance of folic acid in pregnancy

Although folates are very important for health at all stages of life, numerous studies have shown their crucial role especially in the prevention of serious defects in the embryo. Deficiency of this vitamin in pregnant women may increase the risk of congenital malformations in the fetus such as neural tube defects (NTDs) and other abnormalities including cardiovascular, urinary tract, limb, and malformations of the lips and palate (cleft lip). DTNs are abnormalities due to the altered formation of the central nervous system that occurs in the embryo in the first 28 days after conception. 

Spina Bifida is certainly the most serious of the DTNs, being a malformation of the spinal cord. In Italy, the disease affects one in about 1,300 newborns and causes very serious disabilities. A diet rich in fruits, vegetables and legumes containing folate can help reduce the likelihood of the congenital malformations; in fact, some research has observed that populations following a Mediterranean-style diet have a reduced incidence of DTNs. Diet alone is almost never sufficient to cover daily folate requirements, and if pregnancy is planned, it is necessary to take folic acid supplements.Scientific studies have shown that regular use of folic acid (400 mcg per day), started before conception, reduces the risk of developing birth defects such as DTNs by up to 70 percent.Theuse of folic acid supplements also reduces the likelihood of developing other birth defects, such as heart disease and cleft lip, by 20 percent. 

Prevention of birth defects can therefore be achieved by folic acid supplementation in women of childbearing age, before pregnancy and for the first 3 months of gestation. According to the current LARN (Reference Intake Levels of Nutrients and Energy for the Italian Population) recommendations, all women, but especially those who want to have a baby, need 400 micrograms (mcg) of folic acid every day. During pregnancy the recommended amount of folic acid rises to 600 mcg, and in lactation to 500 mcg. It is important to take the supplements even before pregnancy, as women usually realize they are pregnant when the neural tube in the embryo has already formed.

Does folic acid reduce the risk of gestosis?

The protective role of folic acid in pregnancy is not just about the risk of birth defects. Recent research has shown that supplementation before conception and throughout pregnancy can reduce the risk of gestosis (or preeclampsia), a syndrome that affects women during gestation causing very serious damage to the fetus and the mother-to-be, sometimes even fatal. 

Using data collected from a large hospital in Gansu Province, China, researchers examined the relationship between the use of dietary supplements containing folic acid, a folate-rich diet and the risk of preeclampsia in 10,041 pregnant women. Results showed that women who consumed folic acid supplements showed 40 percent lower risk of gestosis, compared with those who did not use it; these results did not change whether the supplements were consumed during the second or third trimester of pregnancy, nor whether the supplement was composed of folic acid alone or as part of a multivitamin complex. 

When the authors estimated folic acid intake from foods in relation to disease, they found no association. This is probably due to the low amount of folate consumed by the women considered in the study; in fact, all of them were taking daily folate intakes of between 152 and 274 mcg, far from the recommended 400 mcg. Considering that the bioavailability of folate from food is highly variable, the results of this study suggest the continued use of folic acid supplements even after the first 3 months of pregnancy.

Folates: good for cardiovascular health and nervous system function

The importance of folic acid is not limited to maternal and child health, but it can help reduce the likelihood of occurrence of other harmful conditions in people of all ages. Folic acid and folates, as mentioned earlier, were initially studied for their role in the prevention of certain forms of anemia, such as megaloblastic anemia characterized by larger-than-normal red blood cells that are deformed, very short-lived, and produced in smaller amounts. 

Folate is, in addition, essential for the synthesis of neurotransmitters, the molecules that transmit signals between neurons, and for carrying out important reactions such as those that reduce concentrations of homocysteine, a substance that in excess is a risk factor for cardiovascular disease. Some studies have shown that folate deficiency can impair neurotransmitter production and be one of the causes of depressed mood, especially in women who have just had a baby, in postmenopausal women, and in the elderly in general.The latter often have a folate deficit because they are unlikely to follow a proper diet. 

During aging, then, many physical changes occur such as alterations in gastrointestinal function that could further affect the absorption of different forms of folate. This deficiency may promote deficits in cognitive function, dementia, and Alzheimer's disease. According to a study by researchers at Columbia University in New York, New York, USA, published in the Journal of the Academy of Nutrition and Dietetics, deficiency of folate and other B vitamins is very common among postmenopausal women due to improper diet. This deficiency was found to be associated with an increased risk of dementia and mild cognitive impairment, suggesting the use of folic acid supplements even later in life.

Folic acid supplements: sometimes they are not enough 

Folic acid, and folates contained in foods, as ingested are inactive, so in order to perform their biological functions they must undergo transformations at the level of intestinal cells and the liver, and be converted to the active form: L-methylfolate, (or 5-MTHF), through a multi-step process. Conversion to the bioactive form occurs through the intervention of certain enzymes, including the enzyme methylenetetrahydrofolate reductase. The ability to convert folic acid is not the same for everyone, but varies from person to person due to normal genetic differences in each person.

Some individuals, for example, possess forms of methylenetetrahydrofolate reductase that are incapable or inefficient at converting folic acid into L-methylfolate. The administration of simple folic acid may have other drawbacks as well: some enzymes involved in the chain of reactions appear to become saturated and thus "block" when too much folic acid is taken. In addition, while gut cells are able to adequately convert folate from food into L-methylfolate, the synthetic folic acid from supplements is converted less efficiently. According to research, reduced bioavailability and accumulation of unmetabolized folic acid affects a large proportion of the population.  

The gene frequency in Europe of the mutation is 3-3.7 percent and results in a condition of heterozygosity (that is, when at least half of the enzyme is synthesized correctly) in about 42-46 percent of the Italian population and homozygosity (when the entirety of the enzyme is synthesized incorrectly) of 15-18 percent. Those with the mutation therefore may show symptoms of folic acid deficiency even if they take supplements. To remedy these problems, a new generation of folic acid supplements has been developed in recent years that already contain the biologically active form.L-methylfolate is up to 3 times more bioavailable than folic acid taken as such, and its concentration in the blood is up to 7 times higher than the non-active form. This increased bioavailability is particularly important in people who have genetic deficiencies that hinder the transformations that the vitamin undergoes after ingestion. Clinical studies have shown that 'supplementation with L-methylfolate, when properly followed, can dramatically increase the concentration of folate in red blood cells, an indicator of the amount of folate, and is the best alternative for supplementation and thus prevention of DTNs.

VitaDHA Maternal

VitaDHA Materna is a dietary supplement produced by U.G.A. Nutraceuticals based on DHA and L-methylfolate (^{Quatrefolic®}), which is ideal in the pre-conception period, during pregnancy and lactation. Each capsule contains: 250 mg of theomega-3 DHA in its best-absorbed form i.e., that in the form of triglyceride and 400 mcg of L-methylfolate glucosamine salt (^{Quatrefolic®}) the active and most bioavailable form of folic acid and which does not require transformation once absorbed.Just take 1 pearl daily, before or during a main meal, to contribute to the proper development of the fetus and the maintenance of the mother's health . This product combines the action of folate, a vitamin now known for its ability to reduce the risk of birth defects, and DHA, the most important omega-3 in the development of the nervous system and vision, being a structural and functional molecule of neurons and the retina.

The effectiveness of a product combining two key components has been confirmed by a number of scientific studies, such as one published in 2007 in theAmerican Journal of Clinical Nutrition, which showed that simultaneous maternal supplementation of fish oil rich in EPA and DHA and L. methylfolate increased the blood concentrations of the substances without causing adverse reactions. 

Sources: Wang Y, Zhao N, Qiu J, He X, Zhou M, Cui H, Lv L, Lin X, Zhang C, et al. Folic acid supplementation and dietary folate intake, and risk of preeclampsia. Eur J Clin Nutr 2015;69:1145-50. McNulty H, Pentieva K. Folate bioavailability. Proc Nutr Soc. 2004 Nov;63(4):529-6. LARN: Reference Intake Levels of Nutrients and Energy for the Italian Population.IV Revision.

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