Folates in pregnancy – which ones to choose and how to supplement?

You can hear about folic acid for pregnant women everywhere – in supplement advertisements on the radio, television, websites – but also in the waiting room at the gynecologist’s. Why are they recommended for pregnant women, what impact do they have on a child’s development, and what should a future mother know to choose the best product for herself and her soon-to-be-baby?

Why are folates essential during pregnancy?

Folates play a crucial role at a very early stage of embryo development, especially in the process of neural tube formation, from which the fetal brain and spinal cord originate. Neural tube closure occurs between the 21st and 28th day after fertilization, often before a woman even knows she is pregnant. Folates participate in nucleotide synthesis and cell divisions, as well as in DNA methylation processes, which determine proper gene expression in rapidly differentiating tissues. Their deficiency during this critical period can lead to neural tube closure defects, resulting in severe developmental abnormalities such as spina bifida or anencephaly.

Supplementation with folates before pregnancy and in its early stages increases the availability of biologically active forms of folic acid in the mother’s body, which promotes the proper course of the described cellular processes. Epidemiological and clinical studies have shown that adequate folate intake significantly reduces the risk of neural tube defects and can also reduce the incidence of other congenital defects related to abnormal tissue and organ development. The protective effect of supplementation results not from “strengthening” the pregnancy, but from preventing deficiencies of a component essential for the basic mechanisms of embryonic development, the proper course of which depends on an adequate folate status from the very beginning of fetal life.

Folates and MTHFR – what should a future mother know?

MTHFR (methylenetetrahydrofolate reductase) is an enzyme involved in the metabolism of folates in the body, specifically in their conversion to a biologically active form participating in methylation processes and DNA synthesis. In the context of pregnancy, MTHFR is important because its efficiency affects how effectively a woman’s body utilizes supplied folates, both from diet and supplements. In some parts of the population, genetic variants of the MTHFR gene occur, with the most frequently described mutations being 677C>T and A1298C. These can be associated with reduced enzyme activity, potentially leading to decreased conversion of synthetic folic acid to its active forms. In practice, this means that for women with such variants, the demand for more readily absorbable forms of folates may differ, and standard folic acid supplementation may not always ensure optimal folate status in the body. For this reason, recommendations increasingly emphasize the importance of already reduced forms, such as 5-methyltetrahydrofolate, especially during the preconception period and early pregnancy, when the demand for folates is particularly high.

How to dose folates during pregnancy?

During pregnancy planning and in its early stages, supplementation with folates (vitamin B9) is most often recommended at a dose of about 400 µg per day, starting even a few weeks before attempting to conceive and continuing throughout the first trimester – this approach aims to maximally support DNA synthesis and prevent neural tube defects, which form very early in fetal development.

In subsequent trimesters, the demand may increase, which is why doses of about 600-800 µg of folates per day are taken, often in combination with other B vitamins, such as B12 or B6, which support homocysteine metabolism and general metabolic processes.

It is worth emphasizing that these data are exemplary guidelines – individual needs may vary depending on health status, diet, and the presence of other risk factors, so every woman who is pregnant or planning a pregnancy should discuss supplementation with her doctor.

Recommendations for MTHFR variants

For individuals with MTHFR gene variants that may reduce the efficiency of converting synthetic folic acid to its active form, specialists sometimes consider changing the supplementation strategy or modifying the dose.

In such cases, doctors may suggest using active forms of folates (e.g., 5-MTHF) or adjusting the dose, always based on clinical evaluation and laboratory tests, and taking into account the patient’s general health and other supplements being taken. Gynecological consultation is crucial here, as there is no universal dose suitable for everyone, and excessive supplementation without indications can be unfavorable.

Best forms of folates for pregnant women

In vitamin B9 supplementation, various chemical forms are distinguished – traditional, synthetic folic acid and its active derivatives, such as 5-MTHF (5-methyltetrahydrofolate).

• Folic acid, used for decades in clinical trials and prophylactic programs, is well-documented for its effectiveness in reducing the risk of neural tube defects at the population level. However, in the body, it must be enzymatically converted to its active form, which in some individuals (e.g., those with MTHFR variants) may occur less efficiently.
• On the other hand, active 5-MTHF (present in forms such as Quatrefolic®) is a form that does not require this metabolic step and is immediately available for use in methylation and DNA synthesis pathways.

For many women, especially those suspected of reduced folic acid conversion (e.g., in the case of MTHFR mutations), such a form may be more metabolically “practical” – although it is worth noting that both supplementation methods can be effective in individuals without these variants.

In practice, the choice of form is often made based on individual circumstances, tolerance, and medical consultation: folic acid has the broadest evidence in the prevention of neural tube defects, while 5-MTHF may be preferred where there are indications regarding folate metabolism or the intake of other medications affecting their conversion.

Bibliography:

• T. Tamura, M. F. Picciano, Folate and human reproduction, American Journal of Clinical Nutrition, no. 83/2006, issue 5.
• C. Dai, Y. Fei, J. Li, et al., A Novel Review of Homocysteine and Pregnancy Complications, BioMed Research International, 2021.
• A. Seremak-Mrozikiewicz, M. Barlik, P. Borowczak et al., The frequency of 677C >T polymorphism of MTHFR gene in the Polish population, Archives of Perinatal Medicine, no. 19/2013, issue 1.
• K. M. Cochrane, R. Elango, A. M. Devlin, et al., Supplementation with (6 S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada, British Journal of Nutrition, no. 131/2024, issue 1
• Position of Experts of the Polish Gynecological and Obstetric Society on the supplementation of active folates, choline and vitamins B6 and B12 in the preconception period, pregnancy and puerperium, March 2024 [access: phttps://www.ptgin.pl/sites/scm/files/2024-03/Foliany%20-%20Stanowisko%20Ekspert%C3%B3w%20PTGiP%20-%20final.pdf]