Main Article Content
Abstract
Background
Proton pump inhibitors (PPI's) remain the superior choice worldwide in antisecretory therapy in the evidence-based treatment of upper gastrointestinal disorders including gastroesophageal reflux disease, erosive esophagitis, dyspepsia and peptic ulcer disease. Nonjudicious use of PPIs creates both preventable financial as well as medical concerns. PPIs have been associated with an increased risk of vitamin and mineral deficiencies.
Objective
To study the effect of Proton Pump Inhibitors (PPI’s) effect on vitamin D levels.
Design
A study To evaluate the effect of PPI's on vitamin D levels in patients who were treated for vitamin D deficiency.
Duration
February 2017 to July 2017.
Setting
Participants
One hundred patients treated for vitamin D deficiency at
Methods
100 patients were included in the study. 40 patients were taking PPI at the time and during the study. 60 patients were not on any medications. Results were assessed by improvement in repeat serum 25(OH) vitamin D levels obtained after replacement therapy. Demographics, vitamin D levels, medical history and medication lists were obtained. Percentage increase in 25‐OH vitamin D levels from baseline was considered the end point. Results were compared between the two groups. Statistics include unpaired t-test done to compare two groups of subjects and p value less than 0.05 was considered statistically significant.
Results
The mean improvement in 25(OH) vitamin D levels for the “PPI” group was 40.9% with a mean raw difference of 9.1. “No PPI” group demonstrated a mean improvement of 59.1 % with a mean difference of 13.8. The improvement in 25(OH) vitamin D levels in the "no PPI" cohort was 64.2% greater than those taking a PPI.
Conclusion
PPIs are associated with an increased risk of vitamin D deficiency impacting vitamin D metabolism.
Keywords
Article Details
References
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- [2]. Sasaki T, Nakayama K, Yasuda H, Yoshida M, Asamura T, Ohrui T, et al. A randomized, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients. J Am Geriatr Soc. 57(8), 2009, 1453–1457.
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- [6]. Dimango E, Walker P, Keating C, Berdella M, Robinson N, Langfelderschwind E, et al. Effect of esomeprazole versus placebo on pulmonary exacerbations in cystic fibrosis. BMC Pulm Med. 14(1), 2014, 1–7. doi: 10.1186/1471-2466-14-21.
- [7]. Kim YJ, Lee JS, Hong KS, Chung JW, Kim JH, Hahm KB. Novel application of proton pump inhibitor for the prevention of colitis-induced colorectal carcinogenesis beyond acid suppression. Cancer Prev Res (Philadelphia, Pa). 3(8), 2010, 963–974. doi: 10.1158/1940-6207.CAPR-10-0033.
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- [9]. Yeo M, Kim DK, Park HJ, Cho SW, Cheong JY, Lee KJ. Blockage of intracellular proton extrusion with proton extrusions with proton pump inhibitor induces apoptosis in gastric cancer. Cancer Sci. 99(1), 2008, 185.
- [10]. Marino ML, Fais S, Djavaheri-Mergny M, Villa A, Meschini S, Lozupone F, et al. Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells. Cell Death Dis. 1, 2010, e87. doi: 10.1038/cddis.2010.67.
- [11]. Udelnow A, Kreyes A, Ellinger S, Landfester K, Walther P, Klapperstueck T, et al. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. PLoS One. 6(5), 2011, e20143. doi: 10.1371/journal.pone.0020143.
- [12]. Canitano A, Iessi E, Spugnini EP, Federici C, Fais S. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma. Cancer Lett. 376(2), 2016, 278–283. doi: 10.1016/j.canlet.2016.04.015.
- [13]. Lee YY, Jeon HK, Hong JE, Cho YJ, Ryu JY, Choi JJ, et al. Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant epithelial ovarian carcinoma. Oncotarget. 6(33), 2015, 35040–35050.
- [14]. Spugnini EP, Buglioni S, Carocci F, Francesco M, Vincenzi B, Fanciulli M, et al. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors. J Transl Med. 12, 2014, 225. doi: 10.1186/s12967-014-0225-y.
- [15]. Wang BY, Zhang J, Wang JL, Sun S, Wang ZH, Wang LP, et al. Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J ExperimenClin Cancer Res. 34, 2015, 85. doi: 10.1186/s13046-015-0194-x.
- [16]. Henry E., Carswell A., Wirz A., Fyffe V., McColl K. Proton pump inhibitors reduce the bioavailability of dietary Vitamin C. Aliment PharmacolTher 22, 2005, 539–545
- [17]. Hirschowitz B., Worthington J., Mohnen J. Vitamin B12 deficiency in hypersecretors during long-term acid suppression with proton pump inhibitors. Aliment PharmacolTher 27, 2008, 1110–1121
- [18]. Hoorn E., van der Hoek J., de Man R., Kuipers E., Bolwerk C., Zietse R. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis 56, 2010, 112–116
- [19]. Ho P., Maddox T., Wang L., Fihn S., Jesse R., Peterson E., et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 301, 2009, 937–944
- [20]. Howden C. Vitamin B12 levels during prolonged treatment with proton pump inhibitors. J ClinGastroenterol 30, 2000, 29–33.
- [21]. Hutchinson C., Geissler C., Powell J., Bomford A Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut 56, 2007, 1291–1295.
- [22]. Inadomi J. On-demand and intermittent therapy for gastro-esophageal reflux disease. Pharmacoeconomics 20, 2002, 565–576.
References
[1]. Long J, Wright E, Molesti E, Temperton N, Barclay W. Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry. F1000Research. 4, 2015, 30.
[2]. Sasaki T, Nakayama K, Yasuda H, Yoshida M, Asamura T, Ohrui T, et al. A randomized, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients. J Am Geriatr Soc. 57(8), 2009, 1453–1457.
[3]. Vanfleteren LE, Spruit MA, Wouters EF, Franssen FM. Management of chronic obstructive pulmonary disease beyond the lungs. Lancet Respir Med. 4(11), 2016, 911–924. doi: 10.1016/S2213-2600(16)00097-7.
[4]. Sasaki T, Nakayama K, Yasuda H, Yamaya M. A new strategy with proton pump inhibitors for the prevention of acute exacerbations in COPD. TherAdvRespir Dis. 5(2), 2011, 91–103. doi: 10.1177/1753465810392264.
[5]. Becker JC, Grosser N, Waltke C, Schulz S, Erdmann K, Domschke W, et al. Beyond gastric acid reduction: proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells. BiochemBiophys Res Commun. 2006;345(3):1014–1021. doi: 10.1016/j.bbrc. 04, 2006, 170.
[6]. Dimango E, Walker P, Keating C, Berdella M, Robinson N, Langfelderschwind E, et al. Effect of esomeprazole versus placebo on pulmonary exacerbations in cystic fibrosis. BMC Pulm Med. 14(1), 2014, 1–7. doi: 10.1186/1471-2466-14-21.
[7]. Kim YJ, Lee JS, Hong KS, Chung JW, Kim JH, Hahm KB. Novel application of proton pump inhibitor for the prevention of colitis-induced colorectal carcinogenesis beyond acid suppression. Cancer Prev Res (Philadelphia, Pa). 3(8), 2010, 963–974. doi: 10.1158/1940-6207.CAPR-10-0033.
[8]. De Milito A, Iessi E, Logozzi M, Lozupone F, Spada M, Marino ML, et al. Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species. Can Res. 67(11), 2007, 5408–5417. doi: 10.1158/0008-5472.CAN-06-4095.
[9]. Yeo M, Kim DK, Park HJ, Cho SW, Cheong JY, Lee KJ. Blockage of intracellular proton extrusion with proton extrusions with proton pump inhibitor induces apoptosis in gastric cancer. Cancer Sci. 99(1), 2008, 185.
[10]. Marino ML, Fais S, Djavaheri-Mergny M, Villa A, Meschini S, Lozupone F, et al. Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells. Cell Death Dis. 1, 2010, e87. doi: 10.1038/cddis.2010.67.
[11]. Udelnow A, Kreyes A, Ellinger S, Landfester K, Walther P, Klapperstueck T, et al. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. PLoS One. 6(5), 2011, e20143. doi: 10.1371/journal.pone.0020143.
[12]. Canitano A, Iessi E, Spugnini EP, Federici C, Fais S. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma. Cancer Lett. 376(2), 2016, 278–283. doi: 10.1016/j.canlet.2016.04.015.
[13]. Lee YY, Jeon HK, Hong JE, Cho YJ, Ryu JY, Choi JJ, et al. Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant epithelial ovarian carcinoma. Oncotarget. 6(33), 2015, 35040–35050.
[14]. Spugnini EP, Buglioni S, Carocci F, Francesco M, Vincenzi B, Fanciulli M, et al. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors. J Transl Med. 12, 2014, 225. doi: 10.1186/s12967-014-0225-y.
[15]. Wang BY, Zhang J, Wang JL, Sun S, Wang ZH, Wang LP, et al. Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J ExperimenClin Cancer Res. 34, 2015, 85. doi: 10.1186/s13046-015-0194-x.
[16]. Henry E., Carswell A., Wirz A., Fyffe V., McColl K. Proton pump inhibitors reduce the bioavailability of dietary Vitamin C. Aliment PharmacolTher 22, 2005, 539–545
[17]. Hirschowitz B., Worthington J., Mohnen J. Vitamin B12 deficiency in hypersecretors during long-term acid suppression with proton pump inhibitors. Aliment PharmacolTher 27, 2008, 1110–1121
[18]. Hoorn E., van der Hoek J., de Man R., Kuipers E., Bolwerk C., Zietse R. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis 56, 2010, 112–116
[19]. Ho P., Maddox T., Wang L., Fihn S., Jesse R., Peterson E., et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 301, 2009, 937–944
[20]. Howden C. Vitamin B12 levels during prolonged treatment with proton pump inhibitors. J ClinGastroenterol 30, 2000, 29–33.
[21]. Hutchinson C., Geissler C., Powell J., Bomford A Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut 56, 2007, 1291–1295.
[22]. Inadomi J. On-demand and intermittent therapy for gastro-esophageal reflux disease. Pharmacoeconomics 20, 2002, 565–576.