Optimizing Metabolism

by Ingrid Kohlstadt, MD, MPH

New Research Questions Proton Pump Inhibitors’ Use

Statistics is common ground for baseball and medicine, as both seek to play the averages. Baseball catcher Yogi Berra (1925–2015) may have put it best, “It’s tough to make predictions, especially about the future.”

Benjamin Lazarus, MBBS, of Johns Hopkins University and his all-star coauthors rose to Berra’s challenge. Their JAMA Internal Medicine article “Proton Pump Inhibitors and Chronic Kidney Disease” links long-term use of a common stomach medicine to kidney disease. While additional studies will help understand the connection, Lazarus’s team found something that can help doctors and their patients “play the averages” about whether to take proton pump inhibitors (PPIs).

How serious is the risk of this medicine to the kidneys? Says Lynda Frassetto, MD, nephrologist and professor of medicine at UCSF for additional perspective, “When I was a medical doctor in training in the 1970s, it was tragically common that people died from bleeding ulcers in the emergency room. That hardly happens anymore because of proton pump inhibitors.” So how can we predict when the risks outweigh the potentially life-saving benefits? Frassetto explains “There’s no straightforward answer.” There are however, four ways that the Lazarus study helps us optimize health outcomes.

PPIs are linked to kidney damage that is difficult to detect early in the process. The Lazarus study reminds clinicians to look more closely for subtle early warning signs.

Early diagnosis is a physician’s equivalent of a baseball player’s great catch ending a play that might otherwise have finished in a grand slam for the opposing team. PPIs are theorized to damage the kidneys by causing repeated episodes of an inflammatory allergic reaction called interstitial nephritis. Interstitial nephritis is diagnosed based on a needle biopsy of the kidney. Since biopsy is not a routine procedure, first a clinician would need to suspect that there is a kidney problem. Suspecting interstitial nephritis is difficult because it lacks clear symptoms for a patient to report to their doctor, and routine kidney blood tests can be in the normal range. Blood tests are more likely to indicate a problem when compared to prior labs. Based on the Lazarus study, practitioners may want to zoom in on even normal range kidney function tests in their patients taking PPIs, especially if the patients are also taking aspirin and antibiotics, other medicines associated with interstitial nephritis.

The Lazarus study reassures us the overall chances of developing kidney disease from PPIs are fairly small.

Sizing up the risk is especially important for patients with multiple medical conditions. When it comes to medication side effects, the people who have the most risk of side effects often derive the most benefit. Dr. Frassetto maintains that this is the case here. People with preexisting kidney disease from high blood pressure and diabetes are more likely to develop bleeding stomach ulcers, against which PPIs protect.

The Lazarus study gives prescribing doctors and over-the-counter users yet another reason to read the package insert.

Most people taking PPIs (up to 70% in this study) aren’t taking them for the right reasons and often incorrectly.¹ But why would people disregard the FDA’s best prediction? Perhaps they think it’s too restrictive. This study wouldn’t support that argument and neither would a concurrently published article in Science with unexpected relevance.² It’s an autopsy report on the world’s oldest patient, Ötzi the Iceman, preserved in Alpine ice for 5300 years. Ötzi was infected with the bacterium associated with stomach ulcers and PPIs would have been indicated were he a patient today. Yet his stomach showed no signs of ulceration. If he had been taking a PPI, he wouldn’t have had enough stomach acid to digest the large portion of ibex meat also found in his stomach. If Ötzi didn’t need PPIs, maybe we don’t either, at least not for reasons off the list.

“The [Lazarus] study reminds us to periodically reevaluate the need for a medication, even one a patient has been taking for years,”

explains Dr. Frassetto. It estimates that 1 in 4 longtime PPI users could stop therapy and remain symptom free, especially if they take Yogi Berra’s famous advice, “When you come to a fork in the road, take it.” In other words, if you can improve your health by changing what you put on your fork – take the fork instead of the medicine! The recently released U.S. dietary guidelines similarly advise Americans to pay attention to “home plate.”³

The most compelling reason to quit unnecessary PPIs may be that across all mammals, waning stomach acid is a sign of old age. While science has assumed that it’s old age which causes stomach acid production to decline, it could be the other way around, too. New understanding of the microbiome adds plausible mechanisms by which inadequate stomach acid could contribute to aging. If that’s the case, PPIs are indeed a curveball, but it’s possible to be a home-run hitter – especially if you ask your doctor the right questions.

Notes

1. Gunaratnam NT, Jessup TP, Inadomi J, Lascewski DP. Sub-optimal proton pump inhibitor dosing is prevalent in patients with poorly controlled gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2006;23(10):1473–1477. http://www.medscape.com/viewarticle/531605_4.

2. Gibbons A. The Iceman had a tummy bug. Science. Jan. 7, 2006. Available at http://www.sciencemag.org/news/2016/01/iceman-had-tummy-bug.

3. U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015 – 2020 Dietary Guidelines for Americans. 8th ed. December 2015. Available at http://health.gov/dietaryguidelines/2015/guidelines.