Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study

Abstract

Background: Emerging evidence suggests that docosahexaenoic acid (DHA, 22:6n-3), the principal omega-3 (n-3) fatty acid in brain gray matter, positively regulates cortical metabolic function and cognitive development. However, the effects of DHA supplementation on functional cortical activity in human subjects are unknown.

Objective: The objective was to determine the effects of DHA supplementation on functional cortical activity during sustained attention in human subjects.

Design: Healthy boys aged 8-10 y (n = 33) were randomly assigned to receive placebo or 1 of 2 doses of DHA (400 or 1200 mg/d) for 8 wk. Relative changes in cortical activation patterns during sustained attention at baseline and endpoint were determined by functional magnetic resonance imaging.

Results: At 8 wk, erythrocyte membrane DHA composition increased significantly from baseline in subjects who received low-dose (by 47%) or high-dose (by 70%) DHA but not in those who received placebo (-11%). During sustained attention, both DHA dose groups had significantly greater changes from baseline in activation of the dorsolateral prefrontal cortex than did the placebo group, and the low-dose and high-dose DHA groups had greater decreases in the occipital cortex and cerebellar cortex, respectively. Relative to low-dose DHA, high-dose DHA resulted in greater decreases in activation of bilateral cerebellum. The erythrocyte DHA composition was positively correlated with dorsolateral prefrontal cortex activation and was inversely correlated with reaction time, at baseline and endpoint.

Conclusion: Dietary DHA intake and associated elevations in erythrocyte DHA composition are associated with alterations in functional activity in cortical attention networks during sustained attention in healthy boys. This trial was registered at clinicaltrials.gov as NCT00662142.

FIGURE 1

Erythrocyte membrane docosahexaenoic acid (DHA) (A) and arachidonic acid (AA) (B) composition [% by wt of total fatty acids (wt % TTL)] at baseline and study endpoint (8 wk) in subjects treated with placebo, low-dose DHA (400 mg/d), or high-dose DHA (1200 mg/d). Values are expressed as group means ± SEMs. ***Significantly different frombaseline and placebo, P ≤ 0.001 (unpaired t test, 2-tailed). ^##,###Significantly different fromlow-dose DHA: ^##P < 0.01, ^###P < 0.001 (unpaired t test, 2-tailed). The time × dose interactions for DHA (P ≤ 0.0001) and AA (P = 0.009) were significant.

FIGURE 2

Statistical parametric maps illustrating group differences from baseline to endpoint in regional activation [positive brain blood oxygen level–dependent activity (BOLD), docosahexaenoic acid (DHA) > placebo] and decreased activation (negative BOLD, placebo > DHA) during performance of the identical-pairs continuous performance task. The top row represents placebo compared with 400 mg DHA/d, and the bottom row represents placebo compared with 1200 mg DHA/d. Images are overlaid on a T1-weighted anatomic image, and the color gradient reflects increasing (red→yellow) statistical significances from a voxel intensity threshold of P ≤ 0.01 and cluster extent threshold of 233 voxels (P ≤ 0.05, corrected) relative to placebo.

FIGURE 3

Statistical parametric maps illustrating the relations between erythrocyte docosahexaenoic acid (DHA) composition and regional activation patterns during performance of the identical-pairs continuous performance task at baseline and endpoint (8 wk) [positive brain blood oxygen level–dependent activity (BOLD), positive correlation with DHA; negative BOLD, negative correlation with DHA]. There were no significant negative correlations between BOLD and DHA at 8 wk.