NutriStack
Valproic Acid and Vitamin D3, a synergy.
Long-term valproic acid use has been associated with lower 25-hydroxyvitamin D and lower bone mineral density, especially in children and patients treated for years. A randomized trial in children on valproate found daily vitamin D supplementation reduced the decline in vitamin D and bone-mineral markers. This is most relevant for chronic therapy, low sun exposure, low dietary intake, or other fracture risks.
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
- Valproic Acid and Vitamin D3
- 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. Long-term valproic acid use has been associated with lower 25-hydroxyvitamin D and lower bone mineral density, especially in children and patients treated for years. A randomized trial in children on valproate found daily vitamin D supplementation reduced the decline in vitamin D and bone-mineral markers. This is most relevant for chronic therapy, low sun exposure, low dietary intake, or other fracture risks.
Mechanism. Valproic acid is not a classic strong enzyme inducer, but long-term use is associated with changes in vitamin D status, bone turnover, and bone mineral density. Vitamin D3 supports calcium absorption and bone mineralization, helping offset part of this chronic risk.
Recommendation. Ask about baseline and follow-up 25-hydroxyvitamin D testing if you take valproic acid long term. Use vitamin D3 supplementation when levels are low or when your clinician recommends prevention. Pair supplementation with bone-health monitoring rather than relying on vitamin D alone.
Sources (2)
- Min L, Chunyan W, Biaoxue R. Effects of valproic acid on skeletal metabolism in children with epilepsy: a systematic evaluation and meta-analysis based on 14 studies. BMC Pediatr. 2020;20(1):97. PMID 32122313
- Mohanraj R, Sahu JK, Prasad K, Tripathi M. Effect of Daily Vitamin D Supplementation on Serum Vitamin D Levels in Children with Epilepsy Receiving Sodium Valproate Monotherapy: A Randomized, Controlled Trial. Indian J Pediatr. 2023;90(5):450-456. PMID 35763213
Stack Score
How this pair moves the number.
Effect on the composite score
If both Valproic Acid 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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