Fish oil supplementation in patients with stable claudication. EDTA treatment of intermittent claudication--a double-blind, placebo-controlled study. Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study. Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma in children. Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled 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. A double-blind, randomized multicentre study was undertaken to evaluate the possible effect of chelation treatment with ethylenediamine-tetraacetic acid (EDTA) in patients with severe intermittent claudication. A total of 153 patients received 20 intravenous infusions of either 3 g Na2EDTA or placebo during a period of 5-9 weeks. Vitamin, mineral and trace element supplements were administered orally. The changes observed in the pain-free and maximal walking distances, measured on a treadmill, were similar in the two groups. During the 3-month (n = 149) and 6-month (n = 123) follow-up period, no long-term therapeutic effect of EDTA could be demonstrated. The ankle-brachial blood pressure index remained unchanged throughout the study period. This study failed to demonstrate any effect of EDTA chelation treatment in intermittent claudication. An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits. We assessed the clinical and biochemical effects in asthmatic children of fish oil supplementation and a diet that increases omega-3 and reduces omega-6 fatty acids. Thirty nine asthmatic children aged 8-12 yrs participated in a double-blind, randomized, controlled trial for 6 months during which they received fish oil capsules plus canola oil and margarine (omega-3 group) or safflower oil capsules plus sunflower oil and margarine (omega-6 group). Plasma fatty acids, stimulated tumour necrosis factor alpha (TNFalpha) production, circulating eosinophil numbers and lung function were measured at baseline and after 3 and 6 months of dietary modification. Day and night symptoms, peak flow rates and medication use were recorded for 1 week prior to laboratory visits. Plasma phospholipid omega-3 fatty acids were significantly greater in the omega-3 group at 3 and 6 months compared to the omega-6 group (p<0.001). In the omega-3 group TNFalpha production fell significantly compared with baseline (p=0.026), but the magnitude of change between groups did not reach significance (p=0.075). There were no significant changes in clinical outcome measures. Dietary enrichment of omega-3 fatty acids over 6 months increased plasma levels of these fatty acids, reduced stimulated tumour necrosis factor alpha production, but had no effect on the clinical severity of asthma in these children. epidemiological studies suggest polyunsaturated fatty acids protect against the development of atherosclerosis. The aim of this study was to perform a randomized controlled trial of gamma-linolenic and eicosapentaenoic acids in patients with lower limb atherosclerosis. Main outcome measures were: cholesterol and lipoprotein concentrations; haemostatic and rheological variables; the ankle brachial pressure index; walking distance; and cardiovascular events and death.
                120 men and women with stable intermittent claudication were randomized to 2 years treatment with either a combination of gamma-linolenic and eicosapentaenoic acids, or placebo.
                39 (65.0 cent) of those taking fatty acids and 36 (60.0 cent) of those taking placebo completed the trial. Lipid concentrations did not differ significantly during the trial. In those taking fatty acids, haematocrit was significantly higher than in the placebo group after 6 months (46.1 cent compared with 44.6 cent, P </= 0.01), and systolic blood pressure was significantly lower after 2 years (150|mmHg compared with 161.8|mmHg, </= 0.05). There was no difference in walking distance, but there was a small reduction in non-fatal coronary events in the fatty acid group (10 cent compared with 15 cent, P > 0.05).
                a combination of polyunsaturated fatty acids produced a statistically significant reduction in systolic blood pressure, but no other significant benefits on risk factors. The trend towards fewer coronary events in those taking fatty acids warrants further investigation. 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.
Omega-3 fatty acids appear to have little haematological benefit in people with intermittent claudication and there is no evidence of consistently improved clinical outcomes (quality of life, walking distance, ankle brachial pressure index or angiographic findings). Supplementation may also cause adverse effects such as nausea, diarrhoea and flatulence. Further research is needed to evaluate fully short- and long-term effects of omega-3 fatty acids on the most clinically relevant outcomes in people with intermittent claudication before they can be recommended for routine use.