Millions rely on proton pump inhibitors, or PPIs, to manage conditions like heartburn and acid reflux, but a growing body of research suggests long-term use of these medications may come at a hidden cost. A new study from Brazil adds to these concerns, finding that extended use of omeprazole—commonly known by the brand name Prilosec—disrupted mineral absorption in rats, potentially increasing the risk of anemia and osteoporosis. The findings, published in ACS Omega on February 26, 2026, underscore the importance of discussing prolonged PPI use with a healthcare provider.
While PPIs like omeprazole, pantoprazole (Protonix) and esomeprazole (Nexium) are effective at reducing stomach acid and alleviating symptoms, researchers are increasingly focused on their potential impact on nutrient absorption. The latest research, conducted by scientists at the Federal University of São Paulo (UNIFESP) and the ABC Medical School (FMABC), provides further evidence of these risks. Understanding the potential side effects of popular acid reflux medication is crucial for both patients and physicians.
Mineral Imbalances Observed in Animal Study
The study involved adult rats divided into control and treatment groups, with the treatment group receiving omeprazole for 10, 30, or 60 days to simulate varying lengths of prolonged use in humans. Researchers focused on how the drug affected the absorption of key minerals—iron, calcium, zinc, magnesium, copper, and potassium—observing significant shifts in their distribution throughout the animals’ bodies. The medication appeared to cause certain minerals to accumulate in the stomach while creating imbalances in the liver and spleen.
Blood tests revealed higher calcium levels and lower iron levels in the treated rats, changes that researchers associate with increased risks of osteoporosis and anemia. Notably, alterations were also observed in immune system cells. “The most worrying finding was the significant increase in calcium in the animals’ bloodstream, which may indicate an imbalance with the removal of the mineral from the bones and a future risk of osteoporosis,” explained Angerson Nogueira do Nascimento, a professor at UNIFESP who coordinated the study, in a statement. “Yet, longer studies are needed to confirm this hypothesis.”
How PPIs Impact Nutrient Absorption
PPIs work by blocking the H+, K+, ATPase enzyme, also known as the proton pump, which controls the final step in hydrochloric acid production in the stomach. By suppressing stomach acid, these drugs effectively reduce symptoms of ulcers, gastritis, and acid reflux. However, stomach acid isn’t just about digestion; it also plays a vital role in helping the body absorb certain nutrients. When acid production is reduced for extended periods, the absorption of minerals that depend on an acidic environment can be compromised.
Growing Concerns Over Long-Term Use and OTC Access
Omeprazole has been available for over 30 years and is frequently used, sometimes for months or even years without direct medical supervision. Andréa Santana de Brito, a researcher at UNIFESP, cautions against the “trivialized use” of the drug, even for mild symptoms. “It isn’t a question of demonizing the drug, which is effective for various gastric conditions. The problem is its trivialized use, even for mild symptoms such as heartburn, and for prolonged periods of months and even years. Its adverse effects shouldn’t be overlooked,” she warned.
Concerns are amplified by a recent decision from the Brazilian Health Regulatory Agency (ANVISA), which authorized over-the-counter sales of 20mg omeprazole in November 2025. Brito fears this increased accessibility could encourage self-medication and continuous use, potentially disregarding the recommended 14-day treatment limit. However, ANVISA maintains that the move is intended to promote responsible use, emphasizing that the 14-day limit reinforces the message that the drug is for mild, temporary symptoms and encourages patients to seek medical evaluation if their symptoms persist. Packages containing more than a 14-day supply will still require a prescription.
Potential Impact Extends to Other PPIs
While the study focused specifically on omeprazole, researchers emphasize that other drugs in the same category—pantoprazole and esomeprazole—function similarly. According to Brito, these newer PPIs may even have a more pronounced effect due to their more potent and longer-lasting action. “In these cases, the effect may be even more intense since these molecules have a more potent and longer-lasting action,” she explained. The team also noted that the link between PPIs and reduced nutrient absorption has been previously recognized, but their research expands on this understanding by examining a wider range of minerals, including magnesium and zinc.
The researchers stress the importance of rational PPI use and, in some cases, assessing the necessitate for nutritional supplementation under medical supervision. “We reinforce the importance of the rational use of these drugs and even of assessing the need for supplementation in some cases. However, medical supervision is necessary to evaluate each case individually,” Nogueira said.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
The Brazilian researchers plan to continue investigating the long-term effects of PPIs, with future studies aimed at confirming the link between prolonged use and osteoporosis risk. Patients currently taking PPIs should discuss their treatment plan with their doctor to determine the appropriate course of action.
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