title: Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin.
abstract: 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.
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom. robert.clarke@ctsu.ox.ac.uk
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.forename: Paul
authors.initials: P
authors.lastname: Sherliker
authors.forename: Harold
authors.initials: H
authors.lastname: Hin
authors.forename: Ebba
authors.initials: E
authors.lastname: Nexo
authors.forename: Anne Mette
authors.initials: AM
authors.lastname: Hvas
authors.forename: Joern
authors.initials: J
authors.lastname: Schneede
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Birks
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Kathleen
authors.initials: K
authors.lastname: Emmens
authors.forename: John M
authors.initials: JM
authors.lastname: Scott
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
authors.forename: John Grimley
authors.initials: JG
authors.lastname: Evans
mesh_terms: 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
chemical_list: D014155:Transcobalamins; D014805:Vitamin B 12