Tag Archives: PPI

Proton pump inhibitors (antacid drugs) can cause severe magnesium deficiency

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Readers here are likely to know that magnesium is necessary for more than two hundred enzymes involved in cell metabolism including the production of ATP (the cellular ‘energy currency’). It is less well known that long term use of proton pump inhibitors (PPIs, such as omeprazole, aka Prilosec; Prevacid, Nexium, Protonix, etc.) can cause severe magnesium deficiencies. The authors of a study published in the journal Clinical Endocrinology set out to…

“…explore the mechanism underlying severe hypomagnesaemia in long-term users of proton-pump inhibitors (PPIs).”

One of the most common symptoms of suboptimal magnesium is muscle spasms or cramps. In the subjects they examined, the deficiency was so severe that they were having hypocalcemic seizures (calcium utilization also depends on magnesium). What did they find?

“Both patients were severely magnesium-depleted and had avid renal magnesium retention, implicating a failure of intestinal magnesium absorption…The hypomagnesaemia could be partially corrected by high dose oral magnesium supplementation, and resolved on withdrawal of PPIs.”

In other words, the kidneys were trying their best to compensate for the failure of intestinal absorption due to the PPIs but it wasn’t enough. Clinicians and any individuals taking PPIs long-term should bear in mind the authors’ conclusions:

“PPI use can inhibit active magnesium transport in the intestine…Long-term PPI users who are highly adherent to treatment can eventually deplete total body magnesium stores and present with severe complications of hypomagnesaemia.“

There are often more physiological therapies effective for conditions such as gastroesophageal reflux disease (GERD) for which PPIs are commonly prescribed.

Proton pump inhibitors to suppress stomach acid increase risk of fracture and infection

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Archives of Internal MedicineA 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.