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Gastrointestinal Medications
Proton Pump Inhibitors


Depletions
Vitamin B12 (Cobalamin)
Mechanism

Omeprazole reduces the absorption of protein-bound vitamin B12 (Marcuard et al. 1994; Saltzman et al. 1994). Prolonged treatment with omeprazole can significantly decrease serum cobalamin levels and cause cobalamin deficiency in some patients (Bellou et al. 1996; Termanini et al. 1998). However, in one study, omeprazole reduced absorption of protein-bound, but not unbound, cyanocobalamin; no change in serum cobalamin was observed in patients after 7 years of treatment (Schenk et al. 1996). It is not known whether lansoprazole adversely affects cobalamin status. Given the uncertainty of the depletion of serum vitamin B12 levels, periodic monitoring may be useful.


Significance of Depletion

Symptomatic vitamin B12 deficiency is rare because complications may appear only after the deficiency has existed for 10 to 15 years (Berger 1985; Carpentier et al. 1976). Low vitamin B12 levels could increase the risk of colon cancer, heart disease, brain dysfunction, birth defects, and irreversible neuropathy (Ames 2000; Covington 1999). Irritability, weakness, numbness, fatigue, glossitis, anorexia, headache, palpitations, and altered mental status, including personality and behavioral changes, are some of the signs and symptoms of vitamin B12 depletion (Covington 1999). Prolonged deficiency leads to pernicious or megaloblastic anemia that may be associated with leukopenia and thrombocytopenia.


Replacement Therapy

Doses of 25 to 250 mcg/day of vitamin B12 have been used to correct nutritional deficiency (Covington 1999). Oral doses between 500 to 1000 mcg/day have been recommended for the treatment of pernicious anemia (Carmel 2000). Replacement therapy should be based on the patient's individual needs, considering the clinical presentation, serum B12 levels, age, gender, dietary habits, and medication regimen.

Note: Unlike protein-bound vitamin B12 in foods, supplemental vitamin B12 is not affected by gastric acid dysfunction (Carmel et al. 1988).


Editorial Note

This information is intended to serve as a concise reference for healthcare professionals to identify substances that may be depleted by many commonly prescribed medications. Depletion of these substances depends upon a number of factors including medical history, lifestyle, dietary habits, and duration of treatment with a particular medication. The signs and symptoms associated with deficiency may be nonspecific and could be indicative of clinical conditions other than deficiency. The material presented in these monographs should not in any event be construed as specific instructions for individual patients.


References

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

Bellou A, Aimone-Gastin I, De Korwin JD, et al. Cobalamin deficiency with megaloblastic anaemia in one patient under long-term omeprazole therapy. J Intern Med. 1996;240(3):161-164.

Berger W. Incidence of severe side effects during therapy with sulfonylureas and biguanides. Horm Metab Res Suppl. 1985;15:111-115.

Carmel R, Sinow RM, Siegel ME, Samloff IM. Food cobalamin malabsorption occurs frequently in patients with unexplained low serum cobalamin levels. Arch Intern Med. 1988;148(8):1715-1719.

Carmel R. Current concepts in cobalamin deficiency. Ann Rev Med. 2000;51:357-375.

Carpentier JL, Bury J, Luyckx A, Lefebvre P. Vitamin B12 and folic acid serum levels in diabetics under various therapeutic regimens. Diabetes Metab. 1976;2(4):187-190.

Covington T, ed. Nonprescription Drug Therapy Guiding Patient Self-Care. St Louis, MO: Facts and Comparisons; 1999:467-545.

Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin. Ann Intern Med. 1994;120(3):211-215.

Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am Coll Nutr. 1994;13(6):584-591.

Schenk BE, Festen HP, Kuipers EJ, et al. Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin. Aliment Pharmacol Ther. 1996;10(4):541-545.

Termanini B, Gibril F, Sutliff VE, et al. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med. 1998;104(5):422-430.


Copyright © 2000 Integrative Medicine Communications

This publication contains information relating to general principles of medical care that should not in any event be construed as specific instructions for individual patients. 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. The reader is advised to check product information (including package inserts) for changes and new information regarding dosage, precautions, warnings, interactions, and contraindications before administering any drug, herb, or supplement discussed herein.