Celiac Disease Risk Linked to Proton Pump Inhibitor Medication

The rate of celiac disease prevalence has been steadily rising. According to a study comparing the stored blood of soldiers with people today, it has increased up to four times within the past 50 years. Looking for the reason behind such a significant rise, many papers have been published investigating possible environmental causes, including one that found a link between celiac disease and an absence of H. pylori in the stomach. Another paper, involving three of the same doctors, found another possible explanation.

Titled “Use of proton pump inhibitors and subsequent risk of celiac disease”, the paper was accepted by Digestive and Liver Disease in August of 2013 but has not yet been published. The authors, led by first author Dr. Benjamin Lebwohl, had several lines of reasoning to look into proton pump inhibitors (PPIs) as well as histamine 2-receptor antagonists (H2RAs). First, the frequency of prescription of PPIs and H2RAs to suppress stomach acid secretion has risen in tandem with the frequency of celiac disease. Second, suppressing stomach acid secretion can affect protein digestion, increasing  one’s small intestine’s exposure to protein antigens like gluten. Third, PPIs increase the permeability of the stomach which could allow gluten to be absorbed into the body to set off an immune response in a person vulnerable for developing celiac disease. Despite this potential link, this is the first study the authors are aware of looking into how PPIs may be related to celiac disease.

PPI Use

The study looked at digital biopsy reports from 28 pathology departments in Sweden, and used the Swedish National Prescribed Drug Registry to see if celiac disease patients and controls were prescribed any PPI or H2RA. In total, the authors included 2934 patients with celiac disease and 14,584 matched controls in their analysis, and of those, 1096 had at least one PPI prescription.

After statistical analysis of the data, the authors found a strong association between patients having celiac disease and having a prescription of PPIs before their diagnosis (16% of patients with celiac disease had a prior PPI prescription as opposed to only 4% of controls). This association remained strong for both genders, as well as all ages, though it was stronger for men and for patients younger than 20 years old. The authors also adjusted for socioeconomic status using each individual’s level of education, and found that the link between prior PPI prescription and celiac disease remained strong. Patients who had only H2RAs prescribed had a higher risk for developing celiac disease than controls, though not as high as patients prescribed PPIs, which was still not as high as patients prescribed both PPIs and H2RAs.

One weakness of this study, the authors admit, is the possibility that celiac disease may have been the cause, rather than the effect. The various symptoms of undiagnosed celiac disease may have led to PPIs or H2RAs being prescribed. In order to account for this occurrence, the authors redid their analysis and excluded any PPI prescription made in the year prior to the celiac disease diagnosis, and the association still remained significant, albeit not as much as in the first analysis. The fact that the relationship remained strong even after eliminating any PPI prescriptions that came in the year before the patient was diagnosed with celiac disease supports the idea that the celiac disease development was caused or influenced by the acid suppression medication, as opposed to the reverse. This is still not necessarily proven however, as many patients can go years with a case of undiagnosed celiac disease. Unfortunately, the source of the data, the Swedish National Prescribed Drug Registry, was only created in 2005 so the authors were unable to exclude prescriptions that came more than a year before the celiac disease diagnosis. Patients that were on more than one kind of acid suppression drug (e.g., PPIs, H2RAs) were more likely to develop celiac disease than those on only one drug which lends more support to the idea that these medications are influencing the development of celiac disease.

Further studies on acid suppression medication like PPIs and H2RAs are needed to determine if these kinds of drugs can cause celiac disease to develop, and if so, how. The authors suggest multiple ways this could happen. When suppressing the acid in the stomach, the pH often rises to more than 4. With a pH that high in the stomach, certain digestive proteins no longer function which allows food to pass through the stomach undigested. PPIs also “increase gastric mucosal permeability” which would let antigens like gluten get into the body more easily. There are already studies, on animal models as well as on human patients, that support the idea that PPIs can have an effect on the immune system, though this is the first study that specifically looks at celiac disease.

The study “Use of proton pump inhibitors and subsequent risk of celiac disease” discussed in this article was published online on September 16th, 2013 by the journal Digestive and Liver Disease and can be found here.