PubMed indexes 8 records that name Phenytoin and Vitamin B9 together, either in the title or in an interaction, co-administration, or pharmacokinetic context. The key findings come first, in the authors’ own words, followed by every study with its design and PubMed link.
A summary of published research, not medical advice. A pharmacist can check any combination against your full list of medicines and supplements.
Reviews and human studies first. Each quote is the authors’ own conclusion about their study, not a NutriStack assessment, and a single study is not a consensus.
“Our meta-analysis indicates that PHT monotherapy is associated with the increase in the serum homocysteine levels and decreased levels of folate and vitamin B12, and hyperhomocysteinaemia may contribute to the acceleration of the atherosclerotic process. Therefore, the patients under these medications should be monitored plasma homocysteine.”
“Dietary folate intakes during treatments 1 and 2 were not significantly different. This study suggests an interdependence between PHT and folic acid and supports the observation that fertile women treated with PHT require folic acid supplementation to maintain a normal serum folate level.”
“Folic acid supplementation should be initiated each time phenytoin therapy commences because of the hypothesized cofactor mechanism, decreased adverse effects associated with folate deficiency, and better seizure control with no perturbation of phenytoin pharmacokinetics.”
The research
8 studies naming Phenytoin and Vitamin B9.
Strongest relevance first: papers naming both substances in the title, then human trials and systematic reviews.
“Our meta-analysis indicates that PHT monotherapy is associated with the increase in the serum homocysteine levels and decreased levels of folate and vitamin B12, and hyperhomocysteinaemia may contribute to the acceleration of the atherosclerotic process. Therefore, the patients under these medications should be monitored plasma homocysteine.”
Journal of the American Dietetic Association · 1995 · PMID 7860949
Clinical TrialRandomized Controlled Trial
“Dietary folate intakes during treatments 1 and 2 were not significantly different. This study suggests an interdependence between PHT and folic acid and supports the observation that fertile women treated with PHT require folic acid supplementation to maintain a normal serum folate level.”
“The results of the study suggest a higher incidence of gingival enlargement with an early onset and increased severity in phenytoin treated epileptic patients with a positive correlation with falling serum folic acid levels as the duration of the therapy increases.”
The Annals of pharmacotherapy · 1995 · PMID 8520091
ReviewHuman subjects
“Folic acid supplementation should be initiated each time phenytoin therapy commences because of the hypothesized cofactor mechanism, decreased adverse effects associated with folate deficiency, and better seizure control with no perturbation of phenytoin pharmacokinetics.”
Drug intelligence & clinical pharmacy · 1984 · PMID 6370643
ReviewHuman subjects
“The supplementation of folic acid to folate-deficient patients taking phenytoin has been shown to result in lowered serum concentrations of phenytoin, and possibly loss of control of the seizure disorder. Folate appears to be associated with the hepatic metabolism of phenytoin, although the effect of folic acid supplementation on phenytoin elimination kinetics is suggested to be individualized.”
“Ratios of urinary metabolites to parent drug increased in those patients showing a decrease in plasma phenytoin caused by folic acid supplementation. This indicated that a folic acid-associated increase in phenytoin oxidative metabolism had occurred.”
Search-based evidence indexes have real limits, and it is worth being explicit about them:
Selection. These records were found by searching PubMed titles and abstracts for both substance names alongside interaction and pharmacokinetic terms. Relevant work that phrases things differently, or is not indexed in PubMed, will be missing.
No effect size. The quoted conclusions are the authors’ words about their own study. We have not extracted effect direction or magnitude, and a single study’s conclusion is not a consensus.
Population mismatch. Findings in healthy volunteers, animals, or a specific patient group may not transfer to you, your dose, or your formulation.
Absence is not safety. Few published studies means the combination is under-studied, which is not the same as established as safe.
How to read this page
A literature summary, not guidance.
A study listed here is not proof that Phenytoin and Vitamin B9 interact. Two substances can be named together in a paper that never tested them in combination, and a source listed as background may cover only one of them.
Findings are quoted from each abstract as the authors wrote them. NutriStack has not re-analysed, pooled, or reconciled them, and they may disagree with each other.
Decisions about prescription medication and supplements belong with your prescriber or pharmacist, who can see your full regimen. Our timing guide and forms guide explain the general mechanisms.
Nearby evidence
Other pairs with published research.
Pages covering Phenytoin or Vitamin B9 alongside a different substance.
NutriStack is a free iPhone app for organising a supplement routine: what you take, when, and what the published record says about it. Its exploratory interaction checker covers Phenytoin, Vitamin B9, and several hundred other substances.
Log your routine, get reminders at the times you choose, and scan a label to add a product. The checker is a research and organisation tool, not a clinical decision aid.
NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.
