Effects of a dairy product (pecorino cheese) naturally rich in cis-9, trans-11 conjugated linoleic acid on lipid, inflammatory and haemorheological variables: a dietary intervention study. The atherosclerotic risk profile is affected differently by fish flesh with a similar EPA and DHA content but different n-6/n-3 ratio. Influence of n-6 versus n-3 polyunsaturated fatty acids in diets low in saturated fatty acids on plasma lipoproteins and hemostatic factors. Effect of CLA supplementation on immune function in young healthy volunteers Fatty acid content of serum lipid fractions and blood lipids in normolipidaemic volunteers fed two types of cheese having different fat compositions: a pilot study Decreased Plasma Cholesterol Concentrations After PUFA-Rich Diets are not Due to Reduced Cholesterol Absorption/Synthesis Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids. The acute effects of a single very high dose of n−3 fatty acids on plasma lipids and lipoproteins in healthy subjects The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects. The effect of palmitic acid on lipoprotein cholesterol levels and endogenous cholesterol synthesis in hyperlipidemic subjects Effects of dietary α-linolenic acid from blended oils on biochemical indices of coronary heart disease in indians The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans. Effects of saturated, monounsaturated, and omega-6 polyunsaturated fatty acids on plasma lipids, lipoproteins, and apoproteins in humans. 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. Linoleic-acid-enriched diet: long-term effects on serum lipoprotein and apolipoprotein concentrations and insulin sensitivity in noninsulin-dependent diabetic patients. Dependence of the effects of dietary cholesterol and experimental conditions on serum lipids in man. II. Effects of dietary cholesterol in a linoleic acid-poor diet. Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45-70 y: the OPTILIP Study. Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F(2)-isoprostanes. Blood pressure lowering in elderly subjects: a double-blind crossover study of omega-3 and omega-6 fatty acids. Plasma cholesterol-lowering potential of edible-oil blends suitable for commercial use. An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women. Acute ingestion of a meal rich in n-3 polyunsaturated fatty acids results in rapid gastric emptying in humans. Does vegetable oil attenuate the beneficial effects of fish oil in reducing risk factors for cardiovascular disease? Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans. Olive oil, corn oil, and n-3 fatty acids differently affect lipids, lipoproteins, platelets, and superoxide formation in type II hypercholesterolemia. Effect on plasma lipids of interesterifying a mix of edible oils. Dietary modification of omega 6 fatty acid intake and its effect on urinary eicosanoid excretion. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. Markers of dietary fat quality and fatty acid desaturation as predictors of total and cardiovascular mortality: a population-based prospective study. Comparison of the effects of medium-chain triacylglycerols, palm oil, and high oleic acid sunflower oil on plasma triacylglycerol fatty acids and lipid and lipoprotein concentrations in humans. High linoleic acid, low vegetable, and high oleic acid, high vegetable diets affect platelet activation similarly in healthy women and men. Plant and marine derived (n-3) polyunsaturated fatty acids do not affect blood coagulation and fibrinolytic factors in moderately hyperlipidemic humans. Increased n-6 polyunsaturated fatty acids do not attenuate the effects of long-chain n-3 polyunsaturated fatty acids on insulin sensitivity or triacylglycerol reduction in Indian Asians. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Dietary supplementation with cis-9,trans-11 conjugated linoleic acid and aortic stiffness in overweight and obese adults. Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids? Cis-9, trans- 11 and trans-10, cis-12 conjugated linoleic acid (CLA) do not affect the plasma lipoprotein profile in moderately overweight subjects with LDL phenotype B. Alpha-linolenic acid in rapeseed oil partly compensates for the effect of fish restriction on plasma long chain n-3 fatty acids. Supplementation of postmenopausal women with fish oil does not increase overall oxidation of LDL ex vivo compared to dietary oils rich in oleate and linoleate. Effects of Diets High in Walnuts and Flax Oil on Hemodynamic Responses to Stress and Vascular Endothelial Function Effects of essential fatty acids on mild to moderate essential hypertension. Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Effect of supplementation with an 80:20 cis9,trans11 conjugated linoleic acid blend on the human platelet proteome. Supplementation With Conjugated Linoleic Acid Causes Isomer-Dependent Oxidative Stress and Elevated C-Reactive Protein: A Potential Link to Fatty Acid-Induced Insulin Resistance Conjugated Linoleic Acid Impairs Endothelial Function Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese. Impact of Mediterranean diet education versus posted leaflet on dietary habits and serum cholesterol in a high risk population for cardiovascular disease. Effects of safflower seed extract supplementation on oxidation and cardiovascular risk markers in healthy human volunteers. Improvement of serum lipids and blood pressure during intervention with n-3 fatty acids was not associated with changes in insulin levels in subjects with combined hyperlipidaemia. Effects of flaxseed oil supplementation on plasma adiponectin levels in dyslipidemic men Supplementation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. The effect of replacing dietary saturated fat with polyunsaturated or monounsaturated fat on plasma lipids in free-living young adults Increased α-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis Effects of conjugated linoleic acid plus n-3 polyunsaturated fatty acids on insulin secretion and estimated insulin sensitivity in men A comparison of the influence on plasma lipids and platelet function of supplements of omega 3 and omega 6 polyunsaturated fatty acids. The effect of cod liver oil and corn oil on platelets and vessel wall in man. Comparing palmolein with different predominantly monounsaturated oils: effect on plasma lipids Effect of altering dietary n-6:n-3 PUFA ratio on cardiovascular risk measures in patients treated with statins: a pilot study. Oily fish reduces plasma triacylglycerols: a primary prevention study in overweight men and women. Comparison of the effects of two low fat diets with different alpha-linolenic:linoleic acid ratios on coagulation and fibrinolysis. Associations of alpha-linolenic acid and linoleic acid with risk factors for coronary heart disease The effect of diet enriched with alpha-linolenic acid on soluble cellular adhesion molecules in dyslipidaemic patients. Different changes of n-6 fatty acids in lipoproteins from hyperlipemic subjects after diets supplemented with n-3 fatty acids. [The effect of omega-3 fatty acids on risk factors for cardiovascular diseases]. Coconut fat and serum lipoproteins: effects of partial replacement with unsaturated fats. Safety of dietary conjugated linoleic acid (CLA) in a 12-weeks trial in healthy overweight Japanese male volunteers. Postprandial oxidative stress is modified by dietary fat: evidence from a human intervention study. Dietary trans alpha-linolenic acid from deodorised rapeseed oil and plasma lipids and lipoproteins in healthy men: the TransLinE Study. Influence of alpha-linolenic acid and fish-oil on markers of cardiovascular risk in subjects with an atherogenic lipoprotein phenotype. The beneficial effects of omega-3 and omega-6 essential fatty acid supplementation on red blood cell rheology. Effect of n-3 Oral Supplements on the n-6/n-3 Ratio in Young Adults The effect of N-6 and N-3 polyunsaturated fatty acids on hemostasis, blood lipids and blood pressure. Dietary fatty acid supplementation alters stress reactivity and performance in man. [Effect of short-term use of omega-3-type polyunsaturated fatty acids in subjects with hypertriglyceridemia]. The effects of low doses of n-3 fatty acid supplementation on blood pressure in hypertensive subjects. A randomized controlled trial. Replacement of dietary fat with palm oil: effect on human serum lipids, lipoproteins and apolipoproteins. The acute effect of a single very high dose of N-3 fatty acids on coagulation and fibrinolysis. Effects of dietary supplementation with n-6 and n-3 long-chain polyunsaturated fatty acids on serum lipoproteins and platelet function in hypertriglyceridaemic patients. Analysis of oxidative DNA damage after human dietary supplementation with linoleic acid. The antihypertensive effects of fish oil. A controlled study of polyunsaturated fatty acid supplements in essential hypertension. The influence of different combinations of gamma-linolenic, stearidonic and eicosapentaenoic acids on the fatty acid composition of blood lipids and mononuclear cells in human volunteers. Oleic acid rich diet protects against the oxidative modification of high density lipoprotein. The comparative effects of n-3 and n-6 polyunsaturated fatty acids on plasma fibrinogen levels: a controlled clinical trial in hypertriglyceridemic subjects. Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial Lipoprotein profile, plasma Ischemia Modified Albumin and LDL density change in the course of postprandial lipemia. Insights from the LIPGENE study
BACKGROUND AND AIM Some studies recently reported a favourable effect for cis-9 , trans-11 conjugated linoleic acid ( CLA ) on plasma lipoprotein profile of healthy subjects . Aim of this crossover intervention study was to evaluate the influence of a short-term dietary intake of a cheese derived from sheep 's milk naturally rich in CLA on several atherosclerotic biomarkers , in comparison with a commercially available cheese . METHODS AND RESULTS Ten subjects ( 6 F ; 4 M ) with a median age of 51.5 followed for 10 weeks a diet containing 200 g/week of cheese naturally rich in CLA ( intervention period ) and for the same period a diet containing a commercially available cheese of the same quantity ( placebo period ) . Consumption of the dairy product naturally rich in cis-9 , trans-11 CLA determined a significant ( p<0.05 ) reduction in inflammatory parameters such as interleukin-6 ( pre : 8.08+/-1.57 vs. post : 4.58+/-0.94 pg/mL ) , interleukin-8 ( pre : 45.02+/-5.82 vs. post : 28.59+/-2.64 pg/mL ) , and tumour necrosis factor-alpha ( pre : 53.58+/-25.67 vs. post : 32.09+/-17.42 pg/mL ) whereas no significant differences in the placebo period were observed . With regard to haemorheological parameters , the test period significantly ameliorated erythrocytes ' filtration rate ( pre : 7.61+/-0.71 % vs. post : 9.12+/-0.97 % ; p=0.03 ) with respect to the placebo period . Moreover , a reduction in the extent of platelet aggregation , induced by arachidonic acid [ pre : 87.8+/-1.76 % vs. post : 77.7+/-3.56 % ; p=0.04 ] was observed during the test period in comparison with the placebo period . CONCLUSIONS Dietary short-term intake of the tested dairy product naturally rich in cis-9 , trans-11 CLA appeared to cause favourable biochemical changes of atherosclerotic markers The aim of this study was to evaluate the effect of consuming gilthead sea bream fillets , with different n-6/ n-3 ratios , on atherosclerotic biomarkers . Twenty healthy subjects were included in a r and omised single-blinded cross-over trial . Participants were r and omized into 2 groups , both of which received approximately 630 g per week of gilthead sea bream fed with either 100 % fishmeal ( FM ) or partial replacement with plant proteins ( PP ) over two consecutive 10 week periods , respectively . Group A consumed firstly the FM fillets followed by the PP fillets , whereas the reverse order was adopted for group B. Group A reported a significant decrease of 29.3 % ( Δ = -26 mg/dL ) in total cholesterol after the first phase of the intervention , before returning to baseline levels after the dietary intervention with fish fed with PP . Similarly , in group A , both LDL-cholesterol and triglycerides decreased significantly by 21.6 % ( Δ = -19 mg/dL ) and 11.7 % ( Δ = -10.7 mg/dL ) , respectively , before increasing again after the intervention . Improvements in the inflammatory cytokines , interleukin-6 and -8 were also noted . Moreover , whole blood viscosity appeared significantly improved in group A , as seen by a significant increase of 7.59 % ( Δ = + 4.59 mPA ) for erythrocyte filtration rate . In conclusion , similar EPA+DHA content with different n- 6/n-3 ratio fish flesh intake was shown to have varied affects on lipid , inflammatory and haemorheological parameters in a group of healthy subjects Modification of dietary fat composition may influence hemostatic variables , which are associated with increased risk of coronary heart disease ( CHD ) . To address this question , we performed a controlled feeding study on 26 healthy male nonsmoking subjects with diets of differing fat composition . For the first 3 weeks , the subjects were given a diet calculated to supply 30 % energy as total fat : 8 % as monounsaturated , 4 % as polyunsaturated , and 16 % energy as saturated fatty acids , respectively ( saturated diet ) . This was followed immediately by two diets taken in r and om order , each of 3-week duration and separated by an 8-week washout period on the subject 's usual diet . Both diets were calculated to supply 30 % of energy as fat : 14 % monounsaturated , 6 % as polyunsaturated , and 8 % energy as saturated fatty acids . They both provided 5 g ( approximately 1.7 % energy ) more of polyunsaturated fatty acids than the saturated fat diet ; in one diet as long-chain n-3 fatty acids ( n-3 diet ) and in the other as linoleic acid ( n-6 diet ) .  Fasting plasma lipids , lipoproteins , and hemostatic factors were measured on the final 3 days of each dietary period . In a subset of 9 subjects the postpr and ial responses to a test meal were studied on the penultimate day of each period , each meal having the fat composition of its parent diet . On the n-3 diet compared with the n-6 diet , plasma triglyceride , HDL3 cholesterol , apoprotein AII , and fibrinogen concentrations were lower and HDL2 cholesterol concentration was higher ( P = .0001 , P = .003 , P = .0001 , P = .004 , and P = .001 , respectively ) . On both the n-3 and n-6 diets compared with the saturated diet , fasting plasma total and LDL cholesterol , apoprotein B , beta-thromboglobulin concentrations , and platelet counts were lower ( P < .0001 , P < .0001 , P < .001 , P < .01 , and P < .05 respectively ) and plasma Lp(a ) and von Willebr and factor concentrations were higher ( P = .02 and P < .01 , respectively ) . Fasting factor VII coagulant activity ( VIIc ) was increased and apoprotein AI concentration reduced following the n-3 diet ( P = .004 and P = .01 , respectively ) compared with the saturated diet . Plasma fibrinogen concentration was significantly greater following the n-6 diet than on the saturated diet ( P = .02 ) . Postpr and ially , plasma triglyceridemia was greater on the n-6 diet and lowest on the n-3 diet ( P < .001 ) with the saturated diet being intermediate . Plasma VIIc was increased at 4 hours following the st and ardized test meals on the n-3 and n-6 diets ( both P < .05 ) but not on the saturated diet . An increased intake of long chain n-3 fatty acids decreases fasting plasma triglyceride and apoprotein AII concentrations and increases HDL2 cholesterol concentrations and results in less postpr and ial lipemia but leads to an increase in VIIc . An increased intake of linoleic acid may raise plasma fibrinogen concentration . Decreasing the intake of saturated fatty acids reduces plasma LDL cholesterol and apoprotein B without affecting HDL cholesterol concentration independent of the type of polyunsaturated fatty acids in the diet . When advice is given to reduce saturated fat intake , it is important to ensure an appropriate ratio of n-3/n-6 fatty acids in the diet Objectives : This study investigated the effect of dietary CLA supplementation ( 3g/day ; 50:50 mix of the two major isomers ) on the immune system and plasma lipids and glucose of healthy human ( male and female ) volunteers . Design : Double-blind , r and omized , reference-controlled study .Subject and intervention : A total of 28 healthy male and female participants aged 25–50 y received either high oleic sunflower oil ( reference ) or 50 % CLA 9–11 and 50 % CLA 10–12 CLA isomers ( 50:50 CLA-triglyceride form ) . The treatments were given as supplements in soft-gel capsules providing a total 3 g ( 6 × 500 mg capsules ) per day in treatment groups for 12 weeks . A 12-week washout period followed the intervention period . Results : Levels of plasma IgA and IgM were increased ( P<0.05 and 0.01 respectively ) , while plasma IgE levels were decreased ( P<0.05 ) . CLA supplementation also decreased the levels of the proinflammatory cytokines , TNF-α and IL-1β ( P<0.05 ) , but increased the levels of the anti-inflammatory cytokine , IL-10 ( P<0.05 ) . Another aspect of immune function , delayed type hypersensitivity ( DTH ) response , was decreased during and after CLA supplementation ( P<0.05 ) . However , plasma glucose , lipids , lymphocyte phenotypic results were not affected significantly by CLA . Conclusion : This is the first study to show that CLA , a fatty acid naturally found in dairy and meat products , can beneficially affect immune function in healthy human volunteers . Sponsorship : This study was supported by Loders-Croklaan , The Netherl and s and SEERAD ( Scottish Executive Environmental Rural and Agriculture Department ) The aim of this r and omised , double-blind , crossover study in normolipidaemic volunteers was to investigate the effect of consumption of an experimental cheese ( from cows fed a grass and maize silage-based diet with 5 % of linseed oil added ) or a control cheese ( without linseed oil ) on both plasma lipids and fatty acid content of serum lipid fractions . A lower content of medium-chain saturated fatty acids as well as a higher content of stearic acid and polyunsaturated fatty acids were found in the experimental cheese ; its consumption was successful in limiting the enhanced blood concentration of atherogenic fatty acids , without affecting fatty acid content of serum lipid fractions . These results indicate that dairy products could be considered as key foods for fat modifications with the objective of optimizing their nutritional quality Plasma cholesterol concentrations increase with consumption of high saturated fatty acid ( SFA ) and decrease with high polyunsaturated fatty acid ( PUFA ) diets , leading to shifts in lipid levels consistent with reduction in heart disease risk . Direct measurements of cholesterol absorption , one of the key regulators of plasma cholesterol levels , have not been performed in humans after consumption of high PUFA diets . Thus , cholesterol absorption and fractional synthesis rates ( FSRs ) were measured in 16 healthy adults ( 8 males and 9 females ) using a r and omized cross-over study with a diet containing high ( PUFA/SFA ) P/S ratio ( 2:1 ) and a low P/S ratio ( 0.5:1 ) . Cholesterol absorption and fractional cholesterol synthetic rates were measured using stable isotopes after 20 days of dietary intervention . Diet did not affect cholesterol absorption or synthesis . There was a significant decrease in plasma cholesterol concentrations ( P < 0.02 ) , specifically LDL-cholesterol ( P < 0.02 ) , without a change in HDL-cholesterol or triacylglycerol concentrations . Intraluminal cholesterol solubilization and plasma sterol ( cholesterol biosynthetic intermediates and plant sterols ) levels were not affected by diet . Thus , consumption of diets with a high P/S ratio reduces plasma total and LDL-cholesterol concentrations independent of shifts in cholesterol absorption or synthesis BACKGROUND Substitution of dietary polyunsaturated for saturated fat has long been recommended for the primary prevention of cardiovascular disease ( CVD ) , but only a few prospect i ve cohort studies have provided support for this advice . METHODS We assessed the association of dietary linoleic and total polyunsaturated fatty acid ( PUFA ) intake with cardiovascular and overall mortality in a population -based cohort of 1551 middle-aged men . Dietary fat composition was estimated with a 4-day food record and serum fatty acid composition . RESULTS During the 15-year follow-up , 78 men died of CVD and 225 of any cause . Total fat intake was not related to CVD or overall mortality . Men with an energy-adjusted dietary intake of linoleic acid ( relative risk [ RR ] 0.39 ; 95 % confidence interval [ CI ] , 0.21 - 0.71 ) and PUFA ( RR , 0.38 ; 95 % CI , 0.20 - 0.70 ) in the upper third were less likely to die of CVD than men with intake in the lower third after adjustment for age . Multivariate adjustment weakened the association somewhat . Mortality from CVD was also lower for men with proportions of serum esterified linoleic acid ( RR , 0.42 ; 95 % CI , 0.21 - 0.80 ) and PUFA ( RR , 0.25 ; 95 % CI , 0.12 - 0.50 ) in the upper vs lower third , with some attenuation in multivariate analyses . Serum and to a lesser extent dietary linoleic acid and PUFA were also inversely associated with overall mortality . CONCLUSIONS Dietary polyunsaturated and more specifically linoleic fatty acid intake may have a substantial cardioprotective benefit that is also reflected in overall mortality . Dietary fat quality seems more important than fat quantity in the reduction of cardiovascular mortality in men Forty healthy volunteers were allocated in a double blind , r and omized study to receive either 20 g of n−3 polyunsaturated fatty acids ( PUFA ) or 20 g of n−6 PUFA at their evening meal . The effect on plasma lipids and lipoproteins of this single dose of fish oilvs . corn oil was studied the next morning , 14 h after ingestion . Plasma triglycerides and very low density lipoprotein-cholesterol significantly decreased ( 33 % ) after n−3 PUFA ( P<0.001 ) , and significantly ( P<0.01 ) more than after intake of n−6 PUFA . The decrease in plasma triglycerides after n−3 PUFA ingestion was more pronounced in subjects with higher baseline levels of triglycerides ( P<0.001 ) . Total cholesterol decreased after both supplements , but did not differ between the supplements . Low density lipoprotein-cholesterol did not change , and high density lipoprotein-cholesterol significantly decreased in subjects given n−3 PUFA compared to baseline , but not when compared to subjects receiving n−6 PUFA . In conclusion , we have shown that a single very high dose of n−3 PUFA has a pronounced hypotriglyceridemic effect , which is directly related to the initial plasma level 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 present study assesses the effect of high vs. low palmitic acid intakes on plasma lipoprotein cholesterol levels and on rates for endogenous synthesis of cholesterol in healthy and hyperlipidemic subjects .  Four diets were formulated to provide combinations of 16:0 at two levels of 18:2n-6 . Subjects received each diet treatment for 21 d , followed by washout periods of 21 d. On day 21 of each diet treatment , a fasting blood sample was drawn for lipoprotein determination and to provide a measure of the background level of deuterium . A priming dose of deuterium was consumed and a second blood sample obtained 24 h after the first sample . Isotope ratio mass spectrometry was used to determine the incorporation of deuterium into the newly synthesized cholesterol molecule , and fractional synthetic rates were calculated . Serum total cholesterol and low density lipoprotein-cholesterol was not significantly affected by the high level of 16:0 when diets also contained a high level of 18:2n-6 . There was no effect of dietary 16:0 on high density liproprotein-cholesterol at either the high or low levels of intake . The results indicate that 16:0 has no effect on serum lipoprotein profiles in the presence of recommended intakes for 18:2n-6 PUFA of the n−6 and n−3 series have beneficial effects on key risk factors of coronary heart disease ( CHD ) . Our earlier studies on the intake of FA and on the FA composition of plasma and platelet phospholipids suggested the need to improve the n−3 PUFA nutritional status in the Indian population . The present long-term study was conducted on 80 middle-aged Indian subjects ( 40 men and 40 women ) using the subjects ' own home-prepared diets to evaluate the effects of dietary n−3 PUFA on biochemical indices of CHD risk .  Substitution of Blend G ( equal proportions of groundnut and canola oils ) for groundnut oil or substitution of Blend S ( equal proportions of sunflower and canola oils ) for sunflower oil  increased α-linolenic acid ( ALNA ) fourfold and decreased the linoleic acid (LA)/ALNA ratio from 35 to 6 and 65 to 9 , respectively . Twelve subjects ( six men and six women ) who received Blend G were switched back to groundnut oil and were administered 0.3 g daily of long-chain ( LC ) n−3 PUFA from fish oil . At the end of the trial period for both blends in both sexes , plasma lipid and apolipoprotein levels had not changed , and ADP-induced aggregation had decreased . In plasma and platelet phospholipids , LA as well as LCn-3 PUFA had increased , suggesting competition between LA and ALNA for metabolism into the respective LC-PUFA . Fish oil supplementation  increased LCn-3 PUFA in plasma and platelet phospholipids , decreased ADP-induced platelet aggregation , and increased plasma cholesterol . On the basis of the increased LCn-3 PUFA in plasma phospholipids , it was calculated that 0.75 % energy ( en% ) ( 2.2 g ) ALNA ( from vegetable oils ) may be required to increase LCn-3 PUFA to about the same extent as 0.1 en% ( 0.3 g ) LCn-3 PUFA ( from fish oils ) . Since both n−6 and n−3 PUFA play a critical role in fetal growth and development and in the programming of diet-related chronic diseases in adults , an improvement in the n−3 PUFA nutritional status in cereal-based diets through long-term use of cooking oils containing 25–40 % LA and 4 % ALNA may contribute to the prevention of CHD in Indians Conjugated linoleic acid ( CLA ) has been suggested by some animal studies to possess antiatherogenic properties . To determine , in humans , the effect of dietary CLA on blood lipids , lipoproteins , and tissue fatty acid composition , we conducted a 93-d study with 17 healthy female volunteers at the Metabolic Research Unit of the Western Human Nutrition Research Center . Throughout the study , subjects were fed a low-fat diet [ 30 energy percent ( en% ) fat , 19 en% protein , and 51 en% carbohydrate ] that consisted of natural foods with the recommended dietary allowances for all known nutrients . After a 30-d stabilization period , subjects were r and omly assigned to either an intervention group ( n=10 ) supplemented daily with capsules containing 3.9 g of CLA or a control group ( n=7 ) that received an equivalent amount of sunflower oil . The CIA capsules ( CLA 65 % ) contained four major cis/trans geometric isomers ( 11.4 % 9 cis-,11 trans-18∶2 ; 10.8 % 8 trans-,10 cis-18∶2 ; 15.3 % 11 cis-,13 trans-18∶2 ; and 14.7 % 10 trans- , 12 cis-18∶2 ) and their corresponding cis/cis ( 6.74 % total ) and trans/trans ( 5.99 % total ) varieties in smaller amounts . Fasting blood was drawn on study days 30 ( end of the stabilization period ) , 60 ( midpoint of the intervention period ) , and 93 ( end of the intervention period ) . Adipose tissue sample s were taken on days 30 and 93 . CLA supplementation for 63 d did not change the levels of plasma cholesterol , low density lipoprotein cholesterol , high density lipoprotein cholesterol , and triglycerides . The weight percentage of CLA in plasma increased from 0.28±0.06 to 1.09±0.31 ( n=10 , P<0.05 ) after the supplementation . The 9 cis-,11 trans-isomer was the most prominent variety followed by the 11 cis-,13 trans- and 10 trans-,12 cis-isomers in lesser amounts . CLA in adipose tissue was not influenced by the supplementation ( 0.79±0.18 to 0.83±0.19 wt% ) ( n=10 ) and the 9 cis-,11 trans-variety was the only isomer present . Thus , contrary to findings from some animal studies , CLA does not seem to offer health benefits , in the short term , regarding the prevention of atherosclerosis in humans .  CLA supplementation for 2 mon did not alter the blood cholesterol or lipoprotein levels of healthy , normolipidemic subjects . The supplementation did increase CLA in the plasma but only 4.23 % of the ingested CLA was present in the plasma at any given time . No adverse effect of CLA supplementation was detected in this study Normal healthy male volunteers ( n=10 ) were fed diets ( high-AA ) containing 1.7 g/d of arachidonic acid ( AA ) for 50 d. The control ( low-AA ) diet contained 210 mg/d of AA . Dietary AA had no statistically significant effect on the blood cholesterol levels , lipoprotein distribution , or apoprotein levels . Adipose tissue fatty acid composition was not influenced by AA feeding . The plasma total fatty acid composition was markedly enriched in AA after 50 d ( P<0.005 ) . The fatty acid composition of plasma lipid fractions , cholesterol esters , triglycerides , free fatty acids , and phospholipid ( PL ) showed marked differences in the degree of enrichment in AA . The PL plasma fraction from the subjects consuming the low-AA diet contained 10.3 % AA while the subjects who consumed the high-AA diet had plasma PL fractions containing 19.0 % AA . The level of 22:4n-6 also was different ( 0.67 to 1.06 % ) in the plasma PL fraction after 50 d of AA feeding . After consuming the high-AA diet , the total red blood cell fatty acid composition was significantly enriched in AA which mainly replaced linoleic acid . These results indicate that dietary AA is incorporated into tissue lipids , but selectively into different tissues and lipid classes . Perhaps more importantly , the results demonstrate that dietary AA does not alter blood lipids or lipoprotein levels or have obvious adverse health effects at this level and duration of feeding After 12 mo in a r and omized , double-blind , placebo-controlled trial of conjugated linoleic acid ( CLA ) supplementation ( 2 groups received CLA as part of a triglyceride or as the free fatty acid , and 1 group received olive oil as placebo ) , 134 of the 157 participants who concluded the study were included in an open study for another 12 mo . The goals of the extension study were to evaluate the safety [ with clinical chemistry analyses and reported adverse events ( AEs ) ] and assess the effects of  CLA on body composition [ body fat mass ( BFM ) , lean body mass ( LBM ) , bone mineral mass ( BMM ) ] , body weight , and BMI . All subjects were supplemented with 3.4 g CLA/d in the triglyceride form . Circulating lipoprotein(a ) and thrombocytes increased in all groups . There was no change in fasting blood glucose . Aspartate amino transferase , but not alanine amino transferase , increased significantly . Plasma total cholesterol and LDL cholesterol were reduced , whereas HDL cholesterol and triglycerides were unchanged . The AE rate decreased compared with the first 12 mo of the study . Body weight and BFM were reduced in the subjects administered the placebo during the initial 12 mo study ( -1.6 + /- 3.2 and -1.7 + /- 2.8 kg , respectively ) . No fat or body weight changes occurred in the 2 groups given CLA during the initial 12 mo . LBM and BMM were not affected in any of the groups . Changes in body composition were not related to diet and /or training . In conclusion , this study shows that CLA supplementation for 24 mo in healthy , overweight adults was well tolerated . It confirms also that CLA decreases BFM in overweight humans , and may help maintain initial reductions in BFM and weight in the long term The effects of dietary fats on plasma cholesterol , serum lipoproteins , and apoproteins ( Apo ) , A-1 , B , and CIII were studied . Twelve men consumed three different cholesterol-free formula diets  in which polyunsaturated and saturated fats were partially substituted ( 20 % of calories ) for monoenoic fats with a constant of 40 % of calories from fat .  Total cholesterol and low-density lipoprotein cholesterol dropped from base-line values of 166 and 103 to 133 and 81 mg/dl ( sat ) , 127 and 71 mg/dl ( mono ) , and 123 and 65 mg/dl ( poly ) , respectively . High-density lipoprotein cholesterol changed very little from base-line values of 46 to 40 mg/dl ( sat ) , 45 mg/dl ( poly ) , and 43 mg/dl ( mono ) . The plasma concentrations of ApoB declined from base-line values of 80.3 mg/dl to 54.6 mg ( mono ) , 51.8 mg ( poly ) , and 59.6 mg ( sat ) while Apo CIII and Apo AI did not show any changes . This study demonstrates that : 1 ) changes in dietary fat affect serum lipids , lipoproteins , and apoproteins even when consumed on a cholesterol-free diet , and 2 ) omega-6 polyunsaturated fat lowers low-density lipoprotein cholesterol , total cholesterol , and ApoB to a greater extent than monounsaturated or saturated fat , 3 ) consumption of a cholesterol-free formula diet results in significant decreases in the concentrations of total and low-density lipoprotein cholesterol in plasma when compared to values obtained on a mixed food home diet containing approximately 300 mg cholesterol/day 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 Long-term ( 30 wk ) effects on serum lipoproteins and insulin sensitivity of two diets , one with a low polyunsaturated to saturated fat ratio ( P : S 0.3 ) and one with a P : S of 1.0 , were compared in 14 patients with noninsulin-dependent diabetes mellitus ( NIDDM ) in a crossover study . Total and LDL-cholesterol levels declined by 7.6 % ( p less than 0.01 ) and 9.8 % ( p less than 0.01 ) , respectively , during the high P : S diet . VLDL- , HDL2- , and HDL3-cholesterol ; triacylglycerol ; and apolipoprotein A1 , A2 , and B levels were not affected by the change in P : S. Despite a modest increase of insulin-mediated glucose disposal at physiologic insulinemia during the high P : S diet , no influence was seen on glycemic control , and on blood glucose , plasma insulin , and C peptide responses to mixed meals . In conclusion , a linoleic-enriched diet in patients with NIDD causes a less atherogenic lipoprotein profile but does not influence glycemic control and carbohydrate tolerance In this experiment the effect of dietary cholesterol in a hinoheic acid-rich diet on serum cholesterol was tested . In a cross-over design 41 young healthy students received a hinoleic acid-rich diet for 4 weeks at two levels of dietary cholesterol . The diet contained 14 to 15 energy% linoleic acid . The high cholesterol diet was obtained by adding two egg yolks a day to the rations . Supplementation of the linoheic acid-rich diet with the egg yolk cholesterol caused a significant rise of serum cholesterol of about 11 mg/lOO ml ( 0.29 mmole/liter ) . The dietary cholesterol did not influence serum triglyceride levels . The influence on serum cholesterol was much less than expected , based on several predictive formulas . It is concluded that the presence of a high content of linoheic acid in the diet reduces the effect of dietary cholesterol on serum cholesterol if the cholesterol is provided as egg yolk . Am . J. Clin . Nutr . 33 : 2183 - 2187 , 1979 . Since the 1950 's numerous studies BACKGROUND Atherosclerosis is a chronic inflammatory disease . We previously reported that a diet high in alpha-linolenic acid ( ALA ) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects . OBJECTIVE The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells ( P BMC s ) from subjects fed the experimental diets . DESIGN A r and omized , controlled , 3-diet , 3-period crossover study design was used . Hypercholesterolemic subjects ( n = 23 ) were assigned to 3 experimental diets : a diet high in ALA ( ALA diet ; 6.5 % of energy ) , a diet high in linoleic acid ( LA diet ; 12.6 % of energy ) , and an average American diet ( AAD ) for 6 wk . Serum interleukin (IL)-6 , IL-1beta , and tumor necrosis factor-alpha ( TNF-alpha ) concentrations and the production of IL-6 , IL-1beta , and TNF-alpha by P BMC s were measured . RESULTS IL-6 , IL-1beta , and TNF-alpha production by P BMC s and serum TNF-alpha concentrations were lower ( P < 0.05 and P < 0.08 , respectively ) with the ALA diet than with the LA diet or AAD .  P BMC production of TNF-alpha was inversely correlated with ALA ( r = -0.402 , P = 0.07 ) and with eicosapentaenoic acid ( r = -0.476 , P = 0.03 ) concentrations in P BMC lipids with the ALA diet . Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by P BMC s ( r = -0.423 , P < 0.05 ) . CONCLUSIONS Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6 , IL-1beta , and TNF-alpha production in cultured P BMC s. Changes in P BMC ALA and eicosapentaenoic acid ( derived from dietary ALA ) are associated with beneficial changes in TNF-alpha release . Thus , the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines BACKGROUND Insulin resistance is associated with elevated plasma triacylglycerol , low HDL concentrations , elevated postpr and ial lipemia , and a predominance of small , dense LDLs ( sdLDLs ) . It has been hypothesized that the dietary ratio of n-6 to n-3 ( n-6:n-3 ) polyunsaturated fatty acids ( PUFAs ) may have favorable effects on these risk factors by increasing insulin sensitivity . OBJECTIVE The objective was to measure changes in insulin sensitivity , lipoprotein size , and postpr and ial lipemia after a 6-mo alteration in n-6:n-3 . DESIGN In a r and omized , parallel design in 258 subjects aged 45 - 70 y , we compared 4 diets providing 6 % of energy as PUFAs with an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1 . The diets were enriched in alpha-linolenic acid , eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , or both . Insulin sensitivity was assessed with the homeostatic model assessment of insulin resistance and the revised quantitative insulin sensitivity test . RESULTS Dietary intervention did not influence insulin sensitivity or postpr and ial lipase activities . Fasting and postpr and ial triacylglycerol concentrations were lower , and the proportion of sdLDLs decreased ( by 12.7 % ; 95 % CI : -22.9 % , 2.4 % ) , with an n-6:n-3 of approximately 3:1 , which was achieved by the addition of long-chain n-3 PUFAs ( EPA and DHA ) . CONCLUSIONS Decreasing the n-6:n-3 does not influence insulin sensitivity or lipase activities in older subjects . The reduction in plasma triacylglycerol after an increased intake of n-3 long-chain PUFAs results in favorable changes in LDL size BACKGROUND Although the replacement of dietary saturated fat with unsaturated fat has been advocated to reduce the risk of cardiovascular disease , diets high in polyunsaturated fatty acids ( PUFAs ) could increase lipid peroxidation , potentially contributing to the pathology of atherosclerosis . OBJECTIVE The objective of this study was to examine indexes of in vivo lipid peroxidation , including free F(2)-isoprostanes , malondialdehyde ( MDA ) , and thiobarbituric acid reacting substances ( TBARS ) , in the plasma of postmenopausal women taking dietary oil supplements rich in oleate , linoleate , and both eicosapentaenoic acid and docosahexaenoic acid . DESIGN Fifteen postmenopausal women took 15 g sunflower oil/d , providing 12.3 g oleate/d ; safflower oil , providing 10.5 g linoleate/d ; and fish oil , providing 2.0 g EPA/d and 1.4 g DHA/d in a 3-treatment crossover trial . RESULTS Plasma free F(2)-isoprostane concentrations were lower after fish-oil supplementation than after sunflower-oil supplementation ( P : = 0.003 ) . When plasma free F(2)-isoprostane concentrations were normalized to plasma arachidonic acid concentrations , significant differences among the supplements were eliminated . Plasma MDA concentrations were lower after fish-oil supplementation than after sunflower-oil supplementation ( P : = 0.04 ) , whereas plasma TBARS were higher after fish-oil supplementation than after sunflower oil ( P : = 0.003 ) and safflower oil ( P : = 0.001 ) supplementation . When plasma MDA concentrations were normalized to plasma PUFA concentrations , significant differences were eliminated , but TBARS remained higher after fish-oil supplementation than after sunflower oil ( P : = 0.01 ) and safflower-oil ( P : = 0.0003 ) supplementation . CONCLUSIONS With fish-oil supplementation , there was no evidence of increased lipid peroxidation when assessed by plasma F(2)-isoprostanes and MDA , although plasma TBARS was higher than with sunflower-oil and safflower-oil supplementation In 46 elderly ( aged greater than or equal to 60 y ) hypertensive subjects with entry systolic blood pressure ( SBP ) greater than or equal to 160 or diastolic blood pressure ( DBP ) greater than or equal to 90 mm Hg , our specific aim in a r and omized , double-blind , crossover study ( two 8-wk treatment periods separated by a 3-wk washout ) was to compare blood pressure-lowering effects of 9 g fish oil/d [ omega-3 ( n-3 ) fatty acid ] vs 9 g corn oil/d [ omega-6 ( n-6 ) fatty acid ] . After a 4-wk baseline period , 22 subjects were r and omly assigned to receive fish oil and 24 to receive corn oil . For both 8-wk treatments there were no between-group differences in the change in blood pressure . There was a treatment difference for st and ing DBP when baseline values were compared with those after treatment 2 ; DBP decreased by 5.1 mm Hg in the fish-oil group vs 0.72 mm Hg in the corn-oil group ( P = 0.024 ) . Within groups during the first treatment , both fish oil and corn oil lowered all four blood pressure measures ( P less than 0.05 ) ; blood pressures were not further lowered during the second treatment compared with the washout period . There were no significant between-group differences in laboratory safety tests or categorical side effects .  Fish oil lowered triglycerides by 0.47 mmol/L ( P less than 0.001 ) . In elderly subjects , diet plus both omega-3 and omega-6 supplements ( 9 g/d ) safely and effectively lower SBP and DBP We tested semihardened blends of edible oils , suitable for commercial food manufacture , with a lower-than-conventional saturated fatty acid content , for their effects on plasma cholesterol .  Twenty-six mildly hypercholesterolemic men took part in a double-blind crossover experiment in which two test blends were compared with two control dietary periods [ which resembled the Australian fat intake : proportions of polyunsaturated , monounsaturated , and saturated fatty acids ( PMS ) 0.4:0.9:1 ] . PMS in the test diets was approximately 0.8:1.3:1 and result ed in significantly lower LDL-cholesterol concentrations ( reductions of less than or equal to 7.7 % ) . HDL cholesterol and plasma triglyceride were unchanged . The trans fatty acid ( mainly elaidic ) content of the blends was 16 % , raising its contribution to energy by 4 % but without apparent effect on LDL and HDL concentrations . Provided the overall ratio of linoleic acid to palmitic acid in commercial edible-oil blends exceeds that in the prevailing national diet , partial hydrogenation will not negate the LDL-lowering potential A mixture of trans-10 , cis-12 ( t10,c12 ) and cis-9 , trans-11 ( c9,t11 ) conjugated linoleic acid ( CLA mixture ) reduced atherosclerosis in animals , thus the effect of these isomers on endothelial dysfunctions leading to inflammation and atherosclerosis is of interest . We gave 75 healthy postmenopausal women a daily supplement of 5.5 g of oil rich in either CLA mixture , an oil rich in the naturally occurring c9,t11 CLA ( CLA milk ) , respectively , or olive oil for 16 wk in a double-blind , r and omized , parallel intervention study . We sample d blood and urine before and after the intervention . The ratios of total cholesterol : HDL cholesterol and concentrations of C-reactive protein , fibrinogen , and plasminogen activator inhibitor-1 were significantly higher in women supplemented with the CLA mixture than in those supplemented with CLA milk .  Plasma triacylglycerol was significantly higher and HDL cholesterol was lower in women supplemented with the CLA mixture than with olive oil . Both CLA supplements increased lipid peroxidation , a marker of in vivo oxidative stress measured as urinary free 8-iso-prostagl and in F(2alpha ) . However , the CLA mixture increased lipid peroxidation more than the CLA milk did . The plasma cytokines interleukin-6 and tumor necrosis factor-alpha were not affected by the treatments , nor were any of the other variables measured . In conclusion , oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease , whereas the c9,t11 CLA isomer is more neutral , except for a small but significant increase in lipid peroxidation compared with olive oil BACKGROUND n-3 Polyunsaturated fatty acids ( PUFAs ) have proven benefits for both the development of atherosclerosis and inflammatory conditions . The effects on atherosclerosis may be partly mediated by the observed reduction in fasting and postpr and ial triacylglycerol concentrations after both acute and chronic n-3 PUFA ingestion . OBJECTIVE The aim of this study was to assess gastric emptying and gastrointestinal hormone release after the consumption of mixed meals rich in n-3 PUFAs or other classes of fatty acids . DESIGN Ten healthy women ( aged 50 - 62 y ) completed 4 separate study visits in a single-blind , r and omized design . On each occasion , subjects consumed 40 g oil rich in either saturated fatty acids , monounsaturated fatty acids , n-6 PUFAs , or n-3 PUFAs as part of a mixed meal . [1-(13)C]Octanoic acid ( 100 mg ) was added to each oil . Gastric emptying was assessed by a labeled octanoic acid breath test , and concentrations of gastrointestinal hormones and plasma lipids were measured . RESULTS Recovery of (13)C in breath was enhanced after n-3 PUFA ingestion ( P < 0.005 ) . The cholecystokinin response after the n-3 PUFA meal was significantly delayed ( P < 0.001 ) , and the glucagon-like peptide 1 response was significantly reduced ( P < 0.05 ) . CONCLUSION The inclusion of n-3 PUFAs in a meal alters the gastric emptying rate , potentially as the result of changes in the pattern of cholecystokinin and glucagon-like peptide 1 release Contradictory reports on the protective effect of fish consumption on cardiovascular disease ( CVD ) risk could be due to variations in the intake of n-3 and n-6 polyunsaturated fatty acids ( PUFAs ) . Metabolic competition between n-3 and n-6 PUFAs suggests that n-6 PUFAs in vegetable oils could attenuate the efficacy of n-3 PUFAs in fish oil to favorably alter endpoints relevant to CVD risk . We determined the effects of varying dietary amounts of fish oil on lipid and thrombotic endpoints relevant to risk factors for CVD and whether these effects were attenuated by vegetable oils . Two r and omized , double-blind , placebo-controlled , parallel studies were conducted in human subjects fed varying amounts of n-3 and n-6 PUFAs ; n-3 PUFA intake was varied by using fish or placebo oil capsules , and n-6 PUFA intake was modified by incorporating varying amounts of safflower oil into the diet . Endpoints included changes in membrane fatty acid composition , blood lipids , and thrombotic profile . The results indicated that absolute amounts of fish oil , and not the relative amounts of fish and vegetable oil ( ratios of n-3 to n-6 PUFAs ) , determined the magnitude of the reduction of arachidonic acid and increase in eicosapentaenoic acid in phospholipids of plasma and platelets . The suppression of plasma triacylglycerols by fish oil was not affected by varying amounts of dietary n-6 PUFAs . Fibrinogen concentrations decreased with 15 g but not with 9 g fish oil/d fed at the same ratio of n-3 to n-6 PUFAs . The efficacy of fish oil in favorably modifying certain risk factors for CVD was not attenuated by vegetable oil Conjugated linoleic acid ( CLA ) alters body composition in animal models , but few studies have examined the effects of CLA supplementation on body composition and clinical safety measures in obese humans . In the present study , we performed a r and omized , double-blind , placebo-controlled trial to examine the changes in body composition and clinical laboratory values following CLA ( 50:50 ratio of cis-9 , trans-11 and trans-10 , cis-12 isomers ) supplementation for 12 wk in otherwise healthy obese humans . Forty-eight participants ( 13 males and 35 females ) were r and omized to receive placebo ( 8 g safflower oil/d ) , 3.2 g/d CLA , or 6.4 g/d CLA for 12 wk . Changes in body fat mass and lean body mass were determined by dual-energy X-ray absorptiometry . Resting energy expenditure was assessed by indirect calorimetry . Clinical laboratory values and adverse-event reporting were used to monitor safety . Lean body mass increased by 0.64 kg in the 6.4 g/d CLA group ( P < 0.05 ) after 12 wk of intervention . Significant decreases in serum HDL-cholesterol and sodium , hemoglobin , and hematocrit , and significant increases in serum alkaline phosphatase , C-reactive protein , and IL-6 , and white blood cells occurred in the 6.4 g/d CLA group , although all values remained within normal limits . The intervention was well tolerated and no severe adverse events were reported , although mild gastrointestinal adverse events were reported in all treatment groups . In conclusion , whereas CLA may increase lean body mass in obese humans , it may also increase markers of inflammation in the short term To evaluate which dietary fat may provide the best response in terms of plasma lipids and lipoproteins and also of platelet aggregability and superoxide formation by white blood cells , 12 type II patients were r and omly allocated to three different diets , which provided polyunsaturated fatty acids ( corn oil ) , monounsaturated fatty acids ( olive oil ) , and a supplementation of ethyl esters of n-3 fatty acids to a prudent diet . Olive oil and , more significantly , n-3 ethyl esters lowered total cholesterol best ( -2.2 % and -5.8 % , respectively ) ; the latter diet , as expected , also significantly lowered triglyceridemia ( -21.4 % ) . The corn-oil diet exerted a small , statistically significant reduction of high-density-lipoprotein cholesterol ( HDL ) ( -4.3 % ) , and it also lowered plasma total apo B concentrations ( -3.8 % ) . n-3 ethyl esters significantly raised both total ( + 3.1 % ) and particularly HDL2 cholesterol ( + 24 % ) . Platelet reactivity was insignificantly reduced by the three regimens , but all three significantly reduced thrombin-stimulated formation of thromboxane B2 . Finally , only the n-3 fatty acid supplementation significantly reduced O2- generation by adherent monocytes . Dietary unsaturated fatty acids are generally effective on the plasma lipid and lipoproteins in type II patients , but significant differences may be found between the three tested regimens The aim was to establish whether interesterification of oils , an alternative to the use of trans fatty acids in margarine manufacture , adversely affects plasma lipids .  Twenty-seven hypercholesterolemic men participated in a double-blind , crossover trial of three margarines : 1 ) high-linoleic acid , moderate trans fatty acids ; 2 ) high-palm oil blend ( predominantly lauric , myristic , palmitic , oleic , and linoleic acids ) ; and 3 ) an interesterified form of the high-palm oil margarine . Both high-palm oil margarines led to similar low-density-lipoprotein ( LDL ) cholesterol concentrations ( 4.43 + /- 0.94 and 4.54 + /- 0.88 mmol/L , respectively ) , which were significantly higher than the LDL concentrations after the high-linoleic acid margarine ( 4.02 + /- 0.85 mmol/L , P < 0.001 ) . Interesterification transferred substantial proportions of palmitic acid into the sn-2 position of glycerides and unsaturated fatty acids into the sn-1,3 positions , and this was reflected in plasma chylomicrons . This study shows that interesterification of oils used to harden margarines does not raise plasma cholesterol more than does the margarine 's constituent fatty acids A group of women were fed two separate diets in a crossover study and urinary eicosanoids were quantified . One diet contained 3.1 % of total energy ( en% ) as polyunsaturated fatty acids ( 3.0 en% linoleic acid ) and the other contained 8.4 en% polyunsaturated fatty acids ( 8.3 en% linoleic acid ) . Carbohydrate replaced fat in the low-polyunsaturated-fat diet . No changes were observed in the urinary excretion of 6-oxo-prostagl and in F1 alpha , its 2,3-dinor metabolite or thromboxane B2 by subjects on either of the diets . Urinary 2,3-dinor-thromboxane B2 excretion was lower ( 206.5 ng/24 h ) when subjects were fed the high-omega 6 polyunsaturated fatty acid diet when compared with the lower-omega 6 polyunsaturated fatty acid diet ( 275.3 ng/24 h ) . Conversely , urinary prostagl and in E2 was higher ( 139.2 ng/g creatinine ) during the higher-omega 6 polyunsaturated fatty acid diet when compared with the lower-omega 6 polyunsaturated fatty acid diet ( 94.4 ng/g creatinine ) BACKGROUND The effect of long-term increased intakes of alpha-linolenic acid ( ALA ; 18:3n-3 ) on cardiovascular risk factors is unknown . OBJECTIVES Our objectives were to assess the effect of increased ALA intakes on cardiovascular risk factors and the estimated risk of ischemic heart disease ( IHD ) at 2 y and the effect of nutritional education on dietary habits . DESIGN Subjects with multiple cardiovascular risk factors ( 124 men and 158 women ) were r and omly assigned in a double-blind fashion to consume a margarine rich in either ALA [ 46 % linoleic acid ( LA ; 18:2n-6 ) and 15 % ALA ; n = 114 ] or LA ( 58 % LA and 0.3 % ALA ; n = 168 ) . An intervention group ( n = 110 ; 50 % ALA ) obtained group nutritional education , and a control group ( n = 172 ; 34 % ALA ) received a posted leaflet containing the st and ard Dutch dietary guidelines . RESULTS Average ALA intakes were 6.3 and 1.0 g/d in the ALA and LA groups , respectively . After 2 y , the ALA group had a higher ratio of total to HDL cholesterol ( + 0.34 ; 95 % CI : 0.12 , 0.56 ) , lower HDL cholesterol ( -0.05 mmol/L ; -0.10 , 0 ) , higher serum triacylglycerol ( + 0.24 mmol/L ; 0.02 , 0.46 ) , and lower plasma fibrinogen ( -0.18 g/L ; -0.31 , -0.04 ; after 1 y ) than did the LA group ( adjusted for baseline values , sex , and lipid-lowering drugs ) . No significant difference existed in 10-y estimated IHD risk . After 2 y , the intervention group had lower saturated fat intakes and higher fish intakes than did the control group . CONCLUSIONS Increased ALA  intakes decrease the estimated IHD risk to an extent similar to that found with increased LA intakes . Group nutritional education can effectively increase fish intake BACKGROUND Desaturase indexes , as markers of endogenous fatty acid desaturation , and a characteristic serum fatty acid ( FA ) composition are related to cardiovascular and metabolic diseases , but the relation to mortality is poorly investigated . OBJECTIVE The objective was to evaluate the relation between dietary fat biomarkers , desaturase indexes , and mortality . DESIGN In this community-based prospect i ve sample , 50-y-old men were followed for a maximum of 33.7 y. Cox proportional hazard analysis was conducted to investigate desaturase indexes ( stearoyl-CoA-desaturase and Delta(6)- and Delta(5)-desaturase ) and the relation of individual serum esterified fatty acids ( FAs ) in relation to total and cardiovascular mortality in the total study sample ( n = 2009 ) and in a healthy sub sample ( n = 1885 ) . Desaturase indexes were estimated as product-to-precursor FA ratios . RESULTS During follow-up , 1012 men in the total sample  died and 931 men in the healthy sub sample  died . Desaturase indexes predicted both total and cardiovascular mortality . The relations were independent of smoking status , physical activity , BMI , total cholesterol , and hypertension . The adjusted and st and ardized ( per SD ) hazard ratios ( HRs ) and 95 % CIs for cardiovascular mortality were 1.15 ( 1.04 , 1.27 ) for stearoyl-CoA-desaturase , 1.12 ( 1.0 , 1.24 ) for Delta(6)-desaturase , and 0.88 ( 0.80 , 0.98 ) for Delta(5)-desaturase , respectively . The proportion of serum linoleic acid was inversely related , whereas serum FAs associated with saturated fat intake ( palmitic , palmitoleic , and dihomo-gamma-linolenic acids ) were directly related to total and cardiovascular mortality . CONCLUSIONS Altered endogenous FA desaturation might contribute to mortality risk because we observed independent associations between desaturase activity indexes and mortality . The proportion of linoleic acid was inversely related , and FAs reflecting saturated fat intake were directly related to mortality Although medium-chain triacylglycerols ( MCTs , composed of medium-chain fatty acids 8:0 and 10:0 ) have long been described as having neutral effects on serum cholesterol concentrations , experimental evidence supporting this cl aim is limited . In a r and omized , crossover , metabolic-ward study , we compared the lipid effects of a natural food diet supplemented with either MCTs , palm oil , or high oleic acid sunflower oil in nine middle-aged men with mild hypercholesterolemia . Rather than having a neutral effect , MCT oil produced total cholesterol concentrations that were not significantly different from those produced by palm oil ( MCT oil : 5.87 + /- 0.75 mmol/L ; palm oil : 5.79 + /- 0.72 mmol/L ) but significantly higher than that produced by high oleic acid sunflower oil ( 5.22 + /- 0.52 mmol/L ) . Low-density-lipoprotein (LDL)-cholesterol concentrations paralleled those of total cholesterol .  MCT oil tended to result in higher triacylglycerol concentrations than either palm oil or high oleic acid sunflower oil , but this difference was not significant . There were no differences in high-density-lipoprotein cholesterol concentrations . The palmitic acid and total saturated fatty acid content of plasma triacylglycerols in the MCT-oil diet was not significantly different from that in the palm oil diet . On the basis of percentage of energy , this study suggests that medium-chain fatty acids have one-half the potency that palmitic acid has at raising total and LDL-cholesterol concentrations Upregulation of protein kinase C ( PKC ) , an important enzyme in platelet activation , could be one step toward platelet hyperactivity . PKC activation can be modulated by dietary components in vitro , but few data are available concerning the in vivo effects . In this strictly controlled human dietary intervention , the influence of dietary unsaturated fatty acids and vegetable compounds on platelet activation was investigated . A high linoleic acid diet ( 10 % of energy ) with small amounts of vegetables ( no berries or apples ) was consumed by 9 women and 4 men ( 24.1 + /- 3.9 y ) , and was compared with a high oleic acid diet ( 12 % of energy ) with considerable amounts of vegetables , berries and apples consumed by 8 women and 4 men ( 24.2 + /- 5.5 y ) . Subjects were healthy Finnish volunteers . Compliance with the experimental protocol was good , as indicated by changes in plasma fatty acids and concentrations of vitamin C , beta-carotene and alpha-tocopherol . No differences between groups were seen in indices of platelet activation , including platelet aggregation , total PKC activity and distribution of PKC isoenzymes alpha , beta(II ) and delta . The results indicate that in apparently healthy and fairly young subjects with adequate vitamin intakes , diets differing markedly in their amounts of linoleic and oleic acids , and vegetables , berries and apples do not differ in platelet activation Dietary alpha-linolenic acid ( ALA ) can be converted to long-chain ( n-3 ) PUFA in humans and may potentially reproduce the beneficial effects of eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids on risk factors for coronary heart disease ( CHD ) . This study compared the effects of increased intakes of ALA with those of dietary EPA and DHA on blood coagulation and fibrinolytic factors in fasting subjects . A placebo-controlled , parallel study was conducted in 150 moderately hyperlipidemic subjects , age 25 - 72 y. Subjects were r and omly assigned to one of five interventions and consumed a total intake of 0.8 or 1.7g/d EPA+DHA , 4.5 or 9.5g/d ALA or control ( linoleic acid ; LA ) for 6 mo . Fatty acids were incorporated into 25 g of fat spread , which replaced the subject 's normal spread and three capsules . Long-term supplementation with either dietary EPA+DHA or estimated biologically equivalent amounts of ALA did not affect factors VIIa , VIIc , VIIag , XIIa , XIIag , fibrinogen concentrations , plasminogen activator inhibitor-1 or tissue plasminogen activator activity compared with the control . ( n-3 ) PUFA of plant or marine origin do not differ from one another or from LA in their effect on a range of blood coagulation and fibrinolytic factors BACKGROUND Indian Asians in Western countries have a higher rate of coronary artery disease than do the indigenous white population s , and this higher rate may be influenced by a dietary imbalance of n-6 and n-3 polyunsaturated fatty acids ( PUFAs ) . OBJECTIVE The objective of the study was to test the hypothesis that a high background dietary intake of n-6 PUFA attenuates the effects of fish-oil supplementation on insulin sensitivity and associated blood lipids of the metabolic syndrome . DESIGN Twenty-nine Indian Asian men were recruited to participate in a 12-wk dietary intervention trial . Volunteers were r and omly assigned to receive either a moderate or a high n-6 PUFA diet featuring modified oils and spreads over a 6-wk period . After this 6-wk period , both groups were supplemented with 4.0 g fish oil/d ( 2.5 g eicosapentaenoic acid + docosahexaenoic acid ) for an additional 6 wk in combination with the dietary treatment . Volunteers participated in a postpr and ial study and an insulin sensitivity test after the 6-wk dietary intervention and again after the fish-oil supplementation period . RESULTS There was no significant time x treatment interaction for blood lipids or insulin action after dietary intervention with the moderate or high n-6 PUFA diets in combination with fish oil . After the 6-wk period of fish oil supplementation , fasting and postpr and ial plasma triacylglycerol concentrations decreased significantly . CONCLUSION The background dietary n-6 PUFA concentration did not modulate the effect of fish-oil supplementation on blood lipids or measures of insulin sensitivity in this ethnic group BACKGROUND Short-term trials showed that conjugated linoleic acid ( CLA ) may reduce body fat mass ( BFM ) and increase lean body mass ( LBM ) , but the long-term effect of CLA was not examined . OBJECTIVE The objective of the study was to ascertain the 1-y effect of CLA on body composition and safety in healthy overweight adults consuming an ad libitum diet . DESIGN Male and female volunteers ( n = 180 ) with body mass indexes ( in kg/m(2 ) ) of 25 - 30 were included in a double-blind , placebo-controlled study . Subjects were r and omly assigned to 3 groups : CLA-free fatty acid ( FFA ) , CLA-triacylglycerol , or placebo ( olive oil ) .  Change in BFM , as measured by dual-energy X-ray absorptiometry , was the primary outcome . Secondary outcomes included the effects of CLA on LBM , adverse events , and safety variables . RESULTS Mean ( + /- SD ) BFM in the CLA-triacylglycerol and CLA-FFA groups was 8.7 + /- 9.1 % and 6.9 + /- 9.1 % , respectively , lower than that in the placebo group ( P < 0.001 ) . Subjects receiving CLA-FFA had 1.8 + /- 4.3 % greater LBM than did subjects receiving placebo ( P = 0.002 ) . These changes were not associated with diet or exercise . LDL increased in the CLA-FFA group ( P = 0.008 ) , HDL decreased in the CLA-triacylglycerol group ( P = 0.003 ) , and lipoprotein(a ) increased in both CLA groups ( P < 0.001 ) compared with month 0 . Fasting blood glucose concentrations remained unchanged in all 3 groups . Glycated hemoglobin rose in all groups from month 0 concentrations , but there was no significant difference between groups . Adverse events did not differ significantly between groups . CONCLUSION Long-term supplementation with CLA-FFA or CLA-triacylglycerol reduces BFM in healthy overweight adults BACKGROUND Animal studies suggest that dietary cis-9,trans-11 ( c9,t11 ) conjugated linoleic acid ( CLA ) may inhibit or regress the development of atherosclerosis . The effect of CLA on atherosclerosis has not been assessed in humans . OBJECTIVE We investigated the effect of c9,t11 CLA supplementation on aortic pulse wave velocity ( a marker of atherosclerosis ) and on cardiovascular risk factors in overweight and obese but otherwise apparently healthy subjects . DESIGN In a double-blind , r and omized , placebo-controlled , parallel-group trial , we r and omly assigned 401 subjects , aged 40 - 70 y and with a body mass index ( in kg/m(2 ) ) > or = 25 , to receive either 4 g CLA/d ( 2.5 g c9,t11 CLA/d and 0.6 g trans-10,cis-12 CLA/d ) or placebo supplements for 6 mo . Aortic pulse wave velocity , blood pressure , anthropometric characteristics , and concentrations of fasting lipid , glucose , insulin , and C-reactive protein were measured before and after supplementation . RESULTS During the intervention , mean ( + /-SE ) pulse wave velocity did not change in the c9,t11 CLA group ( Delta0.00 + /- 0.07 ) compared with the placebo group ( Delta0.09 + /- 0.06 ) . There was no effect of c9,t11 CLA supplementation on blood pressure , body composition , insulin resistance , or concentrations of lipid , glucose , and C-reactive protein . CONCLUSION This study does not support an antiatherosclerotic effect or an effect on cardiovascular risk factors of c9,t11 CLA . This trial was registered at www . clinical trials.gov as NCT00706745 AIM To evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity , insulin secretion , beta-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat , also in relation to their habitual dietary intake of n-6 and n-3 fatty acid .  METHODS AND RESULTS One hundred and sixty-two healthy individuals were r and omly assigned to follow either one of two isoenergetic diets for 3 months , one rich in monounsaturated fats and the other rich in saturated fats . Within each group there was a second r and omisation to fish oil ( n-3 fatty acids 3.6 g/day ) or placebo . At the beginning and at the end of the treatment periods insulin sensitivity ( SI ) , first phase insulin response ( FPIR ) and glucose tolerance ( K(G)-value ) were evaluated by the intravenous glucose tolerance test ( IVGTT ) . Fish oil did not have any effect on SI , FPIR , K(G)-value and disposition index in either diet . Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline , there was no change in SI ( Delta SI 0.42+/-0.34 on fish oil vs 0.14+/-0.23 on placebo for those with n-6/n-3 < 4.85 ; -1.03+/-0.47 on fish oil vs -0.27+/-0.32 on placebo for those with n-6/n-3 > 4.85 ) ( M+/-SE ) , FPIR ( Delta FPIR 135.9+/-78.9 vs 157.2+/-157.5 pmol/L ; 38.8+/-181.7 vs 357.1+/-181.7 pmol/L ) , K(G)-value ( Delta K(G ) 0.14+/-0.15 vs 0.12+/-0.11 ; -0.32+/-0.16 vs 0.15+/-0.15 ) or disposition index ( Delta disposition index 1465.4+/-830.4 vs 953.8+/-690.0 ; -1641.6+/-1034.3 vs 446.6+/-905.1 ) . Considering the 75th percentile of n-6/n-3 ratio ( 5.82 ) the results on insulin sensitivity , insulin secretion and disposition index were confirmed , while , in this more extreme situation , n-3 fatty acid supplementation induced a significant deterioration of K(G)-value ( p=0.02 ) . CONCLUSIONS In healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity , insulin secretion , beta-cell function or glucose tolerance . The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account BACKGROUND Results of a pilot study suggested that cis-9 , trans-11 conjugated linoleic acid ( CLA ) improved LDL phenotype in moderately overweight subjects with LDL phenotype B. OBJECTIVE Initiated by the results of this pilot study , we have specifically design ed a study to test the hypothesis that cis-9 , trans-11 conjugated linoleic acid improves LDL phenotype in moderately overweight subjects with LDL phenotype B. Effects on the serum lipid profile , on plasma glucose and insulin concentrations , and on clinical parameters were also examined . DESIGN Volunteers with LDL phenotype B were divided into three groups consuming daily a drinkable dairy product not enriched with CLA ( placebo , n = 34 ) , the same dairy product enriched with 3 g c9 , t11 CLA ( n = 34 ) , or the dairy product enriched with 3 g t10 , c12 CLA ( n = 19 ) for 13 weeks . RESULTS Median changes in the proportions of plasma small dense LDL were -2.0 % in the control group and -0.1 % in the c9 , t11 CLA and t10 , c12 CLA groups ( p = 0.981 for the differences between the groups ) . c9 , t11 CLA or t10 , c12 CLA did also not affect serum concentrations of LDL and HDL cholesterol , and of triacylglycerol , and plasma concentrations of glucose and insulin . CONCLUSIONS In humans with LDL phenotype B , c9 , t11 CLA and t10 , c12 CLA do not beneficially change risk factors for cardiovascular disease or diabetes OBJECTIVE To examine the ability of alpha-linolenic acid ( ALA ) in low erucic acid rapeseed oil ( RO ) to compensate for the effects of a restriction in fish intake on plasma fatty acid composition . DESIGN AND SUBJECTS Two times 6 weeks ' r and omized dietary intervention was used with blind crossover design in 40 healthy unconfined women and men ( age 20 - 46y ) . INTERVENTIONS Subjects were assigned to two fish restricted diets , namely RO diet and Trisun-sunflower oil ( TSO ) diet , with similar proportions of saturated : monounsaturated : polyunsaturated fatty acids ( 11.5:17.5:8.5 % of total energy , En% ) , but differing in their ALA content ( 2.2 and 0.3 En% ) and n-6 : n-3-ratio ( 3 : 1 and 23 : 1 , respectively ) . The fatty acid compositions of plasma triglycerides ( TG ) , cholesterol esters ( CE ) , and phospholipids ( PL ) were analyzed by gas chromatography . Dietary intake was evaluated based on 3- to 7-day food records . RESULTS The proportion of TG and CE ALA decreased on the TSO diet ( from 1.6 % to 0.9 % and from 0.9 % to 0.4 % , respectively , P < 0.001 ) and increased on the RO diet ( from 1.7 % to 3.4 % and from 0.9 % to 1.3 % , respectively , P < 0.001 ) compared to the baseline level . The proportion of eicosapentaenoic acid ( EPA ) in all three plasma fractions decreased on the TSO diet but not on the RO diet . The proportions of docosa-hexaenoic acid ( DHA ) decreased on both experimental diets and there was no difference in CE DHA between the diets . PL docosa-pentaenoic acid ( DPA ) and PL DHA remained at a higher level on the RO diet compared to the TSO diet ( P < 0.001 and P < 0.05 , respectively ) . CONCLUSIONS ALA is metabolized to EPA in humans to a significant extent . The degree to which rapeseed oil ( ca 50g/day ) affects the proportion of EPA resembled the effect of a weekly portion ( 50 - 100 g ) of fatty fish depending on the fat content of the fish Although replacement of dietary saturated fat with monounsaturated and polyunsaturated fatty acids ( MUFA and PUFA ) has been advocated for the reduction of cardiovascular disease risk , diets high in PUFA could increase low density lipoprotein ( LDL ) susceptibility to oxidation , potentially contributing to the pathology of atherosclerosis . To investigate this possibility , 15 postmenopausal women in a blinded crossover trial consumed 15 g of sunflower oil ( SU ) providing 12.3 g/day of oleate , safflower oil ( SA ) providing 10.5 g/day of linoleate , and fish oil ( FO ) providing 2.0 g/day of eicosapentaenoate ( EPA ) and 1.4 g/day of docosahexaenoate ( DHA ) . During CuSO(4)-mediated oxidation , LDL was depleted of alpha-tocopherol more rapidly after FO supplementation than after supplementation with SU ( P = 0.0001 ) and SA ( P = 0.05 ) . In LDL phospholipid and cholesteryl ester fractions , loss of n-3 PUFA was greater and loss of n-6 PUFA less after FO supplementation than after SU and SA supplementation ( P < 0.05 for all ) , but loss of total PUFA did not differ . The lag phase for phosphatidylcholine hydroperoxide ( PCOOH ) formation was shorter after FO supplementation than after supplementation with SU ( P = 0.0001 ) and SA ( P = 0.006 ) , whereas the lag phase for cholesteryl linoleate hydroperoxide ( CE18:2OOH ) formation was shorter after FO supplementation than after SU ( P = 0.03 ) but not SA . In contrast , maximal rates of PCOOH and CE18:2OOH formation were lower after FO supplementation than after SA ( P = 0.02 and 0.0001 , respectively ) and maximal concentrations of PCOOH and CE18:2OOH were lower after FO supplementation than after SA ( P = 0.03 and 0.0006 , respectively ) . Taken together , our results suggest that FO supplementation does not increase the overall oxidation of LDL ex vivo , especially when compared with SA supplementation . Consequently , health benefits related to increased fish consumption may not be offset by increased LDL oxidative susceptibility.-- Higdon , J. V. , S. H. Du , Y. S. Lee , T. Wu , and R. C. W and er . Supplementation of postmenopausal women with fish oil does not increase overall oxidation of LDL ex vivo compared to dietary oils rich in oleate and linoleate . J. Lipid Res . 2001 . 42 : 407 - -418 Background : Polyunsaturated fatty acids ( PUFA ) have beneficial effects on cardiovascular risk , although the mechanisms are incompletely understood . In a previous article , we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid ( ALA ) from walnuts and flax . Objective : To examine effects of ALA on cardiovascular responses to acute stress , flow-mediated dilation ( FMD ) of the brachial artery , and blood concentrations of endothelin-1 and arginine-vasopressin ( AVP ) . Design : Using a r and omized , crossover study design , cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects , a subset of whom also underwent FMD testing ( n = 12 ) . Participants were fed an average American diet ( AAD ) and 2 experimental diets that varied in the amount of ALA and linoleic acid ( LA ) that they contained . The AAD provided 8.7 % energy from PUFA ( 7.7 % LA , 0.8 % ALA ) . On the LA diet , saturated fat was reduced , and PUFA from walnuts and walnut oil provided 16.4 % of energy ( 12.6 % LA , 3.6 % ALA ) . On the ALA diet , walnuts , walnut oil , and flax oil provided 17 % energy from PUFA ( 10.5 % LA , 6.5 % ALA ) . Results : The ALA and LA diets significantly reduced diastolic blood pressure ( −2 to −3 mm Hg ) and total peripheral resistance ( −4 % ) , and this effect was evident at rest and during stress ( main effect of diet , p < 0.02 ) . FMD increased ( + 34 % ) on the diet containing additional ALA . AVP also increased by 20 % , and endothelin-1 was unchanged . Conclusions : These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax , and further work is needed to identify the bioactives responsible for these effects A double-blind placebo-controlled study with a crossover design was conducted on 25 non-obese black patients with mild-moderate uncomplicated essential hypertension . They were r and omly assigned into two groups . After having received placebo capsules for 4 weeks , they received dietary supplementation with either Efamol-marine ( containing desaturated n-6 and n3 essential fatty acids ) , or sunflower seed and linseed oil capsules for 12 weeks . Thereafter a second 4 weeks placebo phase and a subsequent second 12-week active phase were entered into during which a crossover of the dietary supplementation of the groups was brought about . The mean systolic blood pressure of patients receiving Efamol-marine was significantly lowered after 8 and 12 weeks , while those receiving sunflower/linseed oil supplementation had no significant reduction of blood pressure . This observation may indicate that defective desaturation of the essential fatty acids by the enzyme delta-6-desaturase , could play an important role in the etiology of essential hypertension BACKGROUND Polyunsaturated fatty acids can have beneficial effects on human immune cells , such as peripheral blood mononuclear cells ( P BMC s ) . However , the mechanisms of action of polyunsaturated fatty acids on immune cells are still largely unknown . OBJECTIVE The objective was to examine the effects of supplementation with the polyunsaturated fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) on whole-genome P BMC gene expression profiles , in healthy Dutch elderly subjects participating in a double-blind trial , by using whole-genome transcriptomics analysis . DESIGN The subjects were r and omly allocated to 1 of 3 groups : 1 ) consumption of 1.8 g EPA+DHA/d ( n = 36 ) , 2 ) consumption of 0.4 g EPA+DHA/d ( n = 37 ) , or 3 ) consumption of 4.0 g high-oleic acid sunflower oil (HOSF)/d ( n = 38 ) . All supplements were given in capsules . Before and after 26 wk of intervention , blood sample s were collected . Microarray analysis was performed on P BMC RNA from 23 subjects who received 1.8 g EPA+DHA/d and 25 subjects who received HOSF capsules . Quantitative real-time polymerase chain reaction was performed in all 111 subjects . RESULTS A high EPA+DHA intake changed the expression of 1040 genes , whereas HOSF intake changed the expression of only 298 genes . EPA+DHA intake result ed in a decreased expression of genes involved in inflammatory- and atherogenic-related pathways , such as nuclear transcription factor kappaB signaling , eicosanoid synthesis , scavenger receptor activity , adipogenesis , and hypoxia signaling . CONCLUSION These results are the first to show that intake of EPA+DHA for 26 wk can alter the gene expression profiles of P BMC s to a more antiinflammatory and antiatherogenic status . This trial was registered at clinical trials.gov as NCT00124852 BACKGROUND Replacing SFAs with vegetable PUFAs has cardiometabolic benefits , but the effects on liver fat are unknown . Increased dietary n-6 PUFAs have , however , also been proposed to promote inflammation-a yet unproven theory . OBJECTIVE We investigated the effects of PUFAs on liver fat , systemic inflammation , and metabolic disorders . DESIGN We r and omly assigned 67 abdominally obese subjects ( 15 % had type 2 diabetes ) to a 10-wk isocaloric diet high in vegetable n-6 PUFA ( PUFA diet ) or SFA mainly from butter ( SFA diet ) , without altering the macronutrient intake . Liver fat was assessed by MRI and magnetic resonance proton ( 1H ) spectroscopy ( MRS ) . Proprotein convertase subtilisin/kexin type-9 ( PCSK9 , a hepatic LDL-receptor regulator ) , inflammation , and adipose tissue expression of inflammatory and lipogenic genes were determined . RESULTS A total of 61 subjects completed the study .  Body weight modestly increased but was not different between groups . Liver fat was lower during the PUFA diet than during the SFA diet [ between-group difference in relative change from baseline ; 16 % ( MRI ; P < 0.001 ) , 34 % ( MRS ; P = 0.02 ) ] . PCSK9 ( P = 0.001 ) , TNF receptor-2 ( P < 0.01 ) , and IL-1 receptor antagonist ( P = 0.02 ) concentrations were lower during the PUFA diet , whereas insulin ( P = 0.06 ) tended to be higher during the SFA diet . In compliant subjects ( defined as change in serum linoleic acid ) , insulin , total/HDL-cholesterol ratio , LDL cholesterol , and triglycerides were lower during the PUFA diet than during the SFA diet ( P < 0.05 ) . Adipose tissue gene expression was unchanged . CONCLUSIONS Compared with SFA intake , n-6 PUFAs reduce liver fat and modestly improve metabolic status , without weight loss . A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress . Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs . This trial was registered at clinical trials.gov as NCT01038102 SCOPE The dietary fatty acid cis9,trans11 conjugated linoleic acid ( cis9,trans11 CLA ) has been shown to modify the function of endothelial cells , monocytes , and platelets , all of which are involved in the development of atherosclerosis . Potential mechanisms for the platelet effects have not been assessed previously . In this study , we assessed how supplementation of the diet with an 80:20 cis9,trans11 CLA blend affects the platelet proteome . METHODS AND RESULTS In a double-blind , r and omized , placebo-controlled , parallel-group trial , 40 overweight but apparently healthy adults received either 4 g per day of cis9,trans11 CLA-enriched oil or placebo oil , consisting of palm oil and soybean oil , for 3 months . Total platelet proteins were extracted from washed platelets , separated using two-dimensional gel electrophoresis and differentially regulated protein spots were identified by LC-ESI-MS/MS . Supplementation with the CLA blend , compared with placebo , result ed in significant alterations in levels of 46 spots ( p < 0.05 ) , of which 40 were identified . Network analysis revealed that the majority of these proteins participate in regulation of the cytoskeleton and platelet structure , as well as receptor action , signaling , and focal adhesion . CONCLUSION The platelet proteomics approach revealed novel insights into regulation of cellular biomarkers of atherogenic and thrombotic pathways by an 80:20 cis9,trans11 CLA blend Background —Conjugated linoleic acids ( CLAs ) , a group of fatty acids shown to have beneficial effects in animals , are also used as weight loss supplements . Recently , we reported that the t 10 c 12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms . The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance . Methods and Results —In a double-blind placebo-controlled trial , 60 men with metabolic syndrome were r and omized to one of 3 groups receiving t 10 c 12 CLA , a CLA mixture , or placebo for 12 weeks . Insulin sensitivity ( euglycemic clamp ) , serum lipids , in vivo lipid peroxidation ( determined as urinary 8-iso-PGF2&agr ; [ F2-isoprostanes ] ) , 15-ketodihydro PGF2&agr ; , plasma vitamin E , plasma C-reactive protein , tumor necrosis factor-&agr ; , and interleukin-6 were assessed before and after treatment . Supplementation with t 10 c 12 CLA markedly increased 8-iso-PGF2&agr ; ( 578 % ) and C-reactive protein ( 110 % ) compared with placebo ( P < 0.0001 and P < 0.01 , respectively ) and independent of changes in hyperglycemia or dyslipidemia . The increases in 8-iso-PGF2&agr ; , but not in C-reactive protein , were significantly and independently related to aggravated insulin resistance . Oxidative stress was related to increased vitamin E levels , suggesting a compensatory mechanism . Conclusions —t 10 c 12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men . The oxidative stress seems closely related to induced insulin resistance , suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance . These unfavorable effects of t 10 c 12 CLA might be of clinical importance with regard to cardiovascular disease , in consideration of the widespread use of dietary supplements containing this fatty acid Objectives —To determine the effect of dietary supplementation with conjugated linoleic acid ( CLA ) on body mass index ( BMI ) , body fat distribution , endothelial function , and markers of cardiovascular risk . Methods and Results —Forty healthy volunteers with BMI > 27 kg/m2 were r and omized to receive a CLA isomeric mixture or olive oil in a 12-week double-blind study . Subcutaneous body fat and abdominal/hepatic fat content were assessed using skin-fold thicknesses and computed tomography scanning , respectively . Endothelial function was assessed by brachial artery flow-mediated dilatation ( FMD ) . Plasma isoprostanes were measured as an index of oxidative stress . CLA supplementation did not result in a significant change in BMI index or total body fat . There was a significant decrease in limb ( −7.8 mm , P<0.001 ) , but not torso skin-fold thicknesses or abdominal or liver fat content . Brachial artery FMD declined ( −1.3 % , P=0.013 ) , and plasma F2-isoprostanes increased ( + 91pg/mL , P=0.042 ) . Conclusions —A CLA isomeric mixture had at most modest effects on adiposity and worsened endothelial function . On the basis of these results , the use of the isomeric mixture of CLA as an aid to weight loss can not be recommended Long-term supplementation with conjugated linoleic acid ( CLA ) reduces body fat mass ( BFM ) and increases or maintains lean body mass ( LBM ) . However , the regional effect of CLA was not studied . The study aim ed to evaluate the effect of CLA per region and safety in healthy , overweight and obese adults . A total of 118 subjects ( BMI : 28 - 32 kg/m2 ) were included in a double blind , placebo-controlled trial . Subjects were r and omised into two groups supplemented with either 3 x 4 g/d CLA or placebo for 6 months . CLA significantly decreased BFM at month 3 ( Delta=- 0 x 9 % , P=0 x 016 ) and at month 6 ( Delta=- 3 x 4 % , P=0 x 043 ) compared with placebo . The reduction in fat mass was located mostly in the legs ( Delta=- 0 x 8 kg , P<0 x 001 ) , and in women ( Delta=-1 x 3 kg , P=0 x 046 ) with BMI > 30 kg/m2 ( Delta=-1 x 9 kg , P=0 x 011 ) , compared with placebo . The waist-hip ratio decreased significantly ( P=0 x 043 ) compared with placebo .  LBM increased ( Delta=+0 x 5 kg , P=0 x 049 ) within the CLA group . Bone mineral content was not affected ( P=0 x 70 ) . All changes were independent of diet and physical exercise . Safety parameters including blood lipids , inflammatory and diabetogenic markers remained within the normal range . Adverse events did not differ between the groups . It is concluded that supplementation with CLA in healthy , overweight and obese adults decreases BFM in specific regions and is well tolerated OBJECTIVE To investigate the impact of intensive group education on the Mediterranean diet on  dietary intake and serum total cholesterol after 16 and 52 weeks , compared to a posted leaflet with the Dutch nutritional guidelines , in the context of primary prevention of cardiovascular disease ( CVD ) . DESIGN Controlled comparison study of an  intervention group  given intensive group education about the Mediterranean diet and a  control group of hypercholesterolaemic persons  given usual care by general practitioners ( GPs ) . SETTING A socioeconomically deprived area in the Netherl and s with an elevated coronary heart disease ( CHD ) mortality ratio . SUBJECTS Two hundred and sixty-six hypercholesterolaemic persons with at least two other CVD risk factors . RESULTS After 52 weeks , the intervention group decreased total and saturated fat intake more than the control group ( net differences were 1.8 en% ( 95%CI 0.2 - 3.4 ) and 1.1 en% ( 95%CI 0 . 4 - 1.9 ) , respectively ) . According to the Mediterranean diet guidelines the intake of fish , fruit , poultry and bread increased in the intervention group , more than in the control group . Within the intervention group , intake of fish ( + 100 % ) , poultry ( + 28 % ) and bread ( + 6 % ) was significantly increased after 1 year ( P < 0.05 ) . The intensive programme on dietary education did not significantly lower serum cholesterol level more ( -3 % ) than the posted leaflet ( -2 % ) ( net difference 0.06 mmol l-1 , 95%CI -0.10 to 0.22 ) . Initially , the body mass index ( BMI ) decreased more in the intervention group , but after 1 year the intervention and control group gained weight equally ( + 1 % ) . CONCLUSIONS Despite beneficial changes in dietary habits in the intervention group compared with the control group , after 1 year BMI increased and total fat and saturated fat intake were still too high We previously demonstrated that safflower seed extract ( SSE ) and its major antioxidant constituents , serotonin hydroxycinnamic acid amides , suppressed LDL oxidation in vitro , decreased plasma autoantibody titres to oxidized LDL and attenuated atherosclerotic lesion formation in apoE-deficient mice . In this report , we examined whether SSE , rich in serotonin derivatives , could affect markers of oxidative stress , inflammation and aortic stiffness in healthy human subjects . Twenty Japanese male volunteers were studied at baseline , after 2.1 g SSE supplementation daily ( providing 290 mg serotonin derivatives/d ) for 4 weeks , and after a 4-week washout period . Significant reductions in circulating oxidized LDL , autoantibody titres to malondialdehyde-modified LDL , the soluble form of vascular cell adhesion molecule-1 ( sVCAM-1 ) , and urinary 8-isoprostane were observed after a 4-week intervention . Although there were no statistically significant differences in blood pressure or brachial-ankle pulse wave velocity ( baPWV ) , an index of arterial stiffness , baPWV was lower than baseline in eleven of twenty subjects and was accompanied by a reduction in blood pressure . Statistically significant negative correlations were observed between the extent of initial cardiovascular risk markers ( autoantibody titres , 8-isoprostane , sVCAM-1 and baPWV ) and the effect of intervention . This suggested that individuals with elevated oxidative stress , inflammation , and /or arterial stiffness may receive more benefit from SSE supplementation OBJECTIVES To investigate the effect of an omega-3 fatty acid concentrate K85 on serum lipids , lipoproteins , insulin metabolism and blood pressure in subjects with combined hyperlipidaemia . DESIGN After a run-in dietary period of 10 weeks , subjects were r and omly allocated to receive either encapsulated K85 ( n = 28 ) or corn oil ( n = 29 ) . The intervention was double-blind . SETTING An outpatient centre in Stavanger , Norway . SUBJECTS Fifty-seven of 141 individuals , who , after the run-in period continued to meet the inclusion criteria : serum triglycerides of > or = 2.0 mmol L-1 and total serum cholesterol of > or = 6.0 mmol L-1 . INTERVENTION Encapsulated K85 , containing 85 % eicosapentaenoic acid (EPA)/docosahexaenoic acid ( DHA ) , or corn oil , both administered in a daily dose of 4 g for 12 weeks . MAIN OUTCOME MEASURES Change in metabolic and haemodynamic parameters related to intervention . RESULTS Serum EPA and DHA increased significantly in the K85 group during the treatment period . The body-mass index remained unchanged . A 28 % reduction in serum triglycerides was noted in the K85 group from the first 4 weeks . Total serum cholesterol was significantly reduced with both regimens . Serum high-density lipoprotein cholesterol increased significantly during the first 8 weeks in the K85 group . Significant reductions in systolic and diastolic blood pressures were noted in subjects on K85 . The treatment did not affect serum glucose , plasma insulin and proinsulin levels . Insulin : glucose and proinsulin : glucose ratios remained unchanged . CONCLUSIONS The atherogenic risk profile was improved with K85 in subjects with combined hyperlipidaemia , but n-3 fatty acids supplementation did not affect glucose/insulin homeostasis Background Dietary alpha-linolenic acid ( ALA ) has been associated with reduced risk of development of atherosclerosis . Adiponectin is a hormone specifically secreted by adipocytes and considered to have anti-atherogenic properties . Aim of the study We examined the effect of increased dietary intake of ALA on plasma concentration of adiponectin . Methods Thirty-five non-diabetic , dyslipidemic men , 38–71 years old , were r and omly allocated to take either 15 ml of flaxseed oil rich in ALA ( 8.1 g/day ; n = 18 ) , or 15 ml of safflower oil per day , containing the equivalent n-6 fatty acid ( 11.2 g/day linoleic acid , LA ; n = 17 ) ( control group ) . The intervention period lasted for 12 weeks . Results Plasma levels of adiponectin did not change after the increase in dietary intake of ALA in the flaxseed oil supplementation group , compared to the control group . No changes in body mass index , serum lipid concentrations , LDL density , or plasma TNF-α were found in the flaxseed oil versus the control group . Conclusions Dietary ALA has no effect on plasma adiponectin concentration in dyslipidemic men Abstract Aims /hypothesisHyperproinsulinaemia reflects both beta cell dysfunction and insulin resistance in cross-sectional studies , but it is not known whether changes in proinsulin concentrations are related to insulin resistance over time . As trans10cis12 (t10c12)-conjugated linoleic acid ( CLA ) supplementation induces insulin resistance in obese men , we used this fatty acid to investigate the effects on plasma proinsulin , insulin , C-peptide and adiponectin concentrations , including their associations with change in insulin sensitivity . Methods We r and omised ( double-blind ) 57 non-diabetic abdominally obese men to receive either 3.4 g t10c12CLA , CLA-isomer mixture or control oil for 12 weeks . Insulin sensitivity ( hyperinsulinaemic – euglycaemic clamp ) , intact proinsulin , insulin , the proinsulin : insulin ratio , C-peptide , glucose and adiponectin were assessed before and after supplementation . Results Supplementation with t10c12CLA increased proinsulin ( p<0.01 ) , the proinsulin : insulin ratio ( p<0.05 ) and C-peptide concentrations ( p<0.001 ) in comparison with control subjects . Adiponectin , however , did not change significantly . The change in proinsulin , but not the proinsulin : insulin ratio , was related to impaired insulin sensitivity ( r=−0.58 , p<0.0001 ) , independently of changes in insulin , C-peptide , glucose , adiponectin and BMI . Conversely , the correlation between insulin sensitivity and specific insulin ( r=−0.46 , p<0.001 ) did not remain significant after adjustment for proinsulin . Induced hyperproinsulinaemia was also correlated to adiponectin concentrations ( r=−0.34 , p<0.01 ) . Conclusions /interpretationIn obese men , t10c12CLA induces hyperproinsulinaemia that is related to impaired insulin sensitivity , independently of changes in insulin concentrations . These results are of clinical interest , as hyperproinsulinaemia predicts diabetes and cardiovascular disease . The use of weight-loss supplements containing this fatty acid is worrying BACKGROUND Inflammation plays an important role in the pathogenesis of coronary artery disease . We examined whether dietary supplementation with alpha-linolenic acid ( ALA , 18:3n-3 ) affects the levels of inflammatory markers in dyslipidaemic patients . METHODS We recruited 76 male dyslipidaemic patients ( mean age=51+/-8 years ) following a typical Greek diet . They were r and omly assigned either to 15 ml of linseed oil ( rich in ALA ) per day ( n=50 ) or to 15 ml of safflower oil ( rich in linoleic acid ( LA , 18:2n-6 ) ) per day ( n=26 ) . The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1 . Dietary intervention lasted for 3 months . Blood lipids and C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , and interleukin-6 ( IL-6 ) levels were determined prior and after intervention . CRP and SAA were measured by nephelometry and IL-6 by immunoassay . RESULTS Dietary supplementation with ALA decreased significantly CRP , SAA and IL-6 levels . The median decrease of CRP was 38 % ( 1.24 vs. 0.93 mg/l , P=0.0008 ) , of SAA 23.1 % ( 3.24 vs. 2.39 mg/l , P=0.0001 ) and of IL-6 10.5 % ( 2.18 vs. 1.7 pg/ml , P=0.01 ) . The decrease of inflammatory markers was independent of lipid changes . Dietary supplementation with LA did not affect significantly CRP , SAA and IL-6 concentrations but decreased cholesterol levels . CONCLUSIONS Dietary supplementation with ALA for 3 months decreases significantly CRP , SAA and IL-6 levels  in dyslipidaemic patients . This anti-inflammatory effect may provide a possible additional mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in primary and secondary prevention of coronary artery disease Objective : To examine , in free-living adults eating self-selected diets , the effects on plasma cholesterol of substituting saturated fat rich foods with either n-6 polyunsaturated or monounsaturated fat rich foods while at the same time adhering to a total fat intake of 30–33 % of dietary energy . Design : Two r and omised crossover trials . Setting : General community . Subjects : Volunteer sample of healthy free-living nutrition students at the University of Otago . Trial I , n=29 ; and trial II , n=42 . Interventions : In trials I and II participants were asked to follow for 2½ weeks a diet high in saturated fat yet with a total fat content that conformed to nutrition recommendations ( 30–33 % energy ) . During the 2 1/2 week comparison diet , saturated fat rich foods were replaced with foods rich in n-6 polyunsaturated fats ( trial I ) whereas in trial II the replacement foods were rich in monounsaturated fats . Participants were asked to maintain a total fat intake of 30–33 % of energy on all diets . Main outcome measures : Energy and nutrient intakes , plasma triglyceride fatty acids , and plasma cholesterol . Results : When replacing saturated fat with either n-6 polyunsaturated fat or monounsaturated fat , total fat intakes decreased by 2.9 % energy and 5.1 % energy , respectively . Replacing saturated fat with n-6 polyunsaturated fat ( trial I ) lowered plasma total cholesterol by 19 % [ from 4.87 ( 0.88 ) to 3.94 ( 0.92 ) mmol/l , mean ( s.d . ) ] , low density lipoprotein cholesterol by 22 % [ from 2.87 ( 0.75 ) to 2.24 ( 0.67 ) mmol/l ] , and high density lipoprotein cholesterol by 14 % [ from 1.39 ( 0.36 ) to 1.19 ( 0.34 ) mmol/l ] , whereas replacing saturated fat with monounsaturated fat ( trial II ) decreased total cholesterol by 12 % , low density lipoprotein cholesterol by 15 % , and high density lipoprotein cholesterol by 4 % , respectively . The change in the ratio of total to high density lipoprotein cholesterol was similar during trial I and trial II . Conclusions : Young adults are very responsive to dietary-induced changes in plasma cholesterol even when an isocaloric replacement of saturated fat with n-6 polyunsaturated or monounsaturated fat is not achieved . Replacing saturated fat with either n-6 polyunsaturated or monounsaturated fat is equally efficacious at reducing the total to high density lipoprotein cholesterol ratio . Sponsorship : University of Otago , Meadow Lea Ltd . European Journal of Clinical Nutrition ( 2001 ) 55 , Objective : To investigate the effects of increased alpha-linolenic acid (ALA)-intake on intima – media thickness ( IMT ) , oxidized low-density lipoprotein ( LDL ) antibodies , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , C-reactive protein ( CRP ) , and interleukins 6 and 10 . Design : R and omized double-blind placebo-controlled trial . Subjects : Moderately hypercholesterolaemic men and women ( 55±10 y ) with two other cardiovascular risk factors (n=103).Intervention : Participants were assigned to a margarine enriched with ALA ( fatty acid composition 46 % LA , 15 % ALA ) or linoleic acid ( LA ) ( 58 % LA , 0.3 % ALA ) for 2 y. Results : Dietary ALA intake was 2.3 en% among ALA users , and 0.4 en% among LA users . The 2-y progression rate of the mean carotid IMT  ( ALA and LA : + 0.05 mm ) and femoral IMT ( ALA:+0.05 mm ; LA:+0.04 mm ) was similar , when adjusted for confounding variables . After 1 and 2 y , ALA users had a lower CRP level than LA users ( net differences −0.53 and −0.56 mg/l , respectively , P<0.05 ) . No significant effects were observed in oxidized LDL antibodies , and levels of sICAM-1 , interleukins 6 and 10 . Conclusions : A six-fold increased ALA intake lowers CRP , when compared to a control diet high in LA . The present study found no effects on markers for atherosclerosis . Sponsorship : The Dutch ‘ Praeventiefonds ’ Background / Objectives : Dietary addition of either conjugated linoleic acid ( CLA ) or n-3 long-chain polyunsaturated fatty acids ( n-3 LC-PUFAs ) has been shown to alter adiposity and circulating lipids , risk markers of cardiovascular diseases . However , CLA may decrease insulin sensitivity , an effect that may be reversed by n-3 LC-PUFA . Thus , the potential of CLA plus n-3 LC-PUFA to affect insulin secretion and sensitivity in non-diabetic young and old , lean and obese subjects was tested . Subjects/ Methods : CLA ( 3 g daily ) plus n-3 LC-PUFA ( 3 g daily ) or control oil ( 6 g daily ) was given to lean ( n=12 ; BMI 20–26 kg/m2 ) or obese ( n=10 ; BMI 29–35 kg/m2 ) young ( 20–37 years old ) or lean ( n=16 ) or obese ( n=11 ) older men ( 50–65 years ) for 12 weeks . The study had a double-blind , placebo-controlled r and omized crossover design , and primary end points were insulin secretion and sensitivity during a st and ardized meal test , evaluated by modeling glucose , insulin and C-peptide data . Results : The combination was well tolerated . There was no significant difference in fasting levels of glucose , insulin or C-peptide after CLA/n-3 LC-PUFA treatment compared with control oil . Neither insulin secretion nor estimated sensitivity was affected by CLA/n-3 LC-PUFA in lean or obese young subjects or in older lean subjects . However , in older obese subjects , estimated insulin sensitivity was reduced with CLA/n-3 LC-PUFA compared with control ( P=0.024 ) . Conclusions : The results do not support beneficial effects of CLA/n-3 LC-PUFA for β-cell dysfunction or insulin resistance in humans but suggest that insulin sensitivity in older obese subjects is reduced A r and omized double-blind crossover trial was carried out to compare the influence on plasma lipid concentrations , platelet thromboxane B2 production and platelet aggregation induced by ADP , collagen and U46619 ( a prostagl and in endoperoxide analogue ) , of a daily 10 g supplement of a fish-oil concentrate ( MaxEPA ) , which provided ( g ) : 1.7 20:5 omega 3 , 0.3 22:5 omega 3 and 1.2 22:6 omega 3 , taken for 2 weeks by ten healthy subjects , with one of vegetable oil providing 3.4 18:2 omega 6 . A lower response to platelet aggregation induced by 0.5 micrograms collagen/ml but not by other aggregating agents was observed following both types of supplement . Platelet thromboxane B2 production induced by collagen also tended to be lower following the supplements . Plasma total cholesterol concentrations were unaffected by the supplements . The MaxEPA but not the vegetable-oil supplement lowered the concentration of plasma triglycerides and increased that of high-density-lipoprotein-cholesterol Ten healthy male subjects on an ordinary diet were given daily dietary supplement of 25 ml cod liver oil ( CLO ) or corn oil ( CO ) for periods of 6 weeks in a crossover study . Significant changes were observed in the plasma total fatty acid composition . The main platelet phospholipids fractions were also significantly altered , particularly by CLO with an increase of the eicosapentaenoic acid ( EPA ) : arachidonic acid ( AA ) ratio . Both supplements reduced collagen induced platelet aggregation and TXB2 production , with CLO as the most potent one . No spontaneous release of an antiaggregatory substance or 6-keto-PGF1 alpha from vein tissues were found , and the total urinary excretion of prostagl and in metabolites ( E and F series ) remained unchanged Our group has compared plasma lipids in r and omised crossover trials in which approximately half the fat intake of subjects was changed from palmolein to each of three predominantly monounsaturated oils in a series of experiments in free living volunteers . With canola oil total cholesterols were lower than on palmolein ; part of this reduction was due to lower HDL-cholesterol ( HDL-c ) so that total cholesterol/ HDL-c was only 2 % lower . With olive oil mean total cholesterols were the same as on palmolein but HDL-cholesterols were a little lower and LDL-cholesterols a little higher . Plasma lipid fatty acid patterns confirmed the diet change , showing 5 % higher 16 : 0 on palmolein and 11 % higher 18 : 1 on olive oil . To test the possibility that lack of effect of the extra palmitic acid in the palmolein – olive oil comparison was because subjects were young , thin and active , comparison of a third oil , high oleic sunflower oil ( HOSO ) with palmolein was made in both young and middleaged subjects .  Plasma total and LDL-cholesterols were 7 % lower in the whole group on HOSO but HDL-c was also 5 % lower so total cholesterol/HDL-c was only 3 % lower than on palmolein . There was no difference in lowering of LDL-c on HOSO between young and older subjects . In comparisons of all three predominantly monounsaturated oils with palmolein a higher HDL-c on palmolein reduced the presumed health benefit of lower total cholesterols on canola and high oleic sunflower oil . The reason for no reduction of total cholesterol on olive oil compared with palmolein was presumably due to the higher linoleic and higher phytosterols in palmolein and higher squalene in the olive oil Increasing dietary n-3 PUFA decreases the risk of CHD . Since n-6 PUFA compete with n-3 PUFA for common metabolic enzymes , the n-6:n-3 ratio intake rather than the n-3 PUFA intake levels per se may be critical . We aim ed to examine whether altering the n-6:n-3 ratio affects cardiovascular risk factors in hypercholesterolaemic patients on lipid management with statins .  Adhering to a r and omised , crossover study design , patients on statins ( n 11 ) were placed on one of two dietary interventions ( Diet high-ratio ( HR ) - n-6:n-3 = 30:1 or Diet low-ratio ( LR ) - n-6:n-3 = 1·7:1 ) for 4 weeks followed after an 8-week washout period by the alternate diet . Foods enriched with n-3 or n-6 PUFA were delivered to each patient , who were given clear guidance on consumption expectations for the study . Measures of lipid profile , blood pressure and vascular function were determined . Diet LR significantly reduced body weight , LDL-cholesterol , high-sensitivity C-reactive protein , blood pressure and the apoA-1:apoB ratio . While Diet HR trended towards a similar cardioprotective profile , most of the parameters examined did not reach statistical significance . A direct comparison between diets demonstrated no significant superiority of Diet LR over Diet HR . These results suggest that a dietary intervention focused on n-6 and n-3 fatty acids may improve cardiovascular risk factors in patients over and above st and ard lipid management , but there is no significant advantage of a low n-6:n-3 ratio diet when compared to a high-ratio diet OBJECTIVE Previous studies have demonstrated benefits of high-dose long-chain omega-3 polyunsaturated fatty acid ( LC omega-3 PUFA ) supplements on  metabolic risk .  Effects of increased dietary omega-3 PUFA , via oily fish and /or plant-derived omega-3 PUFAs , are less clear and may be modulated by the omega-6:omega-3 PUFA of the habitual diet . This study examined the effect on  cardiovascular disease risk markers of reducing dietary omega-6:omega-3 PUFA by changes in linoleic acid : alpha-linolenic acid ( LA : LNA ) and /or increasing LC omega-3 PUFA . It tested whether decreases in LA : LNA modulate effects of LC omega-3 PUFA . METHODS One hundred forty-two subjects , recruited to a 24-wk r and omized study , were assigned to a control group or one of four interventions . Intervention groups received two portions of oily fish ( 4.5 g eicosapentaenoic acid + docosahexanoic acid ) or white fish ( 0.7 g eicosapentaenoic acid + docosahexanoic acid ) per week , and replaced habitual household fats with ones high in sunflower ( high LA : LNA ) or rapeseed ( low LA : LNA ) oil . RESULTS Modest dietary manipulations of omega-6 and omega-3 PUFAs result ed in significant group x time interactions for serum triacylglycerols ( TAGs ; P = 0.05 ) ; at 24 wk the control and two oily fish groups showed lower TAG than did the white fish/sunflower group ( P = 0.05 ) . Reductions in TAG , associated with increased oily fish intakes , were maximized when combined with lower dietary LA : LNA . There were no significant changes in several other cardiovascular disease risk markers . CONCLUSIONS Two portions of oily fish per week led to significant reductions in TAG relative to consumption of two portions of white fish per week . Changes in TAG were maximized when combined with lower LA : LNA Fish oils rich in eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) have been demonstrated to alter coagulation and fibrinolysis variables . This study compared the effects of a traditional cholesterol-lowering diet and a similar diet , which had 50 % of the linoleic acid ( LA ) replaced with the 18 carbon n-3 fatty acid , alpha-linolenic acid ( ALA ) , on selected hemostatic variables . After a 2-week run-in diet with 39.5 % total energy ( en ) from fat , 29 healthy male subjects consumed a 31.5 % en fat diet with approximately 7 % en from polyunsaturated fat and an ALA : LA ratio of either 1:1.2 ( ALA-rich , n=15 ) or 1:21 ( LA-rich , n=14 ) for 6 weeks . Blood was collected at the beginning , middle and end of test diets for analysis of Factor VIIc and VIIIc , fibrinogen , von Willebr and factor , activated protein C resistance ( APC resistance ) , tissue plasminogen activator and plasminogen activator inhibitor type-1 activities and /or protein concentrations and platelet fatty acids . The ALA-rich diet tripled the percentage of platelet EPA , ( P < 0.0005 ) but had little effect on coagulation and fibrinolysis . The APC ratio demonstrated increased anticoagulant activity on the ALA-rich diet ( P < 0.001 ) only . Studies in patients with vascular pathologies are indicated to corroborate the current findings . Greater ratios of ALA : LA , achievable only with greater amounts of polyunsaturated fat , may be necessary to produce the effects demonstrated after feeding fish oils Background : Prevention of coronary heart disease ( CHD ) in high-risk subjects . Objective : To investigate the associations of dietary intake of alpha-linolenic acid ( ALA ) and linoleic acid ( LA ) as assessed by food frequency question naire and in the plasma cholesteryl ester ( CE ) , with CHD risk factors . Design : Baseline data of a double-blind , r and omized placebo-controlled trial . Subjects have hypercholesterolemia ( 6.0–8.0 mmol/l ) and at least two other CHD risk factors ( n=266 ) . Results : The reported  dietary ALA and LA intakes and the LA/ALA ratio were associated with the contents in the CE ( r=0.37 , r=0.21 , and r=0.42 , respectively ; P<0.01 ) . In multivariate analysis , CE ALA was inversely associated with diastolic blood pressure ( r=−0.13 ; P<0.05 ) and positively with serum triacylglycerol ( r=0.13 ; P<0.05 ) , and CE LA was inversely associated with serum triacylglycerol ( r=−0.32 ; P<0.01 ) . The CE LA/ALA ratio was strongly inversely associated with CE ALA ( r=−0.95 ; P<0.01 ) . In the lowest quintile of CE ALA , mean dietary intake was 0.4 energy % ALA ( 1.2 g/day ) , 8.4 energy % LA and an LA/ALA ratio of 21 , and in the highest quintile 0.6 energy % ALA ( 1.7 g/day ) , 6.8 energy % LA and 12 ( ratio ) . In the lowest quintile of CE ALA the diastolic blood pressure was 4 mmHg lower ( P trend<0.05 ) , and the serum triacylglycerol 0.3 mmol/l higher ( P trend NS ) when compared with the top quintile . Conclusions : In a CHD high-risk population with LA-rich background diet , these cross-sectional data suggest that replacing LA in the diet by ALA may decrease diastolic blood pressure , and may increase serum triacylglycerol concentration . Sponsorship : Dutch Prevent fund grant no. 28 - 2757 ; Unilever (margarine).European Journal of Clinical Nutrition ( 2000 ) 54 , BACKGROUND Leukocyte adhesion and transendothelial migration , the critical pathogenic components in the development of atherosclerotic lesions , are largely mediated by cellular adhesion molecules ( CAMs ) . We examined whether dietary supplementation with alpha-linolenic acid ( ALA , 18:3n-3 ) affects the levels of soluble forms of CAMs in dyslipidaemic patients . METHODS We recruited 90 male dyslipidaemic patients ( mean age=51+/-8 years ) following a typical Greek diet . They were r and omly assigned either to 15 ml of linseed oil ( rich in ALA ) per day ( n=60 ) or to 15 ml of safflower oil ( rich in linoleic acid [ LA , 18:2n-6 ] ) per day ( n=30 ) . The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1 . Dietary intervention lasted for 12 weeks . Blood lipids , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) and soluble E-selectin ( sE-selectin ) were measured . RESULTS Dietary supplementation with ALA significantly decreased sVCAM-1 levels ( median decrease 18.7 % [ 577.5 ng/ml versus 487 ng/ml , P=0.0001 ] ) . In the LA supplemented group , sVCAM-1 was also significantly decreased but to a lesser extent ( median decrease 10.6 % [ 550.5 ng/ml versus 496 ng/ml , P=0.0001 ] ) . After controlling for smoking habits , no significant difference was observed in the reduction of sVCAM-1 levels between the two treatment arms ( P=0.205 ) . The decrease of sVCAM-1 was independent of lipid changes in both groups . CONCLUSIONS Dietary supplementation with ALA for 12 weeks significantly decreases sVCAM-1 levels in dyslipidaemic patients . This effect presents a potential mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in the prevention of coronary artery disease . In addition , dietary supplementation with LA significantly decreases sVCAM-1 levels , an effect which requires further investigation After diets supplemented with canned mackerel or herring , in a cross-over design , containing different amounts of long-chain n-3 fatty acids ( eicosapentaenoic acid , C20:5n-3-EPA , and docosahexaenoic acid , C22(6)n-3-DHA ) an increase of both EPA and DHA was confirmed in triglycerides ( TG ) , cholesterol esters ( CE ) and phospholipids ( PL ) of very low density ( VLDL ) and low density lipoproteins ( LDL ) as well as in high density lipoproteins ( HDL ) from hyperlipidemic subjects . An unexpected finding was the simultaneous increase of arachidonic acid ( C20:4n-6-AA ) in TG and CE and its constant portion in PL of lipoproteins , whereas linoleic acid ( C18:2n-6-LA ) appeared lower in CE and in PL of VLDL + LDL and HDL . In general , the changes were minor after a diet supplemented with canned herring providing a lower dose of n-3 fatty acids . The results indicate dose-related changes not only of n-3 fatty acids , but also of n-6 fatty acids in serum lipids after fish diets . This different behavior of LA and AA in serum lipids might be a new aspect in the interrelations and the dietary modulation of both families of polyunsaturated fatty acids ( PUFA ) . The accumulation of AA in neutral lipids could be linked with an elevation of prostagl and in I2 , which was found apart from an increased formation of prostagl and in I3 after diets supplemented with n-3 fatty acids . The concomitant increase of prostagl and ins I2 and I3 spotlights widely ignored interrelations within the eicosanoid pathway , which become evident after diets enriched with long-chain n-3 fatty acids UNLABELLED Cardiovascular disease ( CVD ) is associated with dyslipidemia and frequently with insulin resistance , both of which are in general no alleviated by antilipidemic drugs . Our objective was to examine whether a dietary supplement containing omega-3 fatty acids ( n-3 FA ) can reduce the levels of serum lipids , fasting insulin and glucose in documented CVD patients treated by statins or  bezafibrates .  In a double-blind placebo-controlled trial of parallel design , 52 patients , age 69.2 years + /- 3.6 treated by antilipidemic drugs  , were r and omly assigned to receive daily 7 gr of a dietary concentrated supplement containing 67 % n-3 FA ( 185 mg EPA and 465 mg/g DHA ) in a form of spread ( Yamega Ltd , Israel ) or olive oil spread ( placebo ) and recommended to reduce the consumption of omega-6 fatty acids for 12 weeks . The average values + /- SD before and after dietary supplementations were compared . RESULTS 44 patients ( 23 in the n-3 FA group ) completed the study . In the n-3FA group we observed a significant decrease ( p < 0.05 ) of total cholesterol ( 12.2 % ) . LDL-cholesterol ( 16.8 % ) , triglycerides ( 36.1 % ) , insulin in hyperinsulinemic subjects ( > 20 microunits/ml ) ( 34.9 % ) , and no significant changes in HDL-cholesterol and glucose . No hyperglycemia was detected . In the olive oil group we observed a significant decrease ( p < 0.05 ) in the LDL-cholesterol values of 15.5 % and no significant changes in the other parameters . No side effects were reported during the study in any of the participants . Our findings demonstrate that the incorporation of the dietary supplement containing EPA and DHA omega-3 fatty acids reduces significantly the above risk factors for CVD The aim of the present study was to examine the effect of reducing saturated fat in the diet , or partly replacing it with unsaturated fat , on the serum lipoprotein profile of human subjects . The study had two intervention periods , 8 weeks ( phase 1 ) and 52 weeks ( phase 2 ) . In phase 1 , total fat was reduced from 31 to 25 % energy ( polyunsaturated fatty acids (PUFA):saturated fatty acids ( SFA ) ratio increased from 0.2 to 0.4 ) by reducing the quantity of coconut fat ( CF ) in the diet from 17.8 to 9.3 % energy intake . In phase 2 , subjects were r and omised to groups A and B. In group A total fat was reduced from 25 to 20 % energy ( PUFA : SFA ratio increased from 0.4 to 0.7 ) by reducing the quantity of CF in the diet from 9.3 to 4.7 % total energy intake . In group B , the saturated fat content in the diet was similar to group A. In addition a test fat ( a mixture of soyabean oil and sesame oil , PUFA : monosaturated fatty acids ratio 2 ) contributed 3.3 % total energy intake and total fat contributed 24 % energy intake ( PUFA : SFA ratio increased from 0.7 to 1.1 ) . At the end of phase 1 , there was a 7.7 % reduction in cholesterol ( 95 % CI -3.6 , -12.2 ) and 10.8 % reduction in LDL ( 95 % CI -4.9 , -16.5 ) and no significant change in HDL and triacylglycerol . At the end of phase 2 , the reduction in cholesterol in both groups was only about 4 % ( 95 % CI -12 , 3.2 ) partly due the concomitant rise in HDL . The reduction in LDL at 52 weeks was significantly higher in group B ( group A mean reduction 11 % , 95 % CI -20.1 , -2.0 and group B mean reduction 16.2 % 95 % CI -23.5 , -8.9 ) . In phase 2 , triacylglycerol levels showed a mean reduction of 6.5 % in group 2A and a mean increase of 8.2 % in group 2B . The reduction of saturated fat in the diet is associated with a lipoprotein profile that would be expected to reduce cardiovascular risk . The reduction of dietary saturated fat with partial replacement of unsaturated fat brings about changes in total cholesterol , HDL- and LDL-cholesterol that are associated with a lower cardiovascular risk A study was conducted to investigate the short-term safety of dietary conjugated linoleic acid ( CLA ) in overweight Japanese male volunteers . The study design was a r and omized , double-blind placebo-controlled trial including 60 healthy overweight volunteers ( body mass index ( BMI ) , 25 approximately 35 kg/m(2 ) ) . The subjects were r and omly assigned to three groups : 5.4 g CLA-triacylglycerol ( 3.4 g as CLA ) , 10.8 g CLA-triacylglycerol ( 6.8 g as CLA ) and placebo ( 10.8 g safflower oil ) daily for 12 weeks . The CLA-triaclyglycerol contained 9c,11t- and 10t,12c-isomers at an equal proportion . The safety was evaluated by analyses of blood parameters and by clinical examinations at the baseline , and at 6 and 12 weeks , including vital signs and adverse effects . All subjects completed the study . The occurrence of adverse events tended to be higher in the CLA groups than in the placebo group , but all of the adverse events were mild to moderate , within normal ranges , and temporary . Serum aspartate aminotransferase ( AST ) activity did not differ significantly between the groups at 12 weeks , but in the high CLA group it was slightly increased from the baseline . Serum alanine aminotransferase ( ALT ) activity was higher in the high CLA group than in the placebo group after 12 weeks and was higher than at the baseline in both CLA groups . However , statistical analysis of the population of apparently healthy volunteers who had normal blood parameters at the baseline revealed that AST and ALT levels did not differ significantly among the 3 groups at 12 weeks . Moreover , no clinical ly significant changes in vital signs were observed in any of the groups . These results indicate that CLA at a dose of 3.4 g/day is a safe dietary level in healthy Japanese population s in terms of the parameters examined Previous evidence supports the concept that increased oxidative stress may play an important role in MetS ( metabolic syndrome)-related manifestations . Dietary fat quality has been proposed to be critical in oxidative stress and the pathogenesis of the MetS. In the present study , we investigated whether oxidative stress parameters are affected by diets with different fat quantity and quality during the postpr and ial state in subjects with the MetS. Patients were r and omly assigned to one of four isoenergetic diets distinct in fat quantity and quality for 12 weeks : a high-saturated-fatty-acid ( HSFA ) diet , a high-mono-unsaturated-fatty-acid ( HMUFA ) diet and two low-fat/high-complex carbohydrate diets [ supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acid ( LFHCC n-3 ) or with 1 g/day of sunflower oil high in oleic acid ( LFHCC ) as placebo ] . The HMUFA diet enhanced postpr and ial GSH ( reduced glutathione ) levels and the GSH/GSSH ( oxidized glutathione ) ratio , compared with the other three diets . In addition , after the HMUFA-rich  diet postpr and ial lipid peroxide levels , protein carbonyl concentrations , SOD ( superoxide dismutase ) activity and plasma H2O2 levels were lower compared with subjects adhering to the HSFA-rich diet . Both LFHCC diets had an intermediate effect relative to the HMUFA and HSFA diets . In conclusion , our data support the notion that the HMUFA diet improves postpr and ial oxidative stress in patients with the MetS. These findings suggest that the postpr and ial state is important for underst and ing the possible cardioprotective effects associated with mono-unsaturated dietary fat , particularly in subjects with the TRANS : isomers of alpha-linolenic acid , which are formed by deodorization of refined vegetable oils , can be found in significant amounts in edible oils . Effects of trans alpha-linolenic acid on plasma lipoproteins are unknown . We therefore investigated the effects of trans alpha-linolenic acid on plasma lipids and lipoproteins in healthy European men . Eighty-eight healthy men from three European countries ( France , Scotl and , UK and the Netherl and s ) first consumed for 6 weeks a diet with experimental oils ' free ' of trans fatty acids ( run-in period ) . For the next 6 weeks , they were r and omly allocated to a diet with experimental oils ' high ' or ' low ' in trans alpha-linolenic acid . Daily total trans alpha-linolenic acid intake in the high trans group was 1410 ( range 583 - 2642 ) mg . Experimental oils were provided as such , or incorporated into margarines , cheeses , muffins and biscuits . The high trans alpha-linolenic acid diet significantly increased the plasma LDL-:HDL-cholesterol ratio by 8.1 % ( 95 % CI 1.4 , 15.3 ; and the total cholesterol : HDL-cholesterol ratio by 5.1 % ( 95 % CI 0.4 , 9.9 ; compared with the low-trans diet . This was largely explained by an increase in LDL-cholesterol on the high-trans diet , while no change was observed in the low-trans group ( mean treatment effect of 4.7 % ( 95 % CI -0.8 , 10.5 ; No effects were found on total cholesterol and HDL-cholesterol , triacylglycerols , apolipoprotein B and A-1 , and lipoprotein(a ) concentrations . In conclusion , trans alpha-linolenic acid may increase plasma LDL-:HDL-cholesterol and total cholesterol : HDL-cholesterol ratios . Whether diet-induced changes in these ratios truly affects the risk for CHD remains to be established We tested the hypothesis that dietary alpha-linolenic acid ( ALA ) can exert effects on markers of cardiovascular risk similar to that produced by its longer chain counterparts in fish-oil . A dietary intervention study was undertaken to examine the effects of an ALA-enriched diet in 57 men expressing an atherogenic lipoprotein phenotype ( ALP ) . Subjects were r and omly assigned to one of three diets enriched either with flaxseed oil ( FXO : high ALA , n = 21 ) , sunflower oil ( SO : high linoleic acid , n = 17 ) , or SO with fish-oil ( SOF n = 19 ) for 12 weeks , result ing in dietary intake ratios of n-6:n-3 PUFA of 0.5 , 27.9 and 5.2 , respectively . The relative abundance of ALA and EPA in erythrocyte membranes increased on the FXO diet ( p < 0.001 ) , whereas both EPA and DHA increased after fish-oil ( p < 0.001 ) . There were significant decreases in total plasma cholesterol within ( FXO -12.3 % , p = 0.001 ; SOF -7.6 % , p = 0.014 ; SO -7.3 % , p = 0.033 ) and between diets ( p = 0.019 ) , and decreases within diets after 12 weeks for HDL cholesterol on flaxseed oil ( FXO -10 % , p=0.009 ) , plasma TG ( -23 % , p < 0.001 ) and small , dense LDL ( -22 % p = 0.003 ) in fish-oil . Membrane DHA levels were inversely associated with the changes in plasma TG ( p= 0.001 ) and small , dense LDL ( p<0.05 ) after fish-oil . In conclusion , fish-oil produced predictable changes in plasma lipids and small , dense LDL ( sdLDL ) that were not reproduced by the ALA-enriched diet . Membrane DHA levels appeared to be an important determinant of these fish-oil-induced effects Twenty healthy , non-smoking subjects were enrolled into a study to investigate the effects of dietary supplementation with essential fatty acid ( EFAs ) on red blood cell rheology .  Ten subjects were given 3 months dietary supplementation with long chain polyunsaturated EFAs containing omega-3 and omega-6 EFAs while 10 others were given placebo ( sunflower oil ) . Venous sampling was performed at 0 and 12 weeks and red blood cell ( RBC ) aggregation and deformability measured by a filtration system . The results showed a reduction in RBC aggregation in the group given omega-3 and omega-6 EFAs but not in the placebo group . This may be related to changes in the RBC membrane and surface receptor characteristics . Such EFAs may be useful in Raynaud 's phenomenon Epidemiological studies show that n-6/n-3 polyunsaturated fatty acid ( PUFA ) ratios have risen dramatically in Western diets and are associated with numerous chronic inflammation-related diseases . More balanced ratios are linked to less inflammation . This study examines the effects of adding oral supplements containing n-3 eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) to diets of healthy young adults on plasma n-6/n-3 ratios . Thirty volunteers are r and omly assigned to one of two groups : experimental group , EPA ( 1.6 g/day ) and DHA ( 1.2 g/day ) ; and the control group , mineral oil ( 2.4 ml/day ) . Plasma fatty acids , nutrients from foods , and anthropometric measures are evaluated at baseline and at the Week 4 endpoint . The mean ( ±SD ) n-6/n-3 ratio for the experimental group is significantly lower ( 6.3 ± 1.6 ) than the placebo group ( 16.8 ± 3.5 ) by study completion . The results suggest that more balanced n-6/n-3 ratios may be achieved efficiently in healthy , young adults with supplements containing EPA and DHA Diverging results from studies of marine oil supplementation to western diets initiated the undertaking of a double-blind crossover study , with administration to healthy volunteers for 4 weeks of either 10 g of fish oil or 10 g of vegetable oil . Each oil containing approx . 40 % of n-3 and n-6 polyunsaturated fatty acids ( PUFA ) respectively . During the n-3 PUFA period , systolic blood pressure , plasma total lipids , triglycerides and VLDL concentrations fell significantly whereas plasma antithrombin-III ( AT-III ) rose . Cutaneous bleeding time increased significantly . In contrast only AT-III rose during the n-6 PUFA feeding , however , more marked than during the n-3 oil period . It is concluded that a n-3 PUFA oil supplement to the western diet exerts an effect that generally is considered as beneficial in terms of the risk of developing cardiovascular diseases . It is in this respect superior to that of n-6 PUFA , stressing the necessity of a more differentiated approach to advice on dietary PUFA enrichment than presently is exerted Certain dietary polyunsaturated fatty acids , gamma linolenic ( 18:3n-6 ) and eicosapentaenoic ( 20:5n-3 ) acid , attenuate  cardiovascular reactivity  to stress in rats . To study their effects on cardiovascular reactivity to acute stress in man , 30 men were r and omly assigned to one of three groups and given 28 day supplements of borage oil ( containing 18:3n-6 ) , fish oil ( containing 20:5n-3 ) , or olive oil ( placebo ) .  Reactivity to the Stroop colour-word conflict test was assessed prior to and following treatment . Borage oil alone attenuated blood pressure and heart rate responses to stress , increased skin temperature , and improved task performance . These data suggest that diet may be used to alter  stress reactivity  in man OBJECTIVE To study the effect of omega-3 polyunsaturated fatty acid supplementation on lipid profile in hypertriglyceridaemic patients . SETTING General practice . DESIGN Prospect i ve , double blind study of 12 weeks ' duration . PATIENTS AND METHODS Eight patients received fish oil ( 1800 mg C20 : 5 omega-3 eicosapentaenoic acid ( EPA ) and 1200 mg C22:6 omega-3 docosahexaenoic acid ( DHA ) .  Nine patients received corn oil ( 3000 mg C18 : 2 omega-6 linoleic acid daily ) . RESULTS Lipid profile analysis showed a decrease in triglyceride levels after fish oil supplementation . An unexpected and unexplained finding was the rise in total cholesterol and LDH cholesterol with corn oil supplementation . CONCLUSION Fish oil causes a decrease in triglyceride levels in hypertriglyceridaemic patients The potential antihypertensive effects after prolonged use of small doses of fish oils remain undefined . Therefore , we conducted a r and omized , double-blind , controlled crossover study comparing low doses of n-3 fatty acid supplementation with n-6 fatty acids on blood pressure in 33 subjects with mild hypertension . After a 6-week stabilization period , subjects ingested either 2.04 g/d of n-3 fatty acids or safflower oil ( 4.8 g/d of linoleic acid ) for 12 weeks , then crossed over to the alternative encapsulated oil for another 12 weeks , after a 4-week washout period . All antihypertensive drug therapy had been discontinued . For the combined data , there were significant reductions from pretreatment values for supine diastolic ( -2.4 mm Hg ) and sitting systolic ( -4.1 mm Hg ) blood pressure after fish oil ; no significant changes occurred after safflower oil control . Compared with safflower oil , fish oil supplementation was associated with a statistically significant reduction in mean supine diastolic blood pressure of 3.7 mm Hg ( 95 % confidence interval , -7.3 and 0.1 ) . Sitting diastolic and mean arterial pressures showed a sequence effect ; therefore , only the initial period was used in an analysis of their responses . There were significant decreases from pretreatment values for sitting diastolic ( -4.4 mm Hg ) , mean arterial ( -5.1 mm Hg ) , and systolic ( -6.5 mm Hg ) blood pressure after fish oil . The differences between groups after the 12-week period remained statistically significant for sitting diastolic and sitting mean arterial blood pressures . No adverse changes were noted in plasma levels of lipid-related measures Thirty-eight male volunteers participated in a double-blind cross-over trial evaluating the effect of replacing the usual sources of saturated fat in the Dutch diet ( animal fats and hydrogenated oils ) by palm oil , which is virtually free of cholesterol and trans-fatty acids , on serum lipids , lipoproteins and apolipoproteins . Maximum ( about 70 % ) replacement had no significant effect on serum total cholesterol or most lipoprotein fractions , but result ed in an 11 % increase in serum high-density-lipoprotein (HDL)2-cholesterol relative to the control ( P2 = 0.01 ) . The palm-oil diet also caused an 8 % decrease in low-density-lipoprotein (LDL):HDL2 + HDL3-cholesterol ratio ( P2 = 0.02 ) as well as a 9 % decrease in triacylglycerols in the low-density-lipoprotein fractions ( P2 = 0.01 ) . Palm oil consumption result ed in a 4 % increase in serum apolipoprotein AI ( P2 = 0.008 ) and a 4 % decrease in apolipoprotein B ( P2 = 0.01 ) relative to the control diet ; the B : AI apolipoprotein ratio was decreased by 8 % ( P2 < 0.0001 ) . These results were not significantly affected by the different lipoprotein E phenotypes of the volunteers . Although the observed differences were relatively modest , the present study , nonetheless , indicates that dietary palm oil , when replacing a major part of the normal fat content in a Dutch diet , may slightly reduce the lipoprotein- and apolipoprotein-associated cardiovascular risk profiles The objective of the study was to investigate the acute effect of a single very high dose of n-3 PUFA on coagulation and fibrinolysis .  Forty healthy volunteers were r and omized into two groups to receive either 20 grams of n-3 PUFA or 20 grams of n-6 PUFA as a single dose at 6 p.m. with their evening meal .  Coagulation and fibrinolysis were evaluated in the fasting state at 8 a.m. the next morning and compared to values obtained at 8 a.m. the day before , when the participants were on their habitual diets . PAI-1 activity in plasma increased by a mean of 62 % in subjects r and omized to receive n-3 PUFA despite that no changes could be demonstrated in t-PA antigen levels . PAI-1 activity was unaltered in the 20 controls receiving n-6 PUFA .  Plasma fibrinogen , coagulation factor VII , thrombin-antithrombin complexes and D-dimer did not significantly change after either supplement . The substantial increase in levels of PAI-1 activity in plasma after a single very high dose of n-3 PUFA may limit the usefulness of single very high doses of n-3 PUFA in acute clinical conditions Twenty-seven patients with hypertriglyceridaemia were given dietary supplementation either with evening primrose oil rich in gammalinolenic acid ( GLA , 18:3 n-6 ) ( n = 13 ) or a marine oil concentrate containing n-3 fatty acids ( n = 14 ) in a double-blind cross-over design during 8 + 8 weeks with olive oil as placebo . During GLA supplementation , increases in GLA and dihomogammalinolenic acid ( 20:3 n-6 ) were found in plasma lipid esters and platelet phospholipids , whereas platelet function and serum lipoproteins were unaffected . During supplementation with n-3 fatty acids there was a significant decrease in triglycerides in all lipoprotein fractions with a slight increase in high density lipoprotein and low density lipoprotein cholesterol . A marked increase in the long-chain n-3 fatty acids was found both in plasma and platelets , mainly at the expense of the n-6 fatty acids . No pronounced effects on platelet reactivity could be demonstrated . Our results confirm a triglyceride-lowering effect of n-3 fatty acids , whereas no such effect of GLA could be demonstrated It has been hypothesized that oxygen radicals generated by peroxidation of dietary linoleic acid may induce genetic damage and thereby increase cancer risk . We examined the effect of dietary supplementation with linoleic acid on the levels of oxidative DNA damage in peripheral lymphocytes and on the blood plasma antioxidant potential .  Thirty volunteers received during 6 weeks either a high dose of linoleic acid ( 15 g/day ) , an intermediate dose of linoleic acid ( 7.5 g/day ) or an isocaloric supplement without linoleic acid ( 15 g palmitic acid/day ) . After the intervention , no significant increase in oxidative DNA damage , measured as relative amounts of 7,8-dihydro-8-oxo-2'-deoxyguanosine ( 8-oxodG ) in DNA from peripheral lymphocytes , was observed in both high and intermediate linoleic acid-supplemented groups ( increase of respectively 13 and 21 % ; P>0.05 ) . Also , the differences between levels of oxidative DNA damage in the high or intermediate linoleic acid-supplemented group and the control group receiving palmitic acid ( 23 % decrease ) were not significant . Furthermore , no statistically significant differences were found between the total antioxidant capacities of blood plasma from the different experimental groups . Plasma levels of malondialdehyde , an important end-product of lipid peroxidation , were not increased after supplementation , nor were effects found on the plasma concentrations of retinol , alpha-tocopherol and beta-carotene . Despite the experimental design that excludes several forms of bias introduced in studies based on modulation of dietary composition , our results provide no indication of increased oxidative stress or genetic damage as a result of increased dietary intake of linoleic acid . Therefore , we see no scientific basis to reconsider the public health policy to stimulate the intake of polyunsaturated fatty acids aim ed at the reduction of coronary heart diseases Both n-3 and n-6 polyunsaturated fats have been suggested to lower blood pressure , an effect ascribed to altered bio synthesis of eicosanoids . To test these hypotheses , we studied blood pressure and eicosanoid production during supplementation of dietary fat for four weeks in 32 men with mild essential hypertension . Supplementation was preceded and followed by four-week run-in and recovery periods . Groups of eight subjects received either 10 ml or 50 ml of fish oil ( 3 or 15 g of n-3 fatty acids ) daily , 50 ml of safflower oil ( 39 g of n-6 fatty acids ) , or 50 ml of a mixture of oils that approximated the types of fat present in the American diet . The bio synthesis of eicosanoids was assessed by the measurement of urinary metabolites . Blood pressure decreased in the men who received the high dose of fish oil ( systolic pressure by a mean of 6.5 mm Hg [ P less than 0.03 ] and diastolic pressure by 4.4 mm Hg [ P less than 0.015 ] ) , but not in the other groups . Although the formation of vasodilatory prostacyclins ( prostagl and ins I2 and I3 ) increased initially , this increase was not maintained as blood pressure fell . The level of thromboxane A2 metabolites fell ; metabolites of thromboxane A3 were detected in the groups receiving fish oil . The formation of prostagl and in E2 increased during supplementation with safflower oil and tended to decrease with fish oil ; no prostagl and in E3 metabolite was detected . Our data indicate that high doses of fish oil can reduce blood pressure in men with essential hypertension . However , the clinical usefulness and safety of fish oil in the treatment of hypertension will require further study This study set out to identify whether stearidonic acid ( 18:4n-3 ; STA ) can be used to increase the eicosapentaenoic acid ( 20:5n-3 ; EPA ) content of plasma lipids and cells in humans and to underst and more about the effects of increased consumption of gamma-linolenic acid ( 18:3n-3 ; GLA ) , STA and EPA in humans . Healthy young males were r and omised to consume one of seven oil blends for a period of 12 weeks ( 9 g oil/day ) ( n = 8 - 12 subjects/group ) . Palm oil , sunflower oil , an EPA-rich oil , borage oil ( rich in GLA ) , and Echium oil ( rich in STA ) were blended in various combinations to generate a placebo oil and oils providing approximately 2 g GLA + STA + EPA per day , but in different combinations . Blood was collected at 0 , 4 , 8 and 12 weeks and the fatty acid compositions of plasma triacylglycerols , cholesteryl esters and phospholipids and of peripheral blood mononuclear cells ( P BMC s ) determined . Significant effects were observed with each lipid fraction . Neither STA nor its derivative 20:4n-3 appeared in any of the lipid fractions studied when STA ( up to 1g/day ) was consumed . However , STA ( 1g/day ) , in combination with GLA ( 0.9 g/day ) , increased the proportion of EPA in some lipid fractions , suggesting that STA-rich plant oils may offer a novel means of increasing EPA status . Furthermore , this combination tended to increase the dihomo-gamma-linolenic acid ( 20:3n-6 ; DGLA ) content of P BMC s , without an increase in arachidonic acid ( AA ) ( 20:4n-6 ) content . EPA consumption increased the EPA content of all lipid fractions studied . Consumption of GLA ( 2g/day ) , in the absence of STA or EPA , increased DGLA content with a tendency to increase AA content in some fractions . This effect was prevented by inclusion of EPA in combination with GLA . Thus , this study indicates that STA may be used as a precursor to increase the EPA content of human lipids and that combinations of GLA , STA and EPA can be used to manipulate the fatty acid compositions of lipid pools in subtle ways . Such effects may offer new strategies for manipulation of cell composition in order to influence cellular responses and functions in desirable ways Oxidative modifications of lipoproteins could contribute to the development of atherosclerosis , but the influence of dietary fats on high density lipoprotein ( HDL ) oxidative modification is unknown . This study was design ed to determine whether a diet rich in oleic acid could modulate the oxidative modification of HDL3 . Twenty two healthy men were r and omly placed on a 32-wk crossover study of an oleic acid rich diet supplied by a variant of sunflower oil vs a linoleic acid rich diet provided by conventional sunflower oil . Plasma HDL3 obtained after the diet rich in oleic acid showed a significantly higher oleic acid content in the phospholipid than lipoprotein isolated after the linoleic acid rich diet . HDL3 isolated after the oleic acid rich diet had lower values of thiobarbituric acid reactive substances ( TBARS ) than HDL3 obtained after the linoleic acid rich diet both for native ( mean + /- SE ; 0.24 + /- 0.02 vs 0.42 + /- 0.08 nmol MDA/mg protein ; p < 0.01 ) and copper oxidized HDL3 ( 0.75 + /- 0.06 vs 0.95 + /- 0.07 nmol MDA/mg protein ; p < 0.01 ) . Indeed , TBARS for native HDL3 were negatively correlated with the oleic acid to linoleic acid ratio and positively with the percentage of linoleic acid in their phospholipids . Interestingly , HDL3 after both diets had similar antioxidant vitamins A and E content . HDL3 overall composition and fluidity were similar after the two diets . Moreover , HDL3 obtained after both diets produced identical [ 3H ] free cholesterol efflux from human monocyte-derived macrophages ( 29 % ) and fibroblasts ( 26 % ) . In conclusion , HDL3 rich in oleic acid was less easily oxidized regardless of the content of antioxidants such as vitamins A and E. Therefore , dietary monounsaturated fatty acid prevent the oxidative modification of lipoproteins It has previously been shown that fish oil supplementation , compared to olive oil , reduces plasma fibrinogen . Presented here are the results of a r and omized , double-blind , crossover controlled trail that compared the effects of dietary n-3 and n-6 fatty acid supplementation on plasma fibrinogen levels in 10 patients with hyperlipoproteinemia types IIb or IV .  Plasma fibrinogen levels showed statistically significant reductions during both the fish oil and corn oil treatment periods . Other variables related to hemostasis which showed no significant changes from baseline included tissue plasminogen activator activity and inhibitor , protein C antigen , antithrombin III activity , bleeding time , and platelet counts . These data confirm the two previous reports that fish oil supplementation is associated with reductions in plasma fibrinogen levels , thereby modifying a potential nonlipid risk factor for cardiovascular disease . Unlike previous reports , however , n-6 polyunsaturated fatty acids were also associated with significant reductions in fibrinogen levels . Therefore , it is premature to conclude that the fibrinogen-lowering effects of dietary fish oil are unique to n-3 polyunsaturated fatty acids Shorter telomeres have been associated with poor health behaviors , age-related diseases , and early mortality . Telomere length is regulated by the enzyme telomerase , and is linked to exposure to proinflammatory cytokines and oxidative stress . In our recent r and omized controlled trial , omega-3 ( n-3 ) polyunsaturated fatty acid ( PUFA ) supplementation lowered the concentration of serum proinflammatory cytokines . This study assessed whether n-3 PUFA supplementation also affected leukocyte telomere length , telomerase , and oxidative stress . In addition to testing for group differences , changes in the continuous n-6:n-3 PUFA ratio were assessed to account for individual differences in adherence , absorption , and metabolism . The double-blind four-month trial included 106 healthy sedentary overweight middle-aged and older adults who received ( 1 ) 2.5g/day n-3 PUFAs , ( 2 ) l.25g/day n-3 PUFAs , or ( 3 ) placebo capsules that mirrored the proportions of fatty acids in the typical American diet . Supplementation significantly lowered oxidative stress as measured by F2-isoprostanes ( p=0.02 ) . The estimated geometric mean log-F2-isoprostanes values were 15 % lower in the two supplemented groups compared to placebo . Although group differences for telomerase and telomere length were nonsignificant , changes in the n-6:n-3 PUFA plasma ratios helped clarify the intervention 's impact : telomere length increased with decreasing n-6:n-3 ratios , p=0.02 . The data suggest that lower n-6:n-3 PUFA ratios can impact cell aging . The triad of inflammation , oxidative stress , and immune cell aging represents important pre-disease mechanisms that may be ameliorated through nutritional interventions . This translational research broadens our underst and ing of the potential impact of the n-6:n-3 PUFA balance . Clinical Trials.gov identifier : NCT00385723 Abstract Postpr and ial lipemia is associated with elevated risk of cardiovascular disease . Very little data exists regarding postpr and ial response in subjects with metabolic syndrome ( MetS ) . The current study was conducted within the LIPGENE EU Integrated Project . Patients were r and omized to one of the four isocaloric fatty meals ( Oral Fat Tolerance Tests , OFTT ) : ( A ) high-fat , saturated fatty acid (SFA)-rich ( HFSA ) , ( B ) high-fat , monounsaturated fatty acid (MUFA)-rich ( HFMUFA ) , ( C ) low-fat , high-complex carbohydrate with 1.24 g high oleic sunflower oil supplement ( LFHCC ) and ( D ) low-fat high-complex carbohydrate with 1.24 g long chain n-3 poly-unsaturated fatty acid ( LC n-3 PUFA ) supplement ( LFHCCn-3 ) . The total and incremental areas under the curve ( tAUC and iAUC ) of plasma lipid and lipoprotein , Ischemia Modified Albumin ( IMA ) and LDL density were examined in patients with MetS to define effect of OFTT . All types of OFTT transiently increased plasma triglyceride and LDL density ( LDLdens ) . It was paralleled by temporal decrease in total cholesterol ( TC ) , LDL cholesterol ( LDL-C ) , and HDL cholesterol ( HDL-C ) . This last effect was partly alleviated in LFHCCn-3 test . A reversible increase of IMA was statistically significant only in the course of HSFA and HMUFA tests . EPA and DHA supplement in combined high complex-carbohydrate meal may attenuate adverse effect of tested meal on LDL particle profile and plasma ischemia modified albumin . No expected associations between measures of central adiposity ( waist , WHR ) , adipose tissue insulin resistance ( Adipo-IR ) , and postpr and ial responses of TG , TC , LDL-C , HDL-C , LDLdens and IMA/Alb ratio were found in subgroup analysis . Trial registration : Clinical Trials.gov identifier : NCT00429195
BACKGROUND Omega 6 plays a vital role in many physiological functions but there is controversy concerning its effect on cardiovascular disease ( CVD ) risk .
There is conflicting evidence whether increasing or decreasing omega 6 intake results in beneficial effects .
OBJECTIVES The two primary objectives of this Cochrane review were to determine the effectiveness of:1 .
Increasing omega 6 ( Linoleic acid ( LA ) , Gamma-linolenic acid ( GLA ) , Dihomo-gamma-linolenic acid ( DGLA ) , Arachidonic acid ( AA ) , or any combination ) intake in place of saturated or monounsaturated fats or carbohydrates for the primary prevention of CVD.2 .
Decreasing omega 6 ( LA , GLA , DGLA , AA , or any combination ) intake in place of carbohydrates or protein ( or both ) for the primary prevention of CVD .