Longterm use of proton pump inhibitors and their systemic adverse effects: an integrative literature review

Abstract

Proton pump inhibitors (PPIs) are widely used in clinical practice for the treatment of acid-related disorders, such as gastroesophageal reflux disease, peptic ulcer disease, Helicobacter pylori eradication, and prevention of gastric lesions associated with the use of nonsteroidal anti-inflammatory drugs. Despite their efficacy and favorable safety profile when properly indicated, prolonged use, often without periodic reassessment, has raised concerns regarding potential systemic adverse events. This study aimed to identify, through recent scientific literature, the main adverse effects associated with chronic use of PPIs. This is an integrative literature review conducted in the PubMed and SciELO databases in May 2026, using Portuguese and English descriptors related to proton pump inhibitors and adverse effects. Eight articles published between 2018 and 2024 were included. The analyzed studies reported associations between long-term PPI use and metabolic alterations, micronutrient deficiencies, hypomagnesemia, gastrointestinal infections, possible renal changes, and osteomuscular risks in specific populations. It is concluded that PPIs remain effective and relevant medications; however, their use should be guided by clear clinical indication, the lowest effective dose, defined treatment duration, and periodic reassessment of the prescription.