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Anticonvulsant medications - valproic acid derivatives

Editorial Note
Supporting Research


  • Valproic Acid and Derivatives
    • Depacon
    • Depakene
    • Depakote Delayed Release
    • Depakote ER


Carnitine (L-Carnitine)

Although carnitine is made by the body, deficiency can occur and may be associated with anemia, fatigue, increased blood levels of ammonia, lethargy, unexplained stupor, and heart irregularities.


Although copper deficiency is rare, signs and symptoms of long term depletion of copper include anemia, changes in the structure and appearance of hair, heart damage, growth retardation, impaired bone formation, osteoporosis (bone loss), and emphysema (lung disease).


Selenium deficiency may be associated with muscular, digestive, and heart disorders; long-term deficiency may be associated with increased risk of developing certain chronic illnesses such as cancer, diabetes, or liver disease.

Vitamin B9 (Folic Acid)

Low levels of folic acid have been linked to anemia, heart disease, and birth defects.


Signs and symptoms of zinc deficiency include loss of appetite or sense of taste, growth retardation, skin changes, and increased susceptibility to infection.

Editorial Note

The selected depletions information presented here identifies some of the nutrients that may be depleted by certain medications. The signs and symptoms associated with nutrient deficiency may also indicate conditions other than nutrient deficiency. If you are experiencing any of the signs or symptoms mentioned, it does not necessarily mean that you are nutrient deficient. Nutrient depletion depends upon a number of factors, including your medical history, diet, and lifestyle, as well as the length of time you have been taking the medication. Please consult your health care provider; he or she can best assess and address your individual health care needs, and determine if you are at risk for nutrient depletions from these medications, as well as others not listed here.

Supporting Research

Alexander J. Selenium. Novartis Found Symp. 2007;282:143-9; discussion 149-53, 212-8.

Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY Acad Sci. 2000;889:87-106.

Araya M, Pizarro F, Olivares M, Arredondo M, González M, Méndez M. Understanding copper homeostasis in humans and copper effects on health. Biol Res. 2006;39(1):183-7.

Castro-Gago, M, Eiris-Punal J, Novo-Rodriguez MI, et al. Serum carnitine levels in epileptic children before and during treatment with valproic acid, carbamazepine, and phenobarbital. J Child Neurol. 1998;13(11):546-549.

Chung S, Choi J, Hyun T, Rha Y, Bae C. Alterations in the carnitine metabolism in epileptic children treated with valproic acid. JKMS. 1997;12:553-558.

Coulter DL. Carnitine, valproate, toxicity. J Child Neurol. 1991;61(1):7-14.

Donnelly PS, Xiao Z, Wedd AG. Copper and Alzheimer's disease. Curr Opin Chem Biol. 2007;11(2):128-33.

Felipez L, Sentongo T. Drug-Induced Nutrient Deficiencies. Pediatric Clinics of North America. 2009; 56(5).

Goggin T, Gough H, Bissessar A, et al. A comparative study of the relative effects of anticonvulsant drugs and dietary folate on the red cell folate status of patients with epilepsy. Q J Med. 1987;65(247):911-919.

Graf WD, Oleinik OE, Glauser TA, et al. Altered antioxidant enzyme activities in children with a serious adverse experience related to valproic acid therapy. Neuropediatr. 1998;29(4):195-201.

Hoffmann PR. Mechanisms by which selenium influences immune responses. Arch Immunol TherExp (Warsz). 2007; [Epub ahead of print].

Hurd RW, Rinsvelt HA, Wilder RJ, et al. Selenium, zinc, and copper changes with valproic acid: possible relation to drug side effects. Neurol. 1984;34(10):1393-1395.

Kaji M, Ito M, Okuno T, et al. Serum copper and zinc levels in epileptic children with valproate treatment. Epilepsia. 1992;33(3):555-557.

Lerman-Sagie T, Statter M, Szabo G, et al. Effect of valproic acid therapy on zinc metabolism in children with primary epilepsy. Clin Neuropharmacol. 1987;10(1):80-86.

Maret W, Sandstead HH. Zinc requirements and the risks and benefits of zinc supplementation.J Trace Elem Med Biol. 2006;20(1):3-18.

Navarro-Alarcon M, Lopez-Martinez MC. Essentiality of selenium in the human body: relationship with different diseases. Sci Total Environ. 2000;249:347-371.

Pelton R, LaValle J, Hawkins EB, et al. Drug Induced Nutrient Depletion Handbook. Hudson, OH:LexiComp, Inc.;2001:405-408.

Powell SR. The antioxidant properties of zinc. J Nutr. 2000;130(5S Suppl):1447S-54S.

Russell S. Carnitine as an antidote for acute valproate toxicity in children. Curr Opin Pediatr. 2007;19(2):206-10.

Sozuer DT, Baruteu UB, Karakoe Y, et al. The effects of antiepileptic drugs on serum zinc and copper levels in children. J Basic Clin Physiol Pharmacol. 1995;6(3-4):265-269.

Tsai MF, Chen CY. Valproate-induced hyperammonemic encephalopathy treated by hemodialysis. Ren Fail. 2008; 30(8):822-4.

Tubek S, Grzanka P, Tubek I. Role of Zinc in Hemostasis: A Review. Biol Trace Elem Res. 2007; [Epub ahead of print].

Van Wouwe JP. Carnitine deficiency during valproic acid treatment. Int J Vitam Nutr Res. 1995;65(3):211-214.

Yilmaz Y, Tasdemir HA, Paksu MS. The influence of valproic acid treatment on hair and serum zin levels and serum biotinidase activity. Eur J Paediatr Neurol. 2009;13(5):439-43.

Review Date: 4/19/2010
Reviewed By: Steven D. Ehrlich, NMD, Solutions Acupuncture, a private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed HealthCare Network.
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