Risks of PPIs: What’s Real, What Needs More Research

New studies have linked reflux medications to dementia and other diseases. Should you worry? A Michigan Medicine expert explains the science.

7:00 AM

Author | Rene Wisely

For more than 30 years, medications such as omeprazole (Prilosec), lansoprazole (Prevacid) and esomeprazole (Nexium) have been the go-to treatment for acid-related disorders of the digestive tract including gastroesophageal reflux disease (GERD) and peptic ulcer disease.

MORE FROM MICHIGAN: Sign up for our weekly newsletter

Called proton pump inhibitors (PPIs), an estimated 15 million Americans use them — both prescription and over-the-counter varieties.

While acid contributes to the breakdown and digestion of food, sometimes it eats away at the protective mucous barrier that lines the digestive organs, causing ulcers, and can lead to heartburn or regurgitation.

A PPI taken 30-60 minutes before a meal dramatically reduces the acid production of certain cells in the stomach, giving a chance for ulcers to heal and reduce reflux.

"PPIs really improve the quality of life of some patients," says Michigan Medicine's Jacob Kurlander, M.D., a clinical lecturer and gastroenterologist.

Questioning recent research

In the past couple of years, some studies have raised concern about possible adverse effects of long-term PPI use. It's a frightening list, including low magnesium, low vitamin D, stroke, Clostridium difficile (C. diff) infection, bone fractures, heart attacks, stomach cancer, pancreatic cancer, kidney disease and dementia.

SEE ALSO: Is It Safe to Take PPIs? A Gastroenterologist Explains the Risks

"Patients are coming to me with questions," Kurlander says. But worry about these drugs' risks shouldn't be automatic.

When such research is published, the medical community should pause and examine each study individually on its own merits, Kurlander says.

"What's interesting is there are often studies that go both ways, that PPIs may be either protective or harmful," he says. "The key is to look at the quality of the study." This has been the case with dementia, heart attacks and pneumonia.

A common shortcoming of studies showing adverse effects from PPIs is that they are often observational studies. Unlike randomized controlled trials, observational studies can have distorted conclusions because of difficulty accounting for certain unmeasured variables.

A person who is obese, for example, is at an increased risk for reflux because their gut pushes on their stomach, causing the acid to create heartburn. An obese person also is more likely to have cardiovascular disease, so that increases their risk for heart attacks. "Unless these confounders are carefully controlled for and measured in these studies, there is a possibility to find association between PPIs and heart attacks without true causation," Kurlander says.

That said, known risks of PPIs can rarely include flatulence, diarrhea, headache, abdominal pain and nausea.

Hearing both sides

Another issue? Patients don't often hear of follow-up studies, Kurlander says.

For example, an October 2017 study in Gastroenterology debunks a 2016 study in JAMA Neurology that implied that long-term PPI use could contribute to cognitive decline. It's a report that received a lot of traction in mainstream media, yet the new study did not garner the same attention.

"Even if you believe that some of these adverse effects are real, the size of the effects tend to be small," Kurlander says. "Studies suggest that the excess risk of getting a bone fracture from a PPI is on the order of 0.3 percent per year per person. While it is something, people who have GERD or a peptic ulcer frequently find going without PPIs bothersome, and in patients who need PPIs to prevent ulcers, going without a PPI could cause a morbid or disabling bleeding event."

Before PPIs, the solution for ulcers was ugly, Kurlander says. It was typically a grueling surgery that involved cutting nerves or a part of the stomach.

PPIs have helped so many people, even colleagues in his office still take them regularly, says Kurlander.

Finding solutions

One benefit to the controversy surrounding PPIs: It encourages physicians to be more mindful of prescribing them, Kurlander says. Physicians examine why the patient is taking them, what evidence exists to support the decision, and the patient's risk tolerance to any potential long-term effects.

Good old-fashioned clean living has made a comeback as a result as well. Some of Kurlander's patients have elected to alter their lifestyle choices, including losing weight, avoiding trigger foods and eating earlier before bedtime, to cut down on the need for PPIs.

To schedule an appointment to discuss PPIs or digestive issues, call 888-229-7408.


More Articles About: Digestive Health Reflux or GERD Pharmacy Digestive (GI) Conditions
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of health care news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]

734-764-2220

Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Subscribe
Featured News & Stories prescription pad drawn
Health Lab
Reducing dose of popular blood thinners may limit risk of future bleeding
For people taking the popular blood thinners rivaroxaban (brand name Xarelto) and apixaban (brand name Eliquis), after having a blood clot, a reduced dose may limit the future risk of bleeding as well as hospital visits, a Michigan Medicine-led study suggests.
Kid holding pumpkin bowl of candy in skeleton costume
Health Lab
Is chocolate safe for people with IBS?
With Halloween and the holiday season right around the corner, people with IBS may want to reconsider choosing to eat chocolate.
prescription pad blue yellow sketch
Health Lab
Risk of clots, stroke from incorrect blood thinner dosing reduced using online dashboard
Doctors and pharmacists treating people with blood thinners can now reduce the rate of inappropriate dosing — as well as blood clots and strokes that can result from it — using an electronic patient management system.
bacteria blue yellow
Health Lab
New guideline for Helicobacter pylori includes change to primary treatment recommendation
The American Journal of Gastroenterology has published a new guideline on the treatment of Helicobacter pylori (H. pylori) Infection. 
teal background of three people thinking three different things regarding money and health
Health Lab
As election approaches, national poll shows which health topics concern older adults most
Health care costs of different kinds, and financial scams, are top of mind for people age 50 and older going into the November election.
person at counter with medicine brown bottle and pills
Health Lab
Most blood thinner dosing problems happen after initial prescription
More than two-thirds of those people take a type of blood thinner called a direct oral anticoagulant. These DOACs, such as rivaroxaban (brand name Xarelto) and apixaban (brand name Eliquis), are under- or over-prescribed in up to one in eight patents. These prescribing issues can have life-threatening consequences, and they most often occur after a provider writes the initial prescription, according to a study led by Michigan Medicine.