Hypervitaminosis B12 - a new marker and predictor of prognostically unfavorable diseases


Cite item

Full Text

Abstract

A high serum vitamin B12 level (hypercobalaminemia) is a underestimated anomaly. Clinically, it can be paradoxically accompanied by signs of deficiency, which are related to defects in tissue uptake of vitamin B12. The increase in the level of serum cobalamin occurs mainly in serious diseases that require early diagnosis: hemoblastosis, liver and kidney diseases, etc. This review presents data on the metabolism of vitamin B12 and the potential significance of increasing its level as a marker for the early diagnosis of these diseases.

About the authors

V I Podzolkov

Sechenov First Moscow State Medical University (Sechenov University)

д.м.н., проф., зав. каф. факультетской терапии №2 лечебного факультета, директор клиники факультетской терапии УКБ №4; ORCID: 0000-0002-0758-5609 Moscow, Russia

N A Dragomiretskaya

Sechenov First Moscow State Medical University (Sechenov University)

Email: dragomiretskaya_natalia@mail.ru
к.м.н., доц. каф. факультетской терапии №2 лечебного факультета; тел: +7(925)519-56-50; e-mail: dragomiretskayanatalia@mail.ru; ORCID: 0000-0002-6531-6255 Moscow, Russia

O Ts Dambaeva

Sechenov First Moscow State Medical University (Sechenov University)

клинический ординатор каф. факультетской терапии №2 лечебного факультета Moscow, Russia

S T Auvinen

Sechenov First Moscow State Medical University (Sechenov University)

студентка Moscow, Russia

I D Medvedev

Sechenov First Moscow State Medical University (Sechenov University)

к.м.н., доц. каф. факультетской терапии №2 лечебного факультета; ORCID: 0000-0003-4210-2841 Moscow, Russia

References

  1. Chiche L, Jean R, Romain F, Roux F, et al. Implications cliniques de la decouverte d’une hypervitaminemie B12 en medecine interne. Rev Med Interne. 2008;29:187-94. doi: 10.1016/j.revmed.2007.07.007
  2. Arendt J.F.B, Nexo E. Cobalamin related parameters and disease patterns in patients with increased serum cobalamin levels. PLoS ONE. 2012;9:e45979. doi: 10.1371/journal.pone.0045979
  3. Deneuville T, Mario N, Tiev K.P, Toledano C, Josselin-Mahr L, Gain M, et al. Concentration plasmatique elevee de la vitamin B12: un indicateur des maladies hepatiquesou tumorales? Rev Med Interne. 2009;30(Suppl. 2):S73. doi: 10.1016/j.revmed.2012.10.006
  4. Carmel R, Vasireddy H, Aurangzeb I, George K. High serum cobalamin levels in the clinical setting - clinical associations and holo - transcobalamin changes. Clin Lab Haematol. 2001;23:365-71. doi: 10.1046/j.1365-2257.2001.00134.x
  5. Chiche L, Mancini J, Arlet J.B, investigateurs. De l’etude BDOSE. Hypervitamineґmies B12 en medecine interne: resultats de l’etude BDOSE. Rev Med Interne. 2009;30(Suppl. 4):S377. doi: 10.1016/j.revmed.2009.10.142
  6. Воробьева Л.И. Пропионовокислые бактерии и образование витамина В12. М.: МГУ, 1986.
  7. Herbert V. Recommended dietary intakes (RDI) of vitamin B12 in humans. Am J Clin Nutr. 1987;45:671-8. doi: 10.1093/ajcn/45.4.671
  8. Fenech M.F, Dresoti I.E, Rinaldi J.R. Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men. Carcinogenesis. 1997;18:1329-36. doi: 10.1093/carcin/18.7.1329
  9. Kapiszewska M, Kalemba M, Wojciech U, Milewicz T. Uracil misincorporation into DNA of leukocytes of young women with positive folate balance depends on plasma vitamin B12 concentrations and methylenetetrahydrofolate reductase polymorphisms. A pilot study. J Nutr Biochem. 2005;16:467-78. doi: 10.1016/j.jnutbio.2005.01.018
  10. Solomon L.R. Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment. Blood Rev. 2007;21:113-30. doi: 10.1016/j.blre.2006.05.001
  11. Whipple G.H, Hooper C.W, Robscheit F.S. Blood regeneration following anemia. IV. Influence of meat, liver, and various extractives, alone or combined with standard diets. Am J Physiol. 1920;53:236-62. doi: 10.1152/ajplegacy.1920.53.2.236
  12. Minot G.R, Murphy W.P. Treatment of pernicious anemia by special diet. JAMA. 1926;87:470-6. doi: 10.1001/jama.1926.02680070016005
  13. Smith E.L. Purification of anti - pernicious anemia factors from liver. Nature. 1948;161:638-9. doi: 10.1038/161638a0
  14. Rickes E.L, Brink N.G, Koniuszy F.R, Wood T.R, Folkers K. Crystalline vitamin B12. Science. 1948;107:396-7. doi: 10.1126/science.107.2781.396
  15. Castle W.B. Observations on etiologic relationship of achylia gastrica to pernicious anemia. I. Effect of administration to patients with pernicious anemia of contents of normal human stomach recovered after ingestion of beef muscle. Am J Med Sci. 1929;178:748-64.
  16. Castle W.B, Heath C.W, Strauss M.B, Heinle R.W. Observations on etiologic relationship of achylia gastrica to pernicious anemia.VI. Site of interaction of food (extrinsic) and gastric (intrinsic) factors: failure of in vitro incubation to produce thermostable hematopoietic principle. Am J Med Sci. 1937;294:618-25.
  17. Gärsbeck R. Fractionation of human gastric juice and saliva employing starch electrophoresis. Gastroenterologia. 1955;84:99-102. doi: 10.1159/000200176
  18. Kozyraki R, Fyfe J, Kristiansen M, Gerdes C, et al. The intrinsic factor - vitamin B12 receptor, cubilin, is a high - affinity apolipoprotein A-I receptor facilitating endocytosis of high - density lipoprotein. Nat Med. 1999;5:656-61. doi: 10.1038/9504
  19. Tanner S.M, Aminoff M, Wright F.A, Liyanarachchi S, et al. Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia. Nat Genet. 2003;33:426-9. doi: 10.1038/ng1098
  20. Fyfe F.C, Madsen M, Hojrup P, Christensen E.I, et al. The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood. 2004;103:1573-9. doi: 10.1182/blood-2003-08-2852
  21. Gärsbeck R. Imerslund-Gärsbeck syndrome (selective vitamin B(12) malabsorption with proteinuria). Orphanet J Rare Dis. 2006;1:17. doi: 10.1186/1750-1172-1-17
  22. André S.E, Serraj K, Zhu J, Vermorken A.J.M. The pathophysiology of elevated vitamin B12 in clinical practice. Q J Med. 2013;106:505-15 doi: 10.1093/qjmed/hct051
  23. Ermens A.A, Vlasveld L.T, Lindemans J. Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem. 2003;36:585-90. doi: 10.1016/j.clinbiochem.2003.08.004
  24. Lindemans J, Kroes A.C.M, van Geel J, Van Kapel J, et al. Uptake of transcobalamin II - bound cobalamin by HL-60 cells: effects of differentiation induction. J Exp Cell Res. 1989;184:449-60. doi: 10.1016/0014-4827(89)90343-1
  25. Nicolas J.P, Gueant J.L, Fremont S. Cobalamin binding glycoproteins. In: Bhatt H.R, James V.H.T, Besser G.M, Bottazzo G.F, Keen H, eds. Advances in Thomas Addison’s Diseases. Bristol: Journal of Endocrinology Ltd., 1994. P. 253-67.
  26. Gärsbeck R. Intrinsic factor and the other vitamin B12 transport proteins. Prog Hematol. 1969;6:233-60.
  27. Burger R.L, Mehlman C.S, Allen R.H. Human plasma R-type vitamin B12-binding proteins. I. Isolation and characterization of transcobalamin I, transcobalamin III and the normal granulocyte vitamin B12-binding protein. J Biol Chem. 1975;250:7700-6.
  28. Zittoun J. Cobalamins: an update of fundamental and clinical data. Hematologie. 1996;2:119-29.
  29. Li N, Seetharam S, Lindemans J, Alpers D.H, Arwert F, Seetharam B. Isolation and sequence analysis of variant forms of human transcobalamin II. Biochim Biophys Acta. 1993;1172:21-30. doi: 10.1016/0167-4781(93)90264-E
  30. Павлов Ч.В., Дамулин И.В., Шульпекова О.Ю., Андреев Е.А. Неврологические расстройства при дефиците витамина В12. Терапевтический архив. 2019;91(4):122-9. doi: 10.26442/00403660.2019.04.000116
  31. Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr. 2003;78:131-6. doi: 10.1093/ajcn/78.1.131
  32. Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med. 2000;51:357-75. doi: 10.1146/annurev.med.51.1.357
  33. Solomon L.R. More on failures of cobalamin assays in pernicious anemia. N Engl J Med. 2012;367:1570. doi: 10.1056/NEJMc1210169
  34. Baker H, Leevy C.B, De Angelis B, Frank O, Baker E.R. Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue in alcoholics with liver disease. J Am Coll Nutr. 1998; 17:235-8. doi: 10.1080/07315724.1998.10718752
  35. Kanazawa S, Herbert V. Total corrinoid, cobalamin and cobalamin analogue levels may be normal in serum despite cobalamin in liver depletion in patients with alcoholism. Lab Invest. 1985;53:108-10.
  36. Hagelskjaer L, Rasmussen K. Methylmalonic acid concentration in serum not affected in hepatic disease. Clin Chem. 1992;38:493-5
  37. Carmel R, Eisenberg L. Serum vitamin B12 and transcobalamin abnormalities in patients with cancer. Cancer. 1977;40:1348-53. doi: 10.1002/1097-0142(197709)40:3%3C1348::AID-CNCR2820400352% 3E3.0.CO;2-Q
  38. Carmel R. Extreme elevation of serum transcobalamin I in patients with metastatic cancer. N Engl J Med. 1975;292:282-4. doi: 10.1056/NEJM197502062920603
  39. Gimsing P. Cobalamin metabolism in chronic myelogenous leukemia. Dan Med Bull. 1998;45:459-79.
  40. Fremont S, Chamigneulle B, Gerard P, Felden P, et al. Blood transcobalamin levels in malignant hepatoma. Tumor Biol. 1991;12:353-9. doi: 10.1159/000217736
  41. Gimsing P, Hippe E. Increased concentration of transcobalamin I in a patient with metastatic carcinoma of the breast. Scand J Haematol. 1978;21:243-9. doi: 10.1111/j.1600-0609.1978.tb00359.x
  42. Carmel R, Tatsis B, Baril L. Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood. Blood. 1977;49:987-1000.
  43. Bowen R.A, Drake S.K, Vanjani R, Huey E.D, et al. Markedly increased vitamin B12 concentrations attributable to IgG-IgM-vitamin B12 immune complexes. Clin Chem. 2006;52:2107-14. doi: 10.1373/clinchem.2006.073882
  44. Schwartz M, Bastrup-Madsen P. A new vitamin B12 binding protein in serum causing excessively high serum vitamin B12 values. Scand J Haematol. 1968;5:35-40. doi: 10.1111/j.1600-0609.1968.tb01715.x
  45. André S.E, Henoun Loukili N, Noel E, Maloisel F, et al. Oral cobalamin (daily dose of 1000 mg) therapy for the treatment of patients with pernicious anemia. An open label study of 10 patients. Curr Ther Res. 2005;66:13-22. doi: 10.1016/j.curtheres.2005.02.001
  46. Kane S.P, Murray-Lyon I.M, Paradinas F.J, Johnson P.J, et al. Vitamin B12 binding protein as a tumour marker for hepatocellular carcinoma. Gut. 1978;19:1105-9. doi: 10.1136/gut.19.12.1105
  47. Wheeler K, Pritchard J, Luck W, Rossiter M. Transcobalamin I as a marker for fibrolamellar hepatoma. Med Ped Oncol. 1986;14:227-9. doi: 10.1002/mpo.2950140408
  48. Salles N, Herrmann F, Sakbani K, Rapin C.H, Sieber C. High vitamin B12 level: a strong predictor of mortality in elderly in patients. J Am Geriatr Soc. 2005;53:917-8. doi: 10.1111/j.1532-5415.2005.53278_7.x
  49. Gimsing P. The cobalamin forms and analogues in plasma and myeloid cells during the course of chronic myelogenous leukemia related to the clinical condition. Br J Haematol. 1995;89:812-9. doi: 10.1111/j.1365-2141.1995.tb08419.x
  50. Zittoun J, Farcet J.P, Marquet J, Sultan C, Zittoun R. Cobalamin vitamin B12 (vitamin B12) and B12 binding proteins in hypereosinophilic syndromes and secondary eosinophilia. Blood. 1984;63:779-83
  51. Rachmilewitz D, Rachmilewitz E.A, Polliack A, Herchko C.A. Acute promyelocytic leukemia. A report of five cases with a comment on the diagnostic significance of serum vitamin B12 determination. Br J Haematol. 1972;22:87-92. doi: 10.1111/j.1365-2141.1972.tb08789.x
  52. Lambert D, Benhayoun S, Adjalla C, Gelot M.M, et al. Alcoholic cirrhosis and cobalamin metabolism. Digestion. 1997;58:64-71. doi: 10.1159/000201425
  53. Fragasso A. Vitamin B12 Deficiency in Alcoholics. In: Watson R., Preedy V., Zibadi S. (eds). Alcohol, Nutrition, and Health Consequences. Nutrition and Health. Humana Press, Totowa, NJ, 2013. doi: 10.1007/978-1-62703-047-2_10
  54. Fragasso A, Mannarella C, Ciancio A, Sacco A. Functional vitamin B12 deficiency in alcoholics: an intriguing finding in a retrospective study of megaloblastic anemic patients. Eur J Intern Med. 2010;21:97-100. doi: 10.1016/j.ejim.2009.11.012
  55. Hofer L.J, Elian K.M. Parenteral vitamin B12 therapy of hyperhomocysteinemia in end - stage renal disease. Med Clin Exp. 2004;27:10-3.
  56. Reynolds E.H, Bottiglieri T, Laundry M, Stern J, et al. Subacute combined degeneration with high serum vitamin B12 level and abnormal vitamin B12 binding protein. Arch Neurol. 1993;50:739-42. doi: 10.1001/archneur.1993.00540070055015
  57. Molad Y, Rachmilewitz B, Sidi Y, Pinkhas J, Weinberger A. Serum transcobalamin and transcobalamin levels in systemic lupus erythematosus. Am J Med. 1989;88:141-4. doi: 10.1016/0002-9343(90)90463-N
  58. Grindulis K.A, Calverley M, Cox C. Rheumatoid arthritis: is serum vitamin B12 high in active disease? J Rheumatol. 1984;11:211-2.
  59. Kalyoncu U, Buyukasik Y, Akdogan A, Karadag O, et al. Increased serum vitamin B12 levels are associated with adult - onset Still’s disease with reactive macrophage activation syndrome. Joint Bone Spine. 2010;77:131-4. doi: 10.1016/j.jbspin.2009.09.010
  60. Belousov Y.B. Klinicheskaya farmakologiya i farmakoterapiya. M.: GEOTAR-Media, 2010.-S. 624-626, 855-857.
  61. Serraj K, Mecili M, Housni I, André S.E. L’hypervitaminemie B12: physiopathologie et interêt en pratique clinique. Press Med. 2011;40:1120-7. doi: 10.1016/j.lpm.2011.08.010

Copyright (c) 2019 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies