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The Dangers of Taking PPIs for Acid Reflux

There might be serious consequences to taking these drugs long-term.

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You've probably felt it at some point—that sharp, burning sensation that starts in your gut and climbs up the back of your throat, possibly after your second cup of coffee, or that extra helping of fries.

We tend to call it heartburn or acid reflux, but what we most often mean is Gastroesophaegeal Reflux Disease (GERD), in which the contents of the stomach escape up into the esophagus. GERD is one of the most common chronic ailments in the US; an estimated 20 to 60 percent of Americans have it at some point in any given year, and many don't even know it.


Left untreated, chronic GERD can cause everything from chronic cough and shortness of breath to chronic fatigue, insomnia, and sinus infections, according to the Mayo Clinic and the
Cleveland Clinic. It can be hard to pin down because it often masquerades as something else or has no obvious or consistent symptoms. Continuous exposure to acid can also change the cell lining of the esophagus, a condition called Barrett's Esophagus, and those cellular changes can lead to cancer. It's a low risk of progression—less than 1 percent per year—but it happens.

If you go to your doctor complaining of any of these symptoms, including the more vague ones, like coughs or throat clearing, you’ll probably be written a prescription for proton pump inhibitors (PPIs). These meds decrease acid levels by dramatically reducing acid production through glands in the lining of your stomach. They are widely available both over-the-counter and by doctor's prescription under the generic name omeprazole; they’re considered the de facto treatment for chronic GERD. An estimated 15 million Americans in 2013 were prescribed PPIs such as Prilosec, Nexium, Prevacid, and Zegerid, and that doesn't include the much larger number of people buying over-the-counter versions.

Yet for all the $9.5 billion worth of PPIs prescribed in physicians' offices and sold in drugstores each year, doctors aren’t completely sure if pH levels in the stomach are the primary cause of GERD, even though that’s what they’re overwhelmingly treating. There could be other, more mechanical, factors at play, like weakness in the sphincter, which closes off the stomach from the esophagus, delayed gastric emptying, or hiatal hernia, says Nipaporn Pichetshote, a gastroenterologist at Cedars-Sinai Medical Center in Los Angeles. For people who have laryngopharyngeal reflux (LPR), which is reflux that only presents symptoms in the throat like throat clearing and globus, it’s even less clear what causes it, how to diagnose it, or if PPIs are effective at all in treating it.


Despite all this, they’re still turned to as the first line of defense, and researchers are finding that there might be consequences to taking these drugs long-term. Last year the British Medical Journal published a large-sample study that found long-term use of PPIs was correlated with a 25 percent higher chance of death. “This was really eye-opening,” says Ziyad Al-Aly, a kidney specialist at the Veterans Affairs St. Louis Health Care System and the study’s lead investigator. “We knew PPIs [were] associated with a number of adverse effects, but there really was no [prior] big study showing a relationship between PPI use and risk of death.”

Their findings build on several other recent studies that found previously unknown correlations of PPIs and chronic and acute conditions. Together, the studies associated PPI use with a 44 percent heightened risk of developing dementia, 44 percent heightened risk for osteoporotic bone fractures, 20 percent heightened risk for heart attack, 70 percent heightened risk for clostridium difficile infections (which can be life-threatening), 30 to 50 percent heightened risk for chronic kidney disease, and an increased risk of stomach cancer.

PPIs can also cause problems with vitamin and nutrient absorption, like B12, or can lead to a magnesium imbalance and worsen existing kidney disease compared to study patients who took H2 blockers. H2 blocker are another, potentially safer, medication to reduce stomach acid, but they lose their effectiveness with long-term use, and don't appear to work as well or as quickly, according to Pichetshote. (Tonic reached out to Proctor & Gamble, maker of Prilosec, and AstraZeneca, maker of Nexium, but neither chose to comment on the findings or our story.)


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To top it all off, it can also be extremely difficult to quit a PPI once you start one because of an intense withdrawal period. When the proton pumps in your stomach start to produce acid again, you will experience what’s called an acid rebound. Your stomach will make a higher-than-normal amount of acid before eventually tapering off to regular levels. Studies have shown that PPIs can cause reflux symptoms in people who didn’t have them before, when they tried to quit them. This can heighten GERD symptoms and lead people to reach for their meds again, leading to long-term use.

For now, the BMJ study authors caution that their findings shouldn't deter the prescription of PPIs entirely, only that doctors should weigh the benefits of suppressing GERD against the increased risk for other conditions, which vary from patient to patient.“[But] when we evaluate PPI use, the story is consistent,” Al-Aly says. “PPIs are over-prescribed and also used for a longer duration of time than is necessary.” The study's authors stress that the evidence is new and not conclusive, but it suggests PPIs may alter normal cellular processes and erode the ends of chromosomes, both of which interfere with the body's regular maintenance of itself, leaving it vulnerable to soft tissue damage.

The BMJ study's sample was large—6 million people—but the patient group was pretty homogenous: They were mostly older white military veterans. It remains to be seen how PPIs are correlated to the health of younger people, women, and people of different races.


The study probably won’t lead to the discontinuation of PPIS, but encourage doctors to move patients off indefinite use of PPIs and toward episodic use instead. In the near future, a patient may be more likely to be prescribed a PPI for two to four weeks and then taken off it, says Pichetshote. The days of a doctor prescribing a lifetime of PPI use could be coming to an end.

If you want to manage GERD without PPIs or H2 blockers, you might try changing your diet or lifestyle. Small studies have found that people who adhere to low acid diets report less symptoms, or that plant-based Mediterranean diets can be as effective as medication, especially for LPR. It’s a drag to give up your morning coffee and orange juice, but if your symptoms are severe and you don’t want to take a PPI, those–along with tomatoes and spicy foods–are the main offenders to put on the do-not-eat list. Other simple changes you can make are eating smaller meals, avoiding eating a few hours before bedtime, and lifting the head of your bed, so you sleep on an incline.

There are also more controversial home remedies and over-the-counter herbal medications. One untested remedy going around the internet lately is a daily dose of apple cider vinegar. “If it provides relief, I don't think it's harmful,” Pichetshote says. “However, there is acid in apple cider vinegar, so it's promoting the cycle of reflux.” Others find relief in bubbly mineral water, such as Perrier, though many doctors say carbonated beverages exacerbate reflux. Pichetshote cautions that it doesn't prevent reflux or heal anything, and that even carbonated mineral water is acidic. You can also try TUMS, Maalox, or Alka-Seltzer Gold, which is a hard-to-find aspirin-free version. They all work quickly, according to Pichetshote, but they also stop working quickly— within 30-60 minutes—and several have high doses of calcium, of which repeated doses can cause constipation.

Lifestyle changes are your best bet for reducing GERD. Quit smoking, exercise, drink less alcohol, and avoid spicier and fattier foods. If you're already doing these things and still have chronic GERD, though, your options for the foreseeable future are to tough it out with PPIs or H2 blockers in short-duration treatments.

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