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

Randomized controlled trial in older adults aged 75 years or older with moderate vitamin B-12 deficiency (serum vitamin B-12 107-210 pmol/L) and no anemia or overt neurologic or cognitive symptoms. Participants were recruited from 7 general practices in South East England, United Kingdom; 99 participants were randomized to the vitamin B-12 arm.

Oral cyanocobalamin 1 mg once daily for 12 months. The active tablets were identical in appearance to placebo, and adherence was checked by tablet counts.

Vitamin B-12 supplementation did not improve neurologic or cognitive function over 12 months in asymptomatic, nonanemic older adults with moderate deficiency. For the vitamin B-12 and placebo groups, the primary outcome of posterior tibial CMAP amplitude showed no benefit at 12 months, with analyses based on 91 participants per group. The main cognitive outcome, CVLT memory, also showed no effect (mean difference -1.4 words; 95% CI: -2.9, 0.1 words). Biomarkers improved as expected in the active arm, with serum vitamin B-12 rising from 231.3 ± 52.0 to 640.9 ± 199.3 pmol/L and homocysteine falling from 17.1 ± 4.6 to 14.2 ± 4.2 mmol/L, but these biochemical changes did not translate into clinical benefit.

Clinical interpretation is limited by the relatively small active-arm analysis set (91 for neurologic and cognitive outcomes), 12-month follow-up, and enrollment of generally healthy, asymptomatic older adults, which may reduce generalizability. The trial also had some attrition, with 191 of 201 enrolled participants providing outcome data at 12 months, and several secondary outcomes were negative despite biochemical repletion.