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PPI Side Effects

Proton pump inhibitors (PPIs) are medications that are widely used, and concerns about overuse have been raised. This category includes medications such as lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), rabeprazole (AcipHex), and esomeprazole (Nexium). They are prescribed to both prevent and treat ulcers in the duodenum and the stomach. They also counter the various problems that occur when stomach acid escapes into the esophagus, which — if it happens on a regular basis — is a condition called gastroesophageal reflux disease (GERD). In most head-to-head trials, the PPIs have proved to be superior to the H2 blockers like Zantac, Pepcid, or Tagamet.

Many people take PPIs for gastroesophageal reflux disease (GERD). By lowering stomach acid levels, they reduce acid reflux into the esophagus and the resulting heartburn symptoms. Since many people take these medications for a long time, the total exposure time has significantly increased. This comes with a cost. These medications have many side effects including:

  1. Gastrointestinal effects

Clostridium difficile and other intestinal infections — PPI use has been associated with an increased risk of C. difficile infection, even in the absence of antibiotic use Clostridium difficile or C. difficile  in short is a bacteria associated usually with taking antibiotics. It can use diarrhea, abdominal pain and in rare case rupture of intestine.   . Associations with other intestinal  infections, including salmonellosis and campylobacter, have also been reported.


Microscopic colitis — PPI use has been associated with microscopic colitis, which is inflammatory condition of intestine that can cause diarrhea weight loss or intestinal bleeding.


Atrophic gastritis — Patients on long-term PPI therapy have a propensity to develop chronic atrophic gastritis. A condition that the cells of stomach will shrink or start to not function properly. The clinical consequences  of this is uncertain 


Intestinal colonization of multi-drug resistant organisms — PPIs may increase the risk of intestinal colonization with multi-drug resistant organisms. These are bacteria that are hard to treat. Possible mechanisms include an increase in bacteria that survive passage from the stomach to the intestine due to reduction in stomach acid by PPIs and direct alteration of the composition of intestinal microbiota (Healthy bacteria in the intestine).


Inflammatory bowel disease — There is some evidence (based on observational studies) that the risk of inflammatory bowel disease (IBD) was increased in regular PPI users as compared with nonusers.


  1. Malabsorption of minerals and vitamins


Magnesium malabsorption — PPIs can cause low magnesium due to reduced intestinal absorption. Magnesium is a mineral that is needed for many of chemical reactions in the body in multiple organs. Clinical manifestations of low magnesium include neuromuscular excitability (eg, tremor, tetany, convulsions), weakness, and apathy. 


Calcium and fracture risk — Decrease production of acid in the stomach can interfere with absorption of some formats of calcium and thru inducing bone resorption can potentially cause osteoporosis and bone fracture.


Vitamin B12 and Iron malabsorption — Long-term therapy with PPIs has been associated with vitamin B12 and Iron malabsorption. 


Kidney disease — PPIs can cause acute interstitial nephritis (AIN), an inflammatory kidney condition. PPI use has possible association with  an increased risk of chronic kidney disease (CKD), CKD progression, and end-stage kidney disease 


  1. Other associations of unclear significance

COVID-19 — Some studies have demonstrated that patients taking PPIs are at increased risk for severe clinical outcomes of COVID-19 but have not demonstrated an increase in susceptibility to SARS-CoV-2 infection. 


Dementia — Although some studies have found a significant association between use of PPIs and incident dementia, others have not found an association between PPI use and cognitive function 

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