While these drugs are effective at reducing stomach acid, using them longer than recommended by a physician may lead to nutrient deficiencies, including anemia, and may negatively affect bone health. The findings were published in ACS Omega.

Mineral Imbalances Linked to Omeprazole

With funding from FAPESP, the team examined how ongoing use of omeprazole influenced the absorption of key minerals in rats. They focused on iron, calcium, zinc, magnesium, copper, and potassium. Animals treated with the drug showed clear shifts in how these minerals were distributed throughout the body.

The medication appeared to cause certain minerals to build up in the stomach, while creating imbalances in the liver and spleen. Blood tests revealed higher calcium levels and lower iron levels, changes associated with increased risks of osteoporosis and anemia. The researchers also observed notable alterations in immune system cells.

To conduct the experiment, adult rats were separated into two groups: a control group and a group that received omeprazole. The treatment periods lasted 10, 30, and 60 days to reflect different lengths 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,” says Angerson Nogueira do Nascimento, a professor at UNIFESP who coordinated the study in partnership with Fernando Fonseca from FMABC.

How Proton Pump Inhibitors Affect the Body

Medications such as omeprazole, pantoprazole, and esomeprazole work by blocking the H+, K+, ATPase enzyme, also known as the proton pump. This enzyme controls the final step in the production of hydrochloric acid in the stomach. By suppressing stomach acid, these drugs ease symptoms of ulcers, gastritis, and reflux.

However, stomach acid also plays a key 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 may be compromised.

Overuse and Over-the-Counter Access Raise Concerns

Omeprazole has been available for more than 30 years and is frequently used, sometimes for months or even years without medical supervision. “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,” warns Andréa Santana de Brito, a researcher at UNIFESP. The study formed the basis of her master’s research.

She notes that concerns may grow following a new rule from the Brazilian Health Regulatory Agency (ANVISA), which authorized over-the-counter sales of 20mg omeprazole in November 2025. “This ease of access may encourage self-medication and continuous use, disregarding the recommendation to limit treatment to 14 days,” she warns.

ANVISA’s Position on OTC Omeprazole

ANVISA maintains that making omeprazole 20mg available without a prescription is intended to promote responsible use. The agency describes the move as “a step forward in rationalizing its use and promoting its safe and responsible use.”

“By limiting treatment to a maximum of 14 days, the message that the drug should only be used to relieve mild and temporary symptoms is reinforced, encouraging patients to seek a medical evaluation if their symptoms persist or recur,” ANVISA said in a statement to the Agência FAPESP newsroom. “Clear guidelines in the package insert and on the label, such as the duration of use, warning signs, and possible drug interactions, help consumers make informed decisions.”

The agency also states that packages containing more than a 14 day supply cannot be sold without a prescription.

Effects May Extend to Other PPIs

Although the experiments focused on omeprazole, the researchers emphasize that newer drugs in the same category, including pantoprazole and esomeprazole, function in a similar way. According to Brito, these medications may have an even stronger impact because they act more powerfully and for longer periods.

“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 new proton pumps, while omeprazole takes about one to three days, which can intensify side effects,” she explains.

The team notes that the link between PPIs and reduced nutrient absorption was already recognized. However, this research expands that understanding by examining additional minerals, including magnesium and zinc. “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 says.