Abstract
Protein- (chicken serum) bound [57Co]cyanocobalamin absorption was evaluated in five hypochlorhydric patients who had developed B12 deficiency despite having normal absorption of unbound crystalline vitamin B12. All five patients had decreased urinary excretion of protein-bound B12 (0.06–0.34%) as compared to twelve normal controls (0.61–5.6%), P<.001. Improvement in protein-bound B12 absorption in four of the five patients occurred with the exogenous administration of hydrochloric acid, pepsin, gastric intrinsic factor, or a combination thereof. Vitamin B12 deficiency developing in the setting of hypochlorhydria may result from deficiency of acid-peptic digestion of B12 bound to protein and/or a relative deficiency of intrinsic factor. This digestive defect is not detected with tests which measure the absorption of unbound crystalline B12 but is detected by a simple test which employs B12 bound to chicken serum as the form of protein-bound B12.
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References
Toskes PP, Deren JJ: Vitamin B12 absorption and malabsorption. Gastroenterology 65:662–683, 1973
Donaldson RM, Jr: Mechanisms of malabsorption of cobalamin. Cobalamin. M Babior (ed). New York, John Wiley and Sons, 1975, p 337–368
Deller DJ, Richards WCD, Witts LJ: Changes in the blood after partial gastrectomy with special reference to vitamin B12. II. The cause of the fall in serum vitamin B12. Q J Med 31:89–102, 1962
Hines JD, Hoffbrand AV, Mollin DL: The hematological complications following partial gastrectomy. Am J Med 43:555–569, 1967
Mahmud K, Ripley D, Doscherholmen A: Vitamin B12 absorption tests: Their unreliability in postgastrectomy states. J Am Med Assoc 216:1167–1171, 1971
Rygvold O: Hypovitaminosis B12 following partial gastrectomy by the Billroth II method. Scand J Gastroenterol 9 (Suppl 29):57–64, 1974
Streeter AM, Balasubramaniam D, Boyle R, O'Neill BJ, Pheils MT: Malabsorption of vitamin B12 after vagotomy. Am J Surg 128:340–343, 1974
Ross GSM: Vitamin B12 assay in body fluids usingEuglena gracilis. J Clin Pathol 5:250–256, 1952
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
Gottlieb C, Lau K-S, Wasserman LR, Herbert V: Rapid charcoal assay for intrinsic factor (IF), gastric juice unsaturated B12 binding capacity, antibody to IF, and serum unsaturated B12 binding capacity. Blood 25:875–884, 1965
Snedecor GW, Cochran WG: Statistical Methods, 6th ed. Ames, Iowa, Iowa State University Press, 1967
Kidroni G, Grossowicz N: Purification and properties of two vitamin B12 binders from chicken serum. Biochim Biophys Acta 118:113–123, 1969
Sonneborn DW, Hansen HJ: Vitamin B12 binders of chicken serum and chicken proventriculus are immunologically similar. Science 168:591–592, 1970
Cooper BA, Castle WB: Sequential mechanisms in the enhanced absorption of vitamin B12 by intrinsic factor in the rat. J Clin Invest 30:199–214, 1960
Reizenstein PF: Effect of digestive enzymes on bound vitamin B12. Acta Med Scand 165:481–486, 1959
Heyssel RM, Bozian RC, Darby WJ, Bell MC: Vitamin B12 turnover in man: The assimilation of vitamin B12 from natural foodstuff by man and estimates of minimal daily dietary requirements. Am J Clin Nutr 18:176–184, 1966
Adams JF, Kennedy EH, Thompson J, Williamson J: The effect of acid peptic digestion on free and tissue-bound cobalamins. Br J Nutr 22:111–114, 1968
Doscherholmen A, McMahon J, Ripley D; Vitamin B12 assimilation from chicken meat. Am J Clin Nutr 31:825–830, 1978
Adams JF, Ross SK, Mervyn L, Boddy K, King P: Absorption of cyanocobalamin, coenzyme B12, methylcobalamin and hydroxocobalamin at different dose levels. Scand J Gastroenterol 6:249–252, 1971
Herbert V, Sullivan LW: Activity of coenzyme B12 in man. Ann NY Acad Sci 112:855–870, 1964
Okuda K, Takara I, Fujii T: Absorption of liver-bound vitamin B12 in relation to intrinsic factor. Blood 32:313–323, 1968
Schade SG, Schilling RF: Effect of pepsin on the absorption of food vitamin B12 and iron. Am J Clin Nutr 20:636–640, 1967
Ardeman S, Chanarin I: Assay of intrinsic factor in the diagnosis of Addisonian pernicious anaemia. Br J Haematol 11:305–314, 1965
Ardeman S, Chanarin I: Intrinsic factor secretion in gastric atrophy. Gut 7:99–101, 1966
Allen RH, Seetharam B, Allen NC, Podell ER, Alpers DH: Correction of cobalamin malabsorption in pancreatic insufficiency with a cobalamin analogue that binds with high affinity to R protein but not to intrinsic factor. J Clin Invest 61:1628–1634, 1978
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Dr. King is the recipient of a Research Associate Award from the Veterans Administration. During the performance of these studies Dr. Toskes was a Clinical Investigator with the Veterans Administration.
Supported in part by Grant RR-82 from the National Institutes of Health.
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King, C.E., Leibach, J. & Toskes, P.P. Clinically significant vitamin B12 deficiency secondary to malabsorption of protein-bound vitamin B12 . Digest Dis Sci 24, 397–402 (1979). https://doi.org/10.1007/BF01297127
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DOI: https://doi.org/10.1007/BF01297127