Are PPI's worth the risk?

Proton pump inhibitors (PPIs) are a frequently prescribed treatment for gastroesophageal reflux disease (GERD), commonly known as heartburn. Recent studies have drawn attention to potential risks associated with their use. What are the risks of taking PPIs? Should you avoid taking PPIs? What is the data behind PPI use and are they worth the risk?


Why should you take PPI's?

The main reason to use PPIs is if you suffer from heartburn. If you have heartburn and as-needed use of PPIs or other acid blocking medications such as H2-blockers aren't improving your symptoms, you should not avoid using PPIs based on the current data available. Minimizing use to intermittent 2-4 week courses when your heartburn recurs is perfectly reasonable, and like any medication, if you don't need it, don't take it. It's worth knowing that using it for a single day is unlikely to improve your symptoms - it takes a few days for the medicine to actually block stomach acid. If you are going to use it "as needed," do so taking it consistently for two weeks until after your symptoms have resolved, and don't suddenly stop. Taper off, going from daily to every other day, every few days, then stop. In one study, this strategy was effective in 70% of patients with GERD. 

Symptoms aside, there are a few other reasons your doctor may have encouraged you to take a PPI. If you have Barrett's esophagustake NSAIDs (=ibuprofen, naproxen, etc) and steroidsanti-platelet agents such as aspirin, or have a history of GI bleeding, you may have a good reason to take PPIs. However, many patients are started on PPIs during a hospitalization with no true indication to remain on them long-term. You shouldn't hesitate to ask your doctor if you really need your PPI.


What are the risks of using PPI's?

Purported risks of PPIs have been claimed since the 1980s, and have ranged from decreased vitamin absorption, to increased risk of fractures, cancer, chronic kidney disease, and dementia. The long story short is that most of the literature available on this topic is relatively poor, and exclusively observational, meaning research that took giant cohorts of patients and just looked for any associations between chronic diseases and long-term (not short term!) PPI use. Why is that important? Correlation is not causation, and while many of these studies have tried to control for confounders (=other factors contributing to these associations), it is pretty much impossible to eliminate selection bias (i.e. patients on more medications are more likely to be sicker overall).

Do PPI's prevent vitamin absorption?

No. Most patients eating a normal diet will not experience any nutrient deficiencies due to PPI use. Studies showing vitamin deficiencies (specifically B12, iron, and calcium) associated with PPI use have been inconsistent, and routine monitoring of levels is not recommended in patients taking PPIs for this reason. While rare exceptions may occur (i.e. few case reports of low magnesium with PPI use), there is no clear association with vitamin deficiency and PPI use.

Can PPI's increase risk of fractures?

Yes. Confounding is particularly difficult to control for in this patient population (older patients also tend to use PPIs more frequently), and studies have both gone both ways on this one. Although the risk is not high enough to prompt guidelines to recommend screening for osteoporosis (=low bone density) in all patients taking PPIs, data was sufficient enough to prompt the FDA to require that PPI labels warn about the possible increased risk of fractures. 

Can PPI's increase cancer risk?

No. There is no controlled human data supporting increased risk of stomach or colon cancer. It would never be prescribed if so! That said, it has been shown to increase the amount of gastric polyps, however, the data is mixed.

Do PPI's cause kidney disease?

Unclear. A recent study showed an association with PPI and chronic kidney disease, however, it was a relatively small difference (10-year risk of 15.6% in PPI users compared with 13.9% in nonusers). Our understanding of this association is still evolving, but for now the data is not compelling enough to change any guidelines or to have really impacted doctors' clinical practice at this time.

Can PPI's lead to dementia?

No. This is probably the weakest claim of all, was based on a single study that made it to mainstream media in early 2017, with a subsequent, larger study showing no association between PPI use and dementia.


Bottom line on PPI risks?

If you need to use PPIs for your heartburn symptoms, try to use them as needed for 2-4 weeks at a time, then slowly stop using them. If you're unable to do so, staying on them long-term isn't as risky as mainstream media would suggest. You may have other reasons to be on a PPI based on other medications you take or your GI history. Ask your doctor if you absolutely need to be on a PPI, and don't sweat it if the answer is "yes" at least based on the research available at this time.


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