Supplements and Phenytoin.
Phenytoin, sold under the brand names Epanutin, Dilantin, 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
Last reviewed 21 June 2026. Each interaction below lists the evidence its assessment drew on: some rest on studies of the exact pair, others on mechanism evidence, where a citation may support one part of the reasoning rather than the exact combination. The evidence line on each entry says which.
Reduced anticonvulsant level
Amber Does Vitamin B Complex interact with ?
At high doses, the vitamin B6 in a B complex 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.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Folate-anticonvulsant (two-way)
Amber Does Folate interact with ?
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.
Evidence: Supported by human study data.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
CYP induction
Amber Does Ginkgo Biloba interact with ?
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.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does St John's Wort interact with ?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
CYP2C9 inhibition
Amber Does Resveratrol interact with ?
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.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Drug depletes the supplement
Amber Does Vitamin D3 interact with ?
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.
Evidence: Supported by human study data.
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.
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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 methodologyA full supplement review, built around you, not a generic stack.
The free checker answers one interaction question at a time. A Distil report reviews the bigger picture: your goals, diet, medications, current supplements and any blood results you provide, then shows what appears worth keeping, changing, adding or leaving out.
- what your diet already covers, so you are not adding a capsule for something food is already handling
- which evidence-graded compounds are worth considering for your goals, and which were considered but left out
- what to keep, change or stop from what you already take, plus the order to introduce anything new
- how your medications and complete supplement stack fit together, with daily timing and a clear point for reassessment
The interaction check is one section of the full report. You also get the reasoning behind each recommendation and the evidence references used.
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