title: Vitamin B12 treatment normalizes metabolic markers but has limited clinical effect: a randomized placebo-controlled study.
abstract: BACKGROUND
  The clinical significance of increased plasma methylmalonic acid (P-MMA) is unclear. We assessed the efficacy of vitamin B12 treatment in reducing P-MMA and plasma total homocysteine compared with the clinical benefits of treatment.
  
  
  METHODS
  We studied 140 individuals with mildly to modestly increased P-MMA (0.40-2.00 micromol/L), not previously treated with vitamin B12, in a randomized, placebo-controlled study. A detailed medical history was obtained, and laboratory tests as well as an objective neurologic disability score were performed at baseline and 3 months after the start of intervention.
  
  
  RESULTS
  P-MMA (P <0.001) or plasma total homocysteine (P <0.001) decreased in the treatment group vs the placebo group, but no significant difference was found in the change of blood hemoglobin (P = 0.18) and mean cell volume (P = 0.71). Changes in symptom scores did not differ between the groups for symptoms of anemia (P = 0.63), neurologic symptoms (P = 0.21), gastroenterologic symptoms (P = 0.32), or the Neurological Disability Score (P = 0.85).
  
  
  CONCLUSIONS
  Treatment with vitamin B12 reduces P-MMA and plasma total homocysteine, but individuals with a mild to modest increase in P-MMA may have only limited clinical benefit from vitamin B12 treatment, at least in the short term.
authors.affiliation: Department of Hematology, AAS, Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark. am.hvas@dadlnet.dk
authors.forename: A M
authors.initials: AM
authors.lastname: Hvas
authors.forename: J
authors.initials: J
authors.lastname: Ellegaard
authors.forename: E
authors.initials: E
authors.lastname: Nexø
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008764:Methylmalonic Acid / Q000097:blood*; D008875:Middle Aged; D009460:Neurologic Examination; D014805:Vitamin B 12 / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000188:drug therapy
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D014805:Vitamin B 12