Do B vitamins need DHA to improve cognitive function? Original paper

    This study on older adults found that supplementation with two B vitamins (folic acid and vitamin B12) was beneficial for cognitive function, but only with higher levels of DHA in the blood.

    This Study Summary was published on August 23, 2022.


    Elevated levels of homocysteine in the blood is associated with a higher risk of cognitive impairment in aging. Because several B vitamins (e.g., folic acid and vitamin B12) can lower homocysteine levels, a number of clinical trials have tested whether supplementation with B vitamins can also lower the risk of cognitive decline. In general, these trials have been disappointing, with the overall effect appearing quite small. This study examined whether B vitamins’ effect on cognitive function depends on omega–3 status.

    The study

    This was a post hoc analysis (done after the study was completed) of a 2-year randomized controlled trial in which 191 older adults (mean age of 72) with homocysteine levels ≥12 micromoles/liter took a supplement containing either 400 micrograms (µg) of folic acid plus 500 µg of vitamin B12 or a placebo. The participants had a median Mini–Mental State Exam score of 29, indicating normal cognitive function.

    To assess cognitive function, the investigators administered tests for different aspects of cognition, specifically attention and working memory, episodic memory, executive function, and information processing speed. The participants’ scores on individual tests were combined to yield a global cognition score.

    The investigators analyzed the participants separately, according to the amount of omega–3s in their plasma relative to total fatty acids. This included eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total long-chain omega–3s (EPA and DHA).

    The results

    Among participants in the highest tertile (top 33%) of DHA status, supplementation with B vitamins improved global cognition compared with placebo, but there was no difference in the participants in the middle or bottom third of DHA status.

    The effect of B vitamins on cognition was not altered according to EPA status or total long-chain omega–3 status.


    These results don’t necessarily mean DHA itself makes B vitamins beneficial. For example, DHA status is likely influenced by seafood intake, meaning the effect of DHA status could be a proxy for other nutrients found in seafood or even lifestyle factors common among people who eat seafood regularly.

    Because these findings were the result of an unplanned post hoc analysis, they should be viewed with caution.

    This Study Summary was published on August 23, 2022.