Evidence map›Paper›PMID 24736647›Full record

Trial reportPloS one2014

Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives.

Chiara Cipollina, Sonia R Salvatore, Matthew F Muldoon, Bruce A Freeman, Francisco J Schopfer

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00663871 (BioBehavioral Studies of Cardiovascular Disease), which is not on this map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00663871 nacompletednot on this map

BioBehavioral Studies of Cardiovascular Disease

TypeinterventionalSponsorUniversity of PittsburghRan2008 to 2012Enrolled272ConditionsCardiovascular Diseases, Mood Disorders, InflammationArmsFish Oil, Soybean Oil (Placebo)
3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 56 citations in OpenAlex.

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  7. [Nutrigenetics: potentials and applications in cardiovascular diseases and associated risk factors].Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina) · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Chiara CipollinaFondazione Ri.Med, Palermo, Italy; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Sonia R SalvatoreDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Matthew F MuldoonDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh Pennsylvania, United States of America.
Bruce A FreemanDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Francisco J SchopferDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
University of Pittsburgh · USRi.MED · IT

Funding

Vascular Subphenotypes of Lung DiseaseP01HL103455 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLADWIN, MARK T · 2011 to 2020
$26.1M
Translational StudiesP30DK072506 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALCORN, JOHN F · 2005 to 2017
$12.5M
Redox-Derived Pulmonary Anti-Inflammatory MediatorsR01HL064937 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 2000 to 2015
$5.6M
Redox Transduction of Nitric Oxide SignalingR37HL058115 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 2008 to 2017
$5.2M
NITRIC OXIDE REGULATION OF VASCULAR OXIDANT INJURYR01HL058115 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 1998 to 2007
$3.3M
Formation of Omega 3-Derived Electrophiles During InflammationR01AT006822 · NCCIH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCHOPFER, FRANCISCO JOSE · 2011 to 2015
$1.8M
NCCIH NIH HHS R01 AT006822NHLBI NIH HHS P01 HL103455NHLBI NIH HHS P01-HL103455NHLBI NIH HHS R01 HL058115NHLBI NIH HHS R01-HL058115NHLBI NIH HHS R01 HL064937NHLBI NIH HHS R01-HL64937NHLBI NIH HHS R37 HL058115NIDDK NIH HHS P30 DK072506NIDDK NIH HHS P30-DK072506
6 · The paper itself

Abstract

unlabelledDietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2-dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial.

methodsEndogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments.

results5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels.

conclusionsThe endogenous detection of these electrophilic ω-3 fatty acid ketone derivatives supports the precept that the benefit of ω-3 PUFA-rich diets can be attributed to the generation of electrophilic oxygenated metabolites that transduce anti-inflammatory actions rather than the suppression of pro-inflammatory AA metabolites.

trial registrationClinicalTrials.gov NCT00663871.

Indexed as

DietAdultAnti-Inflammatory AgentsArachidonate 5-LipoxygenaseDose-Response Relationship, DrugFatty Acids, Omega-3FemaleHumansKetonesMaleMiddle AgedNeutrophilsAnti-Inflammatory AgentsArachidonate 5-LipoxygenaseFatty Acids, Omega-3Ketones

Identifiers

PMID24736647
PMCPMC3988126
OpenAlexW2012165749

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.