Effect of diet or very long chain omega-3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima-media thickness and by pulse wave propagation in elderly men with hypercholesterolaemia. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Effect of omega 3 fatty acid on plasma lipids, cholesterol and lipoprotein fatty acid content in NIDDM patients. [Effects of diet therapy including eiconol on clinical and metabolic parameters in patients with type 2 diabetes mellitus]. Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus. A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients. A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes. Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study. A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM. Omega-3 polyunsaturated fatty acid in peripheral arterial disease: effect on lipid pattern, disease severity, inflammation profile, and endothelial function. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM. Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients. Effect of dietary fish oil supplementation on peroxidation of serum lipids in patients with non-insulin dependent diabetes mellitus. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study. EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Biological effects of a dietary omega-3 polyunsaturated fatty acids supplementation in cystic fibrosis patients: a randomized, crossover placebo-controlled trial. Fish oil supplementation in patients with heterozygous familial hypercholesterolemia.
This randomized study targeted a comparison of the effect of 3-year diet counselling or omega-3 polyunsaturated fatty acid (PUFA) supplementation (2.4 g/day) on the progression of atherosclerosis in carotid arteries and on finger pulse wave propagation.
                Measurements were assessed by high-resolution B-mode ultrasound and a photopletysmographic finger pulse-sensor, respectively. Altogether, 563 elderly men with long-standing hyperlipidaemia were randomized into four groups: controls (no dietary counselling and placebo); dietary counselling (and placebo); omega-3 PUFA supplementation (no dietary counselling); dietary counselling and omega-3 PUFA supplementation.
                In the diet only group, the carotid intima-media thickness increase (0.929 to 0.967 mm) was significantly less than in the control group (0.909 to 0.977 mm), (P = 0.018). Significant increase in carotid plaques score and plaques area were observed in all four groups, but without between group differences. Changes in carotid intima-media thickness and in high-density lipoprotein-cholesterol were negatively correlated (adjusted P < 0.001). Pulse wave propagation time decreased significantly in the control group (206 to 198 ms; P = 0.002), reflecting reduced arterial elasticity. In the group receiving omega-3 PUFA only, pulse wave propagation time increased significantly when compared with the control group (P = 0.013).
                Reduced progression in carotid intima-media thickness was observed after dietary counselling, whereas omega-3 PUFA supplementation imposed a favourable effect on arterial elasticity. 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 resulted 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. High-density 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.(ABSTRACT TRUNCATED AT 250 WORDS) This study was conducted to examine the effect of omega 3 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 omega 3 supplement periods in a randomized crossover. In these 3-month periods, participants were given a linseed oil supplement equivalent to 35 mg of 18:3 omega 3.kg body weight-1.day-1 or a fish oil supplement equivalent to 35 mg of 20:5 omega 3 + 22:6 omega 3.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 20:5 omega 3 and 22:6 omega 3 content of all lipoprotein lipid classes. Linolenic acid supplementation had no effect on plasma triacylglycerol level, but it increased 18:3 omega 3 content of lipoprotein cholesterol ester fractions (p < 0.05). A slight increase in 20:5 omega 3, but not 22:6 omega 3, content was noted in lipoprotein lipid classes as a result of 18:3 omega 3 supplementation. LDL and HDL cholesterol, insulin, glucagon and C-peptide levels were not affected by either omega 3 supplement. It is concluded that a modest intake of omega 3 fatty acids, such as could be obtained from consuming fish regularly, will reduce plasma triglyceride level without affecting LDL or HDL cholesterol levels. It was investigated the influence of a diet supplemented with PUFA omega-3 ("Eiconol") on dynamic of basal and postprandial glycemia, blood pressure, lipid levels, parameters of lipid peroxidation in 60 patients with non-insulin-dependent diabetes mellitus. Fish oil ("Eiconol") was used as a dietary supplement of PUFA omega-3. The results of investigations indicated that a diet supplemented with "Eiconol" (8 g/day) increased the effect of dietary therapy in correction of essential hypertension and atherogenic lipids. It was not the worsening of the glycemia and activation of lipid peroxidation. 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 randomized 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. Eight male non-insulin-dependent diabetic patients participated in a double-blind randomized cross-over study (2 weeks for each period) evaluating the effects of 10 g/day fish oil dietary supplementation on glucose and lipid metabolism. Fasting serum triglyceride concentrations were decreased by fish oil because of a reduction in VLDL (1.4 +/- 0.2 vs. 1.9 +/- 0.2 mmol/l, P less than 0.025). LDL cholesterol concentration was instead increased (3.4 +/- 0.3 vs. 2.8 +/- 0.3 mmol/l, P less than 0.025) and net changes in VLDL triglyceride and in LDL cholesterol were inversely correlated (r = -0.86, P less than 0.01). Plasma free fatty acids concentrations and turnover rate [( 3H]palmitate method) were similar after fish oil and placebo. Fish oil supplement did not induce significant changes in fasting blood glucose (8.1 +/- 1.1 vs. 8.5 +/- 1.2 mmol/l) and average daily blood glucose (BG) (9.4 +/- 3.2 vs. 9.3 +/- 3.5 mmol/l). Glucose stimulated plasma insulin response during a hyperglycemic clamp was not significantly influenced by fish oil both in the early phase and during steady state. Insulin sensitivity (M/I index) was also unchanged. In conclusion, this study shows that a dietary supplement of fish oil decreases plasma triglyceride levels in non-insulin-dependent diabetic patients, an increased conversion rate of VLDL to LDL playing a role in this change. With this dosage of fish oil no relevant variations in glycemic control, insulin secretion and insulin sensitivity occurred. 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.
                Eleven subjects with type II diabetes were given supplements with LO and FO for 3 months each in a randomized 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.
                HbA1c and lipid values were within the normal range at randomization. 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.
                In a population with well-controlled type II diabetes, 3 months of FO but not LO resulted 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. Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid (PUFA) on patients with attention-deficit hyperactivity disorder (ADHD), changes in plasma PUFA composition were not always assessed following n-3 supplementation. Furthermore, no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD.
                To determine fatty acid (FA) composition, and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children.
                The Strengths and Weaknesses in ADHD and Normal Behaviors (SWAN) and Conners' questionnaires were used to assess changes in ADHD symptoms in 37 children (only 26 children completed the study from zero to 16 weeks). They were divided into two groups (A and B), and participated in a 16-week, double-blind, one-way, crossover randomized study. In the first phase, group A received the n-3 PUFA supplement and group B received n-6 PUFA (sunflower oil) as a placebo. During the second phase, group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study.
                FA differences between groups were observed in the 26 patients. Supplementation with n-3 PUFA resulted in significant increases in eicosapentaenoic and docosahexaenoic acids in group A, while group B was enriched with alpha-linolenic, gamma-linolenic and homo-gamma-linolenic acids. The n-3 PUFA supplement was tolerated without any adverse effects. A statistically significant improvement in symptoms was noted based on the parent version of the Conners' questionnaire from baseline to the end of phase 1, and this amelioration continued from phases 1 to 2, although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group A in phase 1 and in patients from group B in phase 2. A subgroup of eight patients (four in each group) displayed a statistically significant clinical improvement following the administration of the n-3 PUFA supplement, particularly for the inattention and global Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, total Conners' subscales.
                A subgroup of children with ADHD who used n-3 PUFA supplements achieved and maintained symptom control. The data of the present study also supported n-3 PUFA safety and tolerability, but limited changes were noted in the FA profile in French Canadians with ADHD. 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).
                Forty subjects (18 men and 22 women; aged 53.9 +/- 7.0 years) with NIDDM and hyperlipidemia were randomly 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.
                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.
                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. Peripheral arterial disease (PAD) is strongly associated with endothelial dysfunction and inflammation, which portend a high cardiovascular risk. Accordingly, we investigated the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on endothelial function and inflammatory status in affected individuals.
                PAD patients were randomly divided into two groups. In Group I (n=16) pre-enrollment therapy was not modified, while in Group II (n=16) n-3 PUFAs 1 g b.i.d. for 3 months were added to the previous treatment. Endothelial function was assessed by measuring plasma soluble thrombomodulin (sTM) and brachial artery flow-mediated dilation (FMD), and the inflammatory status by measuring high-sensitivity C-reactive protein and myeloperoxidase.
                In Group II, n-3 PUFAs reduced sTM levels from the median value of 33.0 ng/mL (interquartile range 16.7, 37.2) to 17.0 ng/mL (11.2, 33.7) (p=0.04), and improved FMD from 6.7% (3.7, 8.7) to 10.0% (6.2, 14.2) (p=0.02). Conversely, these markers did not change in Group I. After 3 months, the levels of inflammatory markers remained unmodified in both groups.
                In PAD, n-3 PUFAs induced a marked improvement in endothelial function. Conversely, they did not affect the inflammatory status. In future, large, prospective studies are needed to investigate whether n-3 PUFAs, by improving endothelial function, would reduce the incidence of ischemic events in a population at high risk. 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.
                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.
                In a double-blind, placebo-controlled trial of parallel design, 59 subjects were randomly assigned to consume 4 g EPA, DHA, or olive oil/d for 6 wk while continuing to consume their usual diet.
                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.
                EPA and DHA had similar benefits on lipids but adverse effects on short-term glycemic control in hypertensive diabetic patients. The overall implications for cardiovascular disease require long-term evaluation. The aim of the present study was to see whether a moderate dose of omega-3 fatty acids (FA) potentiates the beneficial effects of statins on the high risk for coronary heart disease (CHD) in patients with combined hyperlipemia.
                In the present double-blind parallel study, 42 patients with combined hyperlipemia with serum triglycerides 2-15 mmol/L-1 and serum total cholesterol > 5.3 mmol/L-1 at the end of a three-month dietary run-in period were treated with 10 mg/d atorvastatin for 10 or more weeks. During the last 5 weeks they were randomized into two groups that received either 1.68 g/d omega-3 FA as ethylesters of eicosapentaenoic (45%) and docosahexaenoic acids (39%), or placebo (corn oil). As expected, atorvastatin significantly reduced serum total LDL-cholesterol (LDL-C), triglycerides and apolipoproteins B, E, CII and CIII, whereas HDL-cholesterol (HDL-C) was increased. Addition of omega-3 FA further increased HDL-C (p < 0.03), and reduced systolic blood pressure (< 0.03), while the small dense LDL-particles (LDL III) (p < 0.05) and postprandial hypertriglyceridemia (p < 0.01) were reduced compared with the baseline, though there were no significant differences to the placebo group. This may be related to the large individual variation in these parameters and the small number of patients. No significant effects on basic or postheparin activities of lipoprotein lipase or hepatic lipase were observed after atorvastatin with or without addition of omega-3 FA.
                This study indicates that addition of a low dose of omega-3 FA may further improve the risk profile for CHD in patients with combined hyperlipemia treated with atorvastatin. The effect is related to reduction of postprandial hyperlipemia and redistribution of LDL subfractions. Fish oils, containing omega-3 fatty acids (omega 3FAs), favorably influence plasma lipoproteins in nondiabetic humans and prevent the development of insulin resistance induced by fat feeding in rats. We studied the effects of fish oils in 10 subjects (aged 42-65 yr) with mild non-insulin-dependent diabetes mellitus (NIDDM). Subjects were fed a standard diabetic diet plus 1) no supplementation (baseline), 2) 10 g fish oil concentrate (30% omega 3FAs) daily, and 3) 10 g safflower oil daily over separate 3-wk periods, the latter two supplements being given in radom order by use of a double-blind crossover design. At the end of each diet period, fasting blood glucose (FBG), insulin, and lipids were measured, and insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp performed with [3-3H]glucose. FBG increased 14% during fish oil and 11% during safflower oil supplementation compared with baseline (P less than .05), whereas body weight, fasting serum insulin levels, and insulin sensitivity were unchanged. The absolute increase in FBG during each supplementation period correlated with the baseline FBG (fish oil, r = .83, P less than .005); safflower oil, r = .75, P = .012). Fasting plasma triglyceride levels decreased during fish oil supplementation in the 4 subjects with baseline hypertriglyceridemia (greater than 2 mM) but were not significantly reduced overall. There was no significant change in fasting plasma total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. In summary, dietary fish oil supplementation adversely affected glycemic control in NIDDM subjects without producing significant beneficial effects on plasma lipids. The effect of safflower oil supplementation was not significantly different from fish oil, suggesting that the negative effects on glucose metabolism may be related to the extra energy or fat intake.(ABSTRACT TRUNCATED AT 250 WORDS) 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.
                A total of 42 type 2 diabetic patients were randomized 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.
                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.
                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. 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 standardised 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 randomly 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 resulted 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. There is conflicting evidence on the benefits of foods rich in vitamin E (alpha-tocopherol), n-3 polyunsaturated fatty acids (PUFA), and their pharmacological substitutes. We investigated the effects of these substances as supplements in patients who had myocardial infarction.
                From October, 1993, to September, 1995, 11,324 patients surviving recent (< or = 3 months) myocardial infarction were randomly assigned supplements of n-3 PUFA (1 g daily, n=2836), vitamin E (300 mg daily, n=2830), both (n=2830), or none (control, n=2828) for 3.5 years. The primary combined efficacy endpoint was death, non-fatal myocardial infarction, and stroke. Intention-to-treat analyses were done according to a factorial design (two-way) and by treatment group (four-way).
                Treatment with n-3 PUFA, but not vitamin E, significantly lowered the risk of the primary endpoint (relative-risk decrease 10% [95% CI 1-18] by two-way analysis, 15% [2-26] by four-way analysis). Benefit was attributable to a decrease in the risk of death (14% [3-24] two-way, 20% [6-33] four-way) and cardiovascular death (17% [3-29] two-way, 30% [13-44] four-way). The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint (14% [1-26]) and for fatal events (20% [5-33]).
                Dietary supplementation with n-3 PUFA led to a clinically important and statistically significant benefit. Vitamin E had no benefit. Its effects on fatal cardiovascular events require further exploration. To study the effects of a low dose of omega-3 fatty acids on platelet function and other cardiovascular risk factors in patients with non-insulin-dependent diabetes mellitus (NIDDM).
                We performed a randomized, prospective, double-blind, controlled study of a low dose of omega-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 omega-3 fatty acids or five 1-g safflower oil capsules per day for 6 weeks followed by a 6-week washout period.
                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 omega-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 collagen-induced 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.
                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 omega-3 fatty acids or dietary fish are safe and potentially beneficial in NIDDM patients. This pilot study evaluated the effects of supplementation with PUFA on blood FA composition and behavior in children with Attention-Deficit/Hyperactivity Disorder (AD/HD)-like symptoms also reporting thirst and skin problems. Fifty children were randomized to treatment groups receiving either a PUFA supplement providing a daily dose of 480 mg DHA, 80 mg EPA, 40 mg arachidonic acid (AA), 96 mg GLA, and 24 mg alpha-tocopheryl acetate, or an olive oil placebo for 4 mon of double-blind parallel treatment. Supplementation with the PUFA led to a substantial increase in the proportions of EPA, DHA, and alpha-tocopherol in the plasma phospholipids and red blood cell (RBC) total lipids, but an increase was noted in the plasma phospholipid proportions of 18:3n-3 with olive oil as well. Significant improvements in multiple outcomes (as rated by parents) were noted in both groups, but a clear benefit from PUFA supplementation for all behaviors characteristic of AD/HD was not observed. For most outcomes, improvement of the PUFA group was consistently nominally better than that of the olive oil group; but the treatment difference was significant, by secondary intent-to-treat analysis, on only 2 out of 16 outcome measures: conduct problems rated by parents (-42.7 vs. -9.9%, n = 47, P = 0.05), and attention symptoms rated by teachers (-14.8 vs. +3.4%, n = 47, P = 0.03). PUFA supplementation led to a greater number of participants showing improvement in oppositional defiant behavior from a clinical to a nonclinical range compared with olive oil supplementation (8 out of 12 vs. 3 out of 11, n = 33, P = 0.02). Also, significant correlations were observed when comparing the magnitude of change between increasing proportions of EPA in the RBC and decreasing disruptive behavior as assessed by the Abbreviated Symptom Questionnaire (ASQ) for parents (r = -0.38, n = 31, P < 0.05), and for EPA and DHA in the RBC and the teachers' Disruptive Behavior Disorders (DBD) Rating Scale for Attention (r = -0.49, n = 24, P < 0.05). Interestingly, significant correlations were observed between the magnitude of increase in alpha-tocopherol concentrations in the RBC and a decrease in scores for all four subscales of the teachers' DBD (Hyperactivity, r = -0.45; Attention, r= -0.60; Conduct, r = -0.41; Oppositional/Defiant Disorder, r = -0.54; n = 24, P < 0.05) as well as the ASQ for teachers (r = -0.51, n = 24, P < 0.05). Thus, the results of this pilot study suggest the need for further research with both n-3 FA and vitamin E in children with behavioral disorders. 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. Various anti-inflammatory therapies, including dietary omega-3 polyunsaturated fatty acids (PUFA) supplementation, have been investigated in cystic fibrosis (CF) patients. To further explore this nutritional approach, biological effects of an omega-3 PUFA oral liquid supplementation were measured in 17 CF patients in a double-blind, randomized, crossover without a washout period and placebo-controlled study.
                CF patients (age: 18+/-9 year; weight: 43+/-13 kg) received a liquid dietary supplementation either enriched or not in omega-3 PUFA (390-1170 mg/day according to patient weight) during two 6-month periods.
                Increase in eicosapentaenoic acid was observed in neutrophil membrane following omega-3 PUFA dietary supplementation (from 0.7+/-0.6 to 1.6+/-0.6 micromol%, P<0.01). The leukotriene B(4) (LTB(4))/leukotriene B(5) (LTB(5)) ratio was decreased (from 72+/-27 to 24+/-7, P<0.001) in CF patients taking omega-3 PUFA supplements. In contrast, omega-3 PUFA supplementation affected neither internalization of IL-8 receptors following IL-8 exposure, nor IL-8-induced neutrophil chemotaxis.
                Our results show that omega-3 PUFA are incorporated in neutrophil membranes. The subsequent decrease in LTB(4)/LTB(5) ratio suggests that, in such conditions, neutrophils may produce less pro-inflammatory mediators from the acid arachidonic pathway. These data indicate that omega-3 PUFA intake may have anti-inflammatory effect that still need to be assessed by long-term studies following large groups of patients. Familial hypercholesterolemia is associated with premature coronary heart disease. In patients with familial hypercholesterolemia, monotherapy with hydroxymethylglutaril coenzyme. A reductase inhibitors rarely achieves the goal of desirable low-density lipoprotein levels. Epidemiological studies suggest that populations with a high dietary intake of marine n3 fatty acids are protected against coronary heart disease. Hepatic synthesis and secretion of very low density lipoproteins are reduced during fish oil supplementation while other effects on lipid and lipoprotein metabolism are controversial. Fourteen patients affected by familial heterozygous hypercholesterolemia on chronic treatment with simvastatin were enrolled in a double blind, placebo controlled, randomized crossover trial that evaluated the effect of fish oil ethyl ester (Esapent, 5.1 g/day) on lipid and lipoprotein serum concentrations. Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apoprotein B, apoprotein AI, lipoprotein (a) did not show any significant variation during the four week treatment period with fish oil ethyl ester. The present data suggest that the possible favourable influence of fish oil on the progression of atherosclerosis in these high-risk patients might involve mechanisms which are different from lipid metabolism.
Omega-3 PUFA supplementation in type 2 diabetes lowers triglycerides and VLDL cholesterol, but may raise LDL cholesterol (although results were non-significant in subgroups) and has no statistically significant effect on glycemic control or fasting insulin. Trials with vascular events or mortality defined endpoints are needed.