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Anticonvulsant medications - hydantoin derivatives

Editorial Note
Supporting Research


  • Phenytoin
    • Dilantin



Osteoporosis (bone loss) is the primary disease associated with long term calcium deficiency; it may be associated with bone pain and spinal deformity. Depleted levels can also cause muscle cramps, irregular heartbeat, and depression.

Vitamin B1 (Thiamine)

Symptoms of depleted levels of thiamine include weakness, fatigue, anorexia, constipation, memory loss, confusion, and depression. Deficiency may lead to beriberi, a condition characterized by inflammation of nerves, heart irregularities, and fluid retention.

Vitamin B9 (Folic Acid)

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

Vitamin H (Biotin)

Low levels of biotin are associated with changes in skin color, inflammation of the skin, hair loss, muscle pain, anemia, loss of appetite, depression, insomnia, and elevated levels of cholesterol.

Vitamin D

Vitamin D deficiency leads to abnormal bone formation (rickets) in children and softening of the bones (osteomalacia) in adults. Vitamin D deficiency interferes with calcium absorption, leading to deficiency of that nutrient with all of the associated symptoms (such as increased risk of fractures, osteoporosis (bone loss), and muscle weakness). More recently, vitamin D deficiency has been linked to compromised immunity, cancer, and other chronic conditions. Because this nutrient is fat soluble, prolonged periods of deficiency are required to produce these symptoms.

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

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

Bell RD, Pak CY, Zerwekh J, et al. Effect of phenytoin on bone and vitamin D metabolism. Ann Neurol. 1979;5(4):374-378.

Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: before and after folic acid administration. Epilepsia. 1992;33(4):712-720.

Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc. 1995;95(3):352-256.

Botez MI, et al. Thiamine and folate treatment of chronic epileptic patients: a controlled study with the Wechsler IQ scale. Epilepsy Res. 1993;16(2):157-163.

Boivin MA, Kahn SR. Symptomatic hypocalcemia from oral sodium phosphate: a report of two cases. Am J Gastroenterol. 1998;93(12):2577-9.

Cashman KD. Calcium and vitamin D. Novartis Found Symp. 2007;282:123-38; discussion 138-42, 212-8.

Cashman KD. Diet, nutrition, and bone health. J Nutr. 2007;137(11):2507S-12S.

Dastur D, Dave U. Effect of prolonged anticonvulsant medication in epileptic patients: serum lipids, vitamins B6, B12 and folic acid, proteins and fine structure of liver. Epilepsia. 1987;28:147-159.

Foss MC, Meneghelli UG, Verissimo JM. The effect of the anticonvulsants phenobarbital and diphenylhydantoin on intestinal absorption of calcium. Acta Physiol Lat Am. 1979;29(4-5):223-228.

Gascon-Barre M, Villeneuve JP, Lebrun LH. Effect of increasing doses of phenytoin on the plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations. J Am Coll Nutr. 1984;3(1):45-50.

Gough H, Goggin T, Bissessar A, et al. A comparative study of the relative influence of different anticonvulsant drugs, UV exposure and diet on vitamin D and calcium metabolism in out-patients with epilepsy. Q J Med. 1986;59(230):569-577.

Guardia G, Parikh N, Eskridge T, Phillips E, Divine G, Rao DS. Prevalence of vitamin D depletion among subjects seeking advice on osteoporosis: a five-year cross-sectional study with public health implications. Osteoporos Int. 2007; [Epub ahead of print].

Krause KH, Berlit P, Bonjour JP, et al. Impaired biotin status in anticonvulsant therapy. Ann Neurol. 1982;12(5):485-486.

Krause KH, Bonjour JP, Berlit P, et al. Biotin status of epileptics. Ann NY Acad Sci. 1985;447:297-313.

Lee BY, Yanamandra K, Bocchini JA Jr. Thiamin deficiency: a possible major cause of some tumors? (review). Oncol Rep. 2005;14(6):1589-92.

Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother. 1995;29(7-8):726-735.

Mock DM, Mock NI, Nelson RP, et al. Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy. J Pediatr Gastroenterol Nutr. 1998;26(3):245-250.

Pelton R, LaValle J, Hawkins EB, et al. Drug Induced Nutrient Depletion Handbook. Hudson, OH:LexiComp, Inc.;2001:395-404.

Reunanen MI, Sotaniemi EA, Hakkarainen HK. Serum calcium balance during early phase of diphenylhydantoin therapy. Int J Clin Pharmacol Biopharm. 1976;14(1):15-19.

Scheinfeld N. Phenytoin in cutaneous medicine: its uses, mechanisms and side effects. Dermatol. Online J. 2003; 9(3):6.

Schwaninger M, Ringleb P, Winter R, et al. Elevated concentrations of homocysteine in antiepileptic drug treatment. Epilepsia. 1999;40(3):345-350.

Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J ClinEndocrinol Metab. 1975;41(6):1125-1129.

Somerman MJ, Rifkin Br, Pointon-Miska S, et al. Effect of phenytoin on rat bone resorption in vitro. Arch OralBiol. 1986;31(4):267-268.

Ondrak KS, Morgan DW. Physical activity, calcium intake and bone health in children and adolescents. Sports Med. 2007;37(7):587-600.

Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006;5(11):949-60.

Sheweita SA, Khoshhal KI. Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Curr Drug Metab. 2007;8(5):519-25.

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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