NutriStack
Methylfolate and Phenytoin, a caution.
Phenytoin depletes folate levels through increased catabolism and impaired absorption, potentially causing megaloblastic anemia. However, folate supplementation may reduce phenytoin levels by enhancing its metabolism, creating a bidirectional interaction that requires careful monitoring.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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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
- Methylfolate and Phenytoin
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. Phenytoin depletes folate levels through increased catabolism and impaired absorption, potentially causing megaloblastic anemia. However, folate supplementation may reduce phenytoin levels by enhancing its metabolism, creating a bidirectional interaction that requires careful monitoring.
Mechanism. Phenytoin inhibits folate absorption and increases its catabolism through enzyme induction. Conversely, folate supplementation enhances the activity of enzymes that metabolize phenytoin (CYP2C9/CYP2C19), potentially reducing phenytoin plasma levels. This creates a complex bidirectional interaction.
Recommendation. Folate supplementation (0.5-1mg/day) is generally recommended for patients on phenytoin, but phenytoin levels should be monitored when starting folate. Dose adjustments of phenytoin may be necessary.
Stack Score
How this pair moves the number.
Effect on the composite score
If both Methylfolate and Phenytoin are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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