Alternatives to PPIs and H2 Blockers

Gastroesophageal reflux disease (GERD) is estimated to affect 10-20% of the Western world and up to 30 million people in the United States alone.1 Sixty percent of adults experience the symptoms and the impact of GERD over a period of 12 months, whereas 20% to 30% of individuals have weekly symptoms.1 The most popular treatments, stomach acid reducers, are a booming business. Both H2 blockers and proton pump inhibitors (PPIs) are used widely, with the latter currently being taken by an estimated 15.3 million Americans.2

But is this really the best way to treat GERD? Taking an over-the-counter acid blocker for occasional heartburn symptoms may not be a big issue, but in practice, many patients with chronic reflux are prescribed acid blockers indefinitely. Research suggests that this long-term approach may have significant drawbacks.

A 2017 meta-analysis of 7,703 patients found that the use of gastric acid suppressants was associated with a significantly increased risk of recurrent C. difficile infection (CDI).3 Risk factors for recurrent CDI include older age, concomitant antibiotic use, and comorbid conditions. Up to 50% of patients with CDI are using concomitant gastric acid suppressants.3

A 2017 study in the British Medical Journal Open suggested a substantially increased risk of death among long-term proton pump inhibitor (PPI) users, including those without gastrointestinal conditions.4 Since then, some observational studies have described an association between PPI use and the risk of the development of chronic kidney disease and its progression to end-stage renal disease.5 A meta-review also suggested a correlation between PPI usage with an increased risk of dementia,6 as did a cohort study in JAMA Neurology.7 However, data on the association between gastric acid suppression and dementia are conflicting.8,9 A study investigating the effects of PPIs on cognitive decline in a study of middle-aged and elderly twins in Denmark found no association.9

Given these risks, is there a better way to treat the increasingly common issue of GERD?

Shilpa P. Saxena, MD, is an IFM Certified Practitioner and a board certified family physician who is a faculty member with IFM, the Academy of Integrative & Holistic Medicine, George Washington University’s Metabolic Medicine Institute, and the Functional Medicine Coaching Academy. She is also a fellow & guest faculty for the Arizona Center for Integrative Medicine.

Lifestyle modifications that have been studied for GERD include weight loss, head-of-bed elevation, and avoidance of tobacco, alcohol, and late-night meals.10 Another modification that has been suggested is avoiding foods that can aggravate reflux symptoms—e.g., caffeine, coffee, chocolate, spicy foods, highly acidic foods (oranges, tomatoes), and fatty foods. Recently, a prospective cohort study also found that smoking cessation significantly improved GERD symptoms in patients with normal body mass index and severe symptoms.10

Clinical studies have also suggested a relationship between GERD and anxiety, as well as depression.11 A 2017 cohort study of Australian men observed a strong independent association between GERD, anxiety, and depression, partly mediated by poor sleep quality.11

Clinicians looking for insight into how to treat gastrointestinal conditions safely by addressing the underlying cause and prioritizing lifestyle treatments can attend IFM’s GI Advanced Practice Module (APM). Clinicians will come away with tools and strategies to help prevent GERD, address problems with the microbiome, and improve overall gastrointestinal function.



  1. Tabrez ES, Hussain A, Rao S, Jagadeesh A, Peela JR, Tabrez SSM. Gastoresophageal reflux disease: a review of symptomatic management. Crit Rev Eukaryot Gene Expr. 2018;28(1):87-92. doi:10.1615/CritRevEukaryotGeneExpr.2018022767.
  2. Aitken M, Kleinrock M, Lyle J, Caskey L. Medicine Use and Shifting Costs of Healthcare: A Review of the Use of Medicines in the United States in 2013. Parsippany, NJ: IMS Institute for Healthcare Informatics; 2014. Accessed May 22, 2017.
  3. Tariq R, Singh S, Gupta A, Pardi DS, Khanna S. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177(6):784-791. doi:10.1001/jamainternmed.2017.0212.
  4. Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Risk of death among users of proton pump inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open. 2017;7(6):e015735. doi:10.1136/bmjopen-2016-015735.
  5. Li T, Xie Y, Al-Aly Z. The association of proton pump inhibitors and chronic kidney disease: cause or confounding? Curr Opin Nephrol Hypertens. 2018;27(3):182-187. doi:1097/MNH.0000000000000406.
  6. Wijarnpreecha K, Thongprayoon C, Panjawatanan P, Ungprasert P. Proton pump inhibitors and risk of dementia. Ann Transl Med. 2016;4(12):240. doi:10.21037/atm.2016.06.14.
  7. Gomm W, von Holt K, Thomé F, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416. doi:10.1001/jamaneurol.2015.4791.
  8. Taipale H, Tolppanen AM, Tiihonen M, Tanskanen A, Tiihonen J, Hartikainen S. No association between proton pump inhibitor use and risk of Alzheimer’s disease. Am J Gastroenterol. 2017;112(12):1802-1808. doi:1038/ajg.2017.196.
  9. Wod M, Hallas J, Andersen K, Garcia Rodriguez LA, Christensen K, Gaist D. Lack of association between proton pump inhibitor use and cognitive decline. Clin Gastroenterol Hepatol. 2018;16(5):681-689. doi:10.1016/j.cgh.2018.01.034.
  10. Alzubaidi M, Gabbard S. GERD: diagnosing and treating the burn. Cleve Clin J Med. 2015;82(10):685-692. doi:10.3949/ccjm.82a.14138.
  11. On ZX, Grant J, Shi Z, et al. The association between gastroesophageal reflux disease with sleep quality, depression, and anxiety in a cohort study of Australian men. J Gastroenterol Hepatol. 2017;32(6):1170-1177. doi:10.1111/jgh.13650.

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