Folate and medications.
Folate is classified as a foundation supplement in the Distil database, evidence Grade A. The page below lists every medication we have explicitly assessed it against.
Folate is the B vitamin with the most definitive evidence in supplements: taking it before and in early pregnancy cuts neural tube defects substantially, which is why the NHS recommends 400mcg up to 12 weeks. It also supports methylation, lowers homocysteine, and is studied as an adjunct in depression and male and female fertility. The active form, L-5-MTHF or methylfolate, bypasses the MTHFR enzyme step that an estimated 40% of people convert poorly, so it is the preferred form for fertility, pregnancy, and mental health, though plain folic acid is fine for most others. The interactions that matter are serious. Methotrexate works by blocking folate, so never supplement alongside it without oncology approval. Anticonvulsants such as phenytoin and carbamazepine lower folate and warrant a word with your prescriber. High-dose folic acid can mask a B12 deficiency, so the two are best kept adequate together. It is very well tolerated, with doses above 5mg reserved for medical supervision.
Below are the 4 documented pairs we have explicitly assessed for Folate: 4 amber. The pairs cluster around 3 mechanisms: Absorption interference, Antifolate antagonism, and Folate-anticonvulsant (two-way). Every call is cited to either a clinical reference (PMID) or the British National Formulary. Anything not listed here is either still to be assessed or beyond our database scope. The checker beneath surfaces assessments by medication, and the missing-item form at the bottom of the page routes any uncatalogued medication into our next curation pass.
Documented interactions
Absorption interference
Sulfasalazine reduces how well the gut absorbs folate, so people on it long-term can become low in folate. This is a reason to supplement rather than avoid, and folate is often recommended for people taking sulfasalazine, particularly for inflammatory bowel disease or rheumatoid arthritis. There is no need to space the doses apart in a complicated way: the issue is ongoing absorption, so the usual approach is simply to take a folate supplement and let your prescriber keep an eye on your folate level.
Antifolate antagonism
This one depends entirely on why methotrexate is being taken, so do not change anything yourself. For rheumatoid arthritis, psoriasis or similar conditions, low weekly methotrexate is very often prescribed alongside folic acid on purpose: the folate reduces sickness, mouth ulcers and liver-enzyme problems without stopping the methotrexate from working, and it is usually taken on a different day from the methotrexate. The picture is different for high-dose methotrexate used in cancer treatment, where folate and a related rescue drug are timed precisely by the cancer team and you should never add or adjust folate around it. If you take methotrexate, let whoever prescribes it set your folate, rather than starting or stopping it on your own.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Folate-anticonvulsant (two-way)
Carbamazepine tends to lower folate levels over time, so people on it for a long time often run low on folate, which can also push up a blood marker called homocysteine. This usually works in the direction of needing folate rather than avoiding it, and folate is often supplemented on purpose in people on carbamazepine. As with other epilepsy medicines, it is sensible to start folate with your prescriber's knowledge so your levels and seizure control can be kept under review. Let whoever manages your epilepsy know before you start or stop folate.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Phenytoin and folate affect each other in both directions. Phenytoin lowers folate levels over time, so people on it often run low. But starting a folate supplement can lower the amount of phenytoin in the blood, and if that drop is large enough it can make seizures harder to control. This does not mean folate is off-limits, and it is often given alongside phenytoin on purpose, but it is best started with your prescriber's knowledge so your phenytoin level and seizure control can be checked rather than changed blind. The safest approach is to tell whoever manages your epilepsy before you start or stop folate.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
What this list does not say. Pairs not flagged here are not implicitly safe. They are either not yet in our database, or fall outside our inclusion scope. Use the checker below to surface any medication, and submit a missing item if you take something we have not catalogued.
How we grade severity, choose what's in scope, and what we exclude.
Every call on this page is reasoned. We publish the full rubric for severity tiers, the medication inclusion logic, the evidence grades we accept, and what we deliberately leave out. About three thousand words. Worth reading once if you use this tool more than occasionally.
Read the full methodologyWant this checked across everything you take?
This page checks the pairs you enter. The personalised Distil report goes further:
- the same graded, cited interaction check across your whole stack, not just the pairs you thought to type in
- where your current routine may be leaving you short of your goals
- the evidence-backed compounds worth adding, and the ones worth dropping
It's a paid report: £79, or £49 for the first 25 customers. The interactions check is one section of it, and you can read a real one in full before you buy.
See a real sample reportSomething missing?
If a supplement or medication you take isn't in our autocomplete, tell us. We go through what people flag every week and add what's missing.