Does Chronic PPI Use Cause Ulcers?
No, chronic use of proton pump inhibitors (PPIs) does not cause ulcers—in fact, PPIs are the most effective agents for preventing and healing ulcers, particularly in patients taking NSAIDs, aspirin, or anticoagulants. 1, 2
Mechanism: PPIs Prevent Rather Than Cause Ulcers
PPIs work by suppressing gastric acid production, which promotes healing of peptic ulcers and mucosal erosions while stabilizing thrombi at bleeding sites. 3
Ulcers are caused by acid, NSAIDs, H. pylori infection, or combinations of these factors—not by acid suppression therapy. 3
Standard doses of PPIs significantly reduce both gastric and duodenal ulcers associated with NSAID use in numerous clinical trials using endoscopic endpoints. 1
Evidence Supporting PPI Safety in Long-Term Use
Long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of chronic gastritis, gastric atrophy, or intestinal metaplasia in the absence of H. pylori infection. 4
Serious adverse events are extremely rare with PPIs, and the class is remarkably safe and effective for persons with peptic ulcer disorders. 4
The 2022 American Gastroenterological Association guidelines emphasize that the decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for adverse events. 1
Clinical Context: When PPIs Are Indicated for Ulcer Prevention
Patients with a history of peptic ulcer who need NSAIDs or aspirin require PPI co-therapy, as H. pylori eradication alone is insufficient to prevent upper GI tract damage. 1
Among patients with recent complicated peptic ulcer using naproxen, omeprazole was significantly more effective than H. pylori eradication alone in preventing ulcer bleeding recurrence. 1
PPIs reduce the baseline bleeding risk by 50% in patients on anticoagulant therapy and decrease upper GI bleeding risk by approximately 50% in high-risk patients. 3
Appropriate Long-Term PPI Use
Patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation. 1
Patients with Barrett's esophagus, severe erosive esophagitis, or esophageal strictures from GERD are indicated for long-term PPI use. 2
All patients taking a PPI should have regular review of ongoing indications for use, with this review being the responsibility of the patient's primary care provider. 1
Common Pitfall to Avoid
Do not confuse the physiological response of mild hypergastrinemia (which occurs with any reduction in gastric acid secretion) with a pathological process that causes ulcers. 4
The long-term use of PPIs has not been convincingly proven to cause enterochromaffin-like cell hyperplasia or carcinoid tumors despite the expected rise in gastrin levels. 4
Discontinuation of PPIs may result in rebound acid hypersecretion, which can cause transient upper gastrointestinal symptoms and potentially lead to ulcer formation if the underlying indication for PPI use still exists. 1, 4