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Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment

Oulhaj A, Jernerén F, Refsum H, David Smith A, de Jager CA. (2016) J Alzheimers Dis. 50(2): 547-57. doi: 10.3233/JAD-150777. Epub Jan 6. 

Web URL: View this and related abstracts via PubMed here. Free full text of this article is available online


A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of vitamin treatment.

266 participants with MCI aged ≥70 years were randomized to 
B vitamins (folic acidvitamins 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.

Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the 
B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations.

Among those with good 
omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective.

omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD.


Initial findings from this 2-year clinical trial (the Oxford Vitacog Study) showed significant benefits in older adults with Mild Cognitive Impairment from dietary supplementation with Vitamins B6, B12 and folate for:

This new study shows that the protective effect of B vitamins in slowing cognitive decline and preventing dementia depended on initial blood levels of the long-chain omega-3 fatty acids, EPA and DHA.

When participants were divided into three equal groups, ranked according to their baseline blood omega-3 (EPA+DHA), only those participants with medium or high plasma omega-3 levels showed reduced cognitive and clinical decline following B vitamin supplementation.

Those with the lowest blood omega-3 levels did not benefit from the B vitamins.

These findings mirror those from an earlier study, which showed that the effect of B vitamins in slowing the rate of physical brain shrinkage also depended on good initial omega-3 status. (see Jernerén et al., 2015)

For a summary of this research, see the associated news article:

See also:

and the associated news article (including an exclusive FAB interview with Dr Jernerén)

For details of the initial publications from this Vitacog study, please see: