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Key points
- Proton-pump inhibitors reduce acid in the stomach.
- Reduced stomach acid can lead to dysbiosis in the intestines.
- Over time, dysbiosis can lead to systemic inflammation and dementia.
None of us wants to be reminded that dementia is random, relentless, and frighteningly common. –Laurie Graham
Dementia is horrifying and common, but it may not all be random. Some of it may be a consequence of mistakes we could easily avoid. New research indicates that among those mistakes is long-term use of heartburn remedies known as proton pump inhibitors (PPIs).
Casual use of PPIs is not the concern. But if you use PPIs for four years or more, the study finds that your risk of getting Alzheimer's grows by 33 percent. That is not a trifling matter.
What are PPIs?
PPIs are intended to treat ulcers and acid reflux. They are wildly popular, ranking among the top-10 most prescribed drugs in America. And that doesn’t even count the nonprescription PPIs, which take up a surprisingly large amount of shelf space at the drugstore.
The most common ones include omeprazole, esomeprazole, and lansoprazole. Those that are available over the counter are intended for a maximum of two weeks and are considered to be safe with few side effects. However, there are two associations that have been found over the years involving long-term PPI use and brain problems.
PPIs may induce vitamin B12 and iron deficiency. It is a small effect, but a shortage of B12 and iron can, over time, cause neurological issues. In addition, PPIs interfere with the breakdown of amyloid-beta in the brain. This pernicious molecule is one of the main hallmarks of Alzheimer's disease.
But there is a third connection between PPIs and brain problems: the gut–brain axis. PPIs work by decreasing acid secretion from specialized cells lining the stomach. Lowered acid levels can help with acid reflux. That change in acidity, however, has knock-on effects throughout the rest of the gut.
PPIs alter the composition of gut microbes.
Without acids to degrade them, some pathogens may get a pass to enter the small intestines. So, although it can help the stomach, lowered acidity may hinder proper bacterial colonization in the gut sections that follow.
One of those changes is ominous: greater numbers of Clostridium difficile bacteria, also known as C. diff. This can be a particularly unpleasant microbe, especially for people taking antibiotics. That’s because C. diff is resistant to most antibiotics and, thus, comes to dominate the gut microbiome.
This is the fate of many hospital patients, and when it happens, their life is at risk: They develop diarrhea and start to waste away. More than 30,000 people die of C. diff infections each year.
Right now, the best answer to a C. diff infection is a fecal transplant, where a healthy person’s poop is transferred via enema. That may sound yucky to you, but if you’re suffering from a miserable C. diff infection, you will jump at the chance. The cure rate is astonishingly high: some 90 percent of recipients find quick relief with the procedure.
PPIs for ulcers
Almost all peptic and duodenal ulcers are caused by a bacterium named Helicobacter pylori. This microbe has a special talent for digging through the mucus coating the gut and then boring into the lining itself.
We have known about H. pylori for 40 years, and we know how to treat it. The protocol is to use antibiotics, along with a PPI, for two weeks. It is hard then, to understand why doctors and pharmaceutical companies still push long-term use of PPIs for ulcers.
Outside of ulcers, occasional heartburn may not be a good reason to use PPIs, because they can take up to four days to have an impact. There are older drugs, called H2 blockers, that are faster and may be a better substitute. But many cases of heartburn and acid reflux can be treated without drugs by eating smaller meals and not eating near bedtime. Losing weight can also help.
If you are taking PPIs regularly, you might want to review your dosage with your doctor. You might be able to lower the dose or eliminate them altogether.
What to do
Before your reach for a PPI, try taking better care of your gut. Many gut issues can be solved with a simple switch to a better diet. Rather than looking for pills to fix a dietary problem, why not circumvent the problem in the first place?
What kind of foods are good for you? The go-to diet is Mediterranean. It includes a wide variety of veggies, especially those high in prebiotic fiber. Prebiotic fiber is food for the good bacteria in your gut, which repay you by providing healthy substances like butyrate and feel-good neurotransmitters. The Mediterranean diet also includes a mix of different meats, especially fish rich in omega-3s, which have an anti-inflammatory effect.
The best microbiome is a diverse microbiome, and that is supported by a diverse diet. Try to eat as many different veggies and berries as possible. If you can’t get enough veggies, you might want to try a prebiotic supplement.
Other foods to please your gut include ferments like yogurt, kimchee, sauerkraut, and kefir. Ferments supply a rich mix of both prebiotics and probiotics and are a valuable component of a healthy diet.
In short, PPIs have their place and are normally well-tolerated. But this new research indicates that long-term use may be a bad idea. Fortunately, you now know of some good workarounds.
References
Northuis, Carin, Elizabeth Bell, Pamela Lutsey, Kristen M George, Rebecca F. Gottesman, Tom H. Mosley, Eric A Whitsel, and Kamakshi Lakshminarayan. “Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study.” Neurology, August 9, 2023, 10.1212/WNL.0000000000207747.
Akter, Sanjida, Md. Rajib Hassan, Mohammad Shahriar, Nahia Akter, Md. Golam Abbas, and Mohiuddin Ahmed Bhuiyan. “Cognitive Impact after Short-Term Exposure to Different Proton Pump Inhibitors: Assessment Using CANTAB Software.” Alzheimer’s Research & Therapy 7, no. 1 (December 27, 2015): 79.
