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Taking prescription acid reflux medications called proton pump inhibitors (PPIs) for long periods may increase the risk of dementia, a new study has found.
Scientists said the research highlights the importance of taking the drugs—among the most commonly-prescribed in the U.S.—only when necessary.
“PPIs are typically intended for short-term management of gastrointestinal symptoms,” Pamela Lutsey, PhD, MPH, a study author and professor of epidemiology and community health at the University of Minnesota School of Public Health, told Health. “However, some individuals remain on PPIs for long periods or use PPIs despite not having a documented gastrointestinal diagnosis.”
Up to one-fifth of people in the U.S. experience acid reflux, according to the National Institutes of Health (NIH). PPIs work to relieve chest pain, heartburn, and other acid reflux symptoms by reducing the amount of acid produced by glands lining the stomach.
People shouldn’t take PPIs unless a healthcare provider recommends them, Matthew Hoscheit, MD, a gastroenterologist at Cleveland Clinic, told Health. “The expected length of time that someone needs to take the medication should always be agreed upon with their healthcare provider prior to starting the medication, and the need to continue the medication should be reviewed regularly,” he said.
Lutsey said her team wanted to focus on the association between PPIs and dementia because past research on the relationship between the two hadn’t provided definitive information. “Some studies had looked at the question of dementia in people who used PPI[s], but the results were variable,” she said. “We have very good data on dementia health outcomes, and so we thought we should look at this in our data set.”
For the new study, her team used data from 5,712 people aged 45 and older enrolled in the Atherosclerosis Risk in Communities study, a data collection program run by the NIH since 1985. The age of the participants averaged 75, and none of them had dementia when the study began.
Researchers divided the participants into four groups based on prescription PPI use: Non-users, those who took PPIs for up to 2.8 years, those who took them for between 2.8 and 4.4 years, and those who’d been using them for more than 4.4 years.
The researchers tracked the participants for a median duration of 5.5 years. During that time, 585 people—or 10% of the participants—developed dementia.
After adjusting for other factors that could affect dementia risk, such as age, sex, race, and other diagnoses like high blood pressure and diabetes, the research team concluded that those who took PPIs for more than 4.4 years were 33% more likely to develop dementia than those who never took the medication. The researchers didn’t find that taking PPIs for fewer than 4.4 years significantly increased the risk of dementia.
Because the researchers only looked at prescription medication use, their results don’t extend to people who take over-the-counter PPIs, such as Nexium 24HR, Prevacid 24HR, and Prilosec OTC.
There are multiple theories as to why prolonged PPI use might increase dementia risk, Lutsey said. “There is some human evidence that PPI use may predispose [people] to vitamin B12 deficiency, which can be associated with cognitive decline,” she said. “Also, PPI use may result in changes to the gut microbiome that could impact cognitive health.”
The research was limited by its design, according to Hoscheit. The type of study—known as a population-based study—is considered lower quality than randomized control trials (RCT), which can establish cause-and-effect relationships. This study does not prove that PPI use causes dementia—only that there’s an association between prolonged use of the drug and increased risk.
Additionally, he said, it might have been difficult to determine if participants took PPIs correctly because they only reported their use once a year. “Were patients truly taking them as prescribed, and how can you assess this with only a yearly visit?” he said. “Unfortunately, questions such as these cannot be answered in this study.”
Because of these limitations, researchers should conduct future studies to untangle the relationship between dementia risk and PPI use, he noted.
The amount of time you should take a PPI depends on what you’re taking it for, Hoscheit said. “For reasons such as healing ulcerative disease of the stomach and esophagus, PPIs are generally recommended for eight to 12 weeks,” he explained. For people with chronic acid reflux symptoms, healthcare providers may recommend PPIs for longer than 12 weeks.
Because people need PPIs for varying lengths of time, it’s crucial to make an individualized plan with your doctor to determine the amount of time that’s right for you, Hoscheit stressed.
He noted that PPI use usually isn’t risky enough to avoid the drugs if a healthcare provider recommends them, but he still informs his patients about studies linking their long-term use to several conditions. In addition to dementia, said Hoscheit, research has established ties between the medication and intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, deficiencies of certain vitamins and minerals, heart attacks, and strokes.
“I then go on to tell my patients,” he explained, “ that it is critically important to understand that those studies have flaws, are not considered definitive, and do not establish a cause-and-effect relationship between PPIs and adverse conditions.”
If you’re concerned about the risks associated with PPIs, alternative acid reflux treatment options exist, Hoscheit said. These include medications such as famotidine and calcium carbonate, as well as making lifestyle changes, such as allowing three to four hours between dinner and bedtime and limiting portion sizes. “In certain individuals, weight loss has been shown to be a fantastic way to help improve symptoms as well,” he added.
That said, Hoscheit said he doesn’t think the new research is a compelling enough reason to stop using PPIs if your doctor has recommended them for your symptoms.
“I don’t believe this study moves the needle on how we should view PPIs,” he said. “I always encourage my patients to discuss medication side effects with their respective prescribers. In how PPIs relate to the risk of dementia, I believe this requires further study before we can connect the use of PPI to dementia.”
