Do fish oils prevent restenosis after coronary angioplasty? Biological effects of a dietary omega-3 polyunsaturated fatty acids supplementation in cystic fibrosis patients: a randomized, crossover placebo-controlled trial. Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma. Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk of prostate cancer. Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects. Fatty-acid composition of serum lipids predicts myocardial infarction. Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia.
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. Various anti-inflammatory therapies, including dietary omega-3 polyunsaturated fatty acids (PUFA) supplementation, have been investigated in cystic fibrosis (CF) patients. To further explore this nutritional approach, biological effects of an omega-3 PUFA oral liquid supplementation were measured in 17 CF patients in a double-blind, randomized, crossover without a washout period and placebo-controlled study.
                CF patients (age: 18+/-9 year; weight: 43+/-13 kg) received a liquid dietary supplementation either enriched or not in omega-3 PUFA (390-1170 mg/day according to patient weight) during two 6-month periods.
                Increase in eicosapentaenoic acid was observed in neutrophil membrane following omega-3 PUFA dietary supplementation (from 0.7+/-0.6 to 1.6+/-0.6 micromol%, P<0.01). The leukotriene B(4) (LTB(4))/leukotriene B(5) (LTB(5)) ratio was decreased (from 72+/-27 to 24+/-7, P<0.001) in CF patients taking omega-3 PUFA supplements. In contrast, omega-3 PUFA supplementation affected neither internalization of IL-8 receptors following IL-8 exposure, nor IL-8-induced neutrophil chemotaxis.
                Our results show that omega-3 PUFA are incorporated in neutrophil membranes. The subsequent decrease in LTB(4)/LTB(5) ratio suggests that, in such conditions, neutrophils may produce less pro-inflammatory mediators from the acid arachidonic pathway. These data indicate that omega-3 PUFA intake may have anti-inflammatory effect that still need to be assessed by long-term studies following large groups of patients. Omega-3 polyunsaturated fatty acids have anti-inflammatory effects in vitro, and high dietary levels are associated with a lower incidence of inflammatory diseases. However, only limited effects have been demonstrated in asthma. The effects of dietary supplementation with fish oil for 10 months in 29 children with bronchial asthma was investigated in a randomized controlled fashion. In order to minimize the effects of environmental inhaled allergens and diet, this study was performed in a long-term treatment hospital. Subjects received fish oil capsules containing 84 mg eicosapentaenoic acid (EPA) and 36 mg docosahexaenoic acid (DHA) or control capsules containing 300 mg olive oil. The daily dosages of EPA and DHA were 17.0-26.8 and 7.3-11.5 mg x kg body weight(-1), respectively. Asthma symptom scores decreased and responsiveness to acetylcholine decreased in the fish oil group but not in the control group. In addition, plasma EPA levels increased significantly only in the fish oil group (p<0.0088). No significant side-effects were observed. The present results suggest that dietary supplementation with fish oil rich in the omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid is beneficial for children with bronchial asthma in a strictly controlled environment in terms of inhalant allergens and diet. 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. Dietary supplementation with fish oils high in the omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, may have an antiinflammatory effect. We determined whether patients with cystic fibrosis (CF) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects. In this double-blind study, 12 patients with pancreatic insufficiency who have CF (mean age, 12.2 +/- 5.4 (SD) years) and 13 subjects without CF (mean age, 13.4 +/- 6.3 (SD) years) were randomly assigned to ingest 8 gm daily of either encapsulated fish oil (3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily) or olive oil ethyl esters for 6 weeks. Two of seven and two of five patients with CF who received fish and olive oils, respectively, and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea. Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF randomly assigned to the fish oil treatment. For example, in subjects randomly assigned to receive fish oil, the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold, from 0.04 +/- 0.02 (mean +/- SEM) to 0.39 +/- 0.11 (p = 0.02), in the patients with CF (n = 7) and 23.0-fold, from 0.04 +/- 0.01 to 0.92 +/- 0.17 (p = 0.001), in the subjects without CF (n = 8) who received fish oil (p = 0.02, patients with CF vs subjects without CF at 6 weeks). No clinically or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil. Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinically beneficial antiinflammatory effect in patients with CF. 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. Evidence that the metabolism of phospholipids and polyunsaturated fatty acids (PUFA) is abnormal in schizophrenia provided the rationale for intervention studies using PUFA supplementation. An initial open label study indicating efficacy for n-3 PUFA in schizophrenia led to two small double-blind pilot studies. The first study was designed to distinguish between the possible effects of two different n-3 PUFA: eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA). Forty-five schizophrenic patients on stable antipsychotic medication who were still symptomatic were treated with either EPA, DHA or placebo for 3 months. Improvement on EPA measured by the Positive and Negative Syndrome Scale (PANSS) was statistically superior to both DHA and placebo using changes in percentage scores on the total PANSS. EPA was significantly superior to DHA for positive symptoms using ANOVA for repeated measures. In the second placebo-controlled study, EPA was used as a sole treatment, though the use of antipsychotic drugs was still permitted if this was clinically imperative. By the end of the study, all 12 patients on placebo, but only eight out of 14 patients on EPA, were taking antipsychotic drugs. Despite this, patients taking EPA had significantly lower scores on the PANSS rating scale by the end of the study. It is concluded that EPA may represent a new treatment approach to schizophrenia, and this requires investigation by large-scale placebo-controlled trials.
Three updates of this review have resulted in more included studies and more people randomised but still relatively little useful additional data. The results remain inconclusive. The new trials all compare the omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid and its ester, ethyl-eicosapentaenoic acid. The use of omega-3 polyunsaturated fatty acids for schizophrenia still remains experimental and this review highlights the need for large, well designed, conducted and reported studies.