Vitamin B12 Deficiency in consumption of Metformin and Proton Pump Inhibitors
DOI:
https://doi.org/10.22517/25395203.24762Keywords:
Vitamin B12, Metformin, Proton Pump Inhibitors, Deficiency, Adverse effects, Drug InteractionsAbstract
The spectrum of diseases associated with vitamin B12 deficiency is broad, ranging from no symptoms to malabsorption syndrome, spinal cord injury, neurological symptoms accompanied by paresthesia, myelopathy, or neuropathy. There is suggestive evidence that long-term use of proton pump inhibitors (PPIs) can lower serum levels of vitamin B12. Additionally, previous studies have associated vitamin B12 deficiency with high doses consumption of metformin; however, the mechanism in which this occurs is not clear. An additive association between the administration of proton pump inhibitors / Histamine H2 receptor antagonists, and metformin has been described, which suggest that these promote vitamin B12 malabsorption. Both categories of drugs are widely used, in many cases without a prescription, and its use should not be overlooked. When clinically indicated, their use should be monitored in view of the possibility of vitamin B12 malabsorption and its consequences. This article aims to review general aspects of vitamin B12 and delve into the state of the art regarding vitamin B12 deficiency in patients with metformin and / or proton pump inhibitor consumption.
Downloads
References
Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol. 2004;57(4):422–8.
Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149–60. 3. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cya-nocobalamin (vitamin B12). Ann Intern Med. 1994;120(3):211–5.
Herszényi L, Bakucz T, Barabás L, Tulassay Z. Pharmacological Approach to Gastric Acid Suppression: Past, Present, and Future. Dig Dis. 2020;38(2):104–11.
Hirschowitz BI, Worthington J, Mohnen J. Vitamin B12 deficiency in hypersecretors du-ring long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther. 2008;27(11):1110–21.
Dharmarajan TS, Kanagala MR, Murakonda P, Lebelt AS, Norkus EP. Do Acid-Lowering Agents Affect Vitamin B12 Status in Older Adults? J Am Med Dir Assoc. 2008;9(3):162–7.
Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Topolski R. The prevalence of vitamin B12 deficiency in patients with type 2 diabetes: A cross-sectional study. J Am Board Fam Med. 2009;22(5):528–34.
Reinstatler L, Qi YP, Williamson RS, Garn J V., Oakley GP. Association of biochemical B 12 deficiency with metformin therapy and vitamin B 12 supplements: The National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care. 2012;35(2):327–33.
Tomkin GH, Hadden DR, Weaver JA, Montgomery DAD. Vitamin-B12 Status of Patients on Long-term Metformin Therapy. Br Med J. 1971;2(5763):685.
Hermann LS, Nilsson B, Wettre S. Vitamin B12 status of patients treated with metformin: A cross-sectional cohort study. Br J Diabetes Vasc Dis. 2004;4(6):401–6.
Leung S, Mattman A, Snyder F, Kassam R, Meneilly G, Nexo E. Metformin induces re-ductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabe-tic patients. Clin Biochem [Internet]. 2010;43(9):759–60. Available from: http://dx.doi.org/10.1016/j.clinbiochem.2010.02.011
Nervo M, Lubini A, Raimundo F, Moreira Faulhaber GA, Leite C, Moura Fischer L, et al. Vitamin B12 in metformin-treated diabetic patients: a cross-sectional study in Brazil. Rev Assoc Med Bras. 2011;57(1):46–9.
De Groot-Kamphuis et al. Vitamin B12 Deficiency Among Type 2 Diabetes Patients Using Metformin. Neth J Med. 2013;71(7):386–90.
Ko SH, Ko SH, Ahn YB, Song KH, Han K Do, Park YM, et al. Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes. J Korean Med Sci. 2014;29(7):965–72.
Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guéant JL, Miller JW, et al. Vitamin B12 deficiency. Nat Rev Dis Prim. 2017;3.
Salinas M, Flores E, López-Garrigós M, Leiva-Salinas C. Vitamin B12 deficiency and cli-nical laboratory: Lessons revisited and clarified in seven questions. Int J Lab Hematol. 2018;40(December 2017):83–8.
Stabler SP. Vitamin B 12 Deficiency. 2013;5.
Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobala-min and folate disorders. Br J Haematol. 2014;166(4):496–513.
Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014;349(Septem-ber):1–10.
Martinho KO, Tinôco ALA, Ribeiro AQ. Prevalencia y factores asociados a la deficiencia de vitamina B12 en ancianos de Viçosa/Mg, Brasil. Nutr Hosp. 2015;32(5):2162–8.
Regino WO. Déficit de vitamina B 12 asociado con el consumo de inhibidores de la bomba de protones Vitamin B 12 Deficiency Associated with Consumption of Proton Pump Inhi-bitors. 2017;197–201.
Marín JDM, Riveros SCH, Tovar MHR. Niveles de vitamina B12 en pacientes colombianos con gastritis crónica atrófica. Rev Colomb Gastroenterol. 2010;25(3):261–4. 23.
Ogawa R, Echizen H. Drug-drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet. 2010;49(8):509–33.
Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhi-bitors: An update. Drug Saf. 2014;37(4):201–11.
Budha NR, Frymoyer A, Smelick GS, Jin JY, Yago MR, Dresser MJ, et al. Drug absorption interactions between oral targeted anticancer agents and PPIs: Is pH-dependent solubility the achilles heel of targeted therapy. Clin Pharmacol Ther. 2012;92(2):203–13.
Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: An update. Ann Intern Med. 2002;137(1):25–33.
Shu Y, Brown C, Castro RA, Shi RJ, Lin ET, Owen RP, et al. Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin Pharmacol Ther. 2008;83(2):273–80.
Song IS, Shin HJ, Shim EJ, Jung IS, Kim WY, Shon JH, et al. Genetic variants of the or-ganic cation transporter 2 influence the disposition of metformin. Clin Pharmacol Ther. 2008;84(5):559–62.
Chen Y, Li S, Brown C, Cheatham S, Castro RA, Leabman MK, et al. Effect of genetic varia-tion in the organic cation transporter 2 on the renal elimination of metformin. Pharmaco-genet Genomics. 2009;19(7):497–504.
I CPD, Oliveira A, Ii R, Fernanda M, Castellar M, Iii P, et al. Prevalence of vitamin B12 defi-ciency in type 2 diabetic patients using metformin : a cross-sectional study Prevalência de deficiência de vitamina B12 em pacientes diabéticos do tipo 2. 2016;134(6):473–9.
Wile DJ, Toth C. Association of metformin, elevated homocysteine, and methylmalo-nic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care. 2010;33(1):156–61.
Liu Q, Li S, Quan H, Li J. Vitamin B12 status in metformin treated patients: Systematic review. PLoS One. 2014;9(6):8–13.
Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: A guide for the pri-mary care physician. Arch Intern Med. 1999;159(12):1289–98.
Caspary WF, Zavada I, Reimold W, Deuticke U, Emrich D, Willms B. Diabetologia. 1977;193:187–93.
Bauman WA, SHAW S, JAYATILLEKE E, SPUNGEN AM, HERBERT V. Increased Intake of Calcium Reverses Vitamin B 12 Malabsorption Induced by. Clin care/education/nutrition. 2000;23(9):1227–31.
Adams JF, Clark JS, Ireland JT, Kesson CM, Watson WS. Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia. 1983;24(1):16–8.
DeFronzo RA GA. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med. 1995;333(4):541–9.
De Jager J, Kooy A, Lehert P, Wulffelé MG, Van Der Kolk J, Bets D, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: Ran-domised placebo controlled trial. BMJ. 2010;340(7757):1177.
Hugo Sánchez R, Masferrer D, Lera L, Arancibia E, Ángel B, Albala C. Déficit de vitamina B12 asociado con altas dosis de metformina en adultos mayores diabéticos. Nutr Hosp. 2014;29(6):1394–400.
Ting RZW, Szeto CC, Chan MHM, Ma KK, Chow KM. Risk factors of vitamin B12 deficien-cy in patients receiving metformin. Arch Intern Med. 2006;166(18):1975–9.
Carmel R. C Urrent C Oncepts in. New York. 2000;(1):357–75.
Ruscin JM, Lee R, Ii P, Valuck RJ. Vitamin B 12 Deficiency Associated with Histamine 2 -Receptor Antagonists and a Proton-Pump Inhibitor CONCLUSIONS : 2002;36.
Long AN, Atwell CL, Yoo W, Solomon SS. Vitamin B12 deficiency associated with concomi-tant metformin and proton pump inhibitor use. Diabetes Care. 2012;35(12).
Downloads
-
Vistas(Views): 1120
- PDF (Español (España)) Descargas(Downloads): 479
- PDF Descargas(Downloads): 60
Published
Versions
How to Cite
Issue
Section
License
Cesión de derechos y tratamiento de datos
La aceptación de un artículo para su publicación en la Revista Médica de Risaralda implica la cesión de los derechos de impresión y reproducción, por cualquier forma y medio, del autor a favor de Facultad de Ciencias de la Salud de la Universidad Tecnológica de Pereira. 1995-2018. Todos los derechos reservados ®
por parte de los autores para obtener el permiso de reproducción de sus contribuciones. La reproducción total o parcial de los trabajos aparecidos en la Revista Médica de Risaralda, debe hacerse citando la procedencia, en caso contrario, se viola los derechos reservados.
Asimismo, se entiende que los conceptos y opiniones expresados en cada trabajo son de la exclusiva responsabilidad del autor, sin responsabilizarse ni solidarizarse, necesariamente, ni la redacción, ni la editorial.
Es responsabilidad de los autores poder proporcionar a los lectores interesados copias de los datos en bruto, manuales de procedimiento, puntuaciones y, en general, material experimental relevante.
Asimismo, la Dirección de la revista garantiza el adecuado tratamiento de los datos de carácter personal