Long-term use of proton pump inhibitors (PPIs), the acid-lowering drugs most Americans know as Prilosec, Nexium, Prevacid or Protonix, is associated with a higher risk of stomach cancer. That is the conclusion of a systematic review of 21 meta-analyses published in BMJ Open Gastroenterology on April 19, 2025.
The Karolinska Institute team, led by epidemiologist Nele Brusselaers, found that 20 of the 21 pooled analyses reported statistically significant increases, with relative risks ranging from 1.3 to 2.9. In plain terms, long-term users were roughly 30 percent to nearly three times more likely to develop gastric cancer than non-users.
The scale of exposure is enormous. An estimated 113 million PPI prescriptions are filled each year in the United States, and the same drugs are sold over the counter without a prescription. The active ingredients include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid) and pantoprazole (Protonix).
What the evidence actually shows
The signal is consistent but the studies are observational, meaning they can show association but not prove cause. The review authors flag two important caveats. Reverse causation is one. Patients sometimes get PPIs for stomach symptoms that turn out to be early, undiagnosed cancer, which can make the drug look responsible for a disease it did not cause. The other is Helicobacter pylori, a common stomach bacterium that itself raises cancer risk. Long-term PPI use in people with an active H. pylori infection has been linked to worsening inflammation and stomach lining changes.
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The kidneys have shown a similar pattern. A separate meta-analysis of 12 studies covering 700,125 participants, published in Biomedicines in June 2024, found that PPI users had a 26 percent higher risk of developing chronic kidney disease than non-users (hazard ratio 1.26, 95 percent confidence interval 1.16 to 1.38). The risk was also higher than in patients taking H2 blockers, an older class of acid-reducing drugs.
Short-term relief, long-term drift
PPIs were designed for short courses. The Food and Drug Administration says over-the-counter PPIs should be limited to a 14-day course up to three times a year. In practice, many people take them for years without ever being re-evaluated.
Yale Medicine gastroenterologist William Ravich has warned that patients should not stop the drugs on their own, because acid symptoms can rebound and cause esophageal damage. He said each patient needs to weigh the risks and benefits with their medical provider.
That is the practical takeaway. If you have been on omeprazole, esomeprazole, lansoprazole or pantoprazole for more than a few weeks without a recent check-in, ask your prescriber whether you still need it, whether the dose can be lowered, and whether a step-down or a switch is appropriate for your situation.
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This article is made and published by Emil Martesen, who may have used AI in the preparation.