The effect of supplementation with fish oil during pregnancy on breast milk immunoglobulin A, soluble CD14, cytokine levels and fatty acid composition

BACKGROUND: Breast milk contains many immunomodulatory factors (soluble CD14 (sCD14), IgA and cytokines) with the potential to influence infant immune development. OBJECTIVE: To determine if changes in breast milk omega-3 polyunsaturated fatty acid (n-3 PUFA) composition as a result of maternal dietary fish oil supplementation during pregnancy can modify levels of these immunological parameters in breast milk. METHOD: In a randomized controlled trial, 83 atopic women received either 4 g fish oil capsules (containing 3.7 g n-3 PUFA) (n = 40) or 4 g olive oil capsules (n = 43) from 20 weeks gestation until delivery. Breast milk was collected 3 days post-partum and fatty acids were analysed by gas liquid chromatography and IgA, sCD14 and cytokines (IL-5, IL-6, IL-10, TNF-alpha and IFN-gamma) were quantitated by ELISA or time resolved fluorescence (TRF). RESULTS: Omega-3 docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) levels were significantly higher (P < 0.001) in breast milk from women supplemented with fish oil (n = 33, DHA mean 1.15%, SD 0.47% and EPA mean 0.16%, SD 0.07%) than in samples from the control group (n = 40, DHA mean 0.50%, SD 0.17% and EPA mean 0.05%, SD 0.02%). Breast milk arachidonic acid (AA; 20:4n-6) levels were significantly lower (P = 0.045) in the fish oil group (mean 0.55%, SD 0.12%) compared with the control group (mean 0.61%, SD 0.14%). Breast milk IgA was positively correlated with DHA (P = 0.046) and 22:5n-3 (P = 0.003), but inversely correlated with linoleic acid (LA; 18:2n-6) (P=0.034). Levels of sCD14 were also positively correlated with 22:5n-3 (P=0.009). Cytokines involved in IgA synthesis (IL-10 and IL-6) were also significantly correlated with both IgA and n-3 PUFA levels, although there were no differences in the levels of breast milk IgA, sCD14 or cytokines between study groups. CONCLUSION: Supplementation with fish oil during pregnancy significantly alters early post-partum breast milk fatty acid composition. omega-3 PUFA levels were positively associated with IgA and sCD14 levels, suggesting a relationship between fatty acid status and mucosal immune function.     

血小板、红细胞多不饱和脂肪酸的平衡及低密度脂蛋白的作用

低密度脂蛋白引起血小板、红细胞膜上二十碳四烯酸,二十碳五烯酸、二十二碳六烯酸成份改变,并与它们的功能改变相关。摄入富含二十碳五烯酸,二十二碳六烯酸的鱼油脂肪后,低密度脂蛋白的上述作用减弱。影响n-3型和n-6型多不饱和脂肪酸的平衡可能是低密度脂蛋白对血小板、红细胞的作用机理之一。     

A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer's transgenic mice

Although a number of epidemiologic studies reported that higher intake of omega-3 fatty acids (largely associated with fish consumption) is protective against Alzheimer's disease (AD), other human studies reported no such effect. Because retrospective human studies are problematic and controlled longitudinal studies over decades are impractical, the present study utilized Alzheimer's transgenic mice (Tg) in a highly controlled study to determine whether a diet high in omega-3 fatty acid, equivalent to the 13% omega-3 fatty acid diet of Greenland Eskimos, can improve cognitive performance or protect against cognitive impairment. Amyloid precursor protein (APP)-sw+PS1 double transgenic mice, as well as nontransgenic (NT) normal littermates, were given a high omega-3 supplemented diet or a standard diet from 2 through 9 months of age, with a comprehensive behavioral test battery administered during the final 6 weeks. For both Tg and NT mice, long-term n-3 supplementation resulted in cognitive performance that was no better than that of mice fed a standard diet. In NT mice, the high omega-3 diet increased cortical levels of omega-3 fatty acids while decreasing omega-6 levels. However, the high omega-3 diet had no effect on cortical fatty acid levels in Tg mice. Irrespective of diet, no correlations existed between brain omega-3 levels and cognitive performance for individual NT or Tg mice. In contrast, brain levels of omega-6 fatty acids were strongly correlated with cognitive impairment for both genotypes. Thus, elevated brain levels of omega-3 fatty acids were not relevant to cognitive function, whereas high brain levels of omega-6 were associated with impaired cognitive function. In Tg mice, the omega-3 supplemental diet did not induce significant changes in soluble/insoluble Abeta within the hippocampus, although strong correlations were evident between hippocampal Abeta(1-40) levels and cognitive impairment. While these studies involved a genetically manipulated mouse model of AD, our results suggest that diets high in omega-3 fatty acids, or use of fish oil supplements (DHA+EPA), will not protect against AD, at least in high-risk individuals. However, normal individuals conceivably could derive cognitive benefits from high omega-3 intake if it corrects an elevation in the brain level of n-6 fatty acids as a result. Alternatively, dietary fish may contain nutrients, other than DHA and EPA, that could provide some protection against AD.     

Dietary n-3 polyunsaturated fatty acids modulate purified murine T-cell subset activation

Studies in humans and murine disease models have clearly shown dietary fish oil to possess anti-inflammatory properties, apparently mediated by the n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To determine the mechanisms by which dietary EPA and DHA modulate mouse T-cell activation, female C57BL/6 mice were fed diets containing either 2% safflower oil (SAF), 2% fish oil (FO), or a 2% purified EPA/DHA ethyl ester mixture for 14 days. Splenic CD4 T cells ( approximately 90% purity) or CD8 T cells ( approximately 85% purity) were incubated with agonists which act at the plasma membrane receptor level [anti(alpha)-CD3/anti(alpha)-CD28], the intracellular level (PMA/Ionomycin), or at both the receptor and intracellular levels (alphaCD3/PMA). CD4 T cells stimulated with alphaCD3/alphaCD28 or PMA/Ionomycin proliferated and produced principally IL-2 (i.e. a Th1 phenotype), whereas the proliferation of CD4 T cells stimulated with alphaCD3/PMA was apparently driven principally by IL-4 (i.e. a Th2 phenotype). The IL-4 driven proliferation of putative Th2 CD4 cells was enhanced by dietary n-3 fatty acids (P = 0.02). Conversely, IL-2 production by alphaCD3/alpha CD28-stimulated CD4 T cells was reduced in FO-fed animals (P < 0.0001). The alphaCD3/alphaCD28-stimulated CD8 cells cultured from FO-fed animals exhibited a significant decrease (P < 0.05) in proliferation. There were no dietary effects seen in alphaCD3/PMA-stimulated CD8 cells, which produced both IL-2 and IL-4, or in PMA/Ionomycin-stimulated CD8 cells, which produced principally IL-2. These data suggest that dietary n-3 fatty acids down-regulated IL-2 driven CD4 and CD8 activation, while up-regulating the activation of the Th2 CD4 T-cell subset. Thus, the anti-inflammatory effects of n-3 fatty acids may result in both the direct suppression of IL-2-induced Th1 cell activation and the indirect suppression of Th1 cells by the enhanced cross-regulatory function of Th2 cells.     

Sex-specific effects of brain LC-PUFA composition on locomotor activity in rats

Insufficient availability of n-3 polyunsaturated fatty acids (PUFAs) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain and is associated with sub-optimal sensory and cognitive function in humans, altered behavior in animals, and may contribute to neurodevelopmental disorders such as attention deficit hyperactivity disorder and schizophrenia. This study examined the effects of variation in dietary availability of n-3 PUFAs on brain fatty acid composition and the consequent effects on locomotor activity in male and female Long-Evans rats. Rats were raised from conception using purified diets and breeding protocols designed to produce four groups with distinct brain phospholipid compositions varying in DHA content and/or the proportion of n-3 and n-6 PUFAs. Locomotor behavior was measured for a 2-h period on postnatal days 28, 42, 56, and 70. In males, decreased brain DHA produced alterations in activity that were most pronounced post-adolescence and with the greatest decrease in DHA. However, the behavioral effects in males were not linearly related to brain DHA level. In contrast, no significant effects of variation in brain fatty acid composition were observed in females. This suggests that variation in brain DHA content produces sex-specific alterations in locomotor activity and that the neurochemical alterations underlying the observed behavioral changes vary depending on the degree of DHA depletion.     

Distal Proctocolitis and n-3 Polyunsaturated Fatty Acids (n-3 PUFAs): The Mucosal Effect In Situ

It has been postulated that patients with ulcerative colitis (UC) have altered reactivity of gut-associated lymphoid tissue. In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage. We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) results in significant systemic immune suppression. The aim of this study, therefore, was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis. Each patient received either fish oil extract (EPA 3.2 g, DHA 2.4 g) (n = 9) or sunflower oil (n = 9) daily in a double blind manner for six months. Monthly assessment included: (1) disease activity using clinical, sigmoidoscopic, and histological scores and (2) immunohistochemical analysis (immunoglobulins, CD profiles) of rectal biopsy specimens (before and after six months supplementation) using monoclonal antibodies and quantitative computer-assisted video image analysis. Prior to receiving supplementation, patients with proctocolitis (n = 18) showed significantly higher numbers of cells expressing CD3 (pan T cells) and HLA-DR and IgM containing cells compared with non-colitic controls (n = 8). Six months supplementation with n-3 PUFAs resulted in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis. In patients receiving n-3 PUFA supplementation, there was improvement in the disease activity and histological scores, compared with pretreatment evaluation. This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation. This may have important implication for therapy in patients with ulcerative colitis.     

Fish lipids: more than n-3 fatty acids?

Recent studies have shown that marine oils rich in long-chain (C20 and C22) fatty acids (i.e. certain natural marine oils and partially hydrogenated fish oil) may affect the haemostatic balance in a favourable way with regard to coronary heart disease. Such fats have also been found to increase the content of EPA (eicosapentaenoic ACID = C20:5 n-3) and to decrease the content of arachidonic acid (C20:4 n-6) in blood lipids, thus affecting the ratio of C20:4 n-6 to C20:5 n-3 in a favourable way with regard to eicosanoid production. It is therefore likely that the positive effects of long-chain monoenoic fatty acids on haemostasis are due to increased synthesis of long-chain essential n-3 fatty acids. According to recent theories the final steps in the synthesis of long-chain essential fatty acids occur in the peroxisomes, which also have a controlling function in essential fatty acid synthesis. Long-chain monoenoic fatty acids are known to enhance peroxisomal beta-oxidation. An hypothesis is therefore advanced that marine oils rich in long-chain monoenoic fatty acids improve haemostasis in a favourable way with regard to coronary heart disease through increased peroxisomal beta-oxidation and increased synthesis of long-chain n-3 fatty acids.     

Stress and fatty liver--possible indications for dietary long-chain n-3 fatty acids.

The favourable effects of eicosapentaenoic acid (EPA)- and doco-sahexaenoic acid (DHA)-rich diets (marine fish, fish oil) on several risk factors for cardiovascular disease are well established. The present survey describes possible new indications for diets supplemented with long-chain n-3 fatty acids. During a standardized psychophysiological stress test (arithmetic, sentence completion tasks) systolic blood pressure after 2 weeks of diets supplemented with either 60 ml/day of sunflower or linseed oil was significantly decreased. During the sunflower oil-rich diet 45 g/day of linoleic acid (LA) and during the linseed oil-rich period 38 g/day of alpha-linolenic acid (LNA) were ingested. After a 2-week diet supplemented with mackerel (2 cans/day equivalent to 2.2 g/day of EPA and 2.8 g/day of DHA) systolic and diastolic blood pressure within the same test design appeared significantly lower. After a herring diet providing 2 cans/day, equivalent to 1.0 g of EPA and 1.8 g of DHA, the blood pressure-lowering effect was minor. The increase of thromboxane B2 (TxB2) during the stress test failed to occur after the fish diets. The results suggest a stress-protective effect of polyenoic acid-rich diets, which appears most pronounced and dose-related after long-chain n-3 fatty acids. In human liver an increase of fat droplet size in hepatocytes is associated with a decrease of the percentage of EPA in liver triglycerides. A diminution of plasma free fatty acids (FFA) after a mackerel diet might contribute to a depressed synthesis of liver triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of prostaglandin synthesis in mouse peritoneal macrophages by enrichment of lipids with either eicosapentaenoic or docosahexaenoic acids in vitro

The n-3 polyunsaturated fatty acids (PUFA) of fish oils alter arachidonic acid (AA) metabolism in macrophages. The present investigation studied the efficacy of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), two n-3 PUFA of fish, to alter lipid composition and specific functions of mouse peritoneal macrophages. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were readily incorporated by macrophages in vitro and replaced 25-50% of AA in cellular lipids. The EPA- or DHA-enriched cells synthesized significantly less (50-65%) prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6 keto prostaglandin F1(1) alpha (6 keto PGF1 alpha) when stimulated with opsonized zymosan. The enrichment with EPA or DHA did not affect phagocytosis nor superoxide anion formation in macrophages. These studies demonstrated that EPA or DHA can be used to decrease prostaglandin synthesis selectively without affecting the other physiological functions of macrophages.     

Docosahexaenoic and Eicosapentaenoic Acids Inhibit Human Lymphoproliferative Responses In Vitro but not the Expression of T Cell Surface Activation Markers

The effects of polyunsaturated fatty acids (PUFAs: docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids) on induced lymphocyte proliferation and expression of CD25α chain of interleukin-2 receptor, CD71 and HLA-DR were investigated. PUFAs had no effect on phytohaemagglutinin (PHA)-induced lymphocyte agglutination, but they strongly inhibited the lymphoproliferative response to PHA. This inhibitory effect is PUFA dose-dependent and seems to be more potent with DHA than EPA. Pre-incubation experiments showed that lymphocytes cultured with PUFAs for 6 h, then washed and exposed to PHA, still inhibited lymphocyte proliferation. The authors also showed that this inhibitory activity was time dependent but became non-significant when PUFAs were added after 48 h lymphocyte culture. The addition of excess exogenous human recombinant rIL-2 partly restored PHA-lymphocyte proliferation inhibited by EPA but not by DHA. On the other hand, the authors showed that PUFAs did not inhibit IL-2 stimulated lymphocyte proliferation. The addition of PUFAs to cell culture medium had no inhibitory action on the PHA-induced lymphocyte expression of CD25, CD71 and HLA-DR. Furthermore, this effect appeared independent of eicosanoid synthesis or peroxide formation. Indeed, the inclusion of aspirin and vitamin E in the culture medium did not prevent the inhibitory effects of PUFAs on lymphocyte proliferation. Regardless of the mechanism of action, the inhibitory effect of PUFAs on activated lymphocytes may explain why some clinical trials of fish oil supplemented diets containing high amounts of DHA and EPA have been successful in improving the health status of patients suffering from inflammatory and autoimmune disorders.     

Increases in erythrocyte DHA are not associated with increases in LDL-cholesterol: Cooper center longitudinal study

BackgroundThe effects of fish oil products containing docosahexaenoic acid (DHA) on LDL-C levels are controversial.ObjectiveTo determine if changes in erythrocyte DHA are associated with changes in LDL-C levels.MethodsIn this prospective observational study, erythrocyte DHA levels and LDL-C levels were measured in 9253 individuals who presented for at least two examinations at a medical clinic. Changes in DHA levels and the reported use of omega-3 dietary supplements were correlated with changes in LDL-C in multi-variable adjusted models including the use of LDL-C-lowering drugs.ResultsMean (standard deviation) age at baseline was 52.6 (10.6) years, and the time between exams averaged 1.9 (1.4) years. As a group, erythrocyte DHA increased from 5.0% (1.3) to 5.3% (1.3) (p < 0.001), and LDL-C was not significantly changed (109 (33) to 108 (33) mg/dL, p = 0.875). However, in multivariable-adjusted models of within-participant changes, a 1% increase in erythrocyte DHA was associated with a 1.9 mg/dL reduction in LDL-C (95% confidence interval (1.6, 2.2), p < 0.001). Similar relationships were seen with changes in erythrocyte EPA and EPA + DHA. In adjusted analyses, an increased use of omega-3 supplements was associated with a significant increase in erythrocyte DHA and a decrease in LDL-C in both users and non-users of lipid-lowering drugs.ConclusionsIn a predominantly male, normolipidemic, middle-aged cohort, increases in erythrocyte DHA were associated with decreases in LDL-C, and initiating fish oil supplement use did not increase LDL-C. These findings may serve to reassure individuals who, in adopting a more heart-healthy lifestyle, want to increase their omega-3 fatty acid intake.     

Cardiac physiology and clinical efficacy of dietary fish oil clarified through cellular mechanisms of omega-3 polyunsaturated fatty acids

Reduced cardiac mortality and morbidity have long been observed in association with omega-3 long chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish consumption, without clear physiological explanation. This review seeks to identify mechanisms of action based on evidence: of physiological effects, active components and effective intakes. Fish oil pleiotropic effects reveal actions that are either intrinsic: effects on cardiac function dependent upon membrane incorporation; or extrinsic: indirect cardiac effects through vascular disease. Extrinsic actions require EPA + DHA doses >3 g/day. Intrinsic effects derive from usual dietary intakes, <1 g/day and include improved myocardial oxygen efficiency, heart rate, nutritional preconditioning against ischaemic injury, arrhythmias and heart failure. Myocardial Na⁺ and K⁺ currents are non-selectively modulated by omega-3 and omega-6 PUFA to stabilise cells in vitro, but not by fish oil-induced membrane change. In contrast, cellular Ca²⁺ overload involved in ischaemic injury, arrhythmia and spontaneous pacemaker activity are modulated by both dietary fish oil and in vitro omega-3 LC-PUFA. A potential linking role of bioactive epoxy and hydroxy PUFA derivatives requires investigation. Omega-3 DHA predominates over EPA in population intake, is preferentially incorporated into myocardium and is selectively active in heart rate and arrhythmia modulation, but EPA predominates in clinical trials. Myocardial selectivity for DHA and independent intrinsic and extrinsic physiological mechanisms underpinning diverse clinical endpoints can explain some contradictory outcomes of clinical trials. Intrinsic modulation of intracellular Ca²⁺ handling provides a unifying physiologically plausible basis for intrinsic fish oil actions and insight to nutritional optimisation of cardiac function.     

Inhibitory effect of polyunsaturated fatty acids on apoptosis induced by etoposide, okadaic acid and AraC in Neuro2a cells

Neuronal apoptosis is involved in neurodegenerative diseases such as Alzheimer's disease and Parkinson.s disease. An efficient means of preventing it remains to be found. Some n-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA, 22 : 6n-3) and eicosapentaenoic acid (EPA, 20 : 5n-3) have been reported to be protective against the neuronal apoptosis and neuronal degeneration seen after spinal cord injury (SCI) [1]. However, it is unclear which kinds of PUFAs have the most potent ability to inhibit neuronal apoptosis and whether the simultaneous treatment of PUFAs inhibits the apoptosis. In the present study, we compared the abilities of various n-3- and n-6- PUFAs to inhibit the apoptosis induced after the administration of different apoptotic inducers, etoposide, okadaic acid, and AraC, in mouse neuroblastoma cells (Neuro2a). Preincubation with DHA (22 : 6n-3), eicosapentaenoic acid (EPA, 20 : 5n-3), alpha-linolenic acid (alpha-LNA, 18 : 3n-3), linoleic acid (LA, 18 : 2n-6), arachidonic acid (AA, 20 : 4n-3), and gamma-linolenic acid (gamma-LNA, 18 : 3n-6) significantly inhibited caspase-3 activity and LDH leakage but simultaneous treatment with the PUFAs had no effect on the apoptosis of Neuro2a cells. There were no significant differences of the anti-apoptotic eff ect among the PUFAs. These results suggest that PUFAs may not be effective for inhibiting neuronal cell death after acute and chronic neurodegenerative disorders. However, dietary supplementation with PUFAs may be beneficial as a potential means to delay the onset of the diseases and/or their rate of progression.     

Omega-6/omega-3 essential fatty acid ratio in cultured beluga sturgeon

The balance of omega-6/omega-3 fatty acids is an important factor in human health. High omega-6 fatty acid content in the diet along with a high omega-6/omega-3 ratio can lead to the development of many chronic diseases. Conversely, higher levels of omega-3 fatty acids such as eicosapentaenoic acid (C20:5, EPA) and docosahexaenoic acid (C22:6, DHA) and lower omega-6/omega-3 ratio are desirable for human health. We determined the lipid content in beluga flesh which was 6.5?%. Monounsaturated fatty acids were the main class of fatty acids followed by polyunsaturated and saturated fatty acids. The EPA and DHA contents of cultured beluga flesh were lower than those of other cultured sturgeon species, which may be due to the contents of these fatty acids in the diet. The content of omega-6 fatty acids (25.7?%) was higher than omega-3 fatty acids (8.58?%), giving an omega-6/omega-3 ratio of 3.00.     

Docosahexaenoic acid-rich fish oil modulates the cerebral hemodynamic response to cognitive tasks in healthy young adults

A number of recent studies have assessed the impact of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) on behavioral outcomes; however, very little attention has been given to their impact upon brain function in physiological terms. Sixty-five healthy adults aged 18-29 yrs took part in this double-blind, placebo-controlled study assessing the effects of 12 weeks daily dietary supplementation with docosahexaenoic acid-rich fish oil (1 g, 2 g) or placebo (olive oil). Relative changes in the concentration of oxyhemoglobin and deoxyhemoglobin were assessed in the prefrontal cortex using near-infrared spectroscopy during performance of nine computerized cognitive tasks. Supplementation with both doses of fish oil, in comparison with placebo, resulted in significantly increased concentrations of oxyhemoglobin and total levels of hemoglobin, indicative of increased cerebral blood flow, during the cognitive tasks. Changes in hemodynamic response to tasks were not accompanied by consistent changes in cognitive performance.     

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

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 <.001). All neonatal cytokine (IL-5, IL-13, IL-10, and IFN-gamma) responses (to all allergens) tended to be lower in the fish oil group (statistically significant only for IL-10 in response to cat). Although this study was not designed to examine clinical effects, we noted that infants in the fish oil group were 3 times less likely to have a positive skin prick test to egg at 1 year of age (odds ratio, 0.34; 95% confidence interval, 0.11 to 1.02; 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.     

Fatty acid composition abnormalities in atopic disease: evidence explored and role in the disease process examined

There is a hypothesis causally linking excess intake of n-6 polyunsaturated fatty acids (PUFAs) to atopic disease. Under most dietary conditions, the main precursor of eicosanoids is the n-6 PUFA arachidonic acid (AA). AA-derived eicosanoids play many roles in sensitization to allergens and in allergic inflammation. Long chain n-3 PUFAs inhibit AA incorporation into cell membranes and inhibit AA metabolism to eicosanoids. It is hypothesized that atopy is associated with a higher n-6 PUFA status and with a low n-3 PUFA status. However, measurements of fatty acid composition do not provide a clear picture that such fatty acid abnormalities exist in atopy with no really clear pattern of altered status of a particular fatty acid or a particular fatty acid family. There are few reports of elevated linoleic acid in atopy. Some studies report lower amounts of the n-6 PUFAs, including AA, and of long chain n-3 PUFAs in atopy, although observations on this are not consistent. Taken together these data clearly do not support the hypothesis that atopy is somehow associated with a high exposure to, and status of, n-6 PUFAs. Intervention studies with n-3 PUFAs in pregnant women, infants and children suggest some clinical benefits, although how long lasting these are remains to be determined. The observation that there may be low AA status in atopy suggests that fish oil intervention, which targets AA status and metabolism, may not be ideal and that a combination of fish oil with some longer chain n-6 PUFAs may be more efficacious.     

n-3 polyunsaturated fatty acids prevent disruption of epithelial barrier function induced by proinflammatory cytokines

Defects in tight junction barrier have been considered as an important etiologic factor of Crohn's disease. n-3 polyunsaturated fatty acids (PUFAs) exert beneficial effects on inflammatory bowel disorders. However, the mechanisms remain unknown. We found that docosahexaenoic acid (DHA, 22:6 n-3) and eicosapentaenoic acid (EPA, 20:5 n-3) changed lipid environment in membrane microdomains of tight junction in vitro. n-3 PUFAs treatment effectively prevented the redistribution of occludin and ZO-1 and distortion of TJ morphology, reduced transepithelial electrical resistance induced by IFN-gamma and TNF-alpha. We also observed dramatic reorganization of TJ proteins in epithelial lateral membrane following treatment with these cytokines. Our findings for first time indicate that n-3 PUFAs play an important role in proinflammatory cytokines-induced permeability defects and epithelial barrier dysfunction by modifying lipid environment in membrane microdomains of tight junction.     

Fish oils for cardiovascular disease: Impact on diabetes

The increasing prevalence of overweight and obesity has led to an epidemic of type 2 diabetes mellitus (T2DM), and is likely to be followed by an epidemic of patients with complications of T2DM such as cardiovascular diseases, neuropathy, retinopathy, and nephropathy. Nutritional interventions that incorporate functional foods, such fish oils – in particular n-3 polyunsaturated fatty acids (n-3 PUFAs) – may be a novel strategy to reduce insulin insensitivity, dyslipidemia, hypertension and pro-inflammatory state. The purpose of this article is to examine the impact of fish oil supplementation on blood lipids, glycemic control, blood pressure and inflammation in subjects with T2DM. Overall, the literature suggests that n-3 PUFA supplementation in diet presents many benefits in T2DM management mainly in terms of dyslipidemia; however, the impact of n-3 PUFAs on glucose control, blood pressure, inflammation and oxidations is less definitive. Overall, n-3 PUFA supplementation represents a reasonable therapeutic strategy in individuals with T2DM to decrease the risk of complications.     

Immunomodulation by polyunsaturated fatty acids: mechanisms and effects

Polyunsaturated fatty acids (PUFAs) modulate immune responses, thereby exerting beneficial effects in a variety of inflammatory disorders. PUFAs of the n-3 series that are found in marine fish oils are particularly effective. A variety of molecular mechanisms have been found to explain how PUFAs could interfere with immune cell function. PUFAs alter eicosanoid (prostaglandin, leukotriene) synthesis, orphan nuclear receptor activation (e.g. peroxisome proliferator-activated receptors, liver X receptors) and T lymphocyte signaling by changing the molecular composition of special signaling platforms called lipid rafts. This review discusses these mechanisms in detail with respect to their probable relevance in vivo. In addition, the effects of PUFAs on the immune system in general are summarized, as are clinical effects in rheumatoid arthritis, inflammatory bowel disease and sepsis.