NutriStack
Phenytoin and Vitamin D3, a synergy.
Phenytoin is a potent CYP enzyme inducer that accelerates vitamin D catabolism through increased 24-hydroxylase activity. Long-term phenytoin use commonly causes vitamin D deficiency, osteomalacia, and increased fracture risk. Vitamin D supplementation is recommended during chronic therapy.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Phenytoin and Vitamin D3
- Pair type
- Synergy
- Evidence (highest tier)
- Strong
- Source citations
- 4 sources
- Stack Score effect
- +2 to your Stack Score (per scored synergy row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Synergy · Strong evidence
Synergy
What is happening. Phenytoin is a potent CYP enzyme inducer that accelerates vitamin D catabolism through increased 24-hydroxylase activity. Long-term phenytoin use commonly causes vitamin D deficiency, osteomalacia, and increased fracture risk. Vitamin D supplementation is recommended during chronic therapy.
Mechanism. Phenytoin induces CYP3A4 and CYP24A1 (24-hydroxylase), which accelerates the catabolism of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to inactive metabolites. It may also directly impair calcium absorption independently of vitamin D status.
Recommendation. Supplement with vitamin D3 (1000-4000 IU/day) during long-term phenytoin therapy. Monitor 25-OH vitamin D levels periodically and adjust dosing to maintain adequate levels (>30 ng/mL). Higher doses may be needed than in the general population.
Sources (4)
- Pack AM, Morrell MJ. Epilepsy and bone health in adults. Epilepsy Behav. 2004;5(Suppl 2):S24-S29. PMID 15123009
- Zhang Y, Fang F, Tang J et al.. Association between vitamin D supplementation and mortality: systematic review and meta-analysis.. BMJ. 2019. PMID 31405892
- Chang MC, Choo YJ. Effects of Whey Protein, Leucine, and Vitamin D Supplementation in Patients with Sarcopenia: A Systematic Review and Meta-Analysis.. Nutrients. 2023. PMID 36771225
- Fiamenghi VI, Mello ED. Vitamin D deficiency in children and adolescents with obesity: a meta-analysis.. Jornal de pediatria. 2021. PMID 33022267
Stack Score
How this pair moves the number.
Effect on the composite score
If both Phenytoin and Vitamin D3 are in the same stack, this pair applies +2 to your Stack Score (per scored synergy row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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