DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial.
Level 2 - randomized trial
Post-hoc subgroup analysis of a randomized controlled trial
PubMed 35704085 · doi:10.1007/s00394-022-02924-w
What was done
This post-hoc analysis of the B-proof randomized controlled trial evaluated 191 adults aged 65 years or older with baseline plasma total homocysteine ≥ 12 µmol/L. Participants were randomly assigned to receive daily oral supplementation of 400 µg folic acid and 500 µg vitamin B12 or placebo for 2 years. Global and domain-specific cognitive functioning were assessed at baseline and after 2 years. Multiple linear regression analyses examined intervention effects across tertiles of baseline plasma concentrations of total omega-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).
What was found
Participants had a mean ± SD age of 71.6 ± 5.9 years and a baseline median Mini-Mental State Examination score of 29 [IQR 28–30]. B-vitamin supplementation produced a significantly larger improvement in global cognition in participants in the high DHA tertile compared to the middle DHA tertile (difference in z-score, mean ± SE 0.22 ± 0.10, p = 0.03). No significant interaction was observed between B-vitamin supplementation and combined omega-3 fatty acid tertiles (p = 0.49) or EPA tertiles (p = 0.99). Efficacy on domain-specific cognitive functioning was not linked to omega-3, DHA, or EPA levels.
Why it matters
These findings suggest that baseline DHA status may moderate the cognitive benefits of homocysteine-lowering B-vitamin therapy, potentially explaining conflicting results across prior clinical trials.
Limits
The study is an exploratory post-hoc subgroup analysis with a small sample size (n = 191), increasing the risk of false-positive findings. Significant effects were restricted to global cognition without domain-specific improvements, and the abstract does not report whether the high DHA tertile significantly differed from the lowest DHA tertile.
Cited by
- supports The VITACOG trial and B-PROOF trial demonstrated that lowering elevated homocysteine with B vitamins does not improve cognition or slow cognitive decline unless baseline omega-3 levels are adequate.