Do Proton Pump Inhibitors Exacerbate the Cognitive Effects of Breast Cancer Treatment?

Proton pump inhibitors (PPIs) are widely used medications. They are used to control stomach acid in patients who have reflux disorders such as gastroesophageal reflux disease (GERD) or laryngopharyngeal reflux (LPR) and peptic and other ulcers in the gastrointestinal tract. PPIs are often prescribed for patients with cancer to manage gastrointestinal symptoms and prevent erosion of the gastric mucosal lining caused by cancer treatments. In addition, these drugs are available as over-the-counter (OTC) medications in various strengths and formulations including single-ingredient tablets or capsules, components of chewable antacids, as well as other formulations.

Some reports have linked PPI use to development of mild cognitive impairment and even dementia in the general population. Because clinicians often prescribe these drugs for patients during cancer treatment, researchers from The Ohio State University (OSU) sought to determine whether use of PPIs among patients with breast cancer might be more chronic than in the general population. They hypothesized that although these women are at risk for cognitive issues related to their breast cancer treatment, a relationship may exist between PPI use and cognitive outcomes in breast cancer survivors.

Annelise Madison, a doctoral student in clinical psychology at OSU Institute for Behavioral Medicine Research and lead author of this study, explained that her group considered that breast cancer survivors are already at risk for “brain fog” and poor cognitive outcome after treatment [personal communication, A. Madison, February 2020]. They also noticed that patients with breast cancer could be taking PPIs for a longer time than even the general population because many often use PPIs to self-treat their gastric upset or even to try to prevent possible chemotherapy-related GI upset. After their chemotherapy has started, these patients may continue to take the PPIs to manage their treatment-related GI side effects without their clinicians’ knowledge. As a result, these patients may be using PPIs for a period of time that exceeds their original intended use.

In addition, a novel use for PPIsis just beginning to be investigated: If proton pump inhibitors change not only pH levels in the GI tract but also effect pH levels in the bloodstream in general, could they potentially help to make tumors more responsive to the effects of chemotherapy? This theory is currently under investigation and is another reason why investigating the use of PPIs by breast cancer survivors is important.

Data Shows Extended Use

The OSU researchers reviewed data from 3 prior unrelated studies. Rather than focus on specifically on PPI use, the studies focused on fatigue, yoga practice, and vaccine response in breast cancer survivors and patients. However, participants in each study self-reported use of prescription and nonprescription medications and provided regular self-reports of any cognitive symptoms they experienced.

When they examined the data, Ms Madison’s team found that participants in 2 studies (labeled as study 1 and study 2) who used PPIs reported more severe problems with concentration compared with the nonusers, but did not report problems with their memory. In the third study (labeled as study 3), the women who used PPIs reported more severe memory problems compared with those who did not take PPIs. Participants in this group also reported an overall lower quality of life related to cognitive problems.

Limitations to these data included the researchers had no knowledge of what other medications had been offered to the participants, the data from all 3 studies were self-reported measures, and objective cognitive testing data were not available. Ms Madison said results from study 1 and study 2 showed that 66% and 84% of participants, respectively, were using PPIs at their first visit and continued using PPIs throughout the entire study.

Other research studies have found that breast cancer survivors report cognitive functioning as being important to their quality of life. If patients are reporting more memory problems, that also is potentially affecting their quality of life, Ms Madison explained.

PPIs were originally designed and granted Food and Drug Administration (FDA) approval for short-term use, approximately 14 days; however, PPI use during those studies was for much longer periods. Because these drugs were not meant to be used for such a long time, duration of clinical trials on efficacy and side effects may not have been long enough to include cognitive outcomes. Additionally, the potential of PPIs to make the intestinal barrier more permeable was not well known at that time. Another now-established finding is that PPIs can even cross the blood-brain barrier.