Circulating triacylglycerol and apoE levels in response to EPA and docosahexaenoic acid supplementation in adult human subjects. Comparison of Seal Oil to Tuna Oil on Plasma Lipid Levels and Blood Pressure in Hypertriglyceridaemic Subjects Prior supplementation with long chain omega-3 polyunsaturated fatty acids promotes weight loss in obese adults: a double-blinded randomised controlled trial. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. Reduced mania and depression in juvenile bipolar disorder associated with long-chain ω-3 polyunsaturated fatty acid supplementation Docosahexaenoic Acid Supplementation, Vascular Function and Risk Factors for Cardiovascular Disease: A Randomized Controlled Trial in Young Adults Prenatal Fish Oil Supplementation and Allergy: 6-Year Follow-up of a Randomized Controlled Trial Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid. Maternal fish oil supplementation in lactation: Effect on visual acuity and n−3 fatty acid content of infant erythrocytes The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects. Dose-Dependent Effects of Docosahexaenoic Acid Supplementation on Blood Lipids in Statin-Treated Hyperlipidaemic Subjects The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans EPA, but not DHA, decreases mean platelet volume in normal subjects Higher dose of docosahexaenoic acid in the neonatal period improves visual acuity of preterm infants: results of a randomized controlled trial. Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects. Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function. Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemodynamics in humans. Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study. Visual-acuity development in healthy preterm infants: effect of marine-oil supplementation. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Effect of long-chain n-3 fatty acid supplementation on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia. Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo. A randomized trial of different ratios of linoleic to alpha-linolenic acid in the diet of term infants: effects on visual function and growth. Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans. Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. DHA supplementation improved both memory and reaction time in healthy young adults: a randomized controlled trial. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Dose-dependent effects of docosahexaenoic acid-rich fish oil on erythrocyte docosahexaenoic acid and blood lipid levels. Dose-dependent increases in heart rate variability and arterial compliance in overweight and obese adults with DHA-rich fish oil supplementation. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Maternal fish oil supplementation in lactation: effect on developmental outcome in breast-fed infants. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Cardiac autonomic changes associated with fish oil vs soy oil supplementation in the elderly. n-3 Fatty acid supplementation and regular moderate exercise: differential effects of a combined intervention on neutrophil function. Muscle fatigue resistance in the rat hindlimb in vivo from low dietary intakes of tuna fish oil that selectively increase phospholipid n-3 docosahexaenoic acid according to muscle fibre type. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial Determinants of Erythrocyte Omega‐3 Fatty Acid Content in Response to Fish Oil Supplementation: A Dose–Response Randomized Controlled Trial An adaptogenic role for omega-3 fatty acids in stress; a randomised placebo controlled double blind intervention study (pilot) [ISRCTN22569553] Fish Oil Reduces Heart Rate and Oxygen Consumption During Exercise DHA supplementation during pregnancy does not reduce BMI or body fat mass in children: follow-up of the DHA to Optimize Mother Infant Outcome randomized controlled trial. The effects of docosahexaenoic acid-rich fish oil on behavior, school attendance rate and malaria infection in school children--a double-blind, randomized, placebo-controlled trial in Lampung, Indonesia. Fish Oil Supplementation Alters the Plasma Lipidomic Profile and Increases Long-Chain PUFAs of Phospholipids and Triglycerides in Healthy Subjects Docosahexaenoic acid-rich fish oil improves heart rate variability and heart rate responses to exercise in overweight adults. Docosahexaenoic acid-concentrated fish oil supplementation in subjects with mild cognitive impairment (MCI): a 12-month randomised, double-blind, placebo-controlled trial Visual function in breast-fed term infants weaned to formula with or without long-chain polyunsaturates at 4 to 6 months: a randomized clinical trial. Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women Dietary supplementation with long chain omega-3 polyunsaturated fatty acids and weight loss in obese adults. Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after exercise, and heart rate variability in men with healed myocardial infarctions and depressed ejection fractions. Pitfalls in the use of randomised controlled trials for fish oil studies with cardiac patients. Visual Acuity and the Essentiality of Docosahexaenoic Acid and Arachidonic Acid in the Diet of Term Infants Inclusion of fish or fish oil in weight-loss diets for young adults: effects on blood lipids Long-chain n-3 PUFA supplementation decreases physical activity during class time in iron-deficient South African school children. Effects of dietary supplementation with fish oil on in vivo production of inflammatory mediators in clinically normal dogs. The Omega-3 Index: a new risk factor for death from coronary heart disease? Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants. Dietary intervention with oil rich fish reduces platelet-monocyte aggregation in man. The influence of n-3 polyunsaturated fatty acids and very low calorie diet during a short-term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women. Fish oil fatty acids improve postprandial vascular reactivity in healthy men. Preliminary in vivo evidence of increased N-acetyl-aspartate following eicosapentanoic acid treatment in patients with bipolar disorder Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the OmegAD study. Effects of prenatal fish-oil and 5-methyltetrahydrofolate supplementation on cognitive development of children at 6.5 y of age. Dietary supplementation with n-3 PUFA does not promote weight loss when combined with a very-low-energy diet. Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Fish oil supplementation in the treatment of major depression: A randomised double-blind placebo-controlled trial Fish oil supplementation reduces cortisol basal levels and perceived stress: a randomized, placebo-controlled trial in abstinent alcoholics. Dietary supplementation with n-3 polyunsaturated fatty acids in early childhood: effects on blood pressure and arterial structure and function at age 8 y. Omega-3 supplementation during the first 5 years of life and later academic performance: a randomised controlled trial Effect of Supplementing Pregnant and Lactating Mothers With n-3 Very-Long-Chain Fatty Acids on Children's IQ and Body Mass Index at 7 Years of Age The effect of fish oil on physical aggression in schoolchildren--a randomized, double-blind, placebo-controlled trial. Fish-oil supplementation in pregnancy does not reduce the risk of gestational diabetes or preeclampsia. Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids. Effects of Maternal &OHgr;-3 Supplementation on Fatty Acids and on Visual and Cognitive Development Impaired Fetal Growth and Arterial Wall Thickening: A Randomized Trial of Omega-3 Supplementation Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human pulmonary vein and left atrial electrophysiology in paroxysmal atrial fibrillation. DHA-rich fish oil lowers heart rate during submaximal exercise in elite Australian Rules footballers. Respiratory hospitalisation of infants supplemented with docosahexaenoic acid as preterm neonates. The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Anti-inflammatory and cardioprotective effects of n-3 polyunsaturated fatty acids and plant sterols in hyperlipidemic individuals. Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study. Effects of DHA-enriched fish oil on gene expression levels of p53 and NF-κB and PPAR-γ activity in PBMCs of patients with T2DM: A randomized, double-blind, clinical trial.
High doses of n-3 PUFA found in fish oils can reduce the circulating concentration of triacylglycerol ( TG ) , which may contribute to the positive impact of these fatty acids on the risk of CVD . The present study aim ed to establish the differential impact of EPA and docosahexaenoic ( DHA ) on plasma lipids and apo in adults . Forty-two normolipidaemic adult subjects completed a double-blind placebo controlled parallel study , receiving an EPA-rich oil ( 4.8 g EPA/d ) , DHA-rich oil ( 4.9 g DHA/d ) or olive oil as control , for a period of 4 weeks . No effects of treatment on total cholesterol , LDL-cholesterol or HDL-cholesterol were evident . There was a significant 22 % reduction in TG level relative to the control value following the DHA treatment ( P=0.032 ) , with the 15 % decrease in the EPA group failing to reach significance ( P=0.258 ) . There were no significant inter-group differences in response to treatment for plasma apoA1 , -C3 or -E levels , although a significant 15 % within-group increase in apoE was evident in the EPA ( P=0.006 ) and DHA ( P=0.003 ) groups . In addition , a within-group decrease in the apoA1:HDL-cholesterol ratio was observed in the DHA group , suggesting a positive impact of DHA on HDL particle size . The DHA intervention result ed in a significant increase in the proportion of EPA P=0.000 and DHA P=0.000 in plasma phospholipids , whilst significant increases in EPA P=0.000 and docosapentaenoic acid P=0.002 , but not DHA P=0.193 , were evident following EPA supplementation ( P<0.05 ) . Our present results indicate that DHA may be more efficacious than EPA in improving the plasma lipid profile As meat is a rich source of the omega-3 fatty acid docosapentaenoic acid ( DPA ) and Australians consume six times more meat than fish , investigation of the potential health benefit of DPA is warranted . The aims were to compare the effects of seal oil supplementation with fish oil , on measures of plasma lipids and blood pressure in hypertriglyceridaemic subjects . Forty-eight volunteers were recruited from the Wollongong community and were r and omly allocated to one of three groups either receiving 1 g/day of long-chain omega-3 polyunsaturated fatty acids ( LC n-3 PUFA ) using one of three oils : seal oil capsules ( 340 mg eicosapentaenoic acid ( EPA ) , 230 mg DPA , 450 mg DHA ) , fish oil capsules ( 210 mg EPA , 30 mg DPA , 810 mg DHA ) or placebo capsules ( containing sunola oil ) for 6 weeks . Plasma triglycerides remained unchanged in the placebo group , whilst reductions of 7 and 14 % ( P < 0.05 ) were seen in the fish oil and seal oil groups respectively . Systolic blood pressure improved by 8 and 5 mmHg with seal oil and fish oil respectively ( P < 0.05 ) . The mean arterial pressure was significantly lower after seal oil supplementation ( P < 0.005 ) compared with the placebo group . These results indicate that seal oil is as effective as fish oil in lowering plasma triglycerides and blood pressure Obesity has been linked with low levels of ω-3 fatty acids . Generally , intervention studies have failed to establish benefits of supplementation with ω-3PUFA in reducing  body weight or fat mass in humans . The aim of this study was to investigate whether supplementation with LCω-3PUFA alone , then consumed concomitantly with a very low energy diet ( VLED ) , facilitated weight loss , improvements in blood lipids and positive changes to inflammatory mediators . This was a double blind r and omised controlled trial with two parallel groups . For 4 weeks of prior supplementation , one group consumed 6 × 1 g capsules per day monounsaturated oil ( placebo ) , the other group consumed 6 × 1 g capsules per day LCω-3PUFA ( fish oil ) each comprising 70 mg EPA and 270 mg DHA , while consuming their usual diet . Each group continued with their supplements for another 4 weeks while both groups followed a VLED regimen ( n = 19 placebo , n = 20 fish  oil ) . Fasting blood sample s , anthropometric measurements and 3-day food diaries were collected at baseline , at 4 weeks and at 8 weeks . At 4 weeks levels of EPA and DHA increased two-fold in the fish oil group ( P < 0.001 ) , with no significant changes to anthropometric measurements for either group . At 8 weeks a significant 3-way interaction between time , group and gender was observed for percentage reduction in weight , F(1,35 ) = 5.55 , P = 0.024 , and BMI , F(1,35 ) = 5.3 , P = 0.027 with a greater percentage decrease for females in FO compared to PB for weight ( -7.21 % vs.-5.82 % ) and BMI ( -7.43 % vs.-5.91 % ) respectively ( P < 0.05 for both ) . It would appear that supplementation with LCω-3PUFA had a time dependent effect on weight loss in females CONTEXT Uncertainty about the benefits of dietary docosahexaenoic acid ( DHA ) for pregnant women and their children exists , despite international recommendations that pregnant women increase their DHA intakes . OBJECTIVE To determine whether increasing DHA during the last half of pregnancy will result in fewer women with high levels of depressive symptoms and enhance the neurodevelopmental outcome of their children . DESIGN , SETTING , AND PARTICIPANTS A double-blind , multicenter , r and omized controlled trial ( DHA to Optimize Mother Infant Outcome [ DOMInO ] trial ) in 5 Australian maternity hospitals of 2399 women who were less than 21 weeks ' gestation with singleton pregnancies and who were recruited between October 31 , 2005 , and January 11 , 2008 . Follow-up of children ( n = 726 ) was completed December 16 , 2009 . INTERVENTION Docosahexaenoic acid-rich fish oil capsules ( providing 800 mg/d of DHA ) or matched vegetable oil capsules without DHA from study entry to birth . MAIN OUTCOME MEASURES High levels of depressive symptoms in mothers as indicated by a score of more than 12 on the Edinburgh Postnatal Depression Scale at 6 weeks or 6 months postpartum . Cognitive and language development in children as assessed by the Bayley Scales of Infant and Toddler Development , Third Edition , at 18 months . RESULTS Of 2399 women enrolled , 96.7 % completed the trial . The percentage of women with high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups ( 9.67 % vs 11.19 % ; adjusted relative risk , 0.85 ; 95 % confidence interval [ CI ] , 0.70 - 1.02 ; P = .09 ) . Mean cognitive composite scores ( adjusted mean difference , 0.01 ; 95 % CI , -1.36 to 1.37 ; P = .99 ) and mean language composite scores ( adjusted mean difference , -1.42 ; 95 % CI , -3.07 to 0.22 ; P = .09 ) of children in the DHA group did not differ from children in the control group . CONCLUSION The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000569606 Long-chain ω-3 polyunsaturated fatty acid ( LCn-3PUFA ) supplementation may improve symptoms of depression in children and bipolar disorder ( BD ) in adults . No studies have examined the effectiveness of LCn-3PUFA supplementation in the treatment of mania and depression in juvenile BD ( JBD ) when given as an adjunct to st and ard pharmacological treatment . Eighteen children and adolescents with JBD received supplements containing 360 mg per day eicosapentaenoic acid ( EPA ) and 1560 mg per day docosahexaenoic acid ( DHA ) for 6 weeks in an open-label study . Intake and fasting red blood cell ( RBC ) LCn-3PUFA , mania , depression and global function were assessed before and after supplementation . RBC EPA and DHA were significantly higher following supplementation . Clinician ratings of mania and depression were significantly lower and global functioning significantly higher after supplementation . Parent ratings of internalizing and externalizing behaviours were also significantly lower following supplementation . A larger r and omized controlled trial appears warranted in this participant population Background A high consumption of omega‐3 long‐chain polyunsaturated fatty acids , and particularly docosahexaenoic acid ( DHA ) , has been suggested to reduce the risk of cardiovascular disease ( CVD ) . However , while DHA supplementation may have benefits for secondary prevention , few studies have investigated the role of DHA in the primary prevention of CVD . Here , we tested the hypothesis that DHA supplementation  improves endothelial function and risk factors for CVD . Methods and Results Healthy volunteers ( n=328 ) , aged 18 to 37 years , were r and omly assigned to 1.6 g DHA/day ( from a microalgae source ) together with 2.4 g/day carrier oil ( index group ) or to 4.0 g/day olive oil ( control ) ( both given in eight 500‐mg capsules/day for 16 weeks ) . Flow‐mediated endothelium‐dependent vasodilation ( FMD ) of the brachial artery ( primary outcome ) was measured before and after the intervention ( n=268 ) using high‐resolution vascular ultrasound . FMD was the same in both groups at r and omization ( mean , SD ; 0.27 , 0.1 mm ) , but postintervention was higher in the control group ( 0.29 , 0.1 mm ) compared with the DHA‐supplemented group ( 0.26 , 0.1 mm ; mean difference −0.03 mm ; 95 % CI −0.005 to −0.06 mm ; P=0.02 ) . Of other outcomes , only triglyceride ( mean difference −28 % , 95 % CI −40 % to −15 % ; P<0.0001 ) and very low‐density lipoprotein concentrations were significant lower in DHA‐supplemented individuals compared with controls . Conclusions DHA supplementation did not improve endothelial function in healthy , young adults .  Nevertheless , lower triglyceride concentrations with DHA supplementation was consistent with previous reports and could have benefits for the prevention of CVD . Clinical Trial Registration Information URL : http://www.controlled-trials.com/ Unique identifier : IS RCT N no : 19987575 BACKGROUND AND OBJECTIVE : Evidence from r and omized controlled trials in early infancy suggest that prenatal supplementation with Ω-3 ( n-3 ) long-chain polyunsaturated fatty acids ( LCPUFA ) reduces the incidence of allergic disease characterized by an immunoglobulin E ( IgE ) response . We aim ed to determine whether protective effects were evident in the 6-year-old offspring of women supplemented with n-3 rich fish oil during pregnancy . METHODS : Six-year follow-up of children ( n = 706 ) with a family history of allergic disease from the Docosahexaenoic Acid to Optimize Mother Infant Outcome ( DOMInO ) trial . Women were r and omly allocated to receive n-3 LCPUFA-rich fish oil capsules ( 800 mg/d docosahexaenoic acid DHA and 100mg/d eicosapentaenoic acid ) or vegetable oil capsules ( without n-3 LCPUFA ) . Allergic disease symptoms including eczema , wheeze , rhinitis , and rhino-conjunctivitis , were assessed using the International Study of Asthma and Allergies in Childhood question naire and sensitization to allergens was measured by skin prick test . RESULTS : There was no difference in the percentage of children with any IgE-associated allergic disease between the n-3 LCPUFA and control groups ( 116/367 [ 31.5 % ] vs 106/336 [ 31.5 % ] ; adjusted relative risk , 1.04 ; 95 % confidence interval , 0.82–1.33 ; P = .73 ) . There was a reduction in the percentage of children sensitized to house dust mite Dermatophagoides farinae ( 49/367 [ 13.4 % ] vs 68/336 [ 20.3 % ] ; adjusted relative risk , 0.67 , 95 % confidence interval , 0.44–1.00 ; P = .0495 ) . CONCLUSIONS : Prenatal n-3 LCPUFA supplementation did not reduce IgE-associated allergic disease at 6 years of age . Secondary outcomes were suggestive of a protective effect of the intervention on the incidence of D. farinae sensitization BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary artery disease , EPA treatment reduced major coronary events by 18 % , but this finding was not significant ( 104 [ 1.4 % ] in the EPA group vs 127 [ 1.7 % ] in the control group ; p=0.132 ) . INTERPRETATION EPA is a promising treatment for prevention of major coronary events , and especially non-fatal coronary events , in Japanese hypercholesterolaemic patients BACKGROUND Recent studies suggest that eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids have distinct effects on cardiometabolic risk factors . The Omega-3 Index ( O3I ) , which is calculated as the proportion of EPA and DHA in red blood cell ( RBC ) membranes , has been inversely associated with the risk of coronary heart diseases and coronary mortality . The objective of this study was to compare the effects of EPA and DHA supplementation on the O3I in men and women with abdominal obesity and sub clinical inflammation . METHODS In a double-blind controlled crossover study , 48 men and 106 women with abdominal obesity and sub clinical inflammation were r and omized to a sequence of three treatment phases : 1 - 2.7g/d of EPA , 2 - 2.7g/d of DHA , and 3 - 3g/d of corn oil ( 0 g of EPA+DHA ) . All supplements were provided as 3 × 1 g capsules for a total of 3g/d . The 10-week treatment phases were separated by nine-week washouts . RBC membrane fatty acid composition and O3I were assessed at baseline and the end of each phase . Differences in O3I between treatments were assessed using mixed models for repeated measures . RESULTS The increase in the O3I after supplementation with DHA ( + 5.6 % compared with control , P<0.0001 ) was significantly greater than after EPA ( + 3.3 % compared with control , P<0.0001 ; DHA vs. EPA , P<0.0001 ) . Compared to  control , DHA supplementation decreased ( -0.8 % , P<0.0001 ) while EPA increased ( + 2.5 % , P<0.0001 ) proportion of docosapentaenoic acid ( DPA ) in RBCs ( DHA vs. EPA , P<0.0001 ) . The baseline O3I was higher in women than in men ( 6.3 % vs. 5.8 % , P=0.011 ) . The difference between DHA and EPA in increasing the O3I tended to be higher in men than in women ( + 2.6 % vs. + 2.2 % respectively , P for the treatment by sex interaction=0.0537 ) . CONCLUSIONS The increase in the O3I is greater with high dose DHA supplementation than with high dose EPA , which is consistent with the greater potency of DHA to modulate cardiometabolic risk factors . The extent to which such differences between EPA and DHA in increasing the O3I relates to long-term cardiovascular risk needs to be investigated in the future Studies on formula-fed infants indicate a beneficial effect of dietary DHA on visual acuity . Cross-sectional studies have shown an association between breast-milk DHA levels and visual acuity in breast-fed infants . The objective in this study was to evaluate the biochemical and functional effects of fish oil ( FO ) supplements in lactating mothers . In this double-blinded r and omized trial , Danish mothers with habitual fish intake below the 50th percentile of the Danish National Birth Cohort were r and omized to microencapsulated FO [ 1.3 g/d long-chain n−3 FA ( n−3 LCPUFA ) ] or olive oil ( OO ) . The intervention started within a week after delivery and lasted 4 mon . Mothers with habitual high fish intake and their infants were included as a reference group . Ninety-seven infants completed the trial ( 44 OO-group , 53 FO-group ) and 47 reference infants were followed up . The primary outcome measures were : DHA content of milk sample s ( 0 , 2 , and 4 mon postnatal ) and of infant red blood cell ( RBC ) membranes ( 4 mon postnatal ) , and infant visual acuity ( measured by swept visual evoked potential at 2 and 4 mon of age ) . FO supplementation gave rise to a threefold increase in the DHA content of the 4-mon milk sample s ( P<0.001 ) . DHA in infant RBC reflected milk contents ( r=0.564 , P<0.001 ) and was increased by almost 50 % ( P<0.001 ) . Infant visual acuity was not significantly different in the r and omized groups but was positively associated at 4 mon with infant RBC-DHA ( P=0.004 , multiple regression ) . We concluded that maternal FO supplementation during lactation did not enhance visual acuity of the infants who completed the intervention . However , the results showed that infants with higher RBC levels of n−3 LCPUFA had a better visual acuity at 4 mon of age , suggesting that n−3 LCPUFA may influence visual maturation OBJECTIVE Evaluation of the effects of supplementation of n-3 and n-6 fatty acids on vascular tone and endothelial function in healthy men and women aged 40 to 65 years . METHODS In a double-blind , r and omised , placebo controlled study , 173 healthy volunteers took one of six oil supplements  for 8 months . Supplements were placebo , oleic acid rich sunflower oil , evening primrose oil , soya bean oil , tuna fish oil , and tuna/evening primrose oil mix .  Endothelium-dependent and independent vascular responses were measured in the forearm skin using laser Doppler imaging following iontophoretic applications of acetylcholine and sodium nitroprusside , respectively . RESULTS Acetylcholine , but not sodium nitroprusside responses were significantly improved after tuna oil supplementation ( P=0.02 ) . Additionally , there were significant positive correlations between acetylcholine responses and n-3 fatty acid levels in the plasma and erythrocyte membrane phospholipids after tuna oil supplementation . No significant changes in vascular response were seen after supplementation with any of the other oils . CONCLUSIONS Fish oil supplementation has a beneficial effect on endothelial function , even in normal healthy subjects . Modification of the diet by an increase of 6 % in eicosapentaenoic acid and 27 % in docosahexaenoic acid ( equivalent to eating oily fish 2 - 3 times/week ) might have significant beneficial effects on cardiovascular function and health The objective of the study was to evaluate potential benefits of docosahexaenoic acid ( DHA ) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia . A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides ( averaging 2.2 mmol/L ) were r and omised to take 4 g/day ( n = 15 ) or 8 g/day ( n = 15 ) of tuna oil or olive oil ( placebo , n = 15 ) for 6 months . Plasma lipids , blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial .  Plasma triglycerides were reduced 27 % by 8 g/day DHA-rich fish oil ( P < 0.05 ) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months . Even though total cholesterol was already well controlled by the statin treatment ( mean initial level 4.5 mmol/L ) , there was a further dose-dependent reduction with fish oil supplementation ( r = −0.344 , P < 0.05 ) . The extent of total cholesterol reduction correlated ( r = −0.44 ) with the initial total cholesterol levels ( P < 0.005 ) . In the subset with initial plasma cholesterol above 3.8 mmol/L , plasma very low density lipoprotein ( VLDL ) , intermediate-density lipoprotein ( IDL ) and low-density lipoprotein ( LDL ) were isolated and assayed for cholesterol and apolipoprotein B ( apoB ) at the commencement of the trial and at 3 months of intervention . Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL . There were no changes in IDL cholesterol , IDL apoB and high-density lipoprotein cholesterol . The results demonstrate that DHA-rich fish oil supplementation ( 2.16 g DHA/day ) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months . Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia The effect of dietary docosahexaenoic acid ( DHA ) in the absence of eicosapentaenoic acid ( EPA ) has been studied infrequently in humans under controlled conditions . This 120-d study followed healthy , adult male volunteers who lived in the metabolic research unit ( MRU ) of the Western Human Nutrition Research Center for the entire study . The basal ( low-DHA ) diet consisted of natural foods ( 30 en% fat , 15 en% protein , and 55 en% carbohydrate ) , containing < 50 mg/d of DHA , and met the recommended daily intake for all essential nutrients . The high-DHA ( intervention ) diet was similar except that 6 g/d of DHA in the form of a triglyceride containing 40 % DHA replaced an equal amount of safflower oil in the basal diet . The subjects ( ages 20 to 39 ) were within −10 to + 20 % of ideal body weight , nonsmoking , and not allowed alcohol in the MRU . Their exercise level was constant , and their body weights were maintained within 2 % of entry level . They were initially fed the low-DHA diet for 30 d. On day 31 , six subjects ( intervention , group A ) were placed on the high-DHA diet ; the other four subjects ( controls , group B ) remained on the low-DHA diet . Platelet aggregation in platelet-rich plasma was determined using ADP , collagen , and arachidonic acid . No statistical differences could be detected between the amount of agonist required to produce 50 % aggregation of platelet-rich plasma before and after the subjects consumed the high-DHA diet . The prothrombin time , activated partial thromboplastin time , and the antithrombin-III levels in the subjects were determined , and , again , there were no statistically significant differences in these three parameters when their values were compared before and after the subjects consumed the high-DHA diet . In addition , the in vivo bleeding times did not show any significant difference before and after the subjects consumed the high-DHA diet ( 9.4 ±3.1 min before and 8.0±3.4 min after ) . Platelets from the volunteers exhibited more than a threefold increase in their DHA content from 1.54±0.16 to 5.48±1.21 ( wt% ) during the DHA feeding period . The EPA content of the subjects ’ platelets increased from 0.34±0.12 to 2.67±0.91 ( wt% ) during the high-DHA diet despite the absence of EPA in the subjects ’ diets . The results from this study on blood clotting parameters and in vitro platelet aggregation suggest that adding 6 g/d of dietary DHA for 90 d to a typical Western diet containing less than 50 mg/d of DHA produces no observable physiological changes in blood coagulation , platelet function , or thrombotic tendencies in healthy , adult males The first indication of platelet activation is an increase in mean platelet volume ( MPV ) . n−3 FA are known to inhibit platelet function and to reduce the risk for coronary heart disease . The purpose of this study was to determine the effects of FPA and DHA on MPV . Healthy subjects received olive oil placebo for 4 wk and then were r and omly assigned to receive 4 g of ethyl esters of either safflower oil ( n=11 ) , EPA ( n=10 ) , or DHA ( n=12 ) for 4 wk . At the end of placebo run-in and treatment periods , MPV ( fL ; mean±SEM ) and platelet count ( PLT-CT ; 103/μL blood ) were measured in the basal state and after ex vivo stimulation with collagen ( 10 μg/mL ) , cold ( 4 ° C ) , and heat ( 37 ° C ) . Unlike DHA , EPA lowered MPV as compared with safflower oil ( 7.2±0.1 vs. 7.5±0.1 fL ; P<0.05 ) and raised PLT-CT ( 211±18 vs. 192±18 103/μL ; P<0.05 ) in the fasting state . Collagen and cold significantly increased MPV whereas heat lowered MPV regardless of treatment . All stimuli decreased PLT-CT . EPA significantly increased platelet EPA ( 0.2±0.1 vs. 3.3±0.4 % ) and docosapentaenoic acid ( DPA ; 2.2±0.3 vs. 2.9±0.3 % ) concentrations , but not DHA .  DHA treatment significantly increased DHA ( 1.4±0.2 vs. 4.1±0.5 % ) and DPA ( 2.0±0.4 vs. 3.0±0.4 % ) concentrations , but not EPA . In conclusion , EPA , but not DHA , reduces platelet activation , an early step in platelet aggregation BACKGROUND Preterm infants have improved visual outcomes when fed a formula containing 0.2 - 0.4 % docosahexaenoic acid ( DHA ) compared with infants fed no DHA , but the optimal DHA dose is unknown . OBJECTIVE We assessed visual responses of preterm infants fed human milk ( HM ) and formula with a DHA concentration estimated to match the intrauterine accretion rate ( high-DHA group ) compared with infants fed HM and formula containing DHA at current concentrations . DESIGN A double-blind r and omized controlled trial studied preterm infants born at <33 wk gestation and fed HM or formula containing 1 % DHA ( high-DHA group ) or approximately 0.3 % DHA ( current practice ; control group ) until reaching their estimated due date ( EDD ) . Both groups received the same concentration of arachidonic acid . Sweep visual evoked potential ( VEP ) acuity and latency were assessed at 2 and 4 mo corrected age ( CA ) . Weight , length , and head circumference were assessed at EDD and at 2 and 4 mo CA . RESULTS At 2 mo CA , acuity of the high-DHA group did not differ from the control group [ high-DHA group ( x + /- SD ) : 5.6 + /- 2.4 cycles per degree ( cpd ) , n = 54 ; control group : 5.6 + /- 2.4 cpd , n = 61 ; P = 0.96 ] . By 4 mo CA , the high-DHA group exhibited an acuity that was 1.4 cpd higher than the control group ( high-DHA : 9.6 + /- 3.7 cpd , n = 44 ; control : 8.2 + /- 1.8 cpd ; n = 51 ; P = 0.025 ) . VEP latencies and anthropometric measurements were not different between the high-DHA and control groups . CONCLUSION The DHA requirement of preterm infants may be higher than currently provided by preterm formula or HM of Australian women BACKGROUND Dietary alpha-linolenic acid ( ALA ) can be converted to long-chain n-3 polyunsaturated fatty acids ( PUFAs ) in humans and may reproduce some of the beneficial effects of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) on cardiovascular disease risk factors . OBJECTIVE This study aim ed to compare the effects of increased dietary intakes of ALA and EPA+DHA on a range of atherogenic risk factors . DESIGN This was a placebo-controlled , parallel study involving 150 moderately hyperlipidemic subjects r and omly assigned to 1 of 5 interventions :  0.8 or 1.7 g EPA+DHA/d  , 4.5 or 9.5 g ALA/d , or an n-6 PUFA control for 6 mo . Fatty acids were incorporated into 25 g of fat spread and 3 capsules to be consumed daily . RESULTS The change in fasting or postpr and ial lipid , glucose , or insulin concentrations or in blood pressure was not significantly different after any of the n-3 PUFA interventions compared with the n-6 PUFA control . The mean ( + /- SEM ) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention ( -7.7 + /- 4.99 % ) was significantly ( P < 0.05 ) different from the change after the 9.5-g/d ALA intervention ( 10.9 + /- 4.5 % ) . The ex vivo susceptibility of LDL to oxidation was higher after the 1.7-g/d EPA+DHA intervention than after the control and ALA interventions ( P < 0.05 ) . There was no significant change in plasma alpha-tocopherol concentrations or in whole plasma antioxidant status in any of the groups . CONCLUSION At estimated biologically equivalent intakes , dietary ALA and EPA+DHA have different physiologic effects BACKGROUND Greatly increasing dietary flaxseed oil [ rich in the n-3 polyunsaturated fatty acid ( PUFA ) alpha-linolenic acid ( ALA ) ] or fish oil [ rich in the long-chain n-3 PUFAs eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids ] can reduce markers of immune cell function . The effects of more modest doses are unclear , and it is not known whether ALA has the same effects as its long-chain derivatives . OBJECTIVE The objective was to determine the effects of enriching the diet with ALA or EPA+DHA on immune outcomes representing key functions of human neutrophils , monocytes , and lymphocytes . DESIGN In a placebo-controlled , double-blind , parallel study , 150 healthy men and women aged 25 - 72 y were r and omly assigned to 1 of 5 interventions : placebo ( no additional n-3 PUFAs ) , 4.5 or 9.5 g ALA/d , and 0.77 or 1.7 g EPA+DHA/d for 6 mo . The n-3 PUFAs were provided in 25 g fat spread plus 3 oil capsules . Blood sample s were taken at 0 , 3 , and 6 mo . RESULTS The fatty acid composition of peripheral blood mononuclear cell phospholipids was significantly different in the groups with higher intakes of ALA or EPA+DHA . The interventions did not alter the percentages of neutrophils or monocytes engaged in phagocytosis of Escherichia coli or in phagocytic activity , the percentages of neutrophils or monocytes undergoing oxidative burst in response to E. coli or phorbol ester , the proliferation of lymphocytes in response to a T cell mitogen , the production of numerous cytokines by monocytes and lymphocytes , or the in vivo delayed-type hypersensitivity response . CONCLUSION An intake of < or= 9.5 g ALA/d or < or= 1.7 g EPA+DHA/d does not alter the functional activity of neutrophils , monocytes , or lymphocytes , but it changes the fatty acid composition of mononuclear cells The hemodynamic effects of highly purified eicosapentaenoic acid ( EPA , 20:5n-3 ) and docosahexaenoic acid ( DHA , 22:6n-3 ) have not been evaluated in humans . We therefore conducted a r and omized , double-blind , parallel- design intervention study to assess possible separate effects of EPA and DHA on blood pressure , heart rate , and cardiac mechanics .  Healthy , nonsmoking men aged 36 - 56 y ( n = 224 ) were r and omly assigned to dietary supplementation with 4 g/d of ethyl ester concentrates of DHA or EPA or 4 g corn oil/d ( control ) .  Mean blood pressure at baseline was 122/77 mm Hg and was positively associated with concentrations of serum phospholipid saturated fatty acids . Blood pressure did not change during the intervention . Mean heart rate at baseline was 63.4 beats/min ; it decreased 2.2 beats/min in the DHA group ( P = 0.006 compared with control ) , increased 1.9 beats/min in the EPA group ( P = 0.04 compared with control ) , and remained practically unchanged in the control group . In a pooled analysis , changes in heart rate were independent of baseline heart rate and were associated with changes in concentrations of serum phospholipid DHA and docosapentaenoic acid ( 22:5n-3 ) . Echocardiography in a sub sample of 52 men showed improved left ventricular diastolic filling in the marine oil groups compared with the corn oil group ( P = 0.02 ) . In contrast , an increase in plasma concentrations of saturated fatty acids was associated with delayed diastolic filling . We conclude that dietary DHA and EPA influence heart rate and that the fatty acid composition of plasma phospholipids may affect cardiac mechanics in humans BACKGROUND The lipid-modulatory effects of high intakes of the fish-oil fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) are well established and likely to contribute to cardioprotective benefits . OBJECTIVES We aim ed to determine the effect of moderate EPA and DHA intakes ( < 2 g EPA+DHA/d ) on the plasma fatty acid profile , lipid and apolipoprotein concentrations , lipoprotein subclass distribution , and markers of oxidative status . We also aim ed to examine the effect of age , sex , and apolipoprotein E ( APOE ) genotype on the observed responses . DESIGN Three hundred twelve adults aged 20 - 70 y , who were prospect ively recruited according to age , sex , and APOE genotype , completed a double-blind placebo-controlled crossover study . Participants consumed control oil , 0.7 g EPA+DHA/d ( 0.7FO ) , and 1.8 g EPA+DHA/d ( 1.8FO ) capsules in r and om order , each for an 8-wk intervention period , separated by 12-wk washout periods . RESULTS In the group as a whole , 8 % and 11 % lower plasma triacylglycerol concentrations were evident after 0.7FO and 1.8FO , respectively ( P < 0.001 ) : significant sex x treatment ( P = 0.038 ) and sex x genotype x treatment ( P = 0.032 ) interactions were observed , and the greatest triacylglycerol-lowering responses ( reductions of 15 % and 23 % after 0.7FO and 1.8FO , respectively ) were evident in APOE4 men . Furthermore , lower VLDL-cholesterol ( P = 0.026 ) and higher LDL-cholesterol ( P = 0.010 ) , HDL-cholesterol ( P < 0.001 ) , and HDL2 ( P < 0.001 ) concentrations were evident after fish-oil intervention . CONCLUSIONS Supplements providing EPA+DHA at doses as low as 0.7 g/d have a significant effect on the plasma lipid profile . The results of the current trial , which used a prospect i ve recruitment approach to examine the responses in population subgroups , are indicative of a greater triacylglycerol-lowering action of long-chain n-3 polyunsaturated fatty acids in males than in females Docosahexaenoic acid ( DHA ; 22:6n-3 ) is important for normal visual development . We hypothesized that preterm infants fed formulas with marine oil as a source of DHA  would have better visual acuity than infants fed formulas without marine oil  , as measured by the Teller Acuity Card procedure . Marine oil ( P < 0.001 ) and age ( P < 0.0001 ) influenced visual acuity , by repeated- measures analysis of variance ( ANOVA ) corrected for the effect of subject . Marine-oil-supplemented infants had better visual acuity than those fed st and ard formulas at 2 and 4 mo of age , by Fishers ' least-squares difference ( LSD ) . Acuity of both dietary groups improved through 6.5 mo of age , then plateaued . Through 4 mo of age , acuity was inversely related to oxygen supplementation ( log10 h ) and positively related to DHA status , by general-linear-models ( GLM ) analysis . After 4 mo of age , birth weight and gestational age were the only variables consistently related to visual acuity by GLM . We conclude that marine-oil-supplemented formula improved visual acuity of preterm infants through 4 mo of age by improving DHA status BACKGROUND Regular consumption of n-3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk . OBJECTIVE This study aim ed to determine whether eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids have differential effects on serum lipids and lipoproteins , glucose , and insulin in humans . DESIGN In a double-blind , placebo-controlled trial of parallel design , 59 overweight , nonsmoking , mildly hyperlipidemic men were r and omly assigned to receive 4 g purified EPA , DHA , or olive oil ( placebo ) daily while continuing their usual diets for 6 wk . RESULTS Fifty-six men aged 48.8 + /- 1.1 y completed the study . Relative to those in the olive oil group , triacylglycerols fell by 0.45 + /- 0.15 mmol/L ( approximately 20 % ; P = 0.003 ) in the DHA group and by 0.37 + /- 0.14 mmol/L ( approximately 18 % ; P = 0.012 ) in the EPA group . Neither EPA nor DHA had any effect on total cholesterol . LDL , HDL , and HDL(2 ) cholesterol were not affected significantly by EPA , but HDL(3 ) cholesterol decreased significantly ( 6.7 % ; P = 0.032 ) . Although HDL cholesterol was not significantly increased by DHA ( 3 . 1 % ) , HDL(2 ) cholesterol increased by approximately 29 % ( P = 0.004 ) . DHA increased LDL cholesterol by 8 % ( P = 0.019 ) . Adjusted LDL particle size increased by 0.25 + /- 0.08 nm ( P = 0.002 ) with DHA but not with EPA . EPA supplementation increased plasma and platelet phospholipid EPA but reduced  DHA . DHA supplementation increased DHA and EPA in plasma and platelet phospholipids . Both EPA and DHA increased fasting insulin significantly .  EPA , but not DHA , tended to increase fasting glucose , but not significantly so . CONCLUSIONS EPA and DHA had differential effects on lipids , fatty acids , and glucose metabolism in overweight men with mild hyperlipidemia Healthy preterm infants fed formula with long-chain n-3 fatty acids ( n-3 LCFAs ) from marine oil have better early visual acuity but lower plasma phosphatidylcholine ( PC ) arachidonic acid ( AA ) and growth than infants fed formula containing  linolenic acid ( LLA ) as the sole n-3 fatty acid . This r and omized , double-blind trial was design ed to study the effects of a different source of n-3 LCFAs and a shorter feeding interval on visual acuity ( by Teller Acuity Card ) and growth of preterm infants ( n = 59 ; 747 - 1275 g birth wt ) , some of whom required long periods of supplemental oxygen and developed bronchopulmonary dysplasia ( BPD ) . Infants were studied at 0 , 2 , 4 , 6 , 9 , and 12 mo past term . Plasma PC AA , and normalized weight , length , and head circumference were not influenced by BPD or n-3 LCFAs except that n-3 LCFA-supplemented infants weighed less at 6 ( P<0.05 ) and 9 ( P<0.01 ) mo and had smaller head circumferences at 9 mo ( P<0.05 ) . Compared with control infants , however , those fed n-3 LCFAs had lower weight-for-length at 2 , 6 , 9 , and 12 mo ( P<0.0003 , P<0.0114 , P<0.0008 , and P<0.006 , respectively ) . n-3 LCFAs  improved early ( 2-mo ) but not later acuity among infants without BPD ( P<0.02 ) . Regardless of diet , infants with BPD had poorer grating acuity at 2 ( P<0.0002 ) and 4 ( P<0.04 ) mo but not thereafter BACKGROUND Several studies found a benefit of long-chain polyunsaturated fatty acid ( LCP ) supplementation for visual or mental development , but others found no benefit . Likely contributors to differences among studies are the amount of LCP supplementation , functional outcomes , and sample size . OBJECTIVE We evaluated LCP supplementation in amounts typical for human milk ( based on local and worldwide surveys ) in a large cohort of infants by using sweep visual evoked potential ( VEP ) acuity as the functional outcome . DESIGN The study was a double-masked , r and omized , controlled clinical trial in 103 term infants . By age 5 d , infants were r and omly assigned to receive either formula with no docosahexaenoic acid ( DHA ) or arachidonic acid ( ARA ) or formula supplemented with DHA and ARA as 0.36 % and 0.72 % , respectively , of total fatty acids .  Sweep VEP acuity was the primary outcome . R and om dot stereoacuity , blood lipid profile , growth , and tolerance were secondary outcomes . RESULTS VEP acuity in the LCP-supplemented group was significantly better than that in the control group at ages 6 , 17 , 26 , and 52 wk . Stereoacuity in the LCP-supplemented group was significantly better than that in the control group at age 17 wk but not at ages 39 and 52 wk . By ages 17 and 39 wk , the red blood cell DHA concentration in the LCP-supplemented group was more than double and more than triple , respectively , that in the control group . Growth of infants fed LCP-supplemented and control formulas did not differ significantly , and both diets were well tolerated . CONCLUSION LCP supplementation of term infant formula during the first year of life yields clear differences in visual function and in total red blood cell lipid composition BACKGROUND There are nutritional recommendations that the ratio of linoleic to alpha-linolenic acid ( LA : ALA ) in formula for term infants be between 5:1 and 15:1 . These recommendations were made in the absence of data on functional or clinical outcomes . OBJECTIVE We compared the fatty acid status , visual evoked potential ( VEP ) acuity , and growth of term infants fed formula containing an LA : ALA of 10:1 or 5:1 with those of a breast-fed reference cohort . DESIGN Formula-fed infants were allocated r and omly in a double-blind fashion to receive formula with an LA : ALA of either 10:1 ( 16.9:1.7 ; n = 36 ) or 5:1 ( 16.3:3.3 ; n = 37 ) from near birth to 34 wk of age . Increased ALA was attained by replacing soy oil with low-erucic acid cannola oil . A parallel group of breast-fed infants was also recruited . Infant growth and fatty acid status were assessed at 6 , 16 , and 34 wk of age . VEP acuity was assessed at 16 and 34 wk . RESULTS Infants fed the 5:1 formula had greater docosahexaenoic acid ( DHA ) concentrations in plasma and erythrocyte phospholipids than did infants fed the 10:1 formula , but DHA concentrations of infants fed the 5:1 formula remained less than those in breast-fed infants . The VEP acuity of all formula-fed and breast-fed infants was not significantly different at 16 and 34 wk of age . At birth , infants fed the 5:1 formula were heavier , were longer , and had a greater head circumference than infants assigned to the 10:1 formula group ; this differential was maintained throughout the trial . The rate of gain in weight , length , and head circumference was not significantly different between the 2 formula-fed groups , although breast-fed infants had lower weight and length gains than did formula-fed infants between 16 and 34 wk of age . CONCLUSION Lowering the LA : ALA in formula from 10:1 to 5:1 by using low-erucic acid canola oil result ed in a modest increase in plasma DHA but had no effect on VEP acuity or growth rate BACKGROUND Supplementation of the diet with fish oil , which is rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , is reported to decrease several markers of immune function . However , whether EPA , DHA , or a combination of the 2 exerts these immunomodulatory effects is unclear . OBJECTIVE The objective of the study was to determine the effects of supplementation with an EPA-rich or DHA-rich oil on a range of immune outcomes representing key functions of human neutrophils , monocytes , and lymphocytes in healthy humans . DESIGN In a placebo-controlled , double-blind , parallel study , 42 healthy subjects were r and omly allocated to receive supplementation with either placebo ( olive oil ) , EPA ( 4.7 g/d ) , or DHA ( 4.9 g/d ) for 4 wk . Blood sample s were taken before and after supplementation . RESULTS The fatty acid composition of plasma phospholipids and neutrophils was dramatically altered by supplementation with EPA or DHA , and the effects of EPA differed notably from those of DHA . DHA supplementation decreased T lymphocyte activation , as assessed by expression of CD69 , whereas EPA supplementation had no significant effect . Neither the EPA-rich oil nor the DHA-rich oil had any significant effect on monocyte or neutrophil phagocytosis or on cytokine production or adhesion molecule expression by peripheral blood mononuclear cells . CONCLUSIONS Supplementation with DHA , but not with EPA , suppresses T lymphocyte activation , as assessed by expression of CD69 . EPA alone does not , therefore , influence CD69 expression . No other marker of immune function assessed in this study was significantly affected by either EPA or DHA Depressive symptoms may increase the risk of progressing from mild cognitive impairment ( MCI ) to dementia . Consumption of n-3 PUFA may alleviate both cognitive decline and depression . The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA , DHA and EPA , for depressive symptoms , quality of life ( QOL ) and cognition in elderly people with MCI . We conducted a 6-month double-blind , r and omised controlled trial . A total of fifty people aged > 65 years with MCI were allocated to receive a supplement rich in EPA ( 1·67 g EPA + 0·16 g DHA/d ; n 17 ) , DHA ( 1·55 g DHA + 0·40 g EPA/d ; n 18 ) or the n-6 PUFA linoleic acid ( LA ; 2·2 g/d ; n 15 ) . Treatment allocation was by minimisation based on age , sex and depressive symptoms ( Geriatric Depression Scale , GDS ) . Physiological and cognitive assessment s , question naires and fatty acid composition of erythrocytes were obtained at baseline and 6 months ( completers : n 40 ; EPA n 13 , DHA n 16 , LA n 11 ) . Compared with the LA group , GDS scores improved in the EPA ( P=0·04 ) and DHA ( P=0·01 ) groups and verbal fluency ( Initial Letter Fluency ) in the DHA group ( P=0·04 ) . Improved GDS scores were correlated with increased DHA plus EPA ( r 0·39 , P=0·02 ) . Improved self-reported physical health was associated with increased DHA . There were no treatment effects on other cognitive or QOL parameters . Increased intakes of DHA and EPA benefited mental health in older people with MCI . Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia . This needs to be investigated in larger , depressed sample s with MCI BACKGROUND Docosahexaenoic acid ( DHA ) is important for brain function , and its status is dependent on dietary intakes . Therefore , individuals who consume diets low in omega-3 ( n-3 ) polyunsaturated fatty acids may cognitively benefit from DHA supplementation . Sex and apolipoprotein E genotype ( APOE ) affect cognition and may modulate the response to DHA supplementation . OBJECTIVES We investigated whether a DHA supplement improves cognitive performance in healthy young adults and whether sex and APOE modulate the response . DESIGN Healthy adults ( n = 176 ; age range : 18 - 45 y ; nonsmoking and with a low intake of DHA ) completed a 6-mo r and omized , placebo-controlled , double-blind intervention in which they consumed 1.16 g DHA/d or a placebo .  Cognitive performance was assessed by using a computerized cognitive test battery . For all tests , z scores were calculated and clustered into cognitive domains as follows : episodic and working memory , attention , reaction time ( RT ) of episodic and working memory , and attention and processing speed . ANCOVA was conducted with sex and APOE as independent variables . RESULTS RTs of episodic and working memory improved with DHA compared with placebo [ mean difference ( 95 % CI ) : -0.18 SD ( -0.33 , -0.03 SD ) ( P = 0.02 ) and -0.36 SD ( -0.58 , -0.14 SD ) ( P = 0.002 ) , respectively ] . Sex × treatment interactions occurred for episodic memory ( P = 0.006 ) and the RT of working memory ( P = 0.03 ) . Compared with the placebo , DHA improved episodic memory in women [ 0.28 SD ( 0.08 , 0.48 SD ) ; P = 0.006 ] and RTs of working memory in men [ -0.60 SD ( -0.95 , -0.25 SD ) ; P = 0.001 ] . APOE did not affect cognitive function , but there were some indications of APOE × sex × treatment interactions . CONCLUSIONS DHA supplementation improved memory and the RT of memory  in healthy , young adults whose habitual diets were low in DHA  . The response was modulated by sex . This trial was registered at the New Zeal and Clinical Trials Registry ( http://www.anzctr.org.au/default.aspx ) as ACTRN12610000212055 OBJECTIVE There have been indications that high intake of n-3 long-chain polyunsaturated fatty acids ( PUFAs ) during pregnancy may increase birth weight and gestational length . In addition , n-3 long-chain PUFAs may be important for the neurobiological development of the infants . High levels of docosahexaenoic acid ( DHA , 22:6 n-3 ) are found in the gray matter of the cerebral cortex and in the retina , and it seems as if the availability of long-chain PUFAs may be limiting cerebral development . The fetus and the newborn are dependent on a high supply from their mothers , either via the placenta or via breast milk . We supplemented pregnant and lactating women with n-3 or n-6 long-chain PUFAs to evaluate the effect on birth weight , gestational length , and infant development . DESIGN We performed a double-blind , r and omized study recruiting 590 pregnant , healthy , nulli- or primiparous women ( 19 - 35 years old ) in weeks 17 to 19 of pregnancy . The women were provided 10 mL of either cod liver oil or corn oil daily until 3 months after delivery . MAIN OUTCOME MEASURES Primary outcomes were gestational length and birth weight . Electroencephalography ( EEG ) was done on the second day of life and at 3 months of age . Novelty preference ( Fagan test ) was used as an indicator of cognitive function at 6 and 9 months of age . The fatty acid pattern in umbilical plasma phospholipids and in breast milk was measured , and dietary assessment s were performed , both on the mothers during pregnancy and on the infants at 3 months of age . The growth of the infants was followed up to 1 year of age . RESULTS Three hundred forty-one mothers took part in the study until delivery . There were no significant differences in maternal body mass index before pregnancy and at birth , or parity between the 2 groups . Smoking habits and parental education were also similar in the 2 groups . The mean age of the mothers receiving cod liver oil was , by chance , 1 year higher than the age of the mothers receiving corn oil ( 28.6 [ 3.4 ] vs 27.6 [ 3.2 ] years ) . The maternal dietary intake in the 2 groups receiving cod liver oil or corn oil was similar , except for the supplementation . There were no differences in gestational length or birth weight between the cod liver oil group and the corn oil group ( 279.6 [ 9.2 ] vs 279.2 [ 9.3 ] days ; 3609 [ 493 ] vs 3618 [ 527 ] g , respectively ) . Birth length , head circumference , and placental weight were also similar in the 2 groups . The concentrations of the n-3 fatty acids eicosapentaenoic acid ( 20:5 n-3 ) , docosapentaenoic acid ( 22:5 n-3 ) , and DHA in umbilical plasma phospholipids were higher in the cod liver oil group compared with the corn oil group ( 10.8 [ 7.6 ] vs 2.5 [ 1.8 ] microg/mL , 5.0 [ 2.6 ] vs 2.9 [ 1.3 ] microg/mL , 55.8 [ 20.6 ] vs 45.3 [ 12.8 ] microg/mL , respectively ) . Neonates with high concentration of DHA in umbilical plasma phospholipids ( upper quartile ) had longer gestational length than neonates with low concentration ( lower quartile ; 282.5 [ 8.5 ] vs 275.4 [ 9.3 ] days ) . No differences in EEG scores or Fagan scores were found , but neonates with mature EEG ( N = 70 ) had a higher concentration of DHA in umbilical plasma phospholipids than neonates with immature EEG ( N = 51 ) on the second day of life . Dietary information from 251 infants at 3 months of age was collected and 85 % of these infants were exclusively breastfed , in addition to 12 % who were partly breastfed . The breast milk of mothers supplemented with cod liver oil contained more n-3 long-chain PUFAs and less n-6 long-chain PUFAs than breast milk of mothers supplemented with corn oil . There were no significant differences in infant growth during the first year of life between the 2 groups . CONCLUSIONS This study shows neither harmful nor beneficial effects of maternal supplementation of long-chain n-3 PUFAs regarding pregnancy outcome , cognitive development , or growth , as compared with supplementation with n-6 fatty acids . However , it confirms that DHA concentration may be related to gestational length and cerebral maturation of the newborn Consumption of long-chain n-3 PUFA , particularly DHA , has been shown to improve cardiovascular risk factors but the intake required to achieve benefits is unclear . We sought to determine the relationship between DHA intake , increases in erythrocyte DHA content and changes in blood lipids . A total of sixty-seven subjects ( thirty-six male , thirty-one female , mean age 53 years ) with fasting serum TAG > or = 1.1 mmol/l and BMI > 25 kg/m(2 ) completed a 12-week , r and omized , double-blind , placebo-controlled parallel intervention . Subjects consumed 2 , 4 or 6 g/d of DHA-rich fish oil ( 26 % DHA , 6 % EPA ) or a placebo ( Sunola oil ) .  Fasting blood lipid concentrations and fatty acid profiles in erythrocyte membranes were assessed at baseline and after 6 and 12 weeks . For every 1 g/d increase in DHA intake , there was a 23 % reduction in TAG ( mean baseline concentration 1.9 ( sem 0.1 ) mmol/l ) , 4.4 % increase in HDL-cholesterol and 7.1 % increase in LDL-cholesterol . Erythrocyte DHA content increased in proportion to the dose of DHA consumed ( r 0.72 , P < 0.001 ) and the increase after 12 weeks was linearly related to reductions in TAG ( r - 0.38 , P < 0.01 ) and increases in total cholesterol ( r 0.39 , P < 0.01 ) , LDL-cholesterol ( r 0.33 , P < 0.01 ) and HDL-cholesterol ( r 0.30 , P = 0.02 ) . The close association between incorporation of DHA in erythrocytes and its effects on serum lipids highlights the importance of erythrocyte DHA as an indicator of cardiovascular health status Heart rate ( HR ) variability and large arterial compliance can be improved using fish oils . DHA , a component of fish oil , has cardiovascular health benefits , but its effect on HR variability ( HRV ) and arterial compliance is yet to be quantified . Sixty-seven overweight or obese adults ( thirty-six males and thirty-one females ; 53 ( sem 2 ) year ; BMI 31.7 ( sem 1.1 ) kg/m(2 ) ) were r and omly allocated to consume either 6 g/d sunola oil ( control ; n 17 ) , fish oil ( 260 mg DHA+60 mg EPA per g ) at doses of 2 g/d ( n 16 ) , 4 g/d ( n 17 ) or 6 g/d ( n 17 ) . Blood pressure , HR and compliance of large and small arteries were measured while supine at baseline and after 12 weeks in all participants , and HRV was assessed in a subgroup of forty-six participants . There was no effect of fish oil on blood pressure , small artery compliance or HR . However , the low frequency : high frequency ratio of HRV decreased with increasing doses of fish oil ( r - 0.34 , P = 0.02 ) , while large artery compliance increased ( r 0.34 , P = 0.006 ) . Moreover , the changes in these biomarkers were significantly correlated ( r - 0.31 , P = 0.04 ) and may reflect fish oil-induced improvements in arterial function and cardiac autonomic regulation BACKGROUND Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis . We assessed whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) from fish oil have differential effects on platelet , fibrinolytic and vascular function in patients with both conditions . METHODS In a double-blind placebo-controlled trial of parallel design , 59 treated-hypertensive Type 2 diabetic men and postmenopausal women , were r and omised to 4 g/day of EPA , DHA or olive oil ( placebo ) for 6 weeks . Collagen and PAF-stimulated platelet aggregation , collagen-stimulated thromboxane release ( TXB2 ) , plasma tPA and PAI-1 antigens , von Willebr and factor , p-selectin , and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery , were examined before and at the end of intervention . RESULTS Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study . Relative to placebo , DHA but not EPA supplementation significantly reduced collagen aggregation ( 16.9 % , P=0.05 ) and TXB2 ( 18.8 % , P=0.03 ) . There were no significant changes in either PAF-stimulated platelet aggregation , fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo . CONCLUSION Highly purified DHA may be a more effective anti-thrombotic agent than EPA . However , longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension Docosahexaenoic acid ( DHA ) accumulates in the brain during the 1st and 2nd years of life . The objective of this study was to see if an increased content of DHA in breast-milk via maternal fish oil (FO)-supplementation affects mental development in term infants . one hundred twenty-two Danish mothers with a habitual fish intake below the population median were r and omized to  4.5 g.d(-1 ) of FO or olive oil ( OO ) for the first four months of lactation .  Fifty-three mothers with habitual fish intake in the highest quartile were included as reference group . The effect of the result ing increase in infant DHA-intake and RBC-DHA level was assessed on problem solving ability at nine months and language at one and two years of age . Infants in the three groups performed equally well on the problem test and no association was observed between problem solving and erythrocyte-DHA at four months . Passive vocabulary at one year was lower in the children of the FO- compared with the OO-group ( P < 0.05 ) , but no differences were found at two years of age . Word comprehension at one year was inversely associated with erythrocyte-DHA at four months . The trial indicate a small effect of DHA levels in breast-milk on early language development of breast-fed infants AMR101 is an omega-3 fatty acid agent containing ≥96 % eicosapentaenoic acid ethyl ester and no docosahexaenoic acid . Previous smaller studies suggested that highly purified eicosapentaenoic acid lowered triglyceride ( TG ) levels without increasing low-density lipoprotein ( LDL ) cholesterol levels . TG-lowering therapies such as fibrates , and fish oils containing both eicosapentaenoic acid and docosahexaenoic acid , can substantially increase LDL cholesterol levels when administered to patients with very high TG levels ( ≥500 mg/dl ) . The present double-blind study r and omized 229 diet-stable patients with fasting TG ≥500 mg/dl and ≤2,000 mg/dl ( with or without background statin therapy ) to AMR101 4 g/day  , AMR101 2 g/day , or placebo . The primary end point was the placebo-corrected median percentage of change in TG from baseline to week 12 . The baseline TG level was 680 , 657 , and 703 mg/dl for AMR101 4 g/day , AMR101 2 g/day , and placebo . AMR101 4 g/day reduced the placebo-corrected TG levels by 33.1 % ( n = 76 , p < 0.0001 ) and AMR101 2 g/day by 19.7 % ( n = 73 , p = 0.0051 ) . For a baseline TG level > 750 mg/dl , AMR101 4 g/day reduced the placebo-corrected TG levels by 45.4 % ( n = 28 , p = 0.0001 ) and AMR101 2 g/day by 32.9 % ( n = 28 , p = 0.0016 ) . AMR101 did not significantly increase the placebo-corrected median LDL cholesterol levels at 4 g/day ( -2.3 % ) or 2 g/day ( + 5.2 % ; both p = NS )  . AMR101  significantly reduced non-high-density lipoprotein cholesterol , apolipoprotein B , lipoprotein-associated phospholipase A(2 ) , very low-density lipoprotein cholesterol , and total cholesterol  . AMR101 was generally well tolerated , with a safety profile similar to that of the placebo . In conclusion , the present r and omized , double-blind trial of patients with very high TG levels demonstrated that AMR101 significantly reduced the TG levels and improved other lipid parameters without significantly increasing the LDL cholesterol levels INTRODUCTION Omega-3 fatty acid levels are associated with decreased risk for sudden death ; however , the protective cardiovascular mechanisms of omega-3 are poorly understood . This study addresses the heart rate variability ( HRV ) changes in a cohort of elderly subjects r and omized to receive either a daily high dose of marine-derived omega-3 fatty acids ( fish oil ) or a lower daily dose of a plant-derived omega-3 fatty acid ( alpha-linolenic acid ) in soy oil . METHODS A total of 58 elderly nursing home residents were r and omized to receive 2 g/d of fish oil capsules vs 2 g/d of soy oil capsules , and were subsequently followed up every other day for a period of 6 months with 6-min measurements of HRV while resting supine . An initial control period of 2 months without supplementation was allowed to establish an HRV baseline for each participant . RESULTS The average time- and frequency-domain parameters of HRV increased significantly during the supplementation period in both the fish oil and soy oil groups . In the regression model after adjusting for age and mean heart rate , supplementation with fish oil was associated with a significant increase in the high- and low-frequency components , and SD of normal RR intervals ( SDNN ) , whereas only SDNN increased significantly in the soy oil group . CONCLUSIONS Supplementation with 2 g/d of fish oil was well tolerated and was associated with a significant increase in HRV . Supplementation with 2 g/d of soy oil was associated with a lesser but significant increase in HRV CVD is associated with a cellular inflammatory/immune response .  n-3 PUFA and moderate aerobic exercise independently alter cytokine production and leucocyte function . There is limited evidence for the combined effect of these treatments on immune function , particularly in patients with risk factors for CVD . We hypothesised that exercise would enhance the anti-inflammatory effects of n-3 PUFA . In a r and omised , placebo-controlled study , fifty volunteers were allocated double-blind to consume either sunflower oil ( 6 g/d , placebo ) or DHA-rich fish oil ( 6 g/d ; about 2 g n-3 PUFA ; 1.6 g DHA /d ) for 12 weeks . Volunteers were further r and omised to undertake regular exercise ( walking 3 d/week for 45 min at 75 % of maximum heart rate ) or maintain their usual physical activity for 12 weeks . Immune functions were assessed in blood taken initially and after 12 weeks . There was no effect on cytokine production by T cells and monocytes . Superoxide anion production from stimulated blood neutrophils was decreased by fish oil ( 19.5 ( sem 8.5 ) % , P = 0.016 ) but not by exercise , and this change was negatively correlated with the incorporation of DHA into erythrocytes ( r-0.385 , P = 0.047 ) . Participation in regular exercise maintained neutrophil bactericidal activity , which decreased in non-exercising subjects ( 2.9 ( sem 0.7 ) % , P = 0.013 ) . Neutrophil chemotaxis and adherence were not significantly affected by exercise , oil , or the combination of the two . Thus the combination of moderate exercise and fish-oil supplementation , which reduces cardiovascular risk , may also help to counteract inflammation Dietary fish oil ( FO ) modulates muscle O2 consumption and contractile function , predictive of effects on muscle fatigue . High doses unattainable through human diet and muscle stimulation parameters used engender uncertainty in their physiological relevance . We tested the hypothesis that nutritionally relevant FO doses can modulate membrane fatty acid composition and muscle fatigue . Male Sprague-Dawley rats were r and omised to control ( 10 % olive oil ( OO ) by weight ) or low or moderate FO diet ( LowFO and ModFO ) ( HiDHA tuna fish oil ) for 15 weeks ( LowFO : 0.3 % FO , 9.7 % OO , 0.25 % energy as EPA+DHA ; ModFO : 1.25 % FO , 8.75 % OO , 1.0 % energy as EPA+DHA ) . Hindlimb muscle function was assessed under anaesthesia in vivo using repetitive 5 s burst sciatic nerve stimulation ( 0.05 ms , 7 - 12 V , 5 Hz , 10 s duty cycle , 300 s ) . There were no dietary differences in maximum developed muscle force . Repetitive peak developed force fell to 50 % within 62 ( SEM 10 ) s in controls and took longer to decline in FO-fed rats ( LowFO 110 ( SEM 15 ) s ; ModFO 117 ( sem 14 ) s ) ( P<0.05 ) . Force within bursts was better sustained with FO and maximum rates of force development and relaxation declined more slowly . The FO-fed rats incorporated higher muscle phospholipid DHA-relative percentages than controls ( P<0.001 ) . Incorporation of DHA was greater in the fast-twitch gastrocnemius ( Control 9.3 ( SEM 0.8 ) % , LowFO 19.9 ( SEM 0.4 ) , ModFO 24.3 ( SEM 1.0 ) ) than in the slow-twitch soleus muscle ( Control 5.1 ( SEM 0.2 ) , LowFO 14.3 ( SEM 0.7 ) , ModFO 18.0 ( SEM 1.4 ) ) ( P<0.001 ) , which was comparable with the myocardium , in line with muscle fibre characteristics . The LowFO and ModFO diets , emulating human dietary and therapeutic supplement intake , respectively , both elicited muscle membrane DHA enrichment and fatigue resistance , providing a foundation for translating these physiological effects to humans BACKGROUND No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline . We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention ( physical activity , cognitive training , and nutritional advice ) , alone or in combination , compared with placebo , on cognitive decline . METHODS The Multidomain Alzheimer Preventive Trial was a 3-year , multicentre , r and omised , placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco . Participants were non-demented , aged 70 years or older , and community-dwelling , and had either relayed a spontaneous memory complaint to their physician , limitations in one instrumental activity of daily living , or slow gait speed . They were r and omly assigned ( 1:1:1:1 ) to either the multidomain intervention ( 43 group sessions integrating cognitive training , physical activity , and nutrition , and three preventive consultations ) plus omega 3 polyunsaturated fatty acids ( ie , two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid ) , the multidomain intervention plus placebo , omega 3 polyunsaturated fatty acids alone , or placebo alone . A computer-generated r and omisation procedure was used to stratify patients by centre . All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment , but were unblinded to the multidomain intervention component . Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment . The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests ( free and total recall of the Free and Cued Selective Reminding test , ten Mini-Mental State Examination orientation items , Digit Symbol Substitution Test , and Category Naming Test ) in the modified intention-to-treat population . The trial was registered with Clinical Trials.gov ( NCT00672685 ) . FINDINGS 1680 participants were enrolled and r and omly allocated between May 30 , 2008 , and Feb 24 , 2011 . In the modified intention-to-treat population ( n=1525 ) , there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group . Between-group differences compared with placebo were 0·093 ( 95 % CI 0·001 to 0·184 ; adjusted p=0·142 ) for the combined intervention group , 0·079 ( -0·012 to 0·170 ; 0·179 ) for the multidomain intervention plus placebo group , and 0·011 ( -0·081 to 0·103 ; 0·812 ) for the omega 3 polyunsaturated fatty acids group . 146 ( 36 % ) participants in the multidomain plus polyunsaturated fatty acids group , 142 ( 34 % ) in the multidomain plus placebo group , 134 ( 33 % ) in the polyunsaturated fatty acids group , and 133 ( 32 % ) in the placebo group had at least one serious emerging adverse event . Four treatment-related deaths were recorded ( two in the multidomain plus placebo group and two in the placebo group ) . The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events . INTERPRETATION The multidomain intervention and polyunsaturated fatty acids , either alone or in combination , had no significant effects on cognitive decline over 3 years in elderly people with memory complaints . An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined , particularly in real-world setting s. FUNDING French Ministry of Health , Pierre Fabre Research Institute , Gerontopole , Exhonit Therapeutics , Avid Radiopharmaceuticals Background The erythrocyte membrane content of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , which constitutes the omega‐3 index ( O3I ) , predicts cardiovascular disease mortality . The amount of EPA+DHA needed to achieve a target O3I is poorly defined , as are the determinants of the O3I response to a change in EPA+DHA intake . The objective of this study was to develop a predictive model of the O3I response to EPA+DHA supplementation in healthy adults , specifically identifying factors that determine the response . Methods and Results A r and omized , placebo‐controlled , double‐blind , parallel‐group study was conducted in 115 healthy men and women . One of 5 doses ( 0 , 300 , 600 , 900 , 1800 mg ) of EPA+DHA was given daily as placebo or fish oil supplements for ≈5 months . The O3I was measured at baseline and at the end of the study . There were no significant differences in the clinical characteristics between the groups at baseline . The O3I increased in a dose‐dependent manner ( P<0.0001 ) , with the dose of EPA+DHA alone accounting for 68 % ( quadratic , P<0.0001 ) of the variability in the O3I response . Dose adjusted per unit body weight ( g/kg ) accounted for 70 % ( linear , P<0.0001 ) . Additional factors that improved prediction of treatment response were baseline O3I , age , sex , and physical activity . Collectively , these explained 78 % of the response variability ( P<0.0001 ) . Conclusions Our findings vali date the O3I as a biomarker of EPA+DHA consumption and identify additional factors , particularly body weight , that can be used to tailor EPA+DHA recommendations to achieve a target O3I Background There is evidence for an adaptive role of the omega -3 fatty acid , docosahexaenoic acid ( DHA ) during stress . Mechanisms of action may involve regulation of stress mediators , such as the catecholamines and proinflammatory cytokines . Prevention of stress-induced aggression and hostility were demonstrated in a series of clinical trials . This study investigates whether perceived stress is ameliorated by DHA in stressed university staff . Methods Subjects that scored ≥ 17 on the Perceived Stress Scale were r and omised into a 6-week pilot intervention study . The diet reactive group was supplemented with 6 g of fish oil containing 1.5 g per day DHA , while the placebo group was supplemented with 6 g a day of olive oil . The groups were compared with each other and a wider cross sectional study population that did not receive either active or placebo intervention . Results There was a significant reduction in perceived stress in both the fish oil and the placebo group from baseline . There was also a significant between-group difference between the fish oil group and the no-treatment controls in the rate of stress reduction ( p < 0.05 ) . However , there was not a significant between-group difference between the fish oil and the placebo group , nor the placebo group and the control group . These results are discussed in the context of several method ological limitations . The significant stress reductions in both the fish oil and the placebo group are considered in view of statistical regression , an effect likely to have been exaggerated by the time course of the study , a large placebo effect and the possibility of an active effect from the placebo . Conclusion There were significant differences ( p < 0.05 ) in the fish oil group compared with no-treatment controls . This effect was not demonstrated in the placebo group . As a pilot study , it was not sufficiently powered to find the difference between the fish oil group and the placebo group significant . Further work needs to be undertaken to conclusively demonstrate these data trends . However , the findings from this research support the literature in finding a protective or ' adaptogenic ' role for omega-3 fatty acids in stress Dietary omega-3 polyunsaturated fatty acids ( PUFAs ) are readily incorporated into heart and skeletal muscle membranes where , in the heart , animal studies show they reduce O2 consumption . To test the hypothesis that omega-3 PUFAs alter O2 efficiency in humans , the effects of fish oil ( FO ) supplementation on O2 consumption during exercise were evaluated . Sixteen well-trained men ( cyclists ) , r and omly assigned to receive 8 × 1 g capsules per day of olive oil ( control ) or FO for 8 weeks in a double-blind , parallel design , completed the study ( control : n = 7 , age 27.1 ± 2.7 years ; FO : n = 9 , age 23.2 ± 1.2 years ) . Subjects used an electronically braked cycle ergometer to complete peak O2 consumption tests ( VO2peak ) and sustained submaximal exercise tests at 55 % of peak workload ( from the VO2peak test ) before and after supplementation . Whole-body O2 consumption and indirect measurements of myocardial O2 consumption [ heart rate and rate pressure product ( RPP ) ] were assessed . FO supplementation increased omega-3 PUFA content of erythrocyte cell membranes . There were no differences in VO2peak ( mL kg−1 min−1 ) ( control : pre 66.8 ± 2.4 , post 67.2 ± 2.3 ; FO : pre 68.3 ± 1.4 , post 67.2 ± 1.2 ) or peak workload after supplementation . The FO supplementation lowered heart rate ( including peak heart rate ) during incremental workloads to exhaustion ( P < 0.05 ) . In addition , the FO supplementation lowered steady-state submaximal exercise heart rate , whole-body O2 consumption , and RPP ( P < 0.01 ) . Time to voluntary fatigue was not altered by FO supplementation . This study indicates that FOs may act within the healthy heart and skeletal muscle to reduce both whole-body and myocardial O2 dem and during exercise , without a decrement in performance BACKGROUND The omega-3 ( n-3 ) long-chain polyunsaturated fatty acid ( LCPUFA ) docosahexaenoic acid ( DHA ) has proven effective at reducing fat storage in animal studies . However , a systematic review of human trials showed a lack of quality data to support or refute this hypothesis . OBJECTIVE We sought to determine whether maternal DHA supplementation during the second half of pregnancy results in a lower body mass index ( BMI ) and percentage of body fat  in children . DESIGN We conducted a follow-up at 3 and 5 y of age of children who were born to mothers enrolled in the DOMInO ( DHA to Optimize Mother Infant Outcome ) double-blind , r and omized controlled trial , in which women with a singleton pregnancy were provided with DHA-rich fish-oil capsules ( 800 mg DHA/d ) or vegetable-oil capsules ( control group ) in the second half of pregnancy . Primary outcomes were the BMI z score and percentage of body fat at 3 and 5 y of age . Potential interactions between prenatal DHA and the peroxisome proliferator-activated receptor-γ ( PPARγ ) genotype as a measure of the genetic predisposition to obesity were investigated . RESULTS A total of 1614 children were eligible for the follow-up . Parent or caregiver consent was obtained for 1531 children ( 95 % ) , and these children were included in the analysis . BMI z scores and percentages of body fat of children in the DHA group did not differ from those of children in the control group at either 3 y of age [ BMI z score adjusted mean difference : 0.03 ( 95 % CI : -0.07 , 0.13 ; P = 0.61 ) ; percentage of body fat adjusted mean difference : -0.26 ( 95 % CI : -0.99 , 0.46 ; P = 0.47 ) ] or 5 y of age [ BMI z score adjusted mean difference : 0.02 ( 95 % CI : -0.08 , 0.12 ; P = 0.66 ) ; percentage of body fat adjusted mean difference : 0.11 ( 95 % CI : -0.60 , 0.82 ; P = 0.75 ) ] . No treatment effects were modified by the PPARγ genotype of the child . CONCLUSION Independent of a genetic predisposition to obesity , maternal intake of DHA-rich fish oil during the second half of pregnancy does not affect the growth or body composition of children at 3 or 5 y of age . This trial was registered at www.anzctr.org.au as ACTRN1260500056906 and ACTRN12611001127998 BACKGROUND There are only a very limited number of reports of intervention studies on the effects of fish oil on behavior in normal school children . OBJECTIVE To observe the effects of fish oil on behavior and school attendance rates in school children . DESIGN Fourth to sixth grade rs ( mostly 9 - 12 years of age ) of an elementary school in Lampung Province , Indonesia , were r and omly divided into either a docosahexaenoic acid ( DHA ) group ( n=116 ) or a control group ( n=117 ) in a double-blind manner . The subjects in the DHA group took 6 fish oil capsules per day ( 0.65 g DHA and 0.10 g eicosapentaenoic acid (EPA)/day ) for 3 months . Controls took soybean oil capsules . Two question naires were administered and blood was taken at the start and end of the study . Two question naires were administered at the start and end of the study : Hostility-Aggression Question naire for Children ( HAQ-C ) and Barratt Impulsiveness Scale , version 11 ( BIS-11 ) , for measurement of aggression and impulsivity , respectively . Attendance was recorded during the study period . OUTCOMES The concentrations of DHA and EPA in the phospholipid fraction in red blood cells were significantly increased in the DHA group . Behavior checked with HAQ-C or BIS-11 did not show any differences between groups . However , the odds ratio of inability to attend school regularly during the study period was 0.40 ( 95%CI : 0.23 - 0.71 ) in the DHA group compared with controls ( p=0.002 ) . CONCLUSIONS DHA-rich fish oil may improve the school attendance rate of children in Lampung , Indonesia Background While beneficial health effects of fish and fish oil consumption are well documented , the incorporation of n-3 polyunsaturated fatty acids in plasma lipid classes is not completely understood . The aim of this study was to investigate the effect of fish oil supplementation on the plasma lipidomic profile in healthy subjects . Methodology /Principal Findings In a double-blinded r and omized controlled parallel-group study , healthy subjects received capsules containing either 8 g/d of fish oil ( FO ) ( 1.6 g/d EPA+DHA ) ( n = 16 ) or 8 g/d of high oleic sunflower oil ( HOSO ) ( n = 17 ) for seven weeks . During the first three weeks of intervention , the subjects completed a fully controlled diet period . BMI and total serum triglycerides , total- , LDL- and HDL-cholesterol were unchanged during the intervention period . Lipidomic analyses were performed using Ultra Performance Liquid Chromatography ( UPLC ) coupled to electrospray ionization quadrupole time-of-flight mass spectrometry ( QTOFMS ) , where 568 lipids were detected and 260 identified . Both t-tests and Multi-Block Partial Least Square Regression ( MBPLSR ) analysis were performed for analysing differences between the intervention groups . The intervention groups were well separated by the lipidomic data after three weeks of intervention . Several lipid classes such as phosphatidylcholine , phosphatidylethanolamine , lysophosphatidylcholine , sphingomyelin , phosphatidylserine , phosphatidylglycerol , and triglycerides contributed strongly to this separation . Twenty-three lipids were significantly decreased ( FDR<0.05 ) in the FO group after three weeks compared with the HOSO group , whereas fifty-one were increased including selected phospholipids and triglycerides of long-chain polyunsaturated fatty acids . After seven weeks of intervention the two intervention groups showed similar grouping . Conclusions / Significance In healthy subjects , fish oil supplementation alters lipid metabolism and increases the proportion of phospholipids and triglycerides containing long-chain polyunsaturated fatty acids . Whether the beneficial effects of fish oil supplementation may be explained by a remodeling of the plasma lipids into phospholipids and triglycerides of long-chain polyunsaturated fatty acids needs to be further investigated . Trial Registration Clinical Trials.gov Dietary fish oil supplementation and regular physical activity can improve outcomes in patients with established CVD . Exercise has been shown to improve heart rate variability ( HRV ) , a predictor of cardiac death , but whether fish oil benefits HRV is controversial . Obese adults at risk of future coronary disease have impaired HRV and may benefit from these interventions . We evaluated the effect of DHA-rich tuna fish oil supplementation with and without regular exercise on HRV in sedentary , overweight adults with risk factors for coronary disease . In a r and omised , double-blind , parallel comparison , sixty-five volunteers consumed 6 g fish oil/d ( DHA 1.56 g/d , EPA 0.36 g/d ) or sunflower-seed oil ( placebo ) for 12 weeks . Half of each oil group also undertook regular moderate physical activity ( 3 d/week for 45 min , at 75 % of age-predicted maximal heart rate ( HR ) ) . Resting HR and the HR response to submaximal exercise were measured at weeks 0 , 6 and 12 . In forty-six subjects , HRV was also assessed by power spectrum analysis of 20 min electrocardiogram recordings taken supine at baseline and 12 weeks . Fish oil supplementation improved HRV by increasing high-frequency power , representing parasympathetic activity , compared with placebo ( P = 0.01 ; oil x time interaction ) . It also reduced HR at rest and during submaximal exercise ( P = 0.008 ; oil x time interaction ) . There were no significant fish oil x exercise interactions . Dietary supplementation with DHA-rich fish oil reduced HR and modulated HRV in keeping with an improved parasympathetic-sympathetic balance in overweight adults with risk factors for future coronary disease Rationale Epidemiological studies have suggested a beneficial effect of fish oil supplementation in halting the initial progression of Alzheimer ’s disease . However , it remains unclear whether fish oil affects cognitive function in older people with mild cognitive impairment ( MCI ) . Objectives This study investigated the effects of fish oil supplementation on cognitive function in elderly person with MCI . Methods This was a 12-month , r and omised , double-blind , placebo-controlled study using fish oil supplementation with concentrated docosahexaenoic acid ( DHA ) .  Thirty six low-socioeconomic-status elderly subjects with MCI were r and omly assigned to receive either concentrated DHA fish oil ( n = 18 ) or placebo ( n = 18 ) capsules . The changes of memory , psychomotor speed , executive function and attention , and visual-constructive skills were assessed using cognitive tests . Secondary outcomes were safety and tolerability of the DHA concentrate . Results The fish oil group showed significant improvement in short-term and working memory ( F = 9.890 ; ηp2 = 0.254 ; p < 0.0001 ) , immediate verbal memory ( F = 3.715 ; ηp2 = 0.114 ; p < 0.05 ) and delayed recall capability ( F = 3.986 ; ηp2 = 0.121 ; p < 0.05 ) . The 12-month change in memory ( p < 0.01 ) was significantly better in the fish oil group . Fish oil consumption was well tolerated , and the side effects were minimal and self-limiting . Conclusions This study suggested the potential role of fish oil to improve memory function in MCI subjects . Studies with larger sample sizes , longer intervention periods , different fish oil dosages and genetic determinations should be investigated before definite recommendations can be made OBJECTIVE Breast-fed infants receive docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) in their diet . Upon weaning , infants lose this dietary source of long-chain polyunsaturates because many commercial formulas do not contain these important constituents for neural membrane biogenesis . We evaluated the benefits of postweaning dietary supplementation of DHA + ARA on visual maturation . STUDY DESIGN Healthy term infants ( n = 61 ) were breast-fed to 4 to 6 months , then were r and omly assigned to commercial formula or formula supplemented with DHA ( 0.36 % ) + ARA ( 0.72 % ) . Measurements of red blood cell ( RBC ) fatty acids , visually evoked potential ( VEP ) acuity , and stereoacuity were done before and after weaning . RESULTS At 1 year of age , RBC-DHA in the commercial formula-fed group was reduced by 50 % from the weaning level , whereas there was a 24 % increase in the DHA + ARA-supplemented group . The primary outcome measure , VEP acuity , was significantly more mature in supplemented infants at 1 year of age . Elevated RBC-DHA levels were associated with more mature VEP acuity . There were no significant diet-related differences in stereoacuity . CONCLUSIONS These data extend through the first year of life the critical period in which a dietary supply of DHA and ARA can contribute in optimizing visual development in term infants Background : Obesity , inflammation , insulin resistance and cardiovascular disease ( CVD ) risk are inter-related . Both weight-loss and long-chain n-3 polyunsaturated fatty acids ( LC n-3 PUFA ) are independently known to reduce metabolic risk , but the combined effects are unclear . Objective : This study examines whether addition of LC n-3 PUFA to a low fat/high carbohydrate weight-loss programme results in greater improvements in inflammation , insulin sensitivity and CVD risk , than weight-loss alone . Design : One hundred and sixteen overweight insulin-resistant women entered a 24-week r and omised intervention study . Thirty-nine women were r and omised to a weight-loss programme , with LC n-3 PUFA ( WLFO ) , 38 to a weight-loss programme with placebo oil ( WLPO ) , and 39 to receive placebo oil , with no weight-loss programme ( control ) . Results : Ninety-three women completed the study ( 35 WLFO , 32 WLPO and 26 control ) , with significant weight-loss in WLFO ( 10.8±1.0 % ) and WLPO ( 12.4±1.0 % ) compared to the control group ( P<0.0001 ) . The WLFO , but not WLPO or control group , showed significant increases in adipose tissue LC n-3 PUFA ( 0.34±0.20 vs 0.17±0.10 and 0.16±0.10 % DHA , P<0.0001 ) . Weight-loss showed significant improvements in insulin sensitivity ( P<0.001 ) , lipid profile ( triglycerides P<0.05 ) and inflammation ( sialic acid P<0.05 ) . Time*group effects showed significant decreases in triglycerides ( P<0.05 ) and increases in adiponectin ( P<0.01 ) with LC n-3 PUFA , in the WLFO vs WLPO groups . Conclusions : Weight-loss improved risk factors associated with CVD , with some additional benefits of LC n-3 PUFA on triglycerides and adiponectin . Given the current low dietary intake of LC n-3 PUFA , greater attention should be given to increase these fatty acids in the treatment of obesity BACKGROUND Obesity is associated with elevated levels of inflammation and metabolic abnormalities , with increased risk of developing insulin resistance , type 2 diabetes , stroke and CVD . Nutrients that can assist in weight loss may also reduce the risk of obesity related co-morbidities . AIM The aim of this study was to investigate whether LCn-3PUFA , combined with a reduced energy diet , facilitated weight loss and improvements in blood lipids and inflammatory mediators . DESIGN A double blind r and omised controlled trial with two parallel groups . Both groups followed a low energy diet for 12 weeks , one group consumed 6 × 1 g capsules/d monounsaturated oil ( Placebo ) ( n = 18 ) , the other 6 × 1 g capsules/d LCn-3PUFA ( fish oil ) ( n = 17 ) . Fasting blood sample s , anthropometric measurements and 3-day food diaries were collected at baseline and post intervention . RESULTS There was a two-fold increase in plasma levels of EPA and DHA in the fish oil group ( p < 0.001 ) . There were no significant difference within and between the placebo and the fish oil groups for weight reduction ( 3.37 % and 4.35 % respectively ) , fat mass reduction ( 8.95 % and 9.76 % respectively ) , or changes in inflammatory biomarkers and blood lipids apart from triglycerides , reduced by 27 % in fish oil group ( p < 0.05 ) . For fish oil group there were significant correlations between leptin and weight loss ( p = 0.01 ) and leptin and EPA and DHA ( p < 0.05 for both ) . CONCLUSION Dietary LCn-3PUFA supplementation during a weight loss program does not appear to assist weight loss . Poor dietary compliance may be a contributing factor in accurate assessment of the role of these fatty acids in weight loss We explored possible mechanisms by which recommended intakes of omega-3 fatty acids may decrease the risk for sudden cardiac death in patients with documented coronary heart disease . The cardioprotective effects of omega-3 fatty acids have been documented in epidemiologic and r and omized controlled trials . These fatty acids are presumed to decrease susceptibility to fatal arrhythmias , but whether this is mediated by classic risk factors or direct cardiac mechanisms is not known . Eighteen white men with a history of myocardial infa rct ion and ejection fractions < 40 % were r and omized to placebo or omega-3 fatty acids ( 585 mg of docosahexaenoic acid and 225 mg of eicosapentaenoic acid ) for two 4-month periods in a crossover design . At the end of each period , heart rate ( HR ) , HR variability , and rate of HR recovery after exercise were determined , as were effects on arterial compliance , blood pressure , cardiac function , and fasting serum levels of lipids and inflammatory markers .  Omega-3 fatty acids decreased HR at rest from 73 + /- 13 to 68 + /- 13 beats/min ( p < 0.0001 ) and improved 1-minute HR recovery after exercise ( -27 + /- 10 to -32 + /- 12 beats/min , p < 0.01 ) . HR variability in the high-frequency b and increased ( p < 0.02 ) , but no change was noted in overall HR variability . There were no significant effects on blood pressure , arterial compliance , lipids , or inflammatory markers . These changes are consistent with an increase in vagal activity and may in part explain the observed decrease in risk for sudden cardiac death seen with omega-3 fatty acid supplementation R and omised controlled trials ( RCT ) examining the effects of  fish oil supplementation  on cardiac outcomes have yielded varying results over time . Although RCT are placed at the top of the evidence hierarchy , this methodology arose in the framework of pharmaceutical development . RCT with pharmaceuticals differ in important ways from RCT involving fish oil interventions . In particular , in pharmaceutical RCT , the test agent is present only in the intervention group and not in the control group , whereas in fish oil RCT , n-3 fats are present in the diet and in the tissues of both groups . Also , early phase studies with pharmaceuticals determine pharmacokinetics and pharmacodynamics to design the dose of the RCT intervention so that it is in a predicted linear dose-response range . None of this happens in fish oil RCT , and there is evidence that both baseline n-3 intake and tissue levels may be sufficiently high in the dose-response range that it is not possible to demonstrate a clinical effect with a RCT . When these issues are considered , it is possible that the changing pattern of fish consumption and fish oil use over time , especially in cardiac patients , can explain the disparity where benefit was observed in the early fish oil trials but not in the more recent trials The need for a dietary supply of docosahexaenoic acid ( DHA ) and arachidonic aid ( AA ) in term infants was evaluated in a double-masked r and omized clinical trial of the effects of supplementation of term infant formula with DHA ( 0.35 % of total fatty acids ) or with DHA ( 0.36 % ) and AA(0.72 % ) on visual acuity development . One hundred and eight healthy term infants were enrolled in the study ; 79 were exclusively formula-fed from birth ( r and omized group ) and 29 were exclusively breast-fed ( gold st and ard group ) . Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition , growth , sweep visual evoked potential(VEP ) acuity , and forced choice preferential looking acuity . Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell ( RBC ) lipid composition . Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6 , 17 , and 52 wk of age but not at 26 wk of age , when acuity development reaches a plateau . The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants , whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants . Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol . Infants in all diet groups had similar rates of growth and tolerated all diets well . Thus , early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant Objective : To assess the effects of fish ( lean or oily ) and fish oil consumption on blood lipid concentration during weight loss . Design : R and omized , controlled 8-week trial of energy-restricted diet varying in fish and fish oil content . Subjects , 324 men and women , aged 20–40 years , body mass index 27.5–32.5 kg m−2 , from Icel and , Spain and Irel and , were r and omized to one of four groups : ( 1 ) control ( sunflower oil capsules , no seafood ) , ( 2 ) cod diet ( 3 × 150 g week−1 ) , ( 3 ) salmon diet ( 3 × 150 g week−1 ) , ( 4 ) fish oil ( DHA/EPA capsules , no seafood ) . The macronutrient composition of the diets was similar between the groups and the capsule groups were single-blinded . Measurements : Total cholesterol ( TC ) , high-density lipoprotein ( HDL ) and low-density lipoprotein cholesterol , triacylglycerol ( TG ) and anthropometrics were measured at baseline and end point . Results : The difference in logTG lowering between the control group and the cod diet , salmon diet and fish oil from baseline to end point was −0.036 ( 95 % CI −0.079 to 0.006 ) , −0.060 ( −0.101 to −0.018 ) and −0.037 ( −0.079 to 0.006 ) , respectively . Reduction in TC was about 0.2 mmol l−1 greater in the fish groups ( cod and salmon ) than in the control group , but only of borderline significance when adjusting for weight loss . HDL tended to decrease less in the diet groups consuming a significant amount of n-3 fatty acids ( salmon and fish oil ) . Conclusion : Weight-loss diet including oily fish result ed in greater TG reduction than did a diet without fish or fish oil . Controlled trials using whole fish as a test meal are encouraged to be able to eluci date the role of different constituents of fish for human health Both Fe deficiency and poor n-3 fatty acid status have been associated with behavioural changes in children . In the present study , we investigated the effects of Fe and DHA+EPA supplementation , alone or in combination , on physical activity during school days and on teacher-rated behaviour in healthy Fe-deficient school children . In a 2 × 2 factorial design , children ( n 98 , 6 - 11 years ) were r and omly assigned to receive ( 1 ) Fe ( 50 mg ) plus DHA ( 420 mg)+EPA ( 80 mg ) , ( 2 ) Fe plus placebo , ( 3 ) placebo plus DHA+EPA or ( 4 ) placebo plus placebo as oral supplements ( 4 d/week ) for 8.5 months . Physical activity was measured during four school days at baseline and endpoint using accelerometers , and data were stratified into morning class time ( 08.00 - 10.29 hours ) , break time ( 10.30 - 11.00 hours ) and after-break class time ( 11.01 - 12.00 hours ) for analysis . Classroom behaviour was assessed at endpoint using Conners ' Teacher Rating Scales . DHA+EPA supplementation decreased physical activity counts during morning class time , increased sedentary physical activity , and decreased light- and moderate-intensity physical activities . Consistently , DHA+EPA supplementation increased sedentary physical activity and decreased light-intensity physical activity during after-break class time . Even though there were no treatment effects found on teacher-rated behaviour , lower physical activity during morning class time was associated with lower levels of teacher-rated hyperactivity and oppositional behaviour at endpoint . Despite a positive association between Fe status and physical activity during break time at baseline , Fe supplementation did not affect physical activity during break time and class time . Our findings suggest that DHA+EPA supplementation may decrease physical activity levels during class time , and further indicate that accelerometry might be a useful tool to assess classroom behaviour in healthy children OBJECTIVE To evaluate the effect of diets enriched with eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) on in vivo production of interleukin (IL)-1 , IL-6 , tumor necrosis factor (TNF)-alpha , prostagl and in E2 ( PGE2 ) , and platelet-activating factor ( PAF ) in dogs . ANIMALS 15 young healthy dogs . PROCEDURES Dogs were r and omly allocated to receive an isocaloric ration supplemented with sunflower oil ( n=5 ) , fish oil ( 5 ) , or fish oil plus vitamin E ( 5 ) for 12 weeks . At week 12 , in vivo production of inflammatory mediators was evaluated in serum at multiple time points for 6 hours following stimulation with IV administration of lipopolysaccharide ( LPS ) . RESULTS Serum activity or concentration ( area under the curve ) of IL-1 , IL-6 , and PGE2 significantly increased after LPS injection in all groups but to a lesser extent in dogs receiving the fish oil diet , compared with results for dogs receiving the sunflower oil diet . Serum activity of TNF-alpha and PAF concentration also increased significantly after LPS injection in all groups but did not differ significantly among groups . CONCLUSIONS AND CLINICAL RELEVANCE A fish oil-enriched diet consisting of 1.75 g of EPA/kg of diet and 2.2 g of DHA/kg of diet ( dry-matter basis ) with an n-6:n-3 fatty acid ratio of 3.4:1 was associated with significant reductions in serum PGE2 concentrations and IL-1 and IL-6 activities . Results supported the use of EPA- and DHA-enriched diets as part of antiinflammatory treatments for dogs with chronic inflammatory diseases . Additional studies in affected dogs are warranted to further evaluate beneficial anti-inflammatory effects of EPA- and DHA-enriched diets BACKGROUND Low intakes or blood levels of eicosapentaenoic and docosahexaenoic acids ( EPA + DHA ) are independently associated with increased risk of death from coronary heart disease ( CHD ) . In r and omized secondary prevention trials , fish or fish oil have been demonstrated to reduce total and CHD mortality at intakes of about 1 g/day . Red blood cell ( RBC ) fatty acid ( FA ) composition reflects long-term intake of EPA + DHA . We propose that the RBC EPA + DHA ( hereafter called the Omega-3 Index ) be considered a new risk factor for death from CHD . METHODS We conducted clinical and laboratory experiments to generate data necessary for the validation of the Omega-3 Index as a CHD risk predictor . The relationship between this putative marker and risk for CHD death , especially sudden cardiac death ( SCD ) , was then evaluated in several published primary and secondary prevention studies . RESULTS The Omega-3 Index was inversely associated with risk for CHD mortality . An Omega-3 Index of > or = 8 % was associated with the greatest cardioprotection , whereas an index of < or = 4 % was associated with the least . CONCLUSION The Omega-3 Index may represent a novel , physiologically relevant , easily modified , independent , and grade d risk factor for death from CHD that could have significant clinical utility The influence of dietary long chain polyunsaturated fatty acid ( LCP ) supply , and especially of docosahexaenoic acid ( DHA ) , on evoked potential maturation , was studied in 58 healthy preterm infants using flash visual evoked potentials ( VEPs ) , flash electroretinography ( ERG ) , and brainstem acoustic evoked potentials ( BAEPs )  at 52 weeks of postconceptional age . At the same time , the fatty acid composition of red blood cell membranes was examined . The infants were fed on breast milk ( n = 12 ) , a preterm formula supplemented with LCP ( PF-LCP ) ( n = 21 ) , or a traditional preterm formula ( PF ) ( n = 25 ) . In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar ; in the PF group the morphology was quite different and the wave latencies were significantly longer . This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower . Moreover , a higher level of erythrocyte LCP , especially DHA , was found in breast milk and PF-LCP groups compared with the PF group . ERG and BAEP recordings were the same in all three groups . These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available BACKGROUND Dietary intake of fish rich in omega-3 fatty acids is associated with a reduction in cardiovascular events . The mechanisms for this are uncertain and previous studies investigating effects on platelet function have produced inconsistent results . Platelet-monocyte aggregation is a sensitive marker of platelet activation and may contribute to the initiation and progression of atherothrombosis . This study assessed the effect of dietary intervention with oily fish on platelet-monocyte aggregation in healthy subjects . METHODS Fourteen subjects had their diet supplemented with 500 g of oil-rich fish per week for 4 weeks . A control group of 14 subjects received no dietary intervention  over a 4-week period . Platelet-monocyte aggregates were assessed with flow cytometry . RESULTS Dietary intervention with fish led to an increase in omega-3 fatty acids in plasma phospholipids ( 14.2+/-3.4 % versus 5.8+/-1.3 % , P<0.001 ) . In contrast to the control group , platelet-monocyte aggregates were reduced by 35 % following dietary intervention with oily fish ( 16.0+/-9.0 % versus 24.8+/-10.9 % , P<0.01 ) , and returned to basal levels 4 weeks after discontinuation of supplementation . There was an inverse correlation between platelet-monocyte aggregation and plasma omega-3 fatty acid concentrations ( r=-0.421 , P=0.006 ) . There were no changes in the plasma markers of platelet activation , soluble P-selectin or soluble CD40 lig and . CONCLUSIONS We have demonstrated , for the first time , that dietary intervention with oil-rich fish reduces platelet-monocyte aggregation in man . Our results suggest that reduced platelet activation provides a potential mechanism through which fish oils confer their cardiovascular preventative benefits Polyunsaturated fatty acids of n-3 series ( n-3 PUFA ) were shown to increase basal fat oxidation in humans . The aim of the study was to compare the effect of n-3 PUFA added to a very low calorie diet ( VLCD ) , with VLCD only during three-week inpatient weight reduction . Twenty severely obese women were r and omly assigned to VLCD with n-3 PUFA or with placebo .  Fatty acids in serum lipid fractions were quantified by gas chromatography . Differences between the groups were determined using ANOVA . Higher weight ( 7.55+/-1.77 vs. 6.07+/-2.16 kg , NS ) , BMI ( 2.82+/-0.62 vs. 2.22+/-0.74 , p<0.05 ) and hip circumference losses ( 4.8+/-1.81 vs. 2.5+/-2.51 cm , p<0.05 ) were found in the n-3 group as compared to the control group . Significantly higher increase in beta-hydroxybutyrate was found in the n-3 group showing higher ketogenesis and possible higher fatty acid oxidation . The increase in beta-hydroxybutyrate significantly correlated with the increase in serum phospholipid arachidonic acid ( 20:4n-6 ; r = 0.91 , p<0.001 ) . In the n-3 group significantly higher increase was found in n-3 PUFA ( eicosapentaenoic acid , 20:5n-3 , docosahexaenoic acid , 22:6n-3 ) in triglycerides and phospholipids . The significant decrease of palmitoleic acid ( 16:1n-7 ) and vaccenic acid ( 18:1n-7 ) in triglycerides probably reflected lower lipogenesis . A significant negative correlation between BMI change and phospholipid docosahexaenoic acid change was found ( r = -0.595 , p<0.008 ) . The results suggest that long chain n-3 PUFA enhance weight loss in obese females treated by VLCD . Docosahexaenoate ( 22:6n-3 ) seems to be the active component Chronic fish oil intervention had been shown to have a positive impact on endothelial function . Although high-fat meals have often been associated with a loss of postpr and ial vascular reactivity , studies examining the effects of fish oil fatty acids on vascular function in the postpr and ial phase are limited . The aim of the present study was to examine the impact of the addition of fish oil fatty acids to a st and ard test meal on postpr and ial vascular reactivity .  A total of 25 men received in a r and om order either a placebo oil meal ( 40 g of mixed fat ; fatty acid profile representative of the U.K. diet ) or a fish oil meal ( 31 g of mixed fat and 9 g of fish oil ) on two occasions . Vascular reactivity was measured at baseline ( 0 h ) and 4 h after the meal by laser Doppler iontophoresis , and blood sample s were taken for the measurement of plasma lipids , total nitrite , glucose and insulin . eNOS ( endothelial NO synthase ) and NADPH oxidase gene expression were determined in endothelial cells after incubation with TRLs ( triacylglycerol-rich lipoproteins ) isolated from the plasma sample s taken at 4 h. Compared with baseline , sodium nitroprusside ( an endothelium-independent vasodilator)-induced reactivity ( P=0.024 ) and plasma nitrite levels ( P=0.001 ) were increased after the fish oil meal . In endothelial cells , postpr and ial TRLs isolated after the fish oil meal increased eNOS and decreased NADPH oxidase gene expression compared with TRLs isolated following the placebo oil meal ( P</=0.03 ) . In conclusion , meal fatty acids appear to be an important determinant of vascular reactivity , with fish oils significantly improving postpr and ial endothelium-independent vasodilation EthyL-eicosapentanoic acid ( ethyL-EPA ) may be beneficial in the treatment of bipolar disorder ( BD ) and may have a neurotrophic/neuroprotective role in patients with neuropsychiatric disorders . To investigate this we examined whether ethyl-EPA treatment of BD patients is associated with increased brain Levels of N-acetylaspartate ( NAA ) , a putative marker of neuronal integrity . Fourteen female BD out patients with moderate depressive symptoms were administered 2 g of ethyL-EPA per day or placebo for 12 weeks in a r and omized , double-blind fashion . Quantitative , proton magnetic resonance spectroscopy imaging data were obtained prior to r and omization and after 12 weeks of treatment from a single 12 ml volume of interest centred above the body of the corpus callosum . A significant rise in NAA Levels was observed in the ethyl-EPA treatment group compared with the placebo group ( p = 0.027 ) . These results provide the first evidence for a probable neurotrophic role of ethyl-EPA treatment in BD underlining the need for more detailed investigation of its mechanism of action and therapeutic potential BACKGROUND Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer 's disease ( AD ) . Omega-3 fatty acids ( ω-3 FAs ) found in fish and fish oil have several biological properties that may be beneficial in AD . However , they may also auto-oxidize and induce in vivo lipid peroxidation . OBJECTIVE The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary ω-3 FA . METHODS Forty patients with moderate AD were r and omized to receive 1.7 g DHA ( 22:6 ) and 0.6 g EPA ( 20:5 ) or placebo for 6 months . Urinary sample s were collected before and after supplementation . The levels of the major F2-isoprostane , 8-iso-PGF2α , a consistent in vivo biomarker of oxidative stress , and 15-keto-dihydro-PGF2α , a major metabolite of PGF2α and biomarker of inflammatory response , were measured . RESULTS F2-isoprostane in urine increased in the placebo group after 6 months , but there was no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F2-isoprostanes and 15-keto-dihydro-PGF2α . At baseline , the levels of 15-keto-dihydro-PGF2α showed negative correlative relationships to ω-3 FAs , and a positive correlation to linoleic acid . 8-iso-PGF2α correlated negatively to the ω-6 FA arachidonic acid . CONCLUSION The findings indicate that supplementation of ω-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F2-isoprostane or cyclooxygenase-mediated formation of prostagl and in F2α . The correlative relationships to FAs indicate a potential role of FAs in immunoregulation BACKGROUND The influence of prenatal long-chain polyunsaturated fatty acids ( LC-PUFAs ) and folate on neurologic development remains controversial . OBJECTIVE The objective was to assess the long-term effects of n-3 ( omega-3 ) LC-PUFA supplementation , 5-methyltetrahydrofolate ( 5-MTHF ) supplementation , or both in pregnant women on cognitive development of offspring at 6.5 y of age . DESIGN This was a follow-up study of the NUHEAL ( Nutraceuticals for a Healthier Life ) cohort . Healthy pregnant women in 3 European centers were r and omly assigned to 4 intervention groups . From the 20th week of pregnancy until delivery , they received a daily supplement of 500 mg docosahexaenoic acid ( DHA ) + 150 mg eicosapentaenoic acid [ fish oil ( FO ) ] , 400 μg 5-MTHF , or both or a placebo .  Infants received formula containing 0.5 % DHA and 0.4 % arachidonic acid ( AA ) if they were born to mothers receiving FO supplements or were virtually free of DHA and AA until the age of 6 mo if they belonged to the groups that were not supplemented with FO . Fatty acids and folate concentrations were determined in maternal blood at weeks 20 and 30 of pregnancy , at delivery , and in cord blood . Cognitive function was assessed at 6.5 y of age with the Kaufman Assessment Battery for Children ( K-ABC ) . RESULTS We observed no significant differences in K-ABC scores between intervention groups . Higher DHA in maternal erythrocytes at delivery was associated with a Mental Processing Composite Score higher than the 50th percentile in the offspring . CONCLUSION We observed no significant effect of supplementation on the cognitive function of children , but maternal DHA status may be related to later cognitive function in children . This trial was registered at clinical trials.gov as NCT01180933 Obesity is associated with elevated levels of inflammation and metabolic abnormalities which are linked to CVD . The aim of the present study was to investigate whether long-chain n-3 PUFA ( LCn-3PUFA ) , combined with a very-low-energy diet ( VLED ) , facilitated weight loss and weight maintenance , and improvements in blood lipids and inflammatory mediators . This was a double-blind , r and omised , controlled trial with two parallel groups . For 14 weeks , one group consumed 6 × 1 g capsules/d of monounsaturated oil ( placebo group , PB ) , and the other group consumed 6 × 1 g capsules/d of LCn-3PUFA ( fish oil group , FO ) , each comprising 70 mg EPA and 270 mg DHA . Both groups were on VLED for 4 weeks ( n 14 PB , n 18 FO ) , which was then followed by 10 weeks of weight maintenance ( n 12 PB , n 17 FO ) . Fasting blood sample s , anthropometric measurements and 3 d food diaries were collected at baseline , at 4 and 14 weeks . A greater-than-2-fold increase occurred in plasma levels of EPA and DHA in the FO group ( P < 0·001 ) . At 4 weeks , the mean weight loss was -6·54 ( SD 2·08 ) kg ( -6·9 % ) for PB and -6·87 ( SD 1·83 ) kg ( -7·7 % ) for FO . At week 14 , after the maintenance phase , there was a further mean decrease in weight , -1·57 ( SD 3·7 ) kg ( 1·85 % ) for PB and -1·69 ( SD 2·32 ) kg ( -1·9 % ) for FO . Both groups experienced improved metabolic profiles and there was a significant reduction in fat mass for the FO group at week 14 but not for PB . However , it would appear that supplementation with LCn-3PUFA had no significant effect on weight loss or weight maintenance over the 14 weeks Converging evidence suggests that omega-3 polyunsaturated fatty acids have aetiological importance in depression . To determine the effect of adding fish oil to existing therapy in participants who were being treated for depression in a community setting , 77 participants were r and omly assigned to receive 8 g of either fish or olive oil per day in addition to their existing therapy . Fifty-nine ( 77 % ) participants completed 12 weeks of treatment . Dietary , biochemical and lifestyle factors were measured throughout the study . Mood was assessed using the Short Form Hamilton Depression Rating Scale ( HDRS-SF ) and the Beck Depression Inventory II . Sample size calculations were based on the HDRS-SF . Intention-to-treat and per protocol analyses were carried out using residual maximum likelihood . There was no evidence that fish oil improved mood when compared to the placebo oil , despite an increase in circulating omega-3 polyunsaturated fatty acids . However , mood improved significantly in both groups within the first 2 weeks of the study ( P<0.001 ) and this improvement was sustained throughout . In conclusion , fish oil was no more effective than the control as an add-on therapy for depression in this setting Dietary deficiencies in essential omega-3 polyunsaturated fatty acids derived from fish are associated with depression and some fish oils may have therapeutic benefits . We aim ed to determine whether taking tuna fish oil confers any additional benefit to conventional outpatient treatment for major depression . A r and omized double-blind placebo-controlled four-month trial comparing tuna fish oil versus placebo was conducted on 83 out patients with major depression . Despite large reductions in depression there were no significant differences at any assessment time point between patients receiving fish oil compared to placebo .  Red blood cell incorporation of fatty acids indicated good compliance with oil supplementation , although this sample was not initially deficient in omega-3s . This particular dose and type of fish oil conferred no additional benefit to conventional treatment of depression in this sample . Future studies could target participants with pre-existing omega-3 deficiency and appraise alternate enriched types and higher doses of omega-3 supplementation Behavioral distress and dysfunctions of hypothalamic-pituitary-adrenocortical ( HPA ) axis play a central role in alcohol abuse . Omega-3 fatty acids are proposed as having antistress , regulatory effects on HPA responsiveness , but a possible protective role in ethanol addiction is unexplored . A r and omized , doubleblind , placebo-controlled trial was performed in male alcoholics undergoing residential rehabilitation program , to evaluate the effects of 3-week supplementation with fish-oil providing eicosapentaenoic ( 60 mg/day ) and docosahexaenoic acid ( 252 mg/day ) on perceived stress/anxiety and HPA activity , assessed by measuring saliva basal cortisol levels at various daytimes ( 0730 h , 1130 h , 1600 h , 2000 h , and 2400 h ) and the acute cortisol response to  Trier Social Stress Test . Results showed that in supplemented subjects , before versus after decrease of stress/anxiety ratings was accompanied by reduction of cortisol basal levels throughout the day ; no changes were observed in placebo group . At the end of intervention , amplitude , and duration of stress-evoked cortisol response did not differ between groups ; however , the peak of cortisol response was temporally anticipated in supplemented subjects . In conclusion , an elevated omega-3 intake may reduce distress symptoms and basal cortisol secretion in abstinent alcoholics , thus providing a valid subsidiary measure to increase the efficacy of rehabilitation programs in ethanol addicts BACKGROUND n-3 Fatty acid supplementation in adults results in cardiovascular benefits . However , the cardiovascular effects of n-3 supplementation in early childhood are unknown . OBJECTIVE The objective was to evaluate blood pressure ( BP ) and arterial structure and function in 8-y-old children who had participated in a r and omized controlled trial of dietary n-3 and n-6 modification over the first 5 y of life . DESIGN The children ( n = 616 ; 49 % girls ) were r and omly assigned antenatally to active ( n = 312 ; increase in n-3 intake and decrease in n-6 intake ) or control ( n = 304 ) diet interventions implemented from the time of weaning or introduction of solids until 5 y of age . At age 8.0 + /- 0.1 y , BP , carotid intima-media thickness , carotid artery distensibility , augmentation index , and brachial pulse wave velocity were measured in 405 of these children . Venous blood was collected for measurement of plasma fatty acids , lipoproteins , high-sensitivity C-reactive protein , and asymmetric dimethylarginine . Plasma fatty acid concentrations were also assessed during the intervention . RESULTS Plasma concentrations of n-3 fatty acids were higher and of n-6 were lower in the active than in the control diet group at 18 mo and 3 and 5 y ( P < 0.0001 ) . Concentrations of n-3 and n-6 fatty acids were similar at 8 y. At 8 y of age , no significant differences were found in BP , carotid intima-media thickness , carotid artery distensibility , augmentation index , asymmetric dimethylarginine , high-sensitivity C-reactive protein , or lipoproteins between diet groups . CONCLUSION A dietary supplement intervention to increase n-3 and decrease n-6 intakes from infancy until 5 y does not result in significant improvements in arterial structure and function at age 8 y. This trial was registered at the Australian Clinical Trials Registry as ACTRN012605000042640 Background / objectives : Consumption of oily fish more than once per week has been shown to improve cognitive outcomes in children . However , it is unknown whether similar benefits can be achieved by long-term omega-3 fatty acid supplementation . The objective was to investigate the effect of omega-3 fatty acid supplementation during the first 5 years of life on subsequent academic performance in children by conducting a secondary analysis of the CAPS ( Childhood Asthma Prevention Study ) .Subjects/ methods : A total of 616 infants with a family history of asthma were r and omised to receive tuna fish oil ( high in long-chain omega-3 fatty acids , active ) or Sunola oil ( low in omega-3 fatty acids , control ) from the time breastfeeding ceased or at the age of 6 months until the age of 5 years . Academic performance was measured by a nationally st and ardised assessment of literacy and numeracy ( National Assessment Program Literacy and Numeracy ( NAPLAN ) ) in school years 3 , 5 , 7 and 9 . Plasma omega-3 fatty acid levels were measured at regular intervals until 8 years of age . Between-group differences in test scores , adjusted for maternal age , birth weight and maternal education , were estimated using mixed-model regression . Results : Among 239 children , there were no significant differences in NAPLAN scores between active and control groups . However , at 8 years , the proportion of omega-3 fatty acid in plasma was positively associated with the NAPLAN score ( 0.13 s.d . unit increase in score per 1 % absolute increase in plasma omega-3 fatty acid ( 95 % CI 0.03 , 0.23 ) ) . Conclusions : Our findings do not support the practice of supplementing omega-3 fatty acids in the diet of young children to improve academic outcomes . Further exploration is needed to underst and the association between plasma omega-3 fatty acid levels at 8 years and academic performance OBJECTIVES . Arachidonic acid ( 20:4n-6 ) and docosahexaenoic acid ( 22:6n-3 ) are essential for brain growth and cognitive development . We have reported that supplementing pregnant and lactating women with n-3 very-long-chain polyunsaturated fatty acids promotes higher IQ scores at 4 years of age as compared with maternal supplementation with n-6 polyunsaturated fatty acids . In our present study , the children were examined at 7 years of age with the same cognitive tests as at 4 years of age . We also examined the relation between plasma fatty acid pattern and BMI in children , because an association between arachidonic acid and adipose tissue size has been suggested . METHODS . The study was r and omized and double-blinded . The mothers took 10 mL of cod liver oil or corn oil from week 18 of pregnancy until 3 months after delivery . Their children were tested with the Kaufman Assessment Battery for Children at 7 years of age , and their height and weight were measured . RESULTS . We did not find any significant differences in scores on the Kaufman Assessment Battery for Children test at 7 years of age between children whose mothers had taken cod liver oil ( n = 82 ) or corn oil ( n = 61 ) . We observed , however , that maternal plasma phospholipid concentrations of α-linolenic acid ( 18:3n-3 ) and docosahexaenoic acid during pregnancy were correlated to sequential processing at 7 years of age . We observed no correlation between fatty acid status at birth or during the first 3 months of life and BMI at 7 years of age . CONCLUSION . This study suggests that maternal concentration of n-3 very-long-chain polyunsaturated fatty acids during pregnancy might be of importance for later cognitive function , such as sequential processing , although we observed no significant effect of n-3 fatty acid intervention on global IQs . Neonatal fatty acid status had no influence on BMI at 7 years of age OBJECTIVES The aim of the study was to investigate whether fish oil supplementation affected Japanese schoolchildren 's behavior , with changes in aggression over time as the primary endpoint . DESIGN AND SUBJECTS A placebo-controlled double-blind study with 166 schoolchildren 9 - 12 years of age was performed . The subjects of the fish oil group ( n=83 ) took fish oil-fortified foods ( bread , sausage and spaghetti ) . These foods were provided in amounts such that each subject in the fish oil group had an intake of 3600 mg of docosahexaenoic acid+840 mg of eicosapentaenoic acid (EPA)/week for 3 months . The rest ( the controls , n=83 ) took control supplements . At the start and end of the study , psychological tests were performed to assess their aggression . RESULTS Physical aggression assessed by Hostility-Aggression Question naire for Children in girls increased significantly ( median : 13 to 15 , n=42 ) in the control group and did not change ( 13 to 13 , n=43 ) in the fish oil group with a significant intergroup difference ( P=.008 ) with baseline as covariate . The changes in physical aggression scores over time and those of the ratio of EPA/arachidonic acid in RBC ( DeltaEPA/AA ) were significantly correlated in girls who agreed to blood collection ( r=-.53 , P=.01 , n=23 ) . On the contrary , there were no significant changes in physical aggression in boys . Aggression against others ( extraggression ) assessed by Picture Frustration Study did not change in the control group ( median : 5 to 5 ) but increased significantly in the fish oil group ( 4 to 5 ) with a significant intergroup difference ( P=.02 ) with baseline as covariate . These changes in extraggression might be explained partly by significantly lower baseline values of extraggression in the fish oil group ( P=.02 ) than in the control group . There were no significant correlations between Deltaextraggression and DeltaEPA/AA in blood- sample d children ( n=49 ) . Impulsivity of girls assessed by parents/guardians using the diagnostic criteria for attention deficit/hyperactivity disorder of DSM-IV was reduced in the fish oil group ( 1 to 0 ) with a significant ( P=.008 ) intergroup difference from the control group ( 1 to 1 ) . There were no significant correlations between Delt aim pulsivity and DeltaEPA/AA in blood- sample d girls . In males , impulsivity reduced in both groups without any intergroup differences . CONCLUSION There is a possibility that changes in fatty acid nutrition might affect physical aggression especially in girls BACKGROUND There is uncertainty regarding the efficacy of increasing n-3 long-chain PUFA ( LCPUFA ) intake during pregnancy in reducing the risk of  gestational diabetes mellitus ( GDM ) and preeclampsia .  OBJECTIVES The objective was to determine whether n-3 LCPUFA supplementation in pregnancy reduces the incidence of GDM or preeclampsia . A secondary objective was to assess the effect of n-3 LCPUFA supplementation on perinatal complications . DESIGN This was a double-blind , multicenter r and omized control trial-the DHA to Optimize Mother Infant Outcome ( DOMInO ) trial . Pregnant women ( n = 2399 ) of < 21 wk gestation were r and omly assigned to receive DHA-enriched fish oil ( 800 mg/d ) or vegetable oil capsules without DHA from trial entry to birth . The presence of GDM or preeclampsia was assessed through a blinded audit of medical records . Birth outcomes and prenatal complications were also assessed . RESULTS The overall incidences of GDM and preeclampsia were 8 % and 5 % , respectively , based on clinical diagnosis . The RR of GDM was 0.97 ( 95 % CI : 0.74 , 1.27 ) and of preeclampsia was 0.87 ( 95 % CI : 0.60 , 1.25 ) , and they did not differ significantly between the groups . Birth weight , length , and head circumference z scores also did not differ between the groups . There were 12 perinatal deaths and 5 neonatal convulsions in the control group compared with 3 perinatal deaths and no neonatal convulsions in the DHA group ( P = 0.03 in both cases ) . CONCLUSION DHA supplementation of 800 mg/d in the second half of pregnancy does not reduce the risk of GDM or preeclampsia . Whether supplementation reduces the risk of perinatal death and neonatal convulsions requires further investigation . The DOMInO trial was registered with the Australian New Zeal and Clinical Trials Registry as TRN12605000569606 Full-field electroretinograms ( ERGs ) were obtained from very-low-birth-weight ( VLBW ) neonates to determine whether omega-3 ( omega-3 ) fatty acids are essential for normal human retinal development . Eighty-one infants born at 30.4 ( st and ard deviation , + /- 1.5 ) wk gestation were , within 10 d of birth , either enrolled to receive mother 's milk ( naturally containing both omega-6 and omega-3 essential fatty acids ) or  r and omized to receive one of the infant formulas . Corn oil-based Formula A contained mainly linoleic acid ( 18:2 omega-6 ) and was low in all omega-3 fatty acids . Soy oil-based Formula B contained ample alpha-linolenic acid ( 18:3 omega-3 ) but no long-chain omega-3 . Formula C , supplemented with both alpha-linolenic acid and marine oils , was comparable to human milk in long-chain omega-3 . Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception . Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception . Significant differences were found among groups in rod ERG function . Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain omega-3 ( human milk , Formula C , and intrauterine ) . Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition . Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level . Differences were not present in infants at 57 wk postconception . No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception . Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk . These findings suggest that retinal function varies with the dietary supply of omega-3 fatty acids in VLBW infants Objectives : The aim of the present study was to eluci date whether a dairy drink enriched with & ohgr;-3 long-chain polyunsaturated fatty acid ( LC-PUFA ) could have an impact on the lipid profile of the mother and the newborn , and also whether this intervention could affect the newborns ’ visual and cognitive development . Methods : A total of 110 pregnant women were r and omly assigned to one of the following intervention groups : control group ( n = 54 ) , taking 400 mL/day of the control dairy drink , and supplemented group ( fish oil [ FO ] ) ( n = 56 ) , taking 400 mL/day of the fish oil – enriched dairy drink ( including ∼400 mg eicosapentaenoic acid – docosahexaenoic acid [DHA]/day ) . During the study , the mothers ’ diets were supervised by a nutritionist to encourage compliance with present recommendations of FA intake . Blood fatty acid profiles were determined in the mother 's ( at enrollment , at delivery , and at 2.5 and 4 months ) and newborn ( at delivery and at 2.5 months ) placenta and breast milk ( colostrum and at 1 , 2 , and 4 months ) . Pattern reversal visual evoked potentials ( VEPs ) ( at 2.5 and 7.5 months ) and Bayley test ( at 12 months ) were recorded . Results : DHA percentage was higher in plasma , erythrocyte membranes , and breast milk sample s from the FO group . The ratio of nervonic acid was also higher in plasma and erythrocyte lipids of the mother and newborn 's blood sample s from the FO group . No differences were observed in the Bayley test . No differences were observed in VEPs between both groups . We observed a shorter latency , however , in the lower visual angle ( 7.5′ ) in the boys of the supplemented group . Conclusions : Omega-3 LC-PUFA dietary supplement during pregnancy and lactation influenced the mother and newborn 's fatty acid profile and nervonic acid content but did not show effects on visual and cognitive/psychomotor development OBJECTIVES : Impaired fetal growth is an independent cardiovascular risk factor and is associated with arterial wall thickening in children . No preventive strategy has been identified . We sought to determine whether dietary omega-3 fatty acid supplementation during early childhood prevents the association between impaired fetal growth and carotid arterial wall thickening . METHODS : The Childhood Asthma Prevention Study was a r and omized , controlled single-blind trial in 616 children born at term , recruited antenatally from maternity hospitals in Sydney . Participants were r and omized to either a 500-mg-daily fish oil supplement and canola-based margarines and cooking oil ( omega-3 group ) , or a 500-mg-daily sunflower oil supplement and omega-6 fatty acid – rich margarines and cooking oil ( control group ) , from the start of bottle-feeding or 6 months of age until 5 years of age . Carotid intima-media thickness ( IMT ) , a noninvasive measure of sub clinical atherosclerosis , was the primary endpoint of a cardiovascular sub study ( CardioCAPS ) at age 8 years . We examined the association of fetal growth with carotid IMT in children with birth weight < 90th percentile ( omega-3 group [ n = 187 ] , control group [ n = 176 ] ) . RESULTS : In the control group , fetal growth was inversely associated with carotid IMT , but this was prevented in the omega-3 group ( difference between groups of 0.041 mm [ 95 % confidence interval 0.006 , 0.075 ] per kg birth weight , adjusted for gestational age and gender , Pheterogeneity = .02 ) . CONCLUSIONS : The inverse association of fetal growth with arterial wall thickness in childhood can be prevented by dietary omega-3 fatty acid supplementation over the first 5 years of life Omega-3 polyunsaturated fatty acids in fish oils may have antifibrillatory effects ; however , their electrophysiologic effects in paroxysmal atrial fibrillation ( PAF ) remain unknown . The aim of this study was to investigate the effects of chronic fish oil supplementation on human pulmonary vein ( PV ) and left atrial electrophysiology in PAF . Patients with PAF undergoing PV isolation were r and omized ≥1 month before their procedure into a control group ( n = 18 ) or a fish oil group ( n = 18 ) in an unblinded fashion . The latter were supplemented with fish oil 6 g/day for a mean of 40 ± 12 days . Pulmonary venous and left atrial effective refractory periods ( ERPs ) , PV conduction , and susceptibility to AF initiated within PVs were assessed . Compared to the control group , the fish oil group had ( 1 ) longer left-sided ( p = 0.002 ) and right-sided ( p = 0.001 ) pulmonary venous ERPs ; ( 2 ) less dispersion of pulmonary venous ERPs ( left PVs p = 0.001 , right PVs p = 0.07 ) ; ( 3 ) longer left atrial ERPs ( p = 0.02 ) ; ( 4 ) no difference in pulmonary venous conduction ; ( 5 ) lower incidence of AF initiated from PVs during ERP testing ( 77 % vs 31 % , p = 0.02 ) ; and ( 6 ) prolongation of mean AF cycle length ( p = 0.009 ) and shortest AF cycle length in PVs ( p = 0.04 ) . In conclusion , patients with PAF chronically supplemented with fish oils exhibit distinctive electrophysiologic properties including prolonged pulmonary venous and left atrial ERPs and decreased susceptibility to initiation AF from within PVs . These changes may in part explain the antifibrillatory effect of chronic omega-3 polyunsaturated fatty acid supplementation in patients with PAF Omega-3 fatty acids ( n-3 ) can improve cardiovascular ( CV ) function . This study examined the effects of n-3 on endurance performance , recovery and CV risk factors in elite Australian Rules football players . 25 players were r and omised , double-blind , to 6 g/day of docosahexaenoic acid (DHA)-rich fish oil ( FO ; n=12 ) or sunflower oil ( SO ; n=13 ) during 5 weeks of training . At baseline erythrocyte n-3 content , resting blood pressure ( BP ) , fasting serum triglycerides ( TG ) and heart rate ( HR ) during treadmill running at 10 km/h were assessed . Two treadmill runs ( T1 and T2 ) to exhaustion , separated by 5 min , were then performed at the average speed for a recent 2200 m time-trial . After 5 weeks , erythrocyte n-3 increased ( FO 3.8+/-0.6 % , SO 0.6+/-0.3 % ; P<0.001 ) while TG ( FO -0.32+/-0.09 mmol l(-1 ) , SO 0.08+/-0.05 mmol l(-1 ) ; P<0.001 ) , diastolic BP ( FO 1.3+/-1.3 mmHg , SO 6.8+/-1.7 mmHg ; P=0.04 ) and HR during submaximal exercise ( FO -7.8+/-2.3 beats min(-1 ) , SO -1.9+/-1.9 beats min(-1 ) ; P=0.03 ) decreased in FO compared with SO . Time to exhaustion ( TTE ) during T1 increased by Week 5 ( FO 10.2+/-2.2 % , SO 17.3+/-4.3 % ; P<0.001 for time ) . Recovery ( TTE for T2 as % T1 ) decreased in both groups ( FO , -3.4+/-4.5 % , SO -8.8+/-3.9 % ; P=0.05 for time ) . We conclude that 5 weeks of supplementation with FO improved CV function and reduced CV risk factors , but did not improve endurance performance or recovery in elite Australian Rules footballers AIM To determine the effect of neonatal docosahexaenoic acid ( DHA ) supplementation in preterm infants on later respiratory-related hospitalisations . METHODS We enrolled 657 infants in a multicentre , r and omised , controlled trial design ed to study the long-term efficacy of higher dose dietary DHA in infants born <33 weeks ' gestation . Treatment was with high DHA ( ∼1 % ) compared with st and ard DHA ( ∼0.3 % ) in breast milk or formula , given from the first week of life to term equivalent . Parent-reported hospital admissions to 18 months corrected age were recorded . The proportion of children hospitalised for lower respiratory tract ( LRT ) conditions and the mean number of hospitalisations per infant were determined . RESULTS Twenty-three per cent ( 154/657 ) of infants were hospitalised for LRT conditions . Seventy-three per cent ( 173/238 ) of admissions were for bronchiolitis . There was no significant effect of higher DHA on the proportion of infants admitted for LRT conditions ( high DHA 22 % vs. st and ard DHA 25 % , adjusted relative risk 0.92 , 95 % confidence interval ( CI ) 0.68 - 1.24 , P = 0.57 ) or in the mean number of admissions per infant ( high DHA 0.34 , st and ard DHA 0.38 , adjusted ratio of means 0.91 , 95 % CI 0.63 - 1.32 , P = 0.62 ) . The sexes responded differently to treatment ( interaction P = 0.046 ) , with reduced admissions in boys given high DHA , but this was not statistically significant ( high DHA 19 % , st and ard DHA 28 % , adjusted relative risk 0.69 , 95 % CI 0.46 - 1.04 , P = 0.08 ) . CONCLUSIONS Hospitalisation for LRT problems in the first 18 months for preterm infants was not reduced by neonatal supplementation with 1 % DHA OBJECTIVES Maternal deficiency of the omega-3 fatty acid , docosahexaenoic acid ( DHA ) , has been associated with perinatal depression , but there is evidence that supplementation with eicosapentaenoic acid ( EPA ) may be more effective than DHA in treating depressive symptoms . This trial tested the relative effects of EPA- and DHA-rich fish oils on prevention of depressive symptoms among pregnant women at an increased risk of depression . STUDY DESIGN We enrolled 126 pregnant women at risk for depression ( Edinburgh Postnatal Depression Scale score 9 - 19 or a history of depression ) in early pregnancy and r and omly assigned them to receive EPA-rich fish oil ( 1060 mg EPA plus 274 mg DHA ) , DHA-rich fish oil ( 900 mg DHA plus 180 mg EPA ) , or soy oil placebo . Subjects completed the Beck Depression Inventory ( BDI ) and Mini-International Neuropsychiatric Interview at enrollment , 26 - 28 weeks , 34 - 36 weeks , and at 6 - 8 weeks ' postpartum . Serum fatty acids were analyzed at entry and at 34 - 36 weeks ' gestation . RESULTS One hundred eighteen women completed the trial . There were no differences between groups in BDI scores or other depression endpoints at any of the 3 time points after supplementation . The EPA- and DHA-rich fish oil groups exhibited significantly increased postsupplementation concentrations of serum EPA and serum DHA respectively . Serum DHA- concentrations at 34 - 36 weeks were inversely related to BDI scores in late pregnancy . CONCLUSION EPA-rich fish oil and DHA-rich fish oil supplementation did not prevent depressive symptoms during pregnancy or postpartum CONTEXT Uncertainty exists about the benefit of dietary docosahexaenoic acid ( DHA ) on the  neurodevelopment of preterm infants . OBJECTIVE To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months ' corrected age . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind controlled trial enrolling infants born at less than 33 weeks ' gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals , with follow-up to 18 months . INTERVENTION High-DHA ( approximately 1 % total fatty acids ) enteral feeds compared with st and ard DHA ( approximately 0.3 % total fatty acids ) from day 2 to 4 of life until term corrected age . MAIN OUTCOME MEASURES Bayley Mental Development Index ( MDI ) at 18 months ' corrected age . A priori subgroup analyses were conducted based on r and omization strata ( sex and birth weight < 1250 g vs > or = 1250 g ) . RESULTS Of the 657 infants enrolled , 93.5 % completed the 18-month follow-up . Bayley MDI scores did not differ between the high- and st and ard-DHA groups ( mean difference , 1.9 ; 95 % confidence interval [ CI ] , -1.0 to 4.7 ) . The MDI among girls fed the high-DHA diet was higher than girls fed st and ard DHA in unadjusted and adjusted analyses ( unadjusted mean difference , 4.7 ; 95 % CI , 0.5 - 8.8 ; adjusted mean difference , 4.5 ; 95 % CI , 0.5 - 8.5 ) . The MDI among boys did not differ between groups . For infants born weighing less than 1250 g , the MDI in the high-DHA group was higher than with st and ard DHA in the unadjusted comparison ( mean difference , 4.7 ; 95 % CI , 0.2 - 9.2 ) but did not reach statistical significance following adjustment for gestational age , sex , maternal education , and birth order ( mean difference , 3.8 ; 95 % CI , -0.5 to 8.0 ) . The MDI among infants born weighing at least 1250 g did not differ between groups . CONCLUSION A DHA dose of approximately 1 % total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12606000327583 AMR101 is an ω-3 fatty acid agent containing ≥96 % pure icosapent-ethyl , the ethyl ester of eicosapentaenoic acid . The efficacy and safety of AMR101 were evaluated in this phase 3 , multicenter , placebo-controlled , r and omized , double-blinded , 12-week clinical trial ( ANCHOR ) in high-risk statin-treated patients with residually high triglyceride ( TG ) levels ( ≥200 and < 500 mg/dl ) despite low-density lipoprotein ( LDL ) cholesterol control ( ≥40 and < 100 mg/dl ) . Patients ( n = 702 ) on a stable diet were r and omized to AMR101 4 or 2 g/day or placebo  . The primary end point was median percent change in TG levels from baseline versus placebo at 12 weeks . AMR101 4 and 2 g/day significantly decreased TG levels by 21.5 % ( p < 0.0001 ) and 10.1 % ( p = 0.0005 ) , respectively , and non-high-density lipoprotein ( non-HDL ) cholesterol by 13.6 % ( p < 0.0001 ) and 5.5 % ( p = 0.0054 ) , respectively . AMR101 4 g/day produced greater TG and non-HDL cholesterol decreases in patients with higher-efficacy statin regimens and greater TG decreases in patients with higher baseline TG levels . AMR101 4 g/day decreased LDL cholesterol by 6.2 % ( p = 0.0067 ) and decreased apolipoprotein B ( 9.3 % ) , total cholesterol ( 12.0 % ) , very-low-density lipoprotein cholesterol ( 24.4 % ) , lipoprotein-associated phospholipase A(2 ) ( 19.0 % ) , and high-sensitivity C-reactive protein ( 22.0 % ) versus placebo ( p < 0.001 for all comparisons ) . AMR101 was generally well tolerated , with safety profiles similar to placebo . In conclusion , AMR101 4 g/day significantly decreased median placebo-adjusted TG , non-HDL cholesterol , LDL cholesterol , apolipoprotein B , total cholesterol , very-low-density lipoprotein cholesterol , lipoprotein-associated phospholipase A(2 ) , and high-sensitivity C-reactive protein in statin-treated patients with residual TG elevations BACKGROUND Risk factors of cardiovascular disease such as lipid aberrations , hypertension , abdominal adiposity and elevations in systemic inflammation , are prominent aetiologies in hyperlipidemia . Supplementation with n-3 PUFA is associated with a reduction in cardiovascular events through its hypotriglyceridemic , anti-aggregatory and anti-inflammatory properties . Plant sterols have potent hypocholesterolemic properties , although their effect on the inflammatory cascade is uncertain . This study investigated the effect of combined supplementation with n-3 PUFA and plant sterols on cardiovascular risk factors , blood pressure , body composition , markers of systemic inflammation and overall risk , in hyperlipidemic individuals . METHODS The study was a 3-week r and omised , double-blind , placebo-controlled , 2 x 2 factorial design , in four parallel groups . Sixty hyperlipidemic participants were r and omised to receive either sunola oil or 1.4 g/d n-3 PUFA capsules with or without 2 g plant sterols per day . RESULTS The combination of n-3 PUFA and plant sterols reduced several inflammatory markers . High sensitivity C-reactive protein ( hs-CRP ) was reduced by 39 % ( P=0.009 ) , tumor necrosis factor-alpha ( TNF-alpha ) by 10 % ( P=0.02 ) , interleukin-6 ( IL-6 ) by 10.7 % ( P=0.009 ) , leukotriene B(4 ) ( LTB(4 ) ) by 29.5 % ( P=0.01 ) and adiponectin was increased by 29.5 % ( P=0.05 ) . Overall cardiovascular risk was reduced by 22.6 % ( P=0.006 ) in the combination group . CONCLUSION We have demonstrated , for the first time that dietary intervention with n-3 PUFA and plant sterols reduces systemic inflammation  in hyperlipidemic individuals . Furthermore , our results suggest that reducing inflammation provides a potential mechanism by which the combination of n-3 PUFA and plant sterols are cardioprotective Abstract Introduction : Low dietary intake of docosahexaenoic acid ( DHA ) and /or foods rich in lutein may be associated with increased risk of cognitive decline in the elderly . Subjects and methods : The cognitive benefit of DHA and lutein in unimpaired elder women was explored in the context of a 4-month , double-blind , intervention trial of DHA and lutein supplementation for eye health . Forty-nine women ( aged 60–80 years ) were r and omized to receive DHA ( 800 mg/day ; n = 14 ) , lutein ( 12 mg/day ; n = 11 ) , a combination of DHA and lutein ( n = 14 ) or placebo ( n = 10 ) . Subjects underwent cognitive tests measuring verbal fluency , memory , processing speed and accuracy , and self-reports of mood at r and omization and upon completion of the trial . Results : Following supplementation , verbal fluency scores improved significantly in the DHA , lutein , and combined treatment groups ( P < 0.03 ) . Memory scores and rate of learning improved significantly in the combined treatment group ( P < 0.03 ) , who also displayed a trend toward more efficient learning ( P = 0.07 ) . Measures of mental processing speed , accuracy and mood were not affected by supplementation . Conclusions : These exploratory findings suggest that DHA and lutein supplementation may have cognitive benefit for older adults OBJECTIVE To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing  exudative age-related macular degeneration ( AMD ) . DESIGN The Nutritional AMD Treatment 2 study was a r and omized , placebo-controlled , double-blind , parallel , comparative study . PARTICIPANTS Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye . METHODS Patients were assigned r and omly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid ( EPA ) from fish oil capsules or the placebo ( olive oil capsules ) for 3 years . MAIN OUTCOME MEASURES The primary outcome measure was time to occurrence of choroidal neovascularization ( CNV ) in the study eye . Secondary outcome measures in the study eye were : incidence of CNV developing in patients , changes in visual acuity , occurrence and progression of drusen , and changes in EPA plus DHA level in red blood cell membrane ( RBCM ) . RESULTS Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group ( 19.5±10.9 months and 28.4 % , respectively ) and the placebo group ( 18.7±10.6 months and 25.6 % , respectively ) . In the DHA group , EPA plus DHA levels increased significantly in RBCM ( + 70 % ; P<0.001 ) , suggesting that DHA easily penetrated cells , but this occurred unexpectedly also in the placebo group ( + 9 % ; P = 0.007 ) . In the DHA-allocated group , patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk ( -68 % ; P = 0.047 ; hazard ratio , 0.32 ; 95 % confidence interval , 0.10 - 0.99 ) of CNV developing over 3 years . No marked changes from baseline in best-corrected visual acuity , drusen progression , or geographic atrophy in the study eye were observed throughout the study in either group . CONCLUSIONS In patients with unilateral exudative AMD , 3 years of oral DHA-enriched supplementation had the same effect on CNV incidence in the second eye as did the placebo . However , RBCM fatty acid measurements revealed that CNV incidence was significantly reduced in DHA-supplemented patients showing a steadily high EPA plus DHA index over 3 years . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references BACKGROUND AND AIMS Omega-3 polyunsaturated fatty acids ( PUFAs ) are natural peroxisome proliferator-activated receptor gamma ( PPAR-γ ) lig and s. Activated PPAR-γ protects the cardiovascular system against atherosclerotic lesion formation and exerts its anti-inflammatory role by suppressing cytokines induced by nuclear factor kappa-B ( NF-κB ) in endothelial cells ( ECs ) , and it is hypothesized that apoptosis and cell cycle arrest induced by PPAR-γ lig and s may be mediated by the p53-dependent pathway . The aim of our study was to investigate the effects of docosahexaenoic acid (DHA)-enriched fish oil supplement on PPAR-γ activity and mRNA expression levels of p53 and NF-κB. METHODS AND RESULTS Fifty patients with type 2 diabetes mellitus ( T2DM ) aged 30 - 70 years were r and omly assigned to receive either 2400 mg/d DHA-rich fish oil or placebo for 8 weeks . Metabolic parameters were assessed at baseline and at the end of the intervention . PPAR-γ activity in the peripheral blood mononuclear cells ( P BMC s ) was measured using ELISA-based PPAR-γ Transcription Factor Assay Kit , and the gene expression levels of p53 and NF-κB were assessed using real-time quantitative reverse transcription polymerase chain reaction ( RT-PCR ) . On the basis of our finding , 8 weeks of treatment with DHA-rich fish oil  increased PPAR-γ activity in P BMC s of subjects with T2DM ( p < 0.01 ) compared to that in placebo ( p = 0.4 ) . Between-group comparisons of mean PPAR-γ activity changes showed significant differences ( p = 0.03 ) , whereas mRNA expression levels of the p53 and NF-κB genes did not show significant differences between studied groups ( p = 0.2 and p = 0.5 , respectively ) . CONCLUSION Our findings indicated that short-term DHA-rich fish oil supplementation may modulate PPAR-γ activity in P BMC
ABSTRACT The health benefits of fish oil , and its omega-3 long chain polyunsaturated fatty acid content , have attracted much scientific attention in the last four decades .
Fish oils that contain higher amounts of eicosapentaenoic acid ( EPA ; 20:5n-3 ) than docosahexaenoic acid ( DHA ; 22:6n-3 ) , in a distinctive ratio of 18/12 , are typically the most abundantly available and are commonly studied .
Although the two fatty acids have traditionally been considered together , as though they were one entity , different physiological effects of EPA and DHA have recently been reported .
New oils containing a higher quantity of DHA compared with EPA , such as fractionated and concentrated fish oil , tuna oil , calamari oil and microalgae oil , are increasingly becoming available on the market , and other oils , including those extracted from genetically modified oilseed crops , soon to come .
This systematic review focuses on the effects of high DHA fish oils on various human health conditions , such as the  heart and cardiovascular system , the brain and visual function , inflammation and immune function and growth/Body Mass Index .