Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin

Background: Impaired vitamin B-12 function and decreased vitamin B-12 status have been associated with neurological and cognitive impairment. Current assays analyze total vitamin B-12 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 B-12. Methods: We compared the utility of serum holoTC with conventional vitamin B-12 for detection of vitamin B-12 deficiency in a population-based study of older people, using increased methylmalonic acid (MMA) concentrations as a marker of metabolic vitamin B-12 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 mu mol/L) and 16% had probable (MMA > 0.45 mu mol/L) metabolic vitamin B-12 deficiency. In receiver operating characteristic curves for detection of definite vitamin B-12 deficiency, holoTC had a greater area under the curve (AUC) compared with vitamin B-12 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 B-12 deficiency. Whereas the positive predictive value for both holoTC and vitamin B-12 was greater for detection of probable than definite vitamin B-12 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 B-12 for the detection of vitamin B-12 deficiency, but neither test can be recommended to screen asymptomatic populations. (c) 2007 American Association for Clinical Chemistry.