title: High-oleic rapeseed (canola) and flaxseed oils modulate serum lipids and inflammatory biomarkers in hypercholesterolaemic subjects. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. Flaxseed oil supplementation decreases C-reactive protein levels in chronic hemodialysis patients. Influence of dietary supplementation with long-chain n−3 or n−6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function. Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. α-Linolenic acid increases the G0/G1 switch gene 2 mRNA expression in peripheral blood mononuclear cells from obese patients: a pilot study Effect of flaxseed oil on serum systemic and vascular inflammation markers and oxidative stress in hemodialysis patients: a randomized controlled trial Does grape seed oil improve inflammation and insulin resistance in overweight or obese women? Antihypertensive effect and safety of dietary alpha-linolenic acid in subjects with high-normal blood pressure and mild hypertension. Reduction of Inflammatory Cytokine Concentrations and Improvement of Endothelial Functions in Obese Women After Weight Loss Over One Year Associations of erythrocyte membrane fatty acids with the concentrations of C-reactive protein, interleukin 1 receptor antagonist and adiponectin in 1373 men. Effects of flaxseed oil supplementation on plasma adiponectin levels in dyslipidemic men Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Increased α-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis The effect of diet enriched with alpha-linolenic acid on soluble cellular adhesion molecules in dyslipidaemic patients. Alpha-linolenic acid supplementation and resistance training in older adults. No effect of n-3 fatty acids supplementation on NT-proBNP after myocardial infarction: The Alpha Omega Trial Effects of diets containing olive oil, sunflower oil, or rapeseed oil on the hemostatic system. Supplementation of α-linolenic acid improves serum adiponectin levels and insulin sensitivity in patients with type 2 diabetes. Flaxseed oil does not affect inflammatory markers and lipid profile compared to olive oil, in young, healthy, normal weight adults. A Comparison of Fish Oil, Flaxseed Oil and Hempseed Oil Supplementation on Selected Parameters of Cardiovascular Health in Healthy Volunteers Inflammation markers predict zinc transporter gene expression in women with type 2 diabetes mellitus. Background diet influences the anti-inflammatory effect of alpha-linolenic acid in dyslipidaemic subjects.
abstract: Recently , novel dietary oils with modified fatty acid profiles have been manufactured to improve fatty acid intakes and reduce CVD risk . Our objective was to evaluate the efficacy of novel high-oleic rapeseed ( canola ) oil ( HOCO ) , alone or blended with flaxseed oil ( FXCO ) , on circulating lipids and inflammatory biomarkers v. a typical Western diet ( WD ) . Using a r and omised , controlled , crossover trial , thirty-six hypercholesterolaemic subjects consumed three isoenergetic diets for 28 d each containing approximately 36 % energy from fat , of which 70 % was provided by HOCO , FXCO or WD . Dietary fat content of SFA , MUFA , PUFA n-6 and n-3 was 6 , 23 , 5 , 1 % energy for HOCO ; 6 , 16 , 5 , 7·5 % energy for FXCO ; 11·5 , 16 , 6 , 0·5 % energy for WD . After 28 d , compared with WD , LDL-cholesterol was reduced 15·1 % ( P < 0·001 ) with FXCO and 7·4 % ( P < 0·001 ) with  HOCO . Total cholesterol ( TC ) was reduced 11 % ( P < 0·001 ) with FXCO and 3·5 % ( P = 0·002 ) with HOCO compared with WD . Endpoint TC differed between FXCO and HOCO ( P < 0·05 ) . FXCO consumption reduced HDL-cholesterol by 8·5 % ( P < 0·001 ) and LDL : HDL ratio by 7·5 % ( P = 0·008 ) v. WD . FXCO significantly decreased E-selectin concentration compared with WD ( P = 0·02 ) . No differences were observed in inflammatory markers after the consumption of HOCO compared with WD . In conclusion , consumption of novel HOCO alone or when blended with flaxseed oil is cardioprotective through lipid-lowering effects . The incorporation of flaxseed oil may also target inflammation by reducing plasma E-selectin BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events Malnutrition and chronic inflammation in dialysis patients negatively impact their survival prognosis , and nutrients , such as omega-3 oils , are postulated to reduce proinflammatory response . In this r and omized , double-blind , multicenter , placebo-controlled trial , we investigated the effects of flaxseed oil ( FO ) on the inflammatory state of patients with chronic renal failure undergoing renal replacement therapy with hemodialysis ( HD ) . We hypothesized that FO supplementation lowers C-reactive protein ( CRP ) levels .  One hundred sixty patients with chronic renal failure who received HD therapy of 3 dialysis units over a 3-month period in South Brazil were included . The patients received blind doses of FO ( 1 g twice a day ) and placebo ( mineral oil , 1 g twice a day ) for a period of 120 days . Inflammation was observed in 89 patients ( 61 % ) at the beginning of the study . There was a correlation between CRP and the body mass index ( R(s ) = 0.22 ; P = .022 ) and high-density lipoprotein cholesterol ( R(s ) = -0.23 ; P = .032 ) , and the CRP levels decreased significantly over time in the group that received FO compared with the control group ( P < .001 ) . During the study period , 33.3 % of the FO group changed from an inflamed to a not-inflamed category , whereas only 16.9 % changed in the mineral oil group ( P = .04 ) . We conclude that the administration of FO decreases the CRP levels and that inflammation in HD patients appears to be correlated to their body mass index and reduced high-density lipoprotein cholesterol levels . Studies with a larger number of patients and over a longer duration are necessary to corroborate these findings Greatly increasing the amounts of flaxseed oil [ rich in α-linolenic acid ( ALNA ) ] or fish oil ( FO ) ; [ rich in eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) ] in the diet can decrease inflammatory cell functions and so might impair host defense . The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA , γ-linolenic acid ( GLA ) , arachidonic acid ( ARA ) , DHA , or FO on inflammatory cell numbers and functions and on circulating levels of soluble adhesion molecules .  Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk . The capsules contained placebo oil ( an 80∶20 mix of palm and sunflowerseed oils ) or blends of placebo oil with oils rich in ALNA , GLA , ARA , or DHA or FO . Subjects in these groups consumed 2 g ALNA ; approximately 700 mg GLA , ARA , or DHA ; or 1 g EPA plus DHA ( 720 mg EPA+280 mg DHA ) daily from the capsules . Total fat intake from the capsules was 4 g per day . None of the treatments affected inflammatory cell numbers in the bloodstream ; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli ; production of tumor necrosis factor-α , interleukin-1β , and interleukin-6 in response to bacterial lipopolysaccharide ; or plasma concentrations of soluble intercellular adhesion molecule-1 . In contrast , the ALNA and FO treatments decreased the plasma concentrations of soluble vascular cell adhesion molecule-1 ( 16 and 28 % decrease , respectively ) and soluble E-selectin ( 23 and 17 % decrease , respectively ) . It is concluded that , in contrast to previous reports using higher amounts of these fatty acids , a moderate increase in consumption of long-chain n−6 or n−3 polyunsaturated fatty acids does not significantly affect inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment . Furthermore , we conclude that moderate levels of ALNA and FO , which could be incorporated into the diet , can decrease some markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n−3 fatty acids BACKGROUND Greatly increasing dietary flaxseed oil [ rich in the n-3 polyunsaturated fatty acid ( PUFA ) alpha-linolenic acid ( ALA ) ] or fish oil [ rich in the long-chain n-3 PUFAs eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids ] can reduce markers of immune cell function . The effects of more modest doses are unclear , and it is not known whether ALA has the same effects as its long-chain derivatives . OBJECTIVE The objective was to determine the effects of enriching the diet with ALA or EPA+DHA on immune outcomes representing key functions of human neutrophils , monocytes , and lymphocytes . DESIGN In a placebo-controlled , double-blind , parallel study , 150 healthy men and women aged 25 - 72 y were r and omly assigned to 1 of 5 interventions : placebo ( no additional n-3 PUFAs ) , 4.5 or 9.5 g ALA/d , and 0.77 or 1.7 g EPA+DHA/d for 6 mo . The n-3 PUFAs were provided in 25 g fat spread plus 3 oil capsules . Blood sample s were taken at 0 , 3 , and 6 mo . RESULTS The fatty acid composition of peripheral blood mononuclear cell phospholipids was significantly different in the groups with higher intakes of ALA or EPA+DHA . The interventions did not alter the percentages of neutrophils or monocytes engaged in phagocytosis of Escherichia coli or in phagocytic activity , the percentages of neutrophils or monocytes undergoing oxidative burst in response to E. coli or phorbol ester , the proliferation of lymphocytes in response to a T cell mitogen , the production of numerous cytokines by monocytes and lymphocytes , or the in vivo delayed-type hypersensitivity response . CONCLUSION An intake of < or= 9.5 g ALA/d or < or= 1.7 g EPA+DHA/d does not alter the functional activity of neutrophils , monocytes , or lymphocytes , but it changes the fatty acid composition of mononuclear cells 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 Recent evidence has demonstrated that the G0/G1 switch gene 2 ( G0S2 ) is an important negative regulator of the rate-limiting lipolytic enzyme adipose triglyceride lipase-mediated lipolysis . It has been revealed that α-linolenic acid ( ALA ) , a plant-based essential omega-3 polyunsaturated fatty acids , reduces adipose tissue lipolysis . However , it is not known whether G0S2 is implicated in ALA-induced inhibition of lipolysis . The purpose of this pilot study is to investigate the effect of ALA on G0S2 gene expression in peripheral blood mononuclear cells ( P BMC ) of obese patients and the potential influence of G0S2 gene expression in ALA-induced inhibition of lipolysis . Methods A total of 26 obese patients were r and omly assigned to be  treated with or without ALA treatment ( ~4.0 g daily ) for 12 weeks : the ALA-treated group  ( n = 14 ) or the untreated control group  ( n = 12 ) . Plasma triglyceride ( TG ) , free fatty acids ( FFA ) , glycerol , interleukin-6 ( IL-6 ) and tumor necrosis factor-α ( TNF-α ) , as well as the mRNA expression levels of proliferator-activated receptor gamma ( PPAR-γ ) , G0S2 , and G protein-coupled receptor 120 ( GPR120 ) in P BMC were repeatedly examined from fasting obese patients before and after ALA treatment . Results ALA significantly decreased plasma TG , FFA , glycerol , IL-6 , and TNF-α levels and increased the mRNA expression levels of PPAR-γ , G0S2 , and GPR120 in P BMC , compared with the untreated control group . In obese patients from the ALA-treated group , decreased plasma FFA ( a biomarker for lipolysis ) level was significantly correlated with increased PPAR-γ ( a functional omega-3 fatty acids receptor ) and G0S2 ( a direct target gene of PPAR-γ ) mRNA expression in P BMC , while decreased plasma FFA level was not correlated with increased GPR120 ( another functional omega-3 fatty acids receptor ) mRNA expression in P BMC . Conclusion This study shows that ALA  increases G0S2 gene expression in P BMC in parallel with the decrease of plasma FFA level in obese patients .  Increased G0S2 gene expression might contribute to the beneficial anti-lipolytic effect of ALA in obese patients Purpose The aim of this study was to investigate the effects of flaxseed oil consumption on serum systemic and vascular inflammation markers , and oxidative stress in hemodialysis ( HD ) patients . Methods In this r and omized , double-blind , clinical trial , 34 HD patients were r and omly assigned to either the flaxseed oil or the control group . The patients in the flaxseed oil group received 6 g/day flaxseed oil for 8 week , whereas the control group received 6 g/day medium-chain triglycerides ( MCT ) oil . At baseline and the end of week 8 , serum concentrations of high-sensitive C-reactive protein ( hs-CRP ) , soluble intercellular adhesion molecule type 1 ( sICAM-1 ) , soluble vascular cell adhesion molecule type 1 ( sVCAM-1 ) , sE-selectin , and malondialdehyde ( MDA ) were measured after a 12- to 14-h fast . Results Serum hs-CRP , a systemic inflammation marker , and sVCAM-1 , a vascular inflammation marker , reduced significantly in the flaxseed oil group at the end of week 8 compared to baseline ( P < 0.05 ) , and the reductions were significant in comparison with the MCT oil group ( P < 0.05 ) . There were no significant differences between the two groups in mean changes in serum sICAM-1 , sE-selectin , and MDA . Conclusion This study indicates that daily consumption of 6 g flaxseed oil reduces serum hs-CRP and sVCAM-1 , which are two risk factors for CVD . Therefore , the inclusion of flaxseed oil in the usual diet of HD patients can be considered as a strategy for reducing CVD risk factors Abstract Grape seed oil ( GSO ) is reported to improve oxidative stress and lipid profile . However , the ameliorating effect of GSO on inflammation and insulin resistance has not being noticed so far . We aim ed to examine the effects of GSO consumption on inflammation and insulin resistance in overweight or obese females . The subjects ( n = 44 ) were r and omly assigned into intervention group as “ GSO ” ( consuming 15 % of energy from GSO ) and control group as sunflower oil “ SFO ” ( consuming 15 % of energy from SFO ) through a weight loss diet for 8 weeks . Anthropometric measurements , dietary recall and fasting serum glucose , insulin , high sensitive C-reactive protein ( hs-CRP ) and tumor necrosis factor-alpha ( TNF-α ) were assessed before and after the intervention . Homeostatic model assessment of insulin resistance ( HOMA-IR ) scores , hs-CRP and TNF-α decreased in the GSO group . The hs-CRP was lower in GSO than the SFO group ( p < 0.03 ) . GSO consumption seems to improve inflammatory condition and insulin resistance in overweight/obese women We investigated the antihypertensive effect and safety of alpha-linolenic acid ( ALA ) in human subjects . In Experiment 1 , subjects with high-normal blood pressure and mild hypertension ingested bread containing 14 g of common blended oil ( control oil ) or ALA-enriched oil for 12 weeks . The test oil contained 2.6g/14 g of ALA . The subjects ingested strictly controlled meals during the study period . Systolic blood pressure was significantly lower in the ALA group than in the control group after ingestion of the test diet for 4 , 8 and 12 weeks . Diastolic blood pressure was significantly lower in the ALA group than in the control group after ingestion of the test diet for 12 weeks . In Experiment 2 , we evaluated the safety of high intake of ALA ( 7.8 g/d ) , particularly its effects on oxidation in the body and blood coagulation .  Normotensive , high-normotensive and mildly hypertensive subjects ate bread that contained 42 g of the control oil or the test oil for 4 weeks . No significant difference was noted in the lipid peroxide level , high-sensitive C-reactive protein level , plasma prothrombin time or activated partial thromboplastin time between the two groups . No abnormal changes were noted after test diet ingestion on blood test or urinalysis , and no adverse event considered to have been induced by the test oil was observed in Experiment 1 and 2 . These results suggest that ALA have an antihypertensive effect with no adverse effect in subjects with high-normal blood pressure and mild hypertension Background —Visceral fat is a key regulator site for the process of inflammation , and atherosclerotic lesions are essentially an inflammatory response . Methods and Results —Fifty-six healthy premenopausal obese women ( age range 25 to 44 years , body mass index 37.2±2.2 , waist to hip ratio range 0.78 to 0.92 ) and 40 age-matched normal weight women were studied . Compared with nonobese women , obese women had increased basal concentrations of tumor necrosis factor-&agr ; ( TNF-&agr ; , P < 0.01 ) , interleukin-6 ( IL-6 , P < 0.01 ) , P-selectin ( P < 0.01 ) , intercellular adhesion molecule-1 ( ICAM-1 , P < 0.02 ) , and vascular adhesion molecule-1 ( VCAM-1 , P < 0.05 ) . Vascular responses to l-arginine ( 3 g IV ) , the natural precursor of nitric oxide , were impaired in obese women : reductions in mean blood pressure ( P < 0.02 ) , platelet aggregation to adenosine diphosphate ( P < 0.05 ) , and blood viscosity ( P < 0.05 ) were significantly lower as compared with those in the nonobese group . Concentrations of TNF-&agr ; and IL-6 were related ( P < 0.01 ) to visceral obesity , as well as to adhesin levels and responses to l-arginine . After 1 year of a multidisciplinary program of weight reduction ( diet , exercise , behavioral counseling ) , all obese women  lost at least 10 % of their original weight ( 9.8±1.5 kg , range 7.5 to 13 kg ) . Compared with baseline , sustained weight loss was associated with reduction of cytokine ( P < 0.01 ) and adhesin ( P < 0.02 ) concentrations and with improvement of vascular responses to l-arginine . Conclusion —In obese women , endothelial activation correlates with visceral body fat , possibly through inappropriate secretion of cytokines . Weight loss represents a safe method for downregulating the inflammatory state and ameliorating endothelial dysfunction in obese women Dietary and endogenous fatty acids could play a role in low- grade inflammation . In this cross-sectional study the proportions of erythrocyte membrane fatty acids ( EMFA ) and the concentrations of C-reactive protein ( CRP ) , interleukin-1 receptor antagonist ( IL-1Ra ) and adiponectin were measured and their confounder-adjusted associations examined in 1373 r and omly selected Finnish men aged 45 - 70 years participating in the population based Metsim study in Eastern Finl and . The sum of n-6 EMFAs , without linoleic acid ( LA ) , was positively associated with concentrations of CRP and IL-1Ra ( r partial=0.139 and r partial=0.115 , P<0.001 ) . These associations were especially strong among lean men ( waist circumference < 94 cm ; r partial=0.156 and r partial=0.189 , P<0.001 ) . Total n-3 EMFAs correlated inversely with concentrations of CRP ( r partial=-0.098 , P<0.001 ) . Palmitoleic acid ( 16:1n-7 ) correlated positively with CRP ( r partial=0.096 , P<0.001 ) . Cis-vaccenic acid ( 18:1n-7 ) was associated with high concentrations of adiponectin ( r partial=0.139 , P<0.001 ) . In conclusion , n-6 EMFAs , except for LA , correlated positively with the inflammatory markers . Palmitoleic acid was associated with CRP , whereas , interestingly , its elongation product , cis-vaccenic acid , associated with anti-inflammatory adiponectin 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 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 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 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 Increased inflammation with aging has been linked to sarcopenia . The purpose of this study was to evaluate the effects of supplementing older adults with alpha-linolenic acid ( ALA ) during a resistance training program , based on the hypothesis that ALA decreases the plasma concentration of the inflammatory cytokine tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 , which in turn would improve muscle size and strength . Fifty-one older adults ( 65.4 + /- 0.8 years ) were r and omized to receive ALA in flax oil ( ~14 g.day-1 ) or placebo for 12 weeks while completing a resistance training program ( 3 days a week ) . Subjects were evaluated at baseline and after 12 weeks for muscle thickness of knee and elbow flexors and extensors ( B-mode ultrasound ) , muscle strength ( 1 repetition maximum ) , body composition ( dual energy X-ray absorptiometry ) , and concentrations of TNF-alpha and IL-6 . Males supplementing with ALA  decreased IL-6 concentration over the 12 weeks ( 62 + /- 36 % decrease ; p = 0.003 ) , with no other changes in inflammatory cytokines . Chest and leg press strength , lean tissue mass , muscle thickness , hip bone mineral content and density , and total bone mineral content significantly increased , and percent fat and total body mass decreased with training ( p < 0.05 ) , with the only benefit of ALA being a significantly greater increase in knee flexor muscle thickness in males ( p < 0.05 ) . Total-body bone mineral density improved in the placebo group , with no change in the ALA group ( p = 0.05 ) . ALA supplementation lowers the IL-6 concentration in older men but not women , but had minimal effect on muscle mass and strength during resistance training Background heart failure is a major risk factor for cardiovascular mortality , for which n-3 fatty acids may have beneficial effects . We examined the effect of marine eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , and plant-derived alpha-linolenic acid ( ALA ) on N-Terminal-pro Brain Natriuretic Peptide ( NT-proBNP ) , a biomarker of heart failure . Methods we r and omly assigned 4837 post-myocardial infa rct ion patients , aged 60–80 years ( 82 % men ) , to margarines supplemented with a targeted additional intake of 400 mg/day EPA and DHA , 2 g/day ALA , EPA-DHA plus ALA , or placebo for 40 months . In a r and om selection of 639 patients , NT-proBNP was determined both at baseline and at the end of follow-up . NT-proBNP was loge-transformed and analysed by type of treatment using analysis of covariance adjusting for baseline NT-proNBP . Results patients consumed on average 19.8 g margarine/day , providing an additional amount of 238 mg/day EPA with 158 mg/day DHA , 1.98 g/day ALA , or both , in the active-treatment groups . In the placebo group , the geometric mean level NT-proBNP increased from 245 ng/l ( 95%-confidence interval [ CI ] : 207–290 ) to 294 ng/l ( 95%-CI : 244–352 ) after 40 months ( p = 0.001 ) . NT-proBNP levels were not affected by ALA ( + 8 % versus placebo ; 95%-CI : −8 % to + 25 % ; p = 0.34 ) , EPA-DHA ( + 2 % versus placebo ; 95%-CI : −14 % to + 18 % ; p = 0.78 ) , nor EPA-DHA plus ALA ( + 9 % versus placebo ; 95%-CI : −8 % to + 25 % ; p = 0.31 ) treatment . Conclusions supplementation with modest amounts of EPA-DHA , with or without ALA , did not have a significant effect on NT-proBNP levels in patients with a history of myocardial infa rct ion Various studies have already shown that the fatty acid composition of dietary fat has different effects on hemostasis and platelet function . However , knowledge on this topic is incomplete . In the present study , fifty-eight healthy students received either a 4-week rapeseed oil [ high content of monounsaturated fatty acids ( MUFA ) and high n-3/n-6 PUFA ratio ] , an olive oil ( high content of MUFA , low n-3/n-6 PUFA ratio ) or a sunflower oil ( low content of MUFA , low n-3/n-6 PUFA ratio ) diet . In each group , effects on hemostatic parameters were compared with a wash-in diet rich in saturated fatty acids with respect to intermediate-time effects on the hemostatic system and platelet function . With the olive oil diet , a reduction of coagulation factors VIIc , XIIc , XIIa , and Xc was found , whereas sunflower oil led to lower values of coagulation factors XIIc , XIIa , and IXc . In all study groups levels of plasmin-alpha2-antiplasmin were lower in week 4 than at baseline . Lower fibrinogen binding on platelets was found after the sunflower oil diet , whereas expression of CD62 and spontaneous platelet aggregation were slightly higher after the olive oil diet . However , given the major differences in the fatty acid compositions of the diets , the differences between the groups with respect to hemostasis tended to be small . Therefore , the clinical significance of the present findings remains to be evaluated OBJECTIVE ω-3 Polyunsaturated α-linolenic acid ( ALA ) supplementation has not been studied in the setting of adiponectin levels and insulin sensitivity ( IS ) improvements in patients with type 2 diabetes mellitus ( T2DM ) by hyperinsulinemic-euglycemic clamp ( HEC ) . The aim of this study was to examine the influence of ω-3 ALA on IS and adiponectin . METHODS We conducted a r and omized study in patients with T2DM and assessed IS using HEC . Twenty patients with T2DM were included and r and omly assigned to receive 3 g/d of ALA or placebo for 60 d , in a double-blind design . The assessment of IS by HEC was performed at baseline and after 60 d in all patients ; blood sample s were taken for the measurement of serum lipids , glucose , insulin , adiponectin , and cytokines . The primary outcome variables were an increase of both glucose infusion rate ( GIR ) in steady state and glucose metabolization ( M ) by HEC . The secondary outcomes were an increase in adiponectin levels and a decrease in fasting plasma glucose , glycated hemoglobin , homeostasis model assessment -estimated insulin resistance ( HOMA-IR ) index , lipids and cytokines . The study was conducted at an academic medical center . RESULTS The ALA group improved IS corrected for fat-free mass ( M/FFM ; P = 0.04 ) . Both groups showed increased adiponectin after 60 d ( P = 0.01 ) , however , the increase for the ALA group was greater ( P = 0.04 ) . In the ALA group , adiponectin was positively correlated with GIR ( r = 0.76 ; P = 0.01 ) and M/FFM ( r = 0.62 ; P = 0.06 ) , and negatively correlated with HOMA-IR ( r = -0.61 ; P = 0.03 ) . CONCLUSION ω-3 ALA supplementation improved glucose homeostasis and was associated with an increase in adiponectin . Improvement in the overall metabolic profile with ω-3 ALA suggests a potential clinical utility for this agent and requires further investigation 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 Objective : The impact of dietary polyunsaturated fatty acids ( PUFAs ) of the n-6 and n-3 series on the cardiovascular system is well documented . To directly compare the effects of three dietary oils ( fish , flaxseed and hempseed ) given in concentrations expected to be self-administered in the general population on specific cardiovascular parameters in healthy volunteers . Design : 86 healthy male and female volunteers completed a 12 week double blinded , placebo controlled , clinical trial . They were r and omly assigned to one of the four groups . Subjects were orally supplemented with two 1 gm capsules of placebo , fish oil , flaxseed oil or hempseed oil per day for 12 weeks . Results : Plasma levels of the n-3 fatty acids docosahexanoic acid and eicosapentanoic acid increased after 3 months supplementation with fish oil .  Alpha linolenic acid concentrations increased transiently after flaxseed supplementation . However , supplementation with hempseed oil did not significantly alter the concentration of any plasma fatty acid . The lipid parameters ( TC , HDL-C , LDL-C and TG ) did not show any significant differences among the four groups . Oxidative modification of LDL showed no increase in lag time over the 12 wk period . None of the dietary interventions induced any significant change in collagen or thrombin stimulated platelet aggregation and no increase in the level of inflammatory markers was observed . Conclusion : From a consumer 's perspective , ingesting 2 capsules of any of these oils in an attempt to achieve cardiovascular health benefits may not provide the desired or expected result over a 3 month period The pathology of type 2 diabetes mellitus ( DM ) often is associated with underlying states of conditioned zinc deficiency and chronic inflammation . Zinc and omega-3 polyunsaturated fatty acids each exhibit anti-inflammatory effects and may be of therapeutic benefit in the disease . The present r and omized , double-blind , placebo-controlled , 12-week trial was design ed to investigate the effects of zinc ( 40 mg/day ) and α-linolenic acid ( ALA ; 2 g/day flaxseed oil ) supplementation on markers of inflammation [ interleukin (IL)-1β , IL-6 , tumor necrosis factor (TNF)-α , C-reactive protein ( CRP ) ] and zinc transporter and metallothionein gene expression in 48 postmenopausal women with type 2 DM . No significant effects of  zinc or ALA supplementation were observed on inflammatory marker concentrations or fold change in zinc transporter and metallothionein gene expression . Significant increases in plasma zinc concentrations were observed over time in the groups supplemented with zinc alone or combined with ALA ( P=.007 and P=.009 , respectively ) . An impact of zinc treatment on zinc transporter gene expression was found ; ZnT5 was positively correlated with Zip3 mRNA ( P<.001 ) only in participants receiving zinc , while zinc supplementation abolished the relationship between ZnT5 and Zip10 . IL-6 predicted the expression levels and CRP predicted the fold change of the ZnT5 , ZnT7 , Zip1 , Zip7 and Zip10 mRNA cluster ( P<.001 and P=.031 , respectively ) . Fold change in the expression of metallothionein mRNA was predicted by TNF-α ( P=.022 ) . Associations among inflammatory cytokines and zinc transporter and metallothionein gene expression support an interrelationship between zinc homeostasis and inflammation in type 2 DM Long-chain n-3 PUFA from fish oils are known to have anti-inflammatory effects . We evaluated the effect of alpha-linolenic acid ( ALA ) , precursor of n-3 fatty acids , on serum inflammatory markers and soluble cellular adhesion molecules ( sCAM ) of dyslipidaemic males , relative to their background diet . Participants were assigned to two groups , based upon food intake patterns : ( a ) twenty-one dyslipidaemic subjects who habitually ate a Mediterranean-Cretan-type diet ; ( b ) nineteen dyslipidaemic subjects who normally ate a Westernised Greek diet .  All were supplemented with 8.1 g ALA/d for 12 weeks . We determined serum amyloid A ( SAA ) , C-reactive protein ( CRP ) , macrophage colony-stimulating factor ( MCSF ) , IL-6 , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , soluble intercellular adhesion molecule-1 and soluble E-selectin concentrations at the beginning and the end of the ALA supplementation period . Serum baseline concentrations of inflammatory markers and sCAM were similar across the diet groups . Type of diet had a significant impact on the response of inflammatory markers to ALA supplementation . The Westernised Greek diet group showed a reduction in SAA ( P<0.001 ) , CRP ( P=0.002 ) , MCSF ( P=0.005 ) and IL-6 ( P=0.04 ) concentrations . The Mediterranean-Cretan-type background diet group showed a significant reduction only in MCSF concentrations ( P=0.003 ) . The sVCAM-1 concentrations were significantly reduced in both the Westernised Greek diet group ( P=0.001 ) and the Mediterranean-Cretan-type diet group ( P<0.001 ) . The present study demonstrated that ALA supplementation lowered the serum concentrations of inflammatory markers more profoundly when the background diet was rich in saturated fatty acids and poor in MUFA
target: Subgroup analysis revealed that increasing dietary ALA tends to elevate CRP concentration  in healthy subjects .
  However , the null effect of ALA supplementation on other inflammatory markers was not changed in various subgroups , indicating that the results are stable .
  Meta-regression results revealed a negative relationship between the effect size on CRP and its baseline concentration .
  No significant publication bias was observed for all inflammatory markers as suggested by funnel plot and Begg ’s test .
  Conclusion Our meta- analysis did not find any beneficial effect of ALA supplementation  on reducing inflammatory markers including TNF , IL-6 , CRP , sICAM-1 , and sVCAM-1 .
  However , in healthy subjects  , ALA supplementation might increase CRP concentration
background: Purpose The aim of the current meta- analysis was to investigate the effect of increasing dietary ALA intake on the blood concentration of inflammatory markers including tumor necrosis factor ( TNF ) , interleukin 6 ( IL-6 ) , C-reactive protein ( CRP ) , soluble intercellular adhesion molecule-1 ( sICAM-1 ) , and soluble vascular cell adhesion molecule-1 ( sVCAM-1 )  in adults .