Study warns of nutritional risks of prolonged use of the drug omeprazole

Research conducted on rats reinforces the idea that proton pump inhibitors, which are widely used to treat stomach problems, can affect mineral absorption and compromise bone health.

By Maria Fernanda Ziegler  |  Agência FAPESP – A study conducted in Brazil by researchers at the Federal University of São Paulo (UNIFESP) and the ABC Medical School (FMABC) warns that the prolonged use of proton pump inhibitors (PPIs) can impair nutrient absorption. PPIs are a class of drugs that includes medications such as omeprazole, pantoprazole, and esomeprazole. They are used to treat gastric disorders. Using them inappropriately for periods longer than recommended by physicians can cause nutritional deficiencies, such as anemia, and compromise bone health. The results were published in the journal ACS Omega.

Supported by FAPESP, the research evaluated the effects of continuous use of this medication on the absorption of essential minerals, such as iron, calcium, zinc, magnesium, copper, and potassium, in rats. Animals that received the drug showed changes in the distribution of these nutrients throughout their bodies. The researchers observed that the drug alters the distribution of minerals in the body, causing accumulation in the stomach and imbalances in the spleen and liver. In the blood, they observed an increase in calcium and a decrease in iron, indicating an increased risk of osteoporosis and anemia. Significant changes in immune system cells were also detected.

For the study, adult rats were divided into two groups: a control group and a group treated with omeprazole. The experiments lasted 10, 30, and 60 days to simulate different levels of prolonged human use of the drug.

“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.

Medications such as omeprazole, pantoprazole, and esomeprazole inhibit the H⁺, K⁺, ATPase enzyme. This enzyme, known as the proton pump, is responsible for the final stage of hydrochloric acid production in the stomach. These drugs reduce gastric acidity, relieving symptoms of ulcers, gastritis, and reflux. However, they also hinder the absorption of nutrients that depend on an acidic environment.

Omeprazole has been on the market for over 30 years and is widely used, often for prolonged periods and 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 was the subject of her master’s research.

She points out that the situation may worsen with the new ordinance from the Brazilian Health Regulatory Agency (ANVISA) that approved the sale of 20mg omeprazole without a prescription 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

According to ANVISA, including omeprazole 20mg as an over-the-counter drug represents “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.”

ANVISA also clarifies that packages containing more than 14 days’ worth of capsules cannot be sold without a prescription.

Research with other molecules

The research was conducted with omeprazole; however, the researcher points out that more modern molecules in the same class of drugs, such as pantoprazole and esomeprazole, act through the same mechanism. “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.

According to the researchers, the impact of PPIs on nutrient absorption was already known; however, the study broadens this understanding by including magnesium and zinc in the analyses. “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.

The article “Evaluation of the long-term administration of proton pump inhibitors (PPIs) in the mineral nutrient’s bioavailability” can be read at pubs.acs.org/doi/10.1021/acsomega.5c07700.