NutriStack
Calcium and Valproic Acid, a synergy.
Valproic acid has been linked with lower bone mineral density in people with epilepsy, particularly with longer treatment duration. Adequate calcium intake is part of bone-health prevention for patients on long-term antiseizure therapy, especially when vitamin D status is also being managed. Calcium does not prevent every valproate-related bone effect, but low intake is a modifiable risk factor.
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
- Calcium and Valproic Acid
- Pair type
- Synergy
- Evidence (highest tier)
- Moderate
- 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 · Moderate evidence
Synergy
What is happening. Valproic acid has been linked with lower bone mineral density in people with epilepsy, particularly with longer treatment duration. Adequate calcium intake is part of bone-health prevention for patients on long-term antiseizure therapy, especially when vitamin D status is also being managed. Calcium does not prevent every valproate-related bone effect, but low intake is a modifiable risk factor.
Mechanism. Valproic acid is associated with reduced bone mineral density through mechanisms that may include altered bone turnover and vitamin D-related pathways. Calcium supports hydroxyapatite mineralization and works best as part of a broader bone-health plan that includes vitamin D adequacy.
Recommendation. Make sure your daily calcium intake is appropriate if you take valproic acid long term. Ask about vitamin D testing, dietary calcium review, and bone-density screening if you have fracture risks. Avoid excessive calcium supplementation unless prescribed, particularly if you have kidney stones or kidney disease.
Sources (2)
- Zhong R, Chen Q, Zhang X, Li M, Liang J, Lin W. Bone Mineral Density Loss in People With Epilepsy Taking Valproate as a Monotherapy: A Systematic Review and Meta-Analysis. Front Neurol. 2019;10:1171. PMID 31787923
- Krishnamoorthy G, Nair R, Sundar U, Kini P, Shrivastava M. Early predisposition to osteomalacia in Indian adults on phenytoin or valproate monotherapy and effective prophylaxis by simultaneous supplementation with calcium and 25-hydroxy vitamin D at recommended daily allowance dosage: a prospective study. Neurol India. 2010;58(2):213-219. PMID 20508338
Stack Score
How this pair moves the number.
Effect on the composite score
If both Calcium and Valproic Acid 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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