Supplements and Phenytoin.
Phenytoin, sold under the brand name Epanutin, is an antiepileptic drug. Several agents in this class are strong CYP inducers or inhibitors.
Phenytoin is an antiepileptic medicine. The class is heterogeneous. Enzyme inducers (carbamazepine, phenytoin, phenobarbital) drop plasma levels of many medicines given alongside. Enzyme inhibitors (valproate) raise them. The newer agents (levetiracetam, lacosamide) have quieter interaction profiles. The supplement interactions of greatest clinical importance. St John's Wort is excluded with the inducer antiepileptics on top of an already complex CYP picture. Folate at high doses competes with the folate depletion that antiepileptics drive, in a way that needs neurology team input rather than community pharmacy. Calcium and vitamin D status matter because inducer antiepileptics drive bone density loss over years; the SANAD bone substudy data is the relevant evidence base. Pregnancy planning on an antiepileptic regimen always runs through the neurology team, because of folate timing and the teratogenicity profile specific to each agent (valproate carries the highest, levetiracetam much lower).
Below are the 6 documented pairs we have explicitly assessed against Phenytoin in the Distil database: 6 amber. The pairs cluster around 5 mechanisms: Reduced anticonvulsant level, Folate-anticonvulsant (two-way), CYP induction, CYP2C9 inhibition, and Drug depletes the supplement. Every call is cited to either a clinical reference (PMID) or the British National Formulary. Anything not on this list is either still to be assessed or beyond our database scope. The checker beneath surfaces assessments by supplement, and the missing-item form at the bottom of the page routes any uncatalogued supplement into our next curation pass.
Documented interactions
Reduced anticonvulsant level
A B complex contains vitamin B6. At high B6 doses, B6 can lower the blood level of phenytoin, which may make seizure control less reliable. The B6 in a standard B complex is small and unlikely to matter; high-potency B6 products are the concern. If you take phenytoin, keep your B vitamin intake steady and mention any high-dose B6 to whoever manages your epilepsy rather than starting or stopping it suddenly.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Folate-anticonvulsant (two-way)
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.
CYP induction
There is a report of seizures returning in a person on phenytoin and valproate who was also taking ginkgo, with low blood levels of both seizure medicines. Ginkgo may lower the levels of these medicines, and ginkgo seeds also contain a natural compound that can trigger seizures. If you take phenytoin for epilepsy, it is safer not to add ginkgo without discussing it with the team managing your epilepsy.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
St John's Wort speeds up several of the liver enzymes that clear phenytoin, so it could lower your phenytoin level and let seizures break through. Phenytoin has a narrow safe range and small changes matter. Do not start or stop St John's Wort while taking phenytoin without telling whoever prescribes it, so your level and dose can be checked.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
CYP2C9 inhibition
Resveratrol can slow how the body clears phenytoin by acting on a liver enzyme (CYP2C9), which could raise phenytoin levels. Phenytoin has a narrow safe range and small rises can cause side effects, so tell your epilepsy team before taking resveratrol.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Drug depletes the supplement
Phenytoin speeds up the breakdown of vitamin D in the body, so people on long-term phenytoin often have lower vitamin D levels and, over years, can lose bone density. This is a reason to take vitamin D rather than avoid it: many specialists check vitamin D and supplement people on long-term phenytoin. It is worth letting your prescriber know so your vitamin D level and bone health can be kept under review and the dose set for you.
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 (food-supplement interactions only; for drug-drug interactions, the BNF is authoritative). Use the checker below to surface any supplement, 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.