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1 Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905. Fax 507-284-4542; e-mail klee.george{at}mayo.edu
Vitamin B12 and folate are two vitamins that have interdependent roles in nucleic acid synthesis. Deficiencies of either vitamin can cause megaloblastic anemia; however, inappropriate treatment of B12 deficiency with folate can cause irreversible nerve degeneration. Inadequate folate nutrition during early pregnancy can cause neural tube defects in the developing fetus. In addition, folate and vitamin B12 deficiency and the compensatory increase in homocysteine are a significant risk factor for cardiovascular disease. Laboratory support for the diagnosis and management of these multiple clinical entities is controversial and somewhat problematic. Automated ligand binding measurements of vitamin B12 and folate are easiest to perform and widely used. Unfortunately, these tests are not the most sensitive indicators of disease. Measurement of red cell folate is less dependent on dietary fluctuations, but these measurements may not be reliable. Homocysteine and methylmalonic acid are better metabolic indicators of deficiencies at the tissue level. There are no "gold standards" for the diagnosis of these disorders, and controversy exists regarding the best diagnostic approach. Healthcare strategies that consider the impact of laboratory tests on the overall costs and quality of care should consider the advantages of including methylmalonic acid and homocysteine in the early evaluation of patients with suspected deficiencies of vitamin B12 and folate.
The following articles in journals at HighWire Press have cited this article:
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T. R. Halfdanarson, M. R. Litzow, and J. A. Murray Hematologic manifestations of celiac disease Blood, January 15, 2007; 109(2): 412 - 421. [Abstract] [Full Text] [PDF] |
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L. Feng, T.-P. Ng, L. Chuah, M. Niti, and E.-H. Kua Homocysteine, folate, and vitamin B-12 and cognitive performance in older Chinese adults: findings from the Singapore Longitudinal Ageing Study Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1506 - 1512. [Abstract] [Full Text] [PDF] |
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R. Z.-W. Ting, C. C. Szeto, M. H.-M. Chan, K. K. Ma, and K. M. Chow Risk factors of vitamin B12 deficiency in patients receiving metformin. Arch Intern Med, October 9, 2006; 166(18): 1975 - 1979. [Abstract] [Full Text] [PDF] |
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M. V. Bor, E. Lydeking-Olsen, J. Moller, and E. Nexo A daily intake of approximately 6 {micro}g vitamin B-12 appears to saturate all the vitamin B-12-related variables in Danish postmenopausal women Am. J. Clinical Nutrition, January 1, 2006; 83(1): 52 - 58. [Abstract] [Full Text] [PDF] |
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E.-C. Chan, P.-Y. Chang, T.-L. Wu, and J. T. Wu Enzymatic Assay of Homocysteine on Microtiter Plates or a TECAN Analyzer Using Crude Lysate Containing Recombinant Methionine {gamma}-Lyase Ann. Clin. Lab. Sci., April 1, 2005; 35(2): 155 - 160. [Abstract] [Full Text] [PDF] |
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L. R. Solomon Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing Blood, February 1, 2005; 105(3): 978 - 985. [Abstract] [Full Text] [PDF] |
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E. A. Gomez, D. D. Ehresmann, L. K. Ledebuhr, M. L. Eastvold, R. J. Singh, G. G. Klee, and S. K.G. Grebe Development and Validation of an Automated Chemiluminometric Immunoassay for Human Intrinsic Factor Antibodies in Serum Clin. Chem., January 1, 2005; 51(1): 232 - 235. [Full Text] [PDF] |
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E. Andres, N. H. Loukili, E. Noel, G. Kaltenbach, M. B. Abdelgheni, A. E. Perrin, M. Noblet-Dick, F. Maloisel, J.-L. Schlienger, and J.-F. Blickle Vitamin B12 (cobalamin) deficiency in elderly patients Can. Med. Assoc. J., August 3, 2004; 171(3): 251 - 259. [Abstract] [Full Text] [PDF] |
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H. Refsum, A. D. Smith, P. M. Ueland, E. Nexo, R. Clarke, J. McPartlin, C. Johnston, F. Engbaek, J. Schneede, C. McPartlin, et al. Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion Clin. Chem., January 1, 2004; 50(1): 3 - 32. [Abstract] [Full Text] [PDF] |
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M Vrethem, E Mattsson, H Hebelka, K Leerbeck, A Osterberg, A-M Landtblom, B Balla, H Nilsson, M Hultgren, L Brattstrom, et al. Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid Multiple Sclerosis, June 1, 2003; 9(3): 239 - 245. [Abstract] [PDF] |
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R. A. M. Dhonukshe-Rutten, M. Lips, N. de Jong, M. J. M. Chin A Paw, G. J. Hiddink, M. van Dusseldorp, L. C. P. G. M. de Groot, and W. A. van Staveren Vitamin B-12 Status Is Associated with Bone Mineral Content and Bone Mineral Density in Frail Elderly Women but Not in Men J. Nutr., March 1, 2003; 133(3): 801 - 807. [Abstract] [Full Text] [PDF] |
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R. G. Ziegler, S. J. Weinstein, and T. R. Fears Nutritional and Genetic Inefficiencies in One-Carbon Metabolism and Cervical Cancer Risk J. Nutr., August 1, 2002; 132(8): 2345S - 2349. [Abstract] [Full Text] [PDF] |
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W. Herrmann, H. Schorr, K. Purschwitz, F. Rassoul, and V. Richter Total Homocysteine, Vitamin B12, and Total Antioxidant Status in Vegetarians Clin. Chem., June 1, 2001; 47(6): 1094 - 1101. [Abstract] [Full Text] [PDF] |
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