A study spearheaded by researchers from the Federal University of São Paulo (Unifesp) and the ABC Medical School (FMABC) has issued a significant warning: the prolonged use of proton pump inhibitors (PPIs), including common medications like omeprazole, can severely compromise nutrient absorption and bone health. These findings, relevant for 2025, highlight critical health implications for millions.
The class of drugs, which encompasses omeprazole, pantoprazole, and esomeprazol, is widely prescribed for various gastric disorders. However, extended use beyond medical recommendations poses serious risks, leading to nutritional deficiencies such as anemia and potentially weakening bone structure, a concern that has gained renewed urgency with recent regulatory changes.
Published in the esteemed journal ACS Omega, the research sheds new light on how these medications interfere with essential bodily functions. The investigation, supported by Fapesp, delved into the continuous use of omeprazole and its specific impact on the absorption of vital minerals.
This concern is amplified by a November 2025 decision from the Brazilian National Health Surveillance Agency (Anvisa), which will permit the over-the-counter sale of 20 mg omeprazole without a prescription. Experts fear this increased accessibility could foster self-medication and continuous use, disregarding the recommended 14-day treatment limit.
Omeprazole’s impact on mineral distribution
The Unifesp and FMABC study meticulously evaluated the effects of continuous omeprazole use on the absorption of critical minerals like iron, calcium, zinc, magnesium, copper, and potassium in rats. The animal models that received the medication displayed significant alterations in how these nutrients were distributed throughout their bodies.
Researchers observed an unsettling pattern where the medication altered the systemic distribution of minerals. Specifically, they noted an accumulation of certain minerals in the stomach, while simultaneously observing imbalances in the spleen and liver. These shifts point to a broader disruption of mineral homeostasis crucial for overall health.
In the blood samples of treated animals, a concerning rise in calcium levels was detected alongside a drop in iron, directly indicating an elevated risk for developing osteoporosis and anemia. Furthermore, the study identified substantial changes in immune system cells, suggesting a wider systemic impact beyond just digestive function.
Long-term health implications
Angerson Nogueira do Nascimento, a Unifesp professor who co-led the study with Fernando Fonseca of FMABC, highlighted a particularly alarming discovery. “The most worrying finding was the significant increase in calcium within the animals’ bloodstream,” Nascimento stated. “This could signal an imbalance involving the removal of minerals from bones, posing a future risk of osteoporosis.” He stressed that more extensive, longer-term studies are necessary to conclusively confirm this hypothesis in human populations.
The research protocol divided adult rats into control and omeprazole-treated groups. Experiments were conducted over periods of 10, 30, and 60 days. These specific durations were chosen to accurately simulate varying levels of prolonged omeprazole use commonly observed in humans, providing a clearer picture of chronic exposure.
Understanding the mechanism of action
Omeprazole, along with its counterparts like pantoprazole and esomeprazole, operates by inhibiting the H+, K+, ATPase enzyme, commonly known as the proton pump. This pump is the final arbiter of hydrochloric acid production in the stomach. By reducing gastric acidity, these medications effectively alleviate symptoms associated with ulcers, gastritis, and gastroesophageal reflux disease.
However, this therapeutic reduction in stomach acid comes with a significant trade-off. A less acidic environment in the stomach critically hinders the absorption of numerous essential nutrients that specifically require an acidic milieu for proper assimilation into the body. This mechanism explains the observed mineral deficiencies.
The widespread use and associated concerns
With over three decades on the market, omeprazole has become exceptionally widespread, frequently used for extended periods without adequate medical supervision. “This is not about demonizing an effective medication for various gastric conditions,” clarified Andréa Santana de Brito, a Unifesp researcher whose master’s thesis focused on this study. “The core issue is its trivialized use, even for minor symptoms like heartburn, and its prolonged administration for months, even years. Its adverse effects must not be overlooked.”
The impending November 2025 Anvisa ruling, allowing omeprazole 20 mg sales without a prescription, exacerbates this situation. “This newfound ease could significantly encourage self-medication and continuous use, directly contravening the medical recommendation to limit treatment to a maximum of 14 days,” Brito cautioned, emphasizing the potential for increased public health risks.
Anvisa’s perspective and new regulations for 2025
According to Anvisa, the classification of omeprazole 20 mg as an over-the-counter (MIP) medicine represents a strategic “advancement in rationalizing its use and promoting safe and responsible consumption.” In a statement to Agência Fapesp, Anvisa noted, “By limiting treatment to a maximum of 14 days, the message is reinforced that the medication should only be used for the relief of mild, temporary symptoms, encouraging patients to seek medical evaluation if symptoms persist or recur.”
The agency also highlighted that “clear guidelines in the leaflet and on the label – covering usage duration, warning signs, and potential drug interactions – will assist consumers in making informed decisions.” Furthermore, Anvisa confirmed that packaging containing more capsules than needed for a 14-day treatment period will not be permitted for sale without a medical prescription, reinforcing the short-term use mandate.
Broader implications for PPI class medications
While the primary investigation specifically focused on omeprazole, researchers underscore that newer molecules within the same drug class, such as pantoprazol and esomeprazol, operate through an identical mechanism of action. “In these instances, the effects could potentially be even more pronounced,” explained the researcher. This heightened impact stems from the fact that these modern molecules often exhibit more potent and prolonged action compared to omeprazole.
Some of these advanced PPIs can take more than five days for new proton pumps to regenerate, a process that typically occurs within one to three days with omeprazole. This extended duration of action may intensify potential side effects, including the nutrient absorption issues. Researchers reiterated that while the impact of PPIs on nutrient absorption was previously acknowledged, this study significantly expands that understanding by incorporating magnesium and zinc into the comprehensive analyses. “We emphasize the critical importance of rational medication use and, in specific circumstances, evaluating the necessity of nutritional supplementation,” Nogueira affirmed. “However, such decisions demand personalized medical oversight for each individual case.”
