Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

Abstract

Specialized proresolving mediators (SPMs) induce resolution of inflammation. SPMs are derivatives of n-3 and n-6 PUFAs and may mediate their beneficial effects. It is unknown whether supplementation with PUFAs influences the production of SPMs. Alzheimer's disease (AD) is associated with brain inflammation and reduced levels of SPMs. The OmegAD study is a randomized, double-blind, and placebo-controlled clinical trial on AD patients, in which placebo or a supplement of 1.7 g DHA and 0.6 g EPA was taken daily for 6 months. Plasma levels of arachidonic acid decreased, and DHA and EPA levels increased after 6 months of n-3 FA treatment. Peripheral blood mononuclear cells (PBMCs) were obtained before and after the trial. Analysis of the culture medium of PBMCs incubated with amyloid-β 1-40 showed unchanged levels of the SPMs lipoxin A4 and resolvin D1 in the group supplemented with n-3 FAs, whereas a decrease was seen in the placebo group. The changes in SPMs showed correspondence to cognitive changes. Changes in the levels of SPMs were positively correlated to changes in transthyretin. We conclude that supplementation with n-3 PUFAs for 6 months prevented a reduction in SPMs released from PBMCs of AD patients, which was associated with changes in cognitive function.

Keywords: Alzheimer’s disease; amyloid β; clinical trials; docosahexaenoic acid; fatty acid; fish oil; inflammation; lipoxin; nutrition; peripheral blood mononuclear cell; resolvin.

Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Figures

Fig. 1.

MMSE scores before and after the 6 month trial. Paired individual values are flanked by mean ± SD. No statistical significance was found in the n-3 FA supplementation group, but a decrease was found in the placebo group after the 6 month trial.

Fig. 2.

A–C: Levels of plasma AA, DHA, and EPA before and after the 6 month clinical trial. Paired individual values are flanked by mean ± SD. Supplementation of n-3 FAs significantly decreased plasma AA levels (A) and increased DHA (B) and EPA (C) levels in plasma. There were no changes over time in the placebo group.

Fig. 3.

A–D: Levels of LMs in the medium of PBMCs exposed to Aβ40. Paired individual values are flanked by mean ± SD. A, B: Levels of LXA4 and RvD1 were unchanged in the n-3 FA supplementation group, but there was a significant decrease in these two SPMs in the placebo-supplemented group (P < 0.05). C: Levels of LTB4 were unchanged in both patient groups over time. D: The ratio between LXA4 and LTB4 was not changed in the n-3 FA supplementation group, while it was decreased in the placebo group (P < 0.05).

Fig. 4.

A, B: Correlation between changes in release of SPMs from Aβ40-exposed PBMCs and plasma TTR levels. A: LXA4 changes were positively correlated to changes in plasma TTR levels (Spearman’s rho test, r = 0.735, P < 0.01). B: The sum of changes in LXA4 and RvD1 was also correlated to changes in plasma TTR levels (Spearman’s rho test, r = 0.556, P < 0.05).