Zinc salts provide a novel, prolonged and rapid inhibition of gastric acid secretion.

Abstract

The overproduction of acid and the associated illnesses linked to hypersecretion have a lifetime prevalence of 25-35% in the United States. Although a variety of pharmaceutical agents have been used to reduce the production of acid, alarming new evidence questions the long-term efficacy and safety of the agents. These issues coupled with the delayed onset of action and the return of symptoms in over 60% of the patients is less than satisfactory. The purpose of this study was to determine whether administration of a zinc salt could lead to a rapid and sustained increase in gastric pH in both animals and in humans and provide a new rapid acid suppression therapy. Intracellular pH was measured with 2',7'-bis-(2-carboxyethyl)-5-and-6-carboxy-fluorescein in both human and rat gastric glands following an acid load±a secretagogue. In a separate series of studies, whole stomach acid secretion was monitored in rats. A final study used healthy human volunteers while monitoring with a gastric pH measurement received placebo, zinc salt, or a zinc salt and proton pump inhibitor (PPI). We demonstrate that exposure to ZnCl(2) immediately abolished secretagogue-induced acid secretion in isolated human and rat gastric glands, and in intact rat stomachs. Chronic low-dose zinc exposure effectively inhibited acid secretion in whole stomachs and isolated glands. In a randomized cross-over study in 12 volunteers, exposure to a single dose of ZnCl(2) raised intragastric pH for over 3  h, including a fast onset of effect. Our findings demonstrate that zinc offers a novel rapid and prolonged therapy to inhibit gastric acid secretion in human and rat models.