Brazilian researchers have identified potential links between prolonged use of proton pump inhibitors (PPIs) and disruptions in the body’s ability to absorb essential minerals, raising concerns about long-term health effects. The study, conducted by scientists at the Federal University of São Paulo (UNIFESP) and the ABC Medical School (FMABC), focused on the impact of omeprazole on mineral distribution in rats.
PPIs, including omeprazole, pantoprazole, and esomeprazole, are widely prescribed to treat conditions such as ulcers, gastritis, and acid reflux by reducing stomach acid production. Although effective, the research suggests that extended use may lead to mineral imbalances, potentially increasing the risk of anemia and affecting bone health. The findings were published in the journal ACS Omega.
The UNIFESP and FMABC team, funded by FAPESP, examined how continued omeprazole treatment affected the absorption of iron, calcium, zinc, magnesium, copper, and potassium in rats. Animals receiving the drug exhibited altered mineral distribution, with some minerals accumulating in the stomach while levels decreased in the liver and spleen. Blood tests revealed elevated calcium and reduced iron levels, changes the researchers associate with increased risks of osteoporosis and anemia.
The experiment involved dividing adult rats into control and treatment groups, with the latter receiving omeprazole for 10, 30, and 60 days to simulate varying durations of prolonged use in humans. “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. However, longer studies are needed to confirm this hypothesis,” said Angerson Nogueira do Nascimento, a professor at UNIFESP who coordinated the study in partnership with Fernando Fonseca from FMABC.
PPIs function by blocking the H+, K+, ATPase enzyme, also known as the proton pump, which controls hydrochloric acid production in the stomach. While suppressing acid alleviates symptoms of gastric distress, stomach acid is also crucial for nutrient absorption. Reduced acid production over extended periods can compromise the absorption of minerals dependent on an acidic environment, according to the research.
Concerns about PPI overuse are growing, particularly with the recent decision by the Brazilian Health Regulatory Agency (ANVISA) to authorize over-the-counter sales of 20mg omeprazole in November 2025. Andréa Santana de Brito, a researcher at UNIFESP, warned that increased accessibility could encourage self-medication and prolonged use, potentially disregarding recommended treatment limits. “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,” Brito said, noting her research formed the basis of her master’s thesis.
ANVISA defended its decision, stating that making omeprazole available without a prescription aims to promote responsible use. The agency emphasized that limiting treatment to a maximum of 14 days reinforces the message that the drug should be used for mild, temporary symptoms, and encourages patients with persistent issues to seek medical evaluation. ANVISA also stated that packages containing more than a 14-day supply will still require a prescription. The agency provided this statement to Agência FAPESP.
The researchers caution that the effects observed with omeprazole may extend to other PPIs, such as pantoprazole and esomeprazole, which operate through a similar mechanism. Brito suggested that newer PPIs might even have a more pronounced impact due to their greater potency and longer duration of action. “In these cases, the effect may be even more intense since these molecules have a more potent and longer-lasting action. Some take more than five days to allow the formation of modern proton pumps, while omeprazole takes about one to three days, which can intensify side effects,” she explained.
The study reinforces existing recognition of the link between PPIs and reduced nutrient absorption, expanding the understanding by examining additional minerals like magnesium and zinc. “We reinforce the importance of the rational use of these drugs and even of assessing the demand for supplementation in some cases. However, medical supervision is necessary to evaluate each case individually,” Nogueira said.
