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Detection of Vitamin B₁₂ Deficiency in Older People by Measuring Vitamin B₁₂ or the Active Fraction of Vitamin B₁₂, Holotranscobalamin

¹ Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom.
² Hightown Surgery, Hightown Gardens, Banbury, United Kingdom.
³ Department of Clinical Biochemistry, AS, Aarhus University Hospital, Aarhus, Denmark.
⁴ Department of Clinical Chemistry, Umeå University Hospital, Umeå, Sweden.
⁵ Division of Clinical Geratology, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
⁶ Locus for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway.
⁷ School of Biochemistry and Immunology, Trinity College, Dublin, Republic of Ireland.

^aAddress correspondence to this author at: Clinical Trial Service Unit, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LF, United Kingdom. Fax 00-44-1865-743985; e-mail robert.clarke{at}ctsu.ox.ac.uk.

Background: Impaired vitamin B₁₂ function and decreased vitamin B₁₂ status have been associated with neurological and cognitive impairment. Current assays analyze total vitamin B₁₂ concentration, only a small percentage of which is metabolically active. Concentrations of this active component, carried on holotranscobalamin (holoTC), may be of greater relevance than total vitamin B₁₂.

Methods: We compared the utility of serum holoTC with conventional vitamin B₁₂ for detection of vitamin B₁₂ deficiency in a population-based study of older people, using increased methylmalonic acid (MMA) concentrations as a marker of metabolic vitamin B₁₂ deficiency in the overall population (n = 2403) and in subsets with normal (n = 1651) and abnormal (n = 752) renal function.

Results: Among all participants, 6% had definite (MMA >0.75 µmol/L) and 16% had probable (MMA >0.45 µmol/L) metabolic vitamin B₁₂ deficiency. In receiver operating characteristic curves for detection of definite vitamin B₁₂ deficiency, holoTC had a greater area under the curve (AUC) compared with vitamin B₁₂ in all participants (0.85 vs 0.76; P <0.001) and in subsets with normal (AUC: 0.87 vs 0.79; P <0.001) and abnormal (AUC: 0.85 vs 0.74; P = 0.002) renal function. Similar findings were observed for detection of moderate vitamin B₁₂ deficiency. Whereas the positive predictive value for both holoTC and vitamin B₁₂ was greater for detection of probable than definite vitamin B₁₂ deficiency, both tests were associated with more false-positive than true-positive test results.

Conclusions: HoloTC has a modestly superior diagnostic accuracy compared with conventional vitamin B₁₂ for the detection of vitamin B₁₂ deficiency, but neither test can be recommended to screen asymptomatic populations.

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