To evaluate protein-bound cyanocobalamin (vitamin B12) sub absorption before and after omeprazole (Prilosec) therapy in healthy male volunteers.
Clinical trial in which each volunteer served as his own control.
Outpatient department of a university medical center.
Ten healthy, male volunteers 22 to 50 years old.
Each participant had a modified Schilling test (protein-bound cyanocobalamin) and a gastric analysis, as well as measurements of serum vitamin B12, gastrin, and folate levels. Five patients were then randomly assigned to take either 20 mg or 40 mg of omeprazole daily. After 2 weeks of omeprazole therapy, these tests were repeated.
The modified Schilling test, gastric analysis, serum gastrin level, folate level, and cyanocobalamin level.
At the end of the 2-week treatment period, cyanocobalamin absorption decreased from 3.2% to 0.9% (P = 0.031) in participants receiving 20 mg of omeprazole daily. In patients taking 40 mg of omeprazole daily, cyanocobalamin absorption decreased from 3.4% to 0.4% (P < 0.05).
Omeprazole therapy acutely decreased cyanocobalamin absorption in a dose-dependent manner.
- 1. Lind T, Cederberg C, Ekenved G, Haglund U, Olbe L. Effect of omeprazole—a gastric proton pump inhibitor—on pentagastrin stimulated acid secretion in man. Gut. 1983; 24:270-6. Google Scholar
- 2. Koop H. Review article: Metabolic consequences of long-term inhibition of acid secretion by omeprazole. Aliment Pharmacol Ther. 1992; 6:399-406. Google Scholar
- 3. Maton PN, Vinayek R, Frucht H, McArthur KA, Miller LS, Saeed ZA, et al. Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study. Gastroenterology. 1989; 97:827-36. Google Scholar
- 4. Lee GR. Megaloblastic and nonmegaloblastic macrocytic anemias. In: Wintrobe MM, Lee GR, Bithell TC, Foester J, Athens JW, Lukens JN, eds. Wintrobe's Clinical Hematology. 9th ed. Philadelphia: Lea and Febiger; 1993:745-90. Google Scholar
- 5. Herbert V. Don't ignore low serum cobalamin (vitamin B12) levels (Editorial). Arch Intern Med. 1988; 148:1705-7. Google Scholar
- 6. Herzlich B, Herbert V. Rapid collection of human intrinsic factor uncontaminated with cobalophilin (R binder). Am J Gastroenterol. 1986; 81:678-80. Google Scholar
- 7. Herzlich B, Herbert V. The role of the pancreas in cobalamin (vitamin B12) absorption. Am J Gastroenterol. 1984; 79:489-93. Google Scholar
- 8. Neale G. B12 binding proteins. Gut. 1990; 31:59-63. Google Scholar
- 9. Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjostrand SE, et al. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+) ATPase. Nature. 1981; 290:159-61. Google Scholar
- 10. Fellenius E, Elander B, Wallmark B, Helander HF, Berglindh T. Inhibition of acid secretion in isolated glands by substituted benzimidazoles. Am J Physiol. 1982; 243:G505-10. Google Scholar
- 11. Wallmark B, Jaresten B-M, Larsson H, Ryberg B, Bramdstrom A, Fellenius E. Differentiation among inhibitory actions of omeprazole, cimetidine, and SCN- on gastric acid secretion. Am J Physiol. 1983; 245:G64-71. Google Scholar
- 12. Saccomani G, Helander HF, Crago S, Chang HH, Dailey DW, Sachs G. Characterization of gastric mucosal membranes. X. Immunological studies of gastric (H+ + K+) ATPase. J Cell Biol. 1979; 83(2 Pt 1):271-83. Google Scholar
- 13. Forte JF, Lee HC. Gastric adenosine triphosphatases: a review of their possible role in HCl secretion. Gastroenterology. 1977; 73: 921-6. Google Scholar
- 14. Kittang E, Aaland E, Schjonsby H. Effect of omeprazole on the secretion of intrinsic factor, gastric acid and pepsin in man. Gut. 1985; 26:594-8. Google Scholar
- 15. Herbert V, Drivas G, Manusselis C, Mackler B, Eng J, Schwartz E. Are colon bacteria a major source of cobalaminanalogues in human tissues? 24-hr human stool contains only about 5 µg of apparent analogue (and 200 µg of folate). Trans Assoc Am Physicians. 1984; 97:161-71. Google Scholar
- 16. King CE, Leibach T, Toskes PP. Clinically significant vitamin B12 deficiency secondary to malabsorption of protein-bound vitamin B12. Dig Dis Sci. 1979; 24:397-402. Google Scholar
- 17. Gottlieb C, Lau KS, Wasserman LR, Herbert V. Rapid charcoal assay for human intrinsic factor (IF), gastric juice unsaturated B12 binding capacity, antibody to IF, and serum unsaturated B12 binding capacity. Blood. 1965; 25:875-85. Google Scholar
- 18. Kemp JA, Golner BB, Russell RM. Effect of an acidic dietary drink on absorption of protein-bound vitamin B12 (Abstract). Gastroenterology. 1992; 102:560A. Google Scholar
- 19. Koop H, Bachem MG. Serum iron, ferritin and vitamin B12 during prolonged omeprazole therapy. J Clin Gastroenterol. 1992; 14:288-92. Google Scholar
- 20. Kittang E, Aadland E, Schjonsby H, Rohss K. The effect of omeprazole on gastric acidity and the absorption of liver cobalamins. Scand J Gastroenterol. 1987; 22:156-60. Google Scholar
- 21. Streeter AM, Duraiappali B, Boyle R, O'Neill BJ, Pheils MT. Malabsorption of vitamin B12 after vagotomy. Am J Surg. 1974; 128: 340-3. Google Scholar
- 22. Doscherholmen A, Swaim WR. Impaired assimilation of egg Co57 -vitamin B12 in patients with hypochlorhydria and achlorhydria and after gastric resection. Gastroenterology. 1973; 64:913-9. Google Scholar
- 23. King CE, Leibach J, Toskes PP. Clinically significant vitamin B12 deficiency secondary to malabsorption of protein-bound vitamin B12. Dig Dis Sci. 1979; 24:397-402. Google Scholar
- 24. Streeter AM, Goulston KJ, Bathur FA, Hilmer RS, Crane GG, Pheils MT. Cimetidine and malabsorption of cobalamin. Dig Dis Sci. 1982; 27:13-6. Google Scholar
- 25. Belaiche J, Cattan D, Zittoun J, Marquet J, Yvart J. Effect of ranitidine on cobalamin absorption (Letter). Dig Dis Sci. 1983:28: 667-8. Google Scholar
- 26. Steinberg WM, King CE, Toskes PP. Malabsorption of protein-bound cobalamin but not unbound cobalamin during cimetidine administration. Dig Dis Sci. 1980; 25:188-91. Google Scholar
- 27. Salom IL, Silvis SE, Doscherholmen A. Effect of cimetidine on the absorption of vitamin B12. Scand J Gastroenterol. 1982; 17:129-31. Google Scholar
- 28. Lanzon-Miller S, Pounder RE, Hamilton MR, Ball S, Chronos NA, Raymond F, et al. Twenty-four hour intragastric acidity and plasma gastrin concentration before and during treatment with either ranitidine or omeprazole. Aliment Pharmacol Ther. 1987; 1:239-51. Google Scholar
- 29. Yale CE, Gohdes PN, Schilling RF. Cobalamin absorption and hematologic status after two types of gastric surgery for obesity. Am J Hematol. 1993; 42:63-6. Google Scholar
- 30. Marcuard SP, Sinar DR, Swanson MS, Silverman JF, Levine JS. Absence of luminal intrinsic factor after gastric bypass surgery for morbid obesity. Dig Dis Sci. 1989; 34:1238-42. Google Scholar
- 31. Suter PM, Golner BB, Goldin BR, Morrow FD, Russell RM. Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis. Gastroenterology. 1991; 101:1039-45. Google Scholar
- 32. Festen HP, Tuynman HA, Den Hollander W, Menwissen SG. Repeated high oral doses of omeprazole do not affect intrinsic factor secretion: proof of a selective mode of action. Aliment Pharmacol Ther. 1989; 3:375-9. Google Scholar
- 33. Mohammed R, Clark JS, Adams JF, Hearns JB, Crean GP. The effect of ranitidine hydrochloride, a new histamine H2-receptor antagonist, on intrinsic factor secretion. Clin Ther. 1981; 4:118-20. Google Scholar
- 34. Yeomans ND, Hanson RG, Smallwood RA, Mihaly GW, Louis WJ. Effect of chronic ranitidine treatment on secretion of intrinsic factor. Br Med J (Clin Res Ed). 1982; 285:264. Google Scholar
- 35. Belaiche J, Zittoun J, Marquet J, Nurit Y, Yvart J. (Effect of ranitidine on secretion of gastric intrinsic factor and absorption of vitamin B12). Gastroenterol Clin Biol. 1983; 7:381-4. Google Scholar
Author, Article, and Disclosure Information
Stefan P. Marcuard,
From East Carolina University School of Medicine, Greenville, North Carolina.
Corresponding Author: Stefan P. Marcuard, MD, Section of Gastroenterology, Department of Medicine, East Carolina University School of Medicine, Greenville, NC 287858-4354.
Acknowledgments: The authors thank the Human Health Division of Merck, Inc. for its support; and the Department of Medicines, Text/Information Processing Center for preparation of the manuscript.
Grant Support: In part by grant 585451 from the American College of Gastroenterology.