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
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
Low levels of folic acid have been linked to anemia, heart disease, and birth
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 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). Because this nutrient is
fat-soluble, prolonged periods of deficiency are required to produce these
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 healthcare provider; he or she can best
assess and address your individual healthcare needs, and determine if you are at
risk for nutrient depletions from these medications as well as others not listed
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.
Botez MI, Joyal C, Maag U, et al. Cerebrospinal fluid and blood thiamine
concentrations in phenytoin-treated epileptics. Can J Neurol Sci.
Cashman K, Flynn A. Optimal nutrition: calcium, magnesium and phosphorus.
Proc Nutr Soc. 1999;58:477-487.
Covington T, ed. Nonprescription Drug Therapy Guiding Patient
Self-Care. St Louis, MO: Facts and Comparisons; 1999:467-545.
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.
Holick MF, Krane SM, Potts JT. Calcium, phosphorus, and bone metabolism:
calcium-regulating hormones. In: Fauci AS, Braunwald E, Isselbacher KJ, et al,
eds. Harrison's Principles of Internal Medicine. 14th ed. New
York: McGraw-Hill Companies Health Professional Division; 1998:2221-2222.
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.
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
National Research Council. Recommended Dietary Allowances.
10th ed. Washington, DC: National Academy Press; 1989.
Potts JT. Diseases of the parathyroid gland and other hyper- and hypocalcemic
disorders. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's
Principles of Internal Medicine. 14th ed. New York: McGraw-Hill
Companies Health Professional Division; 1998:2241.
Rao DS. Perspective on assessment of vitamin D nutrition. J Clin
Reunanen MI, Sotaniemi EA, Hakkarainen HK. Serum calcium balance during early
phase of diphenylhydantoin therapy. Int J Clin Pharmacol Biopharm.
Schwaninger M, Ringleb P, Winter R, et al. Elevated concentrations of
homocysteine in antiepileptic drug treatment. Epilepsia.
Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking
anticonvulsant drugs. J ClinEndocrinol Metab.
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.
Valimaki MJ, Tiihonen M, Laitinen K, et al. Bone mineral density measured by
dual-energy x-ray absorptiometry and novel markers of bone formation and
resorption in patients on antiepileptic drugs. BoneMiner Res.
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Review Date: October 2000
Reviewed By: All depletions monographs have been reviewed by a team of experts including
Derrick M. DeSilva, Jr., MD, Raritan Bay Medical Center, Perth Amboy, NJ;
Jacqueline A. Hart, MD, Department of Internal Medicine, Newton-Wellesley
Hospital, Harvard University and Senior Medical Editor, A.D.A.M., Inc., Boston,
MA; John Hinze, PharmD, NMD, Woodbine, IA; Ruth Marlin, MD, Medical Director and
Director of Medical Education, Preventive Medicine Research Institute,
Sausalito, CA; Brian T Sanderoff, PD, BS in Pharmacy, Clinical Assistant
Professor, University of Maryland School of Pharmacy; President, Your
Prescription for Health, Owings Mills, MD; Leonard Wisneski, MD, FACP, George
Washington University, Rockville, MD; Ira Zunin, MD, MPH, MBA, President and
Chairman, Hawaii State Consortium for Integrative Medicine, Honolulu,
The publisher does not accept any responsibility for the accuracy of
the information or the consequences arising from the application, use, or misuse
of any of the information contained herein, including any injury and/or damage
to any person or property as a matter of product liability, negligence, or
otherwise. No warranty, expressed or implied, is made in regard to the contents
of this material. No claims or endorsements are made for any drugs or compounds
currently marketed or in investigative use. This material is not intended as a
guide to self-medication. The reader is advised to discuss the information
provided here with a doctor, pharmacist, nurse, or other authorized healthcare
practitioner and to check product information (including package inserts)
regarding dosage, precautions, warnings, interactions, and contraindications
before administering any drug, herb, or supplement discussed