Proton pump inhibitors (PPIs) are a popular class of drugs used to treat heartburn, acid reflux and other conditions. But these widely used medications also have been linked to a variety of health problems, including kidney damage, bone fractures, and dementia (1). In 2017, a study from Washington University School of Medicine in St. Louis showed that longtime drug use is also associated with an increased risk of death, and in 2019 they also found links to heart and kidney disease and stomach cancer.
Heartburn Drugs Linked To Increased Risk of Death
For the 2017 study, the researchers examined the medical records of some 275,000 users of PPIs and nearly 75,000 people who took another class of drugs – H2 blockers – to reduce stomach acid. The research was published online in the journal BMJ Open. (1)
The findings show that compared to people who did not take either type of medication, those who took PPIs had a 50% higher risk of dying within five years than those who took H2 blockers or no acid suppressants at all.
“No matter how we sliced and diced the data from this large data set, we saw the same thing: There’s an increased risk of death among PPI users,” said senior author Ziyad Al-Aly, MD, an assistant professor of medicine.
Heartburn Drugs Linked to Dementia, Kidney Disease, and Stomach Cancer
The 2019 study found specifically that people who took PPIs and H2 blockers were at higher risk of death from cardiovascular disease (aka heart disease), chronic kidney disease, and upper gastrointestinal cancer. Even at low doses, this risk increases. Other research has also linked PPIs to even more potential health risks. This includes dementia, bone fractures, heart disease, and pneumonia.
“Taking PPIs over many months or years is not safe, and now we have a clearer picture of the health conditions associated with long-term PPI use,” said Ziyad Al-Aly.
The data doesn’t lie. Their research shows specifically, 15 per 1,000 of the PPI users died from heart disease; four per 1,000 from chronic kidney disease, and two per 1,000 from stomach cancer. Death rates due to cardiovascular disease were 88 among the PPI group and 73 among the H2 blockers group. For stomach cancer, death rates were six in the PPI group and four in the H2 blockers group. Death rates due to chronic kidney disease were eight and four in the PPI and H2 blocker groups, respectively.
What’s worse, is that more than half of PPI users were using these medications without actual medical need. Despite this, they had received a prescription to use them. On top of that, the low-dose prescriptions are essentially the same dosage as over-the-counter PPI. This means that there are any number of people purchasing these at drug stores without medical guidance and taking them not knowing of the risks.
“PPIs sold over the counter should have a clearer warning about potential for significant health risks, as well as a clearer warning about the need to limit length of use, generally not to exceed 14 days,” said Ziyad Al-Ali. “People who feel the need to take over-the-counter PPIs longer than this need to see their doctors.”
What Are PPI and H2 Blockers?
Proton pump inhibitors (PPIs) are a common type of acid-suppressing medication. They work by reducing the amount of acid produced in your stomach, which helps to treat heartburn, ulcers and other conditions caused by too much acid in your digestive tract. Histamine 2 receptor antagonists (H2 blockers) are another type of antacid that blocks histamine receptors in the stomach. Both PPIs and H2 blockers are available over the counter and are used to treat a variety of issues, including (2):
- Heartburn and acid reflux (GERD)
- Stomach ulcers
- Peptic ulcer disease (PUD)
- Erosive esophagitis
- Other stomach and intestinal conditions
PPIs are sold under the brand names AcipHex, Nexium and Prevacid. H2 blockers are sold under the brand names Pepcid, Tagamet and Zantac. Both types of antacids can be used together to treat heartburn and other digestive issues.
PPIs and H2 blockers are some of the most commonly prescribed medications in the United States. This equates to millions of people. Previously published studies had already linked these medications to kidney disease and heart problems. To determine whether or not this led to an increased risk of death, the researchers had to dig into some medical records.
They looked at millions of veterans’ medical records in a U.S. Department of Veterans Affairs database. They identified 275,933 people who had been prescribed a PPI and 73,355 people prescribed an H2 blocker between October 2006 and September 2008 and noted how many died and when over the following five years.
They then concluded that for every 500 people taking PPIs for one year, there is one death as a result that wouldn’t have occurred for any other reason. While that may not seem like much, when you take into account the tens of millions of people who take them, this equates to thousands of unnecessary deaths each year. The longer people used the drugs, the higher the risk of death rose.
The recommended treatment length for most of these drugs is two to eight weeks. There are no re-assessments, however, and people end up taking these medications for months or even years.
Read: How to treat H. Pylori Bacteria Causing Heartburn And Bloating + Natural Remedies
What About Over-The-Counter PPIs?
Over-the-counter PPIs are available in almost every pharmacy and many people start using them without a doctor’s prescription. They contain the same ingredients as prescription PPIs, just at lower doses. This has led to an increased risk of severe complications such as fractures or kidney disease, though the exact statistics on this are difficult to obtain. Just like with prescription medications, overuse can cause more harm than good. (3)
PPIs Are Still Necessary, But Caution is Needed
According to the senior author of the Washington University studies, Ziyad Al-Aly, MD PPIs are still a useful and important tool. “PPIs save lives,” Al-Aly said. “If I needed a PPI, I absolutely would take it. But I wouldn’t take it willy-nilly if I didn’t need it. And I would want my doctor to be monitoring me carefully and take me off it the moment it was no longer needed.”
However, Al-Aly also thinks people maybe be taking them, when they aren’t needed. “A lot of people may be taking PPIs unnecessarily,” Al-Aly said. “These people may be exposed to potential harm when it is unlikely the drugs are benefiting their health. Our study suggests the need to avoid PPIs when not medically necessary. For those who have a medical need, PPI use should be limited to the lowest effective dose and shortest duration possible.”
Despite the risks, PPIs still do save lives. They help prevent ulcers from getting worse and causing serious damage to your esophagus. They can help you avoid hospitalization and surgery. For many, they’re the only thing that works. If you’re taking a PPI, you should still see your healthcare provider regularly. They may be able to lower your dosage or change it entirely if they notice that you don’t need it anymore.
As a side note, a more recent 2020 study found no link between Alzheimer’s and PPI use but did note a slight increase in non-Alzheimers dementia (5).
If you have a history of acid reflux, it’s always best to talk with your healthcare provider before taking any medication—even over-the-counter PPIs. Ensure you are well informed on the risks and how to take PPIs properly.
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- “Popular heartburn drugs linked to higher death risk.” Wustl. Tamara Bhandari. July 3, 2017.
- “Heartburn drugs linked to fatal heart and kidney disease, stomach cancer” Wustl. May 30, 2019.
- “Proton Pump Inhibitors: Review of Emerging Concerns.” Mayo Clinic Proceedings. Avinash K. Nehra, MD, et al. February 2018.
- “Popular Acid Reflux Drugs Are Linked To Kidney Disease Risk.’ NPR. Rob Stein. January 11, 2016.
- “Proton pump inhibitors and the risk of Alzheimer’s disease and non-Alzheimer’s dementias” Scientific Reports. December 2020.