Showing papers on "Fish oil published in 2003"

Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease

Abstract: Since the first AHA Science Advisory “Fish Consumption, Fish Oil, Lipids, and Coronary Heart Disease,”1 important new findings, including evidence from randomized controlled trials (RCTs), have been reported about the beneficial effects of omega-3 (or n-3) fatty acids on cardiovascular disease (CVD) in patients with preexisting CVD as well as in healthy individuals.2 New information about how omega-3 fatty acids affect cardiac function (including antiarrhythmic effects), hemodynamics (cardiac mechanics), and arterial endothelial function have helped clarify potential mechanisms of action. The present Statement will address distinctions between plant-derived (α-linolenic acid, C18:3n-3) and marine-derived (eicosapentaenoic acid, C20:5n-3 [EPA] and docosahexaenoic acid, C22:6n-3 [DHA]) omega-3 fatty acids. (Unless otherwise noted, the term omega-3 fatty acids will refer to the latter.) Evidence from epidemiological studies and RCTs will be reviewed, and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid (plant- and marine-derived) supplementation. This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration (FDA) about the presence of environmental contaminants in certain species of fish. ### Coronary Heart Disease As reviewed by Stone,1 three prospective epidemiological studies within populations reported that men who ate at least some fish weekly had a lower coronary heart disease (CHD) mortality rate than that of men who ate none.3–6⇓⇓⇓ More recent evidence that fish consumption favorably affects CHD mortality, especially nonsudden death from myocardial infarction (MI), has been reported in a 30-year follow-up of the Chicago Western Electric Study.7 Men who consumed 35 g or more of fish daily compared with those who consumed none had a relative risk of death from CHD of 0.62 and a relative risk of nonsudden death from MI of 0.33. In an …

Clinical Prevention of Sudden Cardiac Death by n-3 Polyunsaturated Fatty Acids and Mechanism of Prevention of Arrhythmias by n-3 Fish Oils

Abstract: This review will be limited specifically to the beneficial prevention by the n-3 polyunsaturated fatty acids (PUFAs) of arrhythmic deaths, including sudden cardiac death, which annually causes some 300 000 deaths in the United States and millions more worldwide. We will also show that the growing body of positive clinical studies is supported by what has been learned in animal and laboratory studies regarding the mechanism by which n-3 PUFAs prevent cardiac arrhythmias. See p 2632 Figure 1 shows the 2 essential classes of PUFAs, the n-6 (ω6) and n-3 (ω3) classes. Both classes are “essential” because we cannot make them in our bodies. They must come in our diets, and they are essential for normal growth, development, and optimal function of brain, heart, and probably other systems. The parent fatty acid of the n-6 class, linoleic acid (C18:2n-6; LA) has 18 carbon atoms in its acyl chain, and the first C=C double bond is 6 carbons back from the methyl end of the fatty acid, hence the “n-6” appellation. In the bodies of animals, including humans, LA can be elongated and desaturated through a series of enzymatic steps to form arachidonic acid (C20:4n-6; AA). AA is the source of the n-6 eicosanoids that result from oxygenation of AA by cyclooxygenase, lipoxygenase, and epoxygenase enzymes to form prostaglandins, leukotrienes, lipoxines, and P-450 compounds, which in many instances are potent cell messengers. Figure 1. Two classes of essential PUFAs. In the chloroplast of green plants, algae, and phytoplankton, LA can be further desaturated in the n-3 position to yield α-linolenic acid (C18:3 n-3; ALA), the 18-carbon parent fatty acid of the n-3 class. ALA can be further elongated and desaturated by the same enzymes that convert n-6 LA to AA to form the 20-carbon n-3 analog of AA, namely, eicosapentaenoic acid …

Omega-3 Fatty Acids and Cardiovascular Disease New Recommendations From the American Heart Association

Abstract: Since the original American Heart Association (AHA) Science Advisory was published in 1996,1 important new findings have been reported about the benefits of omega-3 fatty acids on cardiovascular disease (CVD). Omega-3 fatty acids are obtained from two dietary sources: seafood and certain nut and plant oils. Fish and fish oils contain the 20-carbon eicosapentaenoic acid (EPA) and the 22-carbon docosahexaenoic acid (DHA), whereas canola, walnut, soybean, and flaxseed oils contain the 18-carbon α-linolenic acid (ALA). ALA appears to be less potent than EPA and DHA. The evidence supporting the clinical benefits of omega-3 fatty acids derive from population studies and randomized, controlled trials, and new information has emerged regarding the mechanisms of action of these nutrients. These are outlined in a recent Scientific Statement, “Fish Consumption, Fish Oil, Omega-3 Fatty Acids and Cardiovascular Disease.”2 See page e20 Large-scale epidemiologic studies suggest that people at risk for coronary heart disease (CHD) benefit from consuming omega-3 fatty acids from plants and marine sources. Although the ideal amount to take is not firmly established, evidence from prospective secondary prevention studies suggests that intakes of EPA+DHA ranging from 0.5 …

Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: A randomized, controlled trial

Abstract: Background There is growing interest in the potential role of anti-inflammatory n-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of allergic disease. Objective We sought to determine whether maternal dietary supplementation with n-3 PUFAs during pregnancy could modify immune responses in infants. Methods In a randomized, controlled trial 98 atopic, pregnant women received fish oil (3.7 g n-3 PUFAs per day) or placebo from 20 weeks' gestation until delivery. Neonatal PUFA levels and immunologic response to allergens were measured at birth. Results Eighty-three women completed the study. Fish oil supplementation (n = 40) achieved significantly higher proportions of n-3 PUFAs in neonatal erythrocyte membranes (mean ± SD, 17.75% ± 1.85% as a percentage of total fatty acids) compared with the control group (n = 43, 13.69% ± 1.22%, P P = .055). Although there was no difference in the frequency of atopic dermatitis at 1 year of age, infants in the fish oil group also had significantly less severe disease (odds ratio, 0.09; 95% confidence interval, 0.01 to 0.94; P = .045). Conclusions These data suggest a potential reduction in subsequent infant allergy after maternal PUFA supplementation. More detailed follow-up studies are required in larger cohorts to establish the robustness of these findings and to ascertain their significance in relation to longer-term modification of allergic disease in children.

N-3 polyunsaturated fatty acids and inflammation: from molecular biology to the clinic.

Abstract: The immune system is involved in host defense against infectious agents, tumor cells, and environmental insults. Inflammation is an important component of the early immunologic response. Inappropriate or dysfunctional immune responses underlie acute and chronic inflammatory diseases. The n-6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds that have important roles in inflammation and in the regulation of immunity. Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA-derived mediators, through several mechanisms, including decreased availability of AA, competition for cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, and decreased expression of COX-2 and 5-LOX. This alone is a potentially beneficial anti-inflammatory effect of n-3 FA. However, n-3 FA have a number of other effects that might occur downstream of altered eicosanoid production or might be independent of this effect. For example, dietary fish oil results in suppressed production of proinflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease and to protect against the effects of endotoxin. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some asthmatics, supporting the idea that the n-3 FA in fish oil are anti-inflammatory. There are indications that the inclusion of fish oil in enteral and parenteral formulae is beneficial to patients.

Dietary lipid sources for seabream and seabass: growth performance, tissue composition and flesh quality

Abstract: Due to its traditionally good availability, digestibility and high content of n − 3 HUFA, fish oil is the main lipid source in fish feeds. However, world demand for this product has grown significantly in recent years, whereas its production, based on fisheries landings, is static. The purpose of the present study was to assess the effect of partial replacement of fish oil in compound diets for gilthead seabream and seabass, by several vegetable oil sources, on growth, dietary fatty acid utilization and flesh quality. Five iso-energetic and isoproteic experimental diets were formulated (25% lipid content). Fish oil was the only added lipid source in the control (FO) diet, and it was included in the other experimental diets at a level high enough (40% of FO diet) to keep the n − 3 HUFA levels well over 3% in order to cover the essential fatty acid requirements of these species. Fish oil was replaced by soyabean oil (SO), rapeseed oil (RO) and linseed oil (LO) or a mixture (Mix) of them. Feed intake in all dietary groups was in the range of results obtained for commercial diets in both species, and growth and feed utilization were very good. The results show that, providing a minimum content of essential fatty acids in the diet, it is possible to replace up to 60% of the fish oil by SO, LO and RO or a mixture of them in diets for seabream and seabass, without compromising fish growth. Fatty acid composition of liver and muscle reflected that of the diet, but utilization of dietary lipids differed between these two tissues and was also different for the different fatty acids. Despite reduction in dietary saturated fatty acids by the inclusion of vegetable oils, their levels in fish liver were as high as in fish fed the fish oil diet, whereas, in muscle, levels were reduced according to that in the diet. Linoleic and linolenic acids were accumulated in the liver proportionally to their levels in the diet, suggesting a lower oxidation of these fatty acids in comparison to other 18C fatty acids. Regarding eicosapentaenoic acid (20 : 5n − 3; EPA), docosahexaenoic acid (22 : 6n − 3; DHA) and arachidonic acid (20 : 4n − 6; ARA), these essential fatty acids were reduced in the liver at a similar rate, whereas DHA was preferentially retained in the muscle in comparison with the other fatty acids, denoting a higher oxidation particularly of EPA, in the muscle. Some other PUFA increased despite their low dietary levels in seabream fed LO diets and in seabass fed SO diet, suggesting the stimulation of delta-6 and delta-5 desaturase activity in marine fish. Despite differences in fatty acid composition, fillet of fish fed vegetable oils was very well accepted by trained judges when assessed cooked.

Effect of dietary fish oil on biohydrogenation of fatty acids and milk fatty acid content in cows

Abstract: Mechanisms underlying milk fat conjugated linoleic acid (CLA) responses to supplements of fish oil were investigated using five lactating cows each fitted with a rumen cannula in a simple experiment consisting of two consecutive 14-day experimental periods. During the first period cows were offered 18 kg dry matter (DM) per day of a basal (B) diet formulated from grass silage and a cereal based-concentrate (0·6 : 0·4; forage : concentrate ratio, on a DM basis) followed by the same diet supplemented with 250 g fish oil per day (FO) in the second period. The flow of non-esterified fatty acids leaving the rumen was measured using the omasal sampling technique in combination with a triple indigestible marker method based on Li-Co-EDTA, Yb-acetate and Cr-mordanted straw. Fish oil decreased DM intake and milk yield, but had no effect on milk constituent content. Milk fat trans-11 C18:1, total trans-C18 : 1, cis-9 trans-11 CLA, total CLA, C18 : 2 (n-6) and total C18 : 2 content were increased in response to fish oil from 1·80, 4·51, 0·39, 0·56, 0·90 and 1·41 to 9·39, 14·39, 1·66, 1·85, 1·25 and 4·00 g/100 g total fatty acids, respectively. Increases in the cis-9, trans-11 isomer accounted for proportionately 0·89 of the CLA response to fish oil. Furthermore, fish oil decreased the flow of C18 : 0 (283 and 47 g/day for B and FO, respectively) and increased that of trans-C18 : 1 fatty acids entering the omasal canal (38 and 182 g/day). Omasal flows of trans-C18 : 1 acids with double bonds in positions from delta-4 to -15 inclusive were enhanced, but the effects were isomer dependent and primarily associated with an increase in trans-11 C18 : 1 leaving the rumen (17·1 and 121·1 g/day for B and FO, respectively). Fish oil had no effect on total (4·36 and 3·50 g/day) or cis-9, trans-11 CLA (2·86 and 2·08 g/day) entering the omasal canal. Flows of cis-9, trans-11 CLA were lower than the secretion of this isomer in milk. Comparison with the transfer of the trans-9, trans-11 isomer synthesized in the rumen suggested that proportionately 0·66 and 0·97 of cis-9, trans-11 CLA was derived from endogenous conversion of trans-11 C18 : 1 in the mammary gland for B and FO, respectively. It is concluded that fish oil enhances milk fat cis-9, trans-11 CLA content in response to increased supply of trans-11 C18:1 that arises from an inhibition of trans-C18 : 1 reduction in the rumen.

Altered Fatty Acid Compositions in Atlantic Salmon (Salmo salar) Fed Diets Containing Linseed and Rapeseed Oils Can Be Partially Restored by a Subsequent Fish Oil Finishing Diet

Abstract: Atlantic salmon postsmolts were fed a control diet or one of 9 experimental diets containing various blends of two vegetable oils, linseed (LO) and rapeseed oil (RO), and fish oil (FO) in a triangular trial design, for 50 wk. After sampling, fish previously fed 100% FO, LO and RO were switched to a diet containing 100% FO for a further 20 wk. Fatty acid compositions of flesh total lipid were linearly correlated with dietary fatty acid compositions (r = 0.99-1.00, P < 0.0001). Inclusion of vegetable oil at 33% of total oil significantly reduced the concentrations of the highly unsaturated fatty acids, eicosapentaenoate [20:5(n-3)] and docosahexaenoate [22:6(n-3)], to approximately 70 and 75%, respectively, of the values in fish fed 100% FO. When vegetable oil was included at 100% of total dietary lipid, the concentrations of 20:5(n-3) and 22:6(n-3) were significantly reduced to approximately 30 and 36%, respectively, of the values in fish fed FO. Transfer of fish previously fed 100% vegetable oil to a 100% FO diet for 20 wk restored the concentrations of 20:5(n-3) and 22:6(n-3) to approximately 80% of the value in fish fed 100% FO for 70 wk, although the values were still significantly lower. However, in fish previously fed either 100% LO or RO, concentrations of 18:2(n-6) remained approximately 50% higher than in fish fed 100% FO. This study suggests that RO and LO can be used successfully to culture salmon through the seawater phase of their growth cycle; this will result in reductions in flesh 20:5(n-3) and 22:6(n-3) concentrations that can be partially restored by feeding a diet containing only marine FO for a period before harvest.

Fatty acids, the immune response, and autoimmunity: A question of n−6 essentiality and the balance between n−6 and n−3

Abstract: The essentiality of n−6 polyunsaturated fatty acids (PUFA) is described in relation to a thymus/thymocyte accretion of arachidonic acid (20∶4n−6, AA) in early development, and the high requirement of lymphoid and other cells of the immune system for AA and linoleic acid (18∶2n−6, LA) for membrane phospholipids. Low n−6 PUFA intakes enhance whereas high intakes decrease certain immune functions. Evidence from in vitro and in vivo studies for a role of AA metabolites in immune cell development and functions shows that they can limit or regulate cellular immune reactions and can induce deviation toward a T helper (Th)2-like immune response. In contrast to the effects of the oxidative metabolites of AA, the longer-chain n−6 PUFA produced by γ-linolenic acid (18∶3n−6, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n−6 PUFA, GLA, dihomo-γ-linolenic acid (20∶3n−6, DHLA) and AA, and certain oxidative metabolites of AA can also induce T-regulatory cell activity, e.g., transforming growth factor (IGF)-β-producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-α production. Low intakes of long-chain n−3 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and th2 responses, proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. Vitamin E has a demonstrable critical role in long-chain n−3 PUFA interactions with immune functions, often reversing the effects of fish oil. The effect of dietary fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long-chain n−3 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, whereas high-fat LA-rich diets increase disease severity. In experimentally induced T cell-mediated autoimmune disease, EFAD diets or diets supplemented with long-chain n−3 PUFA augment disease, whereas n−6 PUFA prevent or reduce the severity. In contrast, in both T cell- and antibody-mediated autoimmune disease, the desaturated/elongated metabolites of LA are protective. PUFA of both the n−6 and n−3 families are clinically useful in human autoimmune-inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Finally, the view that all n−6 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.

Dietary n‐3 Fatty Acids Decrease Osteoclastogenesis and Loss of Bone Mass in Ovariectomized Mice

Abstract: UNLABELLED The mechanisms of action of dietary fish oil (FO) on osteoporosis are not fully understood This study showed FO decreased bone loss in ovariectomized mice because of inhibition of osteoclastogenesis This finding supports a beneficial effect of FO on the attenuation of osteoporosis INTRODUCTION Consumption of fish or n-3 fatty acids protects against cardiovascular and autoimmune disorders Beneficial effects on bone mineral density have also been reported in rats and humans, but the precise mechanisms involved have not been described METHODS Sham and ovariectomized (OVX) mice were fed diets containing either 5% corn oil (CO) or 5% fish oil (FO) Bone mineral density was analyzed by DXA The serum lipid profile was analyzed by gas chromatography Receptor activator of NF-kappaB ligand (RANKL) expression and cytokine production in activated T-cells were analyzed by flow cytometry and ELISA, respectively Osteoclasts were generated by culturing bone marrow (BM) cells with 1,25(OH)2D3 NF-kappaB activation in BM macrophages was measured by an electrophoretic mobility shift assay RESULTS AND CONCLUSION Plasma lipid C16:1n6, C20:5n3, and C22:6n3 were significantly increased and C20:4n6 and C18:2n6 decreased in FO-fed mice Significantly increased bone mineral density loss (20% in distal left femur and 226% in lumbar vertebrae) was observed in OVX mice fed CO, whereas FO-fed mice showed only 10% and no change, respectively Bone mineral density loss was correlated with increased RANKL expression in activated CD4+ T-cells from CO-fed OVX mice, but there was no change in FO-fed mice Selected n-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) added in vitro caused a significant decrease in TRACP activity and TRACP+ multinuclear cell formation from BM cells compared with selected n-6 fatty acids (linoleic acid [LA] and arachidonic acid [AA]) DHA and EPA also inhibited BM macrophage NF-kappaB activation induced by RANKL in vitro TNF-alpha, interleukin (IL)-2, and interferon (IFN)-gamma concentrations from both sham and OVX FO-fed mice were decreased in the culture medium of splenocytes, and interleukin-6 was decreased in sham-operated FO-fed mice In conclusion, inhibition of osteoclast generation and activation may be one of the mechanisms by which dietary n-3 fatty acids reduce bone loss in OVX mice

Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis.

Abstract: Patients with rheumatoid arthritis (RA) improve on a vegetarian diet or supplementation with fish oil. We investigated the effects of both dietary measures, alone and in combination, on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in patients with RA. Methods. Sixty-eight patients with definitive RA were matched into two groups of 34 subjects each. One group was observed for 8 months on a normal western diet (WD) and the other on an anti-inflammatory diet (AID) providing an arachidonic acid intake of less than 90 mg/day. Patients in both groups were allocated to receive placebo or fish oil capsules (30 mg/kg body weight) for 3 months in a double-blind crossover study with a 2-month washout period between treatments. Clinical examination and routine laboratory findings were evaluated every month, and erythrocyte fatty acids, eicosanoids, and cytokines were evaluated before and after each 3-month experimental period. Results. Sixty patients completed the study. In AID patients, but not in WD patients, the numbers of tender and swollen joints decreased by 14% during placebo treatment. In AID patients, as compared to WD patients, fish oil led to a significant reduction in the numbers of tender (28% vs 11%) and swollen (34% vs 22%) joints (P 0.01), 11-dehydro-thromboxane B2 (15% vs 10%, P<0.05), and prostaglandin metabolites (21% vs 16%, P<0.003) were found in AID patients, especially when fish oil was given during months 6–8 of the experiment. Conclusion. A diet low in arachidonic acid ameliorates clinical signs of inflammation in patients with RA and augments the beneficial effect of fish oil supplementation.

Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation.

Abstract: Increased dietary consumption of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20 : 5n-3; EPA) and docosahexaenoic acid (22 : 6n-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function, n-3 PUFA intake and antioxidant co-supplementation is poorly defined. We therefore investigated tumour necrosis factor (TNF)-alpha and interleukin (IL) 6 production by PBMC and phospholipid fatty acid composition in plasma and erythrocytes of healthy male subjects (n 16) receiving supplemental intakes of 0.3, 1.0 and 2.0 g EPA+DHA/d, as consecutive 4-week courses. All subjects were randomised in a double-blind manner to receive a concurrent antioxidant supplement (200 microg Se, 3 mg Mn, 30 mg D-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 microg vitamin A (beta-carotene and retinol)) or placebo. There was a positive dose-dependent relationship between dietary n-3 PUFA intake and EPA and DHA incorporation into plasma phosphatidylcholine and erythrocyte phosphatidylethanolamine, with a tendency towards a plateau at higher levels of intake. Production of TNF-alpha and IL-6 by PBMC decreased with increasing n-3 PUFA intake but tended towards a 'U-shaped' dose response. Both responses appeared to be augmented by antioxidant co-supplementation at intermediate supplementary n-3 PUFA intakes. Thus, increased dietary n-3 PUFA consumption resulted in defined but contrasting patterns of modulation of phospholipid fatty acid composition and PBMC function, which were further influenced by antioxidant intake.

Effect of Fish Oil on Appetite and Other Symptoms in Patients With Advanced Cancer and Anorexia/Cachexia: A Double-Blind, Placebo-Controlled Study

Abstract: Purpose: To determine whether high doses of fish oil, administered over 2 weeks, improve symptoms in patients with advanced cancer and decreased weight and appetite. Patients and Methods: Sixty patients were randomly assigned to fish oil capsules or placebo. Appetite, tiredness, nausea, well-being, caloric intake, nutritional status, and function were prospectively assessed at days 1 and 14. Results: The baseline weight loss was 16 ± 11 and 16 ± 8 kg in the fish oil (n = 30) and placebo (n = 30) group respectively, whereas the baseline appetite (0 mm = best and 10 mm = worst) was 58 ± 24 mm and 67 ± 19 mm, respectively (P = not significant). The mean daily dose was 10 ± 4 (fish oil group) and 9 ± 3 (placebo group) capsules, which provided 1.8 g of eicosapentaenoic acid and 1.2 g of docosahexaenoic acid in the fish oil group. No significant differences in symptomatic or nutritional parameters were found (P < .05), and there was no correlation between changes in different variables between days 1 and 14 and...

Parenteral nutrition with fish oil modulates cytokine response in patients with sepsis.

Abstract: Infusion of fish oil-based (n-3) lipids may influence leukocyte function and plasma lipids in critical care patients. Twenty-one patients with sepsis requiring parenteral nutrition were randomized to receive an n-3 lipid emulsion rich in eicosapentaenoic acid and docosahexaenoic acid or a conventional (n-6) lipid emulsion (index fatty acid: arachidonic acid) for 5 days. The impact on plasma-free fatty acids, mononuclear leukocyte cytokine generation, and membrane fatty acid composition was examined. Cytokine synthesis by isolated mononuclear leukocyte was elicited by endotoxin. Before the onset of lipid infusion therapy, plasma-free fatty acid concentrations were greatly increased in septic patients, with arachidonic acid by far surpassing eicosapentaenoic acid and docosahexaenoic acid, a feature maintained during conventional lipid infusion. Within 2 days of fish oil infusion, free n-3 fatty acids increased, and the n-3/n-6 ratio was reversed, with rapid incorporation of n-3 fatty acids into mononuclear leukocyte membranes. Generation of proinflammatory cytokines by mononuclear leukocytes was markedly amplified during n-6 and was suppressed during n-3 lipid application. After termination of lipid administration, free n-3 fatty acid concentrations and mononuclear leukocyte cytokine synthesis returned to preinfusion values. Use of lipid infusions might allow us to combine intravenous alimentation with differential impact on inflammatory events and immunologic functions in patients with sepsis.

Maternal fish oil supplementation in pregnancy reduces interleukin‐13 levels in cord blood of infants at high risk of atopy

Abstract: Summary Background and objectives The epidemiological association between higher dietary n-3 polyunsaturated fatty acids (PUFA) and lower prevalence of asthma, has led to interest in the role of early dietary modification in allergic disease prevention. In this study we examined the effects of maternal n-3 (PUFA)-rich fish oil supplementation on cord blood (CB) IgE and cytokine levels in neonates at risk of developing allergic disease. Methods In a randomized double-blind, placebo-controlled trial, 83 atopic pregnant women received either fish oil capsules (n = 40) containing 3.7 g n-3 PUFA/day or placebo capsules (n = 43) from 20 weeks gestation until delivery. CB cytokine levels (IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, TNF-α and IFN-γ) and total IgE levels were measured and compared between the two groups. Fatty acid composition of red cell membranes was analysed by gas chromatography and the relationships among PUFA, cytokine and IgE levels were examined. Results Maternal fish oil supplementation resulted in a significant increase in n-3 PUFA levels (P < 0.001) in neonatal erythrocyte membranes. Neonates whose mothers had fish oil supplementation had significantly lower plasma IL-13 (P < 0.05) compared to the control group. There was also a significant inverse relationship between levels of n-3 PUFA in neonatal cell membranes and plasma IL-13. There was no difference in levels of IgE and the other cytokines measured. Conclusions This study provides preliminary evidence that increasing neonatal n-3 PUFA levels with maternal dietary supplementation can achieve subtle modification of neonatal cytokine levels. Further assessment of immune function and clinical follow-up of these infants will help determine if there are any significant effects on postnatal immune development and expression of allergic disease.

Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects.

Abstract: Studies on animal and human subjects have shown that greatly increasing the amount of linseed (also known as flaxseed) oil (rich in the n-3 polyunsaturated fatty acid (PUFA) ?-linolenic acid (ALNA)) or fish oil (FO; rich in the long-chain n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) in the diet can decrease a number of markers of immune function. The immunological effects of more modest doses of n-3 PUFA in human subjects are unclear, dose–response relationships between n-3 PUFA supply and immune function have not been established and whether ALNA has the same effects as its long-chain derivatives is not known. Therefore, the objective of the present study was to determine the effect of enriching the diet with different doses of FO or with a modest dose of ALNA on a range of functional responses of human monocytes and lymphocytes. In a randomised, placebo-controlled, double-blind, parallel study, forty healthy males aged 18–39 years were randomised to receive placebo or 3·5 g ALNA/d or 0·44, 0·94 or 1·9 g (EPA+DHA)/d in capsules for 12 weeks. The EPA:DHA ratio in the FO used was 1·0:2·5. ALNA supplementation increased the proportion of EPA but not DHA in plasma phospholipids. FO supplementation decreased the proportions of linoleic acid and arachidonic acid and increased the proportions of EPA and DHA in plasma phospholipids. The interventions did not alter circulating mononuclear cell subsets or the production of tumour necrosis factor-?, interleukin (IL) 1?, IL-2, IL-4, IL-10 or interferon-? by stimulated mononuclear cells. There was little effect of the interventions on lymphocyte proliferation. The two higher doses of FO resulted in a significant decrease in IL-6 production by stimulated mononuclear cells. It is concluded that, with the exception of IL-6 production, a modest increase in intake of either ALNA or EPA+DHA does not influence the functional activity of mononuclear cells. The threshold of EPA+DHA intake that results in decreased IL-6 production is between 0·44 and 0·94 g/d.

Short-time infusion of fish oil-based lipid emulsions, approved for parenteral nutrition, reduces monocyte proinflammatory cytokine generation and adhesive interaction with endothelium in humans.

Abstract: Potential impact of ω-3 fatty acids, as contained in fish oil, on immunological function has been suggested because observations of reduced inflammatory diseases in Greenland Inuit were published. A fish oil-based lipid emulsion has recently been approved for parenteral nutrition in many countries. We investigated the influence of a short infusion course of fish oil-based (ω-3) vs conventional (ω-6) lipid emulsion on monocyte function. In a randomized design, twelve healthy volunteers received ω-3 or ω-6 lipid infusion for 48 h, with cross-over repetition of the infusion course after 3 mo. Fatty acid profiles, monocyte cytokine release and adhesive monocyte-endothelium interaction were investigated. Resultant ω-6 lipid emulsion increased plasma-free fatty acids including arachidonic acid, whereas the ω-3/ω-6 fatty acid ratio in monocyte membranes remained largely unchanged. It also caused a tendency toward enhanced monocyte proinflammatory cytokine release and adhesive monocyte-endothelium interaction. In contrast, ω-3 lipid emulsion significantly increased the ω-3/ω-6 fatty acid ratio in the plasma-free fatty acid fraction and in monocyte membrane lipid pool, markedly suppressing monocyte generation of TNF-α, IL-1, IL-6, and IL-8 in response to endotoxin. In addition, it also significantly inhibited both monocyte-endothelium adhesion and transendothelial monocyte migration, although monocyte surface expression of relevant adhesive molecules (CD11b, CD18, CD49 days, CCR2) was unchanged. Although isocaloric, ω-3 and ω-6 lipid emulsions exert differential impact on immunological processes in humans. In addition to its nutritional value, fish oil-based ω-3 lipid emulsion significantly suppresses monocyte proinflammatory cytokine generation and features of monocyte recruitment.