EPA Oil Research Articles

Plasma levels of EPA and DHA after ingestion of a single dose of EPA and DHA ethyl esters

AbstractOmega‐3 polyunsaturated fatty acids (n3 PUFA), specifically eicosapentaenoic acid (EPA, 20:5n3), and docosahexaenoic acid (DHA, 22:6n3), are essential for maintaining health. To better understand their biology, it is important to define their bioavailability. The aim of this cross‐over study was to investigate and compare the acute effects on plasma EPA and DHA levels after single doses of EPA oil (99% pure) and DHA (97% pure) ethyl esters. Twelve men aged 20–40 years with a body‐mass‐index of 20–27 kg/m2 and low fish consumption were recruited. Several measures (e.g., 4‐week run‐in period, standardized diet, and blood collection protocols) were taken to reduce the inter‐individual variability of plasma fatty acids levels. Using a cross‐over design, the subjects received 2.2 g of EPA in the first test period and 2.3 g of DHA in the second. The test periods were separated by 2 weeks. Blood samples were taken before dosing and after 2, 4, 6, 8, 12, 24, 48, and 72 h. The mean ± SE maximum concentrations for EPA were higher than for DHA (115 ± 11 μg/mL vs. 86 ± 12 μg/mL; p = 0.05). The mean ± SE incremented area under the plasma concentration curve over 72 h for EPA (2461 ± 279 μg/mL) was 2.4 times higher (p < 0.001) than that for DHA (1021 ± 170 μg/mL). The mean ± SE half‐life was for EPA and DHA was 45 ± 8 and 66 ± 12 h. Our results indicate that EPA administration in single doses leads to higher circulating plasma levels of EPA compared to an effect of an equivalent dose of DHA on DHA plasma levels.

Sustainable Enzymatic Production of Omega-3 Oil from Squid Viscera

Fish oils are widely consumed around the world to increase omega-3 fatty acid intake. Due to negative impacts on marine resources and ecosystems from an increasing demand for fish, alternative sustainable sources are under investigation. Squid viscera contains up to 10% oil by mass and is available as a byproduct from squid processing. Squid viscera oil is a source of EPA and DHA and contains the xanthophyll carotenoid astaxanthin, known for its significant anticancer, antioxidant, antidiabetic, and cardiovascular properties. In the raw form, squid viscera oil has a high free fatty acid (FFA) content, so conventional alkaline refining results in low yield and loss of astaxanthin. As a higher-yielding alternative, the current study optimized lipase-catalyzed glycerolysis of squid viscera oil to convert FFA into acylglycerol using a custom-built one-liter immobilized enzyme reactor. To monitor the reaction progress and assess its impact on the oil, we analyzed lipid classes, fatty acid composition and astaxanthin levels. Under optimized conditions, FFA was reduced from 40% to 2.7% in 10 h and 1.7% in 24 h, with no significant effect on EPA and DHA levels, and astaxanthin being retained. Squid viscera presents a safe and sustainable additional source of marine-derived EPA and DHA oil.

Concomitant oxidation of fatty acids other than DHA and EPA plays a role in the characteristic off-odor of fish oil

The aim of the present research was to explore the development of off-odors in fish oil from the perspective of fatty acid oxidation. It was found that the off-odors elicited by the two major ω-3 PUFAs in fish oil, i.e. DHA and EPA, were different from those by fish oil. Results showed that simultaneous oxidation of fatty acids other than DHA and EPA can be involved. The off-odors of fish oil was successfully simulated by combining oxidized samples of DHA, EPA and sunflower oil. Therefore, oxidation of oleic and linoleic acids also contributed to the off-odors in fish oil. A novel analytical approach that consisted in the combination of gas chromatography-ion mobility spectrometry (GC-IMS) and orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to identify differences in the volatile components between the recombinant oil and the fish oil.

Increases in plasma n-3 tetracosapentaenoic acid and tetracosahexaenoic acid following 12 weeks of EPA, but not DHA, supplementation in women and men

Dietary feeding and stable isotope studies in rodents support that the 24-carbon omega-3 polyunsaturated fatty acids, tetracosapentaenoic acid (24:5n-3, TPAn-3) and tetracosahexaenoic acid (24:6n-3, THA), are immediate precursors to docosahexaenoic acid (DHA, 22:6n-3). In this study, we assessed for the first time, changes in TPAn-3 or THA levels following omega-3 PUFA supplementation in humans, providing insight into human omega-3 PUFA metabolism. In this secondary analysis of a double-blind randomized control trial, women and men (19 – 30 years, n = 10 – 14 per sex, per diet) were supplemented with 3 g/day EPA, DHA, or olive oil control for 12 weeks. Plasma TPAn-3 and THA concentrations were determined by gas chromatography-mass spectrometry to determine changes following supplementation in a sex-specific manner (sex x time). EPA supplementation significantly increased (p < 0.0001) plasma TPAn-3 by 215% (1.3 ± 0.1 – 4.1 ± 0.7, nmol/mL ± SEM) and THA by 112% (1.7 ± 0.2 – 3.6 ± 0.5, nmol/mL ± SEM). Furthermore, women had 111% and 99% higher plasma TPAn-3 and THA in the EPA supplemented group compared to men (p < 0.0001). There were no significant effects of time on plasma TPAn-3 or THA concentrations in the DHA supplemented or olive oil supplemented groups. In conclusion, EPA, but not DHA, supplementation in humans increased plasma TPAn-3 and THA levels, suggesting that THA accumulates prior to conversion to DHA in the n-3 PUFA synthesis pathway. Furthermore, women generally exhibit higher plasma TPAn-3 and THA concentrations compared with men, suggesting that women have a greater ability to accumulate 24-carbon n-3 PUFA in plasma via EPA and DPAn-3 elongation, which may explain the known higher DHA levels in women.Summary: In this secondary analysis of a double-blind randomized control trial, we assessed changes in omega-3 (n-3) tetracosapentaenoic acid (24:5n-3, TPAn-3) and tetracosahexaenoic acid (24:6n-3, THA) plasma levels in women and men (19 – 30 years, n = 10 – 14 per sex, per diet) following 12-weeks of n-3 PUFA supplementation (3 g/day EPA, DHA or olive oil). Women had higher plasma TPAn-3 in all supplementation groups and higher THA levels in the EPA and olive oil groups (p < 0.0001) compared to men. EPA supplementation increased (p < 0.0001) plasma TPAn-3 by 215% (1.3 ± 0.1 – 4.1 ± 0.7, nmol/mL ± SEM) and THA by 112% (1.7 ± 0.2 – 3.6 ± 0.5, nmol/mL ± SEM), but DHA supplementation had no effect. For the first time in humans, we show that plasma TPAn-3 and THA levels are higher in women and increased with EPA, but not DHA supplementation, suggesting an accumulation of THA prior to conversion to DHA in the n-3 PUFA synthesis pathway.

Obtaining DHA–EPA Oil Concentrates from the Biomass of Microalga Chlorella sorokiniana

Microalgae have attracted growing interest all around the world due to their potential applications in multiple sectors of industry, such as energetics, nutraceuticals, pharmaceuticals, agriculture, and ecology. Concepts of biorefinery of microalgae lipids for biodiesel production coupled with other applications have been suggested in several studies. However, very few studies focus on overcoming the degree of unsaturation of microalgae lipids using methods of fractionation. This study presents a method for obtaining two oil fractions from microalgae Chlorella sorokiniana suitable for food and biofuels via urea complex formation with further production of a long-chain PUFA concentrated oil suitable for the nutraceutical industry. A DHA–EPA-rich fraction was obtained from the dry microalga biomass using a succession of extraction, urea-complexation, fractionation, and esterification with glycerol. Analytical and organoleptic methods were used to assess the quality of the final product. Results show that the urea-complexation method allowed the obtaining of two lipid fractions with different fatty acid profiles. The urea complexed fraction (UCF) contained a majority of saturated fatty acids (54.46%); thus, it could find applications in the biofuels or food industry. The non-urea complexed fraction (NUCF) was rich in polyunsaturated fatty acids (PUFA) (81.00%), especially long-chain PUFA with 16.52% EPA and 35.08% DHA. The recovery rates of EPA and DHA in the NUCF reached 59% and 87.14%, respectively. Finally, the physicochemical and organoleptic characteristics of the DHA–EPA oil concentrate were determined and found conform to the norms recommended by the WHO/FAO standards for edible oils and the Russian State Standard GOST 1129-2013.

Different Dietary n-3 Polyunsaturated Fatty Acid Formulations Distinctively Modify Fatty Acid and N-Acylethanolamine Profiles in Rat Brain

Abstract Objectives Dietary n-3 polyunsaturated fatty acids (n-3PUFA) may influence the brain fatty acid (FA) profile and, thereby, the biosynthesis of FA bioactive metabolite, such as N-acylethanolamines (NAE). We investigated the influence of different dietary formulation of n-3PUFA from vegetable or marine oils on rat FA incorporation and modulation of NAE biosynthesis. Methods Rats were fed for 10 weeks with diets containing 12% of fat from milk + 4% soybean oil and 4% of oils with different n-3 PUFA species: soybean oil as control (MilkFat), linseed oil with α-linolenic (ALA) (LSO), Buglossoides arvensis oil with ALA and stearidonic (SDA) (Buglos), fish oil with EPA and DHA (FO), Nannochloropsis microalga oil with EPA (Nanno) or Schizochytrium microalga oil with DHA (Schy). Brain FA and NAE profile were assessed LC-DAD-MS/MS. Statistical Kruskal-Wallis test followed by Dunn's correction was applied. Results Different dietary n-3PUFA formulations induced FA change in the brain, compared to MilkFat group, DHA levels remained unchanged despite its elevated intake with FO and Schy diets. However, we found 9 fold (P &amp;lt; 0.001) increase of EPA with FO, arachidonic (AA) decreased significantly about 16% (P &amp;lt; 0.05) with LSO and FO diets. n-6 PUFA docosatetraenoic (DTA) (26% P &amp;lt; 0.05) and docosapentaenoic (DPA) (73% P &amp;lt; 0.05) were reduced with FO, probably due to a competition with EPA in the incorporation into phospholipids. We observed a 44% (P &amp;lt; 0.05) significant decrease of N-arachidonoylethanolamine (AEA) with LSO and FO, and a reduction of N-linoleoylethanolamine (LEA) by 49% (P &amp;lt; 0.05) with LSO. On the other hand, we found an increase of N-eicosapentanoylethanolamine (EPEA), derived from EPA, by 225% (P &amp;lt; 0.05) with FO, compared to MilkFat group. Conclusions Our data indicate that reduction of AEA levels might attenuate its effects on the CB1 cannabinoid receptors, the main molecular target of the endogenous partial agonist AEA, which regulate physiological processes in the central nervous system. Therefore, in those pathophysiological conditions where is desirable to downregulate an overactive endocannabinoid system, a mixture of EPA and DHA as in FO, and ALA as in LSO, may potentially be a preferred nutritional source of n-3 PUFA. Funding Sources University of Cagliari (FIR 2019) and Fundação FCT (Portugal).

High Fat Diet Dysregulates Hypothalamic-Pituitary Axis Gene Expression Levels which are Differentially Rescued by EPA and DHA Ethyl Esters.

Dietary fat composition can modulate gene expression in peripheral tissues in obesity. Observations of the dysregulation of growth hormone (GH) in obesity indicate that these effects extend to the hypothalamic-pituitary (H-P) axis. The authors thus determine whether specific high fat (HF) diets influence the levels of Gh and other key gene transcripts in the H-P axis. C57BL/6 mice are fed a lean control diet or a HF diet in the absence or presence of OA, EPA, or DHA ethyl esters. Comparative studies are conducted with menhaden fish oil. The HF diet lowered pituitary Gh mRNA and protein levels, and cell culture studies reveal that elevated insulin and glucose can reduce Gh transcripts. Supplementation of the HF diet with OA, EPA, DHA, or menhaden fish oil do not improve pituitary Gh levels. The HF diet also impaired the levels of additional genes in the pituitary and hypothalamus, which are selectively rescued with EPA or DHA ethyl esters. The effects of EPA and DHA are more robust relative to fish oil. A HF diet can affect H-P axis transcription, which can be mitigated in some genes by EPA and DHA, but not fish oil in most cases.

Managing Exposure to Benzene and Total Petroleum Hydrocarbons at Two Oil Refineries 1977-2014.

Air concentrations of and inhalation exposure to total petroleum hydrocarbons (TPH) and benzene was monitored separately at two oil refineries from 1977 to 2014. Prevention policies and control measures that may explain changes were surveyed. The aim was to evaluate how the application of of Occupational Health and Safety Assessment Series OHSAS 18001.04 principles as well as Environmental protection Agency EPA and European Oil Company Organisation for Environment, Health and Safety CONCAWE practices have influenced air concentrations. Benzene air concentrations declined in 11 of 17 units, six of which were associated with declining exposures. Benzene air concentrations declined across all units on average by 46%. This amounts to an average yearly decline of 1.7%. TPH air concentrations declined in 10 of 17 units, seven of which were associated with declining exposures. The average decline in TPH air concentrations was 49%, corresponding to 1.3% per year. As a result, average working day exposure in 10 of 17 units have declined significantly and today, benzene and TPH exposure in most units are well below 10% of the current Occupational Exposure Limit (OEL8h:s). A decline in air concentrations have coincided with consistent implementation of control measures. Such measures include on-line monitoring of leaks; benzene recovery; floating container roofs; improved valves and seals; hermetic pumps; recovery of loading gases and instalment of torches in terminals; cutback in coke combustion; a new production line spanning directly from the dock to aromatics production; and recovery of loading gases in the doc. Other tools in exposure management include personal leak monitors, on-line measurements, monitoring campaigns, risk assessment, and availability and user training of protective equipment. However, improvements are still needed. Hydrocarbon or benzene air concentrations have not declined in 8 of 17 units, in some of which concentrations exceed 10% of the relevant OEL8h value. In addition, for benzene even 10% of the current OEL, 0.1 ppm, might still possess a risk. With this in mind, methods to estimate exposure at the refineries need to be improved to enable measuring benzene concentrations <0.1 ppm. Shut downs of the refinery have been associated with peaks in exposure concentrations. Consequently, effort should be placed on safe working methods pertaining to shutdowns. Also, the connection and detachment of hoses continues to be problematic from the point of view of controlling exposure.

Overview of Aquatic Toxicity Testing under the U.S. EPA Oil Research Program

2017-063 ABSTRACT The U.S. EPA Office of Research and Development is developing baseline data on the ecotoxicity of selected petroleum products, chemical dispersants, and other spill mitigating substances as part of its Oil Research Program. Two diluted bitumens (dilbits) from the Alberta Tar Sands region are being tested for acute and chronic toxicity to standard freshwater and marine organisms given their spill potential during shipment within the United States. Separately, crude oils representing a range of characteristics and representative dispersants are being tested to evaluate acute and chronic toxicity to marine organisms in support of proposed regulatory amendments to Subpart J of the U.S. National Contingency Plan. Water accommodated fractions (WAF) of oil are prepared using traditional slow-stir methods and toxicity tests follow U.S. EPA standard effluent testing guidelines, modified for testing petroleum products. WAFs are characterized for petroleum hydrocarbons including alkyl PAH homologs. Future research plans include evaluating oil spill mitigating substances such as surface washing and bioremediation agents. The results of the research program will assist the U.S. EPA in assessing toxicity of unconventional oils (dilbits), and establish baseline toxicity data for selected crude oils and spill mitigating substances in support of planning and response activities.

Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis.

ObjectiveTo develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.DesignSystematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.ResultsWe identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation.ConclusionsWe demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

Effect of dietary lipid on the growth, fatty acid composition and Δ5 Fads expression of abalone (Haliotis discus hannai Ino) hepatopancreas

This study investigated the effect of dietary lipid on the growth, fatty acid composition and Δ5 fatty acyl desaturase genes (Fads) expression of juvenile abalone (Haliotis discus hannai Ino) hepatopancreas. Six purified diets were formulated to contain tripalmitin (TP), olive oil (OO, 72.87% 18:1n-9), grape seed oil (GO, 68.67% 18:2n-6), linseed oil (LO, 70.48% 18:3n-3), ARA oil (AO, 41.81% ARA) or EPA oil (EO, 44.09% EPA and 23.67% DAH). No significant difference in survival rate was observed among abalone fed with different diets. Weight gain rate (WGR) and daily growth rate of shell length (DGR SL) were significantly increased in abalone fed with diets containing OO, AO and EO, but decreased in abalone fed with LO diet (P < 0.05) in comparison with those fed with TP. High level of dietary 18:2n-6 resulted in higher content of n-6 polyunsaturated fatty acids (PUFAs) in abalone fed with GO than those fed with TP, OO, LO and EO (P < 0.05). n-3 PUFAs in abalone fed with LO was significantly higher than those in abalone fed with TP, OO, GO and AO (P < 0.05). The highest contents of 20:1n-9 and 22:1n-9 were observed in abalone fed with OO. The expression of Δ5 Fads in hepatopancreas of abalone was enhanced by high concentration of 18:3n-3 and suppressed by dietary LC-PUFAs; however it was not affected by dietary high concentration of 18:1n-9 or 18:2n-6. These results provided valuable information for understanding the synthesis of LC-PUFAs and nutritional regulation of Δ5 Fads expression in abalone.

Sustainable source of omega-3 eicosapentaenoic acid from metabolically engineered Yarrowia lipolytica: from fundamental research to commercial production.

The omega-3 fatty acids, cis-5, 8, 11, 14, and 17-eicosapentaenoic acid (C20:5; EPA) and cis-4, 7, 10, 13, 16, and 19-docosahexaenoic acid (C22:6; DHA), have wide-ranging benefits in improving heart health, immune function, mental health, and infant cognitive development. Currently, the major source for EPA and DHA is from fish oil, and a minor source of DHA is from microalgae. With the increased demand for EPA and DHA, DuPont has developed a clean and sustainable source of the omega-3 fatty acid EPA through fermentation using metabolically engineered strains of Yarrowia lipolytica. In this mini-review, we will focus on DuPont’s technology for EPA production. Specifically, EPA biosynthetic and supporting pathways have been introduced into the oleaginous yeast to synthesize and accumulate EPA under fermentation conditions. This Yarrowia platform can also produce tailored omega-3 (EPA, DHA) and/or omega-6 (ARA, GLA) fatty acid mixtures in the cellular lipid profiles. Fundamental research such as metabolic engineering for strain construction, high-throughput screening for strain selection, fermentation process development, and process scale-up were all needed to achieve the high levels of EPA titer, rate, and yield required for commercial application. Here, we summarize how we have combined the fundamental bioscience and the industrial engineering skills to achieve large-scale production of Yarrowia biomass containing high amounts of EPA, which led to two commercial products, New Harvest™ EPA oil and Verlasso® salmon.

Postprandial metabolism of docosapentaenoic acid (DPA, 22:5n−3) and eicosapentaenoic acid (EPA, 20:5n−3) in humans

The study of the metabolism of docosapentaenoic acid (DPA, 22:5n−3) in humans has been limited by the unavailability of pure DPA and the fact that DPA is found in combination with eicosapentaenoic acid (EPA, 20:5n−3) and docosahexaenoic acid (DHA, 22:6n−3) in natural products. In this double blind cross over study, pure DPA and EPA were incorporated in meals served to healthy female volunteers. Mass spectrometric methods were used to study the chylomicron lipidomics. Plasma chylomicronemia was significantly reduced after the meal containing DPA compared with the meal containing EPA or olive oil only. Both EPA and DPA were incorporated into chylomicron TAGs, while there was less incorporation into chylomicron phospholipids. Lipidomic analysis of the chylomicron TAGs revealed the dynamic nature of chylomicron TAGs. The main TAG species that EPA and DPA were incorporated into were EPA/18:1/18:1, DPA/18:1/16:0 and DPA/18:1/18:1. There was very limited conversion of DPA and EPA to DHA and there were no increases in EPA levels during the 5h postprandial period after the DPA meal. In conclusion, EPA and DPA showed different metabolic fates, and DPA hindered the digestion, ingestion or incorporation into chylomicrons of the olive oil present in the meal.

기수산 물벼룩(Diaphanosoma celebensis)의 대량생산을 위한 대체 먹이원의 효과

This study examined the effect of formulated diets (composed of condensed freshwater <TEX>$Chlorella$</TEX> or <TEX>$Schizochytrium$</TEX> sp., <TEX>$Crypthecodinium$</TEX> sp., and EPA oil sources derived from baker's yeast) on the population growth and fatty acid composition of the brackish water flea (<TEX>$Diaphanosoma$</TEX> <TEX>$celebensis$</TEX>) to determine diet effectiveness for mass production. Results indicated that the highest maximum density, fecundity, and population specific growth rate (SGR) of the flea were observed using a diet of <TEX>$Tetraselmis$</TEX> <TEX>$suecica$</TEX> (control). However, results using condensed freshwater <TEX>$Chlorella$</TEX> and the mixed treatment of <TEX>$Schizochytrium$</TEX> sp.+<TEX>$Crypthecodinium$</TEX> sp.+EPA oil did not significantly differ from the control treatment (<TEX>$P$</TEX>>0.05). Thus, <TEX>$T.$</TEX> <TEX>$suecica$</TEX> could be replaced with a combination diet of <TEX>$Schizochytrium$</TEX> sp., <TEX>$Crypthecodinium$</TEX> sp., and EPA oil in condensed freshwater <TEX>$Chlorella$</TEX> without growth interruption of <TEX>$D.$</TEX> <TEX>$celebensis$</TEX>. As the percentage of combination diet (mix of <TEX>$Schizochytrium$</TEX> sp., <TEX>$Crypthecodinium$</TEX> sp., and EPA oil) in condensed freshwater <TEX>$Chlorella$</TEX> increased, the level of ARA, EPA, DHA, and n-3 HUFA in <TEX>$D.$</TEX> <TEX>$celebensis$</TEX> also increased. However, the population density of <TEX>$D.$</TEX> <TEX>$celebensis$</TEX> sharply decreased with the use of treated supplements C5M5 (CHL [50%] and <TEX>$Crypthecodinium$</TEX> sp.+ <TEX>$Schizochytrium$</TEX> sp. + EPA oil [MIX 50%]). The optimum proportions of CHL and MIX for <TEX>$D.$</TEX> <TEX>$celebensis$</TEX> within the mixture were 70% and 30%, respectively. Based on the results, the combination of <TEX>$Schizochytrium$</TEX> sp., <TEX>$Crypthecodinium$</TEX> sp., and EPA oil in condensed freshwater <TEX>$Chlorella$</TEX> appears to be a stable and effective food source for mass production of <TEX>$D.$</TEX> <TEX>$celebensis$</TEX>.

오메가-3와 -9 지방산의 혼합 급이가 계육내 오메가-3 계열 다가불포화지방산의 조성에 미치는 영향

본 연구는 오메가-3 다가불포화지방산의 함량을 높인 육계의 생산을 위하여 n-3 지방산과 올리브유를 혼합한 사료[CON(5% 일반지방), FXO(2.5% 아마씨유+ 2.5% 올리브유), FEO(2.45% 아마씨유+ 0.05% EPA + 2.5% 올리브유), FDO(2.45% 아마씨유+ 0.05% DHA + 2.5% 올리브유) 그리고 FHO(2.5% 어유+ 2.5% 올리브유)]를 육계에게 4주 간 급이하였다. 4주간의 사양 후 도계를 통하여 닭의 간, 가슴살 그리고 다리살을 채취하였다. 채취한 간은 간 무게/생체중의 비율, 육색 그리고 지방산의 조성 분석을 위하여 사용되었으며, 닭 가슴살과 다리살은 지방산 함량 분석을 위하여 사용되었다. FHO 사료를 급이한 육계의 간은 EPA가 유의적으로 낮았으나 DPA와 DHA는 높았다(p<0.05). 가슴 근육은 n-6 지방산인 AA와 DPA 그리고 n-3 지방산에서 FDO 처리구가 이외의 처리구 대비 유의적으로 높았으며(p>0.05), 더욱이 유의적인 차이는 나타나지 않았으나 수치적으로 EPA와 DHA 함량 역시 높았다. LNA 함량은 FEO와 FDO 사료를 급이한 닭의 다리 근육에서 유의적으로 높았으며, AA 함량 또한 FHO와 유사하였다. FHO 사료를 급이한 닭의 다리 근육은 EPA, DHA 그리고 n-3 지방산에서 유의적으로 높은 함량을 나타낸 반면에 AA의 함량과 n-6/n-3 지방산의 비율은 유의적으로 낮았다(p<0.05). 따라서 본 실험은, n-3의 다가불포화지방산의 함량을 증가시킴과 동시에 n-6/n-3 비율의 향상을 위해서는 근섬유 조성에 따라 그 접근법이 달라야 된다는 사실이 조사되었으며, 가슴과 다리 근육 내 n-3 지방산의 함량을 증가시키기 위해서는 각각 FDO와 FHO 사료의 급이가 적합할 것으로 판단된다. To evaluate the effects of n-3 and n-9 fatty acid combination on broiler chicks, diets containing the combinations of five different fat sources including flaxseed oil, fish oil, EPA, DHA and olive oil were provided, and all chicks were processed at 4 weeks of growth. Liver, breast and thigh samples were collected and fatty acid composition and/or CIE <TEX>$L^*$</TEX>, <TEX>$a^*$</TEX> and <TEX>$b^*$</TEX> measurement were measured. Also, live chick and liver weights were weighed and the ratio was provided as an evidence of fat accumulation in liver. No significant difference was determined in both live and liver weight ratio and liver color. EPA was low in FHO as compared to livers from others. In contrast, DHA was significantly high in FHO. In broiler breasts derived from FDO, AA and n-3 fatty acid content was high, but only numerical differences of EPA and DHA were determined in breasts from FDO. The thighs from FHO showed high in EPA, DHA and n-3 fatty acid content but had low in AA and n-6 to n-3 ratio. Therefore, the results indicate that broiler chicken diets containing either FDO or FHO may be possible combination diets increasing n-3 polyunsaturated fatty acids in broiler chicks.

Abstract SY11-04: Factors associated with changes in body weight and the protective effect of chronic versus intermittent calorie restriction on mammary tumorigenesis

Abstract To date one of the most effective strategies for the prevention of mammary tumor development is calorie restriction. Reduced incidence and/or extended latency for the development of spontaneously and carcinogen-induced mammary tumors have been documented following various degrees of reduced calorie intake. In the majority of these studies chronic calorie restriction (CCR) has been implemented whereby the animals are given the same amount of reduced calories every day. Although this is easy to implement in experimental conditions, such an approach may have limited application to humans. Interestingly, we have reported that periods of intermittent calorie restriction (ICR) consisting of periods of 50% reduced intake followed by ad libitum refeeding resulting in an overall restriction of 20-25% was more protective than the same degree of restriction implemented in a CCR protocol. In three separate studies transgenic MMTV-TGF-α mice fed low-fat AIN93M diets had mammary tumor incidences ranging from 3-15% for ICR mice compared to 27-44% for CCR mice and 68-84% for ad libitum-fed (AL) mice (CEBP 11: 836,2002; Exp Biol Med 232:70,2007; Cancer Prev Res 2:712,2009). In a second strain of transgenic mice also susceptible to mammary tumor development, MMTV-neu, there was no protective effect of CCR while ICR resulted in an ∼50% reduction in mammary tumor incidence (Nutrition &amp; Cancer 44:162,2002). To understand why ICR is superior to CCR we have measured circulating growth regulating factors which have been reported to be related to tumorigenesis. In addition we determined protein expression levels of their corresponding receptors in mammary tissues and mammary tumors. We have found that ICR restriction periods are characterized by reductions in serum IGF-I and leptin and following refeeding neither level reached that of AL mice. Further, ICR restriction is characterized by a large increase in the adiponectin:leptin ratio. These observations indicate an environment conducive to reduced cell proliferation and/or enhanced apoptosis based on in vitro studies using human breast cancer cell lines. In mammary tissue CCR and ICR mice had reduced leptin expression compared to AL mice but only ICR mice had elevated AdipoR1 compared to AL and CCR mice, while leptin receptor expression was reduced. Neither CCR nor ICR affected mammary tissue or mammary tumor adiponectin or AdipoR2 expression. Two proteins associated with IGF-I signaling, IGFBP3 and IGF-IR, were also measured, IGFBP3 was higher in mammary tumors from both ICR and CCR mice while only CCR mice had higher expression in mammary tissue. There was no effect of IGF-IRα in either tissue. We have conducted two recent studies expanding on our earlier experiments. In the first we fed a higher fat diet to MMTV-TGF-α mice to determine if we could overcome the protective effect of ICR. Mice were fed diets to provide the same absolute intake of fat on a daily basis over the course of the study (10-82 weeks of age). Despite the increased fat intake during refeeding the protective effect of ICR was maintained with mammary tumor incidence of 4% obtained for ICR mice compared to 52% for CCR mice and 66% for AL mice. In the second study MMTV-neu mice which were only moderately protected by the ICR protocol in the earlier study were fed reduced calories combined with the addition of the omega-3 fatty acid, eicosapentaenoic acid, EPA, to the diet. This was based on studies that suggested a protective effect of EPA and/or fish oil on mammary tumorigenesis. EPA was included in the diet at 71% of fat calories in a diet where 9% of total calories were supplied as fat. Control diets contained soybean oil as the fat source. Mice were enrolled at 10 weeks of age and followed until 60 weeks of age. EPA included in the AL diet had a modest effect on mammary tumor development resulting in a 28% decrease in incidence from 87% in AL-CONTROL mice to 63% in AL-EPA mice. For the calorie restricted mice CCR-CONTROL and CCR-EPA mice had incidence rates of 47% and 40% respectively while ICR-CONTROL mice had an incidence rate of 59%. EPA combined with ICR reduced mammary tumor incidence to only 15%. Serum and tissue analyses are presently underway including determination of mammary tissue, mammary fat pad and mammary tumor SIRT1 and SIRT3 levels. Although the mechanism of action to explain why ICR is superior to CCR for mammary tumor prevention remains unknown ICR may provide a unique approach for cancer prevention Support: CA101858, DOD17-97-7055, KOMEN for the Cure and The Hormel Foundation.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY11-04. doi:10.1158/1538-7445.AM2011-SY11-04

Safety assessment of EPA-rich triglyceride oil produced from yeast: Genotoxicity and 28-day oral toxicity in rats

The 28-day repeat-dose oral and genetic toxicity of eicosapentaenoic acid triglyceride oil (EPA oil) produced from genetically modified Yarrowia lipolytica yeast were assessed. Groups of rats received 0 (olive oil), 940, 1880, or 2820mg EPA oil/kg/day, or fish oil (sardine/anchovy source) by oral gavage. Lower total serum cholesterol was seen in all EPA and fish oil groups. Liver weights were increased in the medium and high-dose EPA (male only), and fish oil groups but were considered non-adverse physiologically adaptive responses. Increased thyroid follicular cell hypertrophy was observed in male high-dose EPA and fish oil groups, and was considered to be an adaptive response to high levels of polyunsaturated fatty acids. No adverse test substance-related effects were observed on body weight, nutritional, or other clinical or anatomic pathology parameters. The oil was not mutagenic in the in vitro Ames or mouse lymphoma assay, and was not clastogenic in the in vivo mouse micronucleus test. In conclusion, exposure for 28days to EPA oil derived from yeast did not produce adverse effects at doses up to 2820mg/kg/day and was not genotoxic. The safety profile of the EPA oil in these tests was comparable to a commercial fish oil.

Supplementation with EPA or fish oil for 11 months lowers circulating lipids, but does not delay the onset of diabetes in UC Davis-type 2 diabetes mellitus rats

EPA or fish oil supplementation has been suggested as treatments for the prevention of type 2 diabetes mellitus (T2DM) due to their lipid-lowering and potential insulin-sensitising effects. We investigated the effects of supplementation with EPA (1 g/kg body weight per d) or fish oil (3 g/kg body weight per d) on the age of onset of T2DM and circulating glucose, insulin, lipids, leptin and adiponectin in UC Davis (UCD)-T2DM rats. Animals were divided into three groups starting at 1 month of age: control, EPA and fish oil. All the animals were followed until diabetes onset or for up to 12 months of age. Monthly fasting blood samples were collected for the measurement of glucose, lipids, hormones and C-reactive protein (CRP). Neither EPA nor fish oil delayed the onset of T2DM or altered fasting plasma glucose, insulin, CRP, adiponectin or leptin concentrations. The groups did not differ in energy intake or body weight. Fish oil treatment lowered fasting plasma TAG concentrations by 39 (sd 7) % (P < 0.001) and EPA lowered fasting plasma NEFA concentrations by 23 (sd 5) % (P < 0.05) at 4 months of age compared with the control group. EPA and fish oil lowered fasting plasma cholesterol concentrations at 4 months of age by 19 (sd 4) and 22 (sd 4) % compared with the control group, respectively (both P < 0.01). In conclusion, EPA and fish oil supplementation lowers circulating lipid concentrations, but does not delay the onset of T2DM in UCD-T2DM rats.

Effect of a Novel Eicosapentaenoic Acid‐Rich Oil on Serum Cholesterol in Man: Comparison to Docosahexaenoic Acid

BackgroundFish oil and DHA raise LDL cholesterol (LDL‐C); the effects of EPA are less defined.Study Design121 healthy volunteers were recruited into a randomized, double‐blinded, placebo‐controlled, parallel‐arm, 6 week study. The placebo group received olive oil; the low dose EPA group (EPA600) received 600 mg/day of a yeast derived EPA; the high dose EPA group (EPA1800) received 1800 mg/day, and the DHA group (DHA600) received 600 mg/day of an algal derived DHA. Notably, the EPA oil did not contain any DHA and the DHA oil did not contain any EPA.Results110 subjects completed the study. The study population was 21–70 yrs of age, 67% male, 33% female, with an average BMI of 27.4. Subjects were not allowed lipid‐lowering medications or omega‐3 dietary supplements during the study and were counseled to maintain their normal diet and exercise programs. The number of subjects who remained free of fishy aftertaste or eructation was 92% for placebo, 85% for EPA600, 72% for EPA1800, and 61% for DHA600. The placebo group exhibited a 6% decrease in LDL‐C (n=26, P&lt;0.01); the EPA600 group a 3% decrease in LDL‐C (n=27, NS), the EPA1800 group a 2% decrease in LDL‐C (n=29, NS); in contrast, the DHA group exhibited a 14% increase in LDL‐C (n=28, P&lt;0.02). HDL and TG levels were relatively unaffected.ConclusionDHA, but not EPA, raised LDL‐C in normal lipidemic subjects at a dietary intake of 600 mg/day for 6 weeks. Funded by DuPont.

A High-Fat Meal Enriched with Eicosapentaenoic Acid Reduces Postprandial Arterial Stiffness Measured by Digital Volume Pulse Analysis in Healthy Men ,

Diets rich in eicosapentaenoic acid [EPA; 20:5(n-3)] are associated with decreased arterial stiffness, but postprandial effects on vascular function are unknown. We investigated whether an EPA-enriched high-fat meal could improve postprandial vascular function. Seventeen healthy men ingested 2 test meals (51 g fat), 1 wk apart, in random order: 5 g EPA plus high-oleic sunflower oil (HOS) vs. HOS only. A second high-fat meal (44 g fat), the same on both study days, was provided 4 h later. Blood pressure and arterial function were measured using digital volume pulse (DVP) to derive a stiffness index (DVP-SI) and reflection index in fasting subjects at 3 and 6 h following the test meal. Blood samples were taken following the test meal for plasma 8-isoprostane F2α, nitric oxide (NO) metabolites (NOx), glucose, insulin, triacylglycerol, and fatty acid analysis. The plasma EPA concentration (mean ± SD) reached a peak of 2.10 ± 0.99 mmol/L following the EPA meal (5 h) and did not rise above 0.27 ± 0.16 mmol/L 1 h following the placebo meal. ∆DVP-SI did not differ between the 2 test meals at 3 h but was greater at 6 h following EPA (6 h −0.65 ± 0.65 m/s) compared with placebo (6 h −0.33 ± 1.26 m/s). Plasma 8-isoprostane F2α concentrations increased by 48% at 6 h compared with baseline following the EPA meal and plasma NOx decreased following both meals, with no differences between the meals in the changes. Changes in other variables measured also did not differ after subjects consumed the 2 meals. In conclusion, adding EPA to a high-fat meal results in acute changes in vascular tone, independent of changes in oxidative stress.