Proton pump inhibitors are among the most commonly used medications worldwide, prescribed to reduce stomach acid and relieve conditions such as heartburn, reflux and ulcers. New research suggests that prolonged use of these drugs may affect how the body absorbs and distributes essential minerals, at least in animals.
In a study conducted by researchers at the Federal University of São Paulo and ABC Medical School and published in ACS Omega, rats given the acid-reducing drug omeprazole over extended periods showed changes in mineral levels linked to bone health, blood health and immune function.
The researchers examined several minerals that play important roles in nutrition and metabolism, including iron, calcium, magnesium, zinc, copper and potassium. Adult rats were divided into a control group and a group treated with omeprazole for 10, 30 or 60 days, durations meant to reflect different lengths of prolonged use in humans.
Compared with controls, rats that received omeprazole showed altered distribution of these minerals throughout the body. Calcium levels increased in the bloodstream, while iron levels declined. The researchers also observed mineral accumulation in the stomach and shifts in mineral levels in organs such as the liver and spleen, along with changes 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. However, longer studies are needed to confirm this hypothesis,” said Angerson Nogueira do Nascimento, a professor at UNIFESP who coordinated the study.
Proton pump inhibitors work by blocking the enzyme responsible for the final step of acid production in the stomach. While reducing acidity can relieve digestive symptoms, stomach acid also plays a role in releasing minerals from food so they can be absorbed. By suppressing acid, these medications may make it harder for the body to absorb certain nutrients, particularly when used continuously for long periods.
Researchers emphasized that the findings should not be interpreted as a reason to avoid PPIs altogether.
“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,” said Andréa Santana de Brito, a researcher at UNIFESP.
The study was conducted in rats, not humans, and the authors caution that mineral changes observed in animals do not automatically translate to real-world health outcomes such as osteoporosis or anemia. Still, the results add to existing evidence that long-term PPI use may warrant closer monitoring, particularly among people who take these medications for months or years.
The researchers also noted that easier access to over-the-counter omeprazole may increase the likelihood of unsupervised, prolonged use. They recommend that extended treatment be guided by medical professionals, with individual assessment of risks, benefits and potential need for nutrient monitoring.
The study was supported by Brazil’s National Council for Scientific and Technological Development, the Brazilian Federal Agency for Support and Evaluation of Graduate Education, the National Institute of Science and Technology in Bioanalytics, the Financier of Studies and Projects and the São Paulo Research Foundation.