Proton pump inhibitor therapy and potential long-term harm

Curr Opin Endocrinol Diabetes Obes. 2014 Feb;21(1):3-8. doi: 10.1097/MED.0000000000000031.


Purpose of review: This review summarizes the recent literature on the potential side-effects of proton pump inhibitors (PPIs) and known interactions with the metabolism/absorption of other drugs.

Recent findings: Data confirm that PPIs are a very well tolerated drug class. Their high safety, efficacy and wide distribution lead to overuse, inappropriate dosage or excessive duration of treatment. Despite the absorption of micronutrients or other plausible effects on the development of bacterial infections linked to PPI-induced hypochlorhydria, it is difficult to demonstrate an association between PPI and specific symptoms. A possible negative effect of PPIs on bone integrity appears weak, but hypomagnesemia is likely a PPI drug class effect. A higher risk of Clostridium difficile infection and other infectious diseases such as small intestinal bacterial overgrowth and spontaneous bacterial peritonitis remain controversial in PPI users. However, the careful use of PPIs in cirrhotic or otherwise fragile patients is mandatory. Short-term or long-term PPI use may trigger microscopic colitis, and the management of this condition may include PPI withdrawal. The effect of PPIs on stimulating exocrine or endocrine gastric cell proliferation is poorly understood. A diagnostic delay or masking of diseases such as gastrinoma is difficult to evaluate.

Summary: Short-term standard dose PPI treatment is low risk. Long-term PPI use may complicate health conditions by various mechanisms linked to PPIs and/or to hypochlorhydria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Achlorhydria / chemically induced*
  • Bone Density / drug effects*
  • Clostridioides difficile / immunology
  • Delayed Diagnosis
  • Disease Susceptibility
  • Drug Interactions
  • Enterocolitis, Pseudomembranous / chemically induced*
  • Enterocolitis, Pseudomembranous / immunology
  • Female
  • Gastroesophageal Reflux / drug therapy*
  • Humans
  • Hypocalcemia / chemically induced*
  • Magnesium Deficiency / congenital
  • Male
  • Practice Patterns, Physicians'
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Renal Tubular Transport, Inborn Errors / chemically induced*
  • Time Factors


  • Proton Pump Inhibitors

Supplementary concepts

  • Hypomagnesemia 1, Intestinal