Long-term proton pump inhibitor therapy in daily clinical practice – balancing benefits and potential risks: a narrative review.

Paulina Głowacka; Aleksandra Bartkowska; Paulina Orzechowska; Gabriela Mastej-Witek; Alicja Okupniak; Gabriela Budziszewska; Mateusz Nieczyporuk; Aneta Dziurdź; Aleksandra Łupicka; Monika Ziemba

doi:10.2478/bgbl-2026-0015

.blurhash-client-img { display: none !important; }

Long-term proton pump inhibitor therapy in daily clinical practice – balancing benefits and potential risks: a narrative review.

Biuletyn Głównej Biblioteki Lekarskiej

Volume 59 (2026): Issue 387 (December 2026)

By: Paulina Głowacka , Aleksandra Bartkowska , Paulina Orzechowska , Gabriela Mastej-Witek , Alicja Okupniak , Gabriela Budziszewska , Mateusz Nieczyporuk , Aneta Dziurdź , Aleksandra Łupicka and Monika Ziemba

Open Access

|Sep 2026

Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017 Mar;152(4):706–715. doi: 10.1053/j.gastro.2017.01.031. PMID: 28257716.
Open DOI Search in Google Scholar Open in PubMed Back to article
Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2022 Jan 1;117(1):27–56. doi: 10.14309/ajg.0000000000001538. PMID: 34807007; PMCID: PMC8754510.
Open DOI Search in Google Scholar Open in PubMed Back to article
Scarpignato C, Gatta L, Zullo A, Blandizzi C; SIF-AIGO-FIMMG Group; Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists, and the Italian Federation of General Practitioners. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med. 2016 Nov 9;14(1):179. doi: 10.1186/s12916-016-0718-z. PMID: 27825371; PMCID: PMC5101793.
Open DOI Search in Google Scholar Open in PubMed Back to article
Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Ther Adv Gastroenterol. 2012 Jul;5(4):219–32. doi: 10.1177/1756283X12437358. PMID: 22778788; PMCID: PMC3388523.
Open DOI Search in Google Scholar Open in PubMed Back to article
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900–20; quiz 1943. doi: 10.1111/j.1572-0241.2006.00630.x. PMID: 16928254.
Open DOI Search in Google Scholar Open in PubMed Back to article
Singh S, Garg SK, Singh PP, Iyer PG, El-Serag HB. Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett’s oesophagus: a systematic review and meta-analysis. Gut. 2014 Aug;63(8):1229–37. doi: 10.1136/gutjnl-2013-305997. Epub 2013 Nov 12. PMID: 24221456; PMCID: PMC4199831.
Open DOI Search in Google Scholar Open in PubMed Back to article
Kastelein F, Spaander MC, Steyerberg EW, Biermann K, Valkhoff VE, Kuipers EJ, et al. Proton pump inhibitors reduce the risk of neoplastic progression in patients with Barrett’s esophagus. Clin Gastroenterol Hepatol. 2013 Apr;11(4):382–8. doi: 10.1016/j.cgh.2012.11.014. Epub 2012 Nov 28. PMID: 23200977.
Open DOI Search in Google Scholar Open in PubMed Back to article
Chen Y, Sun C, Wu Y, Chen X, Kailas S, Karadsheh Z, et al. Do proton pump inhibitors prevent Barrett’s esophagus progression to high-grade dysplasia and esophageal adenocarcinoma? An updated meta-analysis. J Cancer Res Clin Oncol. 2021 Sep;147(9):2681–2691. doi: 10.1007/s00432-021-03544-3. Epub 2021 Feb 11. PMID: 33575855; PMCID: PMC11802092.
Open DOI Search in Google Scholar Open in PubMed Back to article
Jankowski JAZ, de Caestecker J, Love SB, Reilly G, Watson P, Sanders S, et al. Esomeprazole and aspirin in Barrett’s oesophagus (AspECT): a randomised factorial trial. Lancet. 2018 Aug 4;392(10145):400–408. doi: 10.1016/S0140-6736(18)31388-6. Epub 2018 Jul 26. Erratum in: Lancet. 2018 Dec 15;392(10164):2552. doi: 10.1016/S0140-6736(18)32970-2. PMID: 30057104; PMCID: PMC6083438.
Open DOI Search in Google Scholar Open in PubMed Back to article
Ito T, Igarashi H, Uehara H, Jensen RT. Pharmacotherapy of Zollinger-Ellison syndrome. Expert Opin Pharmacother. 2013 Feb;14(3):307–21. doi: 10.1517/14656566.2013.767332. Epub 2013 Jan 30. PMID: 23363383; PMCID: PMC3580316.
Open DOI Search in Google Scholar Open in PubMed Back to article
Ito T, Ramos-Alvarez I, Jensen RT. Long-Term Proton Pump Inhibitor-Acid Suppressive Treatment Can Cause Vitamin B12 Deficiency in Zollinger-Ellison Syndrome (ZES) Patients. Int J Mol Sci. 2024 Jul 2;25(13):7286. doi: 10.3390/ijms25137286. PMID: 39000391; PMCID: PMC11242121.
Open DOI Search in Google Scholar Open in PubMed Back to article
Scally B, Emberson JR, Spata E, Reith C, Davies K, Halls H, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. 2018 Apr;3(4):231–241. doi: 10.1016/S2468-1253(18)30037-2. Epub 2018 Feb 21. PMID: 29475806; PMCID: PMC5842491.
Open DOI Search in Google Scholar Open in PubMed Back to article
Gwee KA, Goh V, Lima G, Setia S. Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits. J Pain Res. 2018 Feb 14;11:361–374. doi: 10.2147/JPR.S156938. PMID: 29491719; PMCID: PMC5817415.
Open DOI Search in Google Scholar Open in PubMed Back to article
Kurlander JE, Barnes GD, Fisher A, Gonzalez JJ, Helminski D, Saini SD, et al. Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis. Am J Med. 2022 Oct;135(10):1231–1243.e8. doi: 10.1016/j.amjmed.2022.05.031. Epub 2022 Jun 7. PMID: 35679879; PMCID: PMC10031639.
Open DOI Search in Google Scholar Open in PubMed Back to article
Abrignani MG, Lombardo A, Braschi A, Renda N, Abrignani V. Proton pump inhibitors and gastro-protection in patients treated with antithrombotic drugs: A cardiologic point of view. World J Cardiol. 2023 Aug 26;15(8):375–394. doi: 10.4330/wjc.v15.i8.375. PMID: 37771340; PMCID: PMC10523195.
Open DOI Search in Google Scholar Open in PubMed Back to article
Lanas A, Gargallo CJ. Management of low-dose aspirin and clopidogrel in clinical practice: a gastrointestinal perspective. J Gastroenterol. 2015 Jun;50(6):626–37. doi: 10.1007/s00535-015-1038-3. Epub 2015 Jan 17. PMID: 25595209.
Open DOI Search in Google Scholar Open in PubMed Back to article
Tran-Duy A, Spaetgens B, Hoes AW, de Wit NJ, Stehouwer CD. Use of Proton Pump Inhibitors and Risks of Fundic Gland Polyps and Gastric Cancer: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2016 Dec;14(12):1706–1719.e5. doi: 10.1016/j.cgh.2016.05.018. Epub 2016 May 20. PMID: 27211501.
Open DOI Search in Google Scholar Open in PubMed Back to article
Martin FC, Chenevix-Trench G, Yeomans ND. Systematic review with meta-analysis: fundic gland polyps and proton pump inhibitors. Aliment Pharmacol Ther. 2016 Nov;44(9):915–925. doi: 10.1111/apt.13800. Epub 2016 Sep 15. PMID: 27634363.
Open DOI Search in Google Scholar Open in PubMed Back to article
Fossmark R, Jianu CS, Martinsen TC, Qvigstad G, Syversen U, Waldum HL. Serum gastrin and chromogranin A levels in patients with fundic gland polyps caused by long-term proton-pump inhibition. Scand J Gastroenterol. 2008 Jan;43(1):20–4. doi: 10.1080/00365520701561959. PMID: 18938772.
Open DOI Search in Google Scholar Open in PubMed Back to article
McCarthy DM. Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids-What Is the Relationship? Int J Mol Sci. 2020 Jan 19;21(2):662. doi: 10.3390/ijms21020662. PMID: 31963924; PMCID: PMC7014182.
Open DOI Search in Google Scholar Open in PubMed Back to article
Serbin MA, Guzauskas GF, Veenstra DL. Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis. J Manag Care Spec Pharm. 2016 Aug;22(8):939–47. doi: 10.18553/jmcp.2016.22.8.939. PMID: 27459657; PMCID: PMC6141192.
Open DOI Search in Google Scholar Open in PubMed Back to article
Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014 Apr;37(4):201–11. doi: 10.1007/s40264-014-0144-0. PMID: 24550106; PMCID: PMC3975086.
Open DOI Search in Google Scholar Open in PubMed Back to article
Guzman-Prado Y, Vita R, Samson O. Concomitant Use of Levothyroxine and Proton Pump Inhibitors in Patients with Primary Hypothyroidism: a Systematic Review. J Gen Intern Med. 2021 Jun;36(6):1726–1733. doi: 10.1007/s11606-020-06403-y. Epub 2021 Jan 19. PMID: 33469743; PMCID: PMC8175524.
Open DOI Search in Google Scholar Open in PubMed Back to article
Fotaki N, Klein S. Mechanistic understanding of the effect of PPIs and acidic carbonated beverages on the oral absorption of itraconazole based on absorption modeling with appropriate in vitro data. Mol Pharm. 2013 Nov 4;10(11):4016–23. doi: 10.1021/mp4003249. Epub 2013 Aug 29. PMID: 23947755.
Open DOI Search in Google Scholar Open in PubMed Back to article
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 Jul;137(1):80–7, 87.e1. doi: 10.1053/j.gastro.2009.03.058. Epub 2009 Apr 10. PMID: 19362552.
Open DOI Search in Google Scholar Open in PubMed Back to article
Lødrup AB, Reimer C, Bytzer P. Systematic review: symptoms of rebound acid hypersecretion following proton pump inhibitor treatment. Scand J Gastroenterol. 2013 May;48(5):515–22. doi: 10.3109/00365521.2012.746395. Epub 2013 Jan 14. PMID: 23311977.
Open DOI Search in Google Scholar Open in PubMed Back to article
Farrell B, Pottie K, Thompson W, Boghossian T, Pizzola L, Rashid FJ, et al. Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Can Fam Physician. 2017 May;63(5):354–364. PMID: 28500192; PMCID: PMC5429051.
Search in Google Scholar Open in PubMed Back to article
Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology. 2022 Apr;162(4):1334–1342. doi: 10.1053/j.gastro.2021.12.247. Epub 2022 Feb 17. PMID: 35183361.
Open DOI Search in Google Scholar Open in PubMed Back to article
Tran-Duy A, Connell NJ, Vanmolkot FH, Souverein PC, de Wit NJ, Stehouwer CDA, et al. Use of proton pump inhibitors and risk of iron deficiency: a population-based case-control study. J Intern Med. 2019 Feb;285(2):205–214. doi: 10.1111/joim.12826. Epub 2018 Sep 17. PMID: 30141278.
Open DOI Search in Google Scholar Open in PubMed Back to article
Nehra AK, Alexander JA, Loftus CG, Nehra V. Proton Pump Inhibitors: Review of Emerging Concerns. Mayo Clin Proc. 2018 Feb;93(2):240–246. doi: 10.1016/j.mayocp.2017.10.022. PMID: 29406201.
Open DOI Search in Google Scholar Open in PubMed Back to article
Kinoshita Y, Ishimura N, Ishihara S. Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use. J Neurogastroenterol Motil. 2018 Apr 30;24(2):182–196. doi: 10.5056/jnm18001. PMID: 29605975; PMCID: PMC5885718.
Open DOI Search in Google Scholar Open in PubMed Back to article
Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf. 2018 Nov 19;10:2042098618809927. doi: 10.1177/2042098618809927. PMID: 31019676; PMCID: PMC6463334.
Open DOI Search in Google Scholar Open in PubMed Back to article
Lespessailles E, Toumi H. Proton Pump Inhibitors and Bone Health: An Update Narrative Review. Int J Mol Sci. 2022 Sep 14;23(18):10733. doi: 10.3390/ijms231810733. PMID: 36142643; PMCID: PMC9504265.
Open DOI Search in Google Scholar Open in PubMed Back to article
Trifan A, Stanciu C, Girleanu I, Stoica OC, Singeap AM, Maxim R, et al. Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis. World J Gastroenterol. 2017 Sep 21;23(35):6500–6515. doi: 10.3748/wjg.v23.i35.6500. PMID: 29085200; PMCID: PMC5643276.
Open DOI Search in Google Scholar Open in PubMed Back to article
Su T, Lai S, Lee A, He X, Chen S. Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth. J Gastroenterol. 2018 Jan;53(1):27–36. doi: 10.1007/s00535-017-1371-9. Epub 2017 Aug 2. PMID: 28770351.
Open DOI Search in Google Scholar Open in PubMed Back to article
Al-Aly Z, Maddukuri G, Xie Y. Proton Pump Inhibitors and the Kidney: Implications of Current Evidence for Clinical Practice and When and How to Deprescribe. Am J Kidney Dis. 2020 Apr;75(4):497–507. doi: 10.1053/j.ajkd.2019.07.012. Epub 2019 Oct 10. PMID: 31606235.
Open DOI Search in Google Scholar Open in PubMed Back to article
Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, et al. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med. 2016 Feb;176(2):238–46. doi: 10.1001/jamainternmed.2015.7193. PMID: 26752337; PMCID: PMC4772730.
Open DOI Search in Google Scholar Open in PubMed Back to article

Authors

Metrics

Articles in this issue

DOI: https://doi.org/10.2478/bgbl-2026-0015 | Journal eISSN: 2956-6851 | Journal ISSN: 0373-174X

Journal RSS Feed

Language: English, Polish

Page range: 65 - 85

Submitted on: Aug 22, 2026

Accepted on: Aug 28, 2026

Published on: Sep 18, 2026

Published by: The Medical Library named after S. Konopka in Warsaw

In partnership with: Paradigm Publishing Services

Publication frequency: 2 issues per year

Keywords:

proton pump inhibitors (PPIs),

hypochlorhydria,

nutritional deficiencies,

Related subjects:

Biomedical engineering

© 2026 Paulina Głowacka, Aleksandra Bartkowska, Paulina Orzechowska, Gabriela Mastej-Witek, Alicja Okupniak, Gabriela Budziszewska, Mateusz Nieczyporuk, Aneta Dziurdź, Aleksandra Łupicka, Monika Ziemba, published by The Medical Library named after S. Konopka in Warsaw
This work is licensed under the Creative Commons Attribution-NonCommercial 4.0 License.

Volume 59 (2026): Issue 387 (December 2026)