A collection of studies published in the latest edition of Archives of Internal Medicine highlights what you may already know about the dangers of powerfully suppressing digestion in the stomach by inhibiting the production of gastric acid with medications like Prilosec, Prevacid, Nexium, etc. As an accompanying editorial notes:

“A staggering 113.4 million prescriptions for proton pump inhibitors (PPIs) are filled each year, making this class of drugs, at $13.9 billion in sales, the third highest seller in the United States…it should come as no surprise that PPIs have been shown to be overprescribed; between 53% and 69% of PPI prescriptions are for inappropriate indications.”

What kind of damage can be done? Stomach acid is mandatory for the digestion of protein. Protein makes of the flexible matrix (“scaffolding”) of bone to which the minerals attach, so the first study that associates proton pump inhibitors with total fractures is not unexpected:

“Use of PPIs was…modestly associated with clinical spine, forearm or wrist, and total fractures.”

Stomach acid is also the body’s first line of defense against gastrointestinal infections. Two additional papers confirm that PPIs are associated with increased risk of Clostridium difficile infection. The authors of the first paper observe:

“Proton pump inhibitors (PPIs) are widely used gastric acid suppressants, but they are often prescribed without clear indications and may increase risk of Clostridium difficile infection (CDI). We sought to determine the association between PPI use and the risk of recurrent CDI.”

What did their data show?

“Proton pump inhibitor use during incident CDI treatment was associated with a 42% increased risk of recurrence.”

The authors of the second paper reached the same conclusion:

“Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection. This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection.”

There is an important difference between treating the underlying causes of conditions like gastroesophageal reflux (which often occurs with stomach acid that is abnormally low) and just suppressing acid production. These studies only scratch the surface of the problems that can occur when the capacity to digest protein and protect the GI tract from infection is suppressed.

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I wonder how many people took note of the extremely important paper published recently in Clinical Gastroenterology and Hepatology. The author marshals twenty additional studies to bolster the finding that, when there is gastroesophageal reflux (GER) disease,  medications for insomnia can make both conditions worse: “Sleep-related GER causes insomnia. Patients might not realize that GER is contributing to their insomnia. When patients complain to their physician about their insomnia, they might not appreciate that GER is a contributing factor, so that instead of intensifying GER therapy during sleep time, they prescribe a non-benzodiazepine hypnotic such as zolpidem. This hypnotic prolongs esophageal acid clearance and delays the arousal response, which can further worsen reflux and thus their insomnia. To avoid this cycle, we should consider sleep-related GER as a possible cause of insomnia and treat GER during the sleep period instead of prescribing a hypnotic medication. This investigation has significant clinical relevance.” The author concludes by admonishing doctors: “…common medications used to manage insomnia depress the arousal response that is vital to esophageal refluxate clearance. The data are impressive. Ask your GER patients what happens during sleep!”

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