Have you stopped taking Prevacid, Prilosec, Nexium and other proton pump inhibitors (PPIs) for your acid reflux because they have been linked to dementia, kidney and liver disease, heart disease, stroke, cancer and other serious health conditions? That is certainly understandable—but you may not have to stop.
Despite the drumbeat of articles reporting these frightening findings, PPIs are generally safe, says gastroenterologist Daniel Freedberg, MD, lead author of a paper published in Gastroenterology analyzing the evidence. His findings: The vast majority of those adverse effects are overstated, and the actual risk of taking PPIs, even long term, is probably so low that it is not a significant factor in the decision of whether or not to take them. Instead, the decision to use (or not use) PPIs should be based on the benefits they have for specific conditions.
That is good news for the nearly 10% of Americans who take these medications to calm the burning and pain caused by acid reflux. Bottom Line Personal recently spoke with Dr. Freedberg to get the details and help you make the right decision…
Studies that link PPIs to significant health risks almost invariably compare the rates of a major health problem such as dementia or chronic kidney disease (CKD) among people who take PPIs to the rates among people who don’t take them. While that sounds reasonable, there is a problem—PPIs may not actually cause those health problems. Rather, some underlying health factor that increases PPI users’ risk for the health problem also increases their risk for acid reflux. Being overweight, depressed, physically inactive and/or smoking all increase the odds of acid reflux as well as the odds of many health issues linked with PPIs. While researchers who conduct PPI studies attempt to factor these things into their studies, it’s almost impossible to do so completely.
When studies are conducted that randomly assign some participants PPIs and other participants placebos, the risk of PPIs almost always disappears. That strongly hints that whatever is causing PPI users to have elevated rates of a long list of health problems almost certainly is not the PPIs themselves. Example: Published studies reviewed by AstraZeneca researchers revealed similar pneumonia rates among patients taking PPIs and those taking placebos, despite earlier research that suggested PPIs increase risk for pneumonia.
Even if you’re not ready to completely dismiss the studies that find links between PPI use and increased risk for health problems, the risk typically is only modest—though the results of these studies sometimes are reported in a way that makes them seem significant. Example: One study conducted in Taiwan that found a link between PPIs and CKD concluded that PPI users’ risk for CKD increases by 10% to 20% annually. That sounds steep, but it doesn’t mean that PPI users have a 10% to 20% chance of developing CKD each year—it means that a PPI user’s odds of developing CKD are, theoretically, 10% to 20% higher than the risk of someone who does not use PPIs. Fortunately, only a very small percentage of the overall population develops CKD, so that 10% to 20% actually amounts to only an additional 0.1% to 0.3% risk even if PPIs do increase risk for CKD…which, as noted above, they probably do not.
Of all the health risks that have been linked to PPI use, only one stands out as probably real—the risk for bacterial infection in the gut, such as Clostridium difficile (C. diff), Salmonella or Campylobacter infection. The associations between PPI use and these bacterial infections are much stronger than those between PPIs and the other health issues. And it also makes sense that taking PPIs would increase risk for bacterial infection in the gut—PPIs combat acid reflux by reducing the stomach’s acid levels, and stomach acid helps kill these and other potentially dangerous gut bacteria.
But even with this risk, that doesn’t mean taking PPIs is necessarily a mistake. The bacterial gut infections people get in the US tend to result in just a day or two of diarrhea and discomfort. All medications have risks and benefits. Many people who have serious acid reflux issues are willing to accept increased risk for occasional intestinal discomfort to greatly reduce their acid reflux symptoms. Exceptions: Some gut infections such as C. diff can be serious. Also, if you live in the developing world where bacterial infections such as cholera are relatively common, this elevated risk might be a reason to avoid PPIs.
There is a second legitimate drawback to PPIs—if you take them daily for multiple months or longer, it can be difficult to quit. Long-term users who stop taking PPIs often experience rebound acid hypersecretion (RAHS) phenomenon—the cells in their stomachs have grown accustomed to the PPIs and produce increased levels of acid. When the PPIs are discontinued, the acid reflux resumes full speed—similar to having your feet on both the gas and brake pedals of your car…when you lift your foot off the brake, your car will move forward. Result: PPI users often conclude that their acid reflux is as bad as ever and quickly start taking PPIs again, perhaps for the rest of their lives. But in reality, that often isn’t necessary—even if they didn’t resume taking the PPIs, the rebound effect would fade after one to three weeks or so of discomfort. Helpful: One way to reduce the discomfort caused by this rebound effect is to use other acid-reflux treatment options during the weeks after discontinuing extended PPI use. Options include antacids (Tums, Alka-Seltzer, Gaviscon, Mylanta, etc.) and histamine 2-receptor antagonists (H2RAs), such as famotidine (Pepcid).
PPIs are generally very safe—but it still is best not to take them if you don’t need to. When PPIs are beneficial…
If you have ulcer-related bleeding, especially when the ulcer is not due to the stomach bacteria H. pylori.
If you have been diagnosed with Barrett’s esophagus, a precancerous condition where the lining of the esophagus changes due to acid reflux.
If you have been diagnosed with “complicated” or “severe” reflux esophagitis—this kind of reflux is likely to recur without long-term PPIs.
Acid reflux sufferers who do not fall into any of these three categories should instead try taking an over-the-counter H2RA, more commonly known as an H2 blocker, such as famotidine (Pepcid) and ranitidine (Zantac). These often are sufficient to control acid reflux, and they are less likely to increase risk for a gut bacterial infection and will not have a rebound effect when discontinued.
If H2 blockers fail to control your acid reflux, then you can consider a PPI even if none of the three categories listed above apply—the acid-reduction benefits that PPIs provide can easily outweigh their drawbacks. Often a few days of a PPI is sufficient to control symptoms.
Helpful: The new acid reflux drug vonoprazan recently was approved for use in the US. It has been available in a number of other countries, including Japan, for some time. Vonoprazan may reduce stomach acid levels even more than PPIs, although there are no studies to date that show it is definitively superior to PPIs.
Bottom line: For typical heartburn symptoms, try an over-the-counter H2RA such as famotidine first. If Pepcid fails, next try two weeks of an over-the-counter PPI. If you still have heartburn or if you find that you are unable to stop taking PPIs, it’s time to talk to a doctor.
