Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial

The American Journal of Clinical Nutrition

Jul 2015

DOI: 10.3945/ajcn.115.110775

Citations:75

Influential Citations:4

Interventional (Human) Studies

Enhanced Details

Methods

Double-blind, randomized, placebo-controlled trial conducted in seven general practices in South East England; participants aged 75 years or older, nonanemic, with moderate vitamin B-12 deficiency (serum vitamin B-12 107–210 pmol/L). 201 participants randomized; 191 provided outcome data.

Intervention

1 mg vitamin B-12 (cyanocobalamin) daily, oral tablet, for 12 months

Results

Biochemical response: serum vitamin B-12 and holotranscobalamin rose; homocysteine fell. No evidence of benefit on the primary outcome (posterior tibial CMAP amplitude at 12 months) or on any secondary neurologic or cognitive outcomes. CVLT: −1.4 words (95% CI −2.9, 0.1). Conclusion: Correcting moderate vitamin B-12 deficiency in nonanemic older adults does not improve neurologic or cognitive function over 12 months.

Limitations

- Population consisted of relatively healthy, high-functioning older adults, limiting generalizability. - 12-month duration may be insufficient to detect long-term benefits. - Sample size may be underpowered to detect small effects.

Abstract

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 μmol/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: −0.2 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. This trial was registered at www.isrctn.com as ISRCTN54195799. show less