Background and aim A randomised trial (VITACOG) in people with Mild Cognitive Impairment (MCI), a prodromal stage of Alzheimer's disease, found that B vitamin treatment to lower homocysteine slowed the rate of brain atrophy and of cognitive and clinical decline. (de Jager et al. Int J. Geriatr. Psychiatry 2012, 27:592–600; Douaud et al. PNAS 2013, 110:9523–28). We reported last year that, in this trial, B vitamins only slowed brain atrophy in subjects with a good baseline omega‐3 fatty acid status (Jerneren et al. AJCN 2015; 102:215–21). We have now used data from the trial to see whether baseline omega‐3 fatty acid status interacts with the effects of B vitamin treatment on cognitive and clinical outcomes.

Methods 266 participants with MCI aged ≥70 years were randomised to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega‐3 fatty acids) were measured.

Results Final scores for episodic memory, global cognition and CDR sum‐of‐boxes were better in the B vitamin‐treated group as the baseline concentration of omega‐3 fatty acids increased, whereas scores in the placebo group did not change across omega‐3 concentrations. Among those with good omega‐3 status, 33% of those on B vitamin treatment had global CDR scores >0 (i.e., worse) after 2 years compared with 59% among those on placebo; in other words, nearly twice as many on placebo progressed towards Alzheimer's disease as those on B vitamins with good omega‐3 status. For all 3 outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins. Eicosapentaenoic acid showed a similar pattern but did not reach significance.