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Clinical Trial
. 2017 Sep-Oct;11(5):1289-1295.
doi: 10.1016/j.jacl.2017.06.011. Epub 2017 Jun 24.

Relationship between the omega-3 index and specialized pro-resolving lipid mediators in patients with peripheral arterial disease taking fish oil supplements

Melinda S Schaller  1 , Greg J Zahner  2 , Warren J Gasper  3 , William S Harris  4 , Michael S Conte  2 , Nancy K Hills  5 , S Marlene Grenon  3
Affiliations
Clinical Trial

Relationship between the omega-3 index and specialized pro-resolving lipid mediators in patients with peripheral arterial disease taking fish oil supplements

Melinda S Schaller et al. J Clin Lipidol. 2017 Sep-Oct.

Abstract

Background: Oral supplementation with n-3 polyunsaturated fatty acids (PUFA) increases the omega-3 index, a biomarker of red blood cell eicosapentaenoic acid and docosahexaenoic acid, and plasma levels of biosynthesis pathway markers and potent lipid mediators involved in the resolution of inflammation among patients with peripheral arterial disease (PAD).

Objective: We aimed to quantify the association between an upstream change in the omega-3 index and downstream changes in lipid mediator production.

Methods: We conducted a secondary analysis of the OMEGA-PAD I Trial, a randomized, placebo controlled trial investigating high-dose n-3 PUFA oral supplementation in PAD patients. Eighty subjects were randomized to either 4.4 g of fish oil or placebo for 1 month. Regression analyses using generalized estimating equation techniques were used to investigate the relationship between changes in the omega-3 index and changes in lipid mediators, pre- and post-intervention.

Results: In the fish oil group, there was a significant increase in the omega-3 index (5 ± 1% to 9 ± 2%, P < .001) as well as in the plasma levels of several downstream lipid mediator pathway markers of resolution, which are involved with the regulation of leukocyte effector function and host defense. A doubling of the omega-3 index correlated with increases of 2.3-fold in 18-hydroxy-eicosapentaenoic acid (HEPE; P < .0001), 1.7-fold in 15-HEPE (P = .03), 1.9-fold in 5-HEPE (P = .04), and 3.6-fold in 4-hydroxy-docosahexaenoic acid (P < .001).

Conclusion: Among subjects with symptomatic PAD who took oral fish oil supplements for 1 month, observed changes in the omega-3 index were strongly associated with increases in downstream mediators in the biochemical pathways of resolution.

Keywords: Fish oil; Lipid mediators; Omega-3 index; Peripheral artery disease; Resolution of inflammation; Specialized pro-resolving mediators; n-3 polyunsaturated fatty acids.

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Conflict of interest statement

Conflicts of Interest

The authors declare no financial conflicts of interest.

Figures

Figure 1
Figure 1
Biosynthetic pathway of identified pathway markers and specialized pro-resolving mediators. EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; HEPE, hydroxyeicosapentaenoic acid; HDHA, hydroxydocosahexaenoic acid.
See this image and copyright information in PMC

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