Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus. Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes Effect of w3 fatty acid on plasma lipids, cholesterol and lipoprotein fatty acid content in NIDDM patients Fish Oil–Induced Changes in Apolipoproteins in IDDM Subjects Dietary supplementation with n-3 fatty acids increases gluconeogenesis from glycerol but not hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. N-3 fatty acids do not lead to an increased diabetic risk in patients with hyperlipidemia and abnormal glucose tolerance. Italian Fish Oil Multicenter Study. 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. Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Fish and Long-Chain &ohgr;-3 Fatty Acid Intake and Risk of Coronary Heart Disease and Total Mortality in Diabetic Women Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. [The effect of fish oil on the secretion and effect of insulin in patients with type II diabetes]. Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients. A Comparison of the Effects of n-3 Fatty Acids From Linseed Oil and Fish Oil in Well-Controlled Type II Diabetes Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses. Effect of Fish Oil Concentrate on Lipoprotein Composition in NIDDM Dietary fish oil augments nitric oxide production or release in patients with Type 2 (non-insulin-dependent) diabetes mellitus Effects of a Small Quantity of ω-3 Fatty Acids on Cardiovascular Risk Factors in NIDDM: A randomized, prospective, double-blind, controlled study Lack of benefit of dietary advice to men with angina: results of a controlled trial Comparison of the effects of simultaneous administration of vitamin C and omega-3 fatty acids on lipoproteins, apo A-I, apo B, and malondialdehyde in hyperlipidemic patients. Dietary supplementation with n-3 fatty acids may impair glucose homeostasis in patients with non-insulin-dependent diabetes mellitus. Long-term effects of fish oil on lipoprotein subfractions and low density lipoprotein size in non-insulin-dependent diabetic patients with hypertriglyceridemia. A Comparison of Fish Oil or Corn Oil Supplements in Hyperlipidemic Subjects with NIDDM Effect of dietary fish oil supplementation on peroxidation of serum lipids in patients with non-insulin dependent diabetes mellitus. Supplementation with n‐3 fatty acids reduces triglycerides but increases PAI‐1 in non‐insulin‐dependent diabetes mellitus Effects of Low-Dose EPA-E on Glycemic Control, Lipid Profile, Lipoprotein(a), Platelet Aggregation, Viscosity, and Platelet and Vessel Wall Interaction in NIDDM Effect of dietary fish supplementation on lipoprotein levels in patients with hyperlipoproteinemia. Long-Term Effects of Fish Oil on Insulin Resistance and Plasma Lipoproteins in NIDDM Patients With 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. Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Effects of Fish Oil Supplements in NIDDM Subjects: Controlled Study Cholesterol measures to identify and treat individuals at risk for coronary heart disease.
In a double-blind , placebo-controlled study we investigated the effects of dietary fish oil supplementation on arterial wall characteristics in 20 patients with non-insulin-dependent diabetes mellitus . Estimates reflecting compliance values in the large arteries and more peripheral vasculature , as measured by pulse-contour analysis , improved significantly after 6 weeks of fish oil therapy compared with values recorded at baseline and after 6 weeks ' administration of olive oil . The large-artery compliance estimate increased from 1.50 ( confidence interval [ CI ] , 1.31 to 1.69 ) mL/mm Hg at baseline to 1.68 ( CI , 1.52 to 1.84 ) mL/mm Hg after fish oil administration ( P < .01 ) . The oscillatory compliance value increased from 0.015 ( CI , 0.011 to 0.019 ) mL/mm Hg at baseline to 0.022 ( CI , 0.016 to 0.028 ) mL/mm Hg after fish oil ingestion ( P < .05 ) . No changes occurred in arterial blood pressure , cardiac output , stroke volume , or systemic vascular resistance with either intervention . The improved compliance estimates with fish oil ingestion occurred without altering fasting blood glucose and cholesterol concentrations . These results support the hypothesis that fish oils alter vascular reactivity and favorably influence arterial wall characteristics in patients with non-insulin-dependent diabetes mellitus . These direct vascular effects , expressed at the level of the vessel wall , may contribute to the cardioprotective actions of fish oil in humans 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 Summary This study was conducted to examine the effect of ω3 fatty acid supplementation on plasma lipid , cholesterol and lipoprotein fatty acid content of non-insulin-dependent diabetic individuals consuming a higher ( 0.65 , n = 10 ) or lower ( 0.44 , n = 18 ) ratio of dietary polyunsaturated to saturated fatty acid ( P/S ) . The participants were initially given an olive oil supplement ( placebo ) equivalent to 35 mg of 18:1 · kg body weight–1 · day–1 for 3 months . This was followed by two ω3 supplement periods in a r and omized crossover . In these 3-month periods , participants were given a linseed oil supplement equivalent to 35 mg of 18:3ω3 · kg body weight–1 · day–1 or a fish oil supplement equivalent to 35 mg of 20:5ω3 + 22:6ω3 · kg body weight–1 · day–1 . At the end of each supplement period , a blood sample was drawn from each participant for lipid , lipoprotein , insulin , glucagon and C-peptide analyses . At the end of each 3-month period a 7-day dietary record was completed to calculate dietary fat intake and P/S ratio . Results indicate that fish oil significantly reduced plasma triacylglycerol level ( p < 0.05 ) and increased 20:5ω3 and 22:6ω3 content of all lipoprotein lipid classes . Linolenic acid supplementation had no effect on plasma triacylglycerol level , but it increased 18:3ω3 content of lipoprotein cholesterol ester fractions ( p < 0.05 ) . A slight increase in 20:5ω3 , but not 22:6ω3 , content was noted in lipoprotein lipid classes as a result of 18:3ω3 supplementation . LDL and HDL cholesterol , insulin , glucagon and C-peptide levels were not affected by either ω3 supplement . It is concluded that a modest intake of ω3 fatty acids , such as could be obtained from consuming fish regularly , will reduce plasma triglyceride level without affecting LDL or HDL cholesterol levels . [ Diabetologia ( 1997 ) 40 : 45–52 The aim of this study was to examine the effect of Max EPA ( a commercially available fish oil preparation ) on serum cholesterol lipoproteins and apolipoproteins in insulin-dependent diabetic ( IDDM ) men with dosages that were likely to be acceptable to patients . Twenty-two male IDDM patients aged 20–41 yr , 6 of whom had retinopathy , were recruited from the Royal Perth Hospital diabetic clinic . After screening , subjects were divided into three groups . Six of the subjects without retinopathy were r and omly selected and allocated to a control group . The remaining 16 patients ( 10 without and 6 with retinopathy ) received a fish oil supplement . All subjects were advised to maintain their usual dietary patterns . Sixteen patients , including the 6 with retinopathy , were instructed to take 15 Max EPA fish oil capsules/day with meals . Patients in the control group did not take Max EPA . Three weeks of Max EPA supplementation without other dietary modification led to a significant rise in total cholesterol ( P < 0.01 ) , which could be accounted for by increases in low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol . The increase in HDL cholesterol was explained by a 33 % rise ( P < 0.001 ) in its HDL2 subclass . Changes in apolipoproteins were examined and showed that the level of apolipoprotein A-l increased after ingestion of fish oil and correlated significantly ( P < 0.05 ) with the rise in HDL cholesterol . Apolipoprotein A-ll showed a significant fall at the end of Max EPA intake in a subgroup of patients with retinopathy , and this correlated significantly ( P < 0.05 ) with the fall in HDL3 cholesterol observed at this time . A significant rise in apolipoprotein B ( P < 0.05 ) was correlated with the rise in LDL cholesterol . Possible adverse effects of the increase in both total and LDL cholesterol after 15 g/day Max EPA may be compensated for by a rise in the protective HDL2 subclass . However , in view of this hypercholesterolemic effect and evidence that suggests that LDL apolipoprotein B may be a risk factor for coronary heart disease , these findings raise questions regarding the safety of fish oils in patients with IDDM Fish-oil supplementation decreases serum triacylglycerols but may worsen hyperglycemia in patients with non-insulin-dependent diabetes mellitus . The reason for the possible deterioration of glycemia is unclear . We examined whether inhibition of triacylglycerol synthesis by n-3 fatty acids changes lipolysis , glycerol gluconeogenesis , or fatty acid oxidation .  Nine obese patients with non-insulin-dependent diabetes mellitus participated in a r and omized double-blind crossover study in which 6 wk of n-3 fatty acid supplementation ( 12 g fish oil ) was compared with 6 wk of corn plus olive oil .  Serum triacylglycerols decreased by 30 % during n-3 fatty acid supplementation . Glycerol gluconeogenesis ( [U-14C]glycerol ) increased by 32 % . However , overall glucose production ( [3 - 3H]glucose ) , glycemic control , and fatty acid oxidation remained unchanged . Thus , 6 wk of n-3 fatty acid supplementation lowers triacylglycerols in patients with non-insulin-dependent diabetes mellitus without worsening glycemic control . However , n-3 fatty acid supplementation increases glycerol gluconeogenesis , which could contribute to deterioration of glycemic control during long-term treatment with high doses of fish-oil supplements A multicenter , r and omized , double-blind , place-bo-controlled study evaluated the possible worsening of glycemic control after a moderate daily intake of n-3 fatty acid ethyl esters in patients with hypertriglyceridemia with and without glucose intolerance or diabetes . A total of 935 patients of both sexes in 63 Italian clinical centers were selected ; 55 % had either impaired glucose tolerance or non-insulin-dependent diabetes mellitus ( NIDDM ) . They received for 2 mo either 1 g n-3 ethyl esters three times a day or a corresponding placebo , followed by 4 mo of either 1 g n-3 ethyl esters twice a day or placebo . In addition to the complete lipid and lipoprotein evaluation , patients with impaired glucose tolerance also underwent an oral-glucose-tolerance test ; in patients with NIDDM , serum insulin and glycated hemoglobin ( Hb A1c ) concentrations were determined . Plasma triacylglycerol concentrations decreased significantly , up to 21.53 % at 6 mo compared with baseline ( decreased 15 % compared with placebo ) , with a tendency toward a progressive reduction with time . There was no evidence for a different response in patients with either NIDDM or impaired glucose tolerance . Among NIDDM patients , the triacylglycerol reduction was greater in those with high-density-lipoprotein cholesterol < or = 0.91 mmol/L. There was no alteration in the major glycemic indexes : fasting glucose , Hb A1c , insulinemia , and oral glucose tolerance in patients with impaired glucose tolerance or NIDDM after treatment with n-3 ethyl esters . Treatment with a moderate daily dose of n-3 ethyl esters over a prolonged period of time significantly reduced triacylglycerol concentrations without any worsening of glucose tolerance in patients with hypertriglyceridemia with and without impaired glycemic regulation 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 BACKGROUND Higher intakes of fish and n-3 fatty acids are associated with a reduced risk of cardiovascular events and mortality . However , limited data exist on the effect of fish intake on actual measures of progression of coronary artery atherosclerosis . OBJECTIVE The aim was to examine the association between fish intake and the progression of coronary artery atherosclerosis in women with coronary artery disease . DESIGN This was a prospect i ve cohort study of postmenopausal women ( n = 229 ) participating in the Estrogen Replacement and Atherosclerosis trial . Usual fish intake was estimated at baseline with a food-frequency question naire . Quantitative coronary angiography was performed at baseline and after 3.2 + /- 0.6 ( x + /- SD ) y to evaluate changes in the mean minimum coronary artery diameter , the mean percentage of stenosis , and the development of new coronary lesions . RESULTS Compared with lower fish intakes , consumption of > or = 2 servings of fish or > or = 1 serving of tuna or dark fish per week was associated with smaller increases in the percentage of stenosis ( 4.54 + /- 1.37 % compared with -0.06 + /- 1.59 % and 5.12 + /- 1.48 % compared with 0.35 + /- 1.47 % , respectively ; P < 0.05 for both ) in diabetic women after adjustments for age , cardiovascular disease risk factors , and dietary intakes of fatty acids , cholesterol , fiber , and alcohol . These associations were not significant in nondiabetic women . Higher fish consumption was also associated with smaller decreases in minimum coronary artery diameter and fewer new lesions . CONCLUSIONS Consumption of fish is associated with a significantly reduced progression of coronary artery atherosclerosis in women with coronary artery disease Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat , high complex carbohydrate diet .  Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation ;  plasma total and HDL cholesterol concentrations did not change . The LDL cholesterol level was significantly increased with fish oil supplementation , suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and /or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease . The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients BACKGROUND Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis . We assessed whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) from fish oil have differential effects on platelet , fibrinolytic and vascular function in patients with both conditions . METHODS In a double-blind placebo-controlled trial of parallel design , 59 treated-hypertensive Type 2 diabetic men and postmenopausal women , were r and omised to 4 g/day of EPA , DHA or olive oil ( placebo ) for 6 weeks . Collagen and PAF-stimulated platelet aggregation , collagen-stimulated thromboxane release ( TXB2 ) , plasma tPA and PAI-1 antigens , von Willebr and factor , p-selectin , and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery , were examined before and at the end of intervention . RESULTS Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study . Relative to placebo , DHA but not EPA supplementation significantly reduced collagen aggregation ( 16.9 % , P=0.05 ) and TXB2 ( 18.8 % , P=0.03 ) . There were no significant changes in either PAF-stimulated platelet aggregation , fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo . CONCLUSION Highly purified DHA may be a more effective anti-thrombotic agent than EPA . However , longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension Background —Although several prospect i ve cohort studies have found an inverse association between fish consumption and risk of coronary heart disease ( CHD ) or sudden cardiac death in the general population , limited data are available among diabetic patients . Methods and Results —We examined prospect ively the association between intake of fish and & ohgr;-3 fatty acids and risk of CHD and total mortality among 5103 female nurses with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline . Between 1980 and 1996 ( 45 845 person-years of follow-up ) , we documented 362 incident cases of CHD ( 141 CHD deaths and 221 nonfatal myocardial infa rct ions ) and 468 deaths from all causes . Compared with women who seldom consumed fish ( < 1 serving/mo ) , the relative risks ( RRs ) ( 95 % CI ) of CHD adjusted for age , smoking , and other established coronary risk factors were 0.70 ( 0.48 to 1.03 ) for fish consumption 1 to 3 times per month , 0.60 ( 0.42 to 0.85 ) for once per week , 0.64 ( 0.42 to 0.99 ) for 2 to 4 times per week , and 0.36 ( 0.20 to 0.66 ) for 5 or more times per week ( P for trend=0.002 ) . Higher consumption of fish was also associated with a significantly lower total mortality ( multivariate RR=0.48 [ 0.29 to 0.80 ] for ≥5 times per week [ P for trend=0.005 ] ) . Higher consumption of long-chain & ohgr;-3 fatty acids was associated with a trend toward lower incidence of CHD ( RR=0.69 [ 95 % CI 0.47 to 1.03 ] , P for trend=0.10 ) and total mortality ( RR=0.63 [ 95 % CI , 0.45 to 0.88 ] , P for trend=0.02 ) . Conclusions —A higher consumption of fish and long-chain & ohgr;-3 fatty acids was associated with a lower CHD incidence and total mortality among diabetic women CONTEXT Current guidelines for cardiovascular risk detection are controversial with regard to the clinical utility of different lipid measures , non-high-density lipoprotein cholesterol ( non-HDL-C ) , lipid ratios , apolipoproteins , and C-reactive protein ( CRP ) . OBJECTIVE To directly compare the clinical utility of total cholesterol , low-density lipoprotein cholesterol ( LDL-C ) , HDL-C , non-HDL-C , apolipoproteins A-I and B(100 ) , high-sensitivity CRP , and the ratios of total cholesterol to HDL-C , LDL-C to HDL-C , apolipoprotein B(100 ) to apolipoprotein A-I , and apolipoprotein B(100 ) to HDL-C as predictors of future cardiovascular events in women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 15,632 initially healthy US women aged 45 years or older ( interquartile range , 48 - 59 years ) who were enrolled between November 1992 and July 1995 . All participants were followed up over a 10-year period for the occurrence of future cardiovascular events . MAIN OUTCOME MEASURE Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for first-ever major cardiovascular events ( N = 464 ) according to baseline levels of each biomarker . RESULTS After adjustment for age , smoking status , blood pressure , diabetes , and body mass index , the HRs for future cardiovascular events for those in the extreme quintiles were 1.62 ( 95 % CI , 1.17 - 2.25 ) for LDL-C , 1.75 ( 95 % CI , 1.30 - 2.38 ) for apolipoprotein A-I , 2.08 ( 95 % CI , 1.45 - 2.97 ) for total cholesterol , 2.32 ( 95 % CI , 1.64 - 3.33 ) for HDL-C , 2.50 ( 95 % CI , 1.68 - 3.72 ) for apolipoprotein B(100 ) , 2.51 ( 95 % CI , 1.69 - 3.72 ) for non-HDL-C , and 2.98 ( 95 % CI , 1.90 - 4.67 ) for high-sensitivity CRP ( P<.001 for trend across all quintiles ) . The HRs for the lipid ratios were 3.01 ( 95 % CI , 2.01 - 4.50 ) for apolipoprotein B(100 ) to apolipoprotein A-I , 3.18 ( 95 % CI , 2.12 - 4.75 ) for LDL-C to HDL-C , 3.56 ( 95 % CI , 2.31 - 5.47 ) for apolipoprotein B(100 ) to HDL-C , and 3.81 ( 95 % CI , 2.47 - 5.86 ) for the total cholesterol to HDL-C ( P<.001 for trend across all quintiles ) . The correlation coefficients between high-sensitivity CRP and the lipid parameters ranged from -0.33 to 0.15 , and the clinical cut points for CRP of less than 1 , 1 to 3 , and higher than 3 mg/L provided prognostic information on risk across increasing levels of each lipid measure and lipid ratio . CONCLUSIONS Non-HDL-C and the ratio of total cholesterol to HDL-C were as good as or better than apolipoprotein fractions in the prediction of future cardiovascular events . After adjustment for age , blood pressure , smoking , diabetes , and obesity , high-sensitivity CRP added prognostic information beyond that conveyed by all lipid measures The metabolic effect of 3-week dietary supplementation with a fish oil concentrate was examined in not markedly obese , not hypertriglyceridemic men with non-insulin-dependent diabetes mellitus ( NIDDM ) treated with hypoglycemic agents . Ten patients were given 15 ml/d of fish oil ( Martens Oil , Norway ) equivalent to 3.1 g of n-3 fatty acid ( FA ) per day , and compared to 10 diabetics treated with placebo ( 15 ml/d saline ) . While fish oil leads to expected increase in the ratio of n-3 to n-6 FA intake , it does not alter fasting and mixed meal stimulated blood glucose , plasma insulin and C-peptide concentrations . There were no changes in insulin action estimated by the metabolic clearance rates of glucose at plasma insulin levels of about 100 microU/ml and 1400 microU/ml during hyperinsulinemic isoglycemic clamp , and no changes were seen in insulin binding to erythrocytes . Even though our short-term study does not warrant authoritative conclusions , no adverse effects of low-dose fish oil on glucose homeostasis have been found in not markedly obese NIDDM patients treated with oral hypoglycemics OBJECTIVE The increased risk of coronary heart disease associated with type 2 diabetes may be partially explained by dyslipidemia characterized by high plasma triacylglycerol ( TAG ) , low HDL cholesterol , and a predominance of atherogenic small dense LDLs . Fish oil reduces plasma TAG and has previously been shown to improve the distribution of LDL subclasses in healthy subjects and might , therefore , be a good nonpharmacological treatment for type 2 diabetic patients . In the present study , we investigate the effect of fish oil supplementation on the fasting lipid profile , including LDL and HDL subclasses . RESEARCH DESIGN AND METHODS A total of 42 type 2 diabetic patients were r and omized to supplementation ( capsules ) with 4 g daily of either fish oil ( n = 20 ) or corn oil ( n = 22 ) for 8 weeks preceded by a 4-week run-in period of corn oil supplementation . Blood was drawn before and after the 8-week intervention period . Plasma lipoproteins , including LDL and HDL subclasses , were separated by ultracentrifugation . RESULTS Fish oil lowered TAG ( group difference : P = 0.025 ) and raised HDL-2b cholesterol ( P = 0.012 ) and HDL-2a cholesterol ( P = 0.007 ) concentrations as compared with corn oil . We observed no significant effects of fish oil on LDL cholesterol , HDL cholesterol , or the concentration of small dense LDL particles . CONCLUSIONS Fish oil supplementation may partially correct the dyslipidemia of type 2 diabetic patients . However , the putative very important aspect of diabetic dyslipidemia-the predominance of small dense LDL particles-was unaffected by fish oil OBJECTIVE Supplementation of type II diabetic diets with n-3 fatty acids ( FAs ) from fish oil ( FO ) has been associated with lowered triglyceride and VLDL levels , although reports of impaired glycemic control have limited their use . Effects of n-3FAs from nonmarine sources are less well documented . Therefore , an investigation comparing the effects of linseed oil ( LO ) with FO supplementation was undertaken in subjects with type II diabetes . RESEARCH DESIGN AND METHODS Eleven subjects with type II diabetes were given supplements with LO and FO for 3 months each in a r and omized double-blind crossover fashion after 3 months of olive oil placebo . Oils were given as 35 mg FA · kg body wt−1 · day−1 . After each 3-month period , fasting glucose and insulin levels , HbA1c , lipid profiles , insulin sensitivity ( SI ) , glucose effectiveness ( SG ) , and acute insulin response to glucose ( AIRG ) were evaluated . RESULTS HbA1c and lipid values were within the normal range at r and omization . Repeated measures analysis of variance testing found no significant differences in weight ; fasting glucose and insulin levels ; HbA1c ; total , LDL , and HDL cholesterol levels ; SI ; SG ; or AIRG with either active oil . FO was associated with significant reductions in triglycerides and a trend toward decreased SI . CONCLUSIONS In a population with well-controlled type II diabetes , 3 months of FO but not LO result ed in lowered triglyceride levels . Neither LO nor FO significantly affected glycemic control , cholesterol values , SG , or insulin secretion , while a nonsignificant trend toward decreased insulin sensitivity was found with FO 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 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 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 OBJECTIVE To study the effects of a low dose of ω-3 fatty acids on platelet function and other cardiovascular risk factors in patients with non-insulin-dependent diabetes mellus ( NIDDM ) . RESEARCH DESIGN AND METHODS We performed a r and omized , prospect i ve , double-blind , controlled study of a low dose of ω-3 fatty acids ( 2.5 g/day ) in 20 ambulatory subjects with NIDDM . Subjects ingested five 1-g fish oil capsules each containing 0.5 g ω-3 fatty acids or five 1-g safflower oil capsules per day for 6 weeks followed by a 6-week washout period . RESULTS Nine subjects completed the study in each group . Both groups exhibited moderate control of glucose levels ; modest elevations in baseline total cholesterol , low-density lipoprotein ( LDL ) cholesterol , and triglyceride ( TG ) levels ; and normal blood pressure values . In the fish oil group , plasma ω-3 fatty acid levels increased significantly . Fish oil significantly reduced the slope of the dose-response curves for collagen-induced platelet aggregation to one-third the value observed with safflower oil . No difference was observed in collageninduced production of thromboxane A2 ( TXA2 , measured as the stable derivative TXB2 ) , or in adenosine-5'-diphosphate- ( ADP ) induced platelet aggregation or TXA2 generation . Patients with high initial collagen-induced platelet TXA2 production showed a significantly larger drop after fish oil than safflower oil . Fish oil significantly reduced TG levels by 44 mg/dl and decreased upright systolic blood pressure ( sBP ) by 8 mmHg compared with safflower oil . Fish oil caused a significant but small increase in HbA1c ( 0.56 % ) and total cholesterol ( 20 mg/dl ) but had no effect on fasting glucose , high-density lipoprotein cholesterol , or LDL-cholesterol levels . CONCLUSIONS Small doses of fish oil inhibit platelet aggregation and TXA2 production , reduce upright sBP and TG levels , and have only a small effect on glucose and cholesterol levels in patients with moderately controlled NIDDM . Small quantities of ω-3 fatty acids or dietary fish are safe and potentially beneficial in NIDDM patients Objective : To see whether mortality among men with angina can be reduced by dietary advice . Design : A r and omized controlled factorial trial . Setting : Male patients of general practitioners in south Wales . Subjects : A total of 3114 men under 70 y of age with angina . Interventions : Subjects were r and omly allocated to four groups : ( 1 ) advised to eat two portions of oily fish each week , or to take three fish oil capsules daily ; ( 2 ) advised to eat more fruit , vegetables and oats ; ( 3 ) given both the above types of advice ; and ( 4 ) given no specific dietary advice .  Mortality was ascertained after 3–9 y. Results : Compliance was better with the fish advice than with the fruit advice . All-cause mortality was not reduced by either form of advice , and no other effects were attributable to fruit advice . Risk of cardiac death was higher among subjects advised to take oily fish than among those not so advised ; the adjusted hazard ratio was 1.26 ( 95 % confidence interval 1.00 , 1.58 ; P=0.047 ) , and even greater for sudden cardiac death ( 1.54 ; 95 % CI 1.06 , 2.23 ; P=0.025 ) . The excess risk was largely located among the subgroup given fish oil capsules . There was no evidence that it was due to interactions with medication . Conclusion : Advice to eat more fruit was poorly complied with and had no detectable effect on mortality . Men advised to eat oily fish , and particularly those supplied with fish oil capsules , had a higher risk of cardiac death . This result is unexplained ; it may arise from risk compensation or some other effect on patients ' or doctors ' behaviour . Sponsorship : British Heart Foundation , Seven Seas Limited , Novex Pharma Limited , The Fish Foundation BACKGROUND Control of hyperlipidemia is vital in patients with cardiovascular disease ( CVD ) .  Omega-3 fatty acids ( n-3FAs ) have desirable effects on serum triglyceride ( TG ) levels , thrombosis , and arrhythmia , but lead to increases in serum low-density lipoprotein ( LDL ) and apo-B as well . OBJECTIVE To determine and compare the effects of administration of n-3FAs , vitamin C ( VitC ) and n-3FAs + VitC on the serum levels of LDL , apoB , other serum lipids , and malondialdehyde ( MDA ) . The present study was performed in Tehran University of Medical Sciences from 2000 to 2001 . DESIGN In a double-blind , placebo trial of parallel design , 68 hyperlipidemic patients [ total cholesterol ( TC ) and TG greater than 200 mg/dL ] were r and omly assigned to receive daily 500 mg VitC , 1 g n-3FAs , 500 mg VitC + 1 g n-3FAs , or placebo ( control ) for 10 weeks . Fasting blood sample s were collected at the beginning and at the end of the period . TG , TC , LDL-cholesterol-C ( LDL-C ) , and high-density lipoprotein-cholesterol ( HDL-C ) were measured enzymatically , VitC and MDA colorimetrically , and apo-B and apo-A-I immunoturbidometrically . The pattern of food consumption , socio-economic , and anthropometric indices were determined ; there was no significant change in these indices during the study . RESULTS There was a significant difference in the blood VitC level at the end of the study in comparison to the initial value in the VitC ( p = 0.001 ) and VitC + n-3FAs ( p = 0.027 ) groups . Similarly , the serum TG level at the end of study was significantly different from the initial value in the n-3FAs group ( p = 0.002 ) and also from the final value in the control group ( p = 0.013 ) . In the VitC group , there was a significant decrease in TC ( p = 0.004 ) , apo-B ( p = 0.005 ) , and MDA ( p = 0.015 ) at the end of study as compared to the respective initial values . There was also a significant increase in blood VitC compared to the control value ( p = 0.018 ) and a significant decrease in MDA compared to the n-3FAs group ( p = 0.034 ) . At the end of study , in the n-3FAs group , there was a significant ( p = 0.04 ) and a marginally significant decrease ( p = 0.05 ) , respectively , in TG/HDL and apo-B levels as compared to the initial values , and the TG/HDL ratio showed a significant decrease as compared to the control group ( p = 0.047 ) . CONCLUSION Simultaneous administration of n-3FAs and VitC had no beneficial effects on the lipid profile of hyperlipidemic patients , but 1 g purified n-3FAs daily for 10 weeks is a beneficial supplement for decreasing TG without any increase in LDL-C , apo-B or MDA . Administration of 500 mg VitC for more than 10 weeks might decrease significantly TC and apo-B in hyperlipidemic patients The effects on lipoprotein and glucose metabolism of addition of n-3 fatty acids were studied in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA ( 3 g n-3 fatty acids ) or placebo ( olive oil ) per day in a r and omized double-blind cross-over study during two consecutive 8-week periods . After MaxEPA treatment , there was a marked increase in long-chain polyunsaturated fatty acids of the n-3 series in the plasma lipid esters and in the platelet phospholipids , while the n-6 fatty acid content decreased . The very low density lipoprotein ( VLDL ) triglyceride concentrations decreased significantly ( by 22 % ) on MaxEPA treatment . However , these changes were not significantly different from those observed during the placebo period . The blood glucose concentration tended to increase during MaxEPA treatment , and to decrease during the placebo period , the changes under the two regimes being significantly different ( P less than 0.01 ) . In addition , the rate constant for glucose disappearance ( k value ) for the intravenous insulin-tolerance test , which reflected the peripheral insulin sensitivity , tended to decrease during MaxEPA treatment and increase during administration of the placebo , there being a significant difference ( P less than 0.03 ) between the changes during the two treatments . The reason for the observed changes in blood glucose concentration and peripheral insulin sensitivity is still unclear The effects of fish oil on lipoprotein subfractions and low density lipoprotein ( LDL ) size in non-insulin-dependent diabetes mellitus ( NIDDM ) patients with hypertriglyceridemia are unknown . To eluci date this , 16 NIDDM hypertriglyceridemic patients ( plasma triglyceride 2.25- 5.65 mmol/l , plasma cholesterol < or = 7.75 mmol/l ) were r and omly assigned to a 6-month period with either moderate amounts of fish oil ( n = 8) or placebo ( n = 8) after 4 weeks of wash-out and 3 weeks of run-in . Diet and hypoglycemic treatment were unchanged throughout the experiment . LDL size were evaluated at baseline and after 6 months . Three VLDL and LDL subfractions were measured at the end of the two periods . The total lipid concentration of all very low density lipoprotein ( VLDL ) subfractions was lower at the end of fish oil treatment compared with placebo ( large VLDL 124.3 + /- 19.7 mg/dl vs 156.7 + /- 45.5 mg/dl ; intermediate VLDL 88.5 + /- 9.5 mg/dl vs 113.9 + /- 23.2 mg/dl ; small VLDL 105.9 + /- 9.7 mg/dl vs 128.9 + /- 40.7 mg/dl ) ( mean + /- SEM ) , although the difference was not statistically significant . Moreover , at the end of the two treatments , the percentage distribution of VLDL subfractions was very similar ( large 37.5 + /- 3.3 % vs 37.6 + /- 2.6 % , intermediate 27.6 + /- 0.9 % vs 31.0 + /- 2.4 % ; small 34.9 + /- 3.7 % vs 31.4 + /- 2.1 % ) . Concerning LDL , no significant change in LDL size was observed after the two treatments ( 255.4 + /- 2.2 A vs 254.2 + /- 1.7 A , fish oil ; 253.7 + /- 2.0 A vs 253.3 + /- 1.7 A , placebo ) . LDL subfraction distribution was also very similar ( large 17 + /- 3 % vs 17 + /- 2 % ; intermediate 62 + /- 3 % vs 65 + /- 3 % ; small 21 + /- 3 % vs 18 + /- 2 % ) , at the end of the two periods , confirming the lack of effects on LDL size . In conclusion , our study indicates that in NIDDM patients with hypertriglyceridemia , fish oil does not induce any improvement in LDL distribution and LDL size despite its positive effects on plasma triglycerides OBJECTIVE To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus ( NIDDM ) . RESEARCH DESIGN AND METHODS Forty subjects ( 18 men and 22 women ; aged 53.9 ± 7.0 years ) with NIDDM and hyperlipidemia were r and omly assigned to one of four treatment groups : 9 g of fish oil , 18 g of fish oil , 9 g of corn oil , or 18 g of corn oil daily supplementation for 12 weeks . RESULTS The level of oil supplements ( 9 g compared with 18 g ) did not have a significant effect within each oil group on glycemic control and lipids . Significant differences ( P < 0.05 ) in lipids were found when the 9-g and 18-g groups were combined . In subjects consuming fish oil , plasma very-low-density lipoprotein ( VLDL ) cholesterol ( P = 0.0001 ) , plasma triglyceride ( TG ) ( P = 0.0001 ) , and plasma VLDL TGs ( P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks ) were significantly lowered compared with subjects consuming corn oil . Plasma VLDL cholesterol increased across time in the corn oil group ( P = 0.04 ) . Plasma low-density lipoprotein ( LDL ) cholesterol was temporarily increased ( P = 0.008 ) in the fish oil group at 6 weeks , but the effect was no longer present at 12 weeks . No significant differences between fish oil – or corn oil-supplemented diets were found in total plasma cholesterol , high-density lipoprotein cholesterol , fasting plasma glucose , glycosylated HbA1c , weight , and blood pressure . CONCLUSIONS In this study , fish oil supplementation improved plasma VLDL cholesterol , VLDL TGs , and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM . Furthermore , fish oil supplementation had no significant deleterious effect on glycemic control Lipid peroxidation may be important in the development of cardiovascular disease , a common cause of mortality and morbidity in non-insulin dependent diabetes mellitus ( NIDDM ) . We assessed the degree of lipid peroxidation by measuring plasma malondialdehyde , as thiobarbituric acid reacting substances ( TBARS ) , in 23 non-insulin diabetic patients .  Plasma levels of st and ardised alpha-tocopherol ( vitamin E ) , lipid content of whole plasma and lipoprotein fractions , glycosylated haemoglobin , glycosylated low density lipoprotein ( LDL ) and fasting blood glucose were also measured . 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 of the active treatment periods at 6 and 18 weeks . Treatment with olive oil did not change levels of TBARS , vitamin E or indices of glycaemic control compared with baseline . Total cholesterol and triglyceride ( TG ) content of plasma and lipoprotein fractions were not significantly altered . Treatment with fish oil result ed in elevation of TBARS ( P < 0.001 ) and reduction of vitamin E ( P < 0.01 ) compared with baseline and olive oil treatment . Plasma cholesterol was unchanged . A reduction in plasma TG compared with baseline occurred but failed to reach significance ( P = 0.07 ) . Changes in apo B containing lipoproteins induced by fish oil failed to reach significance . No significant changes were observed in concentration or composition of high density lipoprotein ( HDL ) .  Fish oil treatment showed no change in glycaemic control as assessed by glycosylated haemoglobin and LDL although a rise in fasting blood glucose just failed to reach significance ( P = 0.06 ) . Lipid peroxidation in NIDDM can be exacerbated by dietary fish oil . This potentially adverse reaction may limit the therapeutic use of fish oils in such patients Abstract . The effects of dietary supplementation with n‐3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non‐insulin‐dependent diabetic patients who were given 10 g of MaxEPA ( 3 g n‐3 fatty acids ) or placebo ( olive oil ) per day in a r and omized double‐blind cross‐over study during two consecutive 8‐week periods . The serum triglyceride ( TG ) concentrations decreased by 27 % ( P < 0.01 ) after addition of MaxEPA with a reduction of VLDL TG by 36 % ( P < 0.05 ) while LDL cholesterol increased by 6 % ( P= 0.05 ) . The fasting blood sugar and HbA1c . concentrations increased significantly after addition of MaxEPA but the changes were not significantly different from those during the placebo period . The highest glucose concentrations at fasting and after an i.v . glucose injection were seen after MaxEPA while the serum insulin concentrations were unchanged . The peripheral insulin sensitivity , as measured by a euglycaemic , hyperinsulinaemic clamp technique , did not change during the study . The mean plasminogen inhibitor‐1 ( PAI‐1 ) activity of the patients was elevated compared with healthy controls . In spite of the reduction of the triglyceride concentrations and unchanged insulin levels , there was a significant increase of the activity of PAI‐1 ( + 21 % , P < 0.01 ) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity . In many situations there seems to be a reduction of PAI‐1 when the triglycerides are lowered . In the diabetic patients given n‐3 fatty acids this was not the case OBJECTIVE To assess the effects of low-dose eicosapentaenoic acid-ethyl-ester on diabetes regulation , lipid metabolism , blood rheology , and platelet reactivity . RESEARCH DESIGN AND METHODS In a double-blind , r and omized , placebo-controlled study , 24 NIDDM subjects received 1800 mg of EPA-E , 900 mg of EPA-E , or a placebo ( 1656 mg olive oil ) daily for 8 wk . RESULTS The EPA : arachidonic acid plasma ratio increased over an 8-wk period , then declined after a 4-wk wash-out period in the fish-oil groups in a dosedependent way . Platelet-activating factor-induced platelet aggregation decreased from 75 ± 7 % at wk 0 to 35 ± 21 % at wk 8 in the 900-mg group ( P = 0.016 ) and from 72 ± 11 to 40 ± 30 % in the 1800-mg group ( P = 0.039 ) , but did not change in the placebo group . No effects on A DP- or collagen-induced aggregation could be attributed to EPA-E. In the 1800-mg group low-density-lipoprotein cholesterol increased significantly , without concomitant rise in apolipoprotein B. Triglycerides , glycemic control , lipoprotein ( a ) , blood and plasma viscosity , erythrocyte deformability , and platelet adhesion to and aggregate formation on extracellular endothelial cell matrix were not significantly influenced . CONCLUSIONS Purified EPA-E in doses of 900 and 1800 mg reduces Plateletactivating factor-induced platelet aggregation without negatively affecting glycemic control . Low-density-lipoprotein cholesterol was elevated in the 1800-mg group Effect of dietary fish was investigated in 51 study group patients and 50 age- and sex-matched control group patients , all with type II-b hyperlipoproteinemia . In the study and control group , 21 and 22 patients , respectively , had well regulated non-insulin dependent diabetes mellitus . Neither the study group nor control group patients smoked or consumed alcohol beverages . Blood pressure was within normal limits ( 16/11 - 20/12 kPa ) in both groups . During a six-month study period , the study group took 0.5 - 1 kg breaded pilchard per week , whereas the control group patients were on their st and ard hypolipoproteinemic diet . The following parameters were determined in both study and control group patients before the study , every 3 months during the study , and 3 months after the completion of the study , total cholesterol , HDL cholesterol ( HDL2 and HDL3 ) , LDL cholesterol , VLDL cholesterol , triglycerides , blood glucose and uric acid . Fish intake was found to statistically significantly decrease the levels of total cholesterol ( -10.7 % ) , LDL cholesterol ( -11.7 % ) , VLDL cholesterol ( -14.8 % ) and triglycerides ( -12.3 % ) ( p < 0.05 ) , whereas a statistically significant increase was observed in the levels of HDL cholesterol ( + 5.3 % ) and HDL3 ( + 7.4 % ) ( p < 0.05 ) . Three months after the completion of the study , when the study group patients had resumed their st and ard hypolipoproteinemic diet without extra fish intake , the levels of lipoprotein fractions returned to those recorded before the study . There were no statistically significant changes in the levels of blood glucose , uric acid and HDL2 . In the control group , no statistically significant changes in lipoprotein fractions were recorded . Our findings suggested that dietary intake of 0.5 - 1 kg fish containing a small amount of omega-3 fatty acids , along with the st and ard hypolipoproteinemic diet , may decrease the level of atherogenic lipoprotein fractions , and increase the level of lipoprotein protective fractions , thus reducing or at least delaying the development of atherosclerosis OBJECTIVE The aim of this study was to evaluate the long-term ( 6-month ) effects of moderate fish oil supplementation on insulin sensitivity and plasma lipoproteins in NIDDM patients with hypertriglyceridemia . RESEARCH DESIGN AND METHODS The study has been performed according to a r and omized double-blind placebo-controlled design with a parallel group sequence . After a washout period of 4 weeks and a run-in period of 3 weeks , 16 NIDDM patients with hypertriglyceridemia ( triglyceride [ TG ] , 2.25–5.65 mmol/l ) were r and omly assigned to either fish oil ( 2.7 g/day eicosapentaenoic plus docosahexaenoic acid for 2 months , then 1.7 g/day for 4 more months ) ( n = 8) or placebo ( n = 8) .  Diet and hypoglycemic drugs remained unchanged throughout the whole experiment . At baseline and after 6 months , insulin sensitivity was measured by euglycemic hyperinsulinemic clamp ( insulin infused , 2.0 mIU · kg−1 body wt · min−1 ) . At the same time , blood glucose control , fasting and postpr and ial serum insulin and nonesterified fatty acid ( NEFA ) concentrations , and fasting plasma lipoprotein concentrations were evaluated . RESULTS In the group treated with ffish oil compared with the baseline , there was : 1 ) a significant reduction in both plasma TG ( 2.92 ± 0.23 vs. 3.85 ± 0.32 [ mean ± SE ] mmol/l , P < 0.001 ) and VLDL-TG ( 2.35 ± 0.24 vs. 4.25 ± 0.66 mmol/l , P < 0.01 ) , without significant changes in blood glucose control ; 2 ) a significant reduction in fasting NEFA concentrations ( 572 ± 100 vs. 825 ± 131 μmol/l , P < 0.01 ) ; and 3 ) a significant enrichment in long-chain ω-3 fatty acids of erythrocyte membrane phospholipids . In the placebo group , there were no changes in any of the variables analyzed . The insulin-mediated glucose uptake was unchanged in both groups ( fish oil , 4.04 ± 0.82 mg · kg−1 · min−1 at baseline and 3.96 ± 0.50 mg · kg−1 · min−1 at 6 months ; placebo , 3.51 ± 0.62 mg · kg−1 · min−1 at baseline and 4.09 ± 0.49 mg · kg−1 · min−1 at 6 months ) . CONCLUSIONS In NIDDM patients with hypertriglyceridemia , moderate amounts of fish oil induce a long-term significant reduction in plasma triglycerides , VLDL triglycerides , and NEFA and a significant enrichment in the erythrocyte phospholipid content of long-chain ω-3 fatty acids , without deteriorating blood glucose control . However , this amount of ω-3 fatty acids was unable to improve insulin sensitivity in this group of patients 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 n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms . Despite this , there has been concern that these fatty acids may increase lipid peroxidation . The data in vivo are inconclusive , due in part to limitations in the method ologies . In this regard , the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress . This study aim ed to assess the effects of supplementation with purified eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) , the two major n-3 fatty acids , on urinary F2-isoprostanes and markers of inflammation , in type 2 diabetic patients . In a double-blind , placebo controlled trial of parallel design , 59 nonsmoking , treated-hypertensive , type 2 diabetic subjects , were r and omized to 4 g daily of purified EPA , DHA , or olive oil for 6 weeks , while maintaining their usual diet . F2-isoprostanes , measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-alpha ) , were measured before and after intervention . Thirty-nine men and 12 women aged 61.2 + /- 1.2 years , with body mass index ( BMI ) , 29.5 + /- 0.5 kg/m2 ; 24 h blood pressure , 138/73 mmHg ; HbA1c , 7.3 + /- 0.1 % and fasting glucose , 7.9 + /- 0.2 mmol/l completed the intervention .  Baseline urinary F2-isoprostanes were positively associated with HbA1c ( p=.011 ) and fasting glucose ( p=.032 ) . Relative to the olive oil group , postintervention urinary F2-isoprostanes were decreased 19 % by EPA ( p=.017 ) and 20 % by DHA ( p=.014 ) . There were no significant changes in CRP , IL-6 , and TNF-alpha following EPA or DHA supplementation . In regression analysis , Delta F2-isoprostanes were positively associated with Delta HbA1c ( p=.007 ) independent of treatment group ; and with Delta TNF-alpha ( p=.034 ) independent of age , gender , BMI , and treatment group . There were no associations with Delta CRP or Delta IL-6 . This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation , in treated hypertensive , type 2 diabetic subjects 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 BACKGROUND Low-density lipoprotein (LDL)-based guidelines are currently used to initiate and monitor cholesterol-lowering therapy . METHODS Using stratified analyses , data from the Framingham Heart Study and the Coronary Primary Prevention Trial were evaluated to determine whether ( 1 ) cholesterol levels  ( total cholesterol [ TC ] or LDL [ low-density lipoprotein ] ) better discriminated risk for coronary heart disease ( CHD ) than cholesterol ratios ( LDL/HDL [ high-density lipoprotein ] or TC/HDL ) ; and ( 2 ) whether changes in ratios better predicted risk reduction than changes in levels . RESULTS Individuals with similar LDL/HDL ratios had similar risks for CHD regardless of whether they had high LDL levels or low LDL levels ( 23 % vs 23 % for the CPPT , 13.8 % vs 14 % for FHS men , and 8.6 % vs 10.9 % for FHS women ) . Among men with similar initial LDL/HDL ratios  and similar changes in LDL/HDL ratios , risks for CHD did not differ ( 20.3 % compared with 21.0 % ; p = 0.96 ) between those with the largest and smallest reductions in LDL levels ( 21.3 % compared with 6.5 % ) . Among men with similar initial LDL levels  and similar LDL reductions  , a 20 % reduction in risk for CHD was seen ( 19.5 % compared with 24.5 % ; p = 0.005 ) between those with the largest and smallest reductions in LDL/HDL ratios ( 23 % compared with 4.6 % ) . TC/HDL had predictive ability similar to LDL/HDL . CONCLUSIONS Cholesterol levels do not provide incremental predictive value over cholesterol ratios in identifying people at risk for CHD . Changes in ratios are better predictors of successful CHD risk reduction than changes in levels . Future guidelines should consider incorporating ratios in initiating and monitoring successful lipid-lowering therapy
Aims /hypothesisTo determine the effects of marine-derived n-3 polyunsaturated fatty acids ( PUFA ) on established and emerging lipid and lipoprotein cardiovascular risk markers in patients with type 2 diabetes .