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?-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

ABSTRACT: IMPORTANCE:The role of ?-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE:To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5?-3), docosapentaenoic acid (DPA; 22:5?-3), and docosahexaenoic acid (DHA; 22:6?-3) and plant-derived ?-linolenic acid (ALA; 18:3?-3) for incident CHD. DATA SOURCES:A global consortium of 19 studies identified by November 2014. STUDY SELECTION:Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ?-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS:Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ?-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES:Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS:The 19 studies comprised 16 countries, 45?637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ?-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ?-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE:On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ?-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

SUBMITTER: Del Gobbo LC

PROVIDER: S-EPMC5183535 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

Del Gobbo Liana C LC Imamura Fumiaki F Aslibekyan Stella S Marklund Matti M Virtanen Jyrki K JK Wennberg Maria M Yakoob Mohammad Y MY Chiuve Stephanie E SE Dela Cruz Luicito L Frazier-Wood Alexis C AC Fretts Amanda M AM Guallar Eliseo E Matsumoto Chisa C Prem Kiesha K Tanaka Tosh T Wu Jason H Y JH Zhou Xia X Helmer Catherine C Ingelsson Erik E Yuan Jian-Min JM Barberger-Gateau Pascale P Campos Hannia H Chaves Paulo H M PH Djoussé Luc L Giles Graham G GG Gómez-Aracena Jose J Hodge Allison M AM Hu Frank B FB Jansson Jan-Håkan JH Johansson Ingegerd I Khaw Kay-Tee KT Koh Woon-Puay WP Lemaitre Rozenn N RN Lind Lars L Luben Robert N RN Rimm Eric B EB Risérus Ulf U Samieri Cecilia C Franks Paul W PW Siscovick David S DS Stampfer Meir M Steffen Lyn M LM Steffen Brian T BT Tsai Michael Y MY van Dam Rob M RM Voutilainen Sari S Willett Walter C WC Woodward Mark M Mozaffarian Dariush D

JAMA internal medicine 20160801 8

<h4>Importance</h4>The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers.<h4>Objective</h4>To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD.<h4>Data sources</h4>A gl ...[more]

PMID: 27357102

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Project description:BackgroundThe therapeutic and health promoting role of highly unsaturated fatty acids (HUFAs) from fish, i.e. eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) are well known. These same benefits may however be shared by some of their precursors, the polyunsaturated fatty acids (PUFAs), such as stearidonic acid (SDA, 18:4 n-3). In order to obtain alternative sources for the large-scale production of PUFAs, new searches are being conducted focusing on higher plants oils which can contain these n-3 and n-6 C18 precursors, i.e. SDA and GLA (18:3n-6, ?-linolenic acid).ResultsThe establishment of the novel Echium acanthocarpum hairy root cultures represents a powerful tool in order to research the accumulation and metabolism of fatty acids (FAs) in a plant particularly rich in GLA and SDA. Furthermore, this study constitutes the first example of a Boraginaceae species hairy root induction and establishment for FA studies and production. The dominant PUFAs, 18:2n-6 (LA, linoleic acid) and 18:3n-6 (GLA), accounted for about 50% of total FAs obtained, while the n-3 PUFAs, 18:3n-3 (ALA, ?-linolenic acid) and 18:4n-3 (SDA), represented approximately 5% of the total. Production of FAs did not parallel hairy root growth, and the optimal productivity was always associated with the highest biomass density during the culture period. Assuming a compromise between FA production and hairy root biomass, it was determined that sampling times 4 and 5 gave the most useful FA yields. Total lipid amounts were in general comparable between the different hairy root lines (29.75 and 60.95 mg/g DW), with the major lipid classes being triacylglycerols. The FAs were chiefly stored in the hairy roots with very minute amounts being released into the liquid nutrient medium.ConclusionsThe novel results presented here show the utility and high potential of E. acanthocarpum hairy roots. They are capable of biosynthesizing and accumulating a large range of polyunsaturated FAs, including the target GLA and SDA fatty acids in appreciable quantities.

Project description:BackgroundPolyunsaturated fatty acids (PUFAs) are associated with a lower risk of multiple diseases. Fatty acid desaturase 1 gene (FADS1) polymorphisms and dietary PUFA intake are both established determinants of circulating PUFA proportions.ObjectiveWe explored the joint effects of FADS1 polymorphisms and dietary PUFA intake on circulating PUFA proportions.DesignWe studied 2288 participants from a nested case-control study of coronary artery disease among participants who provided blood samples in the Nurses' Health Study and the Health Professionals Follow-Up Study. Dietary PUFA intake was obtained from semiquantitative food-frequency questionnaires. FADS1 rs174546 was genotyped by using the Affymetrix 6.0 platform, and circulating PUFA proportions were measured with gas-liquid chromatography. Linear regression models were used to examine the associations between rs174546 and circulating proportions of each fatty acid. Gene-diet interactions were tested by including a cross-product term of dietary intake of each PUFA by rs174546 genotype in the linear regression models.ResultsAfter adjustment for sex and ancestry, each copy of the C allele of rs174546 was associated with higher circulating proportions of arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and lower proportions of linoleic acid and α-linolenic acid. The magnitude of positive association between higher consumption of dietary EPA or DHA and circulating proportions of EPA increased with each copy of the rs174546_T allele (P-interaction = 0.01 and 0.007, respectively). Each 1-SD increment in EPA intake was associated with an average 3.7% increase in circulating EPA proportions among participants with the rs174546_CC genotype and an average 7.8% increase among participants with the TT genotype.ConclusionsCarriers of the T allele at FADS1 rs174546 may need higher doses of dietary EPA and DHA to achieve the same circulating proportions of EPA as carriers of the C allele. The implications of these findings on disease risk and dietary guidelines require further study.

Project description:Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial.The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012.This study promises to be the first trial to provide a novel prevention strategy for PTSD among traumatized people.ClinicalTrials.gov Identifier NCT00671099.

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?-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

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ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

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