Proton Pump Inhibitors (PPIs), commonly known as the ‘Purple Pill’, which people pop routinely to get rid of their heartburn, could, if taken over long term, lead to some serious health risks.

In the US and some countries, these wonder drugs are available as OTC (over the counter) drugs for treating gastric acid reflux diseases (GERD). These drugs are also prescribed for long-term use in our country. The US Food and Drug Administration (USFDA) recommended use of these drugs for 4-8 weeks only.

Now, fresh evidence is emerging that their overuse could lead to trouble for the heart, kidney and brain. Flagging this lurking danger signal is June 10 paper published in the Circulation Research , an American Heart Association Journal.

Chronic use has been found to impact in two ways. First, they can accelerate the aging of the endothelial cells (inner lining of the blood vessels), which plays a key role in the maintenance of blood vessels. Damage of endothelial cells leads to various vascular problems, including hypertension (high blood pressure), coronary heart diseases (heart attack), diabetes, high blood cholesterol, kidney failure, dementia (loss of memory) and many more problems.

Second is the shortening of Telomeres (ends of chromosomes responsible for cells to divide). Maintaining normal telomeres is important for good health.

“These actions observed in laboratory studies quicken the process of endothelial cell aging in the humans, which in turn can reflect in increased risk of cardiovascular problems, dementia and kidney failure,” says Gautham Yepuri, a major contributing author of the publication from the Houston Methodist Research Institute, Texas, US.

$13-billion market

PPIs come in a variety of forms, always ending with the suffix ‘-prazole’. In addition to Nexium, other commercial brands include Prilosec, Protonix, Aciphex and Prevacid. The estimated market is to the tune of $13 billion in annual sales. In addition to GERD and heartburn, the drugs are used in the treatment of ulcer-causing bacteria such as helicobacter pylori. While PPIs are showing long-term affect on ageing of blood vessels, Histamine H2 receptor blockers like Ranitidine sold as Zantac and Tagamet did not adversely affect the endothelium itself.

They are powerful drugs that need to be used with caution as first line of controlling severe acidity related issues. People use the strong medication and sometimes are prescribed long-term treatments as antacids and here in lies the risk, Gautham, who is continuing his Post-Doctoral research at the University of Fribourg, Switzerland, told BusinessLine here.

What the PPIs do is they switch off molecular machines that pump acid into the stomach. Excess or uncontrolled acid production when poured into the stomach causes acid reflux burning the oesophagus, which causes the heartburn. Explaining the mechanism, Gautham said the PPIs reduce acidity in lysosomes of the endothelial cell. The lysosomes are like cellular garbage disposals and need acidic environment or low pH to work properly. “We observed the accumulation of cellular garbage in the endothelial cells, which sped up the aging process in our research,” he says.

The preliminary studies in labs have generated excitement in scientific and medical circles. However, the next step is to see if similar damage occurs in patients in human trials. When taken for the prescribed duration, they don’t seem to have adverse effects.

“Doctors and regulatory agencies should take a second look at the widespread use of PPIs,” according to John Cooke, the paper’s senior and corresponding author at the Houston Methodist Research Institute.

Cooke’s earlier work using pharmacovigilance studies identified 16-21 per cent increased risk of heart attack in general population upon long-term use of PPIs when compared to other antacids.

These conclusions came from data mining analysis of two large patient data bases, one from Stanford University ( 1.8 million patients) and the second from Practice Fusion Inc. (1.1 million patient data base).

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