“Does your heartburn drug make you vulnerable to dementia?” asked the Washington Post last February.
The news flash: In a German study of nearly 74,000 people aged 75 and older, those who took proton pump inhibitor drugs (PPIs) like Prilosec, Prevacid, and Nexium for seven years were 44 percent more likely to get dementia than those who didn’t take PPIs. Occasional users were 16 percent more likely. A similar German study in 2015 found a 38 percent increased risk.
“These were observational studies, so they can’t prove that PPIs caused the higher dementia risk,” notes Scott Gabbard, a gastroenterologist at the Cleveland Clinic. “Patients prescribed PPIs may have poorer lifestyle habits and be generally unhealthier, and that, not the PPIs, may be increasing their risk.”
It’s also possible, adds Joel Rubenstein, that the more often someone seeks medical care, the more likely they are to be prescribed a PPI and, if they also have subtle symptoms of dementia, the more likely they are to be diagnosed with the disease.
“Those sorts of issues can lead to weak associations that aren’t cause and effect between PPI use and the diagnosis of other health problems,” he explains. Rubenstein is a research scientist at the Ann Arbor Veterans Affairs Center for Clinical Management Research and director of the Barrett’s Esophagus Program at the University of Michigan.
What could PPIs have to do with memory?
One possibility: We need stomach acid to absorb the vitamin B-12 in most foods. If PPIs suppress stomach acid enough to cause a B-12 deficiency, that could lead to dementia (though not the Alzheimer’s seen in some of the PPI-taking Germans).
Among more than 200,000 Kaiser Permanente patients in California, those prescribed PPIs for at least two years were 65 percent more likely to have a B-12 deficiency than those not prescribed PPIs.
“Even though it isn’t recommended by any specific guideline, I check vitamin B-12 in my patients on PPIs every two years to make sure they’re not becoming deficient,” says Gabbard.
In a study of 249,000 people in rural Pennsylvania, PPI users had a 16 percent risk of kidney disease over 10 years, versus 14 percent for non-users. People who took an H2 blocker like Tagamet, Zantac, and Pepcid had no greater risk than non-users. Results were similar in a second study of nearly 10,500 people.
The increased risk amounts to one additional case of kidney disease for every 30 to 60 PPI users. “That’s a very weak association that could be due to something else besides PPIs,” says Rubenstein.
“No more Nexium. These are the only bones I’ve got,” Florida IT architect Ross Castillo says he told his doctor six years ago, after he heard that long-term use of PPIs increases the risk of bone fractures. Castillo, then in his late 40s, was overweight, out of shape, smoking cigarettes, eating greasy foods, and had been suffering from chronic acid reflux, or GERD (gastroesophageal reflux disease) for years.
Should Castillo have worried? When researchers looked at nine studies in the United States, Canada, Sweden, and Australia, they found that PPI users were 24 percent more likely than non-users to fracture a hip.
How might PPIs weaken bones? They may reduce the absorption of calcium (and magnesium) from food or supplements.
“But the evidence tying bone fractures to PPI use is inconsistent, and there is reason to be suspicious about the link between the two,” says Rubenstein.
What’s more, a 24 percent increase in risk isn’t huge. For example, in the Nurses’ Health Study of 80,000 women, one in every 100 nurses who weren’t taking PPIs broke a hip over an eight-year period. A 24 percent increase would make it one in every 80 nurses.
“When you give patients real numbers, the risks sound less scary,” says Gabbard.
The value of these drugs
“Proton pump inhibitors are revolutionary drugs,” Cleveland Clinic’s Scott Gabbard explains. “They’re our best treatment for patients who truly have reflux disease or who have erosive esophagitis, which is ulcers in the esophagus.”
But people should be on the lowest dose of the least potent medication that controls their symptoms, advises Rubenstein.
Gabbard agrees. “If someone has heartburn and the symptoms disappear when they take a PPI, they should try to see if a safer H2 blocker works.”
That’s what Ross Castillo did. After taking a PPI for about 10 years, he switched to the H2 blocker ranitidine. He also lost weight, stopped smoking, started exercising, and watched what he ate.
Castillo’s GERD disappeared. Today he takes ranitidine only when he visits his family. “You gotta eat what they dish out and when they eat it,” he explains.
(But don’t stop taking a PPI without talking to your doctor if he or she prescribed it to prevent an ulcer, Rubenstein cautions. “You may not have GERD symptoms, but you don’t want to get a bleeding or perforated peptic ulcer.”)
“Overall, PPIs are very safe, but only a select few patients should be taking them long term,” concludes Gabbard.
“The overuse of PPIs is very common,” adds Rubenstein. “But people who truly need them for chronic acid reflux or GERD shouldn’t live life miserably because they fear the very small possible risks.”
Sources: JAMA Neurol. 73: 410, 2016; Eur. Arch. Psychiatry Clin. Neurosci. 265: 419, 2015; JAMA 310: 2435, 2013; JAMA Intern. Med. 176: 238, 2016; Osteoporos. Int. 27: 339, 2016; BMJ 344: e372, 2012.
- Should People Go on Elimination Diets to Avoid Heartburn?
- What is Silent Reflux?
- Can Losing Weight Help Relieve Acid Reflux?
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