What Actually Causes GERD and Acid Reflux? Why Long-Term PPI Use Often Makes It Worse — Selected primary research

The mechanisms described in this article are drawn from primary research published over the past two decades. Key references include: Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009;137(1):80-87. Yadlapati R, Kahrilas PJ. The "dangers" of chronic proton pump inhibitor use. J Allergy Clin Immunol. 2018;141(1):79-81. Lazarus B, Chen Y, Wilson FP, et al. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med. 2016;176(2):238-246. Compare D, Pica L, Rocco A, et al. Effects of long-term PPI treatment on producing bowel symptoms and SIBO. Eur J Clin Invest. 2011;41(4):380-386. Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11(5):483-490. Fossmark R, Martinsen TC, Waldum HL. Adverse Effects of Proton Pump Inhibitors-Evidence and Plausibility. Int J Mol Sci. 2019;20(20):5203. Brusselaers N, Wahlin K, Engstrand L, Lagergren J. Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden. BMJ Open. 2017;7(10):e017739. Sigterman KE, van Pinxteren B, Bonis PA, et al. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oe