Diana Zuckerman, PhD and Farzana Akkas, MSc,
In 2016, research was published indicating that people who take popular heartburn medications are more likely to develop serious kidney disease. In 2023, research was published showing that people prescribed these popular medications are more likely to develop dementia. If you take any of these drugs, how worried should you be? And are there safer medications that work just as well?
Prilosec, Nexium Prevacid, Kapidex, Aciphex and Protonix are all a type of drugs called Proton Pump Inhibitors (PPI). There are several other drugs of this type as well. They are all used to treat heartburn and acid reflux. In a 2016 study lead by Dr. Morgan Grams of Johns Hopkins University, people who use PPI are more likely to develop chronic kidney disease compared to those who take other types of heartburn medication. The higher the dose or the more often they take these drugs, the more likely they are to develop kidney disease. In the first of several expected settlements, in October 2023 AstraZeneca agreed to pay $425 million to settle about 11,000 lawsuits in the United States that claimed that Nexium and Prilosec caused chronic kidney disease. AstraZeneca did not admit wrongdoing under the settlement, part of broader litigation against makers of PPI that involve several major pharmaceutical companies.
Even more important, the researchers found that most of the 15 million Americans who were prescribed a PPI don’t really need them. One in four of long-term users can stop taking them without suffering from more heartburn or acid reflux.
Since the research on dementia is more recent, let’s focus on that first. The 2023 study of more than 5,000 people ages 45 and older who did not have dementia at the start of the study concluded that those who take PPI for 4.5 years or longer are more likely to develop dementia. The study compared more than 4,000 people who did not take the drugs to 1,490 adults who took PPI for up to 2.8 years, between 2.8 to 4.4 years, or for more than 4.4 years. During the 30 years of the study, 585 people (10%) developed dementia. Of the people who did not take the drugs, 425 people developed dementia, which equals 1.9% per year. Of the 497 people who took the drugs for more than 4.4 years, 58 people developed dementia, which equals 2.4% per year. THESE numbers seem small but they add up over time (for example, 38 compared to 48 over 20 years). Researchers did not find a SIGNIFICANT increase in dementia for people who took the drugs for fewer than 4.4 years. This study does not prove that PPI causes dementia but it shows an association which could be caused by the drugs or could be caused by an unknown behavior or medical condition that causes both heartburn and dementia. More research is needed to determine whether long-term PPI use actually causes dementia.
The evidence regarding PPIs and kidney disease is more conclusive. Even before the 2016 study, research had shown that people who take these drugs are more likely to have painful kidney problems such as acute kidney injury and acute interstitial nephritis.[3, 4, 5, 6, 7] The 2016 study is important because the patients taking a PPI developed chronic kidney disease, which is more serious. It means that their kidneys can no longer filter blood effectively, which can cause kidney failure. Those patients will need dialysis.
Do PPI cause these health problems or does overeating cause these problems? To address this question, the researchers compared results of PPI users to people taking a different type of heartburn medication called H2 blocker users (such as Pepcid, Tagamet and Zantac). After statistically controlling for heath factors such as obesity and hypertension, they found that people who used a PPI were still more likely to develop chronic kidney disease when compared to people using H2 blockers. And, those who took the PPI medication twice a day were more likely to develop chronic kidney disease than those who took it once a day.
Another study, based on more than 190,000 veterans taking heartburn medication came to a similar conclusion. Regardless of their age and health, the PPI users in that study also were more likely to develop chronic kidney disease than the veterans taking H2 blockers.
H2 blockers like Pepcid, Tagamet or Zantac are less expensive and seem to be safer than the PPI medications. Many of them are available without a prescription. And of course, a major cause of heartburn and acid reflux is our health habits. Maintaining a healthy weight and quitting smoking helps reduce the chances of heartburn or acid reflux. If that doesn’t work, some people find it helpful to avoid spicy or greasy food, chocolate, mint, and coffee until the symptoms go away.
All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.
- Lazarus, B., Chen, Y., Wilson, F. P., Sang, Y., Chang, A. R., Coresh, J., & Grams, M. E. (2016). Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Internal Medicine JAMA Intern Med, 238.
- Northuis, C., Bell, E., Lutsey, Pm. George, K., Gottesman, R., Mosley, Tom., Whitsel, E., & Lakshminarayan K. (2023). Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study. American Academy of Neurology.
- Blank ML, Parkin L, Paul C, Herbison P. (2014). A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int., 86(4):837-844.
- Sierra F, Suarez M, Rey M, Vela MF. (2007) Systematic review: proton pump inhibitor–associated acute interstitial nephritis. Aliment Pharmacol Ther.,26(4):545-553.
- Antoniou T, Macdonald EM, Hollands S, et al. (2015) Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open, 3(2):E166-E171.
- Klepser DG, Collier DS, Cochran GL. (2013) Proton pump inhibitors and acute kidney injury: a nested case-control study.BMC Nephrol, 14:150.
- Leonard CE, Freeman CP, Newcomb CW, et al. (2012) Proton pump inhibitors and traditional nonsteroidal anti-inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury. Pharmacoepidemiol Drug Saf, 21(11):1155-1172.
- Xie, Y., Bowe, B., Li, T., Xian, H., Balasubramanian, S., Al-Aly, Z. (2016). Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD. Journal of The American Society of Nephrology, 27.
- Kang, J. H., & Kang, J. Y. (2015). Lifestyle measures in the management of gastro-oesophageal reflux disease: Clinical and pathophysiological considerations. Therapeutic Advances in Chronic Disease, 6(2), 51-64.