Long-term proton pump inhibitor use linked to serious health risks
image: Responses to the medical causality and possibility of occurrence of known major side effects of PPI. C. difficile
Credit: Ather Ahad Mir, Zahoor Ahmad Wani, Ajmal R. Bhat, Khairi M. Fahelelbom 3, Ankush Kumar, Sumeer Ahmed.
Summary:
Proton pump inhibitors (PPIs), widely prescribed for acid-related disorders like GERD and peptic ulcers, are associated with significant adverse effects when used long-term. This review highlights multiple risks, including:
Infections: Increased susceptibility to Clostridium difficile and pneumonia due to gut microbiome disruption and reduced gastric acid barrier function.
Neurological Impact: Potential link to dementia via impaired amyloid-beta clearance, vitamin B12 deficiency, and reduced acetylcholine synthesis.
Bone Health: Higher fracture risk from calcium malabsorption and disrupted bone remodeling (TRPM6/7 channel inhibition).
Kidney Disease: Acute interstitial nephritis, chronic kidney disease (CKD), and vascular calcifications exacerbated by hypomagnesemia.
Metabolic Effects: Elevated risk of type 2 diabetes (T2DM) and metabolic syndrome, possibly due to altered magnesium homeostasis and nitric oxide pathway interference.
Despite their efficacy, PPIs are often overprescribed, with studies showing 50–90% of hospital patients receive them without clear indications. Geographic and genetic factors (e.g., CYP2C19 metabolism) further influence risk variability.
Clinical Recommendations:
Short-term use: Limit to 4–8 weeks for GERD/ulcers.
Monitoring: Regular checks for magnesium, vitamin B12, and kidney function in long-term users.
Alternatives: Consider H2 blockers or lifestyle modifications where possible.
This review underscores the need for judicious PPI prescribing, emphasizing personalized risk-benefit assessments to mitigate widespread complications. Future research should explore molecular mechanisms and alternative therapies.
Key Takeaway: While PPIs remain vital for acid suppression, their long-term use demands caution due to multifaceted systemic risks.