Long term side effects of ppi
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Long-Term Side Effects of Proton Pump Inhibitors (PPIs)
Increased Risk of Infections
Clostridium difficile and Pneumonia
Long-term use of proton pump inhibitors (PPIs) has been associated with an increased risk of infections, particularly Clostridium difficile and pneumonia. Studies have shown that the odds of developing C. difficile infections are significantly higher in PPI users, with an odds ratio of 2.151 4 5. Additionally, the risk of pneumonia is elevated by 27-39% in short-term PPI users, and this risk persists with long-term use1 4 5.
Nutrient Absorption Issues
Vitamin and Mineral Deficiencies
PPIs can impede the absorption of essential vitamins and minerals, leading to deficiencies. Notably, long-term PPI use is linked to decreased absorption of vitamin B12, iron, calcium, and magnesium1 2 4 5 9. This impaired absorption can result in conditions such as anemia, osteoporosis, and hypomagnesemia, which have significant health implications, especially in older adults5 9.
Bone Health
Osteoporotic Fractures
The US FDA has issued warnings about the increased risk of fractures associated with long-term PPI use. This is primarily due to impaired calcium absorption, which is crucial for bone health. Studies have consistently shown a higher incidence of osteoporotic-related fractures among long-term PPI users1 4 5.
Gastrointestinal Issues
Hypergastrinemia and Gastric Cancer
Chronic PPI use can lead to hypergastrinemia, a condition characterized by elevated levels of gastrin. This can result in rebound acid hypersecretion upon discontinuation of PPIs and has been linked to the development of gastric polyps, carcinoids, and potentially gastric cancer3 4 6 9. The increased gastric pH due to prolonged acid suppression also promotes bacterial overgrowth, further complicating gastrointestinal health4 6.
Renal and Cardiovascular Concerns
Chronic Kidney Disease and Cardiovascular Events
Recent studies have highlighted a potential association between long-term PPI use and chronic kidney disease (CKD) as well as cardiovascular events. Although the exact mechanisms are not fully understood, the evidence suggests that PPI-induced hypomagnesemia and interactions with other medications, such as clopidogrel, may contribute to these risks2 5 7 9.
Cognitive and Neurological Effects
Dementia
There is emerging evidence suggesting a link between long-term PPI use and an increased risk of dementia. While the data are still inconclusive and require further research, the potential for cognitive decline is a concern that warrants attention from both patients and healthcare providers2 5 9.
Conclusion
While PPIs are effective and generally safe for short-term use, their long-term use is associated with several significant adverse effects. These include increased risks of infections, nutrient deficiencies, bone fractures, gastrointestinal issues, renal and cardiovascular problems, and potential cognitive decline. Healthcare providers should carefully evaluate the necessity of prolonged PPI therapy and consider alternative treatments or lifestyle modifications to mitigate these risks. Regular monitoring and patient education are crucial to ensure the benefits of PPI use outweigh the potential harms.
Sources and full results
Most relevant research papers on this topic
Perils and pitfalls of long-term effects of proton pump inhibitors
Proton pump inhibitors (PPIs) are associated with serious adverse effects, including increased risk of pneumonia, Clostridium difficile infections, and fractures.
Systematic Review
Highly CitedLong-Term PPI Use: Balancing Potential Harms and Documented Benefits
Long-term proton pump inhibitor (PPI) use is associated with potential harms, including gastric carcinoids, gastric carcinoma, decreased mineral absorption, fractures, enteric infections, pneumonia, hypomagnesemia, and cardiovascular events.
Side Effects of Long‐Term Proton Pump Inhibitor Use: A Review
Long-term PPI use may increase the risk of gastrointestinal infections and rebound acid hypersecretion, but the most important safety issue is to critically evaluate the indication when initiating treatment and reconsidering it in long-term patients.
Literature ReviewHighly CitedPotential risks associated with long-term PPI use.
Long-term PPI therapy may cause side effects such as hypergastrinemia, carcinoid formation, gastric cancer, bacterial overgrowth, Clostridium difficile infection, pneumonia, bone fracture, and vitamin B12 and iron malabsorption.
Meta-AnalysisAdverse effects of proton-pump inhibitor use in older adults: a review of the evidence
Long-term proton-pump inhibitor use in older adults is associated with increased risks of osteoporotic-related fractures, Clostridium difficile infection, pneumonia, vitamin B12 deficiency, kidney disease, and dementia.
Systematic Review
Rigorous JournalHighly CitedA fresh look at proton pump inhibitor (PPI)-associated adverse events through a CYP2C19 pharmacogenetic lens
Proton pump inhibitors (PPIs) have a spectrum of risks, including increased gastric cancer risk, and further prospective studies are needed to measure risk and provide mechanistic insights for adverse effects.
Adverse effects of long-term proton pump inhibitor use: a review for the otolaryngologist.
Long-term proton pump inhibitor use may have epidemiological links to adverse outcomes like altered mineral and vitamin absorption, orthopedic injury, acute coronary syndromes, and infectious risks.
Systematic ReviewDo the benefits outweigh the risks? Potential dangers associated with long-term therapy of proton pump inhibitors
Long-term proton pump inhibitor use may be associated with complications such as infections, decreased nutrients, and various diseases, but the benefits may outweigh the risks for patients with strictly defined indications.
Systematic ReviewLong-term use of proton pump inhibitors as a risk factor for various adverse manifestations.
Long-term use of proton pump inhibitors (PPIs) can lead to increased gastric pH, hypochlorhydria, vitamin and mineral deficiencies, congenital malformations, and other adverse effects.
Literature ReviewProton pump inhibitor therapy and potential long-term harm
Long-term proton pump inhibitor use may complicate health conditions due to various mechanisms linked to PPIs and/or hypochlorhydria.
Literature ReviewHighly Cited