Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial.

Randomized, placebo-controlled trial in older adults aged 70 years and older with mild vitamin B-12 deficiency in the Netherlands. Participants were free-living or living in care facilities and had no dementia or severe cognitive impairment; 195 were randomized across three arms.

Participants received daily oral vitamin B-12 as cyanocobalamin, either 1000 micrograms alone or 1000 micrograms plus folic acid 400 micrograms, for 24 weeks. A placebo capsule served as the comparator; measured capsule content was about 986 micrograms and 987 micrograms of vitamin B-12 in the active capsules, and 357 micrograms of folic acid in the combination capsules.

Oral vitamin B-12 with or without folic acid did not improve cognitive function over 24 weeks compared with placebo. Memory improved in all groups, but the placebo group improved more than the vitamin B-12 alone group for memory (P = 0.0036), and there was a significant time-by-treatment interaction for memory (P = 0.0142). No significant benefits were seen for attention, construction, sensomotor speed, or executive function. Among the six memory tests, significant effects were limited to digit span backward (P = 0.0014) and the 15 word learning recognition test (P = 0.0376); no adverse effects were reported, and compliance was high (mean 99%).

The trial had a modest completion sample, with 31 participants unable to complete and analyses based on 162 completers. The 24-week duration may have been too short to detect cognitive change, and no per-active-arm sample sizes were stated in the extracted packet. Placebo-associated improvement in memory also complicates interpretation of the observed differences.