Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.
Level 2 - randomized trial
Retrospective subgroup interaction analysis of a randomized controlled trial
PubMed 25877495 · doi:10.3945/ajcn.114.103283
What was done
In a retrospective analysis of the VITACOG randomized controlled trial, 168 participants aged 70 years or older with mild cognitive impairment were assigned to receive either daily high-dose B vitamins (0.8 mg folic acid, 20 mg vitamin B-6, 0.5 mg vitamin B-12; n = 85) or placebo (n = 83) for 2 years. Brain atrophy rates were measured using cranial magnetic resonance imaging scans at baseline and 2 years later. Treatment effects were analyzed across tertiles of baseline plasma omega-3 fatty acid concentrations (combined eicosapentaenoic acid and docosahexaenoic acid).
What was found
A significant interaction occurred between B vitamin treatment and baseline plasma omega-3 fatty acid concentrations on brain atrophy rates (P = 0.024). In participants with high baseline omega-3 fatty acids (>590 µmol/L), B vitamin treatment slowed the mean brain atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on atrophy rates among participants with low baseline omega-3 fatty acids (<390 µmol/L). High baseline omega-3 concentrations were associated with slower atrophy rates in the B vitamin group but not in the placebo group.
Why it matters
This study indicates a synergistic relationship between omega-3 fatty acids and B vitamins, suggesting that homocysteine-lowering interventions may only slow structural brain atrophy in individuals with adequate baseline omega-3 status.
Limits
This is a retrospective subgroup analysis of a single trial with a modest sample size (n = 168). Omega-3 status was measured observationally rather than experimentally manipulated via randomized co-supplementation, and the abstract does not report clinical cognitive endpoints or confidence intervals.