Effects of Vitamin B-12 supplementation on neurologic and cognitive function in older people: A randomized controlled trial1,2

Alan D. Dangour*, Elizabeth Allen, Robert Clarke, Diana Elbourne, Astrid E. Fletcher, Louise Letley, Marcus Richards, Ken Whyte, Ricardo Uauy, Kerry Mills

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


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. Design: 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 mmol/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: 20.2 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)639-647
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Issue number3
Publication statusPublished - 1 Sep 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 American Society for Nutrition.


  • Cognitive
  • Neurologic
  • Older people
  • Peripheral and central nerve conduction
  • Vitamin B-12


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