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

Am J Gastroenterol. 2011 Jan;106(1):62-70. doi: 10.1038/ajg.2010.327. Epub 2010 Aug 24.

Abstract

Objectives: 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.

Methods: 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).

Results: 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.

Conclusions: Our findings demonstrate that zinc offers a novel rapid and prolonged therapy to inhibit gastric acid secretion in human and rat models.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Chlorides / administration & dosage*
  • Chlorides / pharmacokinetics
  • Cross-Over Studies
  • Disease Models, Animal
  • Female
  • Gastric Acid / metabolism*
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Male
  • Omeprazole / administration & dosage*
  • Omeprazole / pharmacokinetics
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Risk Assessment
  • Stomach / drug effects*
  • Tissue Culture Techniques
  • Treatment Outcome
  • Zinc Compounds / administration & dosage*
  • Zinc Compounds / pharmacokinetics

Substances

  • Chlorides
  • Proton Pump Inhibitors
  • Zinc Compounds
  • zinc chloride
  • Omeprazole