Folic acid and the pill: can you take both at the same time?

No interaction of this kind has been described, and the most direct argument comes from pills that already contain a folate.

The medicines that genuinely expose you to contraceptive failure are enzyme inducers, such as certain antiepileptics or tuberculosis drugs: they speed up the elimination of hormones, and the product information then calls for an additional method during treatment and for the 28 days after it stops¹. Folate does not belong to this category.

The US Food and Drug Administration has also approved a pill combining ethinylestradiol, drospirenone and levomefolate calcium. Its prescribing information states that these tablets are bioequivalent to the same pill without folate for drospirenone and ethinylestradiol; in other words, adding the folate does not change exposure to the contraceptive hormones¹. This measurement concerns levomefolate, the active form of folate. Folic acid taken separately has not been the subject of an equivalent measurement, and it does not appear among the substances that the prescribing information lists as reducing the effectiveness of oral contraceptives¹. The question does arise the other way round for a few medicines: folate can alter the effect of antifolate treatments such as methotrexate, pyrimethamine or certain antiepileptics, and several medicines, conversely, lower folate¹. The pharmacist checks these combinations against the full prescription.

Nothing stands in the way, and the very existence of enriched pills shows it: the folate is swallowed in the same tablet as the hormones, every day.

No study has compared different times of intake. There is therefore no documented reason to space the two several hours apart, and no established advantage in taking them together. Taking your folate at the same time as your pill is mainly of practical interest, for the sake of regularity, which matters far more than the time of day, since red cell folate takes months to build up.

Reviews do not reach the same verdict: a 2015 meta-analysis measured a fall, whereas a 2011 review judged that the data do not demonstrate one for current pills.

A 2015 Canadian meta-analysis of 17 studies and 2,831 women measured, in users, an average fall in plasma folate of 1.27 µg/L, and a fall in red cell folate of 59.32 µg/L across 12 studies and 1,389 women. Its authors conclude that it is essential for women of childbearing age to continue folate supplementation during oral contraception².

A 2011 US review reads the same research differently. Most of the studies that concluded there was a negative effect date from a time when pills contained much more oestrogen, and many did not control for confounding factors. For its authors, the available data do not allow the conclusion that current pills worsen folate status; they do, however, retain an effect on vitamin B6³.

A study published in The Lancet in 1968, cited by a 2013 review that supports the hypothesis of a fall, reported that folate returned to baseline within three months of stopping the pill. The review’s authors draw from this a recommendation of folic acid for women planning a pregnancy straight after stopping⁴.

Guidelines agree on 400 µg a day from the moment you try to conceive, then until the end of the first trimester, which means starting before stopping the pill rather than after.

The World Health Organization recommends that all women take 400 µg of folic acid a day, from the moment they start trying to conceive until 12 weeks of gestation, and provides for 5 mg a day for women who have already had a pregnancy affected by a neural tube defect⁵. The UK’s NHS advises 400 µg a day, ideally three months before pregnancy and then for the first 12 weeks, with a 5 mg dose on prescription in several situations, including a history of neural tube defects, diabetes, certain blood disorders and treatment for epilepsy or HIV⁶. In France, the national health insurance (Assurance Maladie) describes supplementation prescribed, if possible, at least four weeks before conception and up to 12 weeks after the last menstrual period⁷.

The expected benefit is specific. A Cochrane review of five trials and 7,391 women found a protective effect of periconceptional folic acid against neural tube defects, with a relative risk of 0.31 (95% confidence interval: 0.17 to 0.58) across 6,708 births, and evidence rated as high quality. The same analyses show no clear effect on cleft lip or palate, heart defects or miscarriage⁸.

There is a simple reason for starting several weeks ahead: the neural tube closes before the end of the fourth week of pregnancy⁴, sometimes before the pregnancy is even known. As for the return of fertility, a systematic review of 22 studies and 14,884 women who had stopped contraception reports a pregnancy rate of 83.1% within 12 months, with no significant difference by type of method or by length of pill use⁹. A pregnancy can therefore occur in the very first cycles after stopping.

Several months for red cell folate, which reflects stores, compared with a few weeks for plasma folate.

A double-blind randomised trial followed 379 American women aged 18 to 40 for 24 weeks. In those receiving a pill containing 20 µg of ethinylestradiol and 3 mg of drospirenone with 0.451 mg of levomefolate calcium added, red cell folate rose from 990 to 1,406 nmol/L and plasma folate from 45.0 to 60.8 nmol/L, while values barely fluctuated on the same pill without folate¹⁰.

A second trial, in 172 German women in a country without flour fortification, specifies the timescales. Plasma folate approaches steady state at around 8 weeks, red cell folate at around 24 weeks. After the folate is stopped, the decline is slow: the median time during which red cell folate stays above 906 nmol/L is 10 weeks, and at the end of the 20 weeks of follow-up, 89.3% of women still had red cell folate above their baseline value. Results were comparable with 0.4 mg of standard folic acid¹¹. Both trials were run by the manufacturer of the enriched pill.

This slowness explains why guidelines talk about weeks or months ahead, not a few days.

These are oral contraceptives that contain, in addition to the hormones, levomefolate calcium, the already active form of folate. They are available in some countries, not all.

In the United States, the pill of this type described in the prescribing information cited combines 20 µg of ethinylestradiol, 3 mg of drospirenone and 0.451 mg of levomefolate calcium. Its indication covers contraception and raising folate levels in order to reduce the risk of a neural tube defect in a pregnancy that occurs while taking it or shortly after stopping¹. These pills are not sold in every country.

Its prescribing information points out something that applies to any folate intake, on the pill or not: folate can mask a vitamin B12 deficiency, correcting the blood abnormality without correcting the nerve damage¹. Long-term intake is therefore worth mentioning to your doctor, especially if your diet contains no animal products.

No data indicate that folic acid makes the pill less effective, and this intake comes into its own as soon as a pregnancy becomes possible.

Official guidelines target women who are trying to conceive, with 400 µg a day and a few weeks’ head start⁵⁷. For women with no plans for pregnancy, the guidelines cited here make no provision for routine intake on account of the pill alone, and the available reviews do not even agree on whether folate falls on current pills³.

Two situations are worth discussing with a doctor or pharmacist: a diet low in green vegetables, pulses and cereal products, and taking a medicine that interferes with folate. The discussion will then cover the dose and the duration, and the time of day you take it will remain a detail.