Many Americans who suffer from heartburn find relief from the discomfort by taking proton pump inhibitors – an over-the-counter medication. Although these drugs are widely used, concerns are mounting over their long-term effects on the body. Recent studies have demonstrated links between proton pump inhibitors and a range of health conditions. A new study, published in Circulation Research, finds a potential mechanism to explain these negative health implications.

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Do the risks outweigh the benefits of proton pump inhibitors?

Heartburn, also referred to as esophageal reflux or GERD, occurs when acid from the stomach finds its way into the esophagus.

The condition can be very unpleasant and, because proton pump inhibitors (PPIs) are easily available and clear up symptoms quickly, they have proven very popular.

According to the U.S. Food and Drug Administration (FDA), 1 in 14 Americans have used PPIs at least once. In 2006, an estimated $7 billion was spent on PPIs globally.

Esomeprazole, brand name Nexium, is one of the most commonly purchased PPIs. In 2015, Nexium created almost $2.5 billion of revenue for drug manufacturer AstraZeneca.

Because these drugs are so effective at relieving reflux, and because they do not require a prescription, they are used much more widely than initially predicted. PPIs were never approved for long-term use by regulatory authorities and recent studies have shown a number of worrying correlations.

Heart disease, kidney disease, and dementia have all been linked to long-term PPI usage.

However, studies to date have only been able to demonstrate correlation, rather than causation. Also, until now, no known mechanism has been uncovered that can explain the findings.

Recent research, carried out by Dr. John P. Cooke at Houston Methodist Research Institute, TX, investigated a potential molecular mechanism by which PPIs might induce their negative health effects.

Dr. Cooke believes that premature aging of the endothelial cells that line the interior of blood vessels might be part of the answer.

The researchers investigated the role of two PPIs, one of which was Nexium. They found that prolonged exposure to the drugs led to premature biological aging of these vascular cells.

When healthy, human endothelial cells create a Teflon-like coating that prevents blood from sticking. When older and diseased, the endothelium becomes more like Velcro, with blood elements sticking to the vessel to form blockages.”

Lead author John P. Cooke, M.D., Ph.D.

This change to blood vessel linings might help explain some of the negative health consequences of PPI. Interestingly, it was not the only cellular change that the researchers observed.

PPIs are designed to prevent acid from being produced in the parietal cells of the stomach. They irreversibly bind to the gastric proton pump, stopping gastric acid production almost completely. However, these are not the only acid producing cells that appear to be altered by the drugs.

Lysosomes are present in many cells of the body and are responsible for clearing up unwanted debris. They clear up cellular garbage and break it down using acids. If the metaphorical trash accumulates, cells age faster.

Results from the study showed that PPIs prevented lysosomes from producing an adequate supply of acid. In other words, their ability to remove the rubbish was diminished, causing premature aging of the cells.

Interestingly, other GERD medications that work by a different mechanism – H2 antagonists – do not exhibit this effect on lysosomes.

Dr. Cooke hopes that these results will help convince official bodies to draw up stricter guidelines around the use of PPIs.

Unless otherwise indicated, physicians should consider PPIs only for short-term use for relief of symptoms of GERD, since we now have a ‘smoking gun’ that helps explain the consistent observational evidence of increased risk.”

John P. Cooke, M.D., Ph.D.

Other potential methods for controlling GERD include lifestyle modifications, H2 antagonists and, in some cases, surgery.

The current research centered around in vitro (outside of the body) investigations, so further research in humans will be needed to firm up the findings. If the results are backed up by future studies, they might eventually lead to wide-ranging changes in the way PPIs are regulated.

Learn about PPIs and their links to kidney damage.