In vitro studies of gastric juice in patients with food-cobalamin malabsorption

Abstract

Food-cobalamin absorption depends on the initial release of cobalamin from its binders in food. Therefore, the characterization of patients' gastric juices and their behavior in this process was undertaken. Pentagastrin-stimulated gastric juice specimens from three patients with severe food-cobalamin malabsorption, six patients with mild malabsorption, and five patients with normal absorption were tested for pH, pepsin, intrinsic factor content, and anin vitro method that quantitates transfer of cobalamin from egg yolk to gastric R binder. Transfer of cobalamin correlated best within vivo egg yolk-cobalamin absorption test results in the 14 patients (r=0.731,P<0.005). Transfer also correlated inversely with gastric juice pH (r=−0.619,P<0.02). Basal gastric juice specimens, with their higher pH, from the same subjects failed to promote cobalamin transfer until their pH was lowered to 1.0–1.3. Pepsin levels did not correlate within vitro transfer or with absorptionin vivo; nevertheless, raising the low pepsin concentration of one stimulated gastric juice improved transfer, while inhibiting pepsin activity with pepstatin A inhibited transfer. Mixing experiments with selected stimulated gastric juices demonstrated that poorin vitro transfer, which in a few cases seemed unrelated to pH or pepsin levels, was not due to any inhibitory activity of such gastric juices. These studies confirm that gastric acid and pepsin play a central role in releasing food-bound cobalamin and transferring it to R binder, but suggest that other, still unidentified gastric defects occasionally contribute to impaired transfer; the latter defects are not inhibitory in nature but seem to involve the absence of a permissive activity. The finding that the ability of a gastric juice to promote the transfer of cobalaminin vitro was the best overall indicator of a patient's ability to absorb food cobalaminin vivo suggests that gastric juice defects are responsible for most cases of food-cobalamin malabsorption. The phenomenon may also provide a practicalin vitro estimate of a patient's ability to absorb food cobalamin.