Zinc salts provide a novel, prolonged and rapid inhibition of gastric acid secretion.
OBJECTIVE
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.
Kirchhoff
Philipp
P
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA. pkirchhoff@hotmail.com
Socrates
Thenral
T
Sidani
Shafik
S
Duffy
Andrew
A
Breidthardt
Tobias
T
Grob
Christian
C
Viehl
Carsten T
CT
Beglinger
Christoph
C
Oertli
Daniel
D
Geibel
John P
JP
D000328:Adult; D000818:Animals; D002712:Chlorides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D018570:Risk Assessment; D013270:Stomach / Q000187:drug effects*; D046509:Tissue Culture Techniques; D016896:Treatment Outcome; D017967:Zinc Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics
D002712:Chlorides; D054328:Proton Pump Inhibitors; D017967:Zinc Compounds; C016837:zinc chloride; D009853:Omeprazole