A buzzy new study on heartburn meds and dementia doesn’t actually clarify anything

On Wednesday, the journal Neurology published an attention-grabbing study, reporting a possible link between taking heartburn medications like Prilosec and developing dementia. It generated scary-sounding headlines and reanimated a conversation about the safety of the medications — and, simultaneously, questions about how the general public should understand conflicting results from medical studies.

The latest publication looked at data gathered from people enrolled in an ongoing study that began in 1987 and looked at the long-term health of 5,700 study participants who didn’t have dementia when they first enrolled in the study.

Notably, the study wasn’t originally designed to study dementia risk from these drugs. But in combing through the collected data, the researchers found that participants who took proton pump inhibitors — medications like omeprazole (brand name Prilosec), often abbreviated as PPIs — for more than four and a half years were about 33 percent more likely to develop dementia later on than people not on the medications.

The study’s authors have been careful to explain that the association they’ve shown doesn’t demonstrate causation. But news outlets haven’t been as careful: “Long-Term Use of Acid Reflux Drugs May Increase Your Risk of Dementia,” read one of yesterday’s headlines. The drugs ”may raise the risk of dementia up to a third,” read another.

Importantly, the study comes on the heels of several larger, higher-quality studies showing the exact opposite of its conclusions — namely, that these medications do not portend an increased risk of dementia.

What’s a confused member of the general public to do?

It can be incredibly disorienting when medical studies’ findings conflict. And as people try to sort out what’s true, the devil is in the details, said Madhav Desai, a gastroenterologist at the University of Texas Health Science Center at Houston. “We need to be very cautious in terms of reading the actual study — and more cautious when we are reading the news posts out there,” he said.

After all, the medications play an important role in reducing health risks for many people. “If acid reflux is not controlled well, it can cause a variety of complications, including cancer at a later stage,” said Desai. So people should not be ditching their heartburn medications en masse based on alarming headlines.

When medical science seems to lack consensus, it’s worth taking a little time to understand how conflicting studies are designed and what that design means about the believability of their results.

The simplest explanation for the study’s conclusion suggests people who need heartburn medications shouldn’t fear them

Proton pump inhibitors are a medication many people take at some point in their lives. Heartburn is the most common reason people take them, although people sometimes take them for other reasons — for example, to treat certain types of ulcers in the digestive system.

For the people who need them, they’re very helpful not only for controlling symptoms, but also for reducing the risk of serious complications of disease. In people who take anti-clotting medications, PPIs greatly reduce the risk of internal bleeding in the esophagus and the stomach.

They’re far from risk-free. In high-quality studies, the medications increase the risk of certain types of digestive tract infections, and also decrease the absorption of certain important nutrients from food. However, for people who need PPIs, they are very good at what they do and are an important part of a treatment plan.

Many people will take a PPI at some point; I took them on and off for years for gastritis that turned out to be a food allergy. Desai said about half of the American population will have heartburn at some point in their lives; researchers think about 20 percent of Americans have it at any given moment. Many people who have the symptoms will take a PPI, whether because a doctor prescribed it or because they purchased an over-the-counter formulation on their own.

A lot of research looks at outcomes in people who take PPIs compared with people who don’t. Here, it’s important to note that people who get heartburn — making it more likely they’ll take a PPI — are likely to be different in important ways from people who don’t, said Desai. That’s because heartburn is a common symptom of several common chronic medical conditions.

This is key to understanding why the new study might not be as consequential as some headlines make it out to be.

“Patients with acid reflux, very likely they are overweight, they have hiatal hernia, they have obesity. Sometimes they have other underlying cardiometabolic risk factors: high blood pressure, hyperlipidemia, and so forth,” said Desai. And all of these conditions raise the risk of developing other complications, including cognitive decline and dementia, he said.

Large studies have shown that people taking PPIs are more likely to have other medical conditions than people who aren’t taking them. In a recent study involving 19,000 patients, people who took these medications were more likely to also be taking medications to treat high blood pressure and cholesterol, for example.

These differences are particularly important when dementia is the outcome researchers are looking for because high cholesterol, high blood pressure, and diabetes are themselves thought to increase dementia risk. Indeed, in the study published Wednesday, PPI users were more likely to have high blood pressure and diabetes than nonusers, making them more likely to develop dementia.

That makes it challenging to isolate any risks PPIs might have from the risks associated with the diseases they’re being used to treat, said Desai. However, several large studies have aimed to do so — and it’s worth looking at their results alongside the ones that are currently getting a lot of attention.

The latest study’s findings send a different message than several earlier and better-quality studies

The gold-standard study for answering questions about whether any particular exposure (like taking a medication) is associated with any particular outcome (like developing a medical condition) is a randomized controlled trial. These types of studies randomly select a group of people to take either a medication or a placebo, then compare their outcomes later on to determine whether they’re different.

Fortunately, when it comes to answering questions about PPIs and dementia, that type of study has been done. In 2019, a group of researchers randomized about 17,600 patients to receive a PPI or a placebo. They found no additional risk of dementia, along with a host of other conditions, among the people who took PPIs for three years compared with those who didn’t. (Three years might not be long enough to see dementia develop in some people. However, the study’s size and its participants’ relatively high age — 68, on average — gave its authors confidence in their findings.)

Desai considers this an “ideal study” for answering questions about the risk of dementia with taking PPIs. He should know: In 2020, he led a review of scientific studies examining the question.

For their review, Desai’s study team only included studies that enrolled patients prospectively — that is, following people forward through time to determine which factors are associated with certain outcomes. These studies are generally considered higher quality than those that look retrospectively at patient information that’s already been gathered in large data sets, as the latest study does.

Desai’s study showed no increased risk of dementia in people taking PPIs for years, even when they looked only at people taking the medications for five years or more.

Several other review studies have shown similar results to Desai’s study. And notably, a relatively high-quality prospective study published about two months ago further affirmed the lack of a link between PPIs and dementia.

What confused patients can do when medical studies contradict each other

Although high-quality studies suggest there isn’t much controversy in the medical community about whether PPIs raise the risk of dementia, the latest study — and coverage of it — makes it seem like this is still an open question.

It’s not a bad thing to have conflicting findings in the scientific literature, said Desai. In fact, when well-designed medical studies contradict consensus, it helps move science forward by sparking more and even better-designed studies.

Ultimately, patients who aren’t sure what to do with contradictory study findings should talk to their doctors about what’s best for their particular situation. Different patients have different symptoms, different complications, and different risks, said Desai.

Gastroenterologists typically don’t want their patients to be on these drugs long term if it doesn’t make sense for them, said Desai.

So perhaps the most important question a confused patient could ask their doctor is: How badly do I need this PPI?