NutriStack
Phenytoin and Vitamin B12, a synergy.
Phenytoin therapy is associated with lower vitamin B12 levels and higher homocysteine in multiple studies. B12 deficiency can cause anemia, neuropathy, cognitive symptoms, and can compound folate-related problems already known with phenytoin. Risk is higher with long-term use, older age, vegetarian diets, metformin or acid-suppressing therapy, or baseline B12 deficiency.
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 B12
- Pair type
- Synergy
- Evidence (highest tier)
- Strong
- Source citations
- 2 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 therapy is associated with lower vitamin B12 levels and higher homocysteine in multiple studies. B12 deficiency can cause anemia, neuropathy, cognitive symptoms, and can compound folate-related problems already known with phenytoin. Risk is higher with long-term use, older age, vegetarian diets, metformin or acid-suppressing therapy, or baseline B12 deficiency.
Mechanism. Phenytoin can disturb one-carbon metabolism and is associated with lower serum B12 and folate plus higher homocysteine. Restoring B12 helps correct deficiency-related hematologic and neurologic risk but does not replace phenytoin monitoring.
Recommendation. Ask about periodic B12 testing if you take phenytoin long term or develop numbness, balance problems, fatigue, or macrocytic anemia. Supplement B12 if levels are low or borderline with symptoms. Keep seizure medication dosing unchanged unless your prescriber adjusts it.
Sources (2)
- Xu Y, Zhang N, Xu S, Xu H, Chen S, Xia Z. Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98(12):e14844. PMID 30896627
- Kathiravan M, Kavitha S, Shanthi R. To determine the effect of long-term antiepileptic drug on the serum folate and vitamin B12 among epileptic patients. Sci Rep. 2021;11(1):4393. PMID 33623072
Stack Score
How this pair moves the number.
Effect on the composite score
If both Phenytoin and Vitamin B12 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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