title: Docosahexaenoic Acid Supplementation, Vascular Function and Risk Factors for Cardiovascular Disease: A Randomized Controlled Trial in Young Adults Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers. Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men and women. 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. Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. The Effects of the Mediterranean Diet on Biomarkers of Vascular Wall Inflammation and Plaque Vulnerability in Subjects with High Risk for Cardiovascular Disease. A Randomized Trial Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Multiple Biomarkers for the Prediction of Ischemic Stroke: The PRIME Study Effects of n-3 fatty acids on macro- and microvascular function in subjects with type 2 diabetes mellitus. The chronic intake of a Mediterranean diet enriched in virgin olive oil, decreases nuclear transcription factor kappaB activation in peripheral blood mononuclear cells from healthy men. Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men. Conjugated Linoleic Acid Impairs Endothelial Function The protective effect of the Mediterranean diet on endothelial resistance to GLP-1 in type 2 diabetes: a preliminary report Effects of marine n-3 fatty acids on circulating levels of soluble adhesion molecules in patients with chronic heart failure. Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: The ATTICA Study. Low-dose fish oil supplementation increases serum adiponectin without affecting inflammatory markers in overweight subjects. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients. Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial function in healthy men. The nuts and bolts of PROSPERO: an international prospective register of systematic reviews Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. CLA Does Not Impair Endothelial Function and Decreases Body Weight as Compared with Safflower Oil in Overweight and Obese Male Subjects Soluble adhesion molecules in healthy subjects: a dose-response study using n-3 fatty acids. Flaxseed oil does not affect inflammatory markers and lipid profile compared to olive oil, in young, healthy, normal weight adults. Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homocysteine and inflammatory markers in healthy Malaysian adults. Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic DSS colitis model In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. Effect of low doses of long-chain n-3 PUFAs on endothelial function and arterial stiffness: a randomized controlled trial. Reduced ex vivo interleukin-6 production by dietary fish oil is not modified by linoleic acid intake in healthy men. Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Comparing an olive oil-enriched diet to a standard lower-fat diet for weight loss in breast cancer survivors: a pilot study. Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women. The Mediterranean diet pattern and its main components are associated with lower plasma concentrations of tumor necrosis factor receptor 60 in patients at high risk for cardiovascular disease.
abstract: Background A high consumption of omega‐3 long‐chain polyunsaturated fatty acids , and particularly docosahexaenoic acid ( DHA ) , has been suggested to reduce the risk of cardiovascular disease ( CVD ) . However , while DHA supplementation may have benefits for secondary prevention , few studies have investigated the role of DHA in the primary prevention of CVD . Here , we tested the hypothesis that DHA supplementation  improves endothelial function and risk factors for CVD . Methods and Results Healthy volunteers ( n=328 ) , aged 18 to 37 years , were r and omly assigned to 1.6 g DHA/day ( from a microalgae source ) together with 2.4 g/day carrier oil ( index group ) or to 4.0 g/day olive oil ( control ) ( both given in eight 500‐mg capsules/day for 16 weeks ) . Flow‐mediated endothelium‐dependent vasodilation ( FMD ) of the brachial artery ( primary outcome ) was measured before and after the intervention ( n=268 ) using high‐resolution vascular ultrasound . FMD was the same in both groups at r and omization ( mean , SD ; 0.27 , 0.1 mm ) , but postintervention was higher in the control group ( 0.29 , 0.1 mm ) compared with the DHA‐supplemented group ( 0.26 , 0.1 mm ; mean difference −0.03 mm ; 95 % CI −0.005 to −0.06 mm ; P=0.02 ) . Of other outcomes , only triglyceride ( mean difference −28 % , 95 % CI −40 % to −15 % ; P<0.0001 ) and very low‐density lipoprotein concentrations were significant lower in DHA‐supplemented individuals compared with controls . Conclusions DHA supplementation did not improve endothelial function in healthy , young adults .  Nevertheless , lower triglyceride concentrations with DHA supplementation was consistent with previous reports and could have benefits for the prevention of CVD . Clinical Trial Registration Information URL : http://www.controlled-trials.com/ Unique identifier : IS RCT N no : 19987575 BACKGROUND AND AIMS Virgin olive oil ( VOO ) and nuts are basic components of the Mediterranean diet , a heart-healthy dietary pattern . Nuts have well known cholesterol lowering effects , while evidence is unclear for VOO . We design ed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40 % of the fat in the background diet with VOO , walnuts or almonds . METHODS AND RESULTS After a 4 week run-in period with a healthy diet , eligible c and i date s were r and omized into three diet sequences in a crossover design , with a common background diet enriched with VOO , walnuts or almonds , lasting 4 weeks each . Outcomes were changes of serum lipids and oxidation and inflammation markers , measured by st and ard methods . Plasma fatty acids were determined by gas chromatography to assess compliance . In 18 participants completing the study ( 9 women , mean age 56 y , BMI 25.7 kg/m(2 ) ) , LDL-cholesterol was reduced from baseline by 7.3 % , 10.8 % and 13.4 % after the VOO , walnut and almond diets , respectively ( P = 0.001 , Friedman test ) . Total cholesterol and LDL/HDL ratios decreased in parallel . LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets . No changes of other lipid fractions , oxidation analytes or inflammatory biomarkers were observed . Plasma fatty acid changes after each diet sequence supported good compliance . CONCLUSION The results confirm the cholesterol lowering properties of nut-enriched diets . They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content , which clearly deserves further study The intake of ( n-3 ) long-chain PUFA is associated with a decreased risk of fatal myocardial infa rct ion . Whether this effect is attributable to the effects of docosahexaenoic acid [ 22:6(n-3 ) ( DHA ) ] on vascular function , particularly at intakes < 1 g/d , is unknown . We report a r and omized , double-blind , crossover , placebo controlled trial of 0.7 g DHA/d as a purified algal derived triacylglycerol ( 1.5 g/d ) vs. placebo ( 1.5 g olive oil/d ) on vascular function and biochemical indices of endothelial dysfunction in 38 healthy men and women , aged 40 - 65 y. Each treatment phase lasted 3 mo , separated by a 4 mo washout period . Supplementation increased the proportion of DHA in erythrocytes lipids by 58 % , compared with placebo .  Arterial compliance and endothelium independent and dependent responses , plasma concentrations of C-reactive protein , soluble thrombomodulin , E-selectin , von Willebr and factor antigen , and urinary microalbumin and isoprostane excretion were unaffected by treatment . Diastolic blood pressure decreased by 3.3 mm Hg ( 95 % CI -6.1 to -0.6 ; P = 0.01 ) . Heart rate tended to be 2.1 beats/min lower after DHA treatment than after the placebo period ( P = 0.15 ) . The results indicate that a moderate increase in the daily intake of DHA to approximately 0.7 g DHA lowers diastolic BP but does not influence indices of endothelial function or arterial stiffness in the short term 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 AND PURPOSE Activation of endothelial cells and platelets is an important mediator of atherothrombosis . Markers of endothelial cell and platelet activation such as soluble adhesion molecules can be measured in plasma . We hypothesized that patients with acute ischemic stroke would have increased blood concentrations of soluble E-selectin and von Willebr and factor ( vWF ) , primarily reflecting activation of endothelial cells , and increased concentrations of soluble P-selectin and platelet-derived microvesicles ( PDM ) , primarily reflecting activation of platelets , compared with healthy controls . We also hypothesized that these markers would be differentially elevated in ischemic stroke caused by large- and small-artery atherothrombosis compared with cardiogenic embolism . METHODS We conducted a case-control study of 200 hospital-referred cases of first-ever ischemic stroke and 205 r and omly selected community controls stratified by age , sex , and postal code . Using established criteria , we classified cases of stroke by etiological subtype in a blinded fashion . The prevalence of vascular risk factors and blood concentrations of E-selectin , P-selectin , vWF antigen , and PDM were determined in stroke cases within 7 days and at 3 to 6 months after stroke and in controls . RESULTS Mean blood concentrations of soluble E-selectin , P-selectin , and PDM within 7 days of stroke onset were all significantly higher in cases compared with controls . At 3 to 6 months after stroke , the mean blood concentrations of E-selectin and P-selectin fell significantly below that of controls , and PDM concentrations remained elevated . There was a strong , grade d , and independent ( of age , sex , and vascular risk factors ) association between increasing blood concentrations of E-selectin during the acute phase and all etiological subtypes of ischemic stroke , particularly ischemic stroke caused by large-artery atherothrombosis . There was also a significant , grade d , and independent association between increasing blood concentrations of vWF during the acute phase and ischemic stroke caused by large-artery atherothrombosis . CONCLUSIONS We have demonstrated significant associations between acute elevation of blood markers of endothelial cell and platelet activation and ischemic stroke and between acute elevation of blood markers of endothelial cell activation and ischemic stroke caused by large-artery atherothrombosis . Persistent elevated blood concentrations of PDM may be a marker of increased risk of ischemic stroke BACKGROUND Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis . We assessed whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) from fish oil have differential effects on platelet , fibrinolytic and vascular function in patients with both conditions . METHODS In a double-blind placebo-controlled trial of parallel design , 59 treated-hypertensive Type 2 diabetic men and postmenopausal women , were r and omised to 4 g/day of EPA , DHA or olive oil ( placebo ) for 6 weeks . Collagen and PAF-stimulated platelet aggregation , collagen-stimulated thromboxane release ( TXB2 ) , plasma tPA and PAI-1 antigens , von Willebr and factor , p-selectin , and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery , were examined before and at the end of intervention . RESULTS Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study . Relative to placebo , DHA but not EPA supplementation significantly reduced collagen aggregation ( 16.9 % , P=0.05 ) and TXB2 ( 18.8 % , P=0.03 ) . There were no significant changes in either PAF-stimulated platelet aggregation , fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo . CONCLUSION Highly purified DHA may be a more effective anti-thrombotic agent than EPA . However , longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension Background Adherence to the Mediterranean diet ( MD ) is associated with reduced morbidity and mortality due to cardiovascular disease . However , how the MD exerts its effects is not fully known . Aim To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED ( Prevención con Dieta Mediterránea ) study . Methods A total of 164 participants at high risk for cardiovascular disease were r and omized into three diet groups : MD supplemented with 50mL/d of extra virgin olive oil ( MD+EVOO ) or 30 g/d of nuts ( MD+Nuts ) and a low-fat diet . Changes in classical cardiovascular risk factors , inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention . Results Compared to participants in the low-fat diet group , those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic ( 6mmHg ) and diastolic ( 3mmHg ) blood pressure ( P = 0.02 ; both ) , as well as a reduction of 10 % and 8 % in LDL-cholesterol ( P = 0.04 ) , respectively . Patients in the MD+Nuts group showed a significant reduction of 34 % in CD40 expression on monocyte surface compared to low-fat diet patients ( P = 0.03 ) . In addition , inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45 % and 35 % and 95 % and 90 % in the MD+EVOO and MD+Nuts groups , respectively ( P<0.05 ; all ) compared to the low-fat diet group . Likewise , sICAM and P-selectin were also reduced by 50 % and 27 % , respectively in the MD+EVOO group ( P = 0.04 ) and P-selectin by 19 % in MD+Nuts group ( P = 0.04 ) compared to the low-fat diet group . Conclusions Adherence to the MD is associated with an increase in serum markers of atheroma plaque stability which may explain , at least in part , the protective role of MD against ischemic heart disease . Trial Registration www.controlled-trials.com IS RCT BACKGROUND Adherence to the Mediterranean diet ( Med-Diet ) is associated with a reduced risk of cardiovascular disease ( CVD ) . However , the molecular mechanisms involved are not fully understood . OBJECTIVE The objective was to compare the effects of 2 Med-Diets with those of a low-fat diet on immune cell activation and soluble inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD . DESIGN In a controlled study , we r and omly assigned 112 older subjects with diabetes or > or =3 CVD risk factors to 3 dietary intervention groups : Med-Diet with supplemental virgin olive oil ( VOO ) , Med-Diet with supplemental nuts , and low-fat diet . Changes from baseline in cellular and serum inflammatory biomarkers were assessed at 3 mo . RESULTS One hundred six participants ( 43 % women ; average age : 68 y ) completed the study . At 3 mo , monocyte expression of CD49d , an adhesion molecule crucial for leukocyte homing , and of CD40 , a proinflammatory lig and , decreased ( P < 0.05 ) after both Med-Diets but not after the low-fat diet . Serum interleukin-6 and soluble intercellular adhesion molecule-1 , inflammatory mediators crucial in firm adhesion of leukocytes to endothelial surfaces , decreased ( P < 0.05 ) in both Med-Diet groups . Soluble vascular cellular adhesion molecule-1 and C-reactive protein decreased only after the Med-Diet with VOO ( P < 0.05 ) , whereas interleukin-6 , soluble vascular cellular adhesion molecule-1 , and soluble intercellular adhesion molecule-1 increased ( P < 0.05 ) after the low-fat diet . CONCLUSIONS Med-Diets supplemented with VOO or nuts down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD . The results support the recommendation of the Med-Diet as a useful tool against CVD Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective —To simultaneously evaluate 14 biomarkers from distinct biological pathways for risk prediction of ischemic stroke , including biomarkers of hemostasis , inflammation , and endothelial activation as well as chemokines and adipocytokines . Methods and Results —The Prospect i ve Epidemiological Study on Myocardial Infa rct ion ( PRIME ) is a cohort of 9771 healthy men 50 to 59 years of age who were followed up over 10 years . In a nested case – control study , 95 ischemic stroke cases were matched with 190 controls . After multivariable adjustment for traditional risk factors , fibrinogen ( odds ratio [ OR ] , 1.53 ; 95 % confidence interval [ CI ] , 1.03–2.28 ) , E-selectin ( OR , 1.76 ; 95 % CI , 1.06–2.93 ) , interferon-&ggr;-inducible-protein-10 ( OR , 1.72 ; 95 % CI , 1.06–2.78 ) , resistin ( OR , 2.86 ; 95 % CI , 1.30–6.27 ) , and total adiponectin ( OR , 1.82 ; 95 % CI , 1.04–3.19 ) were significantly associated with ischemic stroke . Adding E-selectin and resistin to a traditional risk factor model significantly increased the area under the receiver-operating characteristic curve from 0.679 ( 95 % CI , 0.612–0.745 ) to 0.785 and 0.788 , respectively , and yielded a categorical net reclassification improvement of 29.9 % ( P=0.001 ) and 28.4 % ( P=0.002 ) , respectively . Their simultaneous inclusion in the traditional risk factor model increased the area under the receiver-operating characteristic curve to 0.824 ( 95 % CI , 0.770–0.877 ) and result ed in an net reclassification improvement of 41.4 % ( P<0.001 ) . Results were confirmed when using continuous net reclassification improvement . Conclusion —Among multiple biomarkers from distinct biological pathways , E-selectin and resistin provided incremental and additive value to traditional risk factors in predicting ischemic stroke BACKGROUND Recent evidence supports the protective effects of n-3 ( omega-3 ) fatty acids ( n-3 FAs ) , such as eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , on vascular function . OBJECTIVE We investigated the effects of EPA and DHA on postpr and ial vascular function in subjects with type 2 diabetes mellitus . DESIGN In a double-blind , placebo-controlled , r and omized , crossover manner , 34 subjects with type 2 diabetes mellitus received daily either 2 g purified EPA/DHA ( termed n-3 FAs ) or olive oil ( placebo ) for 6 wk . At the end of this period , we measured macrovascular ( brachial ultrasound of flow-mediated dilatation ; FMD ) and microvascular [ laser-Doppler measurements of reactive hyperemia ( RH ) of the h and ] function at fasting and 2 , 4 , and 6 h after a high-fat meal ( 600 kcal , 21 g protein , 41 g carbohydrates , 40 g fat ) . RESULTS Fasting vascular function remained unchanged after n-3 FAs and placebo .  Postpr and ial FMD decreased from fasting after placebo , with a maximum decrease ( 38 % ) at 4 h-an effect that was significantly reduced ( P = 0.03 for time x treatment interaction ) by n-3 FA supplementation ( maximum decrease in FMD was at 4 h : 13 % ) . RH remained unchanged after placebo , whereas it improved significantly ( P = 0.04 for time x treatment interaction ) after n-3 FA supplementation ( maximum increase was at 2 h : 27 % ) . CONCLUSIONS In subjects with type 2 diabetes mellitus , 6 wk of supplementation with n-3 FAs reduced the postpr and ial decrease in macrovascular function relative to placebo . Moreover , n-3 FA supplementation improved postpr and ial microvascular function . These observations suggest a protective vascular effect of n-3 FAs OBJECTIVE Nuclear transcription factor kappaB ( NF-kappaB ) plays a key role in the inflammatory response and can be modulate by dietary fat . We have examined the effect of three diets , with different fat composition , on the activation of NF-kappaB on peripheral blood mononuclear cells ( P BMC s ) . METHODS Sixteen healthy men followed three 4-week diets , in a r and omised crossover design : a Western diet , rich in saturated fat ( SFA ) [ 22 % SFA , 12 % monounsaturated fat ( MUFA ) and 0 , 4 alpha-linolenic acid ] ; a Mediterranean diet [ < 10 % SFA , 24 % MUFA and 0.4 % alpha-linolenic acid ] , and a low fat diet enriched in alpha-linolenic acid [ < 10 % SFA , 12 % MUFA and 2 % alpha-linolenic acid ] . NF-kappaB ( electrophoretic mobility shift assay ) in mononuclear cells and plasma concentrations ( ELISA ) of soluble vascular cellular adhesion molecule 1 ( VCAM-1 ) were examined after either diets . RESULTS Western diet increased 2.7-fold NF-kappaB compared with the Mediterranean diet ( p=0.038 ) and 1.79-fold with the alpha-linolenic acid diet ( p=0.07 ) . No differences were found between the last two . Furthermore , an increase on plasma VCAM-1 was observed with the Western diet ( p<0.05 ) . CONCLUSIONS The Mediterranean diet diminished NF-kappaB activation in mononuclear cells , compared with Western diet , supporting its cardioprotective properties . The effect of the n-3 enriched diet was intermediate Both ( n-3 ) long-chain PUFA ( LCPUFA ) and linoleic acid [ LA , 18:2(n-6 ) ] improve cardiovascular disease ( CVD ) risk factors , but a high-LA intake may weaken the effect of ( n-3 ) LCPUFA . In a controlled , double-blind , 2 x 2-factorial 8-wk intervention , we investigated whether fish oil combined with a high- or low-LA intake affects overall CVD risk profile .  Healthy men ( n = 64 ) were r and omized to 5 mL/d fish oil capsules ( FO ) [ mean intake 3.1 g/d ( n-3 ) LCPUFA ] or olive oil capsules ( control ) and to oils and spreads with either a high ( S/B ) or a low ( R/K ) LA content , result ing in a 7.3 g/d higher LA intake in the S/B groups than in the R/K groups . Diet , ( n-3 ) LCPUFA in peripheral blood mononuclear cells , blood pressure ( BP ) , heart rate ( HR ) , and plasma CVD risk markers were measured before and after the intervention . FO lowered fasting plasma triacylglycerol ( TAG ) ( P < 0.001 ) by 51 % and 19 % in the FO+R/K-group and FO+S/B-group , respectively , which was also reflected in postpr and ial TAG measured after the intervention ( P < 0.01 ) . Although a fat x FO interaction was found for monocyte chemoattractant protein-1 , neither the FO nor fat intervention affected fasting plasma cholesterol , glucose , insulin , fibrinogen , C-reactive protein , interleukin-6 , vascular cell adhesion molecule-1 , P-selectin , oxidized LDL , cluster of differentiation antigen 40 lig and ( CD40L ) , adiponectin , or fasting or postpr and ial BP or HR after adjustment for body weight changes . In conclusion , neither fish oil supplementation nor the LA intake had immediate pronounced effects on the overall CVD risk profile  in healthy men , but fish oil lowered plasma TAG in healthy subjects with initially low concentrations 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 Background In type 2 diabetes , acute hyperglycemia worsens endothelial function and inflammation , while resistance to GLP-1 action occurs . All these phenomena seem to be related to the generation of oxidative stress . A Mediterranean diet , supplemented with olive oil , increases plasma antioxidant capacity , suggesting that its implementation can have a favorable effect on the aforementioned phenomena . In the present study , we test the hypothesis that a Mediterranean diet using olive oil can counteract the effects of acute hyperglycemia and can improve the resistance of the endothelium to GLP-1 action . Methods Two groups of type 2 diabetic patients , each consisting of twelve subjects , participated in a r and omized trial for three months , following a Mediterranean diet using olive oil or a control low-fat diet .  Plasma antioxidant capacity , endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels were evaluated at baseline and at the end of the study . The effect of GLP-1 during a hyperglycemic clamp , was also studied at baseline and at the end of the study . Results Compared to the control diet , the Mediterranean diet increased plasma antioxidant capacity and improved basal endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels . The Mediterranean diet also reduced the negative effects of acute hyperglycemia , induced by a hyperglycemic clamp , on endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels . Furthermore , the Mediterranean diet improved the protective action of GLP-1 on endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels , also increasing GLP-1-induced insulin secretion . Conclusions These data suggest that the Mediterranean diet , using olive oil , prevents the acute hyperglycemia effect on endothelial function , inflammation and oxidative stress , and improves the action of GLP-1 , which may have a favorable effect on the management of type 2 diabetes , particularly for the prevention of cardiovascular disease Inflammatory markers as circulating soluble cellular adhesion molecules ( sCAMs ) and high sensitive C-reactive protein ( hsCRP ) are elevated in patients with chronic heart failure ( CHF ) , and may constitute an increased risk of adverse outcome . Marine n-3 polyunsaturated fatty acids ( n-3 PUFA ) may have anti-inflammatory effect and reduce levels of sCAMs ( soluble intercellular adhesion molecule-1 ( sICAM-1 ) , vascular adhesion molecule-1 ( sVCAM-1 ) , P-selectin ) and hsCRP . In a r and omized , controlled trial , 138 patients with NYHA class II-III CHF were allocated to receive a daily supplement of 0.9 g of n-3 PUFA or olive oil for 24 weeks . After supplementation , no significant changes occurred in sCAMs or hsCRP after adjusting for possible confounders . However , a significant reduction was observed in sP-selectin in patients receiving n-3 PUFA , but this result was only of borderline significance in a between-group analysis . In conclusion , a daily supplement with 0.9 g of n-3 PUFA does not significantly affect plasma levels of sCAMs or hs-CRP in patients with CHF . n-3 PUFA may reduce sP-selectin , indicating a possible effect on platelet ( and endothelial ) activation . The results also indicate that the low dose of n-3 PUFA used in many intervention trials does not have deleterious effects on sCAMs or hsCRP OBJECTIVES We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein ( CRP ) , white blood cell counts , interleukin (IL)-6 , tumor necrosis factor (TNF)-alpha , amyloid A , fibrinogen , and homocysteine . BACKGROUND To the best of our knowledge , the mechanism(s ) by which the Mediterranean diet reduces cardiovascular risk are not well understood . METHODS During the 2001 to 2002 period , we r and omly enrolled 1,514 men ( 18 to 87 years old ) and 1,528 women ( 18 to 89 years old ) from the Attica area of Greece ( of these , 5 % of men and 3 % of women were excluded because of a history of cardiovascular disease ) . Among several factors , adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet . Higher values of the score meant closer adherence to the Mediterranean diet . RESULTS Participants who were in the highest tertile of the diet score had , on average , 20 % lower CRP levels ( p = 0.015 ) , 17 % lower IL-6 levels ( p = 0.025 ) , 15 % lower homocysteine levels ( p = 0.031 ) , 14 % lower white blood cell counts ( p = 0.001 ) , and 6 % lower fibrinogen levels ( p = 0.025 ) , as compared with those in the lowest tertile . The findings remained significant even after various adjustments were made . Borderline associations were found regarding TNF-alpha ( p = 0.076 ) , amyloid A levels ( p = 0.19 ) , and diet score . CONCLUSIONS Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers . This may partly explain the beneficial actions of this diet on the cardiovascular system Obesity is associated with an increased risk of cardiovascular disease , whereas long-chain n-3 polyunsaturated fatty acids ( PUFAs ) from fish may have cardioprotective and anti-inflammatory effects . This study aim ed to investigate the hypothesis that acute and short-term supplementation with a low dose of marine n-3 PUFA exerts an anti-inflammatory effect in overweight subjects . In a double-blind , placebo-controlled trial with 2 parallel groups , 50 overweight subjects were r and omized to receive daily supplementation with 2 capsules containing either 2 g of fish oil ( 1.1 g marine n-3 PUFA ) or 2 g of olive oil .  Blood sample s and adipose tissue biopsies were collected at baseline , after 1 day ( acute effect ) , and after 6 weeks ( short-term effect ) of supplementation . No significant effects were seen after supplementation for 1 day , but after 6 weeks , subjects receiving fish oil had a significant increase in the n-3 PUFA content of granulocytes and adipose tissue ( P < .01 ) . Serum adiponectin levels were increased by 0.55 μg/mL ( 95 % confidence interval , 0.02 - 1.08 ) in the fish oil group compared with the control group ( P = .04 ) after 6 weeks of supplementation . Levels of interleukin 6 were inversely correlated to the marine n-3 PUFA content of granulocytes and adipose tissue at baseline ( excluding α-linolenic acid ) . In conclusion , daily supplementation with 1.1 g of marine n-3 PUFA  significantly increased serum adiponectin , but the effect was small , and no overall anti-inflammatory effect of the supplement could be demonstrated BACKGROUND C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events . We report data from a large study of C-reactive protein and other circulating inflammatory markers , as well as up date d meta-analyses , to evaluate their relevance to the prediction of coronary heart disease . METHODS Measurements were made in sample s obtained at base line from up to 2459 patients who had a nonfatal myocardial infa rct ion or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospect i ve study of 18,569 participants .  Measurements were made in paired sample s obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels . RESULTS The long-term stability of C-reactive protein values ( within-person correlation coefficient , 0.59 ; 95 percent confidence interval , 0.52 to 0.66 ) was similar to that of both blood pressure and total serum cholesterol . After adjustment for base-line values for established risk factors , the odds ratio for coronary heart disease was 1.45 ( 95 percent confidence interval , 1.25 to 1.68 ) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third , and similar overall findings were observed in an up date d meta- analysis involving a total of 7068 patients with coronary heart disease . By comparison , the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate ( 1.30 ; 95 percent confidence interval , 1.13 to 1.51 ) and the von Willebr and factor concentration ( 1.11 ; 95 percent confidence interval , 0.97 to 1.27 ) but generally stronger for established risk factors , such as an increased total cholesterol concentration ( 2.35 ; 95 percent confidence interval , 2.03 to 2.74 ) and cigarette smoking ( 1.87 ; 95 percent confidence interval , 1.62 to 2.16 ) . CONCLUSIONS C-reactive protein is a relatively moderate predictor of coronary heart disease . Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be review ed OBJECTIVES The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity . BACKGROUND Endothelial-dependent vasodilatation is impaired during the postpr and ial state , and oxidative stress could play a key role in its development . METHODS Twenty-one hypercholesterolemic volunteers received two breakfasts , using a r and omized sequential crossover design . Both arms received the same olive oil , but one had its phenolic acid content reduced from 400 to 80 ppm . Ischemic reactive hyperemia ( IRH ) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake . Postpr and ial plasma concentrations of lipid fractions , lipoperoxides ( LPO ) , 8-epi prostagl and in-F(2alpha ) , and nitrates/nitrites ( NO(x ) ) were obtained at baseline and after 2 h of the fat meal . RESULTS The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function , as well as a greater increase in concentrations of NO(x ) ( p < 0.001 ) and a lower increase in LPO ( p < 0.005 ) and 8-epi prostagl and in-F2alpha ( p < 0.001 ) than the ones induced by the low polyphenol fat meal . A positive correlation was found to exist between NO(x ) and enhanced endothelial function at the second hour ( r = 0.669 ; p < 0.01 ) . Furthermore , a negative correlation was found between IRH and LPO ( r = -0.203 ; p < 0.05 ) and 8-epi prostagl and in-F2alpha levels ( r = -0.440 ; p < 0.05 ) . CONCLUSIONS A meal containing high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postpr and ial state . This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites Traditional cardiovascular risk factors are associated with endothelial dysfunction . The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat . We propose to determine the chronic effect of three diets with different fat compositions on postpr and ial endothelial function and inflammatory biomarkers . Twenty healthy men followed three 4-week diets in a r and omised cross-over design : a Western diet , rich in saturated fat ( 22 % SFA , 12 % MUFA and 0.4 % alpha-linolenic acid ( ALA ) , all fractions are % of energy ) ; a Mediterranean diet , rich in MUFA ( < 10 % SFA , 24 % MUFA and 0.4 % ALA ) ; a low-fat diet enriched in ALA ( < 10 % SFA , 12 % MUFA and 2 % ALA ) . At the end of each dietary period all subjects underwent a postpr and ial study . Plasma concentrations of lipid parameters , soluble intercellular cell-adhesion molecule-1 , soluble vascular cell-adhesion molecule-1 ( sVCAM-1 ) , nitrates and nitrites ( NOx ) and endothelial function studied by laser Doppler were examined at 0 , 2 , 4 , 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets ( P = 0.031 ) . The 4 h postpr and ial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet ( P = 0.043 ) . The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets ( P = 0.027 ) . We found no differences in the other parameters measured . Chronic ingestion of a Mediterranean diet avoids the postpr and ial deterioration of endothelial function associated with Westernised diets in healthy individuals Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions OBJECTIVES The goal of this study was to prospect ively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events . BACKGROUND Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors . The prospect i ve relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown . METHODS We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery .  Patients were prospect ively followed with an average follow-up of 1.2 years after surgery . RESULTS Thirty-five patients had an event during follow-up , including cardiac death ( 5 patients ) , myocardial infa rct ion ( 17 patients ) , unstable angina ( 10 patients ) , or stroke ( 3 patients ) . Preoperative endothelium-dependent flow-mediated dilation ( FMD ) was significantly lower in patients with an event ( 4.4 + /- 2.8 % ) compared with those without an event ( 7.0 + /- 4.9 % , p < 0.001 ) , whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups . In a Cox proportional-hazards model , independent predictors of events included age ( p = 0.003 ) , more invasive surgery ( surgery other than carotid endarterectomy , p = 0.02 ) , and impaired brachial-artery endothelial function ( p = 0.002 ) . Risk was approximately nine-fold higher in patients with FMD < 8.1 % ( lower two tertiles ) compared with those in the upper tertile ( odds ratio 9.5 ; 95 % confidence interval 2.3 to 40 ) . CONCLUSIONS Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease . The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk Objective : Conjugated linoleic acid ( CLA ) showed a wide range of beneficial biological effects with relevance for cardiovascular health in animal models and humans . Most human studies used olive oil as a reference . This study assessed the effect of CLA as compared with safflower oil on endothelial function and markers of cardiovascular risk in overweight and obese men .  Heated safflower oil and olive oil were given for additional descriptive control . Methods : Eighty-five overweight men ( aged 45–68 years , body mass index 25–35 kg/m2 ) were r and omized to receive 4.5 g/d of the CLA isomeric mixture , safflower oil , heated safflower oil , or olive oil in a 4-week double-blind study .  Endothelial function was assessed by peripheral arterial tonometry ( PAT ) index determination in the fasting and postpr and ial state ( i.e. , 4 hours after consumption of a fat- and sucrose-rich meal ) . Results : CLA as compared with safflower oil consumption did not impair fasting or postpr and ial PAT index but decreased body weight .  CLA as compared with safflower oil did not change total , low-density lipoprotein ( LDL ) , or high-density lipoprotein ( HDL ) cholesterol ; triglycerides ; insulin sensitivity indices ; C-reactive protein ; soluble adhesion molecules ; oxidized LDL ; lipoprotein a ( Lp[a ] ) ; paraoxonase ; or platelet-activating factor acetylhydrolase ( PAF-AH ) activity , but significantly reduced arylesterase activity and increased concentrations of the F2-isoprostane 8-iso-prostagl and in F (PGF)2α . Conclusion : CLA did not impair endothelial function . Other parameters associated with metabolic syndrome and oxidative stress were not changed or were slightly improved . Results suggest that CLA does not increase cardiovascular risk . Increased F2-isoprostane concentrations in this context may not indicate increased oxidative stress BACKGROUND AND AIM Long-chain n-3 polyunsaturated fatty acids ( PUFA ) may protect against atherosclerotic disease , and serum levels of soluble cellular adhesion molecules ( sCAMs ) possibly reflect the inflammatory process underlying atherosclerosis . We studied the effect of n-3 PUFA dietary supplementation on the serum levels of sP-selectin , soluble intercellular adhesion molecule-1 ( sICAM-1 ) and soluble vascular adhesion molecule-1 ( sVCAM-1 ) , and the correlation between sCAMs and the fatty acid composition of granulocyte membranes . METHODS AND RESULTS Sixty healthy volunteers were r and omly assigned to receive a daily supplement of n-3 PUFA 6.6 g , n-3 PUFA 2.0 g , or olive oil for 12 weeks in a double blind design . A significant negative correlation was found between serum sICAM-1 levels and the DHA content of granulocyte membranes at entry . After supplementation with 6.6 g of n-3 PUFA , there was a significant decrease only in sP-selectin , which a gender sub analysis showed to be more marked in men . Among the women , there was a significant decrease in sICAM-1 in the PUFA 2.0 g group and a significant increase in sVCAM-1 in the PUFA 6.6 g group . CONCLUSIONS The results indicate that high-dose supplementation with n-3 PUFA decreases sP-selectin levels in healthy subjects , thus suggesting a decrease in platelet reactivity or endothelial activation . However , the effect of n-3 PUFA on sCAMs is complex and may depend on gender and n-3 PUFA dose OBJECTIVE Olive oil ( OO ) is a rich source of monounsaturated fat and bioactive components that exert strong anti-oxidant and anti-inflammatory properties . Flaxseed oil ( FO ) is rich in α-linolenic n-3 fatty acid ( ALA ) , which also exhibits anti-inflammatory effects . This r and omized , cross-over study aim ed at exploring whether diet 's enrichment with FO could beneficially alter inflammatory markers and lipid profile , compared to OO , in a sample of normal weight , apparently healthy young adults . MATERIAL S AND METHODS Participants were supplied with 15 mL/day of either FO or OO . Each intervention and the wash-out period lasted 6 weeks . Dietary , anthropometric and physical activity variables were recorded at the beginning and the end of each intervention . Serum biochemical and inflammatory markers were measured . Compliance to the intervention was evaluated by fatty acid analysis in erythrocytes . Repeated Measures ANOVA was used to assess the effect of the treatment . RESULTS Thirty seven participants completed the study . No difference between the two interventions was observed in adiponectin , TNF-α , high sensitivity-CRP or glucose levels and lipid profile . At the end of the FO period , participants exhibited significant reductions in total ( -5.0 % ) and LDL-cholesterol ( -6.7 % ) levels ( all P<0.01 ) . During the FO and the OO period serum adiponectin changes were significantly correlated with changes in erythrocyte % ALA ( rs=0.34 , P=0.007 ) and in erythrocyte % EPA ( r(s)=0.47 , P=0.01 ) , respectively . CONCLUSIONS Daily consumption of FO did not confer any benefit in inflammatory or biochemical markers in normal weight young adults , who traditionally use olive oil as the main edible oil BACKGROUND Dietary fat type is known to modulate the plasma lipid profile , but its effects on plasma homocysteine and inflammatory markers are unclear . OBJECTIVE We investigated the effects of high-protein Malaysian diets prepared with palm olein , coconut oil ( CO ) , or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease ( CVD ) in healthy adults . DESIGN A r and omized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects . The 3 test fats , namely palmitic acid (16:0)-rich palm olein ( PO ) , lauric and myristic acid ( 12:0 + 14:0)-rich CO , and oleic acid (18:1)-rich virgin olive oil ( OO ) , were incorporated at two-thirds of 30 % fat calories into high-protein Malaysian diets . RESULTS No significant differences were observed in the effects of the 3 diets on plasma total homocysteine ( tHcy ) and the inflammatory markers TNF-α , IL-1β , IL-6 , and IL-8 , high-sensitivity C-reactive protein , and interferon-γ . Diets prepared with PO and OO had comparable nonhypercholesterolemic effects ; the postpr and ial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower ( P < 0.05 ) than for the CO diet . Unlike the PO and OO diets , the CO diet was shown to decrease postpr and ial lipoprotein(a ) . CONCLUSION Diets that were rich in saturated fatty acids prepared with either PO or CO , and an OO diet that was high in oleic acid , did not alter postpr and ial or fasting plasma concentrations of tHcy and selected inflammatory markers . This trial was registered at clinical trials.gov as NCT00941837 Purpose Recent epidemiological studies have shown that habitual consumption of extra virgin olive oil ( EVOO ) , the characteristic culinary fat of the Mediterranean area , is effective in the prevention of diverse types of digestive disorders such as inflammatory bowel disease . Many of these benefits are , in addition to its high proportion of oleic acid , due to the high content of phenolic compounds . Methods Six-week-old mice were r and omized into three dietary groups : st and ard , EVOO and hydroxytyrosol-enriched EVOO . After 30 days , mice that were exposed to 3 % DSS for 5 days developed acute colitis that progressed to severe chronic inflammation during a regime of 21 days of water . Results Diets enriched with EVOO significantly attenuated the clinical and histological signs of damage , improving results from disease activity index and reducing about 50 % the mortality caused by DSS . Moreover , hydroxytyrosol supplement showed better results . Cytokines study showed that TNF-α was maintained near to sham control and IL-10 levels were significantly improved in EVOO and EVOO plus hydroxytyrosol diet-DSS groups . In the same way , COX-2 and iNOS were downregulated , and the activation of p38 MAPK was reduced . We also observed a higher significant reduction in iNOS in hydroxytyrosol-enriched EVOO compared with EVOO alone . Conclusions EVOO diets exerted a noteworthy beneficial effect in chronic DSS-induced colitis by cytokine modulation and COX-2 and iNOS reduction via downregulation of p38 MAPK . In addition to the beneficial effect by EVOO , supplementation of the diet with hydroxytyrosol may improve chronic colitis through iNOS downregulation plus its antioxidant capacity The aim of the study was to assess whether benefits associated with the traditional Mediterranean diet ( TMD ) and virgin olive oil ( VOO ) consumption could be mediated through changes in the expression of atherosclerosis-related genes . A r and omized , parallel , controlled clinical trial in healthy volunteers ( n=90 ) aged 20 to 50 yr was performed . Three-month intervention groups were as follows : 1 ) TMD with VOO ( TMD+VOO ) , 2 ) TMD with washed virgin olive oil ( TMD+WOO ) , and 3 ) control with participants ' habitual diet . WOO was similar to VOO , but with a lower polyphenol content ( 55 vs. 328 mg/kg , respectively ) . TMD consumption decreased plasma oxidative and inflammatory status and the gene expression related with both inflammation [ INF-gamma ( INFgamma ) , Rho GTPase-activating protein15 ( ARHGAP15 ) , and interleukin-7 receptor ( IL7R ) ] and oxidative stress [ adrenergic beta(2)-receptor ( ADRB2 ) and polymerase ( DNA-directed ) kappa ( POLK ) ] in peripheral blood mononuclear cells . All effects , with the exception of the decrease in POLK expression , were particularly observed when VOO , rich in polyphenols , was present in the TMD dietary pattern . Our results indicate a significant role of olive oil polyphenols in the down-regulation of proatherogenic genes in the context of a TMD . In addition , the benefits associated with a TMD and olive oil polyphenol consumption on cardiovascular risk can be mediated through nutrigenomic effects BACKGROUND The dietary intake of n-3 ( omega-3 ) long-chain PUFAs ( LC-PUFAs ) from fish may improve  endothelial function and arterial stiffness .  OBJECTIVE The objective was to test the hypothesis that increasing intakes of n-3 LC-PUFAs-equivalent to the consumption of 1 , 2 , or 4 portions of oily fish per week-favorably affects endothelial function and arterial stiffness . DESIGN A parallel- design , r and omized , double-blind study compared daily doses of 0.45 , 0.9 , and 1.8 g n-3 LC-PUFAs ( EPA : DHA ratio of 1.51:1 ) with placebo ( refined olive oil ) . The primary and secondary outcomes were changes in flow-mediated dilatation ( FMD ) of the brachial artery , arterial stiffness , and blood pressure .  Nonsmoking men ( n = 142 ) and women ( n = 225 ) aged 45 - 70 y were r and omly assigned to treatment for 12 mo ; 312 subjects completed the intervention . RESULTS Compliance with the intervention was corroborated by significant dose-dependent increases in the proportions of EPA and DHA in erythrocyte lipids and a 16.5 % reduction in serum triacylglycerol concentrations with 1.8 g n-3 LC-PUFAs/d . FMD was lower in men than in women ( P < 0.0001 ) and decreased with age ( ρ = 0.270 , P < 0.001 ) but was not significantly ( P = 0.781 ) related to n-3 LC-PUFA intake . The mean changes in FMD ( 95 % CIs ) compared with placebo were 0.1 % ( -0.9 % , 1.1 % ) , -0.3 % ( -1.3 % , 0.6 % ) , and -0.3 % ( -1.3 % , 0.7 % ) with daily intakes of 0.45 , 0.9 , and 1.8 g n-3 LC-PUFAs , respectively . No significant treatment effects were noted for arterial stiffness and central mean or 24-h ambulatory blood pressure . CONCLUSION Intakes of n-3 LC-PUFAs ≤1.8 g/d do not improve endothelial function in healthy adults . The trial is registered at controlled-trials.com as IS RCT N66664610 Fish oil ( FO ) is considered antiinflammatory , but evidence regarding its effect on human cytokine production is conflicting . High linoleic acid ( LA ) intake may impair any effects of FO . The aim of this study was to investigate how FO combined with high or low LA intake affected ex vivo cytokine production from cultures of whole blood , peripheral blood mononuclear cells ( P BMC ) , and monocytes in healthy men . The study was a double-blinded , controlled , 2 x 2 factorial 8-wk intervention . Sixty-four healthy men were r and omized to 5 mL/d FO or olive oil ( OO ) provided in capsules and to spreads and oils with high or low LA content , result ing in LA intakes of 7 + /- 2 % and 4 + /- 1 % energy , respectively . We measured eicosapentaenoic acid ( EPA ) in P BMC and stimulated cytokine production in whole blood and P BMC 24-h cultures before and immediately after intervention and after an 8-wk wash-out period , and in monocyte cultures immediately after intervention . P BMC -EPA was markedly increased by FO ( P < 0.001 ) . LA intake did not modify the incorporation of FO and tended to have only a slight effect on P BMC -EPA by itself ( P = 0.06 ) . Lipopolysaccharide (LPS)-stimulated whole-blood interleukin (IL)-6 production immediately after intervention was lower with FO than OO ( P = 0.02 ) but did not correlate with P BMC -EPA in the FO groups ( r = -0.12 ; P = 0.53 ; n = 31 ) . The LA intake did not modify IL-6 production or the effect of FO . Neither FO nor LA intake affected the production of tumor necrosis factor-alpha , IL-10 , or interferon-gamma in any of the cultures . In conclusion , FO intake reduced IL-6 production from LPS-stimulated whole blood in healthy men compared with OO , but the effect was not modified by the LA intake n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms . Despite this , there has been concern that these fatty acids may increase lipid peroxidation . The data in vivo are inconclusive , due in part to limitations in the method ologies . In this regard , the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress . This study aim ed to assess the effects of supplementation with purified eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) , the two major n-3 fatty acids , on urinary F2-isoprostanes and markers of inflammation , in type 2 diabetic patients . In a double-blind , placebo controlled trial of parallel design , 59 nonsmoking , treated-hypertensive , type 2 diabetic subjects , were r and omized to 4 g daily of purified EPA , DHA , or olive oil for 6 weeks , while maintaining their usual diet . F2-isoprostanes , measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-alpha ) , were measured before and after intervention . Thirty-nine men and 12 women aged 61.2 + /- 1.2 years , with body mass index ( BMI ) , 29.5 + /- 0.5 kg/m2 ; 24 h blood pressure , 138/73 mmHg ; HbA1c , 7.3 + /- 0.1 % and fasting glucose , 7.9 + /- 0.2 mmol/l completed the intervention .  Baseline urinary F2-isoprostanes were positively associated with HbA1c ( p=.011 ) and fasting glucose ( p=.032 ) . Relative to the olive oil group , postintervention urinary F2-isoprostanes were decreased 19 % by EPA ( p=.017 ) and 20 % by DHA ( p=.014 ) . There were no significant changes in CRP , IL-6 , and TNF-alpha following EPA or DHA supplementation . In regression analysis , Delta F2-isoprostanes were positively associated with Delta HbA1c ( p=.007 ) independent of treatment group ; and with Delta TNF-alpha ( p=.034 ) independent of age , gender , BMI , and treatment group . There were no associations with Delta CRP or Delta IL-6 . This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation , in treated hypertensive , type 2 diabetic subjects BACKGROUND Olive oil polyphenols have been associated with several cardiovascular health benefits . This study aims to examine the influence of a polyphenol-rich olive oil on blood pressure ( BP ) and endothelial function in 24 young women with high-normal BP or stage 1 essential hypertension . METHODS We conducted a double-blind , r and omized , crossover dietary-intervention study . After a run-in period of 4 months ( baseline values ) , two diets were used , one with polyphenol-rich olive oil ( ∼30 mg/day ) , the other with polyphenol-free olive oil . Each dietary period lasted 2 months with a 4-week washout between diets . Systolic and diastolic BP , serum or plasma biomarkers of endothelial function , oxidative stress , and inflammation , and ischemia-induced hyperemia in the forearm were measured . RESULTS When compared to baseline values , only the polyphenol-rich olive oil diet led to a significant ( P < 0.01 ) decrease of 7.91 mm Hg in systolic and 6.65 mm Hg of diastolic BP . A similar finding was found for serum asymmetric dimethylarginine ( ADMA ) ( -0.09 ± 0.01 µmol/l , P < 0.01 ) , oxidized low-density lipoprotein ( ox-LDL ) ( -28.2 ± 28.5 µg/l , P < 0.01 ) , and plasma C-reactive protein ( CRP ) ( -1.9 ± 1.3 mg/l , P < 0.001 ) . The polyphenol-rich olive oil diet also elicited an increase in plasma nitrites/nitrates ( + 4.7 ± 6.6 µmol/l , P < 0.001 ) and hyperemic area after ischemia ( + 345 ± 386 perfusion units (PU)/sec , P < 0.001 ) . CONCLUSIONS We concluded that the consumption of a diet containing polyphenol-rich olive oil can decrease BP and improve endothelial function in young women with high-normal BP or stage 1 essential hypertension BACKGROUND Traditional diets that include moderate to high intakes of extra virgin olive oil have been related to a decrease in breast cancer risk . We hypothesized that an olive oil-enriched diet would lead to greater weight loss and acceptance , compared with a st and ard diet , in women previously diagnosed with invasive breast cancer . METHODS Participants consumed a  National Cancer Institute ( NCI ) diet ( total fat > 15 % and < 30 % ) and a plant-based olive oil diet ( PBOO ; > or = 3 tablespoons of olive oil/day ) for 8 weeks , each with r and om assignment to the order . We established a weight loss goal of at least 5 % of baseline weight . After completion of the two diet trials , each participant self-selected one of the diets for an additional 6 months of follow-up for weight management . Body measures were done before and after each diet and after follow-up ; fasting blood sample s were collected after each diet and after follow-up . RESULTS Forty-four overweight women started and 28 completed the 44-week protocol . Twelve ( 80 % ) of the 15 women who started with the PBOO diet achieved a weight loss of > or = 5 % compared to 4 ( 31 % ) of the 13 who started with the NCI diet ( p < 0.01 ) . Nineteen of the 22 women eligible for follow-up chose the PBOO diet , and all completed the study . Of the 3 women who chose the NCI diet for follow-up , 1 completed the study . The PBOO diet result ed in lower triglycerides ( NCI 105 + /- 46 mg/dL , PBOO 96 + /- 37 mg/dL , p = 0.06 ) and higher high-density lipoprotein cholesterol ( HDL-C ) ( NCI 64 + /- 13 mg/dL , PBOO 68 + /- 12 mg/dL , p = 0.001 ) . CONCLUSIONS An olive oil-enriched diet brought about greater weight loss than a lower-fat diet in an 8-week comparison . Moreover , these women chose , overwhelmingly , the olive oil-enriched diet for 6 months of follow-up . An olive oil-enriched diet may be more efficacious for weight loss in breast cancer survivors than a st and ard lower-fat diet Anta rct ic krill , also known as Euphausia superba , is a marine crustacean rich in both eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) . We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety , tolerability , or selected metabolic parameters . In this r and omized , double-blind parallel arm trial , overweight and obese men and women ( N = 76 ) were r and omly assigned to receive double-blind capsules containing 2 g/d of krill oil , menhaden oil , or control ( olive ) oil for 4 weeks . Results showed that plasma EPA and DHA concentrations increased significantly more ( P < .001 ) in the krill oil ( 178.4 + /- 38.7 and 90.2 + /- 40.3 micromol/L , respectively ) and menhaden oil ( 131.8 + /- 28.0 and 149.9 + /- 30.4 micromol/L , respectively ) groups than in the control group ( 2.9 + /- 13.8 and -1.1 + /- 32.4 micromol/L , respectively ) . Systolic blood pressure declined significantly more ( P < .05 ) in the menhaden oil ( -2.2 + /- 2.0 mm Hg ) group than in the control group ( 3.3 + /- 1.5 mm Hg ) , and the response in the krill oil group ( -0.8 + /- 1.4 mm Hg ) did not differ from the other 2 treatments . Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group ( P < .006 ) . No significant differences for other safety variables were noted , including adverse events . In conclusion , 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated , with no indication of adverse effects on safety parameters Adherence to a Mediterranean diet ( MD ) is associated with a reduced risk of coronary heart disease . However , the molecular mechanisms involved are not fully understood . The aim of this study was to compare the effects of 2 MD with those of a low-fat-diet ( LFD ) on circulating inflammatory biomarkers related to atherogenesis . A total of 516 participants included in the Prevention with Mediterranean Diet Study were r and omized into 3 intervention groups [ MD supplemented with virgin olive oil ( MD-VOO ) ; MD supplemented with mixed nuts ( MD-Nuts ) ; and LFD ] . At baseline and after 1 y , participants completed  FFQ  and adherence to MD  question naires , and plasma concentrations of inflammatory markers including intercellular adhesion molecule-1(ICAM-1 ) , IL-6 , and 2 TNF receptors ( TNFR60 and TNFR80 ) were measured by ELISA . At 1 y , the MD groups had lower plasma concentrations of IL-6 , TNFR60 , and TNFR80 ( P < 0.05 ) , whereas ICAM-1 , TNFR60 , and TNFR80 concentrations increased in the LFD group ( P < 0.002 ) . Due to between-group differences , participants in the 2 MD groups had lower plasma concentrations of ICAM-1 , IL-6 , TNFR60 , and TNFR80 compared to those in the LFD group ( P ≤ 0.028 ) . When participants were categorized in tertiles of 1-y changes in the consumption of selected foods , those in the highest tertile of virgin olive oil ( VOO ) and vegetable consumption had a lower plasma TNFR60 concentration compared with those in tertile 1 ( P < 0.02 ) . Moreover , the only changes in consumption that were associated with 1-y changes in the geometric mean TNFR60 concentrations were those of VOO and vegetables ( P = 0.01 ) . This study suggests that a MD reduces TNFR concentrations in patients at high cardiovascular risk
target: These results provide evidence that olive oil might exert beneficial effects on endothelial function as well as markers of inflammation and endothelial function , thus representing a key ingredient contributing to the cardiovascular-protective effects of a Mediterranean diet .
background: The aim of the present systematic review was to synthesize data from r and omized controlled trials investigating the effects of olive oil on markers of inflammation or endothelial function .