Most Americans are familiar with advertisements touting breakthrough pharmaceutical drugs followed by a litany of frightening side effects. Beyond the list of potential side effects, what appears to be a societal push to be “all natural” could make some even more leery of modern medicine, concoctions that don’t come in an oil or grow up from the ground. And even if we believe in the proven power of medicine, unless pain is unbearable, we may think the devil we know is better than the one we don’t, choosing to suffer through pain sans medication.
Proton-pump inhibitors (PPIs) — medications like esomeprazole (Nexium), omeprazole (Prilosec), lansoprazole (Prevacid, and others) and pantoprazole (Prontonix) — are the most commonly used medications to treat stomach-acid issues. Last month, two new studies questioning the safety of PPIs were published. One, in the journal Gastroenterology, reported an increase in the incidence of intestinal infections but no significant increase in a variety of health issues like dementia or pneumonia development. The second study, published in the British Medical Journal, found that in a population of United States veterans, PPIs were associated with a slight increase in mortality from cardiovascular disease and chronic kidney disease over the study period.
So are PPIs safe or even necessary? Researchers at Penn say the common medication is safe and valuable, provided it’s taken in proper doses and in the right patients.
What Are Proton-Pump Inhibitors?
PPIs aren’t new kids on the block; since the 1980s, they have been used to treat heartburn, reflux, and acid-related issues. H2 blockers (Pepcid and the like) arrived in pharmacies first, but they were “blown out of the water by PPIs,” says David Metz, MD, a professor of Gastroenterology and director of the Acid-Peptic Program at Penn Medicine, and whose research focuses on PPIs. PPIs directly block the action of proton pumps, enzymes found in the acid-producing cells of the stomach, and literally stop them from releasing acid into the stomach.
Metz says people should be taking PPIs for maintenance for one of three reasons: they have some sort of chronic reflux disease like esophagitis or Barrett’s esophagus requiring daily treatment (not just occasional heartburn), they have a very rare condition where the body makes too much acid, or they regularly take anti-inflammatories that aren’t steroids (medications like Aleve, called NSAIDs, or even aspirin) which increase the risk of stomach ulcers. (Side note: too often, people who are on NSAIDs and who would benefit from proactive PPIs aren’t actually prescribed them, Metz says.)
“Most fears surrounding PPI safety come from epidemiological studies showing a correlation between PPIs and something else. But these studies don’t necessarily mean that one thing causes the other,” Metz says, adding that the two recent studies are examples of just that. “I’m not aware of any research published that directly shows PPIs are the primary cause of health issues, except for true allergies which are very rare,” he says. “Cause” is an important and key word when evaluating this research and all research.
Metz notes that when drugs go through approval processes, they must show that the medication itself actually does what it is supposed to do and does so effectively. Many side effects noted for medications are just links and are not proven.
But even association studies regarding PPIs have been challenged by other research. For example, fears over a link to dementia in elderly people taking PPIs began with two studies from the same group of researchers in Germany. Nevertheless, two other studies of both younger and older people found that taking PPIs actually decreases the risk of dementia – results that are completely contrary to those found in the German-led research.
“While multiple studies need to definitively rule out a risk of dementia with PPI use and the situation should be monitored, thinking that PPIs give people dementia isn’t supported by science. You shouldn’t worry, especially if you’re under 70 years old,” says James Reynolds, MD, chief of Gastroenterology and Hepatology and director of the Neurogastroenterology and Motility Program at Penn Medicine.
The medical community regards infections and poor bone-strength as risks that could be correlated to PPIs. But even one of Metz’s recent studies suggested that bone health is not an issue. In the study, postmenopausal women who took two different PPIs for 26 weeks had no significant changes to their bone turnover (the body’s natural replacement of old bone with new bone) compared to women who took a placebo.
“As with all medications, there are potential risks,” Reynolds says. “But acid levels being too high or acid being in places it shouldn’t be are more serious than just a cause of physical discomfort.” Ignoring the fact that you take NSAIDs, have serious, prolonged reflux, or have a disorder that leads to high stomach-acid levels means you could be setting yourself up for long-term consequences such as ulcers, erosion of the stomach lining, esophagus scarring, bleeding, or in serious cases, esophageal cancer.
The truth is, there’s likely a happy medium between reaping the benefits of a PPI while minimizing the risks. Reynolds urges people to speak to their doctor to determine if they need PPIs, for how long, and how often. For occasional heartburn, for example, daily PPIs are likely not appropriate but intermittent, “on demand” therapy may be fine.
Even better, taking PPIs less frequently and even gradually switching to H2 blockers once stomach acid is under control may be a good way to get the benefits while reducing the risks. For Metz, what he calls the first law of medicine, comes to mind: “The bottom line is that you always aim to give patients the lowest effective dose, not more than they need, to limit potential risks.”