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Measurement of Total Vitamin B₁₂ and Holotranscobalamin, Singly and in Combination, in Screening for Metabolic Vitamin B₁₂ Deficiency

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.

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