Vitamin B12 (cobalamin) deficiency in gastroenterological diseases - review
DOI:
https://doi.org/10.12775/QS.2024.20.53131Keywords
Vitamin B12, cobalamin deficiency, gastrointestinal diseases, GERD, IBD, SIBOAbstract
Introduction: Vitamin B12 is a water-soluble vitamin found primarily in animal-derived products such as red meat, dairy, and eggs. An essential substance for its absorption is the intrinsic factor, produced by the parietal cells of the stomach. After absorption in the distal ileum, cobalamin acts as a coenzyme in DNA synthesis and the metabolism of fatty acids and homocysteine. In addition to its well-known influence on the nervous system, it has been associated with gastrointestinal diseases according to numerous authors.
Objective: The objective of this study is to gather and analyze literature regarding the associations between vitamin B12 deficiency and gastrointestinal diseases, including gastroesophageal reflux disease (GERD), gastritis, inflammatory bowel disease (IBD), small intestinal bacterial overgrowth (SIBO), and hepatitis C (HCV).
Materials and Methods: A literature review was conducted using the PubMed database with the following search terms: vitamin B12, cobalamin, deficiency, gastrointestinal diseases, GERD, IBD, SIBO, HCV.
Current Knowledge: Vitamin B12 deficiency can be caused by autoimmune factors, dietary insufficiencies, toxin exposure, and malabsorption disorders related to gastrointestinal diseases. Gastrointestinal conditions such as GERD and IBD can both lead to and be exacerbated by cobalamin deficiency. Furthermore, vitamin B12 deficiency may be worsened by prolonged use of proton pump inhibitors (PPIs) and Helicobacter pylori infection.
Conclusions: An adequate amount of vitamin B12 is crucial for gastrointestinal health. Deficiency can significantly impact the course and symptoms of many gastrointestinal diseases. Therefore, monitoring and supplementation of vitamin B12 should be an integral part of managing patients with gastrointestinal conditions.
References
Ankar A, Kumar A. Vitamin B12 Deficiency. In: StatPearls. Treasure Island (FL): StatPearls Publishing; October 22, 2022.
Guéant, Jean-Louis, et al. “Vitamin B12 Absorption and Malabsorption.” Vitamins and Hormones, vol. 119, 2022, pp. 241–274, pubmed.ncbi.nlm.nih.gov/35337622/, https://doi.org/10.1016/bs.vh.2022.01.016.
González HF, Visentin S. Micronutrients and neurodevelopment: An update. Micronutrientes y neurodesarrollo: actualización. Arch Argent Pediatr. 2016;114(6):570-575. doi:10.5546/aap.2016.eng.570
Vargas-Uricoechea H, Nogueira JP, Pinzón-Fernández MV, Agredo-Delgado V, Vargas-Sierra HD. Population Status of Vitamin B12 Values in the General Population and in Individuals with Type 2 Diabetes, in Southwestern Colombia. Nutrients. 2023;15(10):2357. doi:https://doi.org/10.3390/nu15102357
McLean E, de Benoist B, Allen LH. Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr Bull. 2008;29(2 Suppl):S38-S51. doi:10.1177/15648265080292S107
Vaqar S, Shackelford KB. Pernicious Anemia. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 8, 2023.
Ahmed A, Clarke JO. Proton Pump Inhibitors (PPI). In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 1, 2023.
RICHTER JE. Q: Should patients receiving long-term gastric acid inhibition therapy be evaluated for vitamin B12 deficiency? Cleveland Clinic Journal of Medicine. 2000;67(11):785-787. doi:https://doi.org/10.3949/ccjm.67.11.785
Marcuard SP. Omeprazole Therapy Causes Malabsorption of Cyanocobalamin (Vitamin B_12). Annals of Internal Medicine. 1994;120(3):211. doi:https://doi.org/10.7326/0003-4819-120-3-199402010-00006
Saltzman JR, Kemp JA, Golner BB, Pedrosa MC, Dallal GE, Russell RM. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. Journal of the American College of Nutrition. 1994;13(6):584-591. doi:https://doi.org/10.1080/07315724.1994.10718452
Mumtaz H, Ghafoor B, Saghir H, et al. Association of Vitamin B12 deficiency with long-term PPIs use: A cohort study. Annals of Medicine and Surgery. 2022;82:104762. doi:https://doi.org/10.1016/j.amsu.2022.104762
News briefs: Heartburn medicine users: Watch vitamin B12 levels. Harvard Health. Published March 1, 2014. https://www.health.harvard.edu/digestive-health/news-briefs-heartburn-medicine-users-watch-vitamin-b12-levels
Pereira R de S. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. Journal of Pineal Research. 2006;41(3):195-200. doi:https://doi.org/10.1111/j.1600-079x.2006.00359.x
Jurna I. [Analgesic and analgesia-potentiating action of B vitamins]. Schmerz (Berlin, Germany). 1998;12(2):136-141. doi:https://doi.org/10.1007/s004829800054
Suzuki K, Tanaka H, Ebara M, et al. Electrospun nanofiber sheets incorporating methylcobalamin promote nerve regeneration and functional recovery in a rat sciatic nerve crush injury model. Acta Biomater. 2017;53:250-259. doi:10.1016/j.actbio.2017.02.004
Okada K, Tanaka H, Temporin K, et al. Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model. Exp Neurol. 2010;222(2):191-203. doi:10.1016/j.expneurol.2009.12.017
Fu QG, Carstens E, Stelzer B, Markus Bernhard Zimmermann. B vitamins suppress spinal dorsal horn nociceptive neurons in the cat. Neuroscience Letters. 1988;95(1-3):192-197. doi:https://doi.org/10.1016/0304-3940(88)90655-6
Rahman M, Ferdoush K, Jahan K, et al. ANALGESIC EFFECTS OF VITAMIN B12: A RECENT UPDATE Journal of Global Biosciences. Journal of Global Biosciences. 2020;9(4):2020-7160. https://www.mutagens.co.in/jgb/vol.09/04/090416.pdf
Dholakia K. Vitamin B12 deficiency and gastric histopathology in older patients. World Journal of Gastroenterology. 2005;11(45):7078. doi:https://doi.org/10.3748/wjg.v11.i45.7078
de Groot CPGM, van Staveren WA. OLDER PEOPLE | Nutrition-Related Problems. Encyclopedia of Human Nutrition. Published online 2005:444-449. doi:https://doi.org/10.1016/b0-12-226694-3/00242-8
Cabrera de León A, Almeida González D, Almeida AA, et al. Factors associated with parietal cell autoantibodies in the general population. Immunol Lett. 2012;147(1-2):63-66. doi:10.1016/j.imlet.2012.06.004
Kulnigg-Dabsch S. Autoimmune gastritis. Wiener Medizinische Wochenschrift. 2016;166(13-14):424-430. doi:https://doi.org/10.1007/s10354-016-0515-5
Hershko C, Ronson A, Souroujon M, Maschler I, Heyd J, Patz J. Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. Blood. 2006;107(4):1673-1679. doi:https://doi.org/10.1182/blood-2005-09-3534
Pan Y, Liu Y, Guo H, et al. Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis. Nutrients. 2017;9(4):382. doi:https://doi.org/10.3390/nu9040382
Leddin D, Tamim H, Levy AR. Is folate involved in the pathogenesis of inflammatory bowel disease? Medical Hypotheses. 2013;81(5):940-941. doi:https://doi.org/10.1016/j.mehy.2013.08.025
Shanahan F. The microbiota in inflammatory bowel disease: friend, bystander, and sometime-villain. Nutrition Reviews. 2012;70:S31-S37. doi:https://doi.org/10.1111/j.1753-4887.2012.00502.x
Kellermayer R. Epigenetics and the Developmental Origins of Inflammatory Bowel Diseases. Canadian Journal of Gastroenterology. 2012;26(12):909-915. doi:https://doi.org/10.1155/2012/526408
Bermejo F, Algaba A, Guerra I, et al. Should we monitor vitamin B12 and folate levels in Crohn’s disease patients? Scandinavian Journal of Gastroenterology. 2013;48(11):1272-1277. doi:https://doi.org/10.3109/00365521.2013.836752
Headstrom PD, Rulyak SJ, Lee SD. Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn's disease. Inflamm Bowel Dis. 2008;14(2):217-223. doi:10.1002/ibd.20282
Yakut M, Ustün Y, Kabaçam G, Soykan I. Serum vitamin B12 and folate status in patients with inflammatory bowel diseases. Eur J Intern Med. 2010;21(4):320-323. doi:10.1016/j.ejim.2010.05.007
Erzin Y, Uzun H, Celik AF, Aydin S, Dirican A, Uzunismail H. Hyperhomocysteinemia in inflammatory bowel disease patients without past intestinal resections: correlations with cobalamin, pyridoxine, folate concentrations, acute phase reactants, disease activity, and prior thromboembolic complications. J Clin Gastroenterol. 2008;42(5):481-486. doi:10.1097/MCG.0b013e318046eab0
Filipsson S, Hultén L, Lindstedt G. Malabsorption of fat and vitamin B12 before and after intestinal resection for Crohn's disease. Scand J Gastroenterol. 1978;13(5):529-536. doi:10.3109/00365527809181760
Vagianos K, Bernstein CN. Homocysteinemia and B vitamin status among adult patients with inflammatory bowel disease: a one-year prospective follow-up study. Inflamm Bowel Dis. 2012;18(4):718-724. doi:10.1002/ibd.21785
Kuroki F, Iida M, Tominaga M, et al. Multiple vitamin status in Crohn's disease. Correlation with disease activity. Dig Dis Sci. 1993;38(9):1614-1618. doi:10.1007/BF01303168
Jayaprakash A, Creed T, Stewart L, et al. Should we monitor vitamin B12 levels in patients who have had end-ileostomy for inflammatory bowel disease?. Int J Colorectal Dis. 2004;19(4):316-318. doi:10.1007/s00384-003-0556-2
Lambert D, Benhayoun S, Adjalla C, et al. Crohn's disease and vitamin B12 metabolism. Dig Dis Sci. 1996;41(7):1417-1422. doi:10.1007/BF02088567
Akbulut S. An assessment of serum vitamin B12 and folate in patients with Crohn’s disease. Medicine. 2022;101(50):e31892. doi:https://doi.org/10.1097/md.0000000000031892
Oostenbrug LE, van Dullemen HM, te Meerman GJ, Jansen PL, Kleibeuker JH. Clinical outcome of Crohn's disease according to the Vienna classification: disease location is a useful predictor of disease course. Eur J Gastroenterol Hepatol. 2006;18(3):255-261. doi:10.1097/00042737-200603000-00005
Dyer NH, Dawson AM. Malnutrition and malabsorption in Crohn's disease with reference to the effect of surgery. Br J Surg. 1973;60(2):134-140. doi:10.1002/bjs.1800600211
Roblin X, Phelip JM, Genevois M, Ducros V, Bonaz B. Hyperhomocysteinaemia is associated with osteoporosis in patients with Crohn's disease. Aliment Pharmacol Ther. 2007;25(7):797-804. doi:10.1111/j.1365-2036.2007.03260.x
Vasilopoulos S, Saiean K, Emmons J, et al. Terminal ileum resection is associated with higher plasma homocysteine levels in Crohn's disease. J Clin Gastroenterol. 2001;33(2):132-136. doi:10.1097/00004836-200108000-00008
Battat R, Kopylov U, Byer J, et al. Vitamin B12 deficiency in inflammatory bowel disease. European Journal of Gastroenterology & Hepatology. 2017;29(12):1361-1367. doi:https://doi.org/10.1097/meg.0000000000000970
Duerksen DR, Fallows G, Bernstein CN. Vitamin B12 malabsorption in patients with limited ileal resection. Nutrition. 2006;22(11-12):1210-1213. doi:10.1016/j.nut.2006.08.017
Fromm H, Thomas PJ, Hofmann AF. Sensitivity and specificity in tests of distal ileal function: prospective comparison of bile acid and vitamin B 12 absorption in ileal resection patients. Gastroenterology. 1973;64(6):1077-1090.
Behrend C, Jeppesen PB, Mortensen PB. Vitamin B12 absorption after ileorectal anastomosis for Crohn's disease: effect of ileal resection and time span after surgery. Eur J Gastroenterol Hepatol. 1995;7(5):397-400.
BOOTH CC, MOLLIN DL. The site of absorption of vitamin B12 in man. Lancet. 1959;1(7062):18-21. doi:10.1016/s0140-6736(59)90979-1
Gasche C, Berstad A, Befrits R, et al. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis. 2007;13(12):1545-1553. doi:10.1002/ibd.20285
Roblin X, Phelip JM, Genevois M, Ducros V, Bonaz B. Hyperhomocysteinaemia is associated with osteoporosis in patients with Crohn's disease. Aliment Pharmacol Ther. 2007;25(7):797-804. doi:10.1111/j.1365-2036.2007.03260.x
Chowers Y, Sela BA, Holland R, Fidder H, Simoni FB, Bar-Meir S. Increased levels of homocysteine in patients with Crohn's disease are related to folate levels. Am J Gastroenterol. 2000;95(12):3498-3502. doi:10.1111/j.1572-0241.2000.03367.x
Beeken WL. Absorptive defects in young people with regional enteritis. Pediatrics. 1973;52(1):69-74.
Kennedy HJ, Callender ST, Truelove SC, Warner GT. Haematological aspects of life with an ileostomy. Br J Haematol. 1982;52(3):445-454. doi:10.1111/j.1365-2141.1982.tb03914.x
Fernandez-Banares F, Abad-Lacruz A, Xiol X, et al. Vitamin status in patients with inflammatory bowel disease. Am J Gastroenterol. 1989;84(7):744-748.
Khanna R, Shen B. Adverse metabolic sequelae following restorative proctocolectomy with an ileal pouch. Gastroenterol Hepatol (N Y). 2012 May;8(5):322-6. PMID: 22933864; PMCID: PMC3424428.
Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Colorectal Dis. 2007;9(6):562-566. doi:10.1111/j.1463-1318.2007.01117.x
Battat R, Kopylov U, Szilagyi A, et al. Vitamin B12 Deficiency in Inflammatory Bowel Disease. Inflammatory Bowel Diseases. Published online April 2014:1. doi:https://doi.org/10.1097/mib.0000000000000024
Carmel R. Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. Am J Clin Nutr. 2011;94(1):348S-358S. doi:10.3945/ajcn.111.013441
Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood. 2008;112(6):2214-2221. doi:10.1182/blood-2008-03-040253
Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth: a comprehensive review. Gastroenterol Hepatol (N Y). 2007;3(2):112-122.
Wexler AG, Schofield WB, Degnan PH, Folta-Stogniew E, Barry NA, Goodman AL. Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins. Elife. 2018;7:e37138. Published 2018 Sep 18. doi:10.7554/eLife.37138
Chitti L, Cummins A. COBALAMIN DEFICIENCY and SMALL BOWEL BACTERIAL OVERGROWTH: A COMMON ASSOCIATION. Journal of Gastroenterology and Hepatology. 2001;16:22-22. doi:https://doi.org/10.1111/j.1440-1746.2001.ca01-22.x
BOOTH CC, HEATH J. The effect of E. coli on the absorption of vitamin B12. Gut. 1962;3(1):70-73. doi:10.1136/gut.3.1.70
Madigan KE, Bundy R, Weinberg RB. Distinctive Clinical Correlates of Small Intestinal Bacterial Overgrowth with Methanogens. Clinical Gastroenterology and Hepatology. 2022;20(7):1598-1605.e2. doi:https://doi.org/10.1016/j.cgh.2021.09.035
Lott WB, Takyar SS, Tuppen J, et al. Vitamin B12 and hepatitis C: Molecular biology and human pathology. Proceedings of the National Academy of Sciences. 2001;98(9):4916-4921. doi:https://doi.org/10.1073/pnas.081072798
Partearroyo T, Úbeda N, Montero A, Achón M, Varela-Moreiras G. Vitamin B(12) and folic acid imbalance modifies NK cytotoxicity, lymphocytes B and lymphoprolipheration in aged rats. Nutrients. 2013 Nov 26;5(12):4836-48. doi: 10.3390/nu5124836. PMID: 24288024; PMCID: PMC3875921.
Rocco A, Compare D, Coccoli P, et al. Vitamin B12 supplementation improves rates of sustained viral response in patients chronically infected with hepatitis C virus. Gut. 2013;62(5):766-773. doi:10.1136/gutjnl-2012-302344
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Piotr Zatyka, Dominika Opala, Adam Słomczyński, Agata Pawłowska, Michal Rabneda, Dobromiła Osuch, Piotr Janik
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 132
Number of citations: 0
