Acid inhibition and the acid rebound effect

Dig Dis. 2011;29(5):482-6. doi: 10.1159/000331514. Epub 2011 Nov 16.


Acid secretion from gastric parietal cells is a result of a complex interaction between different stimulatory and inhibitory mediators. One of the most important mediators is gastrin, which stimulates gastric acid secretion from parietal cells mostly indirectly, by the release of histamine from enterochromaffin-like (ECL) cells. Therapy with antisecretory agents leads to hypergastrinemia, mucosal hyperplasia and increased ECL cell mass, which results in increase of gastric acid secretion capacity. This increased secretion capacity has been shown to manifest itself after antisecretory therapy withdrawal as rebound acid hypersecretion (RAH). Various studies have quantified acid hypersecretion after the cessation of therapy with H(2) antagonists and proton-pump inhibitors (PPIs). While most of those studies had small patient numbers, the findings generally demonstrate that RAH after H(2) antagonist therapy is of low magnitude, short duration, and has questionable clinical significance. On the contrary, acid hypersecretion after PPI therapy is more pronounced, lasts longer, and could possibly be the cause of acid-related symptoms. Potential for causing symptoms has recently been confirmed in two randomized placebo-controlled studies, and while we witness the increasing use of PPIs, RAH could become a proven cause of failure to withdraw therapy in a proportion of patients with reflux or dyspeptic symptoms.

Publication types

  • Review

MeSH terms

  • Animals
  • Gastric Acid / metabolism*
  • Histamine H2 Antagonists / pharmacology
  • Humans
  • Models, Biological
  • Proton Pump Inhibitors / pharmacology*
  • Randomized Controlled Trials as Topic


  • Histamine H2 Antagonists
  • Proton Pump Inhibitors