title: Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes A prospective, randomized, and double-blind trial on the effect of fish oil on the incidence of restenosis following PTCA. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. A long-term seal- and cod-liver-oil supplementation in hypercholesterolemic subjects Effect of marine oils supplementation on coagulation and cellular activation in whole blood Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a dose-response study. Docosahexaenoic and eicosapentaenoic acids in plasma phospholipids are divergently associated with high density lipoprotein in humans. Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance Published, JLR Papers in Press, December 1, 2002. DOI 10.1194/jlr.M200282-JLR200 Reduction of blood pressure and plasma triglycerides by omega‐3 fatty acids in treated hypertensives Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses. Effect of atorvastatin and fish oil on plasma high-sensitivity C-reactive protein concentrations in individuals with visceral obesity. Effects of fish oil on VLDL triglyceride kinetics in humans. Effect of Fish Oil Concentrate on Lipoprotein Composition in NIDDM Improvement of serum lipids and blood pressure during intervention with n-3 fatty acids was not associated with changes in insulin levels in subjects with combined hyperlipidaemia. The Independent and Combined Effects of Aerobic Exercise and Dietary Fish Intake on Serum Lipids and Glycemic Control in NIDDM: A randomized controlled study Dietary fish oil augments nitric oxide production or release in patients with Type 2 (non-insulin-dependent) diabetes mellitus 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 Complementary effects of Mediterranean diet and moderate red wine intake on haemostatic cardiovascular risk factors Intake of n-3 fatty acids from fish does not lower serum concentrations of C-reactive protein in healthy subjects The effect of fish oil on blood pressure and high‐density lipoprotein‐cholesterol levels in phase I of the Trials of Hypertension Prevention One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance: reduced triglyceridemia, total cholesterol and increased HDL-C without glycemic alterations. Influence of supplementation with N-3 fatty acids on different coronary risk factors in men--a placebo controlled study. Supplementation with omega3 polyunsaturated fatty acids and all-rac alpha-tocopherol alone and in combination failed to exert an anti-inflammatory effect in human volunteers. Effects of a new fish oil concentrate on plasma lipids and lipoproteins in patients with hypertriglyceridaemia. Effects of a fish oil supplement on blood pressure and serum lipids in patients treated for coronary artery disease. Effects of diets containing olive oil, sunflower oil, or rapeseed oil on the hemostatic system. Fish oils and low-molecular-weight heparin for the reduction of restenosis after percutaneous transluminal coronary angioplasty. The EMPAR Study. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease Safety and Efficacy of Omacor in Severe Hypertriglyceridemia Effects of low-dose omega-3 fatty acid substitution in type-2 diabetes mellitus with special reference to oxidative stress--a prospective preliminary study. Effects of Fish Oil Supplements in NIDDM Subjects: Controlled Study Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.
abstract: Objective : Fish oil supplement has been proposed as a non-pharmacological strategy to correct the atherogenic lipid profile associated with type 2 diabetes mellitus . However , fish oil may have deleterious effects on lipid peroxidation and glycemic control . Design : In this study , 44 type 2 diabetic patients were r and omized to vitamin E st and ardized ( 53.6 mg/day ) supplementation ( capsules ) with 4 g daily of either fish oil ( n=23 ) or corn oil ( n=21 ) for 8 weeks preceded by a 4 week run-in period of corn oil supplementation . LDL was isolated by density gradient ultracentrifugation and oxidized in vitro with Cu2 + . As a marker of in vivo oxidation malondialdehyde concentration in LDL ( LDL-MDA ) was measured . Results : Fish oil reduced both mean lag time ( before , 57.8 ; after , 48.8 min , P<0.001 ) and mean propagation rate ( before , 0.018 ΔOD/min ; after , 0.015 ΔOD/min , P<0.001 ) , whereas corn oil had no influence on lag time and propagation rate . The changes in lag time and propagation rate differed significantly between fish oil and corn oil treatment . LDL-MDA changes differed borderline significantly between groups ( FO , 110.4 pmol/mg protein ; CO , 6.7 pmol/mg protein ; P=0.057 ) . Fish oil supplementation had no influence on glycemic control as assessed from HbA1c and fasting blood glucose . Conclusion : According to our findings , fish oil supplementation leads to increased in vivo oxidation and increased in vitro oxidation susceptibility of LDL particles . More studies are needed to clarify the clinical importance of this finding . Sponsorship : Financially supported by The Danish Heart Association and Dansk Droge A/S. Dansk Droge A/S generously provided the fish oil and corn oil capsules Restenosis after successful coronary angioplasty ( PTCA ) occurs in 25 - 35 % of all procedures . To date , most pharmacologic strategies have failed to reduce the restenosis rate significantly . However , recent studies have suggested a potential benefit of dietary supplementation with omega-3 fatty acids ( fish oil ) on restenosis following PTCA . The benefit of omega-3 polyunsaturated fatty acids on the incidence of coronary artery restenosis following elective PTCA was assessed in 212 consecutive patients ( 41 female , 171 male ) . Following a successful angioplasty , 204 patients received a dietary supplementation with either nine capsules containing fish oil ( 3.15 g omega-3 fatty acids ) or nine placebo capsules containing olive oil . Treatment was started immediately after PTCA and maintained over 4 mon . Compliance was assessed by analysis of lipid fatty acids prior to angioplasty and at 4 mon follow-up . The angiographically determined incidence of restenosis ( stenosis diameter > 50 % ) was 31.2 % per lesion in patients receiving fish oil and 33.7 % in patients receiving olive oil .  Gross progression of coronary artery disease in vessels not subjected to angioplasty was 17 % and 16 % , respectively . In conclusion , low dose fish oil supplementation begun on the day of a successful coronary angioplasty failed to demonstrate any effect on coronary artery restenosis The extent to which women of reproductive age are able to convert the n-3 fatty acid alpha-linolenic acid ( ALNA ) to eicosapentaenoic acid ( EPA ) , docosapentaenoic acid ( DPA ) and docosahexaenoic acid ( DHA ) was investigated in vivo by measuring the concentrations of labelled fatty acids in plasma for 21 d following the ingestion of [U-13C]ALNA ( 700 mg ) . [13C]ALNA excursion was greatest in cholesteryl ester ( CE ) ( 224 ( sem 70 ) micromol/l over 21 d ) compared with triacylglycerol ( 9-fold ) , non-esterified fatty acids ( 37-fold ) and phosphatidylcholine ( PC , 7-fold ) . EPA excursion was similar in both PC ( 42 ( sem 8) micromol/l ) and CE ( 42 ( sem 9 ) micromol/l ) over 21 d. In contrast both [13C]DPA and [13C]DHA were detected predominately in PC ( 18 ( sem 4 ) and 27 ( sem 7 ) micromol/l over 21 d , respectively ) . Estimated net fractional ALNA inter-conversion was EPA 21 % , DPA 6 % and DHA 9 % . Approximately 22 % of administered [13C]ALNA was recovered as 13CO2 on breath over the first 24 h of the study . These results suggest differential partitioning of ALNA , EPA and DHA between plasma lipid classes , which may facilitate targeting of individual n-3 fatty acids to specific tissues . Comparison with previous studies suggests that women may possess a greater capacity for ALNA conversion than men . Such metabolic capacity may be important for meeting the dem and s of the fetus and neonate for DHA during pregnancy and lactation . Differences in DHA status between women both in the non-pregnant state and in pregnancy may reflect variations in metabolic capacity for DHA synthesis In this long-term study , we wanted to explore the effect of dietary supplementation of seal oil ( SO ) as compared cod-liver oil ( CLO ) on subjects with moderate hypercholesterolemia . The test parameters included fatty acid composition in serum , blood lipids , platelet aggregation , and the activity of blood monocytes . After a run-in period of 6 mon , 120 clinical ly healthy hypercholesterolemic ( 7.0–9.5 mmol/L ; 270–366 mg/dL ) subjects were r and omly selected to consume either 15 mL of SO or CLO daily for 14 mon followed by a 4-mon wash-out period . A third group was not given any dietary supplement ( control ) . Consumption of marine oils ( SO and CLO ) changed the fatty acid composition of serum significantly . Maximal levels were achieved after 10 mon . No further changes were seen after 14 mon . A wash-out period of 4 mon hardly altered the level of n−3 fatty acids in serum . Addition of SO gave 30 % higher level of eicosapentaenoic acid , as compared to CLO . Subjects taking SO or CLO had lower whole-blood platelet aggregation than the control group . Neither SO nor CLO had any effects on the levels of serum total cholesterol , high-density lipoprotein cholesterol , postpr and ial triacylglycerol , apolipoproteins A1 and B100 , lipoprotein ( a ) , monocyte function expressed as monocyte-derived tissue factor expression , and tumor necrosis factor A study was performed to explore the effects of supplemental intake of various marine oils known to be part of the Eskimo diet . Healthy men and women ( 134 ) were r and omly selected to consume 15 mL/d of oil from blubber of seal , cod liver , seal/cod liver , blubber of Minke whale , or no oil for ten weeks . Total cholesterol was unchanged in the oil groups , whereas high density lipoprotein cholesterol increased 7 % in the seal/cod liver oil ( CLO ) group ( P<0.05 ) and 11 % in the whale oil group ( P<0.005 ) . Triacylglycerol was significantly reduced in the CLO group only . The concentration of prothrombin fragment 1 + 2 was reduced 25 % ( P<0.05 ) after whale oil supplementation . No change in fibrinogen or factor VIIc was detected . Tumor necrosis factor generation in lipopolysaccharide (LPS)-stimulated blood was 30 % reduced after whale oil ( P<0.05 ) , but was unaffected by intake of seal or CLO . The LPS-induced tissue factor activity in monocytes was reduced to a significant degree only in the seal/CLO group ( 34 % ) and whale oil group ( 35 % ) ( P<0.05 ) . The most dramatic change in thromboxane B2 in LPS-stimulated blood was seen after whale oil intake with 44 % reduction ( P<0.01 ) . Supplementation of a regular diet with a combination of seal oil and CLO and especially with whale oil seems to have beneficial effects on several products thought to be associated with cardiovascular and thrombotic diseases To compare the effects of highly purified ethyl ester concentrates of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) on serum lipids , apolipoproteins , and serum phospholipid fatty acids in humans , we conducted a double-blind , placebo-controlled , parallel design intervention study . Healthy nonsmoking men ( n = 234 ) aged 36 - 56 y were r and omly assigned to dietary supplementation with 3.8 g EPA/d , 3.6 g DHA/d , or 4.0 g corn oil/d ( placebo ) for 7 wk . Serum triacylglycerols decreased 26 % ( P < 0.0001 ) in the DHA group and 21 % ( P = 0.0001 ) in the EPA group compared with the corn oil group . Although not significant , net decreases in serum triacylglycerols were consistently greater in the DHA group across all quartiles of baseline triacylglycerol concentrations . Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L ( P = 0.0002 ) in the DHA group . In the EPA group , serum total cholesterol decreased 0.15 mmol/L ( P = 0.02 ) and apolipoprotein A-I decreased 0.04 g/L ( P = 0.0003 ) . In the DHA group , serum phospholipid DHA increased by 69 % and EPA increased by 29 % , indicating retroconversion of DHA to EPA . In the EPA group , serum phospholipid EPA increased by 297 % whereas DHA decreased by 15 % , suggesting that EPA is not elongated to DHA in humans . The serum phospholipid ratio of n-3 to n-6 fatty acids increased in both groups , whereas the relative changes in n-6 fatty acids suggested possible alterations in liver desaturation activity in the DHA group . We conclude that both DHA and EPA decrease serum triacylglycerols , but have differential effects on lipoprotein and fatty acid metabolism in humans BACKGROUND Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis . OBJECTIVE The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infa rct ion ( MI ) on subsequent cardiac events and serum lipids . DESIGN Three hundred patients with acute MI were r and omly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil , administered in a double-blind manner over 12 - 24 mo . Median follow-up time was 1.5 y. Clinical follow-up , including the drawing of blood sample s , was performed after 6 wk of treatment and later at 0.5-year intervals . RESULTS Forty-two ( 28 % ) patients in the n-3 group and 36 ( 24 % ) in the corn oil group experienced at least one cardiac event ( cardiac death , resuscitation , recurrent MI , or unstable angina ) . No significant difference in prognosis was observed between groups for single or combined cardiac events . Total cholesterol concentrations decreased in both groups , with no significant intergroup differences . On average , the monthly increase in HDL cholesterol was 1.11 % in the n-3 group and 0.55 % in the corn oil group ( P = 0.0016 ) . Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group , whereas they increased by 0.35%/mo in the corn oil group ( P < 0.0001 ) . CONCLUSION No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids BACKGROUND Flaxseed oil is a rich source of 18:3n-3 ( alpha-linolenic acid , or ALA ) , which is ultimately converted to 22:6n-3 ( docosahexaenoic acid , or DHA ) , a fatty acid important for the development of the infant brain and retina . OBJECTIVE The objective of this study was to determine the effect of flaxseed oil supplementation on the breast-milk , plasma , and erythrocyte contents of DHA and other n-3 fatty acids in lactating women . DESIGN Seven women took 20 g flaxseed oil  ( 10.7 g ALA ) daily for 4 wk . Breast-milk and blood sample s were collected weekly before , during , and after supplementation and were analyzed for fatty acid composition . RESULTS Breast milk , plasma , and erythrocyte ALA increased significantly over time ( P < 0.001 ) and after 2 and 4 wk of supplementation ( P < 0.05 ) . Over time , 20:5n-3 ( eicosapentaenoic acid , or EPA ) increased significantly in breast milk ( P = 0.004 ) and in plasma ( P < 0.001 ) . In addition , plasma EPA increased significantly ( P < 0.05 ) after 2 and 4 wk of supplementation . There were significant increases over time in breast-milk 22:5n-3 ( docosapentaenoic acid , or DPA ) ( P < 0.02 ) , plasma DPA ( P < 0.001 ) , and erythrocyte DPA ( P < 0.01 ) . No significant changes were observed in breast-milk , plasma , or erythrocyte DHA contents after flaxseed oil supplementation . CONCLUSIONS Dietary flaxseed oil increased the breast-milk , plasma , and erythrocyte contents of the n-3 fatty acids ALA , EPA , and DPA but had no effect on breast-milk , plasma , or erythrocyte DHA contents BACKGROUND Regular consumption of n-3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk . OBJECTIVE This study aim ed to determine whether eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids have differential effects on serum lipids and lipoproteins , glucose , and insulin in humans . DESIGN In a double-blind , placebo-controlled trial of parallel design , 59 overweight , nonsmoking , mildly hyperlipidemic men were r and omly assigned to receive 4 g purified EPA , DHA , or olive oil ( placebo ) daily while continuing their usual diets for 6 wk . RESULTS Fifty-six men aged 48.8 + /- 1.1 y completed the study . Relative to those in the olive oil group , triacylglycerols fell by 0.45 + /- 0.15 mmol/L ( approximately 20 % ; P = 0.003 ) in the DHA group and by 0.37 + /- 0.14 mmol/L ( approximately 18 % ; P = 0.012 ) in the EPA group . Neither EPA nor DHA had any effect on total cholesterol . LDL , HDL , and HDL(2 ) cholesterol were not affected significantly by EPA , but HDL(3 ) cholesterol decreased significantly ( 6.7 % ; P = 0.032 ) . Although HDL cholesterol was not significantly increased by DHA ( 3 . 1 % ) , HDL(2 ) cholesterol increased by approximately 29 % ( P = 0.004 ) . DHA increased LDL cholesterol by 8 % ( P = 0.019 ) . Adjusted LDL particle size increased by 0.25 + /- 0.08 nm ( P = 0.002 ) with DHA but not with EPA . EPA supplementation increased plasma and platelet phospholipid EPA but reduced  DHA . DHA supplementation increased DHA and EPA in plasma and platelet phospholipids . Both EPA and DHA increased fasting insulin significantly .  EPA , but not DHA , tended to increase fasting glucose , but not significantly so . CONCLUSIONS EPA and DHA had differential effects on lipids , fatty acids , and glucose metabolism in overweight men with mild hyperlipidemia BACKGROUND n-3 Fatty acids lower blood pressure , improve lipids , and benefit other cardiovascular disease risk factors . Effects on glycemia in patients with type 2 diabetes are uncertain . OBJECTIVE We determined whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) have differential effects on glycemic control , including insulin sensitivity and stimulated insulin secretion ; 24-h ambulatory blood pressure ; and serum lipids in type 2 diabetic patients with treated hypertension . DESIGN In a double-blind , placebo-controlled trial of parallel design , 59 subjects were r and omly assigned to consume 4 g EPA , DHA , or olive oil/d for 6 wk while continuing to consume their usual diet . RESULTS Thirty-nine men and 12 postmenopausal women with a mean ( + /- SE ) age of 61.2 + /- 1.2 y completed the study . In comparison with the change from baseline in fasting glucose in the olive oil group , fasting glucose in the EPA and DHA groups increased 1.40 + /- 0.29 mmol/L ( P = 0.002 ) and 0.98 + /- 0.29 mmol/L ( P = 0.002 ) , respectively . Neither EPA nor DHA had significant effects on glycated hemoglobin , fasting insulin or C-peptide , insulin sensitivity or secretion , or blood pressure . Serum triacylglycerols in the EPA and DHA groups decreased 19 % ( P = 0.022 ) and 15 % ( P = 0.022 ) , respectively . There were no significant changes in serum total , LDL , or HDL cholesterol , although HDL(2 ) cholesterol in the EPA and DHA groups increased 16 % ( P = 0.026 ) and 12 % ( P = 0.05 ) , respectively . HDL(3 ) cholesterol decreased 11 % ( P = 0.026 ) with EPA supplementation . CONCLUSIONS EPA and DHA had similar benefits on lipids but adverse effects on short-term glycemic control in hypertensive diabetic patients . The overall implication s for cardiovascular disease require long-term evaluation C-reactive protein ( CRP ) is a sensitive marker for low- grade inflammation . Long-chain n-3 polyunsaturated fatty acids ( PUFA ) have anti-inflammatory effects . The objective of the present study was to investigate the effect on serum levels of CRP of n-3 PUFA at two different doses . We also investigated correlations between CRP and the cellular contents of PUFA . Sixty healthy volunteers ( twenty-five women and thirty-five men ) were r and omly assigned to three treatment groups in a double-blind design . The subjects received a supplement of either 6.6 g n-3 PUFA/d , 2.0 g n-3 PUFA/d or placebo ( olive oil ) for 12 weeks . CRP was measured using a highly sensitive assay . The median serum CRP concentration was 0.78 mg/l . No significant correlations were found between CRP and the content of n-3 PUFA in granulocytes or platelets . Subjects receiving n-3 PUFA had a significant ( P<0.01 ) increase in the cellular contents of 20 : 5n-3 , 22 : 5n-3 and 22 : 6n-3 , with the largest increase occurring in the group receiving 6.6 g PUFA/d . A significant ( P<0.01 ) decrease in cellular content of 18 : 2n-6 and 20 : 4n-6 was observed simultaneously . Serum CRP concentrations , however , were unaffected by the PUFA-containing supplements . The present study shows that dietary supplementation with PUFA-containing supplements has no effect on serum concentrations of CRP , measured with a highly sensitive assay , in healthy subjects The effect of fish oil rich in eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids on serum lipoprotein concentrations is not clear , and it is not known whether EPA and DHA are similarly related to serum lipid or lipoprotein levels . We conducted a r and omized , 10-week , dietary supplementation trial in which the effects of 6 g per day of 85 % EPA and DHA were compared with 6 g per day of corn oil in 156 men and women . Multivariate analyses were used to assess independent relations between plasma phospholipid EPA and DHA and serum lipoprotein levels . In the fish oil group triglycerides fell 21 % ( p less than 0.001 ) and high density lipoprotein cholesterol ( HDL-C ) rose 3.8 % ( p less than 0.05 ) . In the corn oil group triglycerides did not change , but HDL-C rose 6.1 % ( p less than 0.01 ) . Compared with fish oil , apolipoprotein A-I ( apo A-I ) rose 5.1 % after corn oil intake ( p less than 0.05 ) . Plasma EPA and DHA levels rose after fish oil intake and fell after corn oil intake ( all p less than 0.001 ) . The change ( delta ) in EPA was inversely correlated with delta triglycerides ( p = 0.035 ) and positively correlated with delta HDL-C and delta apo A-I ( both p less than 0.001 ) in the multivariate analyses . In contrast , delta DHA was not correlated with delta triglycerides but was inversely correlated with delta HDL-C and delta apo A-I ( both p less than 0.001 ) . St and ardizing for DHA removed the difference in apo A-I levels between groups . This study suggests that EPA and DHA are divergently associated with HDL , possibly through different mechanisms Omega-3 fatty acids ( FAs ) reduce postpr and ial triacylglycerol ( TG ) concentrations . This study was undertaken to determine whether this effect was due to reduced production or increased clearance of chylomicrons . Healthy subjects ( n = 33 ) began with a 4-week , olive oil placebo ( 4 g/d ) run-in period . After a 4-week wash-out period , subjects were r and omized to supplementation with 4 g/d of ethyl esters of either safflower oil ( SAF ) , eicosapentaenoic acid ( EPA ) , or docosahexaenoic acid ( DHA ) for 4 weeks . Results for  EPA and DHA  were similar , and therefore the data were combined into one ω-3 FA group . Omega-3 FA supplementation  reduced the postpr and ial TG and apolipoprotein B ( apo B)-48 and apoB-100 concentrations by 16 % ( P = 0.08 ) , 28 % ( P < 0.001 ) , and 24 % ( P < 0.01 ) , respectively . Chylomicron TG half-lives in the fed state were reduced after ω-3 FA treatment ( 6.0 ± 0.5 vs. 5.1 ± 0.4 min ; P < 0.05 ) , but not after SAF ( 6.9 ± 0.7 vs. 7.1 ± 0.7 min ) . Omega-3 FA supplementation  decreased chylomicron particle sizes ( mean diameter ; 293 ± 44 vs. 175 ± 25 nm ; P < 0.01 ) and increased preheparin lipoprotein lipase ( LPL ; 0.6 ± 0.1 vs. 0.9 ± 0.1 μmol/h/ml ; P < 0.05 ) activity during the fed state , but had no effect on postheparin LPL or hepatic lipase activities . The results suggest that ω-3 FA  supplementation accelerates chylomicron TG clearance by increasing LPL activity , and that EPA and DHA are equally effective Objective : To assess the effects of omega-3 ( n-3 ) fatty acid supplementation on blood pressure and plasma lipids in hypertensives treated with diuretics or beta-blockers . Design : Double-blind placebo-controlled cross-over trial consisting of a 4-week run-in phase and two 6-week intervention phases . Patients : A total of 43 patients of either sex taking a beta-blocker only ( n = 29 ) , a diuretic only ( n = 3 ) or a beta-blocker plus diuretic ( n=11 ) for hypertension were recruited from general practice . One patient from the latter group was withdrawn . Methods : Seated blood pressure was measured every 2 weeks in the clinic with a Dinamap . After the run-in phase , participants were r and omly assigned to take a supplement of either Omacor ( 85 % n-3 fatty acid concentrate ) or corn oil ( four 1-g capsules/day ) for 6 weeks , after which they crossed over to the other supplement . Fasted blood sample s were taken at the end of each phase for lipid analysis . Main outcome measures : The within-individual differences in systolic and diastolic pressure and plasma lipids  between Omacor and corn oil treatment . Results : Systolic/diastolic blood pressures measured during the run-in phase were normal ( 132±2/76±1 mmHg , n = 42 ) but decreased further with n-3 fatty acid supplementation . The mean within-individual difference in blood pressure compared with corn oil supplementation was 3.1 ± 1.0/1.8±0.6 mmHg ( P<0.01 ) . This was accompanied by a 21 % reduction in plasma triglycerides ( P < 0.01 ) and a 15 % increase in high-density lipoprotein-2 cholesterol ( P < 0.01 ) but there were no significant differences in total or low-density lipoprotein cholesterol . Conclusion : The antihypertensive and hypotriglyceridaemic effects of n-3 fatty acid supplementation seen in the present study suggest that it may be a useful adjunct to antihypertensive therapy with beta-blockers or diuretics Fish-oil supplementation can reduce circulating triacylglycerol ( TG ) levels and cardiovascular risk . This study aim ed to assess independent associations between changes in platelet eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) and fasting and postpr and ial ( PP ) lipoprotein concentrations and LDL oxidation status , following fish-oil intervention .  Fifty-five mildly hypertriacylglycerolaemic ( TG 1.5 - 4.0 mmol/l ) men completed a double-blind placebo controlled cross over study , where individuals consumed 6 g fish oil ( 3 g EPA+DHA ) or 6 g olive oil (placebo)/d for two 6-week intervention periods , with a 12-week wash-out period in between . Fish-oil intervention result ed in a significant increase in the platelet phospholipid EPA ( + 491 % , P<0.001 ) and DHA ( + 44 % , P<0.001 ) content and a significant decrease in the arachidonic acid ( -10 % , P<0.001 ) and gamma-linolenic acid ( -24 % , P<0.001 ) levels . A 30 % increase in ex vivo LDL oxidation ( P<0.001 ) was observed . In addition , fish oil result ed in a significant decrease in fasting and PP TG levels ( P<0.001 ) , PP non-esterified fatty acid ( NEFA ) levels , and in the percentage LDL as LDL-3 ( P=0.040 ) , and an increase in LDL-cholesterol ( P=0.027 ) . In multivariate analysis , changes in platelet phospholipid DHA emerged as being independently associated with the rise in LDL-cholesterol , accounting for 16 % of the variability in this outcome measure ( P=0.030 ) . In contrast , increases in platelet EPA were independently associated with the reductions in fasting ( P=0.046 ) and PP TG ( P=0.023 ) , and PP NEFA ( P=0.015 ) , explaining 15 - 20 % and 25 % of the variability in response respectively . Increases in platelet EPA+DHA were independently and positively associated with the increase in LDL oxidation ( P=0.011 ) . EPA and DHA may have differential effects on plasma lipids in mildly hypertriacylglycerolaemic men BACKGROUND Chronic low- grade inflammation may contribute to the increased risk of atherosclerosis in visceral obesity .  Statin and fish oil have been reported to have antiinflammatory effects . We studied whether dyslipidemic , obese individuals have increased plasma high-sensitivity C-reactive protein ( hs-CRP ) concentrations and whether treatment with atorvastatin and fish oil lowered plasma hs-CRP concentrations . METHODS We compared plasma hs-CRP , interleukin-6 ( IL-6 ) , and tumor necrosis factor-alpha ( TNF-alpha ) concentrations in 48 obese individuals with the concentrations in 10 lean normolipidemic men . The obese individuals were then r and omized to treatment with atorvastatin ( 40 mg/day ) , fish oil ( 4 g/day ) , atorvastatin plus fish oil , or matching placebo for 6 weeks . RESULTS Compared with controls , obese individuals had increased hs-CRP [ geometric mean , 2.19 mg/L ( 95 % confidence interval , 2.15 - 3.15 mg/L ) vs 0.49 mg/L ( 0.30- 0.93 mg/L ) ; P < 0.001 ] and IL-6 [ 351 pg/L ( 318 - 449 pg/L ) vs 251 pg/L ( 211 - 305 pg/L ) ; P < 0.01 ] . Atorvastatin treatment had a significant main effect of decreasing plasma hs-CRP ( -0.87 mg/L ; 95 % confidence interval , -0.10 to -1.60 mg/L ; P < 0.01 ) and IL-6 ( -70 pg/L ; 10 to -140 pg/L ; P < 0.01 ) , but this was not seen with fish oil . The reductions in hs-CRP with atorvastatin were not significantly correlated to changes in plasma lipids , IL-6 , insulin resistance , or cholesterogenesis . Plasma TNF-alpha concentrations in obese individuals , however , were neither statistically different from concentrations in the lean controls nor altered with atorvastatin or fish oil treatment . CONCLUSIONS This study shows that visceral obesity is associated with increased plasma hs-CRP and IL-6 and , hence , a low- grade chronic inflammatory state and that treatment with atorvastatin or atorvastatin with fish oil , but not fish oil alone , reverses this abnormality Dietary n-3 fatty acids ( FAs ) found in fish oils markedly lower plasma triglyceride ( TG ) and very low density lipoprotein ( VLDL ) levels in both normal and hypertriglyceridemic subjects . The present study examined the mechanism of this effect . Ten subjects with widely different plasma triglyceride levels ( 82 to 1002 mg/dl ) were fed metabolically controlled diets containing 20 % fat . The control diet contained a blend of cocoa butter and peanut oil ( P/S = 0.8 ) . The test diet contained fish oil ( P/S = 1.1 ) and provided 10 - 17 g of n-3 FAs per day ( depending on calorie intake ) . After 3 to 5 weeks of each diet , the kinetics of VLDL-TG were determined over a 48-h period after the injection of [3H]glycerol . The fish oil diet reduced the VLDL-TG synthetic rate from 23 + /- 14.3 ( mean + /- SD ) to 12.6 + /- 7.5 mg/h per kg ideal weight ( P less than 0.005 ) and increased the fractional catabolic rate ( FCR ) for VLDL-TG from 0.23 + /- 0.12 to 0.38 + /- 0.16 h -1 ( P less than 0.005 ) . At the same time , there was a 66 % reduction of plasma triglyceride levels , result ing largely from a 78 % decrease in VLDL-TG levels ( 398 + /- 317 to 87 + /- 77 mg/dl ; P less than 0.005 ) . There was a strong correlation ( r = 0.83 ; P less than 0.01 ) between the change in synthetic rates and pool sizes , but there was no correlation ( r = 0.24 ; NS ) between changes in FCRs and pool sizes . The VLDL cholesterol : triglyceride ratio increased during the n-3 diet suggesting that smaller VLDL particles were present . These particles would be expected to leave the VLDL fraction more rapidly than larger particles producing a higher FCR . We conclude that the hypotriglyceridemic effect of fish oil appears to be caused primarily by an inhibition of very low density lipoprotein-triglyceride synthesis , but an additional , independent effect upon VLDL catabolism can not be ruled out Non-insulin-dependent diabetes mellitus ( NIDDM ) is associated with elevated very-low-density lipoprotein ( VLDL ) triglyceride concentrations and abnormalities of low-density lipoprotein ( LDL ) composition . Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects , we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM .  Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design . Medications , including antidiabetic therapy , were continued through the study . Compared with safflower oil treatment , fish oil supplementation result ed in a significant reduction of total plasma triglycerides of 24 % at the 4-g dose and a larger reduction of 39 % at the 7.5-g dose . These decreases were due to similar reductions in VLDL triglycerides . LDL cholesterol levels were mildly elevated , but a larger 20 % increase in LDL apolipoprotein B ( apoB ) concentration was observed . During supplementation with the fish oil concentrate , the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values , but not when compared with safflower oil treatment .  Highdensity lipoprotein ( HDL ) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment . At the 7.5-g dose , fasting glucose and glycohemoglobin levels increased by 20 and 12 % , respectively , but were unchanged at the lower level of supplementation . Thus , in NIDDM patients , dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels . However , the observed increase in LDL apoB levels , and the deterioration in glycemic control , indicate thatfurther study will be required to establish whether fish oil has a role in the treatment of NIDDM OBJECTIVES To investigate the effect of an omega-3 fatty acid concentrate K85 on serum lipids , lipoproteins , insulin metabolism and blood pressure in subjects with combined hyperlipidaemia . DESIGN After a run-in dietary period of 10 weeks , subjects were r and omly allocated to receive either encapsulated K85 ( n = 28 ) or corn oil ( n = 29 ) . The intervention was double-blind . SETTING An outpatient centre in Stavanger , Norway . SUBJECTS Fifty-seven of 141 individuals , who , after the run-in period continued to meet the inclusion criteria : serum triglycerides of > or = 2.0 mmol L-1 and total serum cholesterol of > or = 6.0 mmol L-1 . INTERVENTION Encapsulated K85 , containing 85 % eicosapentaenoic acid (EPA)/docosahexaenoic acid ( DHA ) , or corn oil , both administered in a daily dose of 4 g for 12 weeks . MAIN OUTCOME MEASURES Change in metabolic and haemodynamic parameters related to intervention . RESULTS Serum EPA and DHA increased significantly in the K85 group during the treatment period . The body-mass index remained unchanged . A 28 % reduction in serum triglycerides was noted in the K85 group from the first 4 weeks . Total serum cholesterol was significantly reduced with both regimens . Serum high-density lipoprotein cholesterol increased significantly during the first 8 weeks in the K85 group . Significant reductions in systolic and diastolic blood pressures were noted in subjects on K85 . The treatment did not affect serum glucose , plasma insulin and proinsulin levels . Insulin : glucose and proinsulin : glucose ratios remained unchanged . CONCLUSIONS The atherogenic risk profile was improved with K85 in subjects with combined hyperlipidaemia , but n-3 fatty acids supplementation did not affect glucose/insulin homeostasis OBJECTIVE The triglyceride-lowering effects of ω-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM . However , fish oil may impair glycemic control in NIDDM . The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat ( 30 % total energy ) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients . RESEARCH DESIGN AND METHODS In a controlled , 8-week intervention , 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and /or HDL cholesterol < 1.0 mmol/l were r and omly assigned to a low-fat diet ( 30 % daily energy intake ) with or without one fish meal daily ( 3.6 g ω-3/day ) and further r and omized to a moderate ( 55–65 % VO2max ) or light ( heart rate < 100 bpm ) exercise program .  An oral glucose tolerance test ( 75 g ) , fasting serum glucose , insulin , lipids , and GHb were measured before and after intervention . Self-monitoring of blood glucose was performed throughout . RESULTS In the 49 subjects who completed the study , moderate exercise  improved aerobic fitness ( VO2max ) by 12 % ( from 1.87 to 2.07 l/min , P = 0.0001 ) . Fish consumption  reduced triglycerides ( 0.80 mmol/l , P = 0.03 ) and HDL3 cholesterol ( 0.05 mmol/l , P = 0.02 ) and increased HDL2 cholesterol ( 0.06 mmol/l , P = 0.01 ) . After adjustment for age , sex , and changes in body weight , fish diets were associated with increases in GHb ( 0.50 % , P = 0.05 ) and self-monitored glucose ( 0.57 mmol/l , P = 0.0002 ) , which were prevented by moderate exercise . CONCLUSIONS A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients . Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise Summary Decreased release of nitric oxide from damaged endothelium is responsible for the impaired endothelium-dependent vasodilator responses found in animal models of vascular disease . Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations , principally by improving the release of nitric oxide from injured endothelium . Using forearm venous occlusion plethysmography we studied vascular responses to 60 , 120 , 180 and 240 nmol/min of acetylcholine ( an endothelium-dependent vasodilator ) and 3 , 6 and 9 nmol/min of glyceryl trinitrate ( an endothelium-independent vasodilator ) infused into the brachial artery in 23 patients with Type 2 ( non-insulin-dependent ) diabetes mellitus . NG monomethyl-l-arginine was employed to inhibit stimulated and basal release of nitric oxide from the endothelium . On completion of the baseline studies patients r and omly received either fish oil or matching olive oil capsules in a double-blind crossover fashion for 6 weeks followed by a 6-week washout period and a final 6-week treatment phase . Studies , identical to the initial baseline studies , were performed at the end of the active treatment periods at 6 and 18 weeks . Fish oil supplementation significantly improved forearm blood flow responses to each dose of acetylcholine when compared to the vasodilator responses recorded at baseline and after olive oil administration ( p<0.01 ) . Neither fish oil nor olive oil supplementation produced any significant changes in forearm blood flow to the incremental infusions of glyceryl trinitrate when compared with responses recorded during the baseline studies . NG monomethyl-l-arginine significantly reduced forearm blood flow from maximal stimulated values to acetylcholine when compared to the uninhibited decline in flow to acetylcholine infusions at comparable time points ( p<0.01 ) . Treatment with fish oils improved endothelium-dependent responses to acetylcholine without altering endothelium-independent responses to glyceryl trinitrate . By increasing stimulated nitric oxide release from the endothelium fish oils may afford protection against vasospasm and thrombosis in patients with diabetes mellitus 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 ’ Objectives : To compare the effect of alcohol-free Mediterranean-type diet ( MD ) and high-fat diet ( HFD ) on plasma concentration of emergent haemostatic cardiovascular risk factors ( HCVRF ) . Also , to test if red wine supplementation modifies HCVRF , independent of diet . Design , subjects and intervention : Controlled prospect i ve intervention study . Two groups , each of 21 healthy male university students ( 22±3.4 y ) , received either MD or HFD for 90 days . Between days 30 and 60 , both diets were supplemented with 240 ml/day of red wine . Baseline and T30 , T60 and T90-day sample s were drawn . No drop out from the study was observed . Setting : University campus and outpatient nutrition clinic . Results : Volunteers on HFD at T30 had increases in pro-coagulants fibrinogen ( 22 % ) , factor VIIc ( 9 % ) , and factor VIIIc ( 4 % ) , and decreases in natural anticoagulants antithrombin III ( 3 % ) , protein C ( 11 % ) and protein S ( 6 % ) and of 20 % in plasminogen activator inhibitor-1 . At the same time , individuals on MD had increases in fibrinogen ( 4 % ) , antithrombin III ( 5 % ) , protein C ( 3 % ) , protein S ( 2.7 % ) , and decreases in factor VIIIc ( 9 % ) , and plasminogen activator inhibitor-1 ( 21 % ) . After adjusting by baseline values , MD was associated with lower plasma fibrinogen ( P=0.03 ) , factor VIIc ( P=0.034 ) and factor VIIIc ( P=0.0057 ) and with higher levels of protein S ( P=0.013 ) . Red wine supplementation , in both diets , result ed in decreased plasma fibrinogen ( P=0.001 ) and factor VIIc ( P=0.05 ) , and increased tissue plasminogen activator antigen ( P=0.01 ) and plasminogen activator inhibitor-1 antigen ( P=0.0003 ) . Wine consumption was also associated with significantly ( P=0.01 ) divergent effects on antithrombin III : it decreased by 10 % in individuals on HFD but increased slightly in those on MD . No effects of diet or wine were detected in plasma protein C and C-reactive protein . Conclusion : MD and moderate consumption of red wine have complementary , mostly beneficial effects on HCVRF.Sponsorship : P Catholic University of Chile . Descriptors : diet ; wine ; haemostasis ; cardiovascular risk factorsEuropean Journal of Clinical Nutrition ( 2001 ) 55 , Objective : High-sensitivity C-reactive protein ( CRP ) , a marker of systemic inflammation , is a powerful predictor of cardiovascular risk . We hypothesised that n-3 fatty acids reduce underlying inflammatory processes and consequently CRP concentrations in healthy middle-aged subjects . Design : Placebo-controlled , double-blind study .Subjects : A total of 43 men and 41 postmenopausal women aged 50–70 y. Before and after intervention , we measured serum CRP concentrations with an enzyme immunoassay . Interventions : Capsules with either 3.5 g/day fish oil ( 1.5 g/day n-3 fatty acids ) or placebo for 12 weeks . Results : The median CRP change in the fish oil group did not significantly differ from that in the placebo group ( 0.01 vs −0.17 mg/l , P = 0.057 ) . Conclusion : The currently available data —including ours— do not support that beneficial effects on CRP are involved in a mechanism explaining the protective effect on heart disease risk of n-3 fatty acids as present in fish . Sponsorship : Wageningen Centre for Food Sciences Objective To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol . Methods The participants were 350 normotensive men and women aged 30–54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention . They were r and omly assigned to receive placebo or 6 g purified fish oil once a day , which supplied 3 g n-3 polyunsaturated fatty acids for 6 months . Results Baseline blood pressure  was ( mean ± SD ) 123±9/81 ±5mmHg . The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant . There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressures in the upper versus the lower quartile ( 132/87 versus 114/75 mmHg ) , low habitual fish consumption ( 0.4 versus 2.9 times a week ) or low baseline plasma levels of n-3 fatty acids . Fish oil increased HDL2-cholesterol significantly compared with the placebo group . Subgroup analysis showed this effect to be significant in the women but not in the men . Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure . Conclusion Moderate amounts of fish oil ( 6g/day ) are unlikely to lower blood pressure in normotensive persons , but may increase HDL2-cholesterol , particularly in women n-3 Fatty acids in the form of ethyl esters ( EE ) allow lower daily doses and improved compliance . Administration of n-3 fatty acids to patients with glucose intolerance has led to controversial findings , some studies indicating worsening of the disorder , others no effect , or an improvement . A total of 935 patients with hypertriglyceridemia , associated with additional cardiovascular risk factors , i.e. glucose intolerance , NIDDM and /or arterial hypertension were entered a double blind ( DB ) protocol lasting 6 months with n-3 EE versus placebo , followed by a further 6 months of open study ( n = 868 ) on 2 g a day of n-3 EE . At the end of the DB period , triglyceridemia in the total group was reduced significantly more by n-3 EE , without alterations in glycemic parameters . In the 6 months open follow up , patients on n-3 EE with type IIB hyperlipoproteinemia showed a significant reduction of total cholesterol , both in cases with ( -4.15 % vs. the 6 month levels ) and without NIDDM ( -3.8 % ) . HDL-cholesterol had an overall mean rise of 7.4 % , maximal in type IV patients with ( + 9.1 % ) and without ( + 10.1 % ) NIDDM . No alterations in glycemic parameters were detected in treated patients . Administration of n-3 EE to patients with hypertriglyceridemia associated with NIDDM or impaired glucose tolerance appears safe and effective Recent epidemiological studies have shown some beneficial health effects of the long chain ( n-3 ) polyunsaturated fatty acids found in fatty fish . Although the results of these studies are often ambiguous and inconclusive , they have prompted many intervention trials to study the effects of n-3 fatty acids ( FA ) on the cardiovascular risk profile . However screening of the literature revealed that many of the beneficial effects of fish ( oil ) were obtained in intervention studies which had several serious shortcomings in their design . Therefore we started a placebo controlled r and omised trial with increasing doses of n-3FA ( respectively 0 ; 1.12 ; 2.24 and 3.37 g n-3 FA/day ) and in order to have a maximum compliance this study was done in healthy monks . Fifty eight subjects took the fish oil capsules during 12 months and were thereafter followed for another 6 months . We could n't detect any effect of n-3 FA supplementation on total cholesterol , HDL cholesterol , LDL cholesterol , apo A1 , Lp(a ) , HbA1C , glucose , fibrinogen , factor VIII , antithrombin III , plasminogen activator inhibitor , tissue plasminogen activator and von Willebr and factor concentration , on bleeding time or on systolic or diastolic blood pressure . A pronounced significant dose dependent decrease of triglyceride levels was seen , while a slight but statistical significant decrease of apo B levels was observed in the highest fish oil dose . As the importance of triglycerides in the pathogenesis of atherosclerosis is still under discussion , the clinical relevance of these finding is not clear at the moment . It seems therefore improbable that the anti-atherosclerotic action of n-3 FA is due to an effect on the lipid , apoprotein , coagulation or fibrinolysis parameters as measured in our study . Hence further research must be focused on other parameters ( prostagl and ins ) which can be influenced by n-3 FA and which probably play an equally important role in the atherosclerotic process There is growing evidence supporting the importance of inflammation in all stages of atherosclerosis . While both omega-3 polyunsaturated fatty acids ( n3PUFA ) and the lipid-soluble antioxidant alpha-tocopherol ( AT ) have been shown to independently have significant anti-inflammatory effects , there is paucity of data examining the effect of n3PUFA alone and in combination with AT on markers of inflammation and monocyte function . Therefore , we tested the effect of n3PUFA alone , all-rac ( synthetic ) AT alone , and the combination on markers of inflammation and monocyte function . Healthy nonsmoking volunteers were r and omly assigned to 1 of 4 groups ( n = 20 per group ) : 1.5 g/d n3PUFA , 800 IU/d AT , 1.5 g n3PUFA + 800 IU/d AT , or placebo in a parallel double-blinded study . Compared to baseline , 12 weeks of supplementation result ed in no changes in plasma lipids regardless of treatment . Plasma AT was significantly increased only in those groups that received AT ( P < .0001 ) . Similarly , groups receiving n3PUFA showed a significant increase in plasma docosahexaenoic acid ( P < .0001 ) . No significant within- or between-group differences were found for plasma levels of high-sensitivity C-reactive protein ( hsCRP ) . Furthermore , there were no differences in monocyte proinflammatory cytokine release ( interleukin [IL]-1beta , tumor necrosis factor [TNF]-alpha and IL-6 ) after activation with monocyte chemotactic protein-1 ( MCP-1 ) . In conclusion , supplementation with n3PUFA and all-rac AT at these doses is not anti-inflammatory OBJECTIVES The effect of a fish oil preparation , K-85 , in which the omega-3 fatty acid content was concentrated to 92 % of total fat , on serum lipid and lipoprotein concentrations was investigated in patients with primary hypertriglyceridaemia . DESIGN The study was a r and omized , double-blind , placebo-controlled study . SETTING Seven centres participated in the study , five secondary referral centres and two general practice s. SUBJECTS Men and women aged 18 - 70 years with fasting serum triglyceride concentrations between 2 and 10 mmol/l and fasting serum cholesterol concentrations > 5.2 mmol/l were studied . Patients with diabetes mellitus , hypothyroidism , serious illness in the previous 3 months or severe concurrent illness were excluded from the study , as were drug or alcohol abusers and pregnant and lactating women . Ninety-five subjects entered the study , 79 completed the study . INTERVENTIONS Patients were r and omized to receive K-85 2 g twice daily or corn oil 2 g twice daily for 14 weeks . MAIN OUTCOME MEASUREMENTS The serum concentrations of triglycerides and cholesterol , very low-density lipoprotein ( VLDL ) , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) and lipoprotein ( a ) . Fasting blood glucose and blood pressure . RESULTS Serum triglycerides and VLDL-cholesterol were significantly lower in the group treated with K-85 than in the placebo group after 6 , 10 and 14 weeks ( all P < 0.01 ) and there was a decrease in the serum triglyceride concentration from 3.99 ( 2.94 - 9.47 ) to 2.87 ( 1.2 - 9.93 ) mmol/l ( P < 0.001 ) and in VLDL-cholesterol from 1.47 ( 0.77 - 3.63 ) to 1.12 ( 0.21 - 3.67 ) mmol/l ( P < 0.01 ) in patients receiving K-85 .  Serum HDL-cholesterol increased from 0.98 ( 0.95 - 1.01 ) to 1.11 ( 1.07 - 1.15 ) mmol/l ( P < 0.01 ) in the patients with type IV hyperlipoproteinaemia but did not change in those with type IIb . Serum LDL-cholesterol , lipoprotein ( a ) and fasting blood glucose were unaffected by K-85 .  Diastolic blood pressure decreased from 86 + /- 11 to 80 + /- 12 mmHg ( P < 0.02 ) and was also lower than in the placebo group ( P < 0.05 ) . The corn oil placebo did not affect any of the parameters . CONCLUSION K-85 is effective in lowering serum triglycerides and VLDL in patients with primary hypertriglyceridaemia and may have utility as a triglyceride-lowering agent OBJECTIVE The purpose of this study was to evaluate the effects of a concentrate of fish oil on blood pressure and serum lipids in patients treated for coronary artery disease . DESIGN One hundred and twenty-five patients were r and omly assigned to receive 15 g/day MaxEPA ( 4.5 g eicosapentaenoic and docosahexaenoic acids ) or olive oil .  Blood pressure and serum lipids were measured at enrollment and six months thereafter . MAIN RESULTS As an important proportion of antihypertensive or antianginal drug users stopped their usual medication during the trial , blood pressure increased in both groups . The increase in systolic blood pressure was less in the fish oil group than in the control group ( P = 0.002 ) . Serum triglyceride levels decreased markedly in the fish oil group while they remained constant in the control group ( P = 0.0001 ) . Fish oil supplementation had no effect on total cholesterol and only marginal independent influence on high density lipoprotein and low density lipoprotein cholesterol levels . CONCLUSIONS In conclusion , fish oil supplementation has a beneficial effect on blood pressure and serum triglycerides in patients treated for coronary artery disease 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 BACKGROUND Percutaneous transluminal coronary angioplasty ( PTCA ) is complicated by restenosis within 6 months in > 40 % of patients . Theoretical , animal experimental , and human epidemiological and clinical trial findings have suggested that fish oils ( n-3 ) might reduce restenosis . Low-molecular-weight heparin ( LMWH ) has reduced cellular proliferation and restenosis in several experimental systems . METHODS AND RESULTS We r and omized 814 patients to fish oils ( 5.4 g n-3 fatty acids ) or placebo a median of 6 days before PTCA and continued for 18 weeks . At the time of sheath removal , 653 patients with at least one successfully dilated lesion were r and omized to LMWH ( 30 mg SC BID ) or control for 6 weeks in a 2 x 2 factorial design . Follow-up with quantitative coronary angiography ( QCA ; target , 18 weeks ) was interpretable on 96 % of these patients . Restenosis rates per patient were for n-3 , 46.5 % ; placebo , 44.7 % ; LMWH , 45.8 % ; and control , 45.4 % . Restenosis rates per lesion were for n-3 , 39.7 % ; placebo , 38.7 % ; LMWH , 38 % ; and control , 40.4 % . At follow-up QCA , mean minimal lumen diameters were ( mm ) for n-3 , 1.12 ; placebo , 1.10 ; LMWH , 1.12 ; and control , 1.10 . Fifteen percent of patients permanently discontinued n-3/placebo before study completion , and 21 % of patients discontinued LMWH early . There were no significant differences in the occurrences of ischemic events . Bleeding was more common with LMWH , usually was mild , and led to early discontinuation of study medication in only 0.9 % of patients . Gastrointestinal side effects were more common in patients receiving n-3 than placebo . CONCLUSIONS There is no evidence for a clinical ly important reduction of PTCA restenosis in this trial by either n-3 or LMWH . Evaluation of the results for n-3 in the context of previously published data on the reduction of PTCA restenosis indicates that n-3 is not efficacious and that further trials are unwarranted In a prospect i ve , r and omised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infa rct prudent diet .  After a first myocardial infa rct ion , patients were r and omly assigned to the experimental ( n = 302 ) or control group ( n = 303 ) . Patients were seen again 8 weeks after r and omisation , and each year for 5 years . The experimental group consumed significantly less lipids , saturated fat , cholesterol  , and  linoleic acid  but more  oleic  and  alpha-linolenic acids  confirmed by measurements in plasma . Serum lipids , blood pressure , and body mass index remained similar in the 2 groups . In the experimental group , plasma levels of albumin , vitamin E , and vitamin C were increased , and granulocyte count decreased . After a mean follow up of 27 months , there were 16 cardiac deaths in the control and 3 in the experimental group ; 17 non-fatal myocardial infa rct ion in the control and 5 in the experimental groups : a risk ratio for these two main endpoints combined of 0.27 ( 95 % CI 0.12 - 0.59 , p = 0.001 ) after adjustment for prognostic variables . Overall mortality was 20 in the control , 8 in the experimental group , an adjusted risk ratio of 0.30 ( 95 % CI 0.11 - 0.82 , p = 0.02 ) . An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death Background Severe hypertriglyceridemia is a risk factor for acute pancreatitis , therefore decreasing serum triglyceride concentrations is an important component of risk management . Omega-3 fatty acids are well known hypotriglyceridemic agents , but their efficacy in severe forms of the disorder is not well documented . Our objective was to examine the effects of Omacor , a drug composed of 85 % omega-3 fatty acid ethyl esters . Methods Forty-two patients with triglyceride concentrations between 5.65 and 22.60 mmol/l ( 500 and 2000 mg/dl ) were studied in a prospect i ve , double-blind , placebo-controlled trial of Omacor ( 4 g/day for 4 months ) . Results Compared with baseline values , Omacor significantly reduced mean triglyceride concentrations by 45 % ( P < 0.00001 ) , cholesterol by 15 % ( P < 0.001 ) , very-low-density lipoprotein cholesterol by 32 % ( P < 0.0001 ) and cholesterol : High density lipoprotein ( HDL ) cholesterol ratio by 20 % ( P = 0.0013 ) , and increased HDL cholesterol by 13 % ( P = 0.014 ) and low-density lipoprotein cholesterol by 31 % ( P = 0.0014 ) . The placebo had no effect on these parameters . Omacor was well tolerated and no patient discontinued medication because of side effects . Conclusions Four capsules of Omacor per day markedly decreased  triglyceride concentrations in patients with severe hypertriglyceridemia . The availability of a potent and safe omega-3 fatty acid preparation for this patient population should diminish the risk for acute pancreatitis , and may also reduce the long-term risk for cardiovascular disease BACKGROUND A state of increased oxidative stress has been recognised in type 2 diabetes mellitus ( DM ) . The present study was done to assess the effects of low dose omega-3 fatty acids substitution in patients with type 2 DM with special reference to oxidative stress . METHOD Sixty-five patients with type 2 DM of body mass index ( BMI ) < 27 kg/m2 and thirty age and sex matched healthy controls were evaluated for blood glucose , blood pressure and lipid profile and oxidative stress was assessed in them by measuring lipid peroxides ( LP ) , diene conjugates ( DC ) and reduced glutathione ( RG ) in the serum .  Of the 65 , 40 motivated patients were r and omly divided into two groups -- group 1 comprising of fifteen patients prescribed a diabetic diet along with a placebo and group 2 consisting of twenty-five patients on the same diet with the addition of 0.6 g omega-3 fatty acids as one capsule Maxigard ( containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid ) twice daily . All parameters were reassessed after six weeks . RESULTS The levels of lipid peroxides ( micromol/L ) , diene conjugates ( OD units ) and reduced glutathione ( mmol GSH/L ) were significantly altered indicating increased oxidative stress in the diabetics compared to the healthy controls : 4.106 + /- 0.889 , 2.751 + /- 0.424 , 1.344 + /- 0.316 and 1.91 + /- 0.541 , 1.735 + /- 0.315 , 1.919 + /- 0.310 , respectively ( p < 0.001 for all the three ) . Patients in group 1 and 2 were comparable in all respects including oxidative stress at the start of therapy . After six weeks , on comparing the mean % changes in the three parameters of oxidative stress between the two groups , it was seen that the % change was significantly higher in group 2 ( Maxigard group ) compared to group 1 ( Placebo ; 5.22 + /- 1.056 ( p = 0.05 ) , 3.28 + /- 0.608 ( p = 0.01 ) , 5.27 + /- 0.585 ( p < 0.001 ) and 0.82 + /- 0.123 , 0.18 + /- 0.017 , 0.56 + /- 0.035 ( p < 0.001 ) , respectively . The patients in group 2 also exhibited significantly greater improvement in glycemic status , blood pressure and lipid profiles . CONCLUSIONS The present study documented the existence of a state of increased oxidative stress in type 2 diabetics . Significant beneficial effects of low dose omega-3 fatty acids substitution for PUFA-6 were observed not only on oxidative stress parameters but also on blood pressure and metabolic profile The aim of this study was to evaluate the effects of a fish oil preparation ( MaxEPA ) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic ( NIDDM ) subjects . Eighty NIDDM out patients aged 55.9 yr ( mean SD 11.5 yr ) participated in a prospect i ve double-blind placebo-controlled study of MaxEPA capsules ( 10 g/day ) or olive oil ( control ) treatment over 6 wk . Patients received either MaxEPA or olive oil in addition to preexisting therapy .  Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk . Platelet membrane eicosapentaenoic acid ( EPA ) content increased in the treatment group ( P < 0.001 ) . MaxEPA supplementation was associated with a significant fall in total triglycerides ( P < 0.001 ) but did not affect total cholesterol ( P = 0.7 ) compared with control treatment . Fasting plasma glucose increased after 3 wk ( P = 0.01 ) but not after 6 wk ( P = 0.17 ) treatment with MaxEPA .  Spontaneous platelet aggregation in whole blood fell in the MaxEPA group ( P < 0.02 ) after 6 wk , but there were no changes in agonist-induced platelet aggregation , thromboxane generation in platelet-rich plasma , or plasma P-thromboglobulin and platelet factor IV levels . An increase in clotting factor VII ( P = 0.02 ) , without changes in fibrinogen or factor X levels , occurred in the MaxEPA group . Similar reductions in blood pressure were observed in both groups . Dietary supplementation with MaxEPA capsules ( 10 g/day ) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels . Most indices of platelet function are unaffected by this therapy Since the first AHA Science Advisory “ Fish Consumption , Fish Oil , Lipids , and Coronary Heart Disease,”1 important new findings , including evidence from r and omized controlled trials ( RCTs ) , have been reported about the beneficial effects of omega-3 ( or n-3 ) fatty acids on cardiovascular disease ( CVD ) in patients with preexisting CVD as well as in healthy individuals.2 New information about how omega-3 fatty acids affect cardiac function ( including antiarrhythmic effects ) , hemodynamics ( cardiac mechanics ) , and arterial endothelial function have helped clarify potential mechanisms of action . The present Statement will address distinctions between plant-derived ( α-linolenic acid , C18:3n-3 ) and marine-derived ( eicosapentaenoic acid , C20:5n-3 [ EPA ] and docosahexaenoic acid , C22:6n-3 [ DHA ] ) omega-3 fatty acids . ( Unless otherwise noted , the term omega-3 fatty acids will refer to the latter . ) Evidence from epidemiological studies and RCTs will be review ed , and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid ( plant- and marine-derived ) supplementation . This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration ( FDA ) about the presence of environmental contaminants in certain species of fish . # # # Coronary Heart Disease As review ed by Stone,1 three prospect i ve epidemiological studies within population s reported that men who ate at least some fish weekly had a lower coronary heart disease ( CHD ) mortality rate than that of men who ate none.3–6 ⇓ ⇓ ⇓ More recent evidence that fish consumption favorably affects CHD mortality , especially nonsudden death from myocardial infa rct ion ( MI ) , has been reported in a 30-year follow-up of the Chicago Western Electric Study .7 Men who consumed 35 g or more of fish daily compared with those who consumed none had a relative risk of death from CHD of 0.62 and a relative risk of nonsudden death from MI of 0.33 . In an
target: Combining 21 trials evaluating lipid outcomes , fish oil consumption result ed in a summary net change in triglycerides of -27 ( 95 % CI -33 , -20)mg/dL , in HDL cholesterol of + 1.6 ( 95 % CI + 0.8 , + 2.3)mg/dL , and in LDL cholesterol of + 6 ( 95 % CI + 3 , + 8)mg/dL. There was no effect of fish oil on total cholesterol .
  Across studies , higher fish oil dose and higher baseline levels were associated with greater reductions in serum triglycerides .
  The evidence supports a dose-dependent beneficial effect of fish oil on serum triglycerides , particularly among people with more elevated levels .
  Fish oil consumption also modestly improves HDL cholesterol , increases LDL cholesterol levels , but does not appear to adversely affect glucose homeostasis .
  The evidence regarding the effects of omega-3 fatty acids on hs-CRP is inconclusive , as are data on ALA
background: Greater fish oil consumption has been associated with reduced CVD risk , although the mechanisms are unclear .
  Plant- source oil omega-3 fatty acids ( ALA ) have also been studied regarding their cardiovascular effect .