Risks From Common Heartburn Drugs

By Linda Rath | Updated July 11, 2022

Americans spent an estimated $20 billion in 2017 on proton pump inhibitors (PPIs), drugs commonly used to treat heartburn and acid reflux disease. They’re also prescribed for some people with arthritis and other conditions who regularly take nonsteroidal anti-inflammatory drugs (NSAIDs), like naproxen, ibuprofen or aspirin. These medications can lead to life-threatening bleeding ulcers, which PPIs help prevent. PPIs are also used to treat heartburn due to obesity, which occurs with arthritis in many cases, or arthritis medications like prednisone and some disease-modifying anti-inflammatory drugs (DMARDs).

The Good and Bad

PPIs are available over-the-counter and by prescription in both brand-name and generic forms. Prescription-only PPIs include esomeprazole (Nexium) and pantoprazole (Protonix); over-the-counter PPIs include lansoprazole (Prevacid) and omeprazole (Prilosec). Some combination medications contain both NSAID and PPI, like Vimovo. All reduce stomach acid levels, especially when used consistently, but PPIs also may cause serious problems in some cases.

While some of the potential side effects can be quite serious, it’s difficult to determine what risk an individual has of experiencing them. Studies show conflicting results.However, people should be careful about taking PPIs, and avoid them when possible.

“I still prescribe when necessary, though I’m using fewer NSAIDs than I used to, so I cause less heartburn,” says rheumatologist Eric Ruderman, MD, professor of medicine and associate chief of clinical affairs for the Division of Rheumatology at Northwestern University Feinberg School of Medicine. “In particular, I really try to avoid using NSAIDs in older patients, where any potential risk of dementia or osteoporosis with PPI might be a greater concern.”

What Can Go Wrong and Why

Stomach acid helps digest food, absorbs bone-building calcium and magnesium, and kills pathogens in the gut before they make you sick. Suppressing it, especially over the long-term, can have serious health consequences, including:

• C. difficile. PPIs increase the chance of intestinal infection caused by Clostridium difficile bacteria, which can be serious and potentially even fatal. The drugs reduce the acidity in the gut, allowing more C. diff to survive. It mainly affects hospitalized patients taking antibiotics, but a growing number of cases now occur outside hospitals. New, antibiotic-resistant strains of C. diff are more severe and harder to treat. In 2012, the U.S. Food and Drug Administration (FDA) issued a warning linking PPIs to “severe diarrhea that does not improve,” and studies have supported a significant risk, with C. difficile infections almost two times higher in PPI users than in non-users.
• COVID-19. A 2020 study found a strong association between PPIs and COVID-19 — the more often a person took PPIs or the higher the dose, the more the risk increased. In the study, people who took PPIs once a day were twice as likely to have a positive COVID test compared to people who didn’t take them. People who took them twice a day were four times more likely to test positive. Other studies have shown that PPI use does not seem to increase the risk of contracting COVID-19, but it may raise the risk of more severe illness among those who do contract it. As with other infections, researchers suspect that low stomach acid from PPI use creates an environment where SARS-CoV2, the virus responsible for COVID-19, can thrive.
• Dementia. Several studies, including a meta-analysis involving more than 160,000 people, found a strong association between PPIs and dementia, especially in adults 65 and older. Some experts speculate that PPIs affect the brain indirectly by causing unusually low amounts of vitamin B12 and magnesium in the body. Others think they may cause abnormal types of a protein called tau to collect inside neurons. 
• Fractures. The link between fractures and PPIs is unclear. In 2009, Washington University researchers reported a 47% increased risk of spinal fractures and a 26% increased risk of wrist and forearm fractures in postmenopausal women taking PPIs. A decade later, a large-scale study by two researchers at the National Data Bank (NDB) for rheumatic diseases in Wichita, Kansas, didn’t find this association. It did, however, show a significantly heightened chance of all types of fractures in people with RA from opioids, SSRIs (a type of antidepressant) and corticosteroids. The researchers also noted they didn’t study different doses and types of PPIs, which may account for the difference in findings. And since arthritis patients already have an increased risk of fractures and other PPI-related problems, they urged caution in prescribing these and other nonessential drugs.
• Increased risk of autoimmune disease. Drawing on a database of nearly 300,000 patients, a 2021 study found that people taking PPIs had a risk of more than 300% of developing an autoimmune disease compared to those who did not use PPIs. Autoimmune diseases range from rheumatic conditions like lupus and rheumatoid arthritis to thyroid problems (common in people with arthritis) and thrombocytopenic purpura, a blood disorder marked by a low number of blood-clotting platelets. The risk was high no matter what the dose of PPIs. The researchers speculate that PPIs negatively alter the makeup of the gut microbiome.

Other Options

Some doctors think PPIs are overprescribed, even for people who need protection or relief. They say they should be reserved for the most serious conditions like erosive esophageal disease and bleeding ulcers.

For people with arthritis who use NSAIDs, acid-blocking drugs called H2 receptor blockers are a safer choice, according to Theodore Fields, MD, a rheumatologist at Hospital for Special Surgery and a professor of medicine at Weill Cornell Medical College, both in New York City. “Since data came out increasing the list of potential side effects of PPIs, such as low magnesium, increased kidney risk, and increased fracture risk … many [doctors] will substitute [H2-blockers] for PPIs,” he says.

H2 blockers include cimetidine (Tagamet) and famotidine (Pepcid). There’s also the NSAID-H2 blocker combo, Duexis. H2 blockers have side effects but appear less risky than PPIs.

Gastroenterologist Jacqueline Wolf, MD, an associate professor of medicine at Beth Israel Deaconess Medical Center in Boston, says PPIs aren’t intended for garden-variety heartburn. She suggests lifestyle changes instead:

• Lose weight, if needed
• Stop smoking
• Eat smaller meals
• Stop eating at least two to three hours before bed
• Avoid caffeine, carbonated drinks, alcohol, onions, garlic, citrus and tomatoes