Valproate / Depakote
Common brand names: Depakote, Depakene, Depacon, Stavzor
Three nutrients listed against this medication. The most severe is marked critical.
At a glance
One of the three is marked well documented. The other two carry their own evidence levels.
At a glance
- Carnitine (L-Carnitine)Critical · Well documented
- ZincModerate · Mechanism only, no human trial
- SeleniumMild · Traditionally cited, limited evidence
Color shows how serious each listed effect is. The label beside it shows how strong the evidence is. The cards below explain each one and show its evidence.
Nutrients it can lower
Mechanism, Valproate is metabolized via carnitine-acylcarnitine translocase, massively increasing carnitine demand while impairing carnitine biosynthesis and renal reabsorption. Deficiency is associated with potentially fatal hyperammonemic encephalopathy.
Common signs, Hyperammonemia (confusion, lethargy), hepatotoxicity, nausea, fatigue, muscle weakness
Raskind & El-Chaar (Ann Pharmacother, 2000): carnitine deficiency in 50–70% of valproate-treated patients. FDA recommends carnitine in valproate patients with hepatotoxicity.
L-carnitine 1,000 to 3,000 mg daily in divided doses is a range in common use, not from a trial cited on this row; the cited paper reviews the role of carnitine supplementation during valproic acid therapy. Whether to supplement prophylactically is a question for the prescriber.
Mechanism, Increased urinary selenium excretion and impaired selenoprotein synthesis have been proposed as a valproate effect. The two controlled studies that measured serum selenium on valproate did not find one, so this remains a proposed mechanism with negative human data against it.
Common signs, Pancreatitis risk, immune suppression, thyroid dysfunction, oxidative stress
Verrotti et al. (Epilepsy Res, 2002; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 11823111) measured selenium in epileptic children before and after one year of valproate or carbamazepine, and Hamed et al. (J Pharmacol Sci, 2004; PMID 15599105) measured trace elements in epileptic patients on long-term therapy. Neither found a selenium deficit attributable to valproate. Not supported.
Selenium (as selenomethionine) was used at 100–200 mcg daily; intake is monitored and kept under 400 mcg/day.
Mechanism, Valproate forms complexes with zinc in the GI tract, reducing absorption. Zinc deficiency is associated with the hair loss commonly reported with valproate.
Common signs, Hair loss (alopecia), impaired wound healing, immune suppression
Kaji et al. (Epilepsia, 1992; PMID 1592036): serum copper was significantly lower in children on valproate; the zinc result was not a clean depletion signal. Valproate may affect zinc via metallothionein binding, and hair loss is reported, but the human data support copper more than zinc. Treat as mechanistic.
Zinc 25–30 mg daily with food is a range in common use, not from a trial cited on this row; the cited paper measured serum copper and zinc in children on valproate. Long-term zinc at this level is paired with copper 1–2 mg in practice, because sustained zinc can lower copper status.
For your next appointment
It prints or saves as a single page. Whether to add a supplement for a nutrient this medication may lower is a decision for your prescriber.
Disclosure
These statements have not been evaluated by the Food and Drug Administration. Any grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
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