Reduced prostaglandin F2 alpha release from blood mononuclear leukocytes after oral supplementation of omega3 fatty acids: the OmegAD study

Abstract

Omega-3 fatty acids, e.g., dokosahexaenoic acid (DHA) and eikosapentaenoic acid (EPA), ameliorate inflammatory reactions by various mechanisms, but the role of prostaglandins remains unclear. Our aim was to determine if dietary supplementation with a DHA-rich fish oil influenced the release of PGF(2alpha) from peripheral blood mononuclear cells (PBMC). In the OmegAD study, 174 Alzheimer disease patients received either 1.7 g DHA plus 0.6 g EPA or a placebo daily for six months. PBMCs from the 21 (9 on fish oil and 12 on placebo) first-randomized patients were stimulated with either lipopolysaccharide (LPS) or phytohemagglutinin (PHA) before and after 6 months. Our results showed that plasma concentrations of DHA and EPA increased significantly at 6 months in the omega-3 group. PGF(2alpha) release from LPS- (but not from PHA-) stimulated PBMC was significantly diminished in this group; no change was noted in the placebo group. PGF(2alpha) changes correlated inversely with changes in plasma DHA and EPA. Decreased IL-6 and IL-1(beta) levels correlated with decreased PGF(2alpha) levels. The stimulus-specific PGF(2alpha) release from PBMC after 6 months of oral supplementation with the DHA-rich fish oil might be one event related to reduced inflammatory reactions associated with omega-3 fatty acid intake.

Trial registration: ClinicalTrials.gov NCT00211159.

Fig. 1.

Changes in PGF_2α release from PBMC, stimulated with 10 ng LPS/ml. PBMC were obtained from patients with mild to moderate Alzheimer's disease, before and after 6 months of ω3 FAs or placebo oil supplementation. Individual values are flanked by median and 25^th–75^th percentile values. LPS, lipopolysaccharide; PBMC, peripheral blood mononuclear cell; PGF_2α, prostaglandin F_2α.

Fig. 2.

Correlations between changes of PGF_2α and DHA (top left), EPA (top right), IL-6 (bottom left) or IL-1β (bottom right). Values for PGF_2α, IL-6 and Il-1β refer to releases from LPS stimulated PBMC, while values for EPA and DHA refer to plasma concentrations (28). Solid lines = regression line. Dotted lines = the 95% confidence interval for the regression line. DHA, dokosahexaenoic acid; EPA, eikosapentaenoic acid; IL, interleukin; LPS, lipopolysaccharide; PBMC, peripheral blood mononuclear cell; PGF_2α, prostaglandin F_2α.