Eicosapentaenoic Acid/docosahexaenoic Acid Research Articles

The Relationship of Omega-3 Fatty Acids with Dementia and Cognitive Decline: Evidence from Prospective Cohort Studies of Supplementation, Dietary Intake, and Blood Markers

Previous data have linked omega-3 fatty acids with risk of dementia. We aimed to assess the longitudinal relationships of omega-3 polyunsaturated fatty acid intake as well as blood biomarkers with risk of Alzheimer’s disease (AD), dementia, or cognitive decline. Longitudinal data were derived from 1135 participants without dementia (mean age = 73 y) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort to evaluate the associations of omega-3 fatty acid supplementation and blood biomarkers with incident AD during the 6-y follow-up. A meta-analysis of published cohort studies was further conducted to test the longitudinal relationships of dietary intake of omega-3 and its peripheral markers with all-cause dementia or cognitive decline. Causal dose–response analyses were conducted using the robust error meta-regression model. In the ADNI cohort, long-term users of omega-3 fatty acid supplements exhibited a 64% reduced risk of AD (hazard ratio: 0.36, 95% confidence interval: 0.18, 0.72; P = 0.004). After incorporating 48 longitudinal studies involving 103,651 participants, a moderate-to-high level of evidence suggested that dietary intake of omega-3 fatty acids could lower risk of all-cause dementia or cognitive decline by ∼20%, especially for docosahexaenoic acid (DHA) intake (relative risk [RR]: 0.82, I2 = 63.6%, P = 0.001) and for studies that were adjusted for apolipoprotein APOE ε4 status (RR: 0.83, I2 = 65%, P = 0.006). Each increment of 0.1 g/d of DHA or eicosapentaenoic acid (EPA) intake was associated with an 8% ∼ 9.9% (Plinear < 0.0005) lower risk of cognitive decline. Moderate-to-high levels of evidence indicated that elevated levels of plasma EPA (RR: 0.88, I2 = 38.1%) and erythrocyte membrane DHA (RR: 0.94, I2 = 0.4%) were associated with a lower risk of cognitive decline. Dietary intake or long-term supplementation of omega-3 fatty acids may help reduce risk of AD or cognitive decline.

Assessment of lipid composition and eicosapentaenoic acid/docosahexaenoic acid bioavailability in fish oil obtained through different enrichment methods.

In this study, we analyzed the eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) lipid composition of fish oil obtained through enzymatic treatment, fractional distillation and silica gel column purification, and further assessed EPA/DHA bioavailability. Lipid subclass composition information was obtained through ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), and bioavailability tests were performed using the Caco-2 cell monolayer model. Results showed that enzymatic treatment improved the incorporation of EPA/DHA as diacylglycerol (DG) while silica gel column chromatography enriched the content of EPA/DHA as phosphatidylglycerol (PG) (12.58%) and phosphatidylethanolamine (PE) (4.99%). Furthermore, increasing the purity of EPA/DHA could improve its bioavailability and after 24 incubation, binding forms of triglyceride (TG) was superior to ethyl ester (EE) (p < 0.05) at the same purity level. Those findings are helpful to provide research basis for exploring the bioactivity of fish oil.

Lipidomic analysis and triglyceride profiles of fish oil: Preparation through silica gel column and enzymatic treatment

A comprehensive study of lipidomic coupled with triglyceride profiles onto four fish oils was performed through ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). Overall, 1010 lipids belonging to 6 categories and 38 lipid classes were identified. Triglycerides (TGs) were the dominant component in four fish oils (40 %–99 % of total lipids), and glycerophospholipids (GPs) and sphingolipids (SLs) were another two major lipid categories in the fish oil (TG50) which prepared through silica gel column. These results revealed that enzymatic treatment has slight effect on lipid distribution but silica gel column could change the lipids composition. TGs composition of four fish oils were separated completely, and the most TG molecule in TG50 is TG(18:3_14:0_18:0), possessed 13.03 ± 5.07 % relative content, these results implied that silica gel column could protect the nature structure of TGs from destroying which may also limited to further improve eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) purity, but enzymic method was not restricted by this.

Ethyl EPA and ethyl DHA cause similar and differential changes in plasma lipid concentrations and lipid metabolism in subjects with low-grade chronic inflammation

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to similarly lower plasma TG concentrations but differentially regulate plasma LDL-C and HDL-C concentrations. The aim of this study was to evaluate the common and differential effects of these ω-3 fatty acids on plasma lipids and lipoproteins and to assess the metabolic mechanisms of the effects. In a randomized, double-blind, crossover study, we assessed the effect of 10-week supplementation with 3 g/d pure EPA and pure DHA (both as ethyl ester, ≥97% purity) on plasma lipid and lipoprotein concentrations and activities of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) in 21 older (>50 y) men and postmenopausal women with some characteristics of metabolic syndrome and low-grade chronic inflammation. Both EPA and DHA lowered plasma TG concentrations and increased LDL-C/apoB and HDL-C/apoA-I ratios, but only DHA increased LDL-C concentrations. The reductions in plasma TG were inversely associated with the changes in LPL activity after both EPA and DHA supplementation. EPA lowered CETP, while DHA lowered LCAT activity. EPA and DHA worked differently in men and women, with DHA increasing LPL activity and LDL-C concentrations in women, but not in men. EPA and DHA exerted similar effects on plasma TG, but differences were observed in LDL-C concentrations and activities of some enzymes involved in lipoprotein metabolism. It was also noted that EPA and DHA worked differently in men and women, supporting sex-specific variations in lipoprotein metabolism.

Brain PUFA Concentrations Are Differentially Affected by Interactions of Diet, Sex, Brain Regions, and Phospholipid Pools in Mice

PUFAs play vital roles in the development, maintenance, and functioning of circuitries that regulate reward and social behaviors. Therefore, modulations in PUFA concentrations of these brain regions may disrupt reward and social circuitries contributing to mood disorders, developmental disabilities, and addictions. Though much is known about regional and phospholipid-pool-specific PUFA concentrations, less is known about the effects of dietary interventions that concurrently lowers n-6 PUFA and supplements n-3 PUFA, on brain PUFA concentrations. There is even less knowledge on the effects of sex on brain PUFA concentrations. This study aimed to comprehensively examine the interaction effects of diet (D), sex (S), brain regions (BR), and phospholipid pools (PL) on brain PUFA concentrations. Male and female C57BL/6J mice were fed 1 of 4 custom-designed diets varying in linoleic acid (LNA) (8en% or 1 en%) and eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) (0.4 en% or 0 en%) concentrations from in utero to 15 weeks old. At 15 weeks old, the prefrontal cortex, dorsal striatum, and cerebellum were collected. Fatty acids of 5 major PL were quantified by GC-flame ionization detection. Repeated measures ANOVA was used to test for differences among the groups for D, S, BR, and PL. No significant 4-way interactions on PUFA concentrations. DHA, predominant n-3 PUFA, concentrations were dependent on significant D × BR × PL interactions. DHA concentration was not affected by sex. Arachidonic acid (ARA; predominant n-6 PUFA) concentrations were not dependent on 3-way interactions. However, significant 2-way D × PL, BR × PL, and D × Sinteractions affected ARA concentrations. Brain fatty acid concentrations were differentially affected by various combinations of D, S, BR, and PL interactions. Though DHA concentrations are not affected by sex, ARA concentrations are affected by interactions of the 4 variables examined. This study provides comprehensive references in the investigation of complex interactions between factors that affect brain PUFA concentrations in mice.

PSIX-33 Docosahexaenoic Acid (DHA) but not Eicosapentaenoic Acid (EPA) induces the trans-differentiation of C2C12 into white-like adipocytes phenotype

Abstract Muscle-derived stem cells (MDSCs, or myoblasts) play an important role in myotubes regeneration. However, these cells can differentiate into adipocytes once exposed to EPA and DHA, which are highly suggested during pregnancy. The objective of this study aims at determining the effect of isolated EPA and DHA on C2C12 cells undergoing white and brown adipogenic differentiation. Confluent cultured cells were treated with white and brown adipocyte induction medium (WIM and BIM respectively) with 50µM EPA and 50µM DHA separately. DHA treated groups differentiated into white-like adipocyte by down-regulating the expression of myogenic genes such as MyoD, MyoG, and Mrf4; but promoted white adipocyte marker genes(P &amp;lt; 0.05). Moreover, cells treated with WIM and DHA exhibited a decrease in mitochondrial biogenesis through suppressing PGC1a and TFAM expression (P &amp;lt; 0.05). Also, DHA promoted the expression of lipolysis regulating genes. DHA impaired C2C12 cells browning through reducing the mitochondrial biogenesis by significantly suppressing the expression of COX7a1, PGC1a, and UCP3 genes (P &amp;lt; 0.05). DHA treated groups showed an increased accumulation of lipid droplets and suppressed maximal mitochondrial respiration and spare capacity. EPA treatment reduced myogenesis regulating genes (P &amp;lt; 0.05) but did not affect adipogenic genes (P &amp;gt;0.05). Likewise, EPA suppressed the expression of WAT signature genes (P &amp;lt; 0.05), indicating its antagonism to DHA. EPA and WIM treatment suppressed the expression of TFAM and PGC1a, but did not affect PGC1a protein level. Although mitochondrial biogenic gene expression was reduced in EPA and BIDM treated group, no changes in mitochondrial function were observed. EPA supplementation did not affect the differential route of C2C12 into brown adipocytes. To conclude, EPA and DHA may similarly affect the integrity of muscle tissue, but DHA is a potent adipogenic and lipogenic factor that can change the metabolic profile of the body by increasing intramuscular fat.

Chemical Compositional Changes in Over-Oxidized Fish Oils.

A recent study has reported that the administration during gestation of a highly rancid hoki liver oil, obtained by oxidation through sustained exposure to oxygen gas and incident light for 30 days, causes newborn mortality in rats. This effect was attributed to lipid hydroperoxides formed in the omega-3 long-chain polyunsaturated fatty acid-rich oil, while other chemical changes in the damaged oil were overlooked. In the present study, the oxidation condition employed to damage the hoki liver oil was replicated, and the extreme rancidity was confirmed. A detailed analysis of temporal chemical changes resulting from the sustained oxidative challenge involved measures of eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) omega-3 oil oxidative quality (peroxide value, para-anisidine value, total oxidation number, acid value, oligomers, antioxidant content, and induction time) as well as changes in fatty acid content, volatiles, isoprostanoids, and oxysterols. The chemical description was extended to refined anchovy oil, which is a more representative ingredient oil used in omega-3 finished products. The present study also analyzed the effects of a different oxidation method involving thermal exposure in the dark in contact with air, which is an oxidation condition that is more relevant to retail products. The two oils had different susceptibility to the oxidation conditions, resulting in distinct chemical oxidation signatures that were determined primarily by antioxidant protection as well as specific methodological aspects of the applied oxidative conditions. Unique isoprostanoids and oxysterols were formed in the over-oxidized fish oils, which are discussed in light of their potential biological activities.

Effects of dietary essential fatty acid requirements on growth performance, fatty acid composition, biochemical parameters, antioxidant response and lipid related genes expression in juvenile Onychostoma macrolepis

This study was conducted to elucidate effects of dietary essential fatty acid requirements on the growth, physiological characteristics and expressions of some lipid-related genes in juvenile Onychostoma macrolepis. Seven isonitrogenous and isoenergetic purified diets containing tristearin (control group), 2% linoleic acid (LA), 2% α-linolenic acid (LNA), 1% LA + 1% LNA, 1% eicosapentaenoic acid (EPA), 1% docosahexaenoic acid (DHA) and 0.5% EPA + 0.5% DHA were formulated to feed juvenile O.macrolepis (initial body weight:1.51 ± 0.05 g) for eight weeks. The weight gain (WG), specific growth rate (SGR) and feed efficiency (FE) of the fish were significantly higher in the LNA group and the EPA + DHA group than in the control group (P < .05). The growth and feed utilization of the fish in the LNA group were similar to those in the EPA + DHA group. The highest levels of 18:2n-6, 18:3n-3, 20:5n-3and 22:6n-3 in muscle and liver were found in the LA group, the LNA group, the EPA group and the DHA group, respectively. The highest concentrations of serum cholesterol (CHOL) and triglyceride (TG) were observed in the fish fed on the LA diet, and there were no significant differences in serum CHOL and TG between the LA group and the LA + LNA group. Serum malondialdehyde (MDA) content was observed to be the highest in the EPA group, DHA group and EPA + DHA group, and significantly higher in the these groups than in the other groups (P < .05). In liver, the superoxide dismutase (SOD) activities and the malondialdehyde (MDA) content were found to be significantly the lowest and the highest in the EPA, DHA and EPA + DHA groups (P < .05). The body fat content of the fish fed on the LA diet was significantly higher than those of the control ones (P < .05). The fatty acid synthetase (FAS), acetyl-CoA carboxylase 1(ACC1) and sterol regulatory element binding protein-1 (SREBP-1) genes involved in the anabolic pathway had the highest expression levels in the LA group. The adipose triglyceride lipase (ATGL), carnitine palmitoyl transferase 1 (CPT1) and peroxisome proliferators-activated receptor α (PPARα) genes involved in the catabolic pathway had the lowest expression levels in the control group. These results showed that the increase in fish body fat content induced by the LA diet was related to the up-regulation of some lipid biosynthesis metabolism genes. This study recommended that the dietary requirement of fatty acids for the optimal growth and health of juvenile O.macrolepis be 2% LNA or 0.5% EPA + 0.5% DHA (approximately 9% dietary fat). Its results might be conducive to optimizing fish diets while designing optimum dietary fatty acid profiles and proportions.

Docosahexaenoic Acid (DHA) but not Eicosapentaenoic Acid (EPA) induces the trans‐differentiation of C2C12 into white‐like adipocytes phenotype

Muscle derived stem cells (MDSCs) and myoblasts play an important role in the regeneration of myotubes when muscle tissue is injured. However, these cells can be induced to differentiate to other lineages during embryonic development such as adipocytes, osteocytes, and chondrocytes in response to external stimuli like maternal diet enriched with EPA and DHA that are highly suggested during pregnancy because of their neuronal development benefits and positive role in improving retinal and immune functions. The objective of this study is to explore the effect of isolated EPA and DHA on myoblasts undergoing differentiation into brown and white adipocytes. C2C12 myoblasts were cultured to confluency and then treated with white and brown adipogenic differentiation medium with and without 50μM EPA and 50μM DHA separately. DHA treated group but not EPA reprogrammed C2C12 into white like adipocyte phenotype by down‐regulation the expression (P&lt;0.05) of genes involved in regulation the terminal differentiation of myoblasts into myotubes such as MyoD, MyoG, and Mrf4 and up‐regulation the expression of white adipogenesis specific markers including PPARγ, C/EBPα, C/EBPβ, aP2, BMP4, FAT, ZFP423, and Il‐6 (P&lt;0.05). Furthermore, DHA reduced the thermogenic capacity of brown adipocytes derived from C2C12 independent of UCP1 by significantly suppressing (P&lt;0.05) the expression of PGC1α and DIO2 genes and mitochondrial biogenesis by down‐regulation the expression of PGC1α and TFAM followed by decreasing mDNA copy number (P&lt;0.05). Accordingly, DHA treated group showed an increased accumulation of large monocular lipid droplets, suppressed respiration and spare capacity. EPA, on the other hand, reduced the myogenesis process at the terminal stage by inhibiting the expression of MyoD, MyoG, and Mrf4 (P&lt;0.05), but no significant differences were observed in adipogenesis regulating genes such as PPARγ, C/EBPα, C/EBPβ, and aP2 (P&gt;0.05). Likewise, EPA treatment suppressed the expression of WAT signature genes BMP4, FAT, and ZFP423 (P&lt;0.05) indicating its antagonist effect to DHA. Although PGC1α and TFAM expression were reduced in the EPA treated group, no significant changes in mDNA copy number and mitochondrial function were observed. Unlike DHA treatment, EPA supplementation has no effect on the differential route of C2C12 into brown adipocytes. It is to be included that EPA and DHA may similarly affect the integrity of muscle tissue, but DHA is a potent adipogenic and lipogenic factor that can change the metabolic profile of the body by increasing intramuscular fat.

Separation of eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester by simulated moving bed chromatography

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are important ω -3 polyunsaturated fatty acids. Their physiological effects on humans are not exactly the same; therefore, the production of products with high-purity EPA or DHA monomers is significant. In this work, EPA ethyl ester (EPA-EE) and DHA ethyl ester (DHA-EE) were first separated using HPLC with poly(styrene-co-divinylbenzene) (PS/DVB) as the stationary phase. The effects of the mobile phase, PS/DVB particle diameter, and column temperature were systematically evaluated. The results showed that methanol is a suitable mobile phase, having a resolution of 2.75. By comparing resolutions, a PS/DVB particle diameter of 10 μ m was chosen; however, when the pressure drop of PS/DVB is considered, PS/DVB with a particle diameter of 20 μ m is more favorable for large-scale preparations. A column temperature of 40℃ was found to be the most feasible for maintaining efficient separation. Second, eight semi-preparative columns (150 mm×10 mm) of PS/DVB polymer were prepared for the simulated moving bed (SMB) chromatography; the homogeneity of these columns was perfect, with a relative total column porosity error of less than 1%. Finally, an EPA-EE and DHA-EE mixture was separated using the SMB chromatography, and the contents of the extract and the raffinate were determined using GC-FID. The effects of the flow rate of Zone Ⅱ and Zone Ⅲ, the flow rate of the feed, and the feed concentration were investigated. Under optimal conditions, EPA-EE and DHA-EE with favorable purities of 91.6% and 93.6%, respectively, were achievable. The recovery of the EPA-EE was 97.0% and the recovery of the DHA-EE was 91.6%. The productivity and solvent requirements were 5.97 g/(L\5h) and 1.52 L/g, respectively. Therefore, SMB chromatography is an attractive technology for the production of high-value products.

Effect of Altering Dietary n-6:n-3 Polyunsaturated Fatty Acid Ratio with Plant and Marine-Based Supplement on Biomarkers of Bone Turnover in Healthy Adults.

Although there is accumulating evidence for a protective role of n-3 polyunsaturated fatty acids (n-3 PUFAs) on bone health, there are limited studies that examine the effect of altering dietary n-6:n-3 PUFA ratio with plant and marine sources of n-3 PUFA on bone health. Healthy adults (n = 24) were randomized into an eight-week crossover study with a four-week washout between treatments, with each subject consuming three of four diets. The four diets differed in the dietary n-6:n-3 PUFA ratios and either had an algal oil supplement added or not: (Control diet (10:1); α-linolenic acid (ALA) diet (2:1); Eicosapentaenoic acid/Docosahexaenoic acid (EPA/DHA) diet (10:1 plus supplement (S) containing EPA/DHA; Combination diet (2:1 + S)). The supplement was microalgae oil that provided 1 g EPA + DHA/day. Flaxseed oil and walnuts provided 8.6 g of ALA/day in the 2:1 diets. Serum levels of c-telopeptide (CTX), procollagen Type I N-terminal peptide, and osteocalcin showed significant correlation with age but none of the bone markers or peroxisomal proliferator-activated receptor-γ mRNA expression was significantly different between the diets. Serum CTX was negatively associated with red blood cell membrane linoleic acid and ALA and positively associated with membrane DHA. Neither altering dietary n-6:n-3 PUFA ratio from a 10:1 to a 2:1 ratio nor adding EPA/DHA supplement significantly changed bone turnover in the short term in healthy adults.

Effects of simultaneous supplementation of laying hens with α-linolenic acid and eicosapentaenoic acid/docosahexaenoic acid resources on egg quality and n-3 fatty acid profile.

ObjectiveThe aim of this study was to investigate the effects of simultaneous supplementation of laying hens with alpha-linolenic acid (ALA) resources (flax, perilla, and Eucommia ulmoides [E. ulmoides] seeds) and eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) resources (Schizochytrium sp.) on egg quality and n-3 polyunsaturated fatty acids (PUFA) profile.MethodsDietary treatments were as follows: i) diet C (control diet); ii) diet F (diet C+10% flaxseeds); iii) diet P, (diet C+10% perilla seeds); iv) diet E (diet C+10% E. ulmoides seeds); v) diet A (diet C+1.5% microalage); vi) diet AF (diet C+10% flaxseeds+1.5% microalage); vii) diet AP (diet C+10% perilla seeds+1.5% microalgae); viii) diet AE (diet C+10% E. ulmoides seeds+ 1.5% microalage).ResultsEgg weight, yolk weight and production ratio were not significantly affected by either algae or in combination with seeds (p>0.05). No significant difference was observed in ALA and DHA concentration in eggs between flaxseed, perila, and E. ulmodies seeds supplementation alone (p>0.05). N-3 PUFA in eggs was slightly improved by microalgae supplementation. The best supplementation, a combination of microalgae and perilla seeds, elevated (p<0.05) ALA from 19.7 to 202.5 mg/egg and EPA+DHA from 27.5 to 159.7 mg/egg. Highest n-3 PUFA enrichment (379.6 mg/yolk) was observed with supplementation of a combination of perilla seed and microalgae (362.2 mg/yolk), followed by a combination of flaxseed and microalgae (348.4 mg/yolk). The ALA, EPA, and DHA content obtained with a combination of microalgae and seeds surpassed the total sum of that obtained with microalgae or ALA-seeds alone.ConclusionIt is feasible to enrich eggs with n-3 PUFAs by perilla or E. ulmodies seeds instead of flaxseeds. Simultaneous supplementation of microalgae and seeds helped improve the transfer from EPA and docosapentaenoic acid into DHA.

Associations Between Whole Blood and Dietary Omega-3 Polyunsaturated Fatty Acid Levels in Collegiate Athletes.

Omega-3 polyunsaturated fatty acids (PUFAs) have important physiological functions and may offer select benefits for athletic performance and recovery. The purpose of this investigation was to assess dietary and whole blood omega-3 PUFAs among collegiate athletes. In addition, a brief questionnaire was evaluated as a valid tool for quantifying omega-3 PUFA intake. Fifty-eight athletes (9 males, 49 females) completed a 21-item questionnaire developed to assess omega-3 PUFA intake and provided dried whole blood samples to quantify α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and the HS-Omega-3 Index. Geometric means (95% confidence intervals) for the HS-Omega-3 Index were 4.79% (4.37-5.25%) and 4.75% (4.50-5.01%) for males and females, respectively. Median dietary intakes of ALA, EPA, and DHA were all below 100 mg. Among females, several dietary omega-3 PUFA variables were positively associated with whole blood EPA, with total EPA (rho = 0.67, p < .001) and total DHA (rho = 0.69, p < .001) intakes showing the strongest correlations. Whole blood DHA among females showed positive associations with dietary intakes, with total EPA (rho = 0.62, p < .001) and total DHA (rho = 0.64, p < .001) intakes demonstrating the strongest correlations. The HS-Omega-3 Index in females was positively correlated with all dietary variables except ALA. Among males, the only significant correlation was between food and whole blood EPA (rho = 0.83, p < .01). Collegiate athletes had relatively low intakes of omega-3 PUFAs. A 21-item questionnaire may be useful for screening female athletes for poor omega-3 PUFA status.

Omega 3 Polyunsaturated Fatty Acids Suppress the Development of Aortic Aneurysms Through the Inhibition of Macrophage-Mediated Inflammation

Dietary intake of ω3 polyunsaturated fatty acids (ω3-PUFAs) reduces progression of atherosclerosis and prevents future cardiovascular events. Macrophages are key players in the pathogenesis of aortic aneurysm. The effects of ω3-PUFAs on abdominal aortic aneurysm (AAA) formation and macrophage-mediated inflammation remain unclear. METHODS AND RESULTS: The AAA model was developed by angiotensin II infusion in apolipoprotein E-deficient mice. Mice were supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). The development of AAA lesions and macrophage infiltration in the aorta were analyzed. Gene expression of inflammatory markers in aortic tissues and peritoneal macrophages were measured by using quantitative polymerase chain reaction. AAA formation and macrophage infiltration were significantly suppressed after EPA and DHA administration. EPA administration and DHA administration significantly decreased the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-β, matrix metalloproteinases (MMP)-2, MMP-9, and vascular cell adhesion molecule-1 in the aortas. The expression of arginase 2, which is a marker of pro-inflammatory macrophages, was significantly lower and that of Ym1, which is a marker of anti-inflammatory macrophages, and was significantly higher after EPA and DHA administration. The same trends were observed in peritoneal macrophages after EPA and DHA administration. Dietary intake of EPA and DHA prevented AAA development through the inhibition of aortic and macrophage-mediated inflammation.

Poly(ADP) ribose polymerase-1 ablation alters eicosanoid and docosanoid signaling and metabolism in a murine model of contact hypersensitivity.

Poly(ADP‑ribose) polymerase (PARP)‑1 is a pro‑inflammatory protein. The inhibition of PARP‑1 reduces the activity of numerous pro‑inflammatory transcription factors, which results in the reduced production of pro‑inflammatory cytokines, chemokines, matrix metalloproteinases and inducible nitric oxide synthase, culminating in reduced inflammation of the skin and other organs. The aim of the present study was to investigate the effects of the deletion of PARP‑1 expression on polyunsaturated fatty acids (PUFA), and PUFA metabolite composition, in mice under control conditions or undergoing an oxazolone (OXA)‑induced contact hypersensitivity reaction (CHS). CHS was elicited using OXA in both the PARP‑1+/+ and PARP‑1/ mice, and the concentration of PUFAs and PUFA metabolites in the diseased skin were assessed using lipidomics experiments. The levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were shown to be increased in the PARP‑1/ mice, as compared with the control, unsensitized PARP‑1+/+ mice. In addition, higher expression levels of fatty acid binding protein 7 (FABP7) were detected in the PARP‑1/ mice. FABP7 is considered to be a specific carrier of DHA and EPA. Furthermore, the levels of the metabolites of DHA and EPA (considered mainly as anti‑inflammatory or pro‑resolving factors) were higher, as compared with the metabolites of arachidonic acid (considered mainly pro‑inflammatory), both in the unsensitized control and OXA‑sensitized PARP‑1/ mice. The results of the present study suggest that the genetic deletion of PARP‑1 may affect the PUFA‑homeostasis of the skin, resulting in an anti‑inflammatory milieu, including increased DHA and EPA levels, and DHA and EPA metabolite levels. This may be an important component of the anti‑inflammatory action of PARP‑1 inhibition.

Optimization of omega-3 enriched-diacylglycerol production by enzymatic esterification using a response surface methodology

Incorporation of an eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) moiety into diacylglycerol (DAG) oil using lipase-catalyzed esterification was optimized using an ethyl ester form of EPA/DHA. A response surface methodology (RSM) was used to optimize reaction parameters (time, temperature, and substrate mole ratio) for incorporation of DHA and EPA into DAG oil. Predictive models for DHA+EPA contents of DAG and the amount of DAG produced after esterification were adequate and reproducible. DHA+EPA contents of DAG significantly increased with reaction time and substrate mole ratio (p<0.05). In contrast, the reaction temperature negatively affected the amount of DAG after esterification. Synthesis of DHA+EPA-enriched DAG was optimized for a maximum DAG content with the highest DHA+EPA content, in which 630.0 mg of DAG containing 34.8% DHA and EPA was predicted using the RSM model. The optimal reaction conditions were predicted at 20.6 h, 57.9 and a DHA/EPAenriched ethyl ester: DAG oil ratio of 2.5:1.

Update on cardiometabolic health effects of ω-3 fatty acids

The fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may promote cardiometabolic health. This review summarizes the results of recent meta-analyses of prospective studies on cardiovascular diseases, diabetes type 2 and markers of atherosclerosis and thrombosis. The results of recently published meta-analyses of prospective cohort studies showed that eating fish once a week was associated with a 16% lower risk of fatal coronary heart disease (CHD) and a 14% lower risk of stroke incidence, but was not related to heart failure. Fish consumption may be associated with a higher risk of diabetes in Western countries and a lower risk in Asian countries. Recent meta-analyses of randomized controlled trials showed that EPA-DHA supplementation reduced the risk of fatal CHD and sudden death by 10% of which the latter was not significant. Extra EPA-DHA did not reduce the risk of heart failure, stroke and cardiac arrhythmias. ω-3 fatty acid (FA) supplementation did reduce markers of ventricular fibrillation, inflammation and endothelial dysfunction and platelet aggregation. There is strong evidence for a protective effect of ω-3 FA on fatal CHD and for some markers of atherosclerosis and thrombosis. Consistent results were not obtained for other vascular diseases and diabetes. ω-3 FA reduced markers of ventricular fibrillation but did not reduce the risk of atrial fibrillation.

Effects of 1-Year Treatment With Highly Purified Omega-3 Fatty Acids on Depression After Myocardial Infarction

The effects of supplementation of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on prevalence and severity of depression were evaluated in patients after a myocardial infarction. A cross-sectional evaluation (posttest-only design) within the prospective, randomized, controlled, multicenter OMEGA trial was performed in patients after myocardial infarction at 12 months' follow-up (N = 2,081; age, mean = 64 years; men, 76.7%; women, 21.8%) from April 2005 to June 2007. Patients received supplementation with ethyl esters 90 (460-mg EPA and 380-mg DHA) or placebo for 12 months. Depression was assessed with the Beck Depression Inventory-II (BDI-II); a BDI-II cutoff score of ≥ 14 was used as diagnosis of depression. When the total population was evaluated, no effects of EPA/DHA supplementation on depressive symptoms according to BDI-II score (mean [SD]) could be demonstrated: EPA/DHA (n = 1,046), 7.1 (6.9); placebo (n = 1,035), 7.1 (7.0); P = .7. The post hoc analyses of depressed patients with and without antidepressants revealed a tendency toward an antidepressant effect in patients with EPA/DHA supplementation as monotherapy: EPA/DHA (n = 125), 19.4 (5.8); placebo (n = 113), 19.9 (5.1); P = .07. However, in depressed patients with EPA/DHA supplementation as adjunctive to conventional antidepressants, a clinically relevant antidepressant effect was demonstrated: EPA/DHA (n = 33), 20.9 (7.1); placebo (n = 29), 24.9 (8.5); P < .05. EPA/DHA supplementation in the total sample of patients after myocardial infarction had no effect on depressive symptoms. The clinically relevant antidepressant effect in the subgroup of depressed patients with EPA/DHA supplementation as adjunctive to conventional antidepressants that was revealed in the post hoc analysis might provide a basis for a controlled, prospective trial of omega-3 augmentation of antidepressants in patients after myocardial infarction. ClinicalTrials.gov identifier: NCT00251134.

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial

Maternal deficiency of the omega-3 fatty acid, docosahexaenoic acid (DHA), has been associated with perinatal depression, but there is evidence that supplementation with eicosapentaenoic acid (EPA) may be more effective than DHA in treating depressive symptoms. This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression. We enrolled 126 pregnant women at risk for depression (Edinburgh Postnatal Depression Scale score 9-19 or a history of depression) in early pregnancy and randomly assigned them to receive EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA), or soy oil placebo. Subjects completed the Beck Depression Inventory (BDI) and Mini-International Neuropsychiatric Interview at enrollment, 26-28 weeks, 34-36 weeks, and at 6-8 weeks' postpartum. Serum fatty acids were analyzed at entry and at 34-36 weeks' gestation. One hundred eighteen women completed the trial. There were no differences between groups in BDI scores or other depression endpoints at any of the 3 time points after supplementation. The EPA- and DHA-rich fish oil groups exhibited significantly increased postsupplementation concentrations of serum EPA and serum DHA respectively. Serum DHA- concentrations at 34-36 weeks were inversely related to BDI scores in late pregnancy. EPA-rich fish oil and DHA-rich fish oil supplementation did not prevent depressive symptoms during pregnancy or postpartum.

The effect of eicosapentaenoic and docosahexaenoic acid on protein synthesis and breakdown in murine C2C12 myotubes

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been found to stimulate protein synthesis with little information regarding their effects on protein breakdown. Furthermore whether there are distinct effects of EPA and DHA remains to be established. The aim of the current study was to determine the distinct effects of EPA and DHA on protein synthesis, protein breakdown and signalling pathways in C2C12 myotubes. Fully differentiated C2C12 cells were incubated for 24h with 0.1% ethanol (control), 50μM EPA or 50μM DHA prior to experimentation. After serum (4h) and amino acid (1h) starvation cells were stimulated with 2mM l-leucine and protein synthesis measured using 3H-labelled phenylalanine. Protein breakdown was measured using 3H-labelled phenylalanine and signalling pathways (Akt, mTOR, p70S6k, 4EBP1, rps6 and FOXO3a) via Western blots. Data revealed that after incubation with EPA protein synthesis was 25% greater (P<0.05) compared to control cells, with no effect of DHA. Protein breakdown was 22% (P<0.05) lower, compared to control cells, after incubation with EPA, with no effect of DHA. Analysis of signalling pathways revealed that both EPA and DHA incubation increased (P<0.05) p70s6k phosphorylation, EPA increased (P<0.05) FOXO3a phosphorylation, with no alteration in other signalling proteins. The current study has demonstrated distinct effects of EPA and DHA on protein metabolism with EPA showing a greater ability to result in skeletal muscle protein accretion.