docosapentaenoic-acid and stearidonic-acid

The effect and association of omega-3 fatty acids (n-3 FA) intake and biomarker levels with cardiovascular (CV) clinical and intermediate outcomes remains controversial. We update prior Evidence Reports of n-3 FA and clinical and intermediate CV disease (CVD) outcomes.. Evaluate the effect of n-3 FA on clinical and selected intermediate CV outcomes and the association of n-3 FA intake and biomarkers with CV outcomes. The n-3 FA under review include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), stearidonic acid (SDA), and alphalinolenic acid (ALA).. MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CAB Abstracts from 2000 or 2002 to June 8, 2015, and eligible studies from the original reports and relevant existing systematic reviews.. We included randomized controlled trials (RCTs) of any n-3 FA intake compared to no, lower, or other n-3 FA intake with an outcome of interest conducted in healthy adults, those at risk for CVD, or those with CVD. We also included prospective observational studies of the association between baseline n-3 FA intake or biomarker level and followup outcomes. We required 1 year or more of followup for clinical outcomes and 4 weeks for intermediate outcomes (blood pressure [BP] and lipids).. From 11,440 citations (from electronic literature searches and existing systematic reviews), 829 abstracts met basic eligibility criteria; 61 RCTs and 37 longitudinal observational studies (in 147 articles) were included. Most RCTs and observational studies had few risk-of-bias concerns.. Total n-3 FA: There is low strength of evidence (SoE) of no association between total n-3 FA intake and stroke death or myocardial infarction. There is insufficient evidence for other outcomes.. Marine oils, total: There is moderate to high SoE that higher marine oil intake lowers triglycerides (Tg), raises high density lipoprotein cholesterol (HDL-c), and lowers the ratio of total cholesterol to HDL-c but raises low density lipoprotein cholesterol (LDL-c); also that higher marine oil intake does not affect major adverse CV events, all-cause death, total stroke, sudden cardiac death, coronary revascularization, atrial fibrillation, or BP. There is low SoE of associations between higher marine oil intake and decreased risk of CVD death, coronary heart disease (CHD), myocardial infarction, ischemic stroke, and congestive heart failure (CHF). There is low SoE of no association with CHD death or hemorrhagic stroke. There is insufficient evidence for other outcomes.. Marine oil FA individually: There is low SoE of no associations between EPA or DHA intake (separately) and CHD, and between EPA or DPA and atrial fibrillation. There is low SoE of no association between EPA biomarkers and atrial fibrillation, but moderate SoE of no effect of purified DHA supplementation on BP or LDL-c. There is insufficient evidence for other specific marine oil FA and outcomes.. ALA: There is moderate SoE of no effect of ALA intake on BP, LDL-c, HDL-c, or Tg. There is low SoE of no association between ALA intake or biomarker level and CHD, CHD death, atrial fibrillation, and CHF. There is insufficient evidence for other outcomes.. Other n-3 FA analyses: There is insufficient evidence comparing n-3 FA with each other or for SDA.. Subgroup analyses: Nineteen of 22 studies found no interaction of sex on any effect of n-3 FA. Likewise, 19 of 20 studies found no differential effect by statin co-use. Within 16 studies evaluating diabetes subgroups, 2 found statistically significant beneficial effects of n-3 FA in those with diabetes but not in those without diabetes, but no test of interaction was reported.. The 61 RCTs mostly compared marine oil supplements with placebo on CVD outcomes in populations at risk for CVD or with CVD, while the 37 observational studies mostly examined associations between various individual n-3 FA and long-term CVD events in generally healthy populations. Compared with the prior report on n-3 FA and CVD, there is more robust RCT evidence on ALA and on clinical CV outcomes; also, by design there are newly added data on associations between n-3 FA biomarkers and CV outcomes. However, conclusions regarding the effect of n-3 FA intake on CV outcomes or associations with outcomes remain substantially unchanged. Marine oils statistically significantly raise HDL-c and LDL-c by similar amounts (≤2 mg/dL), while lowering Tg in a dose-dependent manner, particularly in individuals with elevated Tg; they have no significant effect on BP. ALA has no significant effect on intermediate outcomes. Limited data were available from RCTs on the effect of n-3 FA on clinical CVD outcomes. Observational studies suggest that higher marine oil intake (including from dietary fish) is associated with lower risk of several CVD outcomes. No clear differences in effects or associations were evident based on population, demographic features, or cointerventions. Future RCTs would be needed to establish adequate evidence of the effect of n-3 FA on CVD outcomes or to clarify differential effects in different groups of people. However, future trials are unlikely to alter conclusions about the effects of n-3 FA supplementation on intermediate cardiovascular outcomes (BP, LDL-c, HDL-c, or Tg).

Topics: Biomarkers; Cardiovascular Diseases; Docosahexaenoic Acids; Eating; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Myocardial Infarction; Stroke

A plant-based strategy to improve long-chain (LC) omega (n)-3 PUFA supply in humans involves dietary supplementation with oils containing α-linolenic acid (ALA) alone or in combination with stearidonic acid (SDA). The study aimed to compare the effects of echium oil (EO) and linseed oil (LO) on LC n-3 PUFA accumulation in blood and on clinical markers.. In two double-blind, parallel-arm, randomized controlled studies, all volunteers started with 17 g/d run-in oil (2 weeks). Thereafter, subjects received diets enriched in study 1 with EO (5 g ALA + 2 g SDA; n = 59) or in study 2 with LO (5 g ALA; n =  9) daily for 8 weeks. The smaller control groups received fish oil (FO; n = 19) or olive oil (OO; n = 18). Participants were instructed to restrict their dietary n-3 PUFA intake throughout the studies (e.g., no fish). To investigate the influence of age and BMI on the conversion of ALA and SDA as well as clinical markers, the subjects recruited for EO and LO treatment were divided into three subgroups (two age groups 20-35 y; 49-69 y with BMI 18-25 kg/m(2) and one group with older, overweight subjects (age 49-69 y; BMI >25 kg/m(2)).. In plasma, red blood cells (RBC), and peripheral blood mononuclear cells (PBMC), EPA and docosapentaenoic acid (DPA) were ~25 % higher following EO compared to LO. Comparing all treatments, the effectiveness of increasing EPA and DPA in plasma, RBC, and PBMC was on average 100:25:10:0 and 100:50:25:0 for FO:EO:LO:OO, respectively. EO led to a lower arachidonic acid/EPA-ratio compared to LO in plasma, RBC, and PBMC. Following EO, final DHA was not greater compared to LO. Higher BMI correlated negatively with increases in plasma EPA and DPA after EO supplementation, but not after LO supplementation. Decreasing effect on plasma LDL-C and serum insulin was greater with EO than with LO.. Daily intake of SDA-containing EO is a better supplement than LO for increasing EPA and DPA in blood. However, neither EO nor LO maintained blood DHA status in the absence of fish/seafood consumption.. ClinicalTrials.gov Reg No. NCT01856179; ClinicalTrials.gov Reg No. NCT01317290.

Topics: Adult; Aged; Dietary Supplements; Double-Blind Method; Echium; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Humans; Leukocytes, Mononuclear; Linseed Oil; Male; Middle Aged; Plant Oils; Young Adult

For many persons who wish to obtain the health benefits provided by dietary n-3 fatty acids, daily ingestion of fish or fish oil is not a sustainable long-term approach. To increase the number of sustainable dietary options, a land-based source of n-3 fatty acids that is effective in increasing tissue concentrations of the long-chain n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is required.. The objective of the study was to examine the ability of dietary stearidonic acid (SDA) to increase tissue concentrations of EPA and DHA in healthy human subjects and to compare the effectiveness of SDA with that of the n-3 fatty acids alpha-linolenic acid (ALA) and EPA.. Encapsulated SDA, ALA, or EPA was ingested daily in doses of 0.75 g and then 1.5 g for periods of 3 wk each by healthy male and postmenopausal female subjects (n = 15/group) in a double-blind, parallel-group design.. Dietary SDA increased EPA and docosapentaenoic acid concentrations but not DHA concentrations in erythrocyte and in plasma phospholipids. The relative effectiveness of the tested dietary fatty acids in increasing tissue EPA was 1:0.3:0.07 for EPA:SDA:ALA.. Vegetable oils containing SDA could be a dietary source of n-3 fatty acids that would be more effective in increasing tissue EPA concentrations than are current ALA-containing vegetable oils. The use of SDA-containing oils in food manufacture could provide a wide range of dietary alternatives for increasing tissue EPA concentrations.

Topics: Adolescent; Adult; Aged; alpha-Linolenic Acid; Cytokines; Dietary Supplements; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Double-Blind Method; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Fish Oils; Humans; Male; Middle Aged; Patient Compliance; Tissue Distribution

Reconstitution of nonnative, very-long-chain polyunsaturated fatty acid (VLC-PUFA) biosynthetic pathways in Arabidopsis thaliana was undertaken. The introduction of three primary biosynthetic activities to cells requires the stable coexpression of multiple proteins within the same cell. Herein, we report that C22 VLC-PUFAs were synthesized from C18 precursors by reactions catalyzed by Δ(6)-desaturase, an ELOVL5-like enzyme involved in VLC-PUFA elongation, and Δ(5)-desaturase. Coexpression of the corresponding genes (McD6DES, AsELOVL5, and PtD5DES) under the control of the seed-specific vicilin promoter resulted in production of docosapentaenoic acid (22:5 n-3) and docosatetraenoic acid (22:4 n-6) as well as eicosapentaenoic acid (20:5 n-3) and arachidonic acid (20:4 n-6) in Arabidopsis seeds. The contributions of the transgenic enzymes and endogenous fatty acid metabolism were determined. Specifically, the reasonable synthesis of omega-3 stearidonic acid (18:4 n-3) could be a useful tool to obtain a sustainable system for the production of omega-3 fatty acids in seeds of a transgenic T3 line 63-1. The results indicated that coexpression of the three proteins was stable. Therefore, this study suggests that metabolic engineering of oilseed crops to produce VLC-PUFAs is feasible.

Topics: Arabidopsis; Arachidonic Acid; Biosynthetic Pathways; Eicosapentaenoic Acid; Fatty Acid Desaturases; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Gene Expression Regulation, Plant; Metabolic Engineering; Plants, Genetically Modified; Seeds

Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders.. The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes.. Supplementation with several EO/BO combinations increased circulating 20-22 carbon (20-22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%.. This study shows that dietary supplementation with BO/EO alters 20-22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation.

Topics: 8,11,14-Eicosatrienoic Acid; Adolescent; Adult; alpha-Linolenic Acid; Asthma; Cells, Cultured; Dietary Supplements; Echium; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Inflammation; Leukocytes, Mononuclear; Leukotrienes; Male; Middle Aged; Plant Oils; Seeds

The incorporation and metabolism of alpha-linolenic acid (18:3n-3) and its delta 6 desaturase product, stearidonic acid (18:4n-3), were compared by NIH-3T3 cells. In the presence of fetal calf serum, cells accumulated exogenously added 18:3n-3 and 18:4n-3 apparently at the expense of oleic acid (18:1n-9). Both 18:3n-3 and 18:4n-3 were elongated and desaturated to eicosatetraenoic acid (20:4n-3), eicosapentaenoic acid (20:5n-3) and docosapentaenoic acid (22:5n-3), but not to docosahexaenoic acid (22:6n-3), and were incorporated into phospholipids and triacylglycerols. Over a 4-d period, the growth of NIH-3T3 cells was slightly stimulated in the presence of 18:3n-3 (20 micrograms/mL) but was strongly inhibited in the presence of 18:4n-3 at the same concentration. This inhibition may be caused by enhanced lipid peroxidation as a result of the high levels of 18:4n-3 present.

Topics: 3T3 Cells; alpha-Linolenic Acid; Animals; Arachidonic Acids; Cell Division; Dose-Response Relationship, Drug; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Linolenic Acids; Mice; Phospholipids; Triglycerides