Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

Randomized controlled trial in older adults over 70 years with mild cognitive impairment recruited in the Oxford area, United Kingdom. A total of 271 participants were randomized 1:1; 266 were analyzed in the intention-to-treat population, and the MRI sub-study included 85 active-arm participants and 83 placebo participants with baseline and 2-year scans.

Participants received an oral B-vitamin combination for 24 months: folic acid 0.8 mg, vitamin B12 (cyanocobalamin) 0.5 mg, and vitamin B6 (pyridoxine HCl) 20 mg once daily. The active product was TrioBe PlusH and was compared with placebo.

Homocysteine-lowering B vitamins slowed brain atrophy in mild cognitive impairment. Annual brain atrophy was 0.76% [95% CI, 0.63-0.90] with B vitamins versus 1.08% [0.94-1.22] with placebo (P = 0.001), and after age adjustment it remained lower at 0.78% versus 1.07% (P = 0.003). In the biologically compliant subset (n = 136), atrophy was 0.73% versus 1.06% (P = 0.004), while noncompliant participants (n = 31) showed no difference (P = 1.00). The active group also showed marked biomarker responses, with plasma folate increasing by nearly 270%, vitamin B12 doubling, and plasma total homocysteine decreasing by 22.5%; no significant safety issues or adverse-event differences were reported.

The main clinical outcome was brain atrophy rather than dementia progression, and cognitive outcomes were not the primary focus. The MRI analysis was based on a smaller sub-study than the full randomized cohort, follow-up was 24 months, and some subgroup findings were post hoc or underpowered. Generalizability is limited to older adults with mild cognitive impairment recruited from one region, and the apparent benefit depended partly on biological compliance.