Proton Pump Inhibitors: Placing Putative Adverse Effects in Proper Perspective

Mitchell L. Schubert


Curr Opin Gastroenterol. 2019;35(6):509-516. 

In This Article


PPIs are well tolerated and effective medications. Nevertheless, there has been an avalanche of articles, over the past several years, ascribing a panoply of potentially serious adverse effects to their use. The quality of evidence linking PPIs to alterations in the microbiome, enteric infection, drug–drug interactions, and microscopic colitis is relatively strong. The quality of evidence linking PPIs to cognitive decline, myocardial infarction, stroke, bone fracture, chronic kidney disease, and death is very weak. It should be emphasized that retrospective observational database studies cannot establish cause-and-effect relationships because of inherent confounding and channeling bias. It is probable that PPIs may rarely induce micronutrient deficiency (magnesium, calcium, iron, and vitamin B12). It is possible that PPIs, by inducing hypergastrinemia and changes in the microbiome, participate in carcinogenesis.

Whenever PPIs are prescribed appropriately, the benefits outweigh potential adverse effects. As the absolute risk to an individual is extremely low, fear of these risks should not dictate prescribing habits. PPIs should be prescribed for valid indications and used at the lowest effective dose. Their long-term use should be periodically assessed. When PPIs are clearly necessitated, it is imperative that their prescription by physicians and use by patients is not quashed by potential unproven risks.