No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study

J Affect Disord. 2004 Sep;81(3):269-73. doi: 10.1016/S0165-0327(03)00169-1.


Background: Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported.

Methods: A randomized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid (0.40-2.00 micromol/l) not previously treated with vitamin B-12. Cognitive function was assessed by the Cambridge Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), and a 12-words learning test. Symptoms of depression were evaluated by the Major Depression Inventory. The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later.

Results: At baseline 78 (56%) individuals had cognitive impairment judged from the CAMCOG score and 40 (29%) according to the MMSE; 18 (13%) individuals had symptoms of depression. No improvement was found in cognitive function comparing the treatment and placebo group (total CAMCOG score: P = 0.43), nor among individuals with only slightly impaired cognitive function (n = 44, total CAMCOG score: P = 0.42). The treatment group did not improve in depression score as compared to the placebo group (P = 0.18).

Limitations: The duration of impaired cognitive function was unknown.

Conclusions: A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function, and a rather high prevalence of depression was observed. However, vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology*
  • Depressive Disorder / complications*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Female
  • Humans
  • Male
  • Placebos
  • Severity of Illness Index
  • Treatment Outcome
  • Vitamin B 12 / pharmacology*
  • Vitamin B 12 / therapeutic use*


  • Placebos
  • Vitamin B 12