Folic acid (B9): why it is started before pregnancy

Saturday morning, last month. A young woman walks in right as the pharmacy opens, slightly worried, and says she took a pregnancy test in the evening that came back positive. She asks which folic acid to buy and whether she is too late. We calculated together: week four to five. I told her what I say in such situations: you start today, you are not hopelessly late, but the best moment to start was two or three months ago. Then I explained why: the baby's neural tube, which becomes the brain and the spinal cord, closes between day 21 and day 28 after conception, in the days when most women do not yet know they are pregnant.

Folic acid is the only vitamin that needs to be in your body before you know you need it. And since nearly half of pregnancies are unplanned, the recommendations address not only couples who are trying, but every woman of childbearing age. In this article I have gathered the things I believe women should know: what this vitamin does, who should take it and in what dose, when the 400 mcg tablet is not enough, and what stands behind the advertisements of the so-called active forms.

Folic acid is the synthetic form of vitamin B9, while folate is the form found in food. The EU-approved health claims for folates are specific and appear on every label: it contributes to maternal tissue growth during pregnancy, to normal amino acid synthesis, to normal blood formation, to normal homocysteine metabolism, to normal psychological function, to the normal function of the immune system and to the reduction of tiredness and fatigue, and it also has a role in the process of cell division.

Supplemental folic acid intake increases maternal folate status (the measure of vitamin B9 in the body), and low maternal folate status is a risk factor in the development of neural tube defects in the developing foetus. Behind this dry wording stands the strongest evidence in all of preventive medicine: when the tube fails to close properly, the result is spina bifida (a defect in which the spine does not close fully around the spinal cord, leading to permanent physical disability) or anencephaly (a severe defect in which much of the brain and skull does not develop; the condition is incompatible with life), and a daily intake of 400 mcg of folic acid, at least 1 month before conception and through the first trimester, reduces this risk dramatically.

Green leafy vegetables gave the vitamin its name: folium is Latin for leaf. Spinach, broccoli, legumes, liver, eggs and citrus fruits provide folate for your table. The problem is in the numbers: folate from food is absorbed more poorly than the synthetic form, so calculations are made in so-called dietary folate equivalents (DFE): 1 mcg DFE equals 1 mcg of food folate, while 0.6 mcg of folic acid from a supplement taken with food equals 1 mcg DFE. The synthetic form has better absorbability, and for this reason the same numerical amount in a tablet provides more usable vitamin for the body than the same figure obtained from food.

The second problem is cooking: folates are fragile and boiling can destroy up to half of the content. The third: unlike the United States, Canada and dozens of other countries, Bulgaria does not fortify flour with folic acid by law, so one of the staple foods on our tables carries no additional intake. That is why, when planning a pregnancy, the supplement does not replace food but complements it with a predictable dose that a salad cannot guarantee.

The scheme behind every major guideline: 400 mcg of folic acid daily, started at least one month before conception and continued through the end of week 12 of pregnancy. The US Preventive Services Task Force gives this recommendation its highest grade and addresses it to every woman who plans or could become pregnant, precisely because the critical window happens before the first test. Daily needs outside this scenario are 400 mcg DFE for adults, 600 mcg DFE during pregnancy and 500 mcg DFE while breastfeeding.

The evidence behind these figures is a rare case of clarity in medicine. The classic MRC study from 1991 was stopped early because the result was unambiguous: in women taking folic acid, recurrent neural tube defects fell by 71%. The Hungarian randomised trial by Czeizel and Dudás confirmed the same effect in first pregnancies, and the 2015 Cochrane review summarised it: periconceptional intake protects against these severe malformations. When three independent levels of evidence point in one direction, the advice at the pharmacy counter is easy.

There is a group of women for whom the standard dose is not sufficient: a previous pregnancy affected by a neural tube defect or one in the family, antiepileptic medicines, diabetes, severe obesity, malabsorption conditions such as coeliac disease (a chronic autoimmune disease in which consuming gluten damages the small intestine), or a state after bariatric surgery. For them the obstetrician prescribes 4-5 mg daily, and that is already a medicinal dose, written on a prescription and monitored. The difference between 400 mcg and 5 mg is not a case of more just in case, but an entirely different scenario with a different justification.

The upper limit for intake without medical supervision is 1000 mcg of folic acid daily for an adult. It was not invented at random: above it, a chronic excess can hide a vitamin B12 deficiency, which I will come to shortly. For this reason high-dose products from the shelf are not combined with one another, and any increase beyond the recommended dose is prescribed by a doctor.

At least once a month a patient with rheumatoid arthritis looks at me in confusion across the counter: their rheumatologist has prescribed methotrexate, which blocks the action of folates in the body, and together with it folic acid. And here follows an explanation to reassure the person: methotrexate is an antagonist (a medicine or substance that blocks or acts opposite to another substance) of folates and that is what makes it effective, but the blockade also hits healthy cells, and from there come some of the side effects: nausea, diarrhoea, mouth sores. The folic acid in parallel with the treatment protects the healthy cells and reduces these complaints, without cancelling the effect on the disease.

The scheme, however, is precise and it is a rheumatologist's job: usually 5 mg of folic acid once a week, always on a different day from the methotrexate, because on the same day the supplement can stop the medicine from doing its work. Those 5 mg are a prescription medicinal product, not a supplement of your own choosing. If you are on methotrexate and nobody has prescribed you folic acid, or you take it on the day of the medicine, that is a question for the rheumatologist at your next visit.

In recent years many products with active folate, methylfolate or 5-MTHF have appeared, accompanied by one and the same thesis: people with a variant of the MTHFR gene cannot process ordinary folic acid and must buy the more expensive form. The thesis sounds scientific but does not survive scrutiny. The MTHFR gene codes for an enzyme in the folate cycle and its common variants do reduce its efficiency, but the US Centers for Disease Control and Prevention are categorical: people with these variants process all types of folate, including folic acid. At the same intake, blood folate in the most severe variant is only about 16% lower, and what determines your levels is the dose you take, not your genotype.

There is a second, more practical argument: folic acid is the only form proven in clinical trials to protect against neural tube defects, while methylfolate has not been tested in such trials. A conclusion from accumulated experience and practice: for the vast majority, standard folic acid in the correct dose does its job at a normal price. And if you have a tested gene variant, a previous pregnancy with such a defect, or another specific condition, the choice of form and dose is a decision to make together with the doctor who follows you.

This is the reason high doses of folic acid are not taken without cause and without control. The two vitamins work in the same team of reactions, and when B12 is missing, folic acid in a large dose can fix the blood count so well that the anemia looks cured. The problem is that the nervous system meanwhile keeps suffering in silence: tingling, an unsteady gait, memory problems, and damage left too long can become irreversible.

That is why in people at risk of B12 deficiency (vegans, people over 60, those taking metformin or acid-reducing medicines) the two vitamins are checked together before long-term intake of high-dose folic acid. The whole logic of this pair, with the numbers and the risk groups, is laid out in the article on vitamin B12, which is worth reading after this one.

This article was written by Donka Arabadzhova, Master of Pharmacy, and is confirmed by the following sources: MRC Vitamin Study Research Group, The Lancet, 1991: prevention of neural tube defects; Czeizel A.E., Dudás I., New England Journal of Medicine, 1992: prevention of the first occurrence of neural tube defects; De-Regil L.M. et al., Cochrane review, 2015: periconceptional folate supplementation; USPSTF, 2023: folic acid for the prevention of neural tube defects; NIH Office of Dietary Supplements, Folate Fact Sheet for Health Professionals; CDC: MTHFR gene variants and folic acid; NHS: methotrexate and folic acid, how and when to take them; Regulation (EU) No 432/2012 (approved health claims for folates); Regulation (EU) No 1135/2014 (neural tube defect risk reduction claim).