Millions rely on proton pump inhibitors (PPIs) like omeprazole, pantoprazole, and esomeprazole to manage conditions such as heartburn, ulcers, and acid reflux. Still, emerging research suggests a potential downside to long-term use of these widely available medications: interference with the body’s ability to absorb essential nutrients. A new study conducted in Brazil highlights potential links between prolonged PPI use and increased risks of anemia and osteoporosis, prompting a closer look at the benefits and risks of these common drugs.
The findings, published in ACS Omega, add to a growing body of evidence suggesting that while PPIs effectively reduce stomach acid, extended use may disrupt the delicate balance of mineral absorption within the body. Researchers at the Federal University of São Paulo (UNIFESP) and the ABC Medical School (FMABC) investigated the impact of omeprazole on mineral levels in rats, revealing concerning shifts in how key nutrients were distributed throughout their systems.
Mineral Imbalances Observed in Animal Study
The research team, supported by funding from FAPESP, focused on the absorption of iron, calcium, zinc, magnesium, copper, and potassium in rats treated with omeprazole. Their investigation revealed that the medication led to an accumulation of certain minerals in the stomach, while simultaneously creating imbalances in the liver and spleen. Notably, blood tests showed elevated calcium levels and decreased iron levels, changes that researchers associate with an increased risk of osteoporosis and anemia. Alterations in immune system cells were also observed during the study.
Researchers divided adult rats into control and treatment groups, administering omeprazole for 10, 30, and 60 days to simulate varying durations of human use. “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 partnership with Fernando Fonseca from FMABC. “However, longer studies are needed to confirm this hypothesis.”
How PPIs Affect Nutrient Absorption
PPIs work by blocking the H+, K+, ATPase enzyme, also known as the proton pump, which is crucial for producing stomach acid. While effectively reducing acid, this suppression can also hinder the absorption of nutrients that rely on an acidic environment. Stomach acid plays a vital role in breaking down food and releasing minerals, making them available for absorption in the intestines. Prolonged reduction of stomach acid can therefore compromise the body’s ability to utilize these essential nutrients.
Concerns Over Overuse and Increased Access
Omeprazole has been available for over 30 years and is frequently used, sometimes for months or even years without consistent medical oversight. Andréa Santana de Brito, a researcher at UNIFESP, cautioned against the “trivialized use” of PPIs, even for mild symptoms like heartburn. “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. Her research formed the basis of her master’s thesis.
These 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 expressed concern that easier access could encourage self-medication and prolonged, unsupervised use, potentially disregarding recommendations to limit treatment to 14 days.
ANVISA’s Stance on Over-the-Counter Access
ANVISA maintains that allowing over-the-counter access to 20mg omeprazole is intended to promote responsible use. The agency described the move as “a step forward in rationalizing its use and promoting its safe and responsible use.” In a statement to Agência FAPESP, ANVISA emphasized that limiting treatment to a maximum of 14 days reinforces the message that the drug should be used for mild, temporary symptoms, encouraging individuals to seek medical evaluation if 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 on omeprazole, researchers emphasize that other drugs in the same class, including 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. “Some take more than five days to allow the formation of new proton pumps, while omeprazole takes about one to three days, which can intensify side effects.”
The research team acknowledges that a link between PPIs and reduced nutrient absorption has been previously recognized, but their work expands on this understanding by examining a broader range of minerals, including magnesium and zinc. Nogueira emphasized the importance of rational PPI use and the potential demand for supplementation in some cases, but stressed that medical supervision is crucial for individualized evaluation.
Further research is needed to determine the extent to which these findings translate to humans and to establish clear guidelines for the safe and effective use of PPIs. As awareness grows regarding the potential long-term effects of these medications, both patients and healthcare providers should engage in informed discussions about the risks and benefits of PPI therapy.
Disclaimer: This article provides informational content and should not be considered medical advice. Always consult with a qualified healthcare professional for diagnosis and treatment of any health condition.
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