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

J Lipid Res. 2015 Mar;56(3):674-681. doi: 10.1194/jlr.P055418. Epub 2015 Jan 23.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / drug therapy
  • Amyloid beta-Peptides / pharmacology
  • Cells, Cultured
  • Cognition / drug effects*
  • Double-Blind Method
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-6 / administration & dosage
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Male
  • Peptide Fragments / pharmacology

Substances

  • Amyloid beta-Peptides
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Inflammation Mediators
  • Peptide Fragments
  • amyloid beta-protein (10-40)