Prospective study of diet, lifestyle, and intermittent claudication in male smokers. Plasma fatty acid composition and 6-year incidence of hypertension in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Fish oil supplements for prevention of restenosis after coronary angioplasty. Fish consumption and risk of stroke in men. Effect of a fish oil diet on asthma: results of a 1-year double-blind study. Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled 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. Prospective study of plasma fatty acids and risk of prostate cancer. alpha-Linolenic acid intake is not beneficially associated with 10-y risk of coronary artery disease incidence: the Zutphen Elderly Study. Prospective study of diet and female colorectal cancer: the New York University Women's Health Study. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Fish consumption and coronary heart disease mortality in Finland, Italy, and The Netherlands. Dietary fat in relation to risk of multiple sclerosis among two large cohorts of women. 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. Effect of six months of fish oil supplementation in stable rheumatoid arthritis. A double-blind, controlled study. Low serum docosahexaenoic acid is a significant risk factor for Alzheimer's dementia. 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. 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 intake and risk of lung cancer: a prospective study of 51,452 Norwegian men and women. Diet and risk of cutaneous malignant melanoma: a prospective study of 50,757 Norwegian men and women. Abnormal fatty acid composition and human atherosclerosis. Fatty-acid composition of serum lipids predicts myocardial infarction. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. A prospective study of diet and adult-onset asthma. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Long-term effects of three fat-modified diets in hypercholesterolemic subjects. 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. One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance: reduced triglyceridemia, total cholesterol and increased HDL-C without glycemic alterations. Fish oil in diabetic nephropathy. Fish consumption and risk of sudden cardiac death. Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. Fish consumption and cardiovascular disease in the physicians' health study: a prospective study. Association of dietary intake of fat and fatty acids with risk of breast cancer. Effects of fish oil on plasma fibrinolysis in patients with mild rheumatoid arthritis. Can supplementation of diet with omega-3 polyunsaturated fatty acids reduce coronary angioplasty restenosis rate? Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis--a double-blind placebo controlled study. Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk of prostate cancer. Dietary polyunsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial (MRFIT). Absence of prophylactic effect of linolenic acid in patients with coronary heart-disease. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians. Fatty acid composition in serum phospholipids and risk of breast cancer: a prospective cohort study in Northern Sweden. 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. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Prevention of postcoronary angioplasty restenosis by omega-3 fatty acids: main results of the Esapent for Prevention of Restenosis ITalian Study (ESPRIT). Distal procto-colitis, natural cytotoxicity, and essential fatty acids. Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. The risk to develop NIDDM is related to the fatty acid composition of the serum cholesterol esters. [Long-term effects of low dosage fish oil on serum lipids and lipoproteins]. Plasma endothelin-1 immunoreactivity is increased following long-term dietary supplementation with omega-3 fatty acids in microalbuminuric IDDM patients. Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men. Usefulness of fish oil supplements in preventing clinical evidence of restenosis after percutaneous transluminal coronary angioplasty. n-3 fatty acids only delay early relapse of ulcerative colitis in remission. No association between fat and fatty acids intake and risk of colorectal cancer. Cod liver oil consumption, smoking, and coronary heart disease mortality: three counties, Norway. A prospective study of dietary fat and risk of prostate cancer. A controlled trial of the effect of linolenic acid on incidence of coronary heart disease. The Norwegian vegetable oil experiment of 1965-66. Do fish oils prevent restenosis after coronary angioplasty? Fish oil treatment of interferon-alpha-induced dyslipidaemia: study in patients with chronic hepatitis C. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study. Dietary fish oil effects on seasonal hay fever and asthma in pollen-sensitive subjects. N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. Coronary Angioplasty Restenosis Trial. Effect of eicosapentaenoic acid on restenosis rate, clinical course and blood lipids in patients after percutaneous transluminal coronary angioplasty. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis. Docosahexaenoic acid supplementation improves the moderately severe dementia from thrombotic cerebrovascular diseases. Prospective study of dietary fat and the risk of age-related macular degeneration. Randomised trial of fish oil for prevention of restenosis after coronary angioplasty. A long-term seal- and cod-liver-oil supplementation in hypercholesterolemic subjects. Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn's disease. A randomized controlled multicenter trial. Study Group Members (German Crohn's Disease Study Group). Long-term effect of eicosapentaenoic acid ethyl (EPA-E) on albuminuria of non-insulin dependent diabetic patients. Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. Intake of fish and omega-3 fatty acids and risk of stroke in women. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. n-3 Fatty acids and 5-y risks of death and cardiovascular disease events in patients with coronary artery disease. A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis. A prospective cohort study of nutrient intake and age at menarche. The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Fish and shellfish consumption in relation to death from myocardial infarction among men in Shanghai, China. Association of energy and fat intake with prostate carcinoma risk: results from The Netherlands Cohort Study. Dietary determinants of long-term incidence of chronic nonspecific lung diseases. The Zutphen Study. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. Dietary fat and incidence of type 2 diabetes in older Iowa women.
The association between dietary and lifestyle factors and intermittent claudication was investigated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort comprised 26,872 male smokers aged 50-69 years who were free of claudication at study entry. At baseline (1985-1988), subjects completed a diet history questionnaire. During a median follow-up period of 4 years (ending in spring 1993), 2,578 men reported symptoms of claudication on the Rose questionnaire, which was administered annually. Smoking status was assessed every 4 months. Smoking, systolic blood pressure, serum total cholesterol, and diabetes mellitus were positively associated with risk for claudication, whereas serum high density lipoprotein cholesterol, education, and leisure time exercise were inversely associated with risk. Dietary carbohydrates, fiber, and n-6 polyunsaturated fatty acids were inversely associated with risk for claudication, as were some dietary and serum antioxidants: dietary vitamin C (highest quartile vs. lowest: relative risk (RR) = 0.86; 95% confidence interval (CI): 0.77, 0.97), dietary gamma-tocopherol (RR = 0.89; 95% CI: 0.79, 1.00), dietary carotenoids (RR = 0.82; 95% CI: 0.73, 0.92), serum alpha-tocopherol (RR = 0.88; 95% CI: 0.77, 1.00), and serum beta-carotene (RR = 0.77; 95% CI: 0.68, 0.86). Smoking cessation reduced subsequent risk for claudication (RR = 0.86; 95% CI: 0.75, 0.99). The authors conclude that classical risk factors for atherosclerosis are associated with claudication. High intakes of antioxidant vitamins may be protective. Further research is needed before antioxidants can be recommended for the prevention of intermittent claudication. The association of baseline fatty acid composition in plasma cholesterol esters with 6-year incidence of hypertension was examined in middle-aged Minneapolis participants of the Atherosclerosis Risk in Communities (ARIC) Study (1987-1995). Compared with those who were never hypertensive (n = 1,975), incident hypertensives (n = 413) had statistically significantly higher baseline levels of palmitic (16:0) and palmitoleic (16:1n7) acids but lower levels of linoleic (18:2n6) acid and the polyunsaturated/saturated fatty acids ratio (P/S ratio). Among polyunsaturated fatty acids, levels of dihomo-gamma-linolenic (20:3n6) and arachidonic (20:4n6) acids were statistically significantly higher in incident hypertensives, compared with normotensives. After adjustment for age, sex, body mass index, waist/hip ratio, smoking status, ethanol intake, education level, physical activity, and baseline systolic blood pressure in separate models, the odds ratio estimates of incident hypertension for an interquartile increment of a fatty acid in cholesterol esters were 1.26 (95% confidence interval (CI): 1.05, 1.51) for 16:0, 1.11 (95% CI: 0.96, 1.28) for 16:1n7, 1.01 (95% CI: 0.85, 1.21) for 20:3n6, 1.14 (95% CI: 1.03, 1.27) for 20:5n3, 0.81 (95% CI: 0.68, 0.96) for 18:2n6, and 0.83 (95% CI: 0.70, 0.99) for the P/S ratio. The authors conclude that reduced levels of linoleic acid and the P/S ratio and elevated levels of palmitic and arachidonic acids are associated with a higher risk of hypertension. We have evaluated the effect of fish oil supplementation in the prevention of restenosis after percutaneous transluminal coronary angioplasty by a randomised trial conducted in 107 patients. The treatment group (n = 58, 96 significant coronary narrowings) received 10 capsules of fish oil (1.8 g eicosapentaenoic acid, 1.2 g docosahexaenoic acid) besides aspirin and calcium blockers, beginning 4.3 (SD 2.9) days before coronary angioplasty. The conventional medical treatment group (n = 49, 81 significant coronary narrowings) received only aspirin and calcium blockers. Enrollment required the presence of angina pectoris and successful dilatation of all significant coronary narrowings. All patients were followed-up for at least 6 months. Restenosis was identified by symptoms and exercise testing and confirmed by angiography. The incidence of angiographic restenosis was 32% in the fish oil group and 27% in the conventional treatment group. Biochemical investigations showed a greater decrease in serum triglyceride levels in fish oil group as compared to the conventional treatment group. There was no significant difference in the cholesterol levels over the treatment period. Administration of fish oil in a dose of 3 g per day did not reduce the incidence of early restenosis after coronary angioplasty. The effect of fish consumption or long-chain omega-3 polyunsaturated fatty acid (PUFA) intake on risk of stroke remains uncertain.
                To examine the relation of fish consumption and long-chain omega-3 PUFA intake and risk of stroke in men.
                The Health Professional Follow-up Study, a US prospective cohort study with 12 years of follow-up.
                A total of 43 671 men aged 40 to 75 years who completed a detailed and validated semiquantitative food frequency questionnaire and who were free of cardiovascular disease at baseline in 1986.
                Relative risk (RR) of stroke by subtype based on cumulative average fish consumption or long-chain omega-3 PUFA intake, ascertained in 1986, 1990, and 1994.
                We documented 608 strokes during the 12-year follow-up period, including 377 ischemic, 106 hemorrhagic, and 125 unclassified strokes. Compared with men who consumed fish less than once per month, the multivariate RR of ischemic stroke was significantly lower among those who ate fish 1 to 3 times per month (RR, 0.57; 95% confidence interval [CI], 0.35-0.95). However, a higher frequency of fish intake was not associated with further risk reduction; the RR was 0.54 (95% CI, 0.31-0.94) for men who consumed fish 5 or more times per week. This lack of linearity was confirmed by spline analyses. By dichotomized fish intake, the multivariate RR for men who consumed fish at least once per month compared with those who ate fish less than once per month was 0.56 (95% CI, 0.38-0.83) for ischemic stroke and 1.36 (95% CI, 0.48-3.82) for hemorrhagic stroke. The inverse association between fish intake and risk of ischemic stroke was not materially modified by use of aspirin. No significant associations were found between fish or long-chain omega-3 PUFA intake and risk of hemorrhagic stroke.
                Our findings suggest that eating fish once per month or more can reduce the risk of ischemic stroke in men. Airway inflammation is a major component of asthma. Food intake of N-3 fatty acids (FA) is associated with a low incidence of inflammatory diseases, such as asthma. We treated 12 asthmatic patients with FA and report the positive results of this 1-year double-blind study. A positive effect on forced expiratory volume in 1 s was observed after the 9 month of treatment. Our results are in favor of the use of FA, but have to be confirmed by other studies. 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. 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. 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. Data on the relation between alpha-linolenic acid intake and coronary artery disease (CAD) are limited. Other dietary components appear to modify the reported relation between alpha-linolenic acid intake and CAD.
                We examined whether dietary alpha-linolenic acid intake was inversely associated with risk of CAD.
                We prospectively studied 667 men aged 64-84 y from the Zutphen Elderly Study who were free of CAD at baseline. Dietary intake was assessed by using a cross-check dietary history method.
                During the 10-y follow-up, we documented 98 cases of CAD. After adjustment for age, standard coronary risk factors, and intake of trans fatty acids and other nutrients, alpha-linolenic acid intake was not significantly associated with CAD risk. The relative risk of CAD for the highest compared with the lowest tertile of alpha-linolenic acid intake was 1.68 (95% CI: 0.86, 3.29). alpha-Linolenic acid intake from sources containing trans fatty acids was also nonsignificantly, yet positively, associated with CAD risk. alpha-Linolenic acid intake from foods that did not contain trans fatty acids was not associated with CAD risk, the relative risk of CAD for the highest compared with the lowest tertile was 1.15 (95% CI: 0.63, 2.11).
                We did not observe a beneficial effect of dietary alpha-linolenic acid intake on the risk of 10-y CAD incidence. Investigating this hypothesis was complicated by the association between intakes of alpha-linolenic acid and trans fatty acids. Given the results of current prospective studies, a protective cardiac effect of alpha-linolenic acid is questionable. The relation between diet and female colorectal cancer was analyzed in a prospective study of 14,727 women aged 34-65 years, who were enrolled at mammographic screening clinics in New York and Florida from 1985 to 1991. They were followed through the end of 1994 (average 7.1 yrs) by a combination of direct contact through mail and telephone and record linkages with regional tumor registries, resulting in 100 incident cases of colorectal cancer. There was no overall positive or inverse association of colorectal cancer risk with intakes of total calories, total or subclasses of fat, carbohydrate, or dietary fiber, whereas there was an inverse association with total protein. Among major food groups, there was a progressive decline in risk of colorectal cancer with increasing intake of fish and shellfish (relative risk for 4th vs. 1st quartile = 0.49, 95% confidence interval = 0.27-0.89). A similar inverse association was also observed for consumption of dairy products, and this association was explained mainly by calcium, not by other nutrients, such as fat or protein. The results of the present study indicated that certain dietary components of fish or dairy products may protect against colorectal cancer, whereas the relations with red meat or total fat remained unclear. 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. 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. 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. 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. Therapeutic effects of fish oil (10 g/day) in rheumatoid arthritis were investigated in a randomized, controlled, double-blind study. Forty-three patients completing the study were evaluated at 0, 3 and 6 months. The nutrient intake in the fish oil group and in the control group was essentially similar. In the fish oil group, the percentage of n-3 fatty acids in serum phosphatidylcholine increased by 9.6 (range 2.6-16.1). Patients in the fish oil group reported a significantly decreased consumption of NSAID at 3 and 6 months, and the status of global arthritic activity improved at 3 months in physician's assessment. Control patients reported an increased global arthritic activity at 6 months. No change was found in patient assessment of pain, duration of morning stiffness or functional capacity. Essentially no change occurred in biochemical markers of inflammation. We conclude that fish oil has small anti-inflammatory effects with at most a NSAID-saving potential. The value of prolonged supplementation remains to be evaluated. nan 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. 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. 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. The relationship between dietary habits and subsequent risk of cutaneous malignant melanoma (CMM) was studied in 25,708 men and 25,049 women aged 16-56 years attending a Norwegian health screening in 1977-1983. Linkage to the Cancer Registry of Norway and the Central Bureau of Statistics of Norway ensured a complete follow-up until December 31, 1992. Diet was recorded through a semi-quantitative food-frequency questionnaire at the time of screening, and 108 cases of CMM were identified during follow-up. Use of cod liver oil supplementation and intake of polyunsaturated fat were associated with significant increased risk and drinking coffee with significant decreased risk of CMM in women. Adjusting for height, body mass index, body surface area, education, smoking or occupational or recreational physical activity did not change the results. No significant association was found between the incidence of CMM and any of the dietary factors in men. Important aspects are residual confounding by sun exposure and social class, as well as concern with multiple comparisons. nan During a follow-up of five to seven years 33 out of 1222 middle-aged men initially free of coronary heart disease sustained fatal or non-fatal myocardial infarction or died suddenly. The fatty-acid composition of serum triglycerides, phospholipids, and cholesterol esters had been measured at the start of the surveillance in these men and in a control group of 64 men matched for age, serum cholesterol and triglyceride concentrations, blood pressure, obesity, smoking, and one-hour glucose tolerance. Palmitic and stearic acids of phospholipids were significantly higher and linoleic and most polyunsaturated fatty acids, including arachidonic acid and eicosapentaenoic acid, of phospholipids were lower in the subjects who sustained coronary events compared with the controls. Linoleic acid tended to correlate negatively with blood pressure while other polyunsaturated fatty acids, especially eicosapentaenoic acid, exhibited a negative correlation with blood pressure and relative body weight in the controls but not in the subjects who sustained coronary events. These findings suggest that the fatty-acid pattern of serum phospholipids is an independent risk factor for coronary heart disease. 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. 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. A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect. 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. Altogether 160 free living subjects (aged 30-60 years) most of whom had moderate hypercholesterolemia were randomised into the following diet groups to find out long-term effects of different fat-modified diets: (1) control diet 35/14:10:4 (energy percents from fat/saturated:monounsaturated:polyunsaturated fatty acids in actual diets); (2) AHA type diet 32/10:8:8; (3) monoene-enriched diet 34/11:11:5; (4) reduced-fat diet 30/12:8:3. LDL cholesterol fell equally with the AHA type diet (4.54 +/- 0.97 vs. 4.21 +/- 0.89 mmol/l (mean +/- S.D., 0 vs. 6 months), P = 0.001) and with the monoene-enriched diet (4.55 +/- 0.95 vs. 4.25 +/- 0.95 mmol/l, P = 0.004) during the 6-month study. Moderate amounts of polyenes or monoenes as part of natural diets did not decrease HDL cholesterol level in the long term. Serum lipid values remained unchanged with the reduced-fat diet. Analysis by apolipoprotein E phenotypes showed a decrease in LDL cholesterol only in subjects with phenotype 3/3 in the monoene-enriched group (-8.6 +/- 8.7 vs. +1.3 +/- 15.4, percent change in LDL cholesterol E 3/3 vs. E 4/3 + 4/4), but in the AHA type group LDL cholesterol decreased similarly in phenotypes E 3/3 and E 4/3 + 4/4 (-6.9 +/- 10.1 vs -6.9 +/- 16.5). 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. n-3 Fatty acids in the form of ethyl esters (EE) allow lower daily doses and improved compliance. Administration of n-3 fatty acids to patients with glucose intolerance has led to controversial findings, some studies indicating worsening of the disorder, others no effect, or an improvement. A total of 935 patients with hypertriglyceridemia, associated with additional cardiovascular risk factors, i.e. glucose intolerance, NIDDM and/or arterial hypertension were entered a double blind (DB) protocol lasting 6 months with n-3 EE versus placebo, followed by a further 6 months of open study (n = 868) on 2 g a day of n-3 EE. At the end of the DB period, triglyceridemia in the total group was reduced significantly more by n-3 EE, without alterations in glycemic parameters. In the 6 months open follow up, patients on n-3 EE with type IIB hyperlipoproteinemia showed a significant reduction of total cholesterol, both in cases with (-4.15% vs. the 6 month levels) and without NIDDM (-3.8%). HDL-cholesterol had an overall mean rise of 7.4%, maximal in type IV patients with (+9.1%) and without (+10.1%) NIDDM. No alterations in glycemic parameters were detected in treated patients. Administration of n-3 EE to patients with hypertriglyceridemia associated with NIDDM or impaired glucose tolerance appears safe and effective. Recent studies in nondiabetic kidney diseases suggest that dietary supplementation with n-3 polyunsaturated fatty acids (fish oil) may have beneficial effects on albuminuria, kidney function, arterial blood pressure, and dyslipidemia. Therefore, we evaluated the long-term effect of fish oil in diabetic nephropathy.
                A 1-year double-blind randomized controlled study comparing fish oil (4.6 g n-3 fatty acids/day) with placebo (olive oil) was performed in an outpatient clinic in a tertiary referral center. Thirty-six normotensive IDDM patients with diabetic nephropathy were included; 18 were treated with fish oil. Seven patients dropped out (four received fish oil), and results for the remaining 29 are presented. Albuminuria (enzyme immunoassay), glomerular filtration rate (51Cr-labeled EDTA plasma clearance), 24-h ambulatory blood pressure, and lipid profile were determined every 6 months.
                Albuminuria increased by 22% (1-46%) (mean [95% CI]) in the fish oil group vs. 15% (-11-49%) in the placebo group (NS). Glomerular filtration rate decreased from 116 +/- 7 to 105 +/- 7 ml.min-1.1.73 m-2 (mean +/- SE) vs. from 108 +/- 6 to 103 +/- 7, fish oil and placebo, respectively (NS). No significant changes occurred in 24-h ambulatory blood pressure: from 141 +/- 4/82 +/- 2 mmHg to 142 +/- 5/83 +/- 2 vs. from 140 +/- 4/78 +/- 2 to 144 +/- 4/80 +/- 3, fish oil and placebo, respectively (NS). In the fish oil group, serum triglycerides (median [range]) decreased from 0.97 (0.5-4.0) mmol/l to 0.8 (0.4-3.0) vs. from 1.01 (0.4-2.0) to 1.09 (0.4-2.0) in the placebo group (P < 0.05) and VLDL cholesterol decreased from 0.45 (0.23-1.88) to 0.37 (0.21-1.43) mmol/l vs. from 0.44 (0.21-0.94) to 0.41 (0.17-1.94) (P < 0.05), but total and LDL cholesterol rose in the fish oil compared with the placebo group.
                Our study does not suggest that fish oil has beneficial effects on albuminuria, kidney function, blood pressure, and dyslipidemia in normotensive IDDM patients suffering from diabetic nephropathy. Dietary fish intake has been associated with a reduced risk of fatal cardiac end points, but not with nonfatal end points. Dietary fish intake may have a selective benefit on fatal arrhythmias and therefore sudden cardiac death.
                To investigate prospectively the association between fish consumption and the risk of sudden cardiac death.
                Prospective cohort study.
                The US Physicians' Health Study.
                A total of 20 551 US male physicians 40 to 84 years of age and free of myocardial infarction, cerebrovascular disease, and cancer at baseline who completed an abbreviated, semiquantitative food frequency questionnaire on fish consumption and were then followed up to 11 years.
                Incidence of sudden cardiac death (death within 1 hour of symptom onset) as ascertained by hospital records and reports of next of kin.
                There were 133 sudden deaths over the course of the study. After controlling for age, randomized aspirin and beta carotene assignment, and coronary risk factors, dietary fish intake was associated with a reduced risk of sudden death, with an apparent threshold effect at a consumption level of 1 fish meal per week (P for trend=.03). For men who consumed fish at least once per week, the multivariate relative risk of sudden death was 0.48 (95% confidence interval, 0.24-0.96; P=.04) compared with men who consumed fish less than monthly. Estimated dietary n-3 fatty acid intake from seafood also was associated with a reduced risk of sudden death but without a significant trend across increasing categories of intake. Neither dietary fish consumption nor n-3 fatty acid intake was associated with a reduced risk of total myocardial infarction, nonsudden cardiac death, or total cardiovascular mortality. However, fish consumption was associated with a significantly reduced risk of total mortality.
                These prospective data suggest that consumption of fish at least once per week may reduce the risk of sudden cardiac death in men. Experimental studies in laboratory animals and humans suggest that alpha-linolenic acid (18:3n-3) may reduce the risk of arrhythmia.
                The objective was to examine the association between dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease (IHD).
                This was a prospective cohort study. The intake of alpha-linolenic acid was derived from a 116-item food-frequency questionnaire completed in 1984 by 76283 women without previously diagnosed cancer or cardiovascular disease.
                During 10 y of follow-up, we documented 232 cases of fatal IHD and 597 cases of nonfatal myocardial infarction. After adjustment for age, standard coronary risk factors, and dietary intake of linoleic acid and other nutrients, a higher intake of alpha-linolenic acid was associated with a lower relative risk (RR) of fatal IHD; the RRs from the lowest to highest quintiles were 1.0, 0.99, 0.90, 0.67, and 0.55 (95% CI: 0.32, 0.94; P for trend = 0.01). For nonfatal myocardial infarction there was only a modest, nonsignificant trend toward a reduced risk when extreme quintiles were compared (RR: 0.85; 95% CI: 0.61, 1.19; P for trend = 0.50). A higher intake of oil and vinegar salad dressing, an important source of alpha-linolenic acid, was associated with reduced risk of fatal IHD when women who consumed this food > or =5-6 times/wk were compared with those who rarely consumed this food (RR: 0.46; 95% CI: 0.27, 0.76; P for trend = 0.001).
                This study supports the hypothesis that a higher intake of alpha-linolenic acid is protective against fatal IHD. Higher consumption of foods such as oil-based salad dressing that provide polyunsaturated fats, including alpha-linolenic acid, may reduce the risk of fatal IHD. 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. 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. As rheumatoid arthritis (RA) patients have been shown to have impaired plasma fibrinolysis and fish oil has been suggested to be useful for RA, this study investigated the effects of fish oil on fibrinolytic parameters in patients with RA. Forty-five RA patients were randomised to receive either fish oil (1.7 gm eicosapentaenoic acid and 1.1 gm docosahexaenoic acid/day) or placebo treatment for at least 6 months. Plasma levels of fibrinogen, tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) activity were measured at 3-month intervals. In the fish oil treatment group, plasma levels of fibrinogen and t-PA activity were reduced at 6 months when compared with baseline [fibrinogen: 3.2 (2.85-3.53) milligrams vs 3.89 (3.56-4.22) milligrams, mean (95% confidence intervals for mean), p < 0.02; t-PA activity 1.4 (1.01-1.78) units/ml vs 1.94 (1.55-2.33) units/ml, p < 0.01]. No significant changes in plasma PAI activity were seen during the treatment period in these patients. Placebo treatment did not significantly alter the plasma levels of fibrinogen or t-PA and PAI activity. In conclusion, fish oil supplementation does not appear to produce an improvement in plasma fibrinolysis. Indeed, plasma fibrinogen levels and t-PA activity were reduced. This could be due to an effect of fish oil on acute phase protein production. Alternatively, as t-PA is produced on an "on demand" basis, its reduction may be related to the lowering of fibrinogen levels following fish oil therapy. 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. Maxepa contains eicosapentaenoic acid (EPA) (171 mg/capsule) and docosahexaenoic acid (DHA) (114 mg/capsule). EPA acts as an alternative substrate to arachidonate, leading to the formation of the less proinflammatory prostaglandins ('3' series) and leukotrienes ('5' series). If Maxepa has anti-inflammatory properties it could be expected to reduce the requirement for NSAIDs in patients with RA. This has not been investigated nor has Maxepa therapy been studied over a full 1-yr period. Sixty-four patients with stable RA requiring NSAID therapy only were studied. Patients received either 10 Maxepa or air-filled placebo capsules per day for 12 months. All then received placebo capsules for a further 3 months. Patients were reviewed at 3-monthly intervals. NSAID requirement at entry visit for each patient was assigned as 100%. Patients were instructed to slowly reduce their NSAID dosage providing there was no worsening of their symptoms. Clinical and laboratory parameters of RA activity were also measured. There was a significant reduction in NSAID usage in patients on Maxepa when compared with placebo from month 3 [mean (95% C.I. for mean) requirement--71.1 (55.9-86.2)% and 89.7 (73.7-105.7)%, respectively]. This effect reached its maximum at month 12 [40.6 (24.5-56.6)% and 84.1 (62.7-105.5)%, respectively] and persisted to month 15 [44.7 (27.6-61.8)% and 85.8 (60.5-111.1)%, respectively] (P < 0.001, ANOVA). These patients were able to reduce their NSAID requirement without experiencing any deterioration in the clinical and laboratory parameters of RA activity. 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. nan nan 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. 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. nan 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. 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. 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. Recently, it has been postulated that patients with ulcerative colitis have altered natural cytotoxicity, in particular natural killer (NK) and lymphokine-activated killer (LAK) cell activities. These cellular mechanisms have been postulated to play an etiological role in the pathogenesis of the disease process. We have shown previously that the essential fatty acids (EFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) specifically inhibit natural cytotoxicity. Our aim was to evaluate the role of omega-3 EFA in the modulation of natural cytotoxicity and disease activity in patients with distal procto-colitis.
                In this pilot study patients were randomized into two groups. Each patient received either fish oil extract (EPA, 3.2 g, and DHA, 2.4 g) (n = 9) or sunflower oil (placebo) (n = 9) daily in a double-blind manner for 6 months. Monthly assessments of disease activity (clinical and sigmoidoscopic scores) and histological evaluation of mucosal biopsies were carried out. Also, the circulating levels and activities of NK and LAK cells, using flow cytometric analysis (CD16+ CD56+) and in vitro 51 chromium release assays (K562), respectively, were monitored.
                After 6 months' supplementation with EFA, there was improvement in the clinical activity compared with pretreatment evaluation. There was significant reduction in the sigmoidoscopic and histological scores in the EFA group compared with the placebo group. Essential fatty acid supplementation for 6 months also induced significant reduction in the circulating numbers of CD16+ and CD56+ cells and the cytotoxic activity of NK cells, compared with the placebo group.
                This pilot study has demonstrated that omega-3 fatty acids can suppress natural cytotoxicity and reduce disease activity in patients with distal procto-colitis. These findings suggest a therapeutic strategy for managing patients with inflammatory bowel disease. The effect of fish oil on the course of ulcerative colitis was investigated in a randomised blinded controlled study. Eighty seven patients received supplements of 20 ml HiEPA fish oil as triglyceride (4.5 g of eicosapentaenoic acid) or olive oil placebo daily for one year. The oils were given in addition to standard drug therapy and trial entry was stratified for disease activity. Fish oil significantly increased the eicosapentaenoic acid content of rectal mucosa to 3.2% of total fatty acids at six months, compared with 0.63% for patients on olive oil. This was associated with increased synthesis of leukotriene B5, and 53% suppression of leukotriene B4 synthesis by ionophore--stimulated neutrophils. Leukotriene B4 suppression persisted for at least two months after treatment was stopped. Treatment with fish oil resulted in measurable, but only limited clinical benefit. For patients entering the trial in relapse (n = 53), there was a significant reduction in corticosteroid requirement after one and two months treatment. There was a trend towards achieving remission (off corticosteroids) faster in the patients on fish oil, although differences were not significant. For patients in remission at trial entry or during the trial (n = 69), there was no significant difference in the rate of relapse by log rank analysis. We conclude that fish oil supplementation produces a modest corticosteroid sparing effect in active disease, but there is no benefit in maintenance therapy. This investigation was undertaken to study whether the risk to develop non-insulin-dependent diabetes mellitus (NIDDM) among 50-year-old men during a 10-year follow-up period was related to the fatty acid composition of their serum cholesterol esters. There were highly significant differences in the initial health survey between the fatty acid composition in serum in subjects who remained normoglycemic (n = 1,753) and in those who later developed NIDDM (n = 75). The main differences were that the latter had higher proportions of saturated fatty acids and palmitoleic acid (16:1 omega-7), a low proportion of linoleic acid (18:2 omega-6), and a relatively high content of gamma-linolenic (18:3 omega-6) and dihomo-gamma-linolenic (20:3 omega-6) acids in the serum cholesterol esters. The picture was similar also after adjusting for differences in body mass index. In a logistic model, a high proportion of dihomo-gamma-linolenic acid remained a significant contributor to the development of diabetes, along with the height of the insulin index, the blood glucose concentration at 60 min, and the fasting insulin concentration. The increased risk to develop NIDDM related to the serum cholesterol ester fatty acid composition may be mediated by diet and/or genetic factors. In a prospective and double-blind study, the long-term effects of low dose fish oil on serum lipids and lipoproteins was tested in patients with normal or moderately elevated serum lipids and compared to the effects of olive oil. The compliance to the study medication was evaluated by analysis of serum fatty acids and proved to be very good. Dietary supplementation with 9 g fish oil, respective 3.15 g n-3 fatty acids per day over one year resulted in a decrease of serum-triglycerides by 26% and increase of HDL-cholesterol by 26%. Treatment with 9 g olive oil resulted in an 18% increase of HDL-cholesterol. There was no effect on serum-triglyceride levels. nan Atherosclerosis and thrombosis may lead to cognitive impairment through cerebral infarcts or white matter hyperintensities. Oxidative stress is now seen as a major contributor to the process of atherogenesis. High intake of polyunsaturated fatty acids, e.g., linoleic acid, or low intake of antioxidants can increase oxidative stress. High intake of n-3 polyunsaturated fatty acids and its main source, fish, may reduce the risk of thrombosis. Little is known, however, about the relation between these dietary factors and cognitive function. The authors investigated this relation with data derived from a cohort of men, aged 69-89 years, who were participants in the Zutphen Elderly Study. The 30-point Mini-Mental State Examination was used to assess cognitive impairment in 1990 (score < or = 25 in 153/476 men, 32%) and cognitive decline from 1990 to 1993 (drop > 2 points in 51/342 men, 15%). Food intake was estimated in 1985 and 1990 by the cross-check dietary history method. High linoleic acid intake was associated with cognitive impairment after adjustment for age, education, cigarette smoking, alcohol consumption, and energy intake (odds ratio (OR) for highest vs. lowest tertile = 1.76, 95% confidence interval (CI) 1.04-3.01). Intake of n-3 polyunsaturated fatty acids was not associated with cognitive impairment, whereas high fish consumption tended to be inversely associated with cognitive impairment (OR = 0.63, 95% CI 0.33-1.21) and cognitive decline (OR = 0.45, 95% CI 0.17-1.16). Intakes of beta-carotene, vitamins C and E, and flavonoids were not inversely associated with cognitive impairment or decline. This study raises the possibility that high linoleic acid intake is positively associated with cognitive impairment and high fish consumption inversely associated with cognitive impairment. 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. Relapse prevention by dietary n-3 fatty acids (5.1 g/day) was studied in a double-blind, placebo-controlled trial of 64 patients with ulcerative colitis in remission and off steroids. 5-ASA compounds were stopped three months after randomization and clinical disease activity monitored for two years. Macroscopic and histologic activity and extension was assessed by colonoscopy at entry and at exit. Both treatment groups were well matched at start. Nine patients on placebo and eight on n-3 fatty acids stopped taking their medication prematurely. Actuarial relapse-free survival was improved by n-3 fatty acids only during months 2 and 3 (2P < 0.05-0.01), but cumulative relapse rate at two years was similar for those taking placebo (18/33 = 55%) and n-3 fatty acids (18/31 = 58%). There was also no consistent difference in clinical, macroscopic, and histologic disease activity between treatment groups. The n-3 fatty acids temporarily retard, but do not prevent, relapse of ulcerative colitis. nan 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. 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. nan 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. Objective: Our study was designed to evaluate the role of omega-3 fatty acids (OFAs) in reducing serum triglyceride levels in patients with chronic hepatitis C receiving treatment with interferon-alpha (IFNalpha). Design: 52 patients (23 males, 29 females) with chronic hepatitis C were randomly assigned to nonblind treatment with IFNalpha 3 million units (MU) three times weekly alone (group A) or in combination with OFAs 3 g/day for 6 months (group B). Results: Hepatitis C virus (HCV) RNA serum levels decreased significantly in both groups compared with baseline, but there was no significant difference in HCV RNA levels between the 2 groups. At the end of treatment there was a statistically significant difference in ALT levels between patients in group A and in group B (72.15 vs 50.05 IU/L; p = 0.01). A statistically significant increase in triglyceride levels occurred in group A during treatment (p = 0.03 vs baseline). In contrast, a statistically significant decrease in triglyceride serum levels occurred in group B (p = 0.001 vs baseline). Conclusion: Concurrent administration of OFAs reversed IFNalpha-induced hypertriglyceridaemia in patients with chronic hepatitis C. To study the long-term effects of supplementation with omega-3 fatty acids (omega 3) in patients with active rheumatoid arthritis.
                Ninety patients were enrolled in a 12-month, double-blind, randomized study comparing daily supplementations with either 2.6 gm of omega 3, or 1.3 gm of omega 3 + 3 gm of olive oil, or 6 gm of olive oil.
                Significant improvement in the patient's global evaluation and in the physician's assessment of pain was observed only in those taking 2.6 gm/day of omega 3. The proportions of patients who improved and of those who were able to reduce their concomitant antirheumatic medications were significantly greater with 2.6 gm/day of omega 3.
                Daily supplementation with 2.6 gm of omega 3 results in significant clinical benefit and may reduce the need for concomitant antirheumatic medication. The effects of taking 18 capsules a day of Max-EPA (3.2 g/day eicosapentaenoic acid) on clinical symptoms and bronchial hyperresponsiveness were studied in pollen-sensitive subjects over a pollen season in a parallel, double-blind, placebo-controlled (olive oil) fashion. The study was conducted over the 1990 and 1991 pollen seasons in London, England. A total of 37 nonsmoking pollen-sensitive asthmatic subjects were entered into the trial, and 25 completed the 6-month study period over the 2 yr. The preseasonal geometric mean PD35 SGaw of histamine for the fish oil (n = 12) and placebo (n = 9) groups were 0.62 and 0.42 mumol, respectively. During the middle of the pollen season, histamine PD35 SGaw fell significantly for both the fish oil (0.11 mumol, p < 0.0001) and placebo groups (0.10 mumol, p < 0.007), indicating increased bronchial reactivity compared with preseasonal values, but there was no significant difference between the groups. Similarly, morning and evening peak expiratory flow (PEF), diurnal variability in PEF, nocturnal cough and wheeze, daytime wheeze, and activity, as well as nasal symptoms and increased usage of medication, were not significantly different between the groups. Compliance was confirmed by neutrophil and plasma phospholipid analysis, which showed significant rises in eicosapentaenoic acid content in the fish oil group but not in the placebo group. We conclude that dietary fish oil supplementation does not prevent seasonal hay fever and asthma in pollen-sensitive subjects during the pollen season. The aim of the study was to investigate whether omega-3 fatty acids (n-3 FA) reduce the occurrence of restenosis after percutaneous transluminal coronary angioplasty.
                Meta-analyses have shown significant reduction of restenosis after coronary angioplasty upon supplementation with n-3 FA.
                In a prospective, placebo-controlled, double-blind study, 500 patients were randomly allocated to treatment with n-3 FA (Omacor, Pronova AS, Oslo, Norway) 5.1 g/day or corn oil (placebo) starting at least two weeks prior to elective coronary angioplasty. The treatment was continued until restenosis evaluation by quantitative coronary angiography after six months. Stenosis was defined as a minimal luminal diameter (MLD) < 40% of the reference diameter. Successful coronary angioplasty was defined as > or = 20% acute gain in MLD and a residual stenosis < 50%. Restenosis was defined as > or = 20% late loss of diameter and stenosis > 50% or an increase in stenosis of > or = 0.7 mm. Three-hundred ninety-two patients fulfilled the criteria for initial stenosis and successful coronary angioplasty, and, except four patients who died, none were lost for follow-up.
                Restenosis occurred in 108/266 (40.6%) of the treated stenoses in the Omacor group and in 93/263 (35.4%) in the placebo group (odds ratio [OR] 1.25, 95% confidence interval [CI] [0.87-1.80] p = 0.21). In the Omacor group one or more restenoses occurred in 90/196 (45.9%) patients as compared with 86/192 (44.8%) in the placebo group (OR 1.05, 95% CI [0.69-1.59] p = 0.82).
                Supplementation with 5.1 g n-3 FA/day for six months, initiated at least two weeks prior to coronary angioplasty did not reduce the incidence of restenosis. In order to study the effects of eicosapentaenoic acid (Maxepa), Maxepa placebo and aspirin/dipyridamole combination on the clinical course and restenosis rate of atherosclerotic lesions after percutaneous transluminal coronary angioplasty 79 men and 29 women were randomly divided into three treatment groups and restudied angiographically within one year of the procedure. Angina recurred less in the Maxepa group than in the other groups, although not statistically so. Restenosis rate was significantly reduced in the Maxepa group (11%) compared to the placebo group (30%) but, while less, was not significantly lower than in the aspirin/dipyridamole group (17%). Maxepa treatment appears to reduce restenosis rate of coronary artery lesions after percutaneous transluminal coronary angioplasty and may be an acceptable and equally effective alternative therapy to aspirin/dipyridamole. 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. Fish oil may be beneficial in the treatment of psoriasis and in RA. We examined the potential benefit of Efamol Marine, a combination of evening primrose oil and fish oil in the treatment of 38 patients with PsA. Patients with PsA were entered in a double-blind placebo controlled study and received either 12 Efamol Marine capsules or 12 placebo capsules daily for 9 months. All patients received placebo capsules for a further 3 months. At month 3 of the study patients were asked to reduce their intake of NSAIDs and maintain that decrease provided there was no worsening of their joint symptoms. Clinical assessments of skin and joint disease severity and activity were performed at 0, 1, 3, 6, 9 and 12 months. All measures of skin disease activity including severity, percentage body affected and itch were unchanged by Efamol Marine. The NSAID requirement remained the same between both treatment groups. In addition, there was no change demonstrated in the activity of arthritis as measured by duration of morning stiffness. Ritchie articular index, number of active joints, ESR and CRP. However, a rise in serum TXB2 was observed in the active group during the placebo phase; in addition a fall in leukotriene B4 production occurred during the active phase period followed by a marked rise during the placebo phase suggesting some laboratory documented anti-inflammatory effect. In conclusion, this study suggests that Efamol Marine may alter prostaglandin metabolism in patients with PsA, although it did not produce a clinical improvement and did not allow reduction in NSAID requirement. A larger dose of essential fatty acid may be needed to produce a clinical benefit. nan The relation between intakes of total fat and specific types of fat and age-related macular degeneration (AMD) remains unclear.
                Our objective was to examine prospectively the association between fat intake and AMD.
                We conducted a prospective follow-up study of participants in the Nurses' Health Study and the Health Professionals Follow-up Study. At baseline (1984 for women and 1986 for men), the study included 42743 women and 29746 men aged > or = 50 y with no diagnosis of AMD who were followed until 1996. Fat intake was assessed with a food-frequency questionnaire.
                We accrued 567 patients with AMD with a visual loss of 20/30 or worse. The pooled multivariate relative risk (RR) for the highest compared with the lowest quintile of total fat intake was 1.54 (95% CI: 1.17, 2.01; P for trend = 0.008). Linolenic acid was positively associated with risk of AMD (top versus bottom quintile of RR: 1.49; 95% CI: 1.15, 1.94; P for trend = 0.0009). Docosahexaenoic acid had a modest inverse relation with AMD (top versus bottom quintile of RR: 0.70; 95% CI: 0.52, 0.93; P for trend = 0.05), and >4 servings of fish/wk was associated with a 35% lower risk of AMD compared with < or = 3 servings/mo (RR: 0.65; 95% CI: 0.46, 0.91; P for trend = 0.009).
                Total fat intake was positively associated with risk of AMD, which may have been due to intakes of individual fatty acids, such as linolenic acid, rather than to total fat intakes per se. A high intake of fish may reduce the risk of AMD. To examine the potential role of fish oil supplementation in the prevention of restenosis after coronary angioplasty (PTCA), a randomised double-blind trial was conducted in 204 patients. The treatment group received 6 g/day of n-3 fatty acids, beginning 5.4 (SD 3.2) days before PTCA, and continuing for 6 months; the control group received olive oil placebo. Compliance was assessed by pill count and plasma levels of eicosapentaenoic acid (EPA). Restenosis was identified by symptoms and exercise testing and confirmed by angiography. PTCA was successful in 186 patients (93%). The incidence of angiographic restenosis was 34% in the fish oil group and 23% in the control group (relative risk 1.7, 95% CI 0.9-3.4). The lack of benefit of fish oil was not influenced by length of pretreatment, compliance with study medication, or the concentrations of plasma EPA achieved. 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. There is no established therapy for maintaining remission in patients with Crohn's disease. Following different suggestions from the literature, two potential interventions for maintaining remission were tested against placebo, using either 5 g/day of a highly concentrated omega-3 fatty acid compound or a carbohydrate-reduced diet (84 g/day).
                A total of 204 patients were recruited after they had had an acute relapse. After remission (CDAI < or = 150) was attained with steroid therapy, patients were randomized to receive either omega-3 fatty acids (n = 70), placebo (n = 65), or diet (n = 69). Low-dose prednisolone was given to all patients for the first 8 weeks of intervention. CDAI and an acute-phase protein (CRP) were used as criteria for a relapse.
                The proportion of patients without relapse within a year were similar in the placebo and active treatment group (intention-to-treat analysis: placebo, 30%; active treatment, 30%; protocol-adhering patients, 29% versus 28%). Patients did gain benefit (53%; p = 0.023) for as long as they maintained the diet. However, intention-to-treat analysis (diet group, 40%) did not show a noticeable difference when compared with placebo.
                Omega-3 fatty acids did not show an effect on extending the remission in Crohn's disease. For the diet patients the question remains whether the noncompliant patients dropped out early because they sensed a relapse approaching or whether their condition deteriorated because they failed to comply with the diet. Dietary cod-liver oil containing eicosapentaenoic acid is effective on microvascular albumin leakage in diabetic patients with albuminuria. We determined the long-term effects of oral pure eicosapentaenoic acid ethyl (EPA-E: 900 mg/day) administration on diabetic nephropathy in non-insulin dependent diabetic (NIDDM) patients. The effects of EPA-E were determined by observing the changes of the index of urine albumin excretion level/urine creatinine (Cr) excretion level (UAI), the ratio of beta 2-microglobulin excretion level/urine Cr excretion level (beta 2-MG/Cr) and the ratio of N-acetyl-D-glucosaminidase excretion level/urine Cr excretion level (NAG/Cr) at 3, 6 and 12 months after the start of the treatment. Oral EPA-E administration immediately improved the increased UAI at 3 months after the start of treatment. A significant improvement of the UAI by EPA-E was sustained 12 months later. EPA E administration also tended to decrease the urine beta 2-MG/Cr ratio from 6 months, but the difference was statistically not significant. However, the urine NAG/Cr ratio was not changed by EPA-E administration. EPA-E administration did not affect blood pressure levels, glycemic control and lipid metabolism in these patients. The present data indicated that EPA-E administration improved increased albumin excretion in NIDDM patients with nephropathy and its effects on albuminuria sustained for at least 12 months after the start of treatment. However, tubular factors were not influenced by EPA-E administration. 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. 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. Patients with Crohn's disease may have periods of remission, interrupted by relapses. Because fish oil has antiinflammatory actions, it could reduce the frequency of relapses, but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects.
                We performed a one-year, double-blind, placebo-controlled study to investigate the effects of a new fish-oil preparation in the maintenance of remission in 78 patients with Crohn's disease who had a high risk of relapse. The patients received either nine fish-oil capsules containing a total of 2.7 g of n-3 fatty acids or nine placebo capsules daily. A special coating protected the capsules against gastric acidity for at least 30 minutes.
                Among the 39 patients in the fish-oil group, 11 (28 percent) had relapses, 4 dropped out because of diarrhea, and 1 withdrew for other reasons. In contrast, among the 39 patients in the placebo group, 27 (69 percent) had relapses, 1 dropped out because of diarrhea, and 1 withdrew for other reasons (difference in relapse rate, 41 percentage points; 95 percent confidence interval, 21 to 61; P < 0.001). After one year, 23 patients (59 percent) in the fish-oil group remained in remission, as compared with 10 (26 percent) in the placebo group (P = 0.003). Logistic-regression analysis indicated that only fish oil and not sex, age, previous surgery, duration of disease, or smoking status affected the likelihood of relapse (odds ratio for the placebo group as compared with the fish-oil group, 4.2; 95 percent confidence interval, 1.6 to 10.7).
                In patients with Crohn's disease in remission, a novel enteric-coated fish-oil preparation is effective in reducing the rate of relapse. 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. In a placebo-controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n = 16), super evening primrose oil (n = 19), or olive oil as placebo (n = 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red-cell membrane concentrations of eicosapentaenoic acid (EPA) at 3 months by three-fold and at 6 months by four-fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red-cell membrane concentrations of dihomogamma-linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P < 0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell-membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit. A cohort of 213 girls (aged 10 y, range +/- 9 mo) whose parents reported their dietary intakes (including nutritional supplements) using a semiquantitative food frequency questionnaire, was followed for 4 y until 82% of the 194 parents who responded to follow-up letters had reported that their daughters had had their first menstrual periods. The relative risk (RR) of menarche before age 12.5 y was 2.0 [95% confidence interval (CI) = 1.1-3.8] for the tallest girls (greater than 150 cm) compared with the shortest girls (less than 130 cm). The RR was 2.1 (95% CI = 1.1-3.8) for the fattest girls [Quetelet's index of relative weight (in kg/m2) greater than 19] vs the leanest girls (less than 15). After adjusting for height and Quetelet's index, menarcheal age was not associated with intake of energy nor energy-adjusted intake of protein, fat, or carbohydrate. The overall results are consistent with the hypothesis that nutritional factors influence age at menarche mainly through their effects on accumulation of adipose tissue. 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. Between 1986 and 1989, 18,244 men aged 45-64 years in Shanghai, China, participated in a prospective study of diet and cancer. All participants completed an in-person, structured interview and provided blood and urine samples. As of September 1, 1998, 113 deaths from acute myocardial infarction were identified. After analyses were adjusted for age, total energy intake, and known cardiovascular disease risk factors, men who consumed >or=200 g of fish/shellfish per week had a relative risk of 0.41 (95% confidence interval: 0.22, 0.78) for fatal acute myocardial infarction compared with men consuming <50 g per week. Similarly, dietary intake of n-3 fatty acids derived from seafood also was significantly associated with reduced mortality from myocardial infarction. Neither dietary seafood nor n-3 fatty acid intake was associated with a reduced risk of death from stroke or ischemic heart disease other than acute myocardial infarction. However, approximately a 20% reduction in total mortality associated with weekly fish/shellfish intake was observed in the study population (relative risk = 0.79, 95% confidence interval: 0.69, 0.91). These prospective data suggest that eating fish and shellfish weekly reduces the risk of fatal myocardial infarction in middle-aged and older men in Shanghai, China. The roles of energy and fat intake as risk factors for prostate carcinoma are still questionable. Therefore, these factors were evaluated in the Netherlands Cohort Study described in this article.
                The cohort study consisted of 58,279 men ages 55-69 years at baseline in 1986. After 6.3 years of follow-up, 642 incident prostate carcinoma cases were available for analysis. Intake of energy, fat, and separate fatty acids were measured by means of a self-administered questionnaire; fat intake was adjusted for energy by regression analysis. The case-cohort method was used to calculate rate ratios (RRs). Analyses were conducted for all prostate carcinoma cases together as well as for case subgroups (latent vs. nonlatent and localized vs. advanced).
                No associations were found in multivariate analyses between prostate carcinoma and intake of energy, total fat, total saturated fatty acids, or total trans unsaturated fatty acids (RR highest vs. lowest quintile: 0.99, 1.10, 1.19, and 0.99, respectively). Oleic acid intake showed a nonsignificant positive association (RR = 1.38, 95% CI: 0.88-2.19). Positive associations were also observed for intake of oleic acid in subgroup analyses. Linoleic (RR = 0.78, 95% CI: 0. 56-1.09) and linolenic (RR = 0.76, 95% CI: 0.66-1.04) acid intake were associated with nonsignificantly decreased risks; only for linolenic acid did these associations persist in subgroup analyses. No associations were found for intake of arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid.
                These data suggest that certain fatty acids might be involved in prostate carcinoma occurrence, although the possibility that these were chance findings cannot be ruled out.
                Copyright 1999 American Cancer Society. The association between diet and the 25-year incidence of chronic nonspecific lung diseases (CNSLD) was studied in 793 middle-aged men in the town of Zutphen, the Netherlands, in 1960-1985. During follow-up, 232 new cases of CNSLD were identified. The incidence rate was 14.1 per 1,000 person-years. Habitual food intake was assessed by the cross-check dietary history method. The intake of linoleic acid was positively associated with the incidence of CNSLD. The relative risk was 1.55 (95% confidence interval (Cl) 1.11-2.16), comparing the highest with the lowest quartile of intake of linoleic acid, independent of potential cofounders (age, cigarette smoking, body mass index, and energy intake). Alcohol consumers showed a significantly lower risk than did non-consumers (relative risk (RR) = 0.72, 95% Cl 0.55-0.95) after adjustment for confounders. In addition, fruit intake was inversely related to incidence of CNSLD (RR = 0.73, 95% Cl 0.53-0.99). No association was observed with intake of several antioxidants. These results suggest that in addition to well-established determinants, such as cigarette smoking and occupational exposure, dietary factors may play a role in the onset of chronic nonspecific lung diseases. 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. To examine the associations between reported intakes of dietary fat and incident type 2 diabetes.
                We studied the relation between dietary fatty acids and diabetes in a prospective cohort study of 35,988 older women who initially did not have diabetes. Diet was assessed with a food frequency questionnaire at baseline, and 1,890 incident cases of diabetes occurred during 11 years of follow-up.
                After adjusting for age, smoking, alcohol consumption, BMI, waist-to-hip ratio, physical activity, demographic factors, and dietary magnesium and cereal fiber, diabetes incidence was negatively associated with dietary polyunsaturated fatty acids, vegetable fat, and trans fatty acids and positively associated with omega-3 fatty acids, cholesterol, and the Keys score. After simultaneous adjustment for other dietary fat, only vegetable fat remained clearly related to diabetes risk. Relative risks across quintiles of vegetable fat intake were 1.00, 0.90, 0.87, 0.84, and 0.82 (P = 0.02). Diabetes risk was also inversely related to substituting polyunsaturated fatty acids for saturated fatty acids and positively correlated to the Keys dietary score.
                These data support an inverse relation between incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty acids for saturated fatty acids and cholesterol.
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.