Long-time readers of this website will remember an article by Dr. Eva Untersmayr linking use of antacids to adult onset of an allergy to Beluga caviar in an individual patient. He had eaten the delicacy at a party with no ill effects, but several months later had a severe reaction after eating more. The Dr. Untersmayr and her colleagues learned that he had been taking antacids during the first ingestion, reducing the crucial acid environment of his stomach. Poorly digested larger protein components found their way into the intestines and the blood, where the immune system went on alert and cranked out allergic antibodies in case it ever happened again. The same pattern was observed for patients with dyspeptic disorders treated using anti-ulcer medication. When Dr. Untersmayr popped up again recently as a co-author of an article in the journal Nature Communications entitled “Country-wide medical records infer increased allergy risk of gastric acid inhibition” which elaborates on the connection between anti-ulcer drugs and allergy, not just to food but to all kinds. She has generously agreed to answer some questions about the new article. – Henry Ehrlich
AAC: Eva, welcome back and thanks for volunteering your time. First, your methodology in this study was fascinating. You were able to access the medical records of 97% of the population of Austria between 2009 and 2013 because the country has near-universal health insurance. As an American I marvel at that all by itself. Simply put, you compared prescriptions of anti-allergy medicine to patients who had previously been taking H2 agonists—antacids–and proton pump inhibitors, or PPIs. How did you arrive that this approach? Also, I know it’s not as easy as it sounds. How did you construct the study? And what protections are there for patient privacy?
Eva: Henry, thank you very much for the invitation and your questions. You are right, our approach sounds straightforward, but it was made only possible within a network of excellent collaborations. The reason why we designed the study that way was to evaluate the impact of this medication on the entire Austrian population. We are very lucky to have compulsory health insurance ensuring nearly complete health care coverage, even paying for most of the medication Austrians are prescribed by medical doctors. In the health insurance databases, in- and outpatient data on medical services covered by the health insurance is available. And of course the study was performed in strict agreement with data protection and patient privacy law. Therefore, a pseudonymized data set was used and only after approval by our ethics committee of course. And in the end the analysis means a lot of statistical calculations and comparisons, which were done by the expert in our team.
AAC: The idea that digestion is impaired by these drugs so that allergenic protein components sneak through is familiar enough. But your study shows that they also activate Th2 mechanisms, which are more generally allergic, as indicated by patients needing medicines that don’t work on food allergies. How do these medicines affect the larger immune system? Could you particularly highlight their effects on the gut and oral microbiome?
Eva: I am not so sure that the concept of digestion impairment and higher risk for allergy development is familiar to everyone working in the field of allergy or gastroenterology. I still get a lot of questions from the audience when I present even our older data at scientific meetings. But you are right, our current data shows that the effect goes beyond food allergy, as we investigated use of anti-allergy medication, which is most frequently used for respiratory allergies and far less frequently in case of food allergies. One mechanism, which we also highlight in our paper, could be the direct effect on the immune response as immune cells have H2 receptors, PPIs can induce mast cell activation and the aluminum-containing Sucralfate might act as an adjuvant. Moreover, anti-ulcer drugs have an enormous effect on microbiota, which is even more prominent than the effect of antibiotics when considering the entire population due to longtime intake of this medication. So there are different layers of mechanisms that might explain our results.
AAC: These changes take place very quickly, don’t they? You mention as few as six days.
Eva: The change in the gastric milieu takes place very quickly. You are right that approximately 5-6 days of PPI intake elevates the gastric pH to around 5. But long-term use of anti-ulcer drugs seems to especially increase the risk for need of anti-allergy medication, which we could also prove in our current study.
AAC: I was particularly struck by how many young boys are on these drugs. Why? Is it because they eat a lot of junk? If so, why are their doctors prescribing these things and not focusing on improving their diets?
Eva: There is not really a difference between anti-ulcer drug prescription between boys and girls in childhood. Around puberty girls are more likely to get prescription for this medication and the female gender dominates until very old age.
AAC: Finally, the paragraph on “imprinting the next generation for allergy” was very troubling. I know that reflux is a big problem during pregnancy. I kind of hate to ask because mothers of food allergic kids are constantly worrying about what they did wrong, but I have to. How does antacid use “imprint” the next generation? Is this an epigenetic change or something else?
Eva: We and other groups have demonstrated this link in previous studies, both in experimental models and in human data. When the mother takes anti-ulcer medication during pregnancy, the child is more prone to become allergic due to skewing the immune response. Moreover, as mentioned above, anti-ulcer drugs affect the microbiota composition and we know how important our microbes are for immune health and how much the mother’s microbiota influences the colonization of the child. But I think much more research is needed until we fully understand all the mechanisms involved here. As an advice for pregnant mothers-to-be suffering from reflux (like I did with my second child): Lifestyle changes are also a good option and can prevent the need for medication. Do not eat too late and try to sleep with your upper body slightly elevated.
AAC: In your previous article, you wrote, “There is evidence that patients and doctors are trading long-term health for short-term comfort. In Europe, and I suspect elsewhere, the sales figures of acid-suppressive drugs are continuously on the rise and they are being used for long periods of time.” Do you have the feeling that patients and their doctors are taking better care of their digestion? Are they eating better? Are they using alkaline water instead of antacids and PPIs? Or is it business as usual?
Eva: Unfortunately I do not see a big difference in caring for a functional gastrointestinal digestion. Nevertheless, it is very important to raise awareness, to constantly inform medical doctors and patients. We once launched an awareness campaigns together with one of our health insurance companies here in Austria and we could really see an impact of this campaign on anti-ulcer drug prescription habits. Making important information available is very helpful!
AAC: Your biography says that you are a trained acupuncturist. The only doctors I know who address digestion as part of treatment for food allergies are also trained in Asian medicine—one in Chinese medicine and one in Ayurvedic medicine. Do you think that Western doctors have something to learn from these disciplines?
Eva: I am personally very keen on a broad approach in medicine. There are so many fields to learn from. Asian traditional medicine is one example, but we also should not forget traditional medical knowledge from our cultures, where much more attention was given to how, when and what to eat.
AAC: Thank you for your time.
Eva: Thank you Henry for your interesting questions and for highlighting our research!
Eva Untersmayr, MD, PhD, is Associate Professor and head of the Gastrointestinal immunology research group at Institute of Pathophysiology and Allergy Research at the Medical University of Vienna. She is a Clinical Immunologist especially interested in the connection between digestion, food allergy and the immune system of the gastrointestinal tract. Her work was continuously funded by several grants of the Austrian Science Fund, the Austria National bank, the EC Horizon 2020 and other funding agencies. Following her medical studies, Dr. Untersmayr also trained as an acupuncturist in Austria.
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