Long-term use of PPIs can cause which of the following?

• A. Weight gain
• B. Hair loss
• C. Liver toxicity
• D. Decreased bone density and risk for C. diff infection

Answer: (D)

Long-term suppression of stomach acid with a proton pump inhibitor changes two important things in the gut: mineral absorption and the protective barrier against pathogens. The acidic environment in the stomach helps dissolve minerals like calcium, which is necessary for bone health. When acid production is chronically reduced, calcium absorption can decrease, contributing to lower bone mineral density and a higher risk of fractures over time, especially in older adults.

At the same time, gastric acidity acts as a barrier to ingested microbes. With less acidity, the gut microbiota can be disrupted, increasing the risk of Clostridioides difficile infection. This organism can take hold more easily when the normal acidic barrier is diminished.

Other potential effects like weight gain, hair loss, or liver toxicity are not typical consequences of long-term PPI use, which is why decreased bone density and C. diff infection are the most clinically relevant risks to watch for.