Polyunsaturated Fatty Acid Ethyl Esters Research Articles

Letter by Halcox Regarding Article, “OMEGA, A Randomized, Placebo-Controlled Trial to Test the Effect of Highly Purified Omega-3 Fatty Acids on Top of Modern Guideline-Adjusted Therapy After Myocardial Infarction”

HomeCirculationVol. 124, No. 1Letter by Halcox Regarding Article, “OMEGA, A Randomized, Placebo-Controlled Trial to Test the Effect of Highly Purified Omega-3 Fatty Acids on Top of Modern Guideline-Adjusted Therapy After Myocardial Infarction” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Halcox Regarding Article, “OMEGA, A Randomized, Placebo-Controlled Trial to Test the Effect of Highly Purified Omega-3 Fatty Acids on Top of Modern Guideline-Adjusted Therapy After Myocardial Infarction” Julian P. Halcox, MA, MD, FRCP Julian P. HalcoxJulian P. Halcox Cardiff University Cardiff, Wales Search for more papers by this author Originally published5 Jul 2011https://doi.org/10.1161/CIRCULATIONAHA.110.016287Circulation. 2011;124:e21To the Editor:I read with interest the results of the OMEGA trial,1 in which the addition of omega-3 polyunsaturated fatty acid (PUFA) ethyl esters to modern, evidence-based treatment of patients who had had a recent myocardial infarction (MI) did not significantly reduce the primary end point of sudden cardiac death (SCD) or other clinical events within 1 year. As would be expected in a trial of contemporary therapy, 78% of OMEGA trial patients underwent coronary revascularization, and 94% received a statin on discharge, in contrast to 5% who underwent coronary revascularization and 29% who received lipid-lowering drugs even after 6 months in the earlier GISSI-P trial.2 An appropriately designed trial of omega-3 PUFAs in the context of modern management of post-MI patients is therefore highly desirable.The absence of significant benefits from omega-3 PUFAs might be explained in part by the OMEGA study design. Sample size was calculated by the use of available MI registry and clinical trial data, the anticipated risk profile of the patients to be enrolled, and with the expectation of a 45% reduction after 1 year in the relative risk of SCD with omega-3 PUFA treatment as seen in GISSI-P. Thus, 1-year SCD rates of 3.5% in the control group and 1.9% in the treated group were predicted. It is significant that the SCD rate in the OMEGA study cohort was >50% lower than anticipated: 1.5% at 1 year in both the placebo and treatment groups. This presumably resulted from modern treatment practices and, as acknowledged, the possible contribution of the lower than anticipated risk profile of the trial population. Consequently, OMEGA was underpowered for the primary end point. Considering the ongoing improvements in acute treatment and secondary prevention since the GISSI-P trial, it may have been reasonable to assume lower rates for overall mortality, the proportion of deaths resulting from SCD, or the relative risk reduction for SCD achieved with active therapy. Although the investigators stated it was not feasible to adopt an event-driven protocol or to enroll the number of patients (≈20 000 rather than 4000) necessary to achieve statistical power with the lower event rates observed, it should be acknowledged that firm conclusions cannot be drawn from this underpowered study.In addition, the 1-year duration of the OMEGA trial aimed to investigate the early benefits of omega-3 PUFAs shown by a post hoc time-course analysis of the first year of treatment in the GISSI-P trial.3 However, more recent trials, such as the GISSI-HF4 and JELIS5 trials, have shown ongoing benefits of omega-3 PUFAs when taken for >3 years. Thus, a longer follow-up period could have increased the power of the OMEGA trial and may also have revealed longer-term benefits of highly purified omega-3 PUFAs post-MI.In light of these important limitations and the consequent difficulty in drawing confident conclusions, changes to current practice in the use of highly purified omega-3 PUFAs for post-MI patients cannot be justified on the basis of the OMEGA trial data. Adequately powered studies are mandatory to elucidate the efficacy and tolerability of high-dose omega-3 PUFAs when given alongside modern evidence-based therapies post-MI.Julian P. Halcox, MA, MD, FRCP Cardiff University Cardiff, WalesAcknowledgmentsMedical writing support was provided by Gail Rickard.Sources of FundingThis work was funded by Abbott Laboratories.DisclosuresDr Halcox has received honoraria for lecturing and consultancy fees from Abbott Laboratories.

Cost‐effectiveness of highly purified omega‐3 polyunsaturated fatty acid ethyl esters in the treatment of chronic heart failure: results of Markov modelling in a UK setting

A recent randomized placebo-controlled clinical trial has reported reductions in mortality and hospitalizations in patients with chronic heart failure (CHF) who were prescribed highly purified omega-3 polyunsaturated fatty acid ethyl esters (n-3 PUFA). This study aimed at evaluating the cost and benefits associated with their use in the treatment of CHF in a UK setting. Results from a recent clinical trial were used to develop a Markov model to project clinical outcomes while capturing relevant costs and patient quality of life. The model captured outcomes over a lifetime horizon from a UK National Health Service perspective, with direct costs accounted in 2009 GBP (£) and discounted at 3.5% together with clinical benefits. Results are presented in terms of life expectancy, quality-adjusted life expectancy, direct costs, and incremental cost-effectiveness ratios. In addition to standard therapy, n-3 PUFA vs. placebo increased lifetime direct costs by £993 (≈€1150), with additional quality-adjusted life expectancy of 0.079 quality-adjusted life years (QALYs), and mean lifetime costs of £12,636 (≈€14,600) per QALY gained. Probabilistic sensitivity analyses suggested a 60% likelihood of n-3 PUFA being regarded as cost-effective versus placebo at a willingness-to-pay threshold of £30,000 (≈€34,600) per QALY gained. By currently accepted standards of value for money in the UK; the addition of n-3 PUFA to optimal medical therapy for patients with heart failure is likely to be cost-effective.

Eicosapentaenoic acid (EPA) from highly concentrated n−3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability

ObjectiveTo examine n−3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability. Methods and resultsPatients awaiting carotid endarterectomy (n=121) were randomised to consume control capsules or n−3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher (P<0.0001) in carotid plaque phospholipids in patients in the n−3 PUFA group. Plaques from patients in the n−3 PUFA group had fewer foam cells (P=0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability (P=0.0209), plaque inflammation (P=0.0108), the number of T cells in the plaque (P=0.0097) and a summary score considering a range of plaque features (P=0.0425). Plaques from patients who received n−3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 (P=0.0055), -9 (P=0.0048) and -12 (P=0.0044) and for interleukin-6 (P=0.0395) and intercellular adhesion molecule 1 (P=0.0142). ConclusionsAtherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability.

Dietary n-3 Polyunsaturated Fatty Acids and Direct Renin Inhibition Improve Electrical Remodeling in a Model of High Human Renin Hypertension

We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II-induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA- or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180+/-3 mm Hg) compared with dTGRs (208+/-5 mm Hg). Aliskiren-treated dTGRs and Sprague-Dawley rats were normotensive (110+/-3 and 119+/-6 mm Hg, respectively). Both n-3 PUFA-treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QT(c) intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy.

Supercritical CO2 extraction and concentration of n-3 polyunsaturated fatty acid ethyl esters from tuna cooking juice

Cooking is an important step in the tuna canning process; it usually produces functional solubilized proteins and lipids. The objective of this study was to recover and increase the concentration of functional n−3 fatty acids from the lipids in cooking juice. The lipids contained 12.98% eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) after ethyl esterification and increased to 37.4% with subsequent urea adduct fractionation. Supercritical carbon dioxide extraction was further used to increase the concentration of EPA and DHA ethyl esters. The ratio of EPA+DHA ethyl esters (high-molecular-weight components) to that of C16 and C18∶1 fatty acid ethyl esters (low-molecular-weight components) was used as a separation index for evaluating the process variables. Experimental results indicated that a high CO2 density caused a low separation factor. At 1500 psig and 328.2 K, the extraction collected over 600 L CO2, displaying an accepted concentration factor of EPA+DHA ethyl esters herein. About 80% yield of EPA and DHA was obtained and the ethyl esters increased from 37.4% to 54.3%.

Comparative study of the product components of lipid oxidation in aqueous and organic systems

Ethyl esters and phosphatidylcholines (PCs) of polyunsaturated fatty acids (PUFAs) were oxidized in organic solvents, aqueous emulsions, and liposomes in the presence of a radical inducer. Oxidation products and the positional distribution of monohydroperoxide (MHP) were determined by gas chromatography-mass spectrometry (GC-MS) analysis. The total amount of the oxidation products, of PUFA ethyl esters and PCs in organic solvents, increased with an increase in the number of bis-allylic positions. However, the opposite results were obtained in an aqueous emulsion and liposomes. The distribution pattern of MHPs obtained from oxidation of the linolate and α-linolenate showed little difference between a chloroform solution and an aqueous emulsion or liposomes. However, there were differences between these systems with the arachidonate, the icosapentaenoate, and docosahexaenoate. These results may be due to the different rate of hydrogen abstraction from bis-allylic positions in the fatty acid moieties, and/or 1,3-cyclization of hydroperoxides in the systems.

The effects of dietary n-3 vs. n-6 fatty acids on ex-vivo LTB4 generation by canine neutrophils.

Dietary n-3 polyunsaturated fatty acids are widely used for amelioration of inflammatory skin disease in dogs. In this study, a diet containing two different sources of n-3 polyunsaturated fatty acid-triglyceride (from menhaden oil) and concentrated ethyl esters-was fed to one group of six purpose-bred dogs, while an isocaloric isonitrogenous diet with corn oil (n-6 polyunsaturated fatty acids) was fed to another group of eight purpose-bred dogs for six weeks. Peripheral blood neutrophils, isolated at week-1 (baseline), week 2 and week 6, were stimulated with calcium ionophore A23187 and the amount of leukotriene B4 produced was determined via reversed-phase high performance liquid chromatography. Analysis of variance of log-transformed data revealed a significant effect for diet (P = 0.005) at six weeks, with dogs fed the high n-3 polyunsaturated fatty acid diet having significantly less mean ex vivo neutrophil leukotriene B4 production than dogs fed the high n-6 polyunsaturated fatty acid diet. Further studies on the clinical usefulness of n-3 polyunsaturated fatty acid ethyl esters are warranted.

Phase equilibria of long-chain polyunsaturated fish oil fatty acid ethyl esters and carbon dioxide, ethane, or ethylene at reduced gas temperatures of 1.03 and 1.13

Phase equilibria of a mixture of long-chain polyunsaturated fish oil fatty acid ethyl esters (FAEEs) with carbon dioxide were measured at 313.2 and 343.2 K, with ethane at 314.0 and 344.6 K, and with ethylene at 290.9 and 318.6 K. The temperatures correspond to reduced gas temperatures of approximately 1.03 and 1.13. The experimental pressures range from 1.6 to 25 MPa. The FAEE mixture is rich in eicosapentaenoic acid ethyl ester (EPA, 52.5 wt.%), and docosahexaenoic acid ethyl ester (DHA, 36.1 wt.%), and a total of 10 components were identified. The experimental temperatures, pressures, solubilities, mass fractions, and calculated equilibrium ratios are reported in tables and graphs. The mass fractions and the equilibrium ratios are reported on a solvent-free basis.

Kinetic Analysis of the Autoxidation of Ethyl Eicosapentaenoate at Different Oxygen Levels.

The autoxidation of such n-3 polyunsaturated fatty acid (PUFA) ethyl esters as ethyl eicosapentaenoate and ethyl docosahexaenoate was investigated at various temperatures. Extensive studies of the oxidative reaction for ethyl eicosapentaenoate were carried out at different oxygen levels. At the same oxygen level and temperature, the autocatalytic reaction rate, by which oxidation progressed in the first half period, was about 1.5-2.5 times larger than the first-order reaction rate which governed the oxidation in the second half period. The reaction rate constants for ethyl eicosapentaenoate at different oxygen levels correlated well with the Langmuir-type equation of the oxygen concentration, in which the Langmuir parameter was independent of temperature.

Multiple intensified performance of an enzyme-catalyzed reaction in organic medium.

A lipase-catalyzed glycerolysis reaction (a transesterification between polyunsaturated fatty acid ethyl ester [PUFA] and glycerol) was investigated. Its performance was multiply intensified by (1) using a lipase having high specific activity, high activity in organic solvent, and high tolerance in organic solvent; (2) immobilization on fine CaCO3 powder (cheap and safe material, easy physical adsorption method of immobilization, reusable); (3) reaction in vacuo resulting in 100% conversion and effective avoidance of oxidative deterioration of PUFA; (4) high volumetric productivity because of no use of solvent; and (5) no need of further separation and purification of the oil product. It is emphasized that performance of biocatalytic reactions in organic media should be enhanced manifold for industrial implementation.

Enzymatic synthesis of glycerides from DHA-enriched PUFA ethyl ester by glycerolysis under vacuum

Pseudomonas lipase immobilized on CaCO 3 powder was used for the glycerolysis of n−3 polyunsaturated fatty acid ethyl esters to prepare nutritionally valuable glycerides. The initial ethyl ester contained 65 or 99% docosahexaenoic acid ethyl ester (DHAEE) which is very unstable and readily oxidized. The process performance was intensified by: (1) using Pseudomonas lipase which has good specificity for docosahexaenoic acid (DHA), (2) shifting the reaction equilibrium by evaporation of the resulted ethanol under vacuum and (3) enhancing the enzyme operational stability by immobilization on CaCO 3 powder. Under these conditions, over 90% conversion of DHAEE was achieved in 5 h and the oxidative deterioration of DHA was avoided. The final product contained 53% partial glyceride and, thus, had good emulsifying power. The catalyst was reused 5 times showing a very good stability in this system. Other lipases were tried for this reaction and different glyceride compositions were obtained depending on the enzyme specificity for the 1(3)-position of glycerol.

A fish oil derived concentrate enriched in eicosapentaenoic and docosahexaenoic acid as ethyl ester suppresses the formation and growth of intestinal polyps in the Min mouse.

We examined whether the n-3 polyunsaturated fatty acid ethyl ester enriched fish oil K85 (54.4% of eicosapentaenoic acid and 30.3% of docosahexaenoic acid as ethyl esters) could inhibit the intestinal tumorigenesis in Min mice, a murine model of familial adenomatous polyposis (FAP). Min mice that are heterozygous for a nonsense mutation in the Apc gene, develop spontaneously multiple intestinal neoplasms, primarily in the small intestine. K85 was dissolved in corn oil (vehicle) and mixed into the AIN-76A diet. The total oil content (K85 + corn oil) was 12% in all diets. The various experimental diets contained 0 (vehicle control), 0.4, 1.25 or 2.5% of K85. In the small intestine, the mean number of tumors/mouse was 105 +/- 18 (SEM) in control males and 70 +/- 11 in control females. Dietary K85 treatment reduced the number of small intestinal tumors: in males, the maximum reduction was 66% (P = 0.002) with 0.4% of K85; and in females, the maximum reduction was 48% (P = 0.043) with 2.5% of K85, but the inhibition was only slightly increased from 0.4% to 2.5% of K85. The mean tumor diameter was 1.33 +/- 0.08 mm in control males and 1.06 +/- 0.08 in control females, and the diameter ranged from <0.1 mm (monocryptal adenomas) to 4 mm. The small intestinal tumor diameter was reduced by K85 in a dose-dependent manner: in males, with a maximum reduction of 26% (r = -0.64, P = 0.004); and in females, with a maximum reduction of 38% (r = -0.61, P < 0.004). In the large intestine, the mean number of tumors/mouse was 1.0 +/- 0.5 in males and 0.8 +/- 0.2 in females. Although K85 treatment tended to reduce the number and diameter of the large intestinal tumors, these effects did not reach statistical significance. Aberrant crypt foci not elevated from the flat mucosa (ACF(Min)) occurring in the colon of Min mice were also scored. The mean number of ACF(Min)/colon (3.8 +/- 0.9) and the crypt multiplicity (1.49 +/- 0.28) in females were reduced by 73% (P = 0.03) and 60% (P = 0.048) with 2.5% of K85, respectively, whereas no significant effect could be observed in the males.

N-3 PUFA supplementation, monocyte PCA expression and interleukin-6 production

n-3 polyunsaturated fatty acids (PUFA) can affect several monocyte functions and the biochemistry of blood cells, thus possibly influencing the initiation of thrombosis, inflammatory disease and atherosclerosis. In this study, we have investigated the effect of dietary supplementation with n-3 PUFA ethyl esters on procoagulant activity (PCA) and interleukin-6 (IL-6) production by human mononuclear cells. Nine healthy volunteers received 4 g/d of n-3 PUFA ethyl esters (4 × 1 g capsules with at least 85% eicosapentaenoic + docosahexaenoic acid ethyl esters) for 18 weeks. Before and at the end of the treatment, mononuclear cells were obtained from peripheral citrated blood by Ficoll-Hypaque density gradient centrifugation. Cellular suspensions (10 7 cells/ml) were incubated at 37°C for 4 h in the absence and presence of lipopolysaccharide (10 μg/ml); PCA was determined by one-stage clotting assay and IL-6 concentrations were assayed in supernatants by specific ELISA. After 18-week treatment, both unstimulated and stimulated monocyte PCA were significantly reduced by 66% and 63%, respectively ( P < 0.01). Similarly, a significant inhibitory effect by n-3 PUFA treatment on basal and LPS-stimulated IL-6 monocyte production was observed (50% and 46%, respectively, P < 0.05). These data indicate that 18-week n-3 PUFA supplementation may influence monocyte activities, which play a specific role in atherosclerosis and its thrombotic complications.

Effect of n-3 polyunsaturated fatty acid intake on phospholipid fatty acid composition in plasma and erythrocytes

To characterize the time course of plasma and red blood cell (RBC) changes after n-3 polyunsaturated fatty acid (PUFA) supplementation, 20 healthy male volunteers were randomly assigned to receive either four 1-g capsules of n-3 PUFA ethyl esters or four 1-g capsules of olive oil (as placebo) for a period of 4 mo, followed by a 3-mo washout period. Fatty acids of plasma and RBC phospholipid fractions were analyzed at 0, 2, and 4 mo of treatment and at 1, 2, and 3 mo of washout. During n-3 PUFA supplementation, accumulations of eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids were marked after 2 mo with differences among different fractions of plasma and RBCs in further accumulation up to 4 mo. During the first and second months of the washout, slight differences were observed in changes of various fatty acids among different phospholipid fractions, but after 3 mo of washout, only minor alterations were still detectable with respect to pretreatment values. These data confirm the complex relations among different fatty acid pools after n-3 PUFA supplementation.

Extraction of polyunsaturated fatty acid ethyl esters from sardine oil using Ag +-containing o/w/o emulsion liquid membranes

Using silver ion as a carrier in o/w/o type emulsion liquid membranes, batch-wise extraction experiments were performed to separate polyunsaturated fatty acid ethyl esters originating in sardine oil. It was possible to separate polyunsaturated fatty acid (PUFA) esters from the mixture of PUFA and saturated fatty acid esters. The operating conditions for stable liquid membranes were experimentally determined. A new membrane breakage model that successfully describes the membrane stability behavior is proposed.

Effect of n-3 fatty acid ethyl ester supplementation on fatty acid composition of the single platelet phospholipids and on platelet functions

Twenty healthy male volunteers were randomly assigned to receive either four 1-g capsules of n-3 polyunsaturated fatty acids (PUFA) ethyl esters or four 1-g capsules of olive oil (as placebo) for a period of 4 months, followed by a 3-month wash-out period. Fatty acids of platelet phospholipid fractions, platelet aggregation, and thromboxane B 2 (TXB 2) formation were analyzed at 0, 2, and 4 months of treatment and at 1, 2, and 3 months of wash-out. During n-3 PUFA supplementation, accumulations of eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids were markedly increased after 2 months, with slight differences in further accumulation up to 4 months among the various phospholipid fractions. Significant decreases in platelet sensitivity to collagen, serum TXB 2 levels, and urinary TXB 2 metabolites were also observed following n-3 PUFA treatment. During the first and second month of wash-out, slight differences were observed in changes of various fatty acids among different phospholipid fractions, but after 3 months of wash-out, alterations were no longer detectable with respect to pretreatment values. After 3 months of wash-out, platelet function parameters also were returned to baseline. Thus, both platelet lipids and function are influenced by n-3 PUFA ethyl ester supplementation, and significant alterations are still detectable after 2 months of wash-out.

No changes in PAI-1 levels after four-month n-3 PUFA ethyl ester supplementation in healthy subjects

Recent studies have indicated that diets rich in fish or supplemented with fish oils may increase PAI-1 plasma levels. However, this finding has not been consistent and could be related, at least in part, to the type of supplementation. Aim of this study was to investigate the effects of medium-term treatment with n-3 polyunsaturated fatty acid (PUFA) ethyl esters on fibrinolysis. Twenty normolipemic healthy male subjects (age 27 to 41 yrs) were randomly assigned to receive either 4 x 1 g capsules of n-3 PUFA ethyl esters (ESAPENT, Farmitalia-Carlo Erba, Milan, Italy) or 4 x 1 g capsules of olive oil (as placebo) for 4 months in a double blind study. Blood samples for lipid and hemostatic studies were obtained at 0, 2, and 4 months of treatment and 1, 2 and 3 months of wash-out. Plasma lipids, fibrinolytic system, lipoprotein (a)-Lp(a)-, fibrinogen (Fbg) and prothrombin activation fragment 1+2 (F1+2) were assayed. No changes in these parameters were observed in the group of ten subjects treated with olive oil. After n-3 PUFA supplementation no significant alterations were found in plasma lipids, even if a trend to lower triglyceride and Lp(a) levels was detectable. No changes in either PAI-1 activity or PAI-1 antigen levels or F1+2 plasma levels were observed. A trend to lower Fbg levels was found after n-3 PUFA, but changes were not statistically significant. The results of this study indicate that a 4-month treatment with 4 g daily n-3 PUFA ethyl esters does not affect PAI-1 plasma levels.

Phase Equilibria of Urea-Fractionated Fish Oil Fatty Acid Ethyl Esters and Supercritical Carbon Dioxide

Measurements of phase equilibria of urea-fractionated fish oil fatty acid ethyl esters (FAEEs) in supercritical carbon dioxide were performed at pressures from 8 to 26 MPa and temperatures of 313.2 and 343.2 K. Experimental temperatures, pressures, and mass fractions are reported in tubular form. The equilibrium ratios of the esters depend strongly on the system pressure and temperature, and a comparison with previous equilibrium measurements on the fatty acid ethyl ester mixture before the urea fractionation shows that they also depend on the composition of the ester mixture. The data show that high selectivity and low solubility are obtained at low operating pressures, while at high operating pressures the selectivity is low but the solubility is high. Twenty-nine components corresponding to more than 90% of the natural mixture are identified. The three polyunsaturated FAEEs, C 18:4n3 , C 20:5n3 , and C 22:6n3 , correspond to more than 80% of the urea-fractionated mixture

Antimalarial effects of purified and α-tocopherol—fortified n-3 polyunsaturated fatty acids

A vitamin E-deficient diet containing fish oil is known to afford a protection against malaria in mice. In the present study we examined whether the dietary supplementation with α-tocopherol—fortified n-3 polyunsaturated fatty acid (PUFA) ethyl esters (eicosapentaenoic acid (EPA) ethyl ester and docosahexaenoic acid (DHA) ethyl ester) had a protective effect against malaria. Four groups of mice were each given one of the following diets: (1). powered standard chow (REF group); (2). 90% (wt) lipid-free diet with 8% lard and 2% safflower oil (SAF group); (3). 90% lipid-free diet with 8% lard and 2% EPA ethyl ester (EPA group); and (4). 90% lipid-free diet with 8% lard and 2% DHA ethyl ester (DHA group). Safflower oil, EPA, and DHA were fortified with 0.2% α-tocopherol before mixing dietary components. After 6 weeks on these diets, mice were inoculated with Plasmodium yoelii, and the same diets were continued until the end of the experiment. The survival rates of the four groups 46 days after the inoculation were 1 2 , 0 12 , 5 12 , and 4 10 in the REF, SAF, EPA, and DHA groups, respectively. There was a significant difference in the survival rates ( P < 0.025) among the groups. It may be possible to conduct a clinical trial with malarial patients using EPA or DHA ethyl ester fortified with α-tocopherol.

Nitrite stabilization of lipids in cured pork

Peroxidation studies indicated that phospholipids, microsomes and mitochondria from cured pork samples are less susceptible to metmyoglobin/hydrogen peroxide-catalyzed peroxidation than their counterparts from nitrite-free pork samples. The reaction of phospholipids and polyunsaturated fatty acid ethyl esters with dinitrogen trioxide increased their stability to peroxidative changes. Phospholipids from cured pork and those lipids reacted with dinitrogen trioxide were capable of nitrosating a secondary amine. These data, together with infrared analyses, indicate that nitrite or dinitrogen trioxide reacts with unsaturated lipids to form nitro-nitroso derivatives, thus stabilizing the lipids toward peroxidation changes. This mechanism can, in part, explain the antioxidant role of nitrite in cured meats.