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Nutrition |
1 Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA.
2 ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT.
3 Department of Nutrition, University of California, Davis, and US Department of Agriculture Western Human Nutrition Research Center, Sacramento, CA.
4 Department of Epidemiology, University of Michigan, Ann Arbor, MI.
aAddress correspondence to this author at: University of California, Davis Medical Center, Department of Pathology and Laboratory Medicine, PATH Building–Room 1106, 4400 V St., Sacramento, CA 95817. Fax 916-734-2652; e-mail ralph.green{at}ucdmc.ucdavis.edu.
Background: The standard screening test for vitamin B12 deficiency, measurement of total plasma vitamin B12, has limitations of sensitivity and specificity. Plasma vitamin B12 bound to transcobalamin (holoTC) is the fraction of total vitamin B12 available for tissue uptake and therefore has been proposed as a potentially useful alternative indicator of vitamin B12 status.
Methods: We compared the diagnostic accuracy of total vitamin B12, holoTC, and a combination of both measures to screen for metabolic vitamin B12 deficiency in an elderly cohort (age 
60 years). Plasma methylmalonic acid and homocysteine were used as indicators of vitamin B12 deficiency.
Results: Low total vitamin B12 (<148 pmol/L) and low holoTC (<35 pmol/L) were observed in 6.5% and 8.0%, and increased methylmalonic acid (>350 nmol/L) and homocysteine (>13 µmol/L) were observed in 12.1% and 17.0% of the study participants. In multiple regression models, holoTC explained 5%–6% more of the observed variance in methylmalonic acid and homocysteine than did total vitamin B12 (P 
0.004). ROC curve analysis indicated that total vitamin B12 and holoTC were essentially equivalent in their ability to discriminate persons with and without vitamin B12 deficiency. Individuals with low concentrations of both total vitamin B12 and holoTC had significantly higher concentrations of methylmalonic acid and homocysteine than did individuals with total vitamin B12 and/or holoTC within the reference intervals (P <0.001).
Conclusions: HoloTC and total vitamin B12 have equal diagnostic accuracy in screening for metabolic vitamin B12 deficiency. Measurement of both holoTC and total vitamin B12 provides a better screen for vitamin B12 deficiency than either assay alone.
The following articles in journals at HighWire Press have cited this article:
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  J. W Miller, M. G Garrod, L. H Allen, M. N Haan, and R. Green Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate Am. J. Clinical Nutrition, December 1, 2009; 90(6): 1586 - 1592. [Abstract] [Full Text] [PDF]
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 D. S. Bhat, N. V. Thuse, H. G. Lubree, C. V. Joglekar, S. S. Naik, L. V. Ramdas, C. Johnston, H. Refsum, C. H. Fall, and C. S. Yajnik Increases in Plasma Holotranscobalamin Can Be Used to Assess Vitamin B-12 Absorption in Individuals with Low Plasma Vitamin B-12 J. Nutr., November 1, 2009; 139(11): 2119 - 2123. [Abstract] [Full Text] [PDF]
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I. Elmadfa and I. Singer Vitamin B-12 and homocysteine status among vegetarians: a global perspective Am. J. Clinical Nutrition, May 1, 2009; 89(5): 1693S - 1698S. [Abstract] [Full Text] [PDF]
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R. Green Is it time for vitamin B-12 fortification? What are the questions? Am. J. Clinical Nutrition, February 1, 2009; 89(2): 712S - 716S. [Abstract] [Full Text] [PDF]
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S. E Cusick, Z. Mei, D. S Freedman, A. C Looker, C. L Ogden, E. Gunter, and M. E Cogswell Unexplained decline in the prevalence of anemia among US children and women between 1988-1994 and 1999-2002 Am. J. Clinical Nutrition, December 1, 2008; 88(6): 1611 - 1617. [Abstract] [Full Text] [PDF]
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 A. Vogiatzoglou, H. Refsum, C. Johnston, S. M. Smith, K. M. Bradley, C. de Jager, M. M. Budge, and A. D. Smith Vitamin B12 status and rate of brain volume loss in community-dwelling elderly Neurology, September 9, 2008; 71(11): 826 - 832. [Abstract] [Full Text] [PDF]
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 M. G. Garrod, R. Green, L. H. Allen, D. M. Mungas, W. J. Jagust, M. N. Haan, and J. W. Miller Fraction of Total Plasma Vitamin B12 Bound to Transcobalamin Correlates with Cognitive Function in Elderly Latinos with Depressive Symptoms Clin. Chem., July 1, 2008; 54(7): 1210 - 1217. [Abstract] [Full Text] [PDF]
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J. Brady, L. Wilson, L. McGregor, E. Valente, and L. Orning Active B12: A Rapid, Automated Assay for Holotranscobalamin on the Abbott AxSYM Analyzer Clin. Chem., March 1, 2008; 54(3): 567 - 573. [Abstract] [Full Text] [PDF]
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M. M. Murphy, A. M. Molloy, P. M. Ueland, J. D. Fernandez-Ballart, J. Schneede, V. Arija, and J. M. Scott Longitudinal Study of the Effect of Pregnancy on Maternal and Fetal Cobalamin Status in Healthy Women and Their Offspring J. Nutr., August 1, 2007; 137(8): 1863 - 1867. [Abstract] [Full Text] [PDF]
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R. Clarke, P. Sherliker, H. Hin, E. Nexo, A. M. Hvas, J. Schneede, J. Birks, P. M. Ueland, K. Emmens, J. M. Scott, et al. Detection of Vitamin B12 Deficiency in Older People by Measuring Vitamin B12 or the Active Fraction of Vitamin B12, Holotranscobalamin Clin. Chem., May 1, 2007; 53(5): 963 - 970. [Abstract] [Full Text] [PDF]
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J. W Miller Assessing the association between vitamin B-12 status and cognitive function in older adults Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1259 - 1260. [Full Text] [PDF]
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