Dose- and time-dependent increase in circulating anti-inflammatory and pro-resolving lipid mediators following eicosapentaenoic acid supplementation in patients with major depressive disorder and chronic inflammation.
Eicosapentaenoic acid (EPA)
Omega-3 fatty acids
Pro-resolving lipid mediators (SPM)
major depressive disorder (MDD)
Journal
Prostaglandins, leukotrienes, and essential fatty acids
ISSN: 1532-2823
Titre abrégé: Prostaglandins Leukot Essent Fatty Acids
Pays: Scotland
ID NLM: 8802730
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
21
07
2020
revised:
23
11
2020
accepted:
24
11
2020
pubmed:
15
12
2020
medline:
3
6
2021
entrez:
14
12
2020
Statut:
ppublish
Résumé
Eicosapentaenoic acid (EPA) supplementation is an effective treatment option in major depressive disorder (MDD) associated with chronic low-grade inflammation. EPA is the precursor of specialized pro-resolving lipid mediators (SPMs) termed resolvins (Rv), that serve important roles in the resolution of inflammation. The objective of this study was to assess the effects of different doses of EPA on plasma concentrations of EPA metabolites and SPMs in MDD patients. In a 2-site study, 61 MDD patients with body mass index >25 kg/m Plasma EPA and SPM concentrations did not change in the placebo group during 12 weeks of treatment. Plasma EPA and EPA-derived metabolites increased significantly and dose-dependently in all EPA supplementation arms. The increase in 18-hydroxyeicosapentaenoic acid (18-HEPE), the precursor of RvE1-3, was significantly greater with the 4 g/d EPA dose than the other doses from week 4 to 12. RvE1 was undetected in all treatment groups, while RvE2 was detected in half of the subjects both at baseline and after treatment, with dose-dependent increases. RvE3 was detected only after supplementation, dose-dependently. A significant reduction in plasma arachidonic acid (AA), relative to baseline, was observed in all EPA arms. This was in contrast with an increase in AA-derived SPM lipoxin B4 (LXB4) in the 4 g/d arm. Our results show a robust effect of EPA 4 g/d supplementation in increasing plasma EPA and 18-HEPE levels, associated with improved conversion to RvE2-3, and LXB4 levels.
Sections du résumé
BACKGROUND
Eicosapentaenoic acid (EPA) supplementation is an effective treatment option in major depressive disorder (MDD) associated with chronic low-grade inflammation. EPA is the precursor of specialized pro-resolving lipid mediators (SPMs) termed resolvins (Rv), that serve important roles in the resolution of inflammation. The objective of this study was to assess the effects of different doses of EPA on plasma concentrations of EPA metabolites and SPMs in MDD patients.
METHODS
In a 2-site study, 61 MDD patients with body mass index >25 kg/m
RESULTS
Plasma EPA and SPM concentrations did not change in the placebo group during 12 weeks of treatment. Plasma EPA and EPA-derived metabolites increased significantly and dose-dependently in all EPA supplementation arms. The increase in 18-hydroxyeicosapentaenoic acid (18-HEPE), the precursor of RvE1-3, was significantly greater with the 4 g/d EPA dose than the other doses from week 4 to 12. RvE1 was undetected in all treatment groups, while RvE2 was detected in half of the subjects both at baseline and after treatment, with dose-dependent increases. RvE3 was detected only after supplementation, dose-dependently. A significant reduction in plasma arachidonic acid (AA), relative to baseline, was observed in all EPA arms. This was in contrast with an increase in AA-derived SPM lipoxin B4 (LXB4) in the 4 g/d arm.
CONCLUSIONS
Our results show a robust effect of EPA 4 g/d supplementation in increasing plasma EPA and 18-HEPE levels, associated with improved conversion to RvE2-3, and LXB4 levels.
Identifiants
pubmed: 33316626
pii: S0952-3278(20)30177-0
doi: 10.1016/j.plefa.2020.102219
pmc: PMC7855824
mid: NIHMS1654304
pii:
doi:
Substances chimiques
Eicosapentaenoic Acid
AAN7QOV9EA
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
102219Subventions
Organisme : NCRR NIH HHS
ID : S10 RR027926
Pays : United States
Organisme : NCCIH NIH HHS
ID : UG3 AT008857
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Références
Prostaglandins Other Lipid Mediat. 2014 Jun;109-111:23-31
pubmed: 24667634
Psychiatry Res. 2015 Sep 30;229(1-2):485-9
pubmed: 26188642
Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):3963-3968
pubmed: 28356517
Psychosom Med. 2011 Jul-Aug;73(6):462-8
pubmed: 21715300
J Exp Med. 2000 Oct 16;192(8):1197-204
pubmed: 11034610
J Immunol. 2003 Jun 15;170(12):6266-72
pubmed: 12794159
Nat Immunol. 2005 Dec;6(12):1191-7
pubmed: 16369558
J Immunol. 2012 May 1;188(9):4527-34
pubmed: 22450811
Trends Immunol. 2007 Apr;28(4):176-83
pubmed: 17337246
Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:21-9
pubmed: 24880049
Prostaglandins Leukot Essent Fatty Acids. 2020 Jul;158:102033
pubmed: 31740197
Immunity. 2014 Mar 20;40(3):315-27
pubmed: 24656045
Biochem Soc Trans. 2017 Oct 15;45(5):1105-1115
pubmed: 28900017
FASEB J. 2008 Oct;22(10):3595-606
pubmed: 18559988
Sci Rep. 2018 Dec 21;8(1):18050
pubmed: 30575798
J Lipid Res. 2005 Jul;46(7):1474-83
pubmed: 15834128
J Leukoc Biol. 2019 Jan;105(1):25-36
pubmed: 29601102
Am J Clin Nutr. 2019 May 1;109(5):1251-1263
pubmed: 31006007
N Engl J Med. 1999 Jan 14;340(2):115-26
pubmed: 9887164
J Psychiatr Res. 2018 Dec;107:48-56
pubmed: 30317101
J Biol Chem. 2012 Mar 23;287(13):10525-34
pubmed: 22275352
Mol Psychiatry. 2016 Jan;21(1):71-9
pubmed: 25802980
Circ Res. 2020 Jan 3;126(1):75-90
pubmed: 31829100
J Lipid Res. 2014 Jun;55(6):1150-64
pubmed: 24634501
J Lipid Res. 2010 Aug;51(8):2074-81
pubmed: 19671931
Anal Chem. 2012 Feb 7;84(3):1483-90
pubmed: 22224852
PLoS One. 2015 Dec 16;10(12):e0144996
pubmed: 26672987
J Lipid Res. 2011 May;52(5):991-1003
pubmed: 21296957
Inflamm Allergy Drug Targets. 2006 Apr;5(2):91-106
pubmed: 16613568
Prev Chronic Dis. 2006 Jul;3(3):A77
pubmed: 16776878
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1751-6
pubmed: 12578976
Prostaglandins Leukot Essent Fatty Acids. 2005 Sep-Oct;73(3-4):141-62
pubmed: 16005201
N Engl J Med. 2019 Jan 3;380(1):11-22
pubmed: 30415628
FASEB J. 2019 Nov;33(11):12750-12759
pubmed: 31469599
Circ J. 2010 Feb;74(2):213-20
pubmed: 20065609
J Pharmacol Sci. 2018 Sep;138(1):86-88
pubmed: 30293959
Transl Psychiatry. 2019 Aug 5;9(1):190
pubmed: 31383846
Haematologica. 2020 Aug;105(8):2056-2070
pubmed: 31780628
Acta Psychiatr Scand. 2017 May;135(5):373-387
pubmed: 28122130
FASEB J. 2014 Nov;28(11):4835-46
pubmed: 25059230
Psychother Psychosom. 2019;88(5):263-273
pubmed: 31480057