The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Effect of omega 3 fatty acid on plasma lipids, cholesterol and lipoprotein fatty acid content in NIDDM patients. 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. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Effects of a small quantity of omega-3 fatty acids on cardiovascular risk factors in NIDDM. A randomized, prospective, double-blind, controlled study. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma in children. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Dietary fat intake and risk of lung cancer: a prospective study of 51,452 Norwegian men and women. Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Effect of dietary fish oil supplementation on peroxidation of serum lipids in patients with non-insulin dependent diabetes mellitus. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. Association of dietary intake of fat and fatty acids with risk of breast cancer. A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM. Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study. A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians. Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM. Do fish oils prevent restenosis after coronary angioplasty? A prospective study of dietary fat and risk of prostate cancer. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Fish oil supplementation in patients with heterozygous familial hypercholesterolemia. Fish consumption and cardiovascular disease in the physicians' health study: a prospective study. Can supplementation of diet with omega-3 polyunsaturated fatty acids reduce coronary angioplasty restenosis rate? Intake of fish and omega-3 fatty acids and risk of stroke in women. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Comparison of low-fat versus Mediterranean-style dietary intervention after first myocardial infarction (from The Heart Institute of Spokane Diet Intervention and Evaluation Trial). Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study. n-3 Fatty acids and 5-y risks of death and cardiovascular disease events in patients with coronary artery disease. Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects. Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival--4. Fish consumption and coronary heart disease mortality in Finland, Italy, and The Netherlands. Cod liver oil consumption, smoking, and coronary heart disease mortality: three counties, Norway. Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Double-blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary angioplasty. Lack of benefit of dietary advice to men with angina: results of a controlled trial. The effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group. Dietary fat in relation to risk of multiple sclerosis among two large cohorts of women. Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk of prostate cancer. Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Effect of dietary omega-3 fatty acids on retinal function of very-low-birth-weight neonates. Feasibility of a randomized trial of a low-fat diet for the prevention of breast cancer: dietary compliance in the Women's Health Trial Vanguard Study. Effects of n-3 fatty acids on cognitive decline: a randomized, double-blind, placebo-controlled trial in stable myocardial infarction patients. Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes. The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum disorder. A long-term study on the effect of spontaneous consumption of reduced fat products as part of a normal diet on indicators of health. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Usefulness of fish oil supplements in preventing clinical evidence of restenosis after percutaneous transluminal coronary angioplasty. Prospective study of plasma fatty acids and risk of prostate cancer. One-year results from a brief, computer-assisted intervention to decrease consumption of fat and increase consumption of fruits and vegetables. Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients. Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study. Omega-3 fatty acid supplementation in patients with recurrent self-harm. Single-centre double-blind randomised controlled trial. 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 low-dose omega-3 fatty acid substitution in type-2 diabetes mellitus with special reference to oxidative stress--a prospective preliminary study. Prevention of postcoronary angioplasty restenosis by omega-3 fatty acids: main results of the Esapent for Prevention of Restenosis ITalian Study (ESPRIT). Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Effects on health of dietary supplementation with 100 mg d-alpha-tocopheryl acetate, daily for 6 years. A long-term seal- and cod-liver-oil supplementation in hypercholesterolemic subjects. Plasma lipid levels and platelet and neutrophil function in patients with vascular disease following fish oil and olive oil supplementation. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Long-term comparison of three dietary prescriptions in the treatment of NIDDM. Fish oil supplementation in patients with stable claudication. Omega-3/omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents. Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients. Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids. A randomised controlled trial of the effect of low fat diet advice on dietary response in insulin independent diabetic women. Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy. Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS) Is antioxidant and n-3 supplementation able to improve functional status in poststroke patients? Results from the Nutristroke Trial. A 9-mo randomized clinical trial comparing fat-substituted and fat-reduced diets in healthy obese men: the Ole Study. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. A randomised double blind placebo controlled trial of fish oil in high risk pregnancy. Effects of fish oil supplements in NIDDM subjects. Controlled study.
Epidemiologic studies, studies of mechanisms of action, and many animal studies indicate that dietary intake of omega-3 fatty acids has antiatherosclerotic potential. Few trials in humans have examined this potential.
                To determine the effect of dietary intake of omega-3 fatty acids on the course of coronary artery atherosclerosis in humans.
                Randomized, double-blind, placebo-controlled, clinically controlled trial.
                University preventive cardiology unit.
                223 patients with angiographically proven coronary artery disease.
                Fish oil concentrate (55% eicosapentaenoic and docosahexaenoic acids) or a placebo with a fatty acid composition resembling that of the average European diet, 6 g/d for 3 months and then 3 g/d for 21 months.
                The results of standardized coronary angiography, done before and after 2 years of treatment, were evaluated by an expert panel (primary end point) and by quantitative coronary angiography. Patients were followed for clinical and laboratory status.
                Pairs of angiograms (one taken at baseline and one taken at 2 years) were evaluated for 80 of 112 placebo recipients and 82 of 111 fish oil recipients. At the end of treatment, 48 coronary segments in the placebo group showed changes (36 showed mild progression, 5 showed moderate progression, and 7 showed mild regression) and 55 coronary segments in the fish oil group showed changes (35 showed mild progression, 4 showed moderate progression, 14 showed mild regression, and 2 showed moderate regression) (P = 0.041). Loss in minimal luminal diameter, as assessed by quantitative coronary angiography, was somewhat less in the fish oil group (P > 0.1). Fish oil recipients had fewer cardiovascular events (P = 0.10); other clinical variables did not differ between the study groups. Low-density lipoprotein cholesterol levels tended to be greater in the fish oil group.
                Dietary intake of omega-3 fatty acids modestly mitigates the course of coronary atherosclerosis in humans. The aim of the current prospective, randomized control study was to investigate the effect of dietary omega-3 polyunsaturated fatty acids plus vitamin E on the immune status and survival of well-nourished and malnourished patients with generalized malignancy.
                Sixty patients with generalized solid tumors were randomized to receive dietary supplementation with either fish oil (18 g of omega-3 polyunsaturated fatty acids, PUFA) or placebo daily until death. Each group included 15 well-nourished and 15 malnourished patients. The authors measured total T cells, T-helper cells, T-suppressor cells, natural killer cells, and the synthesis of interleukin-1, interleukin-6, and tumor necrosis factor by peripheral blood mononuclear cells before and on Day 40 of fish oil supplementation. Karnofsky performance status, nutritional state, and survival were also estimated.
                The ratio of T-helper cells to T-suppressor cells was significantly lower in malnourished patients. Omega-3 PUFA had a considerable immunomodulating effect by increasing this ratio in the subgroup of malnourished patients. There were no significant differences in cytokine production among the various groups, except for a decrease in tumor necrosis factor production in malnourished cancer patients, which was restored by omega-3 fatty acids. The mean survival was significantly higher for the subgroup of well-nourished patients in both groups, whereas omega-3 fatty acids prolonged the survival of all the patients.
                Malnutrition appears to be an important predictor of survival for patients with end stage malignant disease. Omega-3 polyunsaturated fatty acids had a significant immunomodulating effect and seemed to prolong the survival of malnourished patients with generalized malignancy. 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. 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. The relation of intakes of specific fatty acids and the risk of coronary heart disease was examined in a cohort of 21,930 smoking men aged 50-69 years who were initially free of diagnosed cardiovascular disease. All men participated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and completed a detailed and validated dietary questionnaire at baseline. After 6.1 years of follow-up from 1985-1988, the authors documented 1,399 major coronary events and 635 coronary deaths. After controlling for age, supplement group, several coronary risk factors, total energy, and fiber intake, the authors observed a significant positive association between the intake of trans-fatty acids and the risk of coronary death. For men in the top quintile of trans-fatty acid intake (median = 6.2 g/day), the multivariate relative risk of coronary death was 1.39 (95% confidence interval (CI) 1.09-1.78) (p for trend = 0.004) as compared with men in the lowest quintile of intake (median = 1.3 g/day). The intake of omega-3 fatty acids from fish was also directly related to the risk of coronary death in the multivariate model adjusting also for trans-saturated and cis-monounsaturated fatty acids (relative risk (RR) = 1.30, 95% CI 1.01-1.67) (p for trend = 0.06 for men in the highest quintile of intake compared with the lowest). There was no association between intakes of saturated or cis-monounsaturated fatty acids, linoleic or linolenic acid, or dietary cholesterol and the risk of coronary deaths. All the associations were similar but somewhat weaker for all major coronary events. 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. Higher consumption of fish and omega-3 fatty acids has been associated with a lower risk of coronary heart disease (CHD) in men, but limited data are available regarding women.
                To examine the association between fish and long-chain omega-3 fatty acid consumption and risk of CHD in women.
                Dietary consumption and follow-up data from 84 688 female nurses enrolled in the Nurses' Health Study, aged 34 to 59 years and free from cardiovascular disease and cancer at baseline in 1980, were compared from validated questionnaires completed in 1980, 1984, 1986, 1990, and 1994.
                Incident nonfatal myocardial infarction and CHD deaths.
                During 16 years of follow-up, there were 1513 incident cases of CHD (484 CHD deaths and 1029 nonfatal myocardial infarctions). Compared with women who rarely ate fish (<1 per month), those with a higher intake of fish had a lower risk of CHD. After adjustment for age, smoking, and other cardiovascular risk factors, the multivariable relative risks (RRs) of CHD were 0.79 (95% confidence interval [CI], 0.64-0.97) for fish consumption 1 to 3 times per month, 0.71 (95% CI, 0.58-0.87) for once per week, 0.69 (95% CI, 0.55-0.88) for 2 to 4 times per week, and 0.66 (95% CI, 0.50-0.89) for 5 or more times per week (P for trend =.001). Similarly, women with a higher intake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, 0.93, 0.78, 0.68, and 0.67 (P<.001 for trend) across quintiles of intake. For fish intake and omega-3 fatty acids, the inverse association appeared to be stronger for CHD deaths (multivariate RR for fish consumption 5 times per week, 0.55 [95% CI, 0.33-0.90] for CHD deaths vs 0.73 [0.51-1.04]) than for nonfatal myocardial infarction.
                Among women, higher consumption of fish and omega-3 fatty acids is associated with a lower risk of CHD, particularly CHD deaths. We assessed the clinical and biochemical effects in asthmatic children of fish oil supplementation and a diet that increases omega-3 and reduces omega-6 fatty acids. Thirty nine asthmatic children aged 8-12 yrs participated in a double-blind, randomized, controlled trial for 6 months during which they received fish oil capsules plus canola oil and margarine (omega-3 group) or safflower oil capsules plus sunflower oil and margarine (omega-6 group). Plasma fatty acids, stimulated tumour necrosis factor alpha (TNFalpha) production, circulating eosinophil numbers and lung function were measured at baseline and after 3 and 6 months of dietary modification. Day and night symptoms, peak flow rates and medication use were recorded for 1 week prior to laboratory visits. Plasma phospholipid omega-3 fatty acids were significantly greater in the omega-3 group at 3 and 6 months compared to the omega-6 group (p<0.001). In the omega-3 group TNFalpha production fell significantly compared with baseline (p=0.026), but the magnitude of change between groups did not reach significance (p=0.075). There were no significant changes in clinical outcome measures. Dietary enrichment of omega-3 fatty acids over 6 months increased plasma levels of these fatty acids, reduced stimulated tumour necrosis factor alpha production, but had no effect on the clinical severity of asthma in these children. It has been hypothesized that a diet containing n-3 fatty acids from fish reduces the risk of coronary heart disease, but few large epidemiologic studies have examined this question.
                In 1986, 44,895 male health professionals, 40 to 75 years of age, who were free of known cardiovascular disease completed detailed and validated dietary questionnaires as part of the Health Professionals Follow-up Study. During six years of follow-up, we documented 1543 coronary events in this group: 264 deaths from coronary disease, 547 nonfatal myocardial infarctions, and 732 coronary-artery bypass or angioplasty procedures.
                After controlling for age and several coronary risk factors, we observed no significant associations between dietary intake of n-3 fatty acids or fish intake and the risk of coronary disease. For men in the top fifth of the group in terms of intake of n-3 fatty acids (median, 0.58 g per day), the multivariate relative risk of coronary heart disease was 1.12 (95 percent confidence interval, 0.96 to 1.31), as compared with the men in the bottom fifth (median, 0.07 g per day). For men who consumed six or more servings of fish per week, as compared with those who consumed one serving per month or less, the multivariate relative risk of coronary disease was 1.14 (95 percent confidence interval, 0.86 to 1.51). The risk of death due to coronary disease among men who ate any amount of fish, as compared with those who ate no fish, was 0.74 (95 percent confidence interval, 0.44 to 1.23), but the risk did not decrease as fish consumption increased.
                Although the possibility of residual confounding by unmeasured factors cannot be entirely excluded, these data suggest that increasing fish intake from one to two servings per week to five to six servings per week does not substantially reduce the risk of coronary heart disease among men who are initially free of cardiovascular disease. Although several prospective 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.
                We examined prospectively the association between intake of fish and omega-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 infarctions) 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 > or =5 times per week [P for trend=0.005]). Higher consumption of long-chain omega-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).
                A higher consumption of fish and long-chain omega-3 fatty acids was associated with a lower CHD incidence and total mortality among diabetic women. The relationship between incidence of lung cancer and intake of dietary fats, high-fat foods, fish, and fish products was studied in 25,956 men and 25,496 women aged 16-56 years attending Norwegian health screening between 1977 and 1983. Linkage to the Cancer Registry of Norway and the Central Bureau of Statistics of Norway ensured a complete follow-up until 31 December 1991. Diet was recorded on a semiquantitative food-frequency questionnaire, and 153 cases of lung cancer were identified during follow-up. Mean age at diagnosis was 56 years. After adjusting for smoking status, gender, age at screening, and attained age, significant lower risks were found for cod liver oil supplement (incidence rate ratio (IRR) = 0.5, 95% CI = 0.3-1.0) and for skim milk compared to whole milk (IRR = 0.5, 95% CI = 0.3-0.9)). No association was found with dietary cholesterol and saturated fat. A threshold of increased risk starting at the second quartile was seen for mono- and polyunsaturated fat. The potential protective effect of cod liver oil, a supplement rich in preformed vitamin A, omega-3 fatty acids, and monounsaturated fat, has to our knowledge, not been reported before. Confounding from lifestyle is possible, but the result deserves further investigation. Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.
                To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.
                Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.
                Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.
                Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).
                By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.
                Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.
                ClinicalTrials.gov Identifier: NCT00000611. 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) 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. Experimental data suggest that long-chain n-3 polyunsaturated fatty acids found in fish have antiarrhythmic properties, and a randomized trial suggested that dietary supplements of n-3 fatty acids may reduce the risk of sudden death among survivors of myocardial infarction. Whether long-chain n-3 fatty acids are also associated with the risk of sudden death in those without a history of cardiovascular disease is unknown.
                We conducted a prospective, nested case-control analysis among apparently healthy men who were followed for up to 17 years in the Physicians' Health Study. The fatty-acid composition of previously collected blood was analyzed by gas-liquid chromatography for 94 men in whom sudden death occurred as the first manifestation of cardiovascular disease and for 184 controls matched with them for age and smoking status.
                Base-line blood levels of long-chain n-3 fatty acids were inversely related to the risk of sudden death both before adjustment for potential confounders (P for trend = 0.004) and after such adjustment (P for trend = 0.007). As compared with men whose blood levels of long-chain n-3 fatty acids were in the lowest quartile, the relative risk of sudden death was significantly lower among men with levels in the third quartile (adjusted relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.87) and the fourth quartile (adjusted relative risk, 0.19; 95 percent confidence interval, 0.05 to 0.71).
                The n-3 fatty acids found in fish are strongly associated with a reduced risk of sudden death among men without evidence of prior cardiovascular disease. High intakes of fat and specific fatty acids, including total, animal, saturated, polyunsaturated, and trans-unsaturated fats, have been postulated to increase breast cancer risk.
                To determine whether intakes of fat and fatty acids are associated with breast cancer.
                Cohort study (Nurses' Health Study) conducted in the United States beginning in 1976.
                A total of 88795 women free of cancer in 1980 and followed up for 14 years.
                Relative risk (RR) of invasive breast cancer for an incremental increase of fat intake, ascertained by food frequency questionnaire in 1980, 1984, 1986, and 1990.
                A total of 2956 women were diagnosed as having breast cancer. Compared with women obtaining 30.1% to 35% of energy from fat, women consuming 20% or less had a multivariate RR of breast cancer of 1.15 (95% confidence interval [CI], 0.73-1.80). In multivariate models, the RR (95% CI) for a 5%-of-energy increase was 0.97 (0.94-1.00) for total fat, 0.98 (0.96-1.01) for animal fat, 0.97 (0.93-1.02) for vegetable fat, 0.94 (0.88-1.01) for saturated fat, 0.91 (0.79-1.04) for polyunsaturated fat, and 0.94 (0.88-1.00) for monounsaturated fat. For a 1% increase in energy from trans-unsaturated fat, the values were 0.92 (0.86-0.98), and for a 0.1% increase in energy from omega-3 fat from fish, the values were 1.09 (1.03-1.16). In a model including fat, protein, and energy, the RR for a 5% increase in total fat, which can be interpreted as the risk of substituting this amount of fat for an equal amount of energy from carbohydrate, was 0.96 (95% CI, 0.93-0.99). In similar models, no significant association of risk was evident with any major types of fat.
                We found no evidence that lower intake of total fat or specific major types of fat was associated with a decreased risk of breast cancer. 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. An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits. This study evaluated whether increased intake of fish oils (eicosapentaenoic and docosahexaenoic acids) might reduce the risk of coronary heart disease.
                Observational and clinical studies have suggested that increased intake of fish oils, as reflected in plasma levels of fish oils, may reduce the risk of myocardial infarction.
                A nested case-control study was conducted among the 14,916 participants in the Physicians' Health Study with a sample of plasma before randomization. Each participant with myocardial infarction occurring during the first 5 years of follow-up was matched by smoking status and age with a randomly chosen control participant who had not developed coronary heart disease.
                Mean levels of fish oils (with 95% confidence interval [CI] for paired differences and p values) in case and control participants, expressed as percent of total fatty acids, were, for eicosapentaenoic acid, 0.26 versus 0.25 (95% CI -0.03 to 0.05, p = 0.70) in cholesterol esters and 0.56 versus 0.54 (95% CI -0.04 to 0.09, p = 0.44) in phospholipids, and for docosahexaenoic acid, 0.23 versus 0.24 (95% CI -0.07 to 0.04, p = 0.64) in cholesterol esters and 2.22 versus 2.14 (95% CI -0.10 to 0.27, p = 0.36) in phospholipids. Results adjusted for major cardiovascular risk factors showed a very similar lack of association between fish oil levels and the incidence of myocardial infarction.
                These results indicate no beneficial effect of increased fish oil consumption on the incidence of a first myocardial infarction. However, the effect of very high levels of fish oils could not be evaluated. To determine whether a low fat diet supplemented with omega-3 positively affects quality of life (QOL) in relapsing-remitting MS (RRMS) patients. In this 1-year long double-blind, randomized trial, patients were randomized to two dietary interventions: the "Fish Oil" (FO) group received a low fat diet (15% fat) with omega-3 FOs and the "Olive Oil" (OO) group received the AHA Step I diet (fat 30%) with OO supplements. The primary outcome measure was the Physical Components Summary Scale (PCS) of the Short Health Status Questionnaire (SF-36). Additional measures using MS specific QOL questionnaires, neurological status and relapse rate were obtained.
                31 RRMS patients were enrolled, with mean follow up over 11 +/- SD 2.9 months. Clinical benefits favoring the FO group were observed on PCS/SF-36 (P = 0.050) and MHI (P = 0.050) at 6 months. Reduced fatigue was seen on the OO diet at 6 months (P = 0.035). The relapse rate decreased in both groups relative to the rates during the 1 year preceding the study: mean change in relapse rate in the FO group: -0.79 +/- SD 1.12 relapses/year (P = 0.021) vs. -0.69 +/- SD 1.11 (P = 0.044) in the OO group. This study suggests that a low fat diet supplemented with omega-3 PUFA can have moderate benefits in RRMS patients on concurrent disease modifying therapies. 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 omega-3 polyunsaturated fatty acids derived from fish oils have been shown to modulate many factors believed to affect the pathogenesis of atherosclerosis. Because certain features of restenosis following angioplasty mimic some of the early changes of atherogenesis, some researchers have suggested that fish oil might prevent restenosis following angioplasty. We report the effects of omega-3 fatty acids on the rate of restenosis following percutaneous intraluminal coronary angioplasty (PTCA).
                From August 1989 through September 1992, 551 patients were randomized to start receiving a daily dietary supplement of ten 1.0-g capsules containing 80.6% ethyl esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid (EPA) and 2.8 g docosahexaenoic acid (DHA) for 6 months or an equal amount of an ethyl ester of corn oil. Four hundred seventy subjects who were well matched for risk factors completed successful angioplasty of one or multiple lesions in native coronary vessels and constituted the study cohort, of whom 447 were evaluable at 6 months after PTCA. The criteria for restenosis were that the quantitative coronary angiography at 6 months show a > 30% increase in narrowing at the stenosis site or loss of at least half of the gain achieved at the time of PTCA and final restenosis with < 50% luminal diameter remaining. In 93% of the patients, the end point was determined by angiography and in all except 1% of these by quantitative coronary angiography. Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids. The restenosis rate among analyzable patients was 46% for corn oil and 52% for fish oil (P = .37). The addition of 200 mg alpha-tocopherol for all subjects during the study had no effect on restenosis rates.
                This was the largest of such trials to date, and a supplement of 8 g/d of omega-3 fatty acids failed to prevent the usual high rate of restenosis after PTCA. No adverse effects were attributable to this large daily supplement of omega-3 fatty acids. The strong correlation between national consumption of fat and national rate of mortality from prostate cancer has raised the hypothesis that dietary fat increases the risk of this malignancy. Case-control and cohort studies have not consistently supported this hypothesis.
                We examined prospectively the relationship between prostate cancer and dietary fat, including specific fatty acids and dietary sources of fat. We examined the relationship of fat consumption to the incidence of advanced prostate cancer (stages C, D, or fatal cases) and to the total incidence of prostate cancer.
                We used data from the Health Professionals Follow-up Study, which is a prospective cohort of 51529 U.S. men, aged 40 through 75, who completed a validated food-frequency questionnaire in 1986. We sent follow-up questionnaires to the entire cohort in 1988 and 1990 to document new cases of a variety of diseases and to update exposure information. As of January 31, 1990, 300 new cases of prostate cancer, including 126 advanced cases, were documented in 47855 participants initially free of diagnosed cancer. The Mantel-Haenszel summary estimator was used to adjust for age and other potentially confounding variables. Multiple logistic regression was used to estimate relative risks (RRs) when controlling simultaneously for more than two covariates.
                Total fat consumption was directly related to risk of advanced prostate cancer (age- and energy-adjusted RR = 1.79, with 95% confidence interval [CI] = 1.04-3.07, for high versus low quintile of intake; P [trend] = .06). This association was due primarily to animal fat (RR = 1.63; 95% CI = 0.95-2.78; P [trend] = .08), but not vegetable fat. Red meat represented the food group with the strongest positive association with advanced cancer (RR = 2.64; 95% CI = 1.21-5.77; P = .02). Fat from dairy products (with the exception of butter) or fish was unrelated to risk. Saturated fat, monounsaturated fat, and alpha-linolenic acid, but not linoleic acid, were associated with advanced prostate cancer risk; only the association with alpha-linolenic acid persisted when saturated fat, monounsaturated fat, linoleic acid, and alpha-linolenic acid were modeled simultaneously (multivariate RR = 3.43; 95% CI = 1.67-7.04; P [trend] = .002).
                The results support the hypothesis that animal fat, especially fat from red meat, is associated with an elevated risk of advanced prostate cancer.
                These findings support recommendations to lower intake of meat to reduce the risk of prostate cancer. The potential roles of carcinogens formed in cooking animal fat and of alpha-linolenic acid in the progression of prostate cancer need to be explored. There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders.
                We conducted a randomized, double-blind, placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids (.84 g/d eicosapentaenoic acid, .7 g/d docosahexaenoic acid) supplementation in 13 children (aged 5 to 17 years) with autistic disorders accompanied by severe tantrums, aggression, or self-injurious behavior. The outcome measure was the Aberrant Behavior Checklist (ABC) at 6 weeks.
                We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity. No clinically relevant adverse effects were elicited in either group.
                The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism. 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. The authors examined the association between dietary intake of fish and omega 3 fatty acids from seafood and the risk of cardiovascular disease in a prospective cohort study of 21,185 US male physicians who are participants in the Physicians' Health Study. In 4 years of follow-up, there were 281 incident cases of total (fatal and nonfatal) myocardial infarction, 173 cases of stroke, and 121 cardiovascular deaths. There was no evidence for association between dietary intake of fish and any cardiovascular endpoint, including myocardial infarction, stroke, and cardiovascular death. The relative risks of total myocardial infarction, adjusted for age and randomized treatment assignment, for categories of fish intake were: 1.0 for < 1 meal/week (referent), 1.6 (95% confidence interval (Cl) 1.1-2.3) for 1 fish meal/week; 1.4 (95% Cl 1.0-2.0) for 2-4 fish meals/week; and 1.2 (95% Cl 0.6-2.2) for > or = 5 fish meals/week; chi 2 for trend = 0.9, p = 0.34. The relative risks were similar for omega 3 fatty acid intake and for specific types of fish, and did not change after adjustment for history of hypertension, hypercholesterolemia, diabetes mellitus, or angina pectoris, parental history of myocardial infarction before age 60 years, obesity, exercise, smoking, alcohol use, saturated fat intake, and vitamin supplement use. These data do not support the hypothesis that moderate fish consumption lowers the risk of cardiovascular disease. The objective of this blinded, randomized, prospective study was to assess whether supplementation of normal diet with omega-3 polyunsaturated fatty acids can reduce angiographically defined restenosis following coronary angioplasty. The study included all patients undergoing coronary angioplasty in this institution between January 1988 and January 1989. One hundred and twenty patients enrolled, 60 in each treatment group. All were randomized to either supplementation of normal diet with 3 g of omega-3 polyunsaturated fatty acids per day started 1-2 days prior to angioplasty and continued for 6 months (treatment group), or to receive standard therapy only (control group). Quantitative angiographically defined restenosis was assessed at 6 months post angioplasty. Restenosis occurred in 27.8% (95% CI 18.0-37.7%) of lesions in the treatment group and in 28.3% (CI 16.9-39.7%) of lesions in the control group, but the difference was not statistically significant. The study showed that diet supplemented with 3 g of omega-3 polyunsaturated fatty acids started 1-2 days preceding angioplasty does not reduce angiographically defined restenosis rate. Some prospective studies have shown an inverse association between fish intake and risk of stroke, but none has examined the relationship of fish and omega-3 polyunsaturated fatty acid intake with risk of specific stroke subtypes.
                To examine the association between fish and omega-3 polyunsaturated fatty acid intake and risk of stroke subtypes in women.
                Prospective cohort study of women in the Nurses' Health Study cohort, aged 34 to 59 years in 1980, who were free from prior diagnosed cardiovascular disease, cancer, and history of diabetes and hypercholesterolemia and who completed a food frequency questionnaire including consumption of fish and other frequently eaten foods. The 79 839 women who met our eligibility criteria were followed up for 14 years.
                Relative risk of stroke in 1980-1994 compared by category of fish intake and quintile of omega-3 polyunsaturated fatty acid intake.
                After 1 086 261 person-years of follow-up, 574 incident strokes were documented, including 119 subarachnoid hemorrhages, 62 intraparenchymal hemorrhages, 303 ischemic strokes (264 thrombotic and 39 embolic infarctions), and 90 strokes of undetermined type. Among thrombotic infarctions, 90 large-artery occlusive infarctions and 142 lacunar infarctions were identified. Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke: the multivariate relative risks (RRs), adjusted for age, smoking, and other cardiovascular risk factors, were 0.93 (95% confidence interval [CI], 0.65-1.34) for fish consumption 1 to 3 times per month, 0.78 (95% CI, 0.55-1.12) for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week (P for trend =.06). Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93). Women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids had reduced risk of total stroke and thrombotic infarction, with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively. When stratified by aspirin use, fish and omega-3 polyunsaturated fatty acid intakes were inversely associated with risk of thrombotic infarction, primarily among women who did not regularly take aspirin. There was no association between fish or omega-3 polyunsaturated fatty acid intake and risk of hemorrhagic stroke.
                Our data indicate that higher consumption of fish and omega-3 polyunsaturated fatty acids is associated with a reduced risk of thrombotic infarction, primarily among women who do not take aspirin regularly, but is not related to risk of hemorrhagic stroke. A randomised controlled trial with a factorial design was done to examine the effects of dietary intervention in the secondary prevention of myocardial infarction (MI). 2033 men who had recovered from MI were allocated to receive or not to receive advice on each of three dietary factors: a reduction in fat intake and an increase in the ratio of polyunsaturated to saturated fat, an increase in fatty fish intake, and an increase in cereal fibre intake. The advice on fat was not associated with any difference in mortality, perhaps because it produced only a small reduction (3-4%) in serum cholesterol. The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised. This effect, which was significant, was not altered by adjusting for ten potential confounding factors. Subjects given fibre advice had a slightly higher mortality than other subjects (not significant). The 2 year incidence of reinfarction plus death from ischaemic heart disease was not significantly affected by any of the dietary regimens. A modest intake of fatty fish (two or three portions per week) may reduce mortality in men who have recovered from MI. 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. Whether a Mediterranean-style diet reduces cardiovascular events and mortality more than a low-fat diet is uncertain. The objectives of this study were to actively compare low-fat and Mediterranean-style diets after first myocardial infarction (MI) in a randomized, controlled clinical trial and to compare dietary intervention per se with usual care in a case-control analysis. First MI survivors were randomized to a low-fat (n = 50) or Mediterranean-style (n = 51) diet. The 2 diets were low in saturated fat (< or =7% kcal) and cholesterol (< or =200 mg/day); the Mediterranean-style diet was distinguished by greater omega-3 fat intake (>0.75% kcal). Participants received individual dietary counseling sessions, 2 within the first month and again at 3, 6, 12, 18, and 24 months, along with 6 group sessions. Combined dietary intervention groups (cases, n = 101) were compared with a usual-care group (controls, n = 101) matched for age, gender, MI type and treatment, and status of diabetes mellitus and hypertension. Primary-outcome-free survival (a composite of all-cause and cardiac deaths, MI, hospital admissions for heart failure, unstable angina pectoris, or stroke) did not differ between low-fat (42 of 50) and Mediterranean-style (43 of 51) diet groups over a median follow-up period of 46 months (range 18 to 72; log-rank p = 0.81). Patients receiving dietary intervention had better primary-outcome-free survival (85 of 101) than usual-care controls (61 of 101) (log-rank p <0.001), with unadjusted and adjusted odds ratios of 0.33 (95% confidence interval 0.18 to 0.60, p <0.001) and 0.28 (95% confidence interval 0.13 to 0.63, p = 0.002), respectively. In conclusion, active intervention with either a low-fat or a Mediterranean-style diet similarly and significantly benefits overall and cardiovascular-event-free survival after MI. Previous findings concerning the serum levels of fish-derived (n-3) fatty acids and coronary heart disease are inconsistent. The purpose of this study was to investigate the association between the serum n-3 end-product fatty acids docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid and the risk of acute coronary events in middle-aged men.
                We studied this association in the Kuopio Ischaemic Heart Disease Risk Factor Study, a prospective population study in Eastern Finland. Subjects were randomly selected and included 1871 men aged 42 to 60 years who had no clinical coronary heart disease at baseline examination. A total of 194 men had a fatal or nonfatal acute coronary event during follow-up. In a Cox proportional hazards' model adjusting for other risk factors, men in the highest fifth of the proportion of serum DHA+DPA in all fatty acids had a 44% reduced risk (P=0.014) of acute coronary events compared with men in the lowest fifth. Men in the highest fifth of DHA+DPA who had a low hair content of mercury (</=2.0 microgram/g) had a 67% reduced risk (P=0.016) of acute coronary events compared with men in the lowest fifth who had a high hair content of mercury (>2.0 microgram/g). There was no association between proportion of eicosapentaenoic acid and the risk of acute coronary events.
                Our data provide further confirmation for the concept that fish oil-derived fatty acids reduce the risk of acute coronary events. However, a high mercury content in fish could attenuate this protective effect. Data on the association of n-3 fatty acid content in serum lipids with mortality in patients with coronary artery disease (CAD) are limited.
                We hypothesized that a high proportion of n-3 fatty acids in serum lipids would be associated with reduced risks of death and coronary events in patients with established CAD.
                We measured dietary intakes via food records and the fatty acid composition of serum cholesteryl esters (CEs) in 285 men and 130 women with CAD (x age: 61 y; range: 33-74 y). The patients participating in the EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) study were followed up for 5 y.
                During the follow-up, 36 patients died, 21 had myocardial infarctions, and 12 had strokes. The relative risks (RRs) of death adjusted for cardiovascular disease risk factors for subjects in the highest tertile of fatty acids in CEs compared with those in the lowest tertile were 0.33 (95% CI: 0.11, 0.96) for alpha-linolenic acid, 0.33 (0.12, 0.93) for eicosapentaenoic acid, and 0.31 (0.11, 0.87) for docosahexaenoic acid (P for trend = 0.063, 0.056, and 0.026, respectively). A high proportion of eicosapentaenoic acid in CEs was associated with a low risk of CAD death. Compared with no consumption, consumption of fish tended to be associated with a lower risk of death [1-57 g/d, RR = 0.50 (0.20, 1.28); > 57 g/d, RR = 0.37 (0.14, 1.00); P for trend = 0.059].
                High proportions of n-3 fatty acids in serum lipids are associated with a substantially reduced risk of death. Dietary supplementation with fish oils high in the omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, may have an antiinflammatory effect. We determined whether patients with cystic fibrosis (CF) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects. In this double-blind study, 12 patients with pancreatic insufficiency who have CF (mean age, 12.2 +/- 5.4 (SD) years) and 13 subjects without CF (mean age, 13.4 +/- 6.3 (SD) years) were randomly assigned to ingest 8 gm daily of either encapsulated fish oil (3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily) or olive oil ethyl esters for 6 weeks. Two of seven and two of five patients with CF who received fish and olive oils, respectively, and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea. Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF randomly assigned to the fish oil treatment. For example, in subjects randomly assigned to receive fish oil, the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold, from 0.04 +/- 0.02 (mean +/- SEM) to 0.39 +/- 0.11 (p = 0.02), in the patients with CF (n = 7) and 23.0-fold, from 0.04 +/- 0.01 to 0.92 +/- 0.17 (p = 0.001), in the subjects without CF (n = 8) who received fish oil (p = 0.02, patients with CF vs subjects without CF at 6 weeks). No clinically or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil. Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinically beneficial antiinflammatory effect in patients with CF. This randomized clinical trial tested whether fish oil supplements can improve human coronary atherosclerosis.
                Epidemiologic studies of populations whose intake of oily fish is high, as well as laboratory studies of the effects of the polyunsaturated fatty acids in fish oil, support the hypothesis that fish oil is antiatherogenic.
                Patients with angiographically documented coronary heart disease and normal plasma lipid levels were randomized to receive either fish oil capsules (n = 31), containing 6 g of n-3 fatty acids, or olive oil capsules (n = 28) for an average duration of 28 months. Coronary atherosclerosis on angiography was quantified by computer-assisted image analysis.
                Mean (+/- SD) baseline characteristics were age 62 +/- 7 years, plasma total cholesterol concentration 187 +/- 31 mg/dl (4.83 +/- 0.80 mmol/liter) and triglyceride levels 132 +/- 70 mg/dl (1.51 +/- 0.80 mmol/liter). Fish oil lowered triglyceride levels by 30% (p = 0.007) but had no significant effects on other plasma lipoprotein levels. At the end of the trial, eicosapentaenoic acid in adipose tissue samples was 0.91% in the fish oil group compared with 0.20% in the control group (p < 0.0001). At baseline, the minimal lumen diameter of coronary artery lesions (n = 305) was 1.64 +/- 0.76 mm, and percent narrowing was 48 +/- 14%. Mean minimal diameter of atherosclerotic coronary arteries decreased by 0.104 and 0.138 mm in the fish oil and control groups, respectively (p = 0.6 between groups), and percent stenosis increased by 2.4% and 2.6%, respectively (p = 0.8). Confidence intervals exclude improvement by fish oil treatment of > 0.17 mm, or > 2.6%.
                Fish oil treatment for 2 years does not promote major favorable changes in the diameter of atherosclerotic coronary arteries. In a randomized, placebo-controlled trial, the effects of treatment with fish oil (eicosapentaenoic acid, 1.08 g/day) and mustard oil (alpha-linolenic acid, 2.9 g/day) were compared for 1 year in the management of 122 patients (fish oil, group A), 120 patients (mustard oil, group B), and 118 patients (placebo, group C) with suspected acute myocardial infarction (AMI). Treatments were administered about (mean) 18 hours after the symptoms of AMI in all three groups. The extent of cardiac disease, rise in cardiac enzymes, and lipid peroxides were comparable among the groups at entry into the study. After 1 year total cardiac events were significantly less in the fish oil and mustard oil groups compared with the placebo group (24.5% and 28% vs. 34.7%, p < 0.01). Nonfatal infarctions were also significantly less in the fish oil and mustard oil groups compared with the placebo group (13.0% and 15.0% vs. 25.4%, p < 0.05). Total cardiac deaths showed no significant reduction in the mustard oil group; however, the fish oil group had significantly less cardiac deaths compared with the placebo group (11.4% vs. 22.0%, p < 0.05). Apart from the decrease in the cardiac event rate, the fish oil and mustard oil groups also showed a significant reduction in total cardiac arrhythmias, left ventricular enlargement, and angina pectoris compared with the placebo group. Reductions in blood lipoproteins in the two intervention groups were modest and do not appear to be the cause of the benefit in the two groups. Diene conjugates showed a significant reduction in the fish oil and mustard oil groups, indicating that a part of the benefit may be caused by the reduction in oxidative stress. The findings of this study suggest that fish oil and mustard oil, possibly due to the presence of n-3 fatty acids, may provide rapid protective effects in patients with AMI. However, a large study is necessary to confirm this suggestion. Fish consumption seems to protect against death from coronary heart disease (CHD). If this association is due to n-3 polyunsaturated fatty acids, especially fatty fish may be responsible for this protective effect. The association between total, lean, and fatty fish consumption and the risk of CHD mortality was examined in 1,088 Finnish, 1,097 Italian, and 553 Dutch men participants in the Seven Countries Study who were aged 50-69 years and free of CHD around 1970. After 20 years of follow-up, 242 (22.2%) men in Finland, 116 (10.6%) men in Italy, and 105 (19.0%) men in the Netherlands had died of CHD. Cox proportional hazards analysis showed no association between total fish consumption and CHD mortality. After adjustments were made for age, body mass index, smoking, energy intake, and relevant dietary variables, the pooled relative risk for the highest quartile of total fish compared with no fish consumption in the three countries was 1.08 (95% confidence interval: 0.76, 1.53). Lean fish consumption also was not associated with CHD mortality in any country. Fatty fish compared with non-fatty-fish consumption was associated with lower CHD mortality; the adjusted, pooled relative risk for fatty fish consumers was 0.66 (95% confidence interval: 0.49, 0.90). These data suggest that especially fatty fish is protective against CHD mortality. It has been hypothesized that omega-3 fatty acid consumption may lessen the adverse effect of smoking on coronary heart disease (CHD) risk. Thus, we explored whether cod liver oil consumption was protective of coronary heart disease in a cohort of men and women participating in a cardiovascular disease screening in Norway. The study population was aged 35-54 at the time of the baseline screening conducted by the National Health Screening Service of Norway in 1977-1983. Of 56,718 age-eligible men and women, 52,138 participated, of whom 42,612 (82%) completed a dietary questionnaire. Cod liver oil use was reported by 12.5%. At baseline, cod liver oil users had lower triglycerides, adjusting for age, body mass index, time since last meal and income (p < or = .05). As of December 1992, 639 and 118 CHD deaths were observed among the men and women, respectively. Overall, we observed no effect of cod liver oil consumption reported at baseline and CHD mortality in Cox Proportional Hazards analyses [Hazard Ratio (HR) = 1.0 (0.8-1.3)]. In analyses, stratified by smoking status, never smokers and current smokers showed non-significant beneficial associations between cod liver oil use and CHD mortality (HR = 0.7, 95% CI = 0.4-1.5; and HR = 0.8, 95% CI = 0.6-1.2, respectively). However, among former smokers a non-significant excess risk of CHD mortality was associated with cod liver oil use (HR = 1.6, 95% CI = 0.9-2.6). Smokers, regardless of their cod liver oil use were at a substantially higher risk for CHD mortality relative to non-smokers. Omega-3 fatty acid supplementation, as practiced in this cohort, provided no significant benefits to CHD risk among study participants. Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis.
                The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infarction (MI) on subsequent cardiac events and serum lipids.
                Three hundred patients with acute MI were randomly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil, administered in a double-blind manner over 12-24 mo. Median follow-up time was 1.5 y. Clinical follow-up, including the drawing of blood samples, was performed after 6 wk of treatment and later at 0.5-year intervals.
                Forty-two (28%) patients in the n-3 group and 36 (24%) in the corn oil group experienced at least one cardiac event (cardiac death, resuscitation, recurrent MI, or unstable angina). No significant difference in prognosis was observed between groups for single or combined cardiac events. Total cholesterol concentrations decreased in both groups, with no significant intergroup differences. On average, the monthly increase in HDL cholesterol was 1.11% in the n-3 group and 0.55% in the corn oil group (P = 0.0016). Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group, whereas they increased by 0.35%/mo in the corn oil group (P < 0.0001).
                No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids. Previous studies suggest that recurrence of coronary stenosis after percutaneous transluminal coronary angioplasty (PTCA) might be prevented with dietary supplements rich in omega-3 fatty acids. The purpose of the present study was to evaluate this hypothesis. In addition, the relation between usual dietary consumption of omega-3 fatty acids and restenosis was assessed.
                A double-blind, randomized, controlled trial was conducted in which 205 patients undergoing a first PTCA received 15 capsules per day containing 1 g of either fish oil (2.7 g/day of eicosapentaenoic acid, 1.8 g/day of docosahexaenoic acid) or olive oil. The treatment was started 3 weeks before PTCA and continued for 6 months thereafter. Dietary intake was assessed by food frequency questionnaire. At 6 months after PTCA, patients underwent a control angiography. All angiographic lesions were measured by quantitative computer analysis. Four criteria were used to define restenosis. Restenosis occurred less often in the fish oil group (22.0-35.6% depending on the definition) than in the control group (40.0-53.3%). After controlling for other risk factors of restenosis, the association of fish oil supplementation with a lower frequency of restenosis was statistically significant (p = 0.03) for three of four definitions. After adjustment, a dietary intake of omega-3 fatty acids of more than 0.15 g/day was also associated with a lower frequency of restenosis (p less than or equal to 0.03).
                This trial documented the protective effect of fish oil supplements on the recurrence of coronary stenosis 6 months after PTCA. The study results suggest that a dietary intervention could be useful in preventing restenosis. To see whether mortality among men with angina can be reduced by dietary advice.
                A randomized controlled factorial trial.
                Male patients of general practitioners in south Wales.
                A total of 3114 men under 70 y of age with angina.
                Subjects were randomly 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.
                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.
                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. To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol.
                The participants were 350 normotensive men and women aged 30-54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention. They were randomly assigned to receive placebo or 6 g purified fish oil once a day, which supplied 3 g n-3 polyunsaturated fatty acids for 6 months.
                Baseline blood pressure was (mean +/- SD) 123 +/- 9/81 +/- 5 mmHg. The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant. There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressures in the upper versus the lower quartile (132/87 versus 114/75 mmHg), low habitual fish consumption (0.4 versus 2.9 times a week) or low baseline plasma levels of n-3 fatty acids. Fish oil increased HDL2-cholesterol significantly compared with the placebo group. Subgroup analysis showed this effect to be significant in the women but not in the men. Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL2-cholesterol and decreases in systolic blood pressure.
                Moderate amounts of fish oil (6 g/day) are unlikely to lower blood pressure in normotensive persons, but may increase HDL2-cholesterol, particularly in women. Ecologic correlations suggest that higher intake of saturated fat and lower intake of polyunsaturated fat might increase the risk of multiple sclerosis (MS), but the results of case-control studies have been inconsistent. Because no prospective data are available, the authors examined these associations in two large cohorts, the Nurses' Health Study, which consisted of 92,422 women with 14 years of follow-up (1980-1994) and the Nurses' Health Study II, which consisted of 95,389 women with 4 years of follow-up (1991-1995). They documented 195 new cases of MS. The pooled multivariate relative risks comparing women in the highest quintile with those in the lowest were 1.1 (95% confidence interval: 0.7, 1.7) for total fat, 0.7 (95% confidence interval: 0.5, 1.2) for animal fat, 1.2 (95% confidence interval: 0.7, 2.1) for vegetable fat, 0.8 (95% confidence interval: 0.5, 1.3) for saturated fat, 1.1 (95% confidence interval: 0.7, 1.7) for monounsaturated fat, 1.7 (95% confidence interval 1.0, 2.8) for n-6 polyunsaturated fat, 1.3 (95% confidence interval: 0.8, 2.0) for trans unsaturated fat, and 0.7 (95% confidence interval: 0.4, 1.1) for cholesterol. Omega-3 fatty acids from fish were also unrelated to risk. However, the authors observed a nonsignificantly lower risk of MS for a higher intake of linolenic acid. These findings do not support relations between intakes of total fat or major specific types of fat and the risk of MS. Ecological and case-control studies have demonstrated a positive correlation between consumption of fat and the risk of prostate cancer. Two recent human studies have focused on alpha-linolenic acid as a risk factor for prostate cancer. Animal experiments have shown that dietary omega-6 polyunsaturated fatty acids have generally stimulated tumour development, whereas omega-3 polyunsaturated fatty acids have diminished it. The aim of our study was to investigate the association between these fatty acids and the subsequent risk of prostate cancer. Blood donors to the Janus serum data bank in Norway, who later developed prostate cancer, were matched to blood donors without prostate cancer (141 matched sets); the proportional level of fatty acids measured before diagnosis in the donors' serum was examined. The risk of later prostate cancer was analysed by conditional logistic regression. Increasing risk for prostate cancer was found with increasing quartiles of palmitoleic, palmitic and alpha-linolenic acid. An inverse risk association was found with increasing levels of tetracosanoic acid, for the ratios of linoleic to alpha-linolenic acid and arachidonic to eicosapentaenoic acid. There was no clear association between the risk effect of total omega-3 and total omega-6 fatty acids. There were no indications of a relationship between fatty acids and more aggressive cancers. Our results verify recent findings of a positive association between alpha-linolenic acid and a negative association between the ratio of linoleic to alpha-linolenic acid and the risk of prostate cancer. Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease (CVD) risk. In contrast, randomized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events.
                The study population consisted of men and women > or =40 years old with an LDL cholesterol level > or =3.37 mmol/L (130 mg/dL) and no clinical signs or symptoms of CVD. Eligible participants were randomized to DL-alpha-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years. The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness (IMT) assessed by computer image-processed B-mode ultrasonograms. A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates. Compared with placebo, alpha-tocopherol supplementation significantly raised plasma vitamin E levels (P<0.0001), reduced circulating oxidized LDL (P=0.03), and reduced LDL oxidative susceptibility (P<0.01). However, vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects randomized to placebo.
                The results are consistent with previous randomized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD. Omega-3 polyunsaturated fatty acids have anti-inflammatory effects in vitro, and high dietary levels are associated with a lower incidence of inflammatory diseases. However, only limited effects have been demonstrated in asthma. The effects of dietary supplementation with fish oil for 10 months in 29 children with bronchial asthma was investigated in a randomized controlled fashion. In order to minimize the effects of environmental inhaled allergens and diet, this study was performed in a long-term treatment hospital. Subjects received fish oil capsules containing 84 mg eicosapentaenoic acid (EPA) and 36 mg docosahexaenoic acid (DHA) or control capsules containing 300 mg olive oil. The daily dosages of EPA and DHA were 17.0-26.8 and 7.3-11.5 mg x kg body weight(-1), respectively. Asthma symptom scores decreased and responsiveness to acetylcholine decreased in the fish oil group but not in the control group. In addition, plasma EPA levels increased significantly only in the fish oil group (p<0.0088). No significant side-effects were observed. The present results suggest that dietary supplementation with fish oil rich in the omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid is beneficial for children with bronchial asthma in a strictly controlled environment in terms of inhalant allergens and diet. Retinal function was assessed by electroretinogram in 32 neonates randomly assigned to formulas of different omega-3 fatty acid content and in 10 infants fed human milk. All neonates had a birth weight of 1000-1500 g and were fed study diets from d 10 to 45 or discharge. Group A received formula containing predominantly 18:2 omega-6. Group B received a balanced mix of 18:2 omega-6 and 18:3 omega-3. Group C was given a formula containing both essential fatty acids and supplemented with marine oil to provide 22:6 omega-3 content similar to that of human milk. The fatty acid composition of plasma and red blood cell (RBC) lipids were similar for all groups on entry but marked diet-induced differences were found after feeding the study diets. Group C was comparable to the human milk-fed group, but group A had lower 22:6 omega-3 and omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in plasma and RBC membranes. Cone function was not affected by dietary essential fatty acids. Rod electroretinogram thresholds were significantly higher for group A relative to the human milk-fed group and group C and significantly correlated with RBC omega-3 LCPUFA (r = -0.63, p less than 0.0001); 44% of the variance could be explained by RBC and plasma omega-3 LCPUFA content.(ABSTRACT TRUNCATED AT 250 WORDS) The Women's Health Trial Vanguard Study was conducted to examine the feasibility of a nationwide, randomized multicenter intervention trial to test the hypothesis that a low-fat diet followed for a period of 10 years will reduce breast cancer risk. Women ages 45-69 years at increased risk of breast cancer were randomized into intervention (low-fat diet, n = 184) and control (usual diet, n = 119) groups. On the basis of 4-day food records, baseline fat intakes were comparable in the two groups, averaging 1,718 kcal with 39% of energy as fat. Intervention women reported substantially lower fat intake at 6 (20.9% kcal), 12 (21.6%), and 24 months (22.6% kcal). In contrast, control women reported only slight reductions in fat intake (37.3% kcal at 12 months and 36.8% kcal at 24 months). Evidence that these women were indeed complying with the low-fat dietary intervention comes from (a) the reasonable nature of reported nutrient changes within food groups in the intervention women and (b) agreement between observed and expected differences in plasma total cholesterol between the control and the intervention groups. At 12 months, the observed control - intervention plasma cholesterol difference was 13.1 +/- 4.6 mg/dl while the expected difference based on the Keys equation was 15.1 +/- 1.1 mg/dl; at 24 months, the observed difference was 15.5 +/- 4.3 mg/dl and the expected difference was 12.0 +/- 1.2 mg/dl. These analyses indicate that the intervention women made substantial dietary changes and have successfully maintained these changes over a 2-year period. This study thus demonstrates the feasibility of a randomized trial with an intensive low-fat dietary intervention. Epidemiological studies suggest a protective effect of n-3 fatty acids derived from fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) against cognitive decline. For α-linolenic acid (ALA) obtained from vegetable sources, the effect on cognitive decline is unknown. We examined the effect of n-3 fatty acid supplementation on cognitive decline in coronary heart disease patients.
                The analysis included 2911 coronary patients (78% men) aged 60 to 80 years who participated in a double-blind placebo-controlled trial of n-3 fatty acids and cardiovascular diseases (Alpha Omega Trial). By using a 2 × 2 factorial design, patients were randomly assigned to margarines that provided 400 mg/d of EPA-DHA, 2 g/d of ALA, both EPA-DHA and ALA, or placebo for 40 months. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) at baseline and after 40 months. The effect of n-3 fatty acids on change in MMSE score was assessed using analysis of variance. Logistic regression analysis was used to examine the effects on risk of cognitive decline, defined as a decrease of 3 or more points in MMSE score or incidence of dementia.
                Patients in the active treatment groups had an additional intake of 384 mg of EPA-DHA, 1.9 g of ALA, or both. The overall MMSE score in this cohort was 28.3 ± 1.6 points, which decreased by 0.67 ± 2.25 points during follow-up. Changes in MMSE score during intervention did not differ significantly between EPA-DHA and placebo (-0.65 vs -0.69 points, P = .44) or between ALA and placebo (-0.60 vs -0.74 points, P = .12). The risk of cognitive decline was 1.03 (95% confidence interval: 0.84-1.26, P = .80) for EPA-DHA (vs placebo) and 0.90 (0.74-1.10, P = .31) for ALA (vs placebo).
                This large intervention study showed no effect of dietary doses of n-3 fatty acids on global cognitive decline in coronary heart disease patients.
                Copyright © 2012 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. The Minnesota Coronary Survey was a 4.5-year, open enrollment, single end-time double-blind, randomized clinical trial that was conducted in six Minnesota state mental hospitals and one nursing home. It involved 4393 institutionalized men and 4664 institutionalized women. The trial compared the effects of a 39% fat control diet (18% saturated fat, 5% polyunsaturated fat, 16% monounsaturated fat, 446 mg dietary cholesterol per day) with a 38% fat treatment diet (9% saturated fat, 15% polyunsaturated fat, 14% monounsaturated fat, 166 mg dietary cholesterol per day) on serum cholesterol levels and the incidence of myocardial infarctions, sudden deaths, and all-cause mortality. The mean duration of time on the diets was 384 days, with 1568 subjects consuming the diet for over 2 years. The mean serum cholesterol level in the pre-admission period was 207 mg/dl, falling to 175 mg/dl in the treatment group and 203 mg/dl in the control group. For the entire study population, no differences between the treatment and control groups were observed for cardiovascular events, cardiovascular deaths, or total mortality. A favorable trend for all these end-points occurred in some younger age groups. 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. 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. To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue.
                A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2-month washout interval, in a double-blind crossover design.
                For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue.
                A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol-lowering capacities. We conducted a pilot randomized controlled trial to determine the feasibility and initial safety and efficacy of omega-3 fatty acids (1.3 g/day) for the treatment of hyperactivity in 27 children ages 3-8 with autism spectrum disorder (ASD). After 12 weeks, hyperactivity, as measured by the Aberrant Behavior Checklist, improved 2.7 (± 4.8) points in the omega-3 group compared to 0.3 (± 7.2) points in the placebo group (p = 0.40; effect size = 0.38). Correlations were found between decreases in five fatty acid levels and decreases in hyperactivity, and the treatment was well tolerated. Although this pilot study did not find a statistically significant benefit from omega-3 fatty acids, the small sample size does not rule out small to moderate beneficial effects. The growing public concern with the adverse effects on health of a high fat intake has led to a proliferation on the market of reduced fat products. However, no consensus exists on the effectivity of reduced fat products to decrease energy intake. The studies that have investigated this topic have included small numbers of subjects, studied under laboratory conditions and over a relatively short period of time. Therefore, we have executed a long-term study in which volunteers had free access to both reduced fat, commercially available products in the laboratory as well as to products obtained from regular shops. We here report the feasibility of such a type of study and the effects of consumption of reduced fat products on blood levels of cholesterol, haemostasis variables, antioxidants and parameters of the immune system. The study was a multicentre parallel comparison trial of six months (so-called MSFAT-study). 241 volunteers received either reduced fat products or full-fat products and the products were clearly labelled as such. Two months before the start of the study, a 1 month adaptation period was executed to optimize the experimental procedures. Food intake was recorded before the start of the adaptation period and 2-4 weeks, 3 months and 6 months after the start of the study. Blood samples were taken before, after 2, 4 and 6 months of the study. In addition, a selection of the reduced fat and full-fat products was sensorically evaluated three times during the study by a subgroup of the volunteers. 220 volunteers completed the study. The reduced fat group consumed on average 46% less fat from the so-called MSFAT-products obtained from the shop at the laboratory than the control group and consumption of these MSFAT-products did not decrease in either of the groups during the time course of the study. The palatability of the reduced fat and full-fat products was similar and as expected, the perceived fattiness of the full-fat products was higher than that of the reduced fat products. No effects were found on blood levels of cholesterol, haemostasis variables, parameters of antioxidant status and immune system characteristics. In conclusion, the experimental manipulation of the fat content of the diet that was achieved and that remained stable throughout the 6 months of the study indicates that this type of set-up is feasible to assess the effects of long-term nutritional intervention in large groups of volunteers under semi-controlled conditions. The regular use of reduced fat products did not positively but also not adversely affect blood cholesterol levels, antioxidant status, haemostasis factors and the body's immune system. Epidemiologic and experimental data suggest that a high dietary intake of long-chain polyunsaturated n-3 fatty acids may reduce the risk of atherothrombotic disease. In a randomized, controlled study, 610 patients undergoing coronary artery bypass grafting were assigned either to a fish oil group, receiving 4 g/day of fish oil concentrate, or to a control group. All patients received antithrombotic treatment, either aspirin or warfarin. Their diet and serum phospholipid fatty acid profiles were monitored. The primary end point was 1-year graft patency, which was assessed by angiography in 95% of patients. Vein graft occlusion rates per distal anastomoses were 27% in the fish oil group and 33% in the control group (odds ratio 0.77, 95% confidence interval, 0.60 to 0.99, p = 0.034). In the fish oil group, 43% of the patients had > or = 1 occluded vein graft(s) compared with 51% in the control group (odds ratio 0.72, 95% confidence interval, 0.51 to 1.01, p = 0.05). Moreover, in the entire patient group, there was a significant trend to fewer patients with vein graft occlusions with increasing relative change in serum phospholipid n-3 fatty acids during the study period (p for linear trend = 0.0037). Thus, in patients undergoing coronary artery bypass grafting, dietary supplementation with n-3 fatty acids reduced the incidence of vein graft occlusion, and an inverse relation between relative change in serum phospholipid n-3 fatty acids and vein graft occlusions was observed. This study assesses the effect of dietary supplements with high dose omega-3 fatty acid (N3FA) on the frequency of clinical restenosis during the 6 months after successful percutaneous transluminal coronary angioplasty (PTCA). One hundred ninety-four patients (214 significant coronary narrowings) were randomized after successful PTCA to receive conventional medical therapy or to an identical regimen supplemented by high dose N3FA (4.5 g/day). Enrollment required angina pectoris and successful dilatation of all significant coronary narrowings. The subjects were randomly assigned to either no N3FA (control, n = 99) or N3FA supplementation (n = 95). After a 1-week trial period, 11 (group 2) declined further treatment because of side effects. The remaining 84 subjects (group 1) continued N3FA throughout the 6-month period. Monthly clinical follow-up was obtained in all patients. Ninety-two percent of patients had cardiac testing for evaluation of recurrent ischemia. Except for a greater percentage of women in the group refusing N3FA supplementation (group 2), the 3 groups were similar in demographic data, medical history, dietary habits, history of previous PTCA and angiographic characteristics. Of the 194 subjects, 56 had clinical restenosis (45 by cardiac catheterization, 8 by exercise testing and 3 by symptoms alone [refused further clinical testing]). Reocclusion rates were: group 1 19%, group 2 46%, and control 35%. Analysis both in accordance with the principle of intention to treat and for subjects who actually received N3FA revealed a significant effect of N3FA on preventing clinical restenosis (p less than 0.04 and p = 0.008, respectively). These data suggest that high dose N3FA supplements reduce the clinical restenosis rate after successful PTCA. Although some evidence suggests that dietary fat intake is related to prostate cancer, epidemiologic studies have been inconsistent.
                Our purpose was to assess the association between plasma lipid levels, particularly linoleic and alpha-linolenic acids, and the development of prostate cancer.
                In 1982, at the start of the Physicians' Health Study, 14916 U.S. male physicians provided plasma samples, which were frozen at -82 degrees C. Data accumulated from a series of questionnaires were used to assess the intake of various foods. We used a nested case-control design to compare the fatty acid compositions in plasma from 120 men who later developed prostate cancer with 120 matched controls who did not. Individual fatty acids were measured in plasma as a percentage of total fatty acids, using capillary gas chromatography. Conditional logistic regression models were used to obtain odds ratio estimates while adjusting simultaneously for the effects of one or more potential confounders.
                The relative risks (RRs) of prostate cancer for men in successively higher quartiles of plasma alpha-linolenic acid level were 3.0 (95% confidence interval [CI] = 1.2-7.3), 3.4 (95% CI = 1.6-7.5), and 2.1 (95% CI = 0.9-4.9), compared with those with levels below the detection threshold (P trend = .03). For linoleic acid, RRs in successively higher quartiles were 0.7 (95% CI = 0.4-1.5), 0.8 (95% CI = 0.4-1.6), and 0.6 (95% CI = 0.3-1.3), with the lowest quartile as referent (P trend = .24). The effect estimates were not notably altered by adjustment for exercise, body mass, meat and dairy consumption, or other fatty acid levels in the plasma. The RR for eating red meat at least five times per week compared with less than once a week was 2.5 (95% CI = 0.9-6.7) and was little changed by adjustment for alpha-linolenic acid, although alpha-linolenic acid levels were correlated with intake of red meat and butter. The association of alpha-linolenic acid levels with prostate cancer was greater among men with low linoleic acid and reduced meat intake.
                These results suggest that low plasma levels of alpha-linolenic acid might be associated with reduced risk of prostate cancer, independently of high meat intake. High linoleic acid and low marine fatty oils were not associated with increased risk, as previously hypothesized.
                The effects of dietary alpha-linolenic acid, particularly from vegetable sources, warrant further study. The effects of dietary linoleic acid and marine fatty acids seen in animal bioassays might not apply to human prostate cancer. Current cancer prevention recommendations include reducing consumption of fat and increasing consumption of fruits and vegetables.
                Healthy women health maintenance organization members (n = 616) ages 40-70 were randomly assigned to either a nutrition intervention or a control intervention unrelated to diet. Intervention included two 45-min counseling sessions plus two brief follow-up telephone contacts. Counseling sessions included a 20-min, interactive, computer-based intervention using a touch-screen format. Intervention goals were reducing dietary fat and increasing fruit and vegetable consumption. Outcome measures included a food frequency questionnaire and the Fat and Fiber Behavior Questionnaire (FFBQ). Total serum cholesterol was also measured at baseline and 12 months.
                Twelve-month follow-up data showed improvements on all dietary outcome variables. Compared to the control, intervention participants reported significantly less fat consumption (3.75 points less for percentage of energy from fat), significantly greater consumption of fruit and vegetables combined (0.93 more servings per day), and a significant reduction in a behavioral measure of fat consumption (0.20 point change in the FFBQ). Group differences in total serum cholesterol, while in the desired direction, were not significant.
                In appropriate circumstances, moderate-intensity dietary interventions can show significant effects for periods of at least 1 year. 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. Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management.
                A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided.
                Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status.
                A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment. Trials have demonstrated benefits of long-chain omega-3 essential fatty acid (n-3 EFA) supplementation in a variety of psychiatric disorders.
                To assess the efficacy of n-3 EFAs in improving psychological well-being in patients with recurrent self-harm.
                Patients (n=49) presenting after an act of repeated self-harm were randomised to receive 1.2 g eicosapentaenoic acid plus 0.9 g decosahexaenoic acid (n=22) or placebo (n=27) for 12 weeks in addition to standard psychiatric care. Six psychological domains were measured at baseline and end point.
                At 12 weeks, the n-3 EFA group had significantly greater improvements in scores for depression, suicidality and daily stresses. Scores for impulsivity, aggression and hostility did not differ.
                Supplementation achieved substantial reductions in surrogate markers of suicidal behaviour and improvements in well-being. Larger studies are warranted to determine if insufficient dietary intake of n-3 EFAs is a reversible risk factor for self-harm. 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. 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.
                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 randomly 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.
                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.
                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. Previous trials of omega-3 fatty acids (omega-3 FA) for restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA) have yielded conflicting results. We tested the hypothesis that long-term administration of omega-3 FA before PTCA may have significant effects on restenosis.
                We randomized 339 patients in a double-blind, placebo-controlled study of omega-3 FA (as an ethyl ester preparation given as 6 1-g capsules providing 3 g eicosapentaenoic acid and 2.1 g docosahexaenoic acid/d started 1 month before PTCA and given for 1 month thereafter, then continued at half-dose for 6 months) versus an olive oil placebo. Of these, 257 patients (125 on omega-3 FA, 132 on placebo) well matched for risk factors underwent successful balloon-only PTCA (280 total lesions) and were evaluable at 6 months with repeat angiography. Restenosis was defined at quantitative angiography as a recurrence of >50% diameter stenosis in the dilated vessel (Definition I) and as >50% loss of the short-term gain immediately after PTCA (Definition II).
                Restenosis rates per vessel were 29.4% and 31.6% in the omega-3 FA group, and 39.6% and 35.4% in the placebo group according to Definitions I (P =.04) and II (P = not significant), respectively. Restenosis rates per patient were 31.2% and 33.6% in the omega-3 FA group, and 40.9% and 37.1% in the placebo group according to Definitions I (P =.05) and II (P = not significant), respectively.
                With a long treatment before PTCA, omega-3 FA produced a small but significant decrease in the restenosis rate compared with placebo. Increased consumption of n-3 (omega-3) long-chain polyunsaturated fatty acids (LC PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may maintain cognitive function in later life.
                We tested the hypothesis that n-3 LC PUFA supplementation would benefit cognitive function in cognitively healthy older people.
                At total of 867 cognitively healthy adults, aged 70-79 y, from 20 general practices in England and Wales were randomly assigned into a double-blind controlled trial of daily capsules providing 200 mg EPA plus 500 mg DHA or olive oil for 24 mo. Treatment-allocation codes were obtained from a central computerized randomization service. Trained research nurses administered a battery of cognitive tests, including the primary outcome, the California Verbal Learning Test (CVLT), at baseline and 24 mo. Intention-to-treat analysis of covariance, with adjustment for baseline cognitive scores, age, sex, and age at leaving full-time education, included 748 (86%) individuals who completed the study.
                The mean age of participants was 75 y; 55% of the participants were men. Withdrawals and deaths were similar in active (n = 49 and n = 9, respectively) and placebo (n = 53 and n = 8, respectively) arms. Mean (+/-SD) serum EPA and DHA concentrations were significantly higher in the active arm than in the placebo arm at 24 mo (49.9 +/- 2.7 mg EPA/L in the active arm compared with 39.1 +/- 3.1 mg EPA/L in the placebo arm; 95.6 +/- 3.1 mg DHA/L in the active arm compared with 70.7 +/- 2.9 mg DHA/L in the placebo arm). There was no change in cognitive function scores over 24 mo, and intention-to-treat analysis showed no significant differences between trial arms at 24 mo in the CVLT or any secondary cognitive outcome.
                Cognitive function did not decline in either study arm over 24 mo. The lack of decline in the control arm and the relatively short intervention period may have limited our ability to detect any potential beneficial effect of fish oil on cognitive function in this study. The Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) Study was registered at www.controlled-trials.com as ISRCTN 72331636. To evaluate the clinical antioxidant effects of vitamin E, 161 healthy volunteers aged 39 to 56 years, were given 100 or 3 mg of d-alpha-tocopheryl acetate orally daily for 6 years using a randomized, double-blind design. Among the 147 volunteers who qualified for the analysis, seven of the 73 volunteers receiving 3 mg d-alpha-tocopheryl acetate daily and none of the 74 volunteers receiving 100 mg had coronary disorders including myocardial damage (P < 0.02). ST or T wave abnormalities on electrocardiograms were considered to indicate coronary disorders (four volunteers). The mean serum total tocopherol (TOC) concentration in the 100-mg group was significantly higher than that in the 3-mg group 6 months after the start of the study, and this raised value was maintained throughout the study; the level in the 3-mg group did not change significantly from the baseline value. The low-density lipoprotein cholesterol/total TOC ratio, a parameter of the inhibition of peroxidation of low-density lipoprotein cholesterol, was the only serum lipid parameter that was significantly different, at baseline, in the volunteers with coronary disorders compared with the others. These findings indicate that long-term supplementation with 100 mg tocopheryl acetate daily may prevent the early stages of coronary atherosclerosis by decreasing peroxidation of low-density lipoprotein cholesterol. In this long-term study, we wanted to explore the effect of dietary supplementation of seal oil (SO) as compared cod-liver oil (CLO) on subjects with moderate hypercholesterolemia. The test parameters included fatty acid composition in serum, blood lipids, platelet aggregation, and the activity of blood monocytes. After a run-in period of 6 mon, 120 clinically healthy hypercholesterolemic (7.0-9.5 mmol/L; 270-366 mg/dL) subjects were randomly selected to consume either 15 mL of SO or CLO daily for 14 mon followed by a 4-mon wash-out period. A third group was not given any dietary supplement (control). Consumption of marine oils (SO and CLO) changed the fatty acid composition of serum significantly. Maximal levels were achieved after 10 mon. No further changes were seen after 14 mon. A wash-out period of 4 mon hardly altered the level of n-3 fatty acids in serum. Addition of SO gave 30% higher level of eicosapentaenoic acid, as compared to CLO. Subjects taking SO or CLO had lower whole-blood platelet aggregation than the control group. Neither SO nor CLO had any effects on the levels of serum total cholesterol, high-density lipoprotein cholesterol, postprandial triacylglycerol, apolipoproteins Al and B100, lipoprotein (a), monocyte function expressed as monocyte-derived tissue factor expression, and tumor necrosis factor. This double-blind study was designed to examine and compare the effects of supplementing the existing diet with fish oil or olive oil on lipids and cell function in patients with peripheral vascular disease. Thirty-two patients with symptomatic and angiographically demonstrated peripheral vascular disease were screened, matched, and randomly allocated to take either 15 g/d fish oil or olive oil for 4 weeks. Fish oil reduced serum triglyceride levels by 26%, but increased total cholesterol levels due to a significant increase in both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein-2 cholesterol (HDL2-C). There was a nonsignificant decrease in HDL3-C levels. Olive oil reduced total cholesterol levels, accountable to a significantly decrease in LDL-C levels. Serum thromboxane B2 (TXB2) levels remained unchanged following fish oil, but were significantly increased by olive oil. Urinary excretion of TXB2 and 6-keto-PGF1 alpha was unaffected by either oil supplement. Platelet aggregation, which was measured in platelet-rich plasma in response to two doses of collagen or platelet-activating factor (PAF), was significantly reduced after fish oil, but was increased by olive oil. Following fish oil, there was a significant increase in eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) levels and a decrease in arachidonic acid content of platelet phospholipids. The platelet fatty acid composition after olive oil was unchanged. Fish oil decreased neutrophil leukotriene B4 (LTB4) generation following calcium ionophore stimulation by 33%, while leukotriene B5 levels increased significantly. Neutrophil PAF production and plasma lyso-PAF were unaffected by either oil.(ABSTRACT TRUNCATED AT 250 WORDS) Omega3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, 2 effective treatments for bipolar disorder. The present study was performed to examine whether omega3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder.
                A 4-month, double-blind, placebo-controlled study, comparing omega3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder.
                A Kaplan-Meier survival analysis of the cohort found that the omega3 fatty acid patient group had a significantly longer period of remission than the placebo group (P = .002; Mantel-Cox). In addition, for nearly every other outcome measure, the omega3 fatty acid group performed better than the placebo group.
                Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder. To compare three sets of dietary guidelines for the treatment of non-insulin-dependent diabetes (NIDDM) in free-living individuals and to observe the effects on metabolic control over an 18-month period.
                Seventy volunteer subjects with NIDDM were randomly assigned to one of three diets, a weight-management diet, a high-carbohydrate/fiber diet, or a modified-lipid diet and followed for 18 months. Nutrient intakes, weight, blood lipids, and glycemic control were measured.
                In all diet groups, glycated hemoglobin (HbA1) fell significantly before diet intervention began, remaining lower throughout the study and at follow-up 9 months later. Low-density lipoprotein (LDL) cholesterol showed a sustained fall in all groups after diet intervention. Apart from transient changes in high-density lipoprotein (HDL) cholesterol and triglyceride (TG) in the diet groups with the higher carbohydrate intake, no lasting differences were found between the three diet groups.
                In the long term, there were few differences in the outcome of the three dietary prescriptions. Even with intensive instruction, participants found it difficult to meet recommended nutrient intakes; however, specific dietary advice did result in an improvement in LDL cholesterol. Adverse changes in HDL cholesterol and TG because of diet intervention were transient. The significant improvement in glycemic control during the recruitment phase may have been the result of participants' previous dietary knowledge and the increased attention that they received during the intervention. Increased blood viscosity occurs in patients with claudication. This increase in viscosity, which is mainly due to elevated fibrinogen levels and a decreased red cell deformability, adversely influences blood flow. In addition to a positive effect on blood pressure, blood lipids, and platelet responsiveness, fish oil may improve blood flow due to a favorable influence on hemorrheology. In a prospective, randomized, double-blind study, we evaluated the effect of six capsules of fish oil (1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid) versus six capsules of corn oil (3 g linoleic acid), administered for 4 months, on walking distances, pressure indices during rest and after exercise, blood pressure, red cell deformability, fibrinogen, and lipid levels in 32 patients with stable claudication. No significant changes in walking distances and pressure indices during rest and after exercise occurred, despite a significant increase in red cell deformability in the fish oil group. Fibrinogen levels did not change in either group. In the fish oil group, a favorable change in blood lipids was noted; high-density cholesterol increased and triglycerides decreased. Mean arterial blood pressure declined to a similar extent in both groups. Thus, short-term supplementation with fish oil does not lead to clinically significant improvement of symptoms in patients with stable claudication. This suggests that red cell deformability is of minor importance in the arterial blood flow in the legs of these patients. The aim of the study was to assess omega 3/6 fatty acids (eye q) in attention deficit hyperactivity disorder (ADHD).
                The study included a randomized, 3-month, omega 3/6 placebo-controlled, one-way crossover trial with 75 children and adolescents (8-18 years), followed by 3 months with omega 3/6 for all. Investigator-rated ADHD Rating Scale-IV and Clinical Global Impression (CGI) scale were outcome measures.
                A majority did not respond to omega 3/6 treatment. However, a subgroup of 26% responded with more than 25% reduction of ADHD symptoms and a drop of CGI scores to the near-normal range. After 6 months, 47% of all showed such improvement. Responders tended to have ADHD inattentive subtype and comorbid neurodevelopmental disorders.
                A subgroup of children and adolescents with ADHD, characterized by inattention and associated neurodevelopmental disorders, treated with omega 3/6 fatty acids for 6 months responded with meaningful reduction of ADHD symptoms. Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.
                To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.
                The Women's Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.
                Participants were randomly assigned to the dietary modification intervention (n = 19,541; 40%) or the comparison group (n = 29,294; 60%). The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern.
                Invasive colorectal cancer incidence.
                A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention.
                In this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up.
                ClinicalTrials.gov Identifier: NCT00000611. 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. Increasing evidence supports n-3 fatty acid (FA) supplementation for patients with psychiatric disorders, such as attention deficit hyperactivity disorder. However, the exact metabolic fate of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on different glyceride carriers remains unclear.
                We investigated whether conjugation of EPA and DHA to phospholipid (PL-n-3) or to triacylglycerol (fish oil; FO) affects their incorporation in blood compartments and influences executive functioning.
                Children aged 8-13 y with impaired visual sustained attention performance received placebo, 250 mg/d EPA + DHA esterified to PL-n-3 (300 mg/d phosphatidylserine), or FO for 3 mo in a randomized double-blind manner. Main outcome measures included plasma and erythrocyte FA profile and continuous performance test results (Test of Variables of Attention; TOVA).
                Sixty of the 83 children enrolled completed the interventions (n = 18-21 per group). There was an enrichment of EPA (1.5-2.2-fold), docosapentaenoic acid (DPA; 1.2-fold), and DHA (1.3-fold) in the PL fraction in the plasma of FO- and PL-n-3-fed children. In erythrocytes, only PL-n-3 resulted in a significant reduction (approximately 30%) of very-long-chain saturated FAs (C20-24) and in an increase (1.2- and 2.2-fold, respectively) in linoleic acid and DPA. Total TOVA scores increased in the PL-n-3 (mean +/- SD: 3.35 +/- 1.86) and FO (1.72 +/- 1.67) groups but not in the placebo group (-0.42 +/- 2.51) (PL-n-3 > FO > placebo; P < 0.001). A significant correlation between the alterations in FAs and increased TOVA scores mainly occurred in the PL-n-3 group.
                Consumption of EPA+DHA esterified to different carriers had different effects on the incorporation of these FAs in blood fractions and on the visual sustained attention performance in children. This trial was registered at clinicaltrials.gov as NCT00382616. Type 2 (insulin independent) diabetic women were randomly allocated to receive advice for low fat diets or low carbohydrate diets. By 24 h weighted dietary intakes before and after a mean interval of six months, patients in the low fat group had reduced their fat intake from 41% to 31% of total energy, while carbohydrate percentage of total energy intake increased from 38% to 46%. Percentage energy intake from fat and carbohydrate in the control group remained unchanged. Body weight fell in both groups especially for patients in the low fat group who were obese (weight/height2 greater than or equal to 28 kg/m2). Mean plasma glucose, HbA1, and triglycerides were unchanged. Mean plasma total cholesterol fell significantly in the low fat group compared with the controls (p less than 0.001), but there was no significant difference in the small reduction of high density lipoprotein cholesterol observed in both groups. Thus, adherence to low fat diets occurred without deterioration of diabetes and with benefit for weight and total cholesterol. Maternal intake of omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy. Aim: To describe the effects of maternal omega-3 long-chain PUFA supplementation during pregnancy and lactation on the incidence of allergic disease in infancy. Methods: One hundred and forty-five pregnant women, affected by allergy themselves or having a husband or previous child with allergies, were included in a randomized placebo-controlled trial. Daily maternal supplementation with either 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo was given from the 25(th) gestational week to average 3-4 months of breastfeeding. Skin prick tests, detection of circulating specific immunoglobulin E (IgE) antibodies and clinical examinations of the infants were performed. Results: The period prevalence of food allergy was lower in the omega-3 group (1/52, 2%) compared to the placebo group (10/65, 15%, p < 0.05) as well as the incidence of IgE-associated eczema (omega-3 group: 4/52, 8%; placebo group: 15/63, 24%, p < 0.05). Conclusion: Maternal omega-3 fatty acid supplementation may decrease the risk of food allergy and IgE-associated eczema during the first year of life in infants with a family history of allergic disease. Tissue levels of n-3 fatty acids reflect dietary intake, but quantitative data about rate of incorporation and levels as a function of intake are scarce. We fed 58 men 0, 3, 6, or 9 g/d of fish oil for 12 months and monitored fatty acids in serum cholesteryl esters, erythrocytes, and subcutaneous fat during and after supplementation. Eicosapentaenoic acid (EPA) in cholesteryl esters plateaued after 4-8 weeks; the incorporation half-life was 4.8 days. Steady-state levels increased by 3.9 +/- 0.3 mass % points (+/- SE) for each extra gram of EPA eaten per day. Incorporation of docosahexaenoic acid (DHA) was erratic; plateau values were 1.1 +/- 0.1 mass % higher for every g/d ingested. Incorporation of EPA into erythrocyte membranes showed a half-life of 28 days; a steady state was reached after 180 days. Each g/d increased levels by 2.1 +/- 0.1 mass %. C22:5n-3 levels increased markedly. Changes in DHA were erratic and smaller. EPA levels in adipose tissue rose also; the change after 6 months was 67% of that after 12 months in gluteal and 75% in abdominal fat. After 12 months each gram per day caused an 0.11 +/- 0.01 mass % rise in gluteal fat for EPA, 0.53 +/- 0.07 for C22:5n-3, and 0.14 +/- 0.03 for DHA. Thus, different (n-3) fatty acids were incorporated with different efficiencies, possibly because of interconversions or different affinities of the enzymatic pathways involved. EPA levels in cholesteryl esters reflect intake over the past week or two, erythrocytes over the past month or two, and adipose tissue over a period of years. These findings may help in assessing the intake of (n-3) fatty acids in epidemiological studies. To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis, we set up a randomised, controlled, end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infarction. Another intervention group received diet and cholestyramine, to determine the effect of a greater reduction in circulating cholesterol concentrations. 90 men with coronary heart disease (CHD), who had a mean (SD) plasma cholesterol of 7.23 (0.77) mmol/l were randomised to receive usual care (U, controls), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 (SD 3.5) months. Mean plasma cholesterol during the trial period was 6.93 (U), 6.17 (D), and 5.56 (DC) mmol/l. The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions (U 46%, D 15%, DC 12%), whereas the proportion who showed an increase in luminal diameter rose significantly (U 4%, D 38%, DC 33%). The mean absolute width of the coronary segments (MAWS) studied decreased by 0.201 mm in controls, increased by 0.003 mm in group D, and increased by 0.103 mm in group DC (p less than 0.05), with improvement also seen in the minimum width of segments, percentage diameter stenosis, and edge-irregularity index in intervention groups. The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period. Both interventions significantly reduced the frequency of total cardiovascular events. Dietary change alone retarded overall progression and increased overall regression of coronary artery disease, and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter. These findings support the use of a lipid-lowering diet, and if necessary of appropriate drug treatment, in men with CHD who have even mildly raised serum cholesterol concentrations. To test whether supplementary antioxidants and n-3 fatty acids, alone or in combination, could improve functional status in stroke survivors.
                We performed a randomized, double-blind, placebo-controlled clinical trial in 72 stroke patients (47 males; age 65.3 +/- 12.9 years) admitted to a rehabilitation hospital for sequelae of first-ever ischemic stroke, and divided them into 4 subgroups. Group 1 patients received daily oral antioxidants, group 2 received n-3 polyunsaturated fatty acids, group 3 both supplements, and group 4 placebo, all for 12 months. No difference at baseline was observed among groups in neurological severity or in disability. All measures were repeated after 6 and 12 months of treatment. All major clinical events were recorded.
                At baseline, 25% of the patients had a low plasma vitamin status, and 48.5% was at risk of undernutrition. At the 1-year follow-up, we observed a trend for lower mortality (p = 0.060) in subgroups treated with n-3 fatty acids, but without significant differences in rehabilitation result status among groups.
                Malnutrition is widely observed in patients admitted to a rehabilitative hospital for stroke rehabilitation, and dietary supplementation, even if not able to improve rehabilitation results, is likely to reduce mortality at the 1-year follow-up.
                Copyright 2009 S. Karger AG, Basel. Dietary fat has been implicated as a risk factor for cardiovascular disease and obesity.
                We evaluated the effect on body weight, body fat, lipids, glucose, and insulin of replacing dietary fat with olestra in moderately obese men.
                Forty-five healthy overweight men were randomly assigned to 1 of 3 diets: control diet (33% fat), fat-reduced diet (25% fat), or fat-substituted diet (one-third of dietary fat replaced by olestra to achieve a diet containing 25% metabolizable fat). Body fat was measured by dual-energy X-ray absorptiometry and visceral and subcutaneous abdominal fat by computed tomography.
                Thirty-six men completed the 9-mo study. Body weight and body fat in the fat-substituted group declined by a mean (+/- SEM) of 6.27 +/- 1.66 and 5.85 +/- 1.34 kg, respectively, over 9 mo compared with 3.8 +/- 1.34 and 3.45 +/- 1.0 kg in the control group and 1.79 +/- 0.81 and 1.68 +/- 0.75 kg in the fat-reduced diet group. At 9 mo, the mean difference in body fat between the fat-reduced and fat-substituted groups was -4.19 +/- 1.19 kg (95% CI: -6.57, -1.81), that between the control and fat-substituted groups was -2.55 +/- 1.21 kg (-0.13, -4.97), and that between the control and fat-reduced groups was 1.63 +/- 1.18 kg (3.96, -0.70). The men eating the fat-reduced diet asked for almost no extra foods, in contrast with the significantly higher requests (P < 0.05) from both of the other 2 groups.
                Replacement of dietary fat with olestra reduces body weight and total body fat when compared with a 25%-fat diet or a control diet containing 33% fat. The effect of long-term increased intakes of alpha-linolenic acid (ALA; 18:3n-3) on cardiovascular risk factors is unknown.
                Our objectives were to assess the effect of increased ALA intakes on cardiovascular risk factors and the estimated risk of ischemic heart disease (IHD) at 2 y and the effect of nutritional education on dietary habits.
                Subjects with multiple cardiovascular risk factors (124 men and 158 women) were randomly assigned in a double-blind fashion to consume a margarine rich in either ALA [46% linoleic acid (LA; 18:2n-6) and 15% ALA; n = 114] or LA (58% LA and 0.3% ALA; n = 168). An intervention group (n = 110; 50% ALA) obtained group nutritional education, and a control group (n = 172; 34% ALA) received a posted leaflet containing the standard Dutch dietary guidelines.
                Average ALA intakes were 6.3 and 1.0 g/d in the ALA and LA groups, respectively. After 2 y, the ALA group had a higher ratio of total to HDL cholesterol (+0.34; 95% CI: 0.12, 0.56), lower HDL cholesterol (-0.05 mmol/L; -0.10, 0), higher serum triacylglycerol (+0.24 mmol/L; 0.02, 0.46), and lower plasma fibrinogen (-0.18 g/L; -0.31, -0.04; after 1 y) than did the LA group (adjusted for baseline values, sex, and lipid-lowering drugs). No significant difference existed in 10-y estimated IHD risk. After 2 y, the intervention group had lower saturated fat intakes and higher fish intakes than did the control group.
                Increased ALA intakes decrease the estimated IHD risk to an extent similar to that found with increased LA intakes. Group nutritional education can effectively increase fish intake. To determine whether n-3 fatty acid (EPA/DCHA) prophylaxis is beneficial in high risk pregnancies.
                A randomised, double blind, placebo controlled trial.
                Antenatal clinic of St James's University Hospital, Leeds.
                Two hundred and thirty-three pregnant women at high risk of developing proteinuric or nonproteinuric pregnancy induced hypertension or asymmetrical intrauterine growth retardation.
                Active treatment was 2.7 g of MaxEpa daily (1.62 g of eicosapentaenoic acid and 1.08 g of docosahexaenoic acid). Placebo were matching air-filled capsules.
                Occurrence of proteinuric, nonproteinuric pregnancy induced hypertension or birthweight < 3rd centile.
                There was no difference in an intention to treat analysis between the placebo and active treatment groups for occurrence of proteinuric pregnancy induced hypertension (relative risk (RR) = 0.88; 95% CI 0.47-1.66), nonproteinuric pregnancy induced hypertension (RR = 0.89; 95% CI 0.48-1.64), birthweight < 3rd centile (RR = 0.89; 95% CI 0.48-1.64), or the duration of pregnancy (difference of mean durations = 0.1 days; 95% CI -4.8 to 4.9 days). Analyses stratified by use of tobacco, and analyses excluding known major protocol violators gave essentially identical results.
                There is no evidence from this study for any useful effect of fish oil supplementation for women at high risk of adverse outcomes from a pregnancy, but a small protective effect remains a possibility. 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 outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective 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 less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 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 less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-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.
It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events or cancers in people with, or at high risk of, cardiovascular disease or in the general population. There is no evidence we should advise people to stop taking rich sources of omega 3 fats, but further high quality trials are needed to confirm suggestions of a protective effect of omega 3 fats on cardiovascular health.
There is no clear evidence that omega 3 fats differ in effectiveness according to fish or plant sources, dietary or supplemental sources, dose or presence of placebo.