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Plasma oxylipins respond in a linear dose-response manner with increased intake of eicosapentaenoic and docosahexaenoic acids: results from a randomized controlled trial in healthy humans

Plasma oxylipins respond in a linear dose-response manner with increased intake of eicosapentaenoic and docosahexaenoic acids: results from a randomized controlled trial in healthy humans
Plasma oxylipins respond in a linear dose-response manner with increased intake of eicosapentaenoic and docosahexaenoic acids: results from a randomized controlled trial in healthy humans
Background
The health effects of long-chain omega-3 polyunsaturated fatty acids (n–3 PUFAs) are partly mediated by their oxidized metabolites, i.e., eicosanoids and other oxylipins. Some intervention studies have demonstrated that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase systemic concentrations of n–3 PUFA–derived oxylipins and moderately decrease arachidonic acid–derived oxylipins. There is no information on the dose-response of oxylipin concentrations after n–3 PUFA intake.

Objective
The aim of this study was to quantify oxylipins in human plasma samples from an intervention study in which participants were randomly assigned to different daily intakes of EPA and DHA for 12 mo.

Methods
Healthy adult men and women with low habitual fish consumption (n = 121) were randomly assigned to receive capsules providing doses of n–3 PUFAs reflecting 3 patterns of consumption of oily fish [1, 2, or 4 portions/wk with 3.27 g EPA + DHA (1:1.2, wt:wt) per portion] or placebo. Oxylipins were quantified in plasma after 3 and 12 mo. Relative and absolute changes of individual oxylipins were calculated and concentrations were correlated with the dose and the content of EPA and DHA in blood lipid pools.

Results
Seventy-three oxylipins, mostly hydroxy-, dihydroxy-, and epoxy-PUFAs, were quantified in the plasma samples. After 3 and 12 mo a linear increase with dose was observed for all EPA- and DHA-derived oxylipins. Cytochrome-P450-derived anti-inflammatory and cardioprotective epoxy-PUFAs increased linearly with n–3 PUFA dose and showed low interindividual variance (r2 > 0.95). Similarly, 5, 12-, and 15-lipoxygenase–derived hydroxy-PUFAs as well as those formed autoxidatively increased linearly. These include the precursors of so-called specialized pro-resolving lipid mediators (SPMs), e.g., 17-hydroxy-DHA and 18-hydroxy-EPA.

Conclusions
Plasma concentrations of biologically active oxylipins derived from n–3 PUFAs, including epoxy-PUFAs and SPM-precursors, increase linearly with elevated intake of EPA and DHA. Interindividual differences in resulting plasma concentrations are low. This trial was registered at controlled-trials.com as ISRCTN48398526.
0002-9165
1251-1263
Ostermann, Annika I.
9650d021-eac7-4ae6-8fc8-bfae1ed14459
West, Annette
c1923242-802f-4331-b743-31de45d3883c
Schoenfeld, Kirsten
b932bf33-4ed4-4aba-bb4a-98603349d704
Browning, Lucy M.
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Walker, Celia G.
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Jebb, Susan A.
11904a4d-1abb-43ba-9d4b-d5da37ae1ebd
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Schebb, Nils Helge
16843e52-c7b0-4a9a-b1c0-c380957becd9
Ostermann, Annika I.
9650d021-eac7-4ae6-8fc8-bfae1ed14459
West, Annette
c1923242-802f-4331-b743-31de45d3883c
Schoenfeld, Kirsten
b932bf33-4ed4-4aba-bb4a-98603349d704
Browning, Lucy M.
5512da89-c00a-4799-a6d5-c877a4dac4d6
Walker, Celia G.
fd803965-580a-4002-b5b6-b13a5be8da0d
Jebb, Susan A.
11904a4d-1abb-43ba-9d4b-d5da37ae1ebd
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Schebb, Nils Helge
16843e52-c7b0-4a9a-b1c0-c380957becd9

Ostermann, Annika I., West, Annette, Schoenfeld, Kirsten, Browning, Lucy M., Walker, Celia G., Jebb, Susan A., Calder, Philip and Schebb, Nils Helge (2019) Plasma oxylipins respond in a linear dose-response manner with increased intake of eicosapentaenoic and docosahexaenoic acids: results from a randomized controlled trial in healthy humans. American Journal of Clinical Nutrition, 109 (5), 1251-1263. (doi:10.1093/ajcn/nqz016).

Record type: Article

Abstract

Background
The health effects of long-chain omega-3 polyunsaturated fatty acids (n–3 PUFAs) are partly mediated by their oxidized metabolites, i.e., eicosanoids and other oxylipins. Some intervention studies have demonstrated that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase systemic concentrations of n–3 PUFA–derived oxylipins and moderately decrease arachidonic acid–derived oxylipins. There is no information on the dose-response of oxylipin concentrations after n–3 PUFA intake.

Objective
The aim of this study was to quantify oxylipins in human plasma samples from an intervention study in which participants were randomly assigned to different daily intakes of EPA and DHA for 12 mo.

Methods
Healthy adult men and women with low habitual fish consumption (n = 121) were randomly assigned to receive capsules providing doses of n–3 PUFAs reflecting 3 patterns of consumption of oily fish [1, 2, or 4 portions/wk with 3.27 g EPA + DHA (1:1.2, wt:wt) per portion] or placebo. Oxylipins were quantified in plasma after 3 and 12 mo. Relative and absolute changes of individual oxylipins were calculated and concentrations were correlated with the dose and the content of EPA and DHA in blood lipid pools.

Results
Seventy-three oxylipins, mostly hydroxy-, dihydroxy-, and epoxy-PUFAs, were quantified in the plasma samples. After 3 and 12 mo a linear increase with dose was observed for all EPA- and DHA-derived oxylipins. Cytochrome-P450-derived anti-inflammatory and cardioprotective epoxy-PUFAs increased linearly with n–3 PUFA dose and showed low interindividual variance (r2 > 0.95). Similarly, 5, 12-, and 15-lipoxygenase–derived hydroxy-PUFAs as well as those formed autoxidatively increased linearly. These include the precursors of so-called specialized pro-resolving lipid mediators (SPMs), e.g., 17-hydroxy-DHA and 18-hydroxy-EPA.

Conclusions
Plasma concentrations of biologically active oxylipins derived from n–3 PUFAs, including epoxy-PUFAs and SPM-precursors, increase linearly with elevated intake of EPA and DHA. Interindividual differences in resulting plasma concentrations are low. This trial was registered at controlled-trials.com as ISRCTN48398526.

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2019-02-08_MS_clean - Accepted Manuscript
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More information

Accepted/In Press date: 23 January 2019
e-pub ahead of print date: 21 April 2019
Published date: 1 May 2019

Identifiers

Local EPrints ID: 429831
URI: http://eprints.soton.ac.uk/id/eprint/429831
ISSN: 0002-9165
PURE UUID: 21d37fe9-64dd-4369-b196-946a62801ad6
ORCID for Annette West: ORCID iD orcid.org/0000-0002-3331-0684
ORCID for Philip Calder: ORCID iD orcid.org/0000-0002-6038-710X

Catalogue record

Date deposited: 05 Apr 2019 16:30
Last modified: 26 Nov 2021 05:32

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Contributors

Author: Annika I. Ostermann
Author: Annette West ORCID iD
Author: Kirsten Schoenfeld
Author: Lucy M. Browning
Author: Celia G. Walker
Author: Susan A. Jebb
Author: Philip Calder ORCID iD
Author: Nils Helge Schebb

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