A scientific study conducted in Brazil has renewed attention to the potential nutritional risks associated with the long-term use of proton pump inhibitors (PPIs), a class of medicines widely prescribed for gastric disorders such as reflux, gastritis and peptic ulcers. The findings indicate that extended use of these drugs may interfere with the body’s ability to absorb essential minerals, with possible consequences for bone integrity, blood composition and immune function.
The investigation was carried out by researchers from the Federal University of São Paulo (Unifesp) in collaboration with the ABC School of Medicine (FMABC), with financial support from the São Paulo Research Foundation (FAPESP). The results were published in the peer-reviewed journal ACS Omega, reinforcing concerns already raised in international scientific literature regarding prolonged acid suppression therapy.
Using an experimental animal model, the Brazilian researchers evaluated adult rats exposed to continuous administration of omeprazole, one of the most commonly used PPIs worldwide. The animals were monitored over periods equivalent to short-, medium- and longer-term use in humans, allowing the scientists to observe progressive physiological changes linked to mineral metabolism.
According to the study, sustained suppression of gastric acid altered the distribution of key minerals such as iron, calcium, magnesium, zinc, copper and potassium. While some minerals accumulated in the stomach, imbalances were observed in organs including the liver and spleen. Blood analyses revealed a reduction in iron levels alongside elevated calcium concentrations, a combination associated in clinical settings with an increased risk of anaemia and compromised bone health.
The rise in circulating calcium was identified as one of the most concerning findings. Researchers noted that this pattern may suggest mobilisation of calcium from bone tissue into the bloodstream, a mechanism that, if confirmed in long-term human studies, could contribute to osteoporosis. Alterations in immune-related cells were also documented, pointing to broader systemic effects beyond the digestive tract.
PPIs such as omeprazole, pantoprazole and esomeprazole act by inhibiting the H⁺/K⁺-ATPase enzyme, often referred to as the gastric proton pump. This enzyme is responsible for the final stage of hydrochloric acid production in the stomach. While reducing acidity is effective for symptom control and mucosal healing, an acidic environment is also essential for the proper absorption of several micronutrients, particularly iron and calcium.
Although the study focused on omeprazole, the researchers emphasised that newer PPIs share the same mechanism of action and may exert similar or even more pronounced effects. Some of these compounds suppress acid secretion for longer periods, potentially extending the window during which nutrient absorption is impaired.
The findings are particularly relevant in the Brazilian context, where PPIs have been available for more than three decades and are frequently used beyond recommended treatment durations. In November 2025, Brazil’s health regulator, the National Health Surveillance Agency (Anvisa), authorised the over-the-counter sale of omeprazole 20 mg for short-term relief of mild symptoms. While Anvisa maintains that clear labelling and a 14-day usage limit promote responsible self-care, researchers warn that easier access may inadvertently encourage prolonged, unsupervised use.
Experts involved in the study stress that PPIs remain effective and important medicines when prescribed appropriately. However, they argue that indiscriminate or long-term use without medical monitoring should be avoided. International clinical reviews have similarly reported associations between chronic PPI therapy and mineral deficiencies, fractures and anaemia, underscoring the need for cautious prescribing and regular reassessment of treatment necessity.
The Brazilian researchers conclude that rational use of PPIs is essential and that, in selected cases, monitoring of nutritional status or targeted supplementation may be required. They also highlight the importance of further long-term studies, particularly in human populations, to better define risks and guide evidence-based clinical practice.
As PPIs continue to play a central role in the management of gastric conditions worldwide, the study from Brazil adds to a growing body of evidence suggesting that their benefits must be carefully balanced against potential nutritional and systemic effects when used over extended periods.