What are the long-term effects of taking Proton Pump Inhibitors (PPIs) for years?

From the Guidelines

Long-term use of Proton Pump Inhibitors (PPIs) can lead to several potential health concerns, including vitamin and mineral deficiencies, kidney problems, and increased risk of fractures, and therefore, it is recommended to use the lowest effective dose and regularly monitor vitamin and mineral levels with supplementation if needed. The most established risks include vitamin and mineral deficiencies, particularly vitamin B12, magnesium, calcium, and iron, as PPIs reduce stomach acid which is needed for proper nutrient absorption 1. This can contribute to anemia and osteoporosis with increased fracture risk over time. Kidney problems, including chronic kidney disease and acute interstitial nephritis, have been associated with long-term PPI use. Some studies suggest increased risks of dementia, certain infections like Clostridium difficile and pneumonia due to altered gut bacteria, and small intestinal bacterial overgrowth. There's also concern about potential increased risk of gastric cancer with very long-term use, though this relationship isn't fully established.

• Key considerations for long-term PPI use include:
  • Regular monitoring of vitamin and mineral levels, with supplementation if necessary
  • Evaluation of the need for continued PPI use, considering alternative treatments like H2 blockers for less severe symptoms
  • Use of the lowest effective dose to minimize potential risks
  • Awareness of potential interactions with other medications and health conditions If you've been taking PPIs for years, don't stop abruptly as this can cause rebound acid hypersecretion. Instead, work with your healthcare provider to evaluate if continued use is necessary and to develop a plan for safe and effective management of your condition 1.

From the Research

Long-term Effects of Proton Pump Inhibitors (PPIs)

The long-term effects of taking Proton Pump Inhibitors (PPIs) for years have been studied in various research papers. Some of the key findings include:

• Increased risk of fracture, particularly hip fracture, with long-term PPI use, depending on the dose and duration of treatment 2
• Risk of bacterial overgrowth and spontaneous bacterial peritonitis with PPI therapy, but not with histamine-2 receptor antagonists (H2RA) 2
• Slight increase in the risk of community-acquired pneumonia (CAP) in the early stages of PPI use, particularly at high doses 2
• No significant difference in vitamin B12, folic acid, vitamin D, and calcium values with long-term PPI use 2
• Increased risk of hypomagnesemia with PPI use, particularly in patients with reduced kidney function, using diuretics, or over 65 years of age 2
• Reduced zinc absorption with PPI use, as shown in quasi-experimental studies 2
• Increased risk of fundic polyps with long-term PPI use (>1 year) 2

Best Practice Advice for Long-term PPI Use

According to the American Gastroenterological Association, the following best practice advice is recommended for long-term PPI use:

• Patients with gastroesophageal reflux disease (GERD) and acid-related complications should take a PPI for short-term healing, maintenance of healing, and long-term symptom control 3
• Patients with uncomplicated GERD who respond to short-term PPIs should attempt to stop or reduce them 3
• Patients with Barrett's esophagus and symptomatic GERD should take a long-term PPI 3
• Asymptomatic patients with Barrett's esophagus should consider a long-term PPI 3
• The dose of long-term PPIs should be periodically reevaluated to prescribe the lowest effective dose 3

Potential Problems Related to Long-term PPI Use

Some potential problems related to long-term PPI use include:

• Increased risk of osteoporosis and fractures 4, 2
• Gastric polyps 4
• Higher serum gastrin levels 4
• Reduced bone density, particularly in the hip and lumbar regions 4
• Increased risk of infections, such as Clostridium difficile-associated diarrhea and community-acquired pneumonia 5, 2