Showing papers on "Docosahexaenoic acid 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 …

Consumption of Fish and n-3 Fatty Acids and Risk of Incident Alzheimer Disease

Abstract: Background Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies, but there is limited study of whether this type of fat protects against Alzheimer disease. Objective To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease. Design Prospective study conducted from 1993 through 2000, of a stratified random sample from a geographically defined community. Participants were followed up for an average of 3.9 years for the development of Alzheimer disease. Patients A total of 815 residents, aged 65 to 94 years, who were initially unaffected by Alzheimer disease and completed a dietary questionnaire on average 2.3 years before clinical evaluation of incident disease. Main Outcome Measure Incident Alzheimer disease diagnosed in a structured neurologic examination by means of standardized criteria. Results A total of 131 sample participants developed Alzheimer disease. Participants who consumed fish once per week or more had 60% less risk of Alzheimer disease compared with those who rarely or never ate fish (relative risk, 0.4; 95% confidence interval, 0.2-0.9) in a model adjusted for age and other risk factors. Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease, as was intake of docosahexaenoic acid (22:6n-3). Eicosapentaenoic acid (20:5n-3) was not associated with Alzheimer disease. The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions. Conclusion Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease.

Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age.

Abstract: Objectives. Docosahexaenoic acid (DHA; 22:6 n-3) and arachidonic acid (AA; 20:4 n-6) are important for development of the central nervous system in mammals. There is a growth spurt in the human brain during the last trimester of pregnancy and the first postnatal months, with a large increase in the cerebral content of AA and DHA. The fetus and the newborn infant depend on maternal supply of DHA and AA. Our hypothesis was that maternal intake of DHA during pregnancy and lactation is marginal and that high intake of this fatty acid would benefit the child. We examined the effect of supplementing pregnant and lactating women with very-long-chain n-3 polyunsaturated fatty acids (PUFAs; cod liver oil) on mental development of the children, compared with maternal supplementation with long-chain n-6 PUFAs (corn oil). Methods. The study was randomized and double-blinded. Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver oil or corn oil until 3 months after delivery. The cod liver oil contained 1183 mg/10 mL DHA, 803 mg/10 mL eicosapentaenoic acid (20:5 n-3), and a total of 2494 mg/10 mL ∑ n-3 PUFAs. The corn oil contained 4747 mg/10 mL linoleic acid (18:2 n-6) and 92 mg/10 mL α-linolenic acid (18:3 n-3). The amount of fat-soluble vitamins was identical in the 2 oils (117 μg/mL vitamin A, 1 μg/mL vitamin D, and 1.4 mg/mL dl-α-tocopherol). A total of 590 pregnant women were recruited to the study, and 341 mothers took part in the study until giving birth. All infants of these women were scheduled for assessment of cognitive function at 6 and 9 months of age, and 262 complied with the request. As part of the protocol, 135 subjects from this population were invited for intelligence testing with the Kaufman Assessment Battery for Children (K-ABC) at 4 years of age. Of the 135 invited children, 90 came for assessment. Six children did not complete the examination. The K-ABC is a measure of intelligence and achievement designed for children aged 2.5 years through 12.5 years. This multisubtest battery comprises 4 scales: Sequential Processing, Simultaneous Processing, Achievement (not used in the present study), and Nonverbal Abilities. The Sequential Processing and Simultaneous Processing scales are hypothesized to reflect the child’s style of problem solving and information processing. Scores from these 2 scales are combined to form a Mental Processing Composite, which serves as the measure of intelligence in the K-ABC. Results. We received dietary information from 76 infants (41 in the cod liver oil group and 35 in the corn oil group), documenting that all of them were breastfed at 3 months of age. Children who were born to mothers who had taken cod liver oil ( n = 48) during pregnancy and lactation scored higher on the Mental Processing Composite of the K-ABC at 4 years of age as compared with children whose mothers had taken corn oil ( n = 36; 106.4 [7.4] vs 102.3 [11.3]). The Mental Processing Composite score correlated significantly with head circumference at birth ( r = 0.23), but no relation was found with birth weight or gestational length. The children’s mental processing scores at 4 years of age correlated significantly with maternal intake of DHA and eicosapentaenoic acid during pregnancy. In a multiple regression model, maternal intake of DHA during pregnancy was the only variable of statistical significance for the children’s mental processing scores at 4 years of age. Conclusion. Maternal intake of very-long-chain n-3 PUFAs during pregnancy and lactation may be favorable for later mental development of children.

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 …

Habitual Dietary Intake of n-3 and n-6 Fatty Acids in Relation to Inflammatory Markers Among US Men and Women

Abstract: Background— Polyunsaturated fatty acid intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, high intake of n-6 fatty acids may attenuate the known beneficial effects of n-3 fatty acids. Methods and Results— We investigated habitual dietary n-3 fatty acid intake and its interaction with n-6 fatty acids in relation to the plasma inflammatory markers C-reactive protein, interleukin 6, and soluble tumor necrosis factor receptors 1 and 2 (sTNF-R1 and R2) among 405 healthy men and 454 healthy women. After adjustment for other predictors of inflammation, intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was inversely associated with plasma levels of sTNF-R1 and sTNF-R2 (P=0.03 and P<0.001, respectively) and somewhat less so for C-reactive protein (P=0.08). n-3 α-linolenic acid and n-6 cis-linoleic acid were not significantly related to the inflammatory markers. We found little if any association between n-3 fatty acid (EPA+...

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.

Essential fatty acids and the brain.

Abstract: Objective: To review the role of essential fatty acids in brain membrane function and in the genesis of psychi- atric disease. Results: The fatty acid composition of neuronal cell membrane phospholipids reflects their intake in the diet. The degree of a fatty acid's desaturation determines its 3-dimensional structure and, thus, membrane fluidity and function. The ratio between omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), in particular, in- fluences various aspects of serotoninergic and catecholaminergic neurotransmission, as shown by studies in animal models. Phospholipase A2 (PLA2) hydrolyzes fatty acids from membrane phospholipids: liberated omega-6 PUFAs are metabolized to prostaglandins with a higher inflammatory potential, compared with those generated from the omega-3 family. Thus the activity of PLA2 coupled with membrane fatty acid composition may play a central role in the development of neuronal dysfunction. Intervention trials in human subjects show that omega-3 fatty acids have possible positive effects in the treatment of various psychiatric disorders, but more data are needed to make conclusive directives in this regard. Conclusion: The ratio of membrane omega-3 to omega-6 PUFAs can be modulated by dietary intake. This ra- tio influences neurotransmission and prostaglandin formation, processes that are vital in the maintenance of normal brain function. (Can J Psychiatry 2003;48:195-203)

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.

A Double-Blind, Placebo-Controlled Study of the Omega-3 Fatty Acid Docosahexaenoic Acid in the Treatment of Major Depression

Abstract: OBJECTIVE: This study was an evaluation of the omega-3 fatty acid docosahexaenoic acid (DHA) for the treatment of major depression. METHOD: Thirty-six depressed patients were randomly assigned to receive DHA, 2 g/day, or placebo for 6 weeks. Response was defined a priori as a ≥50% reduction in the score on the Montgomery-Asberg Depression Rating Scale. Thirty-five participants were evaluable; 18 received DHA, and 17 received placebo. RESULTS: Response rates were 27.8% in the DHA group and 23.5% in the placebo group. The difference in response rates between groups did not reach statistical significance. CONCLUSIONS: This trial failed to show a significant effect of DHA monotherapy in subjects with major depression.

Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients.

Abstract: Oxidative stress-mediated cell damage has been considered in the pathophysiology of schizophrenia. Abnormal findings have often been considered related to differences in ethnicity, life style, dietary patterns and medications, all of which influence indices of oxidative stress and oxidative cell damage. To minimize these confounds, schizophrenic patients were compared with age-matched control subjects with the same ethnic background and similar lifestyle, as well as with bipolar mood disorder (BMD) patients. Levels of antioxidant defense enzymes (i.e. superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) were lower in schizophrenic patients than in controls, indicating conditions for increased oxidative stress. The contents of plasma thiobarbituric acid reactive substances (TBARS) were only marginally higher in schizophrenic patients, who had normal levels of arachidonic acid (AA), a major source of TBARS, indicating no significant oxidative membrane lipid peroxidation. Levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), however, were significantly lower in schizophrenic patients. When the same indices in BMD patients were compared with findings in matched controls, levels of only SOD and CAT were lower in the patients, whereas GPx was not. Again, as in schizophrenia, the contents of TBARS were marginally higher in BMD patients with no change in levels of AA. Levels of alpha-linolenic acid and EPA were significantly lower and levels of DHA were slightly lower in BMD patients. These data indicate that certain biochemical characteristics may be common to a spectrum of psychiatric disorders, and suggest supplementation of antioxidants and essential fatty acids might affect clinical outcome.

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.

Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer's disease: a case–control study

Abstract: Low n-3 polyunsaturated fatty acid (PUFA) status may be associated with neuro-degenerative disorders, in particular Alzheimer's disease, which has been associated with poor dietary fish or n-3 PUFA intake, and low docosahexaenoic acid (DHA) status. The present case-control study used an established biomarker of n-3 PUFA intake (serum cholesteryl ester-fatty acid composition) to determine n-3 PUFA status in patients with Alzheimer's disease, who were free-living in the community. All cases fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Detailed neuropsychological testing and neuroimaging established the diagnosis in all cases. The subjects (119 females and twenty-nine males) aged 76.5 (SD 6.6) years had a clinical dementia rating (CDR) of 1 (SD 0.62) and a mini mental state examination (MMSE) score of 19.5 (SD 4.8). The control subjects (thirty-six females and nine males) aged 70 (SD 6.0) years were not cognitively impaired (defined as MMSE score <24): they had a mean MMSE score of 28.9 (SD 1.1). Serum cholesteryl ester-eicosapentaenoic acid and DHA levels were significantly lower (P<0.05 and P<0.001 respectively) in all MMSE score quartiles of patients with Alzheimer's disease compared with control values. Serum cholesteryl ester-DHA levels were progressively reduced with severity of clinical dementia. DHA levels did not differ in patients with Alzheimer's disease across age quartiles: all were consistently lower than in control subjects. Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR. It remains to be determined whether low DHA status in Alzheimer's disease is a casual factor in the pathogenesis and progression of Alzheimer's disease.

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

High-cell-density fed-batch cultivation of the docosahexaenoic acid producing marine alga Crypthecodinium cohnii.

Abstract: The heterotrophic marine alga Crypthecodinium cohnii is known to produce docosahexaenoic acid (DHA), a polyunsaturated fatty acid with food and pharmaceutical applications, during batch cultivation on complex media containing sea salt, yeast extract, and glucose. In the present study, fed-batch cultivation was studied as an alternative fermentation strategy for DHA production. Glucose and acetic acid were compared as carbon sources. For both substrates, the feed rate was adapted to the maximum specific consumption rate of C. cohnii. In glucose-grown cultures, this was done by maintaining a significant glucose concentration (between 5 and 20 g/L) throughout fermentation. In acetic acid-grown cultures, the medium feed was automatically controlled via the culture pH. A feed consisting of acetic acid (50% w/w) resulted in a higher overall volumetric productivity of DHA (r(DHA)) than a feed consisting of 50% (w/v) glucose (38 and 14 mg/L/h, respectively). The r(DHA) was further increased to 48 mg/L/h using a feed consisting of pure acetic acid. The latter fermentation strategy resulted in final concentrations of 109 g/L dry biomass, 61 g/L lipid, and 19 g/L DHA. These are the highest biomass, lipid, and DHA concentrations reported to date for a heterotrophic alga. Vigorous mixing was required to sustain aerobic conditions during high-cell-density cultivation. This was complicated by culture viscosity, which resulted from the production of viscous extracellular polysaccharides. These may present a problem for large-scale industrial production of DHA. Addition of a commercial polysaccharide-hydrolase preparation could decrease the viscosity of the culture and the required stirring.

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 altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men.

Abstract: The effect of increased dietary intakes of alpha-linolenic acid (ALNA) or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 2 months upon plasma lipid composition and capacity for conversion of ALNA to longer-chain metabolites was investigated in healthy men (52 (SD 12) years). After a 4-week baseline period when the subjects substituted a control spread, a test meal containing [U-(13)C]ALNA (700 mg) was consumed to measure conversion to EPA, docosapentaenoic acid (DPA) and DHA over 48 h. Subjects were then randomised to one of three groups for 8 weeks before repeating the tracer study: (1) continued on same intake (control, n 5); (2) increased ALNA intake (10 g/d, n 4); (3) increased EPA+DHA intake (1.5 g/d, n 5). At baseline, apparent fractional conversion of labelled ALNA was: EPA 2.80, DPA 1.20 and DHA 0.04 %. After 8 weeks on the control diet, plasma lipid composition and [(13)C]ALNA conversion remained unchanged compared with baseline. The high-ALNA diet resulted in raised plasma triacylglycerol-EPA and -DPA concentrations and phosphatidylcholine-EPA concentration, whilst [(13)C]ALNA conversion was similar to baseline. The high-(EPA+DHA) diet raised plasma phosphatidylcholine-EPA and -DHA concentrations, decreased [(13)C]ALNA conversion to EPA (2-fold) and DPA (4-fold), whilst [(13)C]ALNA conversion to DHA was unchanged. The dietary interventions did not alter partitioning of ALNA towards beta-oxidation. The present results indicate ALNA conversion was down-regulated by increased product (EPA+DHA) availability, but was not up-regulated by increased substrate (ALNA) consumption. This suggests regulation of ALNA conversion may limit the influence of variations in dietary n-3 fatty acid intake on plasma lipid compositions.