Abstract
Proton pump inhibitors (PPIs) have been increasingly used over the last decades and there are concerns about overuse and the numerous reported side-effects. It is uncertain whether associations between PPI use and potential side effects are causal. However, important evidence from experimental and mechanistic studies that could support a causal relationship may have been underestimated by epidemiologists and meta-analysists. In the current manuscript we review the combined epidemiological and mechanistic evidence of the adverse effects of PPI use.
Highlights
Proton pump inhibitors (PPIs) are irreversible inhibitors of the gastric H+ K+ ATPase in parietal cells and they reduce acid secretion
Numerous of side effects of PPIs have been proposed and we have in this review focused on theNumerous increased types risk of neoplasia, disease, bone and fractures, impaired absorption of of gastric side effects of PPIskidney have been proposed we have in this review focused micronutrients, dementia, and liver disease
Some this may bereviewed explained inter-individual variation acid inhibitionworldwide in humans use andof that a of theofside-effects arebyrelatively rare in contrast toin the widespread users have more profound and long-lasting acid inhibition following ingestion, Some of this may be explained by inter-individual variation in acid inhibition in humans and that which is reflected by variations serum gastrin concentrations
Summary
Proton pump inhibitors (PPIs) are irreversible inhibitors of the gastric H+ K+ ATPase in parietal cells and they reduce acid secretion. An increase in PPI use has been well described in many countries over the last decades [5,6] This increase is perceived to be caused by the widespread use of PPIs in treatment of dyspepsia and prevention of gastrointestinal bleeding in patients prescribed antiplatelet therapy or non-steroid anti-inflammatory drugs (NSAIDs), coupled with the belief that PPIs have few adverse effects. Short-term effects of PPIs are relatively well studied, but the consequences of long-term profound acid inhibition are not fully known, as the observation time in epidemiological studies is often too short for the detection of diseases that develop over many years. Another problem with epidemiologic studies is the inherent potential of unmeasured confounding factors.
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