Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Effect of six months of fish oil supplementation in stable rheumatoid arthritis. A double-blind, controlled study. Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients. A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians. A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM. Dietary fish oil in renal transplant recipients treated with cyclosporin-A: no beneficial effects shown. Fish oil supplementation in patients with stable claudication. Prophylaxis of hemodialysis graft thrombosis with fish oil: double-blind, randomized, prospective trial.
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. High intake of n-3 polyunsaturated fatty acids may protect against age-related cognitive decline. However, results from epidemiologic studies are inconclusive, and results from randomized trials in elderly subjects without dementia are lacking.
                To investigate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on cognitive performance.
                Double-blind, placebo-controlled trial involving 302 cognitively healthy (Mini-Mental State Examination score > 21) individuals aged 65 years or older. Participants were randomly assigned to 1,800 mg/d EPA-DHA, 400 mg/d EPA-DHA, or placebo capsules for 26 weeks. Cognitive performance was assessed using an extensive neuropsychological test battery that included the cognitive domains of attention, sensorimotor speed, memory, and executive function.
                The mean age of the participants was 70 years, and 55% were male. Plasma concentrations of EPA-DHA increased by 238% in the high-dose and 51% in the low-dose fish oil group compared with placebo, reflecting excellent compliance. Baseline scores on the cognitive tests were comparable in the three groups. Overall, there were no significant differential changes in any of the cognitive domains for either low-dose or high-dose fish oil supplementation compared with placebo.
                In this randomized, double-blind, placebo-controlled trial, we observed no overall effect of 26 weeks of eicosapentaenoic acid and docosahexaenoic acid supplementation on cognitive performance. 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. Nephrotoxicity is the main untoward effect of cyclosporine (CsA) treatment. Experimental and clinical data suggest that dietary supplementation with fish oil may lessen cyclosporine nephrotoxicity, possibly by lowering renal thromboxane (Tx) production. We have studied the renal effects of a daily supplementation for 2 months of 12 g fish oil (18% C20:5 n-3 eicosapentaenoic acid [EPA] and 12% C22:6 n-3 docosahexanoic acid [DHA]) in a placebo-controlled (12 g corn oil), prospective, randomized, double-blind study of stable CsA-treated liver transplant recipients. Thirteen patients ingested corn oil capsules and 13 fish oil. Compliance with dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentrations of EPA (from 0.4 +/- 0.02% to 4.6 +/- 0.5%, P < .0001) and DHA (from 1.8 +/- 0.2% to 3.9 +/- 0.1%, P < .0001) in the fish oil group and increased plasma concentration of linoleic acid (C18:2 n-6) in the corn oil group (from 25 +/- 2% to 28.4 +/- 2%, P < .001). At the end of the 2 months of the study, in the fish oil group the effective renal plasma flow increased by 22% (P = .012), the glomerular filtration rate increased by 33% (P = .057), the renal blood flow increased by 17% (P = .024), and the calculated total renal vascular resistances decreased by 20% (P = .034). In contrast, none of these parameters changed in the corn oil group. The renal functional reserve determined during L-arginine infusion, plasma renin activity (PRA), and plasma aldosterone (PA) remained unchanged during the study in either group.(ABSTRACT TRUNCATED AT 250 WORDS) This study evaluated whether increased intake of fish oils (eicosapentaenoic and docosahexaenoic acids) might reduce the risk of coronary heart disease.
                Observational and clinical studies have suggested that increased intake of fish oils, as reflected in plasma levels of fish oils, may reduce the risk of myocardial infarction.
                A nested case-control study was conducted among the 14,916 participants in the Physicians' Health Study with a sample of plasma before randomization. Each participant with myocardial infarction occurring during the first 5 years of follow-up was matched by smoking status and age with a randomly chosen control participant who had not developed coronary heart disease.
                Mean levels of fish oils (with 95% confidence interval [CI] for paired differences and p values) in case and control participants, expressed as percent of total fatty acids, were, for eicosapentaenoic acid, 0.26 versus 0.25 (95% CI -0.03 to 0.05, p = 0.70) in cholesterol esters and 0.56 versus 0.54 (95% CI -0.04 to 0.09, p = 0.44) in phospholipids, and for docosahexaenoic acid, 0.23 versus 0.24 (95% CI -0.07 to 0.04, p = 0.64) in cholesterol esters and 2.22 versus 2.14 (95% CI -0.10 to 0.27, p = 0.36) in phospholipids. Results adjusted for major cardiovascular risk factors showed a very similar lack of association between fish oil levels and the incidence of myocardial infarction.
                These results indicate no beneficial effect of increased fish oil consumption on the incidence of a first myocardial infarction. However, the effect of very high levels of fish oils could not be evaluated. To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus (NIDDM).
                Forty subjects (18 men and 22 women; aged 53.9 +/- 7.0 years) with NIDDM and hyperlipidemia were randomly assigned to one of four treatment groups: 9 g of fish oil, 18 g of fish oil, 9 g of corn oil, or 18 g of corn oil daily supplementation for 12 weeks.
                The level of oil supplements (9 g compared with 18 g) did not have a significant effect within each oil group on glycemic control and lipids. Significant differences (P < 0.05) in lipids were found when the 9-g and 18-g groups were combined. In subjects consuming fish oil, plasma very-low-density lipoprotein (VLDL) cholesterol (P = 0.0001), plasma triglyceride (TG) (P = 0.0001), and plasma VLDL TGs (P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks) were significantly lowered compared with subjects consuming corn oil. Plasma VLDL cholesterol increased across time in the corn oil group (P = 0.04). Plasma low-density lipoprotein (LDL) cholesterol was temporarily increased (P = 0.008) in the fish oil group at 6 weeks, but the effect was no longer present at 12 weeks. No significant differences between fish oil- or corn oil-supplemented diets were found in total plasma cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, glycosylated HbA1c, weight, and blood pressure.
                In this study, fish oil supplementation improved plasma VLDL cholesterol, VLDL TGs, and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM. Furthermore, fish oil supplementation had no significant deleterious effect on glycemic control. This study aimed to determine whether dietary supplementation with fish oil has a beneficial effect on graft function and the incidence of rejection in renal allograft recipients treated with cyclosporin A (CsA). Renal function, blood pressure, the incidence of acute rejection episodes, graft survival, and renal histology and immunochemistry were investigated. In a randomized, placebo-controlled, double-blind trial, groups of 25 recipients of primary cadaveric renal allografts who had been treated with CsA took fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3) or coconut oil (63% C8:0 and 36% C10:0) at 6 g/day for 3 months. There were no differences between the two patient groups with regard to HLA matching, panel-reactive antibody titers, or the demographic characteristics of donors or recipients. The GFR and effective RPF were determined at 1, 3, and 12 months after transplantation by simultaneous measurement of (125I-)iothalamate and (131I-)hippuran clearances. At 1 yr after transplantation, patients treated with fish oil showed better renal function than did the control patients, but this difference was not statistically significant. Blood pressure and antihypertensive drug use were similar in both groups. The number of rejection episodes was also similar, and renal histopathological and immunohistochemical studies showed no significant differences between the fish-oil group and the control patients. It is concluded that fish oil, at a dose of 6 g/day, has no beneficial effect after renal transplantation within the time scale of the study. Increased blood viscosity occurs in patients with claudication. This increase in viscosity, which is mainly due to elevated fibrinogen levels and a decreased red cell deformability, adversely influences blood flow. In addition to a positive effect on blood pressure, blood lipids, and platelet responsiveness, fish oil may improve blood flow due to a favorable influence on hemorrheology. In a prospective, randomized, double-blind study, we evaluated the effect of six capsules of fish oil (1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid) versus six capsules of corn oil (3 g linoleic acid), administered for 4 months, on walking distances, pressure indices during rest and after exercise, blood pressure, red cell deformability, fibrinogen, and lipid levels in 32 patients with stable claudication. No significant changes in walking distances and pressure indices during rest and after exercise occurred, despite a significant increase in red cell deformability in the fish oil group. Fibrinogen levels did not change in either group. In the fish oil group, a favorable change in blood lipids was noted; high-density cholesterol increased and triglycerides decreased. Mean arterial blood pressure declined to a similar extent in both groups. Thus, short-term supplementation with fish oil does not lead to clinically significant improvement of symptoms in patients with stable claudication. This suggests that red cell deformability is of minor importance in the arterial blood flow in the legs of these patients. Diets enriched with fish oil may favorably affect the vascular perturbations underlying synthetic graft thrombosis. Therefore, these studies were designed to test the hypothesis that diets enriched with fish oil would decrease the incidence of thrombosis in newly constructed polytetrafluorethylene grafts. A double-blind, randomized trial was conducted. Twenty-four patients were randomized to receive 4000 mg of fish oil or 4000 mg of control oil. Both preparations were enriched with antioxidants and deodorized with peppermint. Patients began therapy within 2 wk after graft placement and were monitored for 12 mo or until thrombosis developed. With a permuted-block randomization schedule, 12 patients received fish oil and 12 patients received control oil. The primary patency rates at 365 d were 14.9% for the control group and 75.6% for the fish oil-treated group. Survival analysis revealed a significant difference between fish oil-treated and untreated patients (P < 0.03, Mantel-Cox test), with a power of 90%. Moreover, analysis of covariables, including age of > or =50 yr, gender, race, body weight, diabetes mellitus, bleeding times, and lipid profiles, indicated that this effect occurred principally as a result of fish oil administration. Importantly, fish oil treatment also decreased venous outflow resistance and systemic BP, compared with control values. Fish oils possess unique biologic properties that favorably affect the incidence of polytetrafluorethylene graft thrombosis, and they thus represent a potential treatment strategy for the prevention of access thrombosis.
The current data does not allow for a definitive conclusion regarding the efficacy of fish oil. There is no adequate information to make recommendations for clinical practice. More research is required.