Vitamin B12 and cognitive function: an evidence-based analysis

Ont Health Technol Assess Ser. 2013 Nov 1;13(23):1-45. eCollection 2013.


Background: More than 2.9 million serum vitamin B12 tests were performed in 2010 in Ontario at a cost of $40 million. Vitamin B12 deficiency has been associated with a few neurocognitive disorders.

Objective: To determine the clinical utility of B12 testing in patients with suspected dementia or cognitive decline.

Methods: Three questions were addressed: Is there an association between vitamin B12 deficiency and the onset of dementia or cognitive decline? Does treatment with vitamin B12 supplementation improve cognitive function in patients with dementia or cognitive decline and vitamin B12 deficiency? What is the effectiveness of oral versus parenteral vitamin B12 supplementation in those with confirmed vitamin B12 deficiency? A literature search was performed using MEDLINE, Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the Centre for Reviews and Dissemination database, from January 2002 until August 2012.

Results: Eighteen studies (7 systematic reviews and 11 observational studies) were identified to address the question of the association between B12 and the onset of dementia. Four systematic reviews were identified to address the question of the treatment of B12 on cognitive function. Finally, 3 randomized controlled trials were identified that compared oral B12 to intramuscular B12.

Conclusions: Based on very low quality evidence, there does appear to be an association between elevated plasma homocysteine levels (a by-product of B vitamins) and the onset of dementia. Based on moderate quality evidence, but with less than optimal duration of follow-up, treatment with B12 supplementation does not appreciably change cognitive function. Based on low to moderate quality of evidence, treatment with vitamin B12 and folate in patients with mild cognitive impairment seems to slow the rate of brain atrophy. Based on moderate quality evidence, oral vitamin B12 is as effective as parenteral vitamin B12 in patients with confirmed B12 deficiency.

Plain language summary: Low levels of vitamin B12 have been associated with neurocognitive disorders. This evidence-based analysis assessed the usefulness of serum vitamin B12 testing as it relates to brain function. This review found very low quality evidence that suggests a connection between high plasma homocysteine levels (a by-product of B vitamin metabolism in the body) and the onset of dementia. Moderate quality of evidence indicates treatment with vitamin B12 does not improve brain function. Moderate quality of evidence also indicates treatment using oral vitamin B12 supplements is as effective as injections of vitamin B12.

Publication types

  • Review

MeSH terms

  • Blood Chemical Analysis / economics
  • Blood Chemical Analysis / standards
  • Blood Chemical Analysis / trends
  • Cognition / drug effects*
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / epidemiology
  • Dementia / drug therapy*
  • Dementia / epidemiology
  • Dietary Supplements
  • Evidence-Based Practice
  • Homocysteine / blood
  • Homocysteine / metabolism
  • Humans
  • Injections, Intramuscular
  • Longitudinal Studies
  • Ontario
  • Practice Guidelines as Topic
  • Randomized Controlled Trials as Topic
  • Research Design
  • Treatment Outcome
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / pharmacology
  • Vitamin B 12 / therapeutic use*
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / drug therapy*
  • Vitamin B 12 Deficiency / epidemiology
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / pharmacology
  • Vitamin B Complex / therapeutic use*


  • Homocysteine
  • Vitamin B Complex
  • Vitamin B 12