Acids In Fish Oil Research Articles

Omega-3 fatty acids improve the diagnosis-related clinical outcome*

Supplementation of clinical nutrition with omega-3 fatty acid in fish oil exerts immune-modulating and organ-protective effects, even after short-term application. The aim of this study was to evaluate dose-dependent effects of parenteral supplementation of a 10% fish oil emulsion (Omegaven, Fresenius-Kabi, Bad Homburg, Germany) on diagnosis- and organ failure-related outcome. Prospective, open label, multiple-center trial. A total of 661 patients from 82 German hospitals receiving total parenteral nutrition for > or =3 days were enrolled in this study. The sample included 255 patients after major abdominal surgery, 276 with peritonitis and abdominal sepsis, 16 with nonabdominal sepsis, 59 after multiple trauma, 18 with severe head injury, and 37 with other diagnoses. The primary study end point was survival; secondary end points were length of hospital stay and use of antibiotics with respect to the primary diagnosis and the extent of organ failure. Multiple quasi-linear and logistic regression models were used for calculating diagnosis-related fish oil doses associated with best outcome. The patients enrolled in this survey were (mean +/- sd) 62.8 +/- 16.5 yrs old, with a body mass index of 25.1 +/- 4.2 and Simplified Acute Physiology Score (SAPS) II score of 32.2 +/- 13.6. Length of hospital stay was 29.1 +/- 18.7 days (12.5 +/- 14.8 days in the intensive care unit). Total parenteral nutrition, including fish oil (mean, 0.11 g.kg(-1).day(-1)), was administered for 8.7 +/- 7.5 days and lowered hospital mortality as predicted by Simplified Acute Physiology Score II from 18.9% (95% confidence interval, 17.4-20.4%) to 12.0% (p < .001). The fish oil dose.kg.day did correlate with beneficial outcome (intensive care unit stay, hospital stay, mortality). Fish oil had the most favorable effects on survival, infection rates, and length of stay when administered in doses between 0.1 and 0.2 g.kg(-1).day(-1). Lower antibiotic demand by 26% was observed when doses of 0.15-0.2 g.kg(-1).day(-1) were infused as compared with doses of <0.05 g.kg(-1).day(-1). After peritonitis and abdominal sepsis, multiple quasi-linear regression models revealed a fish oil dose for minimizing intensive care unit stay of 0.23 g.kg(-1).day(-1) and an inverse linear relationship between dosage and intensive care unit stay in major abdominal surgery. Administration of omega-3 fatty acid may reduce mortality, antibiotic use, and length of hospital stay in different diseases. Effects and effect sizes related to fish oil doses are diagnosis dependent. In view of the lack of substantial study literature concerning diagnosis-related nutritional single-substrate intervention in the critically ill, the present data can be used in formulating hypotheses and may serve as reference doses for randomized, controlled studies, which may, for instance, confirm the value of omega-3 fatty acid in the adjunctive therapy of peritonitis and abdominal sepsis.

Docosahexaenoic acid inhibits adipocyte differentiation and promotes lipolysis in 3T3‐L1 cells

Docosahexaenoic acid (DHA, C22:6), an effective n-3 fatty acid in fish oil, has been shown to decrease body fat and fat accumulation in animals. We investigated the effect of DHA on adipogenesis, lipolysis, and apoptosis in 3T3-L1 adipocytes. When added to postconfluent preadipocytes, DHA inhibited differentiation-induced mitotic clonal expansion (218.8±2.7; 171.9±3.2; 161.5±3.4 for 0, 50, 200uM DHA, respectively, at 72 h, expressed as percent of 0 h, p<0.001). After DHA treatment for 6 days with differentiation medium, adipogenesis was monitored by Oil-Red-O staining and analyzed by image scanning. DHA decreased markedly mean droplet size (733.8±70.9; 365.6±31.0; 123.5±14.7 for 0, 50, 200uM DHA, respectively, p<0.001) and percent lipid area (25.6±1.0; 15.3±1.1; 9.4±0.6 for 0, 50, 200uM DHA, respectively, p<0.001) in a dose-dependent manner. In fully differentiated adipocytes, DHA increased basal lipolysis compared with the control (149% for 50uM and 193% for 200uM, p<0.001). Apoptosis was measured after treatment of mature adipocytes with 0, 50, 200uM DHA for 24 and 48 h. Caspase 3/7 activity was not altered. Only the high dose of DHA induced apoptosis after 24 h incubation as determined by ssDNA ELISA assay (144% for 200uM DHA; p=0.05). These results demonstrate that DHA acts primarily by blocking preadipocyte differentiation to adipocytes and promoting lipolysis, therefore it could mediate a reduction of body fat.

Influence of dietary source of docosahexaenoic and arachidonic acids on their incorporation into membrane phospholipids of red blood cells in term infants

Here we studied whether the chemical structure of dietary arachidonic and docosahexaenoic acids in full-term infant diets affects their incorporation into erythrocyte membrane phospholipids. From birth to 3 months, infants were fed breast milk ( n = 9 ) or formula milk containing arachidonic acid and docosahexaenoic acid provided by egg phospholipids ( n = 10 ) or by low-eicosapentaenoic acid fish oil and fungal triglycerides ( n = 10 ). We compared the fatty acid composition of erythrocyte phosphatidylethanolamine, phosphatidylcholine and sphingomyelin before and after administration of the experimental diet. At 3 months, infants on formula milk showed lower concentrations of docosahexaenoic acid (in phosphatidylcholine and in phosphatidylethanolamine) and arachidonic acid (in phosphatidylcholine) than those receiving breast milk. We conclude the incorporation of the two fatty acids into erythrocyte phospholipids depends mainly on the lipid composition of the diet received rather than the chemical form in which they are delivered.

Detection of radical development by ESR spectroscopy techniques for assessment of oxidative susceptibility of fish oils

Detection of radical development by two different Electron Spin Resonance (ESR) spectroscopy techniques has been evaluated for obtaining objective analytical information about oxidative susceptibility of fish oils under mild oxidation conditions. Two oils from different by-products in the fish industry, salmon viscera oil (SVO) and cod liver oil (CLO), were used. In addition, radical formation in the ethyl ester of docosahexaenoic acid (DHA) was studied as representing polyunsaturated fatty acids in fish oils that are very prone to oxidation. The ESR spin trapping technique, using the spin trap α-phenyl-N-tert-butylnitrone, and the ESR spin scavenging technique, using the stable nitroxyl radical 2,2,6,6-tetramethyl-1-piperidinyl-1-oxyl (TEMPO) to be scavenged by radicals generated in the oxidative process, were applied to detect radical development at 40 °C in the dark. For comparative purposes, oxidative susceptibility was evaluated by determination of peroxide value (PV) and the TBARS test under the same oxidation conditions. Results were also compared to the oil stability index (OSI) obtained at 60 °C. Results obtained by ESR spin trapping were consistent with results obtained in the OSI test, as well as those obtained for PV and the TBARS test. Therefore, detection of radical formation by ESR spin trapping provided objective information upon the relative oxidative susceptibility of SVO and CLO. On the other hand, results obtained by ESR spin scavenging were not concluding to establish the different oxidative susceptibility of the two oils found by the other determinations applied. The kinetic curves of TEMPO were similar for both oils, which suggests that mechanisms other than that based on the expected radical-radical interactions might be involved.

Inflammation control gets fishy

A new study explains how a diet high in oily fish like salmon and mackerel improves inflammatory conditions, particularly in combination with low doses of aspirin. On page 713, Arita et al. decipher the structure of an antiinflammatory lipid in humans that is derived from an essential fatty acid in fish oil.

Letter Regarding Article by Mozaffarian et al, “Fish Intake and Risk of Incident Atrial Fibrillation”

To the Editor: The beneficial effect of fish oils on sudden cardiac death is well recognized and is believed to be due to an antiarrhythmic effect of the long-chained n-3 fatty acids in fish oils.1 Therefore, it is of major interest that Mozaffarian and colleagues now report that fish intake might reduce the incidence of atrial fibrillation (AF).2 Although this prospective study does not prove causality between fish intake and the incidence of AF, it is reasonable to mention biologically plausible mechanisms that could explain the effect. However, several of the mechanisms …

Eicosapentaenoic acid prevents lipopolysaccharide-stimulated DNA binding of activator protein-1 and c-Jun N-terminal kinase activity

Activator protein-1 (AP-1) is a transcription factor that plays an important role in regulating the expression of proinflammatory cytokines including tumor necrosis factor-α (TNF-α). Many studies have shown that fish oil supplementation inhibits TNF-α production in mice and humans; however, the mechanisms remain unclear. In this study, the effects of eicosapentaenoic acid (EPA), a major n-3 fatty acid in fish oil, on lipopolysaccharide (LPS)-stimulated activation of AP-1 were investigated in human monocytic THP-1 cells. The results demonstrated that AP-1 DNA binding activity stimulated by LPS was suppressed by preincubating cells with EPA. Lipopolysaccharide-stimulated increase of c-Jun and c-Fos protein levels was also attenuated by EPA pretreatment. In addition, EPA pretreatment decreased LPS-induced c-Jun phosphorylation and c-Jun N-terminal kinase (JNK) activation. The results suggest that suppression of TNF-α expression by EPA may be partly mediated by its inhibitory effect on AP-1 activation.

Omega-3 Fatty Acids in the Treatment of Psychiatric Disorders

The importance of omega-3 fatty acids for physical health is now well recognised and there is increasing evidence that omega-3 fatty acids may also be important to mental health. The two main omega-3 fatty acids in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have important biological functions in the CNS. DHA is a major structural component of neuronal membranes, and changing the fatty acid composition of neuronal membranes leads to functional changes in the activity of receptors and other proteins embedded in the membrane phospholipid. EPA has important physiological functions that can affect neuronal activity. Epidemiological studies indicate an association between depression and low dietary intake of omega-3 fatty acids, and biochemical studies have shown reduced levels of omega-3 fatty acids in red blood cell membranes in both depressive and schizophrenic patients. Five of six double-blind, placebo-controlled trials in schizophrenia, and four of six such trials in depression, have reported therapeutic benefit from omega-3 fatty acids in either the primary or secondary statistical analysis, particularly when EPA is added on to existing psychotropic medication. Individual clinical trials have suggested benefits of EPA treatment in borderline personality disorder and of combined omega-3 and omega-6 fatty acid treatment for attention-deficit hyperactivity disorder. The evidence to date supports the adjunctive use of omega-3 fatty acids in the management of treatment unresponsive depression and schizophrenia. As these conditions are associated with increased risk of coronary heart disease and diabetes mellitus, omega-3 fatty acids should also benefit the physical state of these patients. However, as the clinical research evidence is preliminary, large, and definitive randomised controlled trials similar to those required for the licensing of any new pharmacological treatment are needed.

TREATING CYSTIC FIBROSIS WITH FISH OIL

14 July 2004 Dear Editor, In 1997, I published the results of a small open study reporting the beneficial effect of omega 3 fatty acid (eicosopentanoic acid-fish oil) supplements in the management of children with cystic fibrosis (CF) and chronic lung disease1. One of the five subjects had severe disease and died during the study, and her parameters effectively cancelled the positive effects of the other four, thus distracting from the impact of the potential of this therapy. Now, Karp et al. have demonstrated that the major problem in CF airways is the inability to produce lipoxins, anti-inflammatory mediators, which results in an exaggerated pro inflammatory propensity, up-regulating neutrophil response and in turn contributing to persistence of pseudomonas aeruginosa infection2. In laboratory experiments using human bronchial epithelial cells, and also a CF mouse model, all of these changes were reversed by adding lipoxins. Another class of anti-inflammatory lipid mediators, ‘resolvins’, share many of the biological activities of lipoxins. These resolvins are generated from omega 3 fatty acids, and their levels are determined by substrate availability3. Patients with CF, and cystic fibrosis transport regulator (CFTR) -/- mice show deficiencies in omega 3 fatty acids in tissues expressing CFTR4. Thus, supplementing omega 3 fatty acids may increase resolvins and thence reduce inflammation and pseudomonas aeruginosa bacterial load. These reports add a strong basis to the practical application of using omega 3 fatty acids to reduce chronic airway inflammation in CF, and hopefully will encourage a controlled trial of this relatively cheap, neglected and harmless intervention.

O4-03-05 Dietary omega-3 docosahexaenoic acid DHA regulates CNS insulin signaling and related kinase pathways involved in actin assembly, synaptic plasticity and memory in an Alzheimer (AD) model

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the primary omega-3 fatty acids in fish oil, have been shown to reduce cardiovascular disease (CVD) risk.This study aimed to examine the independent effects of EPA and DHA on lipid and apolipoprotein levels, as well as on inflammatory biomarkers of CVD risk, using doses often used in the general population.A blinded, randomized 6-week trial was performed in 121 healthy, normolipidemic subjects who received olive oil placebo 6 g/d, EPA 600 mg/d, EPA 1800 mg/d, or DHA 600 mg/d. The EPA was derived from genetically modified yeast.The subjects tolerated the supplements well with no safety issues; and the expected treatment-specific increases in plasma EPA and DHA levels were observed. Compared to placebo, the DHA group had significant decreases in postprandial triglyceride (TG) concentrations (− 20%, − 52.2 mg/dL, P = 0.03), significant increases in fasting and postprandial low-density lipoprotein cholesterol (LDL-C) (+ 18.4%, 17.1 mg/dL, P = 0.001), with no significant changes in inflammatory biomarkers. No significant effects were observed in the EPA 600 mg/d group. The high-dose EPA group had significant decreases in lipoprotein-associated phospholipase A2 concentrations (Lp-PLA2) (− 14.1%, − 21.4 ng/mL, P = 0.003).The beneficial effects of EPA 1800 mg/d on CVD risk reduction may relate in part to the lowering of Lp-PLA2 without adversely affecting LDL-C. In contrast, DHA decreased postprandial TG, but raised LDL-C. Our observations indicate that these dietary fatty acids have divergent effects on cardiovascular risk markers.

Role of fatty acids in adipocyte growth and development.

Fat is typically added to diets as a source of energy. The alternative aspects considered here are the use of specific fats to alter the fatty acid profile of adipose tissue toward creation of value-added products and the potential for individual fatty acids to alter gene expression and control adipose tissue development. Emphasis is placed on the omega-3 fatty acids, such as those found in fish oil, and on CLA. The most common association of fatty acids with adipose tissue is related to their storage as triglycerides in mature adipocytes and the consequences of excess accumulation in obesity. Fatty acids and their derivatives also can have hormone-like effects and have been be shown to regulate gene expression in preadipocytes, which ultimately effects their proliferation and differentiation. Long-chain, saturated, and polyunsaturated fatty acids have been shown to regulate transcription factors, such as CCAAT/enhancer binding protein, peroxisome proliferator activated receptor, and other adipose-specific genes, very early in adipocyte development. These effects have the potential to affect fat cell number at maturity. Specifically, there is evidence that the fatty acids in fish oil, such as docosahexaenoic and eicosopentaenoic acids, and fatty acids in the CLA series, decrease preadipocyte proliferation in cell lines and reduce adiposity in rodents. There is little direct evidence of the ability of fatty acids to manipulate adipocyte development in non-rodent species. The genetic, nutritional, and pharmacological manipulation of adipose tissue in meat animals has long been of interest to animal scientists. An understanding of the ability of fatty acids to regulate factors such as adipocyte size and number, particularly in meat animals, would be of great interest. The evidence for regulatory roles of fatty acids in development from rodent and in vitro studies and their potential application to meat animals are reviewed.

Eicosapentaenoic Acid Prevents LPS-Induced TNF-α Expression by Preventing NF-κB Activation

Background: Many studies have shown that fish oil supplementation inhibits tumor necrosis factor-α (TNF-α) production in mice and human subjects; however, the mechanisms remain unclear. Nuclear factor-κB (NF-κB) is a transcription factor that plays an important role in controlling the expression of pro-inflammatory genes including TNF-α. Activation of NF-κB has been shown to mediate the maximal expression of TNF-α in human monocytes. NF-κB is kept in an inactive form in the cytoplasm by IκB, the inhibitory subunit of NF-κB complex. Phosphorylation and subsequent degradation of IκB lead to NF-κB activation.Objectives: The effect of eicosapentaenoic acid (EPA), a major n-3 fatty acid in fish oil, on the lipopolysaccharide (LPS)-induced expression of TNF-α and activation of NF-κB were investigated. The mechanism underlying EPA modulation of NF-κB activation was also studied.Methods: Human monocytic THP-1 cells were pre-incubated with EPA and stimulated with LPS. The levels of secreted TNF-α were determined by ELISA. The DNA binding activity of NF-κB was analyzed by EMSA. The degradation and phosphorylation of IκB-α were examined by Western blot analysis.Results: TNF-α production and expression induced by LPS were significantly decreased in cells pre-incubated with EPA. LPS-induced NF-κB activation, translocation of p65 subunit to the nucleus, phosphorylation and degradation of IκB-α were partially prevented by EPA.Conclusions: The results suggest that suppression of the TNF-α expression by EPA is partly attributed to its inhibitory effect on NF-κB activation. EPA appears to prevent NF-κB activation by preventing the phosphorylation of IκB-α.

Electrophysiologic properties of lidocaine, cocaine, and n-3 fatty-acids block of cardiac Na + channels

Lidocaine and cocaine, two local anesthetics, and n-3 polyunsaturated fatty acids in fish oils, inhibit the voltage-gated Na + channels of cardiomyocytes. This inhibition by lidocaine and n-3 fish oil is associated with antiarrhythmic effects, whereas with cocaine lethal arrhythmias may occur. These electrophysiologic studies show that at the concentrations tested, the n-3 fish oil fatty acids and lidocaine share three actions on I Na: a potent inhibition of I Na; a strong voltage-dependence of this inhibition; and a large shift of the steady-state inactivation to hyperpolarized potentials. By contrast cocaine shares only the potent inhibition of I Na. The voltage-dependence of the inhibition is much decreased with cocaine, which produces only a very small leftward shift of the voltage-dependence of inactivation. The large leftward shift of the steady-state inactivation seems very important in the prevention of fatal arrhythmias by the n-3 fatty acids. Thus, we suggest that it is lack of this effect by cocaine, which is one factor, that eliminates its ability to prevent fatal cardiac arrhythmias. Further we report that in cultured neonatal rat cardiomyocytes n-3 fish oil fatty acids terminate the tachycardia induced by the α 1 adrenergic agonist, phenylephrine, whereas cocaine accelerates the tachycardia and causes bouts of tachyarythmias.

Characterization and determination of fatty acids in fish oil using gas chromatography–mass spectrometry coupled with chemometric resolution techniques

Characterization and determination of a complex mixture of fatty acid methyl esters was performed for commercial fish oil using two-dimensional GC–MS data coupled with resolution techniques. Various principle component analysis methods such as significant factor analysis and fixed size moving window evolving factor analysis were used for the number of factors, zero concentration and selective regions. Then, the convoluted chromatograms were resolved into pure chromatograms and mass spectra using heuristic evolving latent projections (HELP) method. Fatty acids of C 16:1ω7, C 18:4ω3, C 18:1ω11, C 18:1ω9, C 18:0, C 20:2ω6, C 20:1ω9, C 22:1ω11, C 22:1ω9 and C 24:1ω9 were resolved and identified by using similarity searches between deconvoluted mass spectra and MS database, in different parts of total ion current chromatogram. Window target testing factor analysis is also applied for confirming the presence or absence of target analytes. The results of the present work show that combination of hyphenated chromatographic methods and resolution techniques provide a complementary method for accurate analysis of real multi-component systems such as fish oil.

Effects of flaxseed oil on serum lipids and atherosclerosis in hypercholesterolemic rabbits.

Flaxseed oil has very high content of alpha-linolenic acid (C18:3n-3, omega-3 [n-3] fatty acid). Based on the usefulness of n-3 fatty acid in fish oil against cardiovascular diseases, flaxseed oil is marketed as a health food. The n-3 fatty acid in flaxseed oil is different than that of fish oil. Indirect evidence suggests that the omega-3 fatty acid in flaxseed oil is not effective in lowering serum lipids and hypercholesterolemic atherosclerosis. The effects of flaxseed oil on serum lipids and hypercholesterolemic atherosclerosis are not known. An investigation, therefore, was made of flaxseed oil on high-cholesterol diet-induced atherosclerosis, serum lipids (triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, risk ratio of total cholesterol to high-density lipoprotein cholesterol), serum and aortic malondialdehyde, an index of levels of reactive oxygen species, aortic chemiluminescence (a measure of antioxidant reserve), and reactive oxygen species-producing activity of white blood cell chemiluminescence in rabbits. The rabbits were assigned to four groups: Group I, regular diet (control); Group II, 5% flaxseed oil in regular diet; Group III, 0.5% cholesterol diet; Group IV, diet containing 0.5% cholesterol and 5% flaxseed oil. Blood samples were collected before and after 4 and 8 weeks of experimental diets for measurement of serum lipids, serum malondialdehyde, and white blood cell chemiluminescence. At the end of 8 weeks of the experimental diet, aortas were removed for measurement of atherosclerotic plaques, aortic malondialdehyde, and antioxidant reserve. Serum total cholesterol, triglycerides, and low-density and high-density lipoprotein cholesterol, and risk ratio of total cholesterol to high-density lipoprotein cholesterol, were elevated to a similar extent in Groups III and IV compared to Groups I and II. The extent of atherosclerosis in Groups III and IV was similar (56.74% +/- 11.14% vs 58.01% +/- 10.95%). Groups III and IV both had similar increases in serum and aortic malondialdehyde and antioxidant reserve. Reactive oxygen species-producing activity of white blood cells increased in Group III, and flaxseed oil prevented the cholesterol-induced increase in white blood cell chemiluminescence in Group IV. These results suggest that flaxseed oil does not produce an alteration in serum lipids or in the extent of hypercholesterolemic atherosclerosis; however, it decreases white blood cell chemiluminescence. The ineffectiveness of flaxseed oil was associated with its ineffectiveness in altering the levels of oxidative stress.

Diet and Lung Cancer Risk From a 14-Year Population-Based Prospective Study in Japan: With Special Reference to Fish Consumption

N-3 polyunsaturated fatty acids in fish oil exhibit a variety of health benefits, and there is evidence that they can inhibit the development of human lung mucoepidermoid and other carcinomas. To examine the hypothesis that fish consumption reduces the risk of lung cancer, we conducted a population-based prospective study, following 5,885 residents for 14 yr. Person-years were used to calculate the relative risk (RR) by the Cox proportional hazards model, with adjustment for potential confounding factors. A total of 51 incident lung cancer cases were observed, and we found linearly decreasing RRs for lung cancer with increased frequency of consumption of fish and shellfish (RRs = 1.00, 0.99, and 0.32, P for trend = 0.003) but not with intake of dried/salted fish. Decreased RRs were apparent with both broiling and boiling cooking methods, but reduction with raw and deep-fried fish consumption was not statistically significant. We conclude that frequent fresh fish consumption, irrespective of the cooking method, may reduce the risk of lung cancer.

Cytochrome p-450 epoxygenase metabolites of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels.

Diets enriched in docosahexaenoic acid, a major n-3 fatty acid in fish oil, have hypotensive properties. One mechanism that can lower blood pressure is the direct dilation of arterioles by docosahexaenoic metabolites. Vascular endothelium contains cytochrome P-450 epoxygenases that transform the n-6 fatty acid arachidonate into epoxyeicosatrienoic acids (EETs), potent dilators of coronary arterioles and activators of large-conductance calcium-activated potassium (BK(Ca)) channels. To test whether analogous activations occur for docosahexaenoate, we compared the potency of docosahexaenoate and its five cytochrome P-450 epoxygenase metabolites, epoxydocosapentaenoates (EDPs), in dilating porcine coronary arterioles (<135 microm in diameter) precontracted with endothelin. The five EDP regioisomers had dilation EC(50) values ranging from 0.5 to 24 pM (n = 5-6). In contrast, the EDP hydrolysis product 13,14-dihydroxydocosapentaenoic acid (13,14-DHDP) had an EC(50) value of 30 +/- 22 nM (n = 7), whereas docosahexaenoate only dilated vessels at > or =1.0 microM (n = 7). Using patch-clamp techniques in the inside-out configuration, we determined that the 13,14-EDP regioisomer potently activated (EC(50) value of 6.6 +/- 0.6 pM; n = 5) BK(Ca) channels in myocytes from the porcine coronary arterioles. Moreover, 13,14-EDP potently activated BK(Ca) channels in myocytes from rat coronary small arteries (150-300 microm in diameter); with an EC(50) value of 2.2 +/- 0.6 pM (n = 7), 13,14-EDP was 1000-fold more potent than EETs in activating BK(Ca) channels. We conclude that EDPs potently dilate coronary microvessels and are the most potent fatty epoxides known to activate BK(Ca) channels in coronary smooth muscle cells. Both actions may contribute to the hypotensive effects of dietary fish oils.

Determination of Docosahexaenoic Acid and n-3 Fatty Acids in Refined Fish Oils by H-NMR Spectroscopy: IUPAC Interlaboratory Study

A high-resolution proton nuclear magnetic resonance (NMR) method for determining the concentration (mg/g) of docosahexaenoic acid (DHA), the molar proportion (mol%) of DHA, and the molar proportion of total n-3 fatty acids in fish oils was validated by an IUPAC interlaboratory study (the Commission VI-6 on Oils, Fats, and Derivatives WG 3/98). Thirteen laboratories from 5 countries tested 6 pairs of blind duplicate fish oils: a refined tuna oil, 2 extracted tuna oils, an extracted bonito oil, an extracted salmon oil, and an extracted sardine oil ranging from 9 to 30 mol% DHA and from 20 to 35 mol% n-3 fatty acids. Before 1 D-proton NMR measurements with 300-500 MHz instruments, oil samples were weighed and diluted with deuterochloroform solution containing ethylene glycol dimethyl ether as internal standard. To achieve precise performance, a detailed procedure for signal area measurement was described in the protocol, and all participants were instructed about the critical importance of following the protocol. Statistical performances with invalid and outlier data removed were as follows: repeatability relative standard deviations (RSDr) ranged from 0.91 to 2.62% and reproducibility relative standard deviation (RSDR) ranged from 1.73 to 4.27% for DHA concentration (mg/g); RSDr ranged from 0.39 to 2.06%, and RSDR ranged from 0.59 to 3.46% for mol% DHA; RSDr ranged from 0.23 to 0.90% and RSDR ranged from 0.85 to 2.01 % for mol% total n-3 fatty acids. The method is expected to be recommended by IUPAC.

Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPARα

Omega-3 fatty acids, which are abundant in fish oil, improve the prognosis of several chronic inflammatory diseases although the mechanism for such effects remains unclear. These fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. We show that oxidized, but not native unoxidized, EPA significantly inhibited human neutrophil and monocyte adhesion to endothelial cells in vitro by inhibiting endothelial adhesion receptor expression. In transcriptional coactivation assays, oxidized EPA potently activated the peroxisome proliferator-activated receptor alpha (PPAR alpha), a member of the nuclear receptor family. In vivo, oxidized, but not native, EPA markedly reduced leukocyte rolling and adhesion to venular endothelium of lipopolysaccharide (LPS)-treated mice. This occurred via a PPAR alpha-dependent mechanism because oxidized EPA had no such effect in LPS-treated PPAR alpha-deficient mice. Therefore, the beneficial effects of omega-3 fatty acids may be explained by a PPAR alpha-mediated anti-inflammatory effect of oxidized EPA.

Inflammatory bowel disease in children and adolescents: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Inflammatory bowel disease in children and adolescents: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.