title: Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial.
abstract: BACKGROUND
  Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125-200 pM/l is lacking. We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo.
  
  
  METHODS
  This multicentre (13 general practices, two nursing homes, and one primary care center in western Switzerland), parallel, randomised, controlled, closed-label, observer-blind trial included 50 patients with serum vitamin B12 levels between 125-200 pM/l who were randomized to receive either oral vitamin B12 (1000 μg daily, N = 26) or placebo (N = 24) for four weeks. The institution's pharmacist used simple randomisation to generate a table and allocate treatments. The primary outcome was the change in serum methylmalonic acid (MMA) levels after one month of treatment. Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels. Blood samples were centralised for analysis and adherence to treatment was verified by an electronic device (MEMS; Aardex Europe, Switzerland).
  
  
  BACKGROUND
  ISRCTN 22063938.
  
  
  RESULTS
  Baseline characteristics and adherence to treatment were similar in both groups. After one month, one patient in the placebo group was lost to follow-up. Data were evaluated by intention-to-treat analysis. One month of vitamin B12 treatment (N = 26) lowered serum MMA levels by 0.13 μmol/l (95%CI 0.06-0.19) more than the change observed in the placebo group (N = 23). The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 (95% CI 1.7-6.4). A significant change was observed for the B12 serum level, but not for the homocysteine level, hematocrit, or mean corpuscular volume. After three months without active treatment (at four months), significant differences in MMA levels were no longer detected.
  
  
  CONCLUSIONS
  Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency. However, a one-month daily treatment with 1000 μg oral vitamin B12 was not sufficient to normalise the deficiency markers for four months, and treatment had no effect on haematological signs of B12 deficiency.
authors.affiliation: Department of Ambulatory Care and Community Medicine, University of Lausanne, Bugnon 44, CH-1011 Lausanne, Switzerland. bernard.favrat@hospvd.ch
authors.forename: Bernard
authors.initials: B
authors.lastname: Favrat
authors.forename: Paul
authors.initials: P
authors.lastname: Vaucher
authors.forename: Lilli
authors.initials: L
authors.lastname: Herzig
authors.forename: Bernard
authors.initials: B
authors.lastname: Burnand
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Ali
authors.forename: Olivier
authors.initials: O
authors.lastname: Boulat
authors.forename: Thomas
authors.initials: T
authors.lastname: Bischoff
authors.forename: François
authors.initials: F
authors.lastname: Verdon
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001800:Blood Specimen Collection; D019587:Dietary Supplements; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D010349:Patient Compliance; D013557:Switzerland; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000188:drug therapy*; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D014803:Vitamin B Complex; D008764:Methylmalonic Acid; D014805:Vitamin B 12