title: Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial.
abstract: BACKGROUND
  Moderate vitamin B-12 deficiency is relatively common in older people. However, there is little robust evidence on the effect of vitamin B-12 supplementation on neurologic and cognitive outcomes in later life.
  
  
  OBJECTIVE
  We investigated whether vitamin B-12 supplementation benefits neurologic and cognitive function in moderately vitamin B-12-deficient older people.
  
  
  METHODS
  We conducted a double-blind, randomized, placebo-controlled trial in 7 general practices in South East England, United Kingdom. Study participants were aged ≥75 y and had moderate vitamin B-12 deficiency (serum vitamin B-12 concentrations: 107-210 pmol/L) in the absence of anemia and received 1 mg crystalline vitamin B-12 or a matching placebo as a daily oral tablet for 12 mo. Peripheral motor and sensory nerve conduction, central motor conduction, a clinical neurologic examination, and cognitive function were assessed before and after treatment.
  
  
  RESULTS
  A total of 201 participants were enrolled in the trial, and 191 subjects provided outcome data. Compared with baseline, allocation to vitamin B-12 was associated with a 177% increase in serum concentration of vitamin B-12 (641 compared with 231 pmol/L), a 331% increase in serum holotranscobalamin (240 compared with 56 pmol/L), and 17% lower serum homocysteine (14.2 compared with 17.1 μmol/L). In intention-to-treat analysis of covariance models, with adjustment for baseline neurologic function, there was no evidence of an effect of supplementation on the primary outcome of the posterior tibial compound muscle action potential amplitude at 12 mo (mean difference: -0.2 mV; 95% CI: -0.8, 0.3 mV). There was also no evidence of an effect on any secondary peripheral nerve or central motor function outcome, or on cognitive function or clinical examination.
  
  
  CONCLUSIONS
  Results of the trial do not support the hypothesis that the correction of moderate vitamin B-12 deficiency, in the absence of anemia and of neurologic and cognitive signs or symptoms, has beneficial effects on neurologic or cognitive function in later life. This trial was registered at www.isrctn.com as ISRCTN54195799.
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom; alan.dangour@lshtm.ac.uk.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Dangour
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Allen
authors.affiliation: Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom;
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom;
authors.forename: Diana
authors.initials: D
authors.lastname: Elbourne
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom;
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Fletcher
authors.affiliation: Medical Research Council General Practice Research Framework, London, United Kingdom;
authors.forename: Louise
authors.initials: L
authors.lastname: Letley
authors.affiliation: Medical Research Council Unit for Lifelong Health and Ageing at University College London, London, United Kingdom; and.
authors.forename: Marcus
authors.initials: M
authors.lastname: Richards
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom;
authors.forename: Ken
authors.initials: K
authors.lastname: Whyte
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom;
authors.forename: Ricardo
authors.initials: R
authors.lastname: Uauy
authors.affiliation: Department of Clinical Neurosciences, King's College, London, United Kingdom.
authors.forename: Kerry
authors.initials: K
authors.lastname: Mills
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D010349:Patient Compliance; D016896:Treatment Outcome; D006113:United Kingdom; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000188:drug therapy
chemical_list: D014805:Vitamin B 12
keywords: cognitive; neurologic; older people; peripheral and central nerve conduction; vitamin B-12