The demand for folate increases when human cell growth is very active, such as in pregnancy. Studies have found that low dietary intake of folate increases the risk of delivering a child with several types of birth defects, particularly neural tube defects (NTD) and possibly leading to poor growth in the fetus or placenta

Periconceptional and the first period after conception are particularly important for folate supplementation especially because a woman often does not know she is pregnant.

It is recommended that for all women folate levels should be high for at least one month prior to possible conception and continued at that level for the first three months of pregnancy.

Quatrefolic® as a source of (6S)-5-methyltetrahydrofolate might be particularly useful to provide the nutritionally active form of folate during preconceptions, pregnancy and lactation.

Why do pregnant women need folate?

Adequate folate levels are critical for a healthy pregnancy, aiding proper foetal development by supporting cell growth and division and DNA repair, as well as preventing birth defects. During pregnancy, folate requirements increase by 5 fold to 10-fold to support embryonic and foetal development, as well as maternal tissue growth. 

Folates also reduce risk of preterm birth, low birth weight, developmental birth defects like cleft lip and palate, and neural tube defects like spina bifida. These birth defects happen in the early stages of pregnancy when the neural tube does not form properly, preventing normal development of the baby’s brain and spinal cord. Humans cannot make folate.

Like many essential nutrients, we must instead get it from our diet. 

Folate is found in many foods, including spinach, green leafy vegetables, and whole grains, however many governments and health authorities recommend – and even mandate – folate or folic acid supplementation for women before and during pregnancy because they generally do not consume enough through diet.

Folic acid vs. active folate: What’s the difference?

While often used interchangeably, folic acid and folate are not the same. Folic acid is the inactive precursor to active folate that is used in many supplements and fortified foods. However, to become biologically active, folic acid needs to go through several transformation steps in the body in order to be converted into active folate, which is known as 5-methyltetrahydrofolate (5-MTHF), as found in the ingredient Quatrefolic®.

For a long time, fortified foods and supplements were made with folic acid as the only source of vitamin B9 because it was shown that folic acid was more stable and bioavailable than the forms of folate found in foods. 

However, new findings over the last decade show that not everybody can convert folic acid to active folate in the same way – meaning that taking supplements containing folic acid can be ineffective for some people. These people have a specific genetic trait known as a MTHFR polymorphism, which means they cannot produce enough of the enzyme that helps convert folic acid into active 5-MTHF folate.

Conversion into active folate is not required for reduced and methylated folates like Quatrefolic®; they are already in the active form.

How much folate should a pregnant women take?

Because many pregnancies can be unplanned, folate is recommended for sexually-active women of childbearing age. The European Food Safety Authority (EFSA) has set dietary reference values (DRV) for folate in healthy adults over the age of 18 at 330 micrograms per day. However, DRV for pregnancy and lactation are higher, at 600 micrograms and 500 micrograms per day, respectively.

The U.S. Food and Drug Administration (FDA) has set a Daily Value (DV) of 400 micrograms per day for healthy adults but also recommends that individuals who are pregnant should consume 600 micrograms daily, while those who are breastfeeding should consume 500 micrograms per day.

There can be big variations in how efficiently folic acid and other inactive versions of vitamin B9 are converted to the bioactive form of folate in the body. As the active form of folate that does not require any conversion steps, Quatrefolic® maximizes the protective benefits of folate and has clear benefits for pre-conception, pregnancy, and lactation.

Genetic differences: What are MTHFR gene polymorphisms?

Folic acid is converted into 5-MTHF through a multi-step process involving an important enzyme known as methylenetetrahydrofolate reductase (MTHFR). Even a slight variation in the MTHFR gene can mean the MTHFR enzymes it creates cannot function correctly, and so the conversion from inactive folic acid to active folate hits a bottleneck.

A total of 9 common variants have now been identified by researchers. The two most common are known as C677T and A1298C. Studies have shown that polymorphic MTHFR may function with only around 55% to 70% efficacy compared to up to 100% in non-polymorphic people. 

Given that pregnancy increases the body’s demand for folate between 5 and 10-fold, these variations in genetic make-up can have dramatic implications. MTHFR polymorphism during pregnancy has been linked with a higher incidence of preeclampsia, mood impairment and postpartum depression (PPD), and hyperhomocysteinemia in recurrent pregnancy loss.

This also means that people with MTHFR polymorphism often do not benefit from folic acid supplementation, even at very high doses. This is where active folates like Quatrefolic® come into play, bypassing the metabolism function the gene would normally provide.   

How common is MTHFR polymorphism?

Variations to the MTHFR gene are known to differ widely around the world. It is estimated that more than 40% of the global population have a genetic variation that may impact folate conversion. 

Both the C677T and A1298C MTHFR gene polymorphisms have been reported to vary by ethnic group and region, with current research showing that MTHFR polymorphism is especially common in Caucasian women from North American origin, Italian and Hispanic people, Mexican women, and women in the Northern part of China.

However, testing pregnant woman for variations to the MTHFR gene is not a standard medical practice, and is only usually performed by specialist doctors in specific medical situations – such as in women with high homocysteine levels or in cases where there have been incidence of spina bifida or other birth defects in previous pregnancies.

Which form of folate should I take?

Choosing the right vitamins like the active form of folate Quatrefolic®, can be a great advantage during pregnancy, since you are able to guarantee that you are taking the bioactive form of 5-MTHF. 

By providing the natural and bioactive dose of folate directly, without the need for metabolization or enzymes like MTHFR, Quatrefolic® is immediately available for use in the body.

Even today in Europe and the United States half of pregnancies are unplanned and expose these women to a serious risk since defects of the brain and spine (Neural Tube Defects) develop in the first 28 days of pregnancy – before many women even know that they are pregnant. Clinical evidence suggests that supplementation of the natural form, 5-MTHF, is a better alternative to supplementation of folic acid, and that can effectively improve folate biomarkers in young women in early pregnancy to prevent NTDs.

Quatrefolic® may be particularly useful during preconception, pregnancy, and also lactation because it provides the “natural” and “bioactive” dose of folate directly, without metabolization by MTHFR.

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