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 micromol/L) and 16% had probable (MMA >0.45 micromol/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.
Clarke
Robert
R
Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom. robert.clarke@ctsu.ox.ac.uk
Sherliker
Paul
P
Hin
Harold
H
Nexo
Ebba
E
Hvas
Anne Mette
AM
Schneede
Joern
J
Birks
Jacqueline
J
Ueland
Per M
PM
Emmens
Kathleen
K
Scott
John M
JM
Molloy
Anne M
AM
Evans
John Grimley
JG
D000368:Aged; D006801:Humans; D008875:Middle Aged; D015203:Reproducibility of Results; D014155:Transcobalamins / Q000032:analysis*; D014805:Vitamin B 12 / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000175:diagnosis* / Q000453:epidemiology
D014155:Transcobalamins; D014805:Vitamin B 12