Abstract
The suppressive effects of cimetidine on acid, pepsin, and intrinsic factor secretion have been well documented; however, the effect of cimetidine on cobalamin absorption has not been assessed. The absorption of both unbound [57Co] cyanocobalamin and protein-bound [57Co] cyanocobalamin was evaluated in 12 patients with duodenal ulcer disease during and after discontinuation of cimetidine therapy. Cimetidine administration did not lead to malabsorption of unbounds cobalamin but caused malabsorption of protein-bound cobalamin (0.22±0.08%, [mean±1sem] versus 2.3±0.10% in control subjects,P<0.01). This malabsorption was reversible upon discontinuation of cimetidine. Patients on cimetidine therapy malabsorb protein-bound cobalamin and, during long-term treatment, are at risk for developing cobalamin deficiency. This malabsorption of protein-bound cobalamin is not detectable by the usual tests of cobalamin absorption which employ unbound cobalamin.
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Henn RM, Isenberg JI, Maxwell V, Sturdevant RAL: Inhibition of gastric acid secretion by cimetidine in patients with duodenal ulcer. N Engl J Med 293:371–375, 1975
Aadland E, Berstad A, Semb LS: Inhibition of pentagastrinstimulated gastric secretion by cimetidine in healthy subjects on cimetidine.In Proceedings of the Second International Symposium on Histamine H2 Receptor Antagonists. WL Burland, MA Simkins (eds). Amsterdam, Excerpta Medica, 1977, pp 87–100
Longstreth GF, Go VLW, Malagelada JR: Cimetidine suppression of nocturnal gastric secretion in active duodenal ulcer. N Engl J Med 294:801–804, 1976
Binder HJ, Donaldson RM: Effect of cimetidine on intrinsic factor and pepsin secretion in man. Gastroenterology 74:371–375, 1978
Burland WL, Mills JG, Sharpe PC, Horton MA, Mollin DL: The effect of cimetidine on intrinsic factor secretion.In Proceedings of the Second International Symposium on Histamine H2 Receptor Antagonists. WL Burland, MA Simkins (eds). Amsterdam, Excerpta Medica, 1977, pp 177–183
Fielding LP, Chalmers DM, Chanarin I, Levi AJ: Inhibition of intrinsic factor secretion by cimetidine. Br Med J 1:818–819, 1978
Fielding LP, Chalmers DM, Stafford DM, Levi AJ: Short communication. Cimetidine and intrinsic factor secretion.In Proceedings of the Second International Symposium on Histamine H2 Receptor Antagonists. WL Burland, MA Simkins (eds). Amsterdam, Excerpta Medica, 1977, pp 184–186
Schilling RF: Intrinsic factor studies II. The effect of gastric juice on the urinary excretion of radioactivity after the oral administration of radioactive vitamin B12. J Lab Clin Med 42:860–866, 1953
Doscherholmen A, Swaim WR: Impaired assimilation of egg57Co-vitamin B12 in patients with hypochlorhydria and achlorhydria and after gastric resection. Gastroenterology 64:913–919, 1973
Streeter AM, Balasubramaniam D, Boyle R, O'Neill BJ, Pheills MT: Malabsorption of vitamin B12 after vagotomy. Am J Surg 128:340–343, 1974
King CE, Leibach JR, Toskes PP: Clinically significant vitamin B12 deficiency secondary to malabsorption of proteinbound vitamin B12. Dig Dis Sci 24:397–402, 1979
Walkenstein SS, Dubb JW, Randolph WC, Westlake WJ, Stote RM, Intoccia AP: Bioavailability of cimetidine in man. Gastroenterology 74:360–365, 1978
Gottlieb E, Lau K-S, Wasserman LR, Herbert V: Rapid charcoal assay for intrinsic factor gastric juice unsaturated B12 binding capacity. Blood 25:875–884, 1965
Berstad A: A modified hemoglobin substrate method for the estimation of pepsin in gastric juice. Scand J Gastroenterol 4:343–348, 1970
Snedecor GW, Cochran WG: Statistical Methods, 6th ed. Ames, Iowa, Iowa State University Press, 1967, p 117
Gilbert HS: Effect of low pH on affinity of vitamin binding proteins for vitamin B12: Inhibition of TC II and enhancement of R binders. Fed Proc 33:1453, 1974
Newmark P, Mester S: Effect of pH on vitamin B12 binding by transcobalamins. Biochim Biophys Acta 343:627–631, 1974
Sonneborn DW, Hansen HJ: Vitamin B12 binders of chicken serum and chicken proventriculus are immunologically similar. Science 168:591–592, 1970
Doscherholmen A, McMahon J, Ripley D: Inhibitory effect of eggs on vitamin B12 absorption. Description of a simple ovalbumin57Co-vitamin B12 absorption test. Br J Haematol 33:261, 1976
Doscherholmen A, McMahon J, Ripley D: Vitamin B12 assimilation from chicken meat. Am J Clin Nutr 31:825–830, 1978
Doscherholmen A, McMahon J, Ripley D: Physiologic role of gastric acid and pepsin in the assimilation of vitamin B12 from food. Clin Res 26:661A, 1978
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During the performance of these investigations Dr. King was the recipient of a Research Associate Award and Dr. Toskes, a Clinical Investigation Award, from the Veteran Administration.
Supported in part by grant RR-82 and training grant AM07209 from the National Institutes of Health.
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Steinberg, W.M., King, C.E. & Toskes, P.P. Malabsorption of protein-bound cobalamin but not unbound cobalamin during cimetidine administration. Digest Dis Sci 25, 188–192 (1980). https://doi.org/10.1007/BF01308137
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DOI: https://doi.org/10.1007/BF01308137