Proton pump inhibitors, or PPIs, are a class of drug commonly used to treat acid-related conditions such as stomach ulcers and gastroesophageal reflux disease (GERD). They work by decreasing the amount of acid in the stomach by blocking a chemical system known as the “proton pump” in cells of the stomach lining that make stomach acid.

Short-Term Side Effects of PPIs

PPIs include such brand names as Prilosec, Prevacid, Protonix, and Nexium, and they are used very frequently because they are generally effective and most patients don’t experience side effects. Short-term side effects of PPIs can include headaches, nausea, diarrhea, and other gastrointestinal discomfort.

However, as with most medications, even if the patient does not experience any short-term side effects, there can be side effects that occur with long-term use of the drug. These long-term side effects may be serious, and recent research has looked more closely at the dangers of PPIs that can accompany chronic usage of this class of drugs.

Long-Term Side Effects of PPIs

The main function of PPIs is to decrease the amount of stomach acid that is being secreted. However, stomach acid serves an important function in the body by aiding in digestion and preventing infection, so it makes sense that decreasing acidity of the stomach long-term could have some effects on the body other than the reduction of symptoms associated with acid reflux.

It turns out that long-term use of PPIs basically results in two categories of negative consequences: it can increase the risk of infections, and it can inhibit the absorption into the body of important vitamins.

How PPIs Can Increase Your Risk of Serious Infections

Let’s start with infections. The reason long-term PPI use can increase the risk of infections is that “gastric acid secretions act as a defense mechanism against bacteria, and the increased gastric pH during PPI use allows for colonization of opportunistic microbes.” The basic gist of this is that PPIs result in less acid in the stomach, which creates an environment that is more friendly to bacteria.

PPI use has been associated with pneumonia.  Something called aspiration occurs while people are lying flat at night; basically, “small amounts of stomach contents tend to travel up the esophagus and get into the trachea.” PPIs make the environment of the stomach less acidic, and since bacteria are more likely to thrive in a less acidic environment, when normal aspiration occurs during sleep, bacteria may be carried to the lungs, resulting in pneumonia.

There is also a link between PPIs and Clostridium difficile: several studies have indicated PPIs as a possible risk factor for acquiring a Clostridium difficile infection, a highly contagious infection that can cause life-threatening diarrhea, especially in the elderly. Since PPIs lower the acid levels of the stomach, it is possible that C. difficile bacteria may have an easier time taking root in the stomach after being swallowed. One study found that patients who were taking a PPI had a 2.9-fold increase in their risk of catching C difficile.

How PPIs Can Affect Your Body’s Absorption of Essential Vitamins

Now let’s talk about how PPIs can interfere with the absorption into the body of several essential vitamins. To begin with, lowering stomach acid levels may inhibit the body’s ability to absorb calcium and B12. The body’s inability to properly absorb calcium could place an individual at higher risk for either bone fractures or osteoporosis. A link between long-term PPI use and hip fractures has been found; additionally, B12 levels may be affected because stomach acid is needed to “uncouple the vitamin from protein in food.”

Long-term PPI use has also been associated with decreased absorption of magnesium (hypomagnesemia), although it is unclear exactly how PPIs contribute to this. Hypomagnesemia symptoms include seizures, arrhythmias, hypotension, and muscle spasms, and “approximately 1% of patients who experienced an adverse effect while on a PPI experienced hypomagnesemia.”

Finally, as if the above risks weren’t enough, some research has found that taking PPIs in combination with Plavix, a medication used to prevent blood clots, may increase the risk of cardiac events.

What Can You Do?

Worried about the long-term side effects of PPIs? The good news is that there are other treatment options for helping you effectively manage your acid reflux or GERD. These include lifestyle changes, the use of H2-blockers—a different class of anti-reflux medications—or possible anti-reflux surgery if your goal is to be medication-free.

More research is being done regarding the long-term side effects of PPIs, and it may turn out that there are other dangers than just the ones listed above. As always, consult with your physician and pharmacist to weight the benefits and the risks before deciding which course of treatment is right for you.