Proton Pump Inhibitors (PPIs) are a class of medications commonly used to treat conditions such as acid reflux, ulcers, and heartburn. They include omeprazole (Prilosec, Zegerid), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (AcipHex), Dexlansoprazole (Dexilant), and pantoprazole (Protonix). Several of these are available without a prescription.
While PPIs are generally considered safe and effective, several studies have suggested a potential association between PPI use and several medical and neurological problems. These include osteoporosis, kidney problems, impaired hearing, vision, memory, and an increased risk of conditions such as migraines, dementia, peripheral neuropathies, and seizures. The evidence is circumstantial and not definitive. However, considering the large number of studies and a large number of conditions, PPIs are probably not safe for long-term use.
In the case of migraines, one study found that past and current use of PPI increased the odds of migraine by 2.56-fold and 4.66-fold, respectively. The exact reason for this link is still a mystery, but researchers are exploring several possibilities:
Nutrient deficiencies: PPIs can interfere with the absorption of important nutrients like vitamin B12, other B vitamins, and magnesium, which can contribute to headaches.
Gut microbiome changes: PPIs can alter the gut microbiome, which may indirectly impact brain function and migraine susceptibility.
Inflammation: Some studies suggest PPIs might trigger low-grade inflammation, a potential factor in migraine development.
This post was prompted by a recent study showing an association between PPI intake and the risk of dementia. Those who used PPIs for a cumulative four and a half years or longer had a 33% higher risk of developing dementia.
Stopping a PPI can cause severe rebound acidity. This is why people get stuck taking them for years. The way to try is by replacing the PPI with an H2 blocker such as famotidine (Pepcid, Zantac 360) along with an antacid such as Rolaids (it’s better than Tums because it contains not only calcium but also magnesium) or Gaviscon. After a few weeks, people can often stop famotidine and after another few weeks, stop the antacid. Famotidine does not cause problems associated with PPIs.
If you cannot stop or have a condition that requires long-term intake of a PPI (e.g. Barrett’s esophagitis), make sure to take a variety of vitamins and minerals. However, the lack of acidity can prevent the absorption of supplements. We usually do a blood test to check vitamin B12, RBC magnesium, vitamin D, and others. Some of our patients come in for monthly infusions of magnesium and other nutrients they are deficient in.
