Polyunsaturated Fatty Acids In Fish Oil Research Articles

Does vegetable oil attenuate the beneficial effects of fish oil in reducing risk factors for cardiovascular disease?

Contradictory reports on the protective effect of fish consumption on cardiovascular disease (CVD) risk could be due to variations in the intake of n-3 and n-6 polyunsaturated fatty acids (PUFAs). Metabolic competition between n-3 and n-6 PUFAs suggests that n-6 PUFAs in vegetable oils could attenuate the efficacy of n-3 PUFAs in fish oil to favorably alter endpoints relevant to CVD risk. We determined the effects of varying dietary amounts of fish oil on lipid and thrombotic endpoints relevant to risk factors for CVD and whether these effects were attenuated by vegetable oils. Two randomized, double-blind, placebo-controlled, parallel studies were conducted in human subjects fed varying amounts of n-3 and n-6 PUFAs; n-3 PUFA intake was varied by using fish or placebo oil capsules, and n-6 PUFA intake was modified by incorporating varying amounts of safflower oil into the diet. Endpoints included changes in membrane fatty acid composition, blood lipids, and thrombotic profile. The results indicated that absolute amounts of fish oil, and not the relative amounts of fish and vegetable oil (ratios of n-3 to n-6 PUFAs), determined the magnitude of the reduction of arachidonic acid and increase in eicosapentaenoic acid in phospholipids of plasma and platelets. The suppression of plasma triacylglycerols by fish oil was not affected by varying amounts of dietary n-6 PUFAs. Fibrinogen concentrations decreased with 15 g but not with 9 g fish oil/d fed at the same ratio of n-3 to n-6 PUFAs. The efficacy of fish oil in favorably modifying certain risk factors for CVD was not attenuated by vegetable oil.

N-3 Fish Oil Polyunsaturated Fatty Acids and Bleeding

Moderate intakes of n-3 fish oil polyunsaturated fatty acids (PUFAs) may reduce the risk of coronary heart disease by lowering the prothrombotic tendency of platelets and endothelial cells by regulating arachidonic acid metabolism. Concern that moderate fish oil intakes might reduce platelet aggregation to the extent of enhancing bleeding tendency and increasing the risk of haemorrhagic stroke appears to be unfounded however. Even though some studies have measured significantly decreased platelet aggregation and prolonged bleeding times the values have remained within normal limits. Moreover, epidemiological data from Japan, where haemorrhagic stroke incidence is comparatively high, show that in those areas with higher fish consumption, the risk of brain haemorrhage is lower, a finding that has been confirmed in other countries. In clinical intervention studies with n-3 fish oil PUFAs there was no evidence of abnormal bleeding tendency even though the concentrations used were up to nine times the recommen...

High Peroxidative Susceptibility of Fish Oil Polyunsaturated Fatty Acid in Cultured Rat Hepatocytes

The peroxidative susceptibility in cultured rat hepatocytes of eicosapentaenoic acid (EPA) and other polyunsaturated fatty acids (PUFA) with different numbers of double bonds was examined. Lipid peroxidation was evaluated using a newly developed HPLC procedure which includes the determination of malondialdehyde (MDA). Following exposure to 0.25-1.0 mM EPA adsorbed to BSA (EPA-BSA), cultured hepatocytes produced MDA in the fatty acid concentration- and incubation time-dependent manner. The rate of MDA production by hepatocytes varied greatly with the degree of PUFA unsaturation, and ranked as follows: docosahexaenoic acid > EPA > arachidonic acid > α-linolenic acid = γ-linolenic acid > linoleic acid > oleic acid. Prolonged exposure of cultured hepatocytes to 1.0 mM EPA-BSA resulted in substantial leakage of LDH into the medium. The cell injury was associated with the loss of cellular GSH and protein thiol groups. Cotreatment of the EPA-supplemented hepatocytes with a GSH-depleting agent, diethylmaleate, promoted the cellular protein thiol loss and LDH leakage. An iron chelator, deferoxamine, and other antioxidants such as N,N-diphenyl- p-phenylenediamine and γ-tocopherol efficiently prevented MDA production and consequently LDH leakage in the EPA-supplemented hepatocytes. These results show that peroxidative deterioration in excess of GSH-dependent defense mechanisms may occur in hepatocytes loaded with highly peroxidizable fish oil PUFA.

Differential effects of dietary fish oil on myocardial prostaglandin I2 and thromboxane A2 production

Marmoset monkeys (Callithrix jacchus) were maintained for 24 mo on a standard primate diet [reference (Ref) diet] or this diet supplemented (8% wt/wt) with either sheep fat (SF), sunflower seed oil (SSO), or tuna fish oil (TFO). The polyunsaturated fatty acids (PUFA) of myocardial phospholipids demonstrated significant alterations as a result of the dietary (n-3) or (n-6) lipid supplementation. The reduction (P less than 0.05) in prostaglandin (PG) I2 in PUFA diet-fed groups (SSO, 113.8 +/- 7.8; TFO, 87.9 +/- 8.2 compared with Ref, 153.9 +/- 7.4 pg/mg dry wt) seems to be due to the rate limitation of the endogenous substrate, because the addition of exogenous arachidonic acid (AA) has obliterated the dietary difference. However, AA did not increase the basal PGI2 production in the Ref or SF dietary groups, which differed from that for thromboxane (Tx) A2 where 2- to 5-fold stimulation was observed. It is suggested that there exists a preferential channeling mechanism to direct AA derived from phospholipase hydrolysis of membrane phospholipids toward PGI2 synthesis. Conversely, the bulk of the AA for TxA2 biosynthesis appears to be supplied by a cytosolic nonesterified fatty acid pool. The effective replacement of AA of this pool and a specific inhibition of TxA2 synthetase enzyme complex by the (n-3) PUFA of fish oil are offered as likely mechanisms for the greater inhibition of TxA2 compared with PGI2 production observed in the present and previous studies. The present data on myocardial eicosanoids correlate well with the beneficial qualities of (n-3) and (n-6) dietary PUFA on cardiac function that we have reported previously.

Insulin-tumour interrelationships in EL4-lymphoma or thymoma-bearing mice. II. Effects of dietary omega-3 and omega-6 polyunsaturated fatty acids

Male C57BL/65 mice received a basal diet supplemented with 4% soya-bean oil, linseed oil or fish oil, in which the major polyunsaturated fatty acids were linoleic acid, alpha-linolenic acid and long chain omega-3 fatty acids, respectively. Groups of animals were injected into the right flank with EL4-lymphoma cells, others with thymoma cells. Tumour implantation caused a gradual decrease in food consumption with both types of tumour, while body weight increased, especially in the EL4-bearing animals receiving the soya-bean diet. The weight gain was due to body water accumulation and was accompanied by decreases in body fat and minor changes in carcass protein and ash contents. The dietary treatments did not produce significant differences in tumour incidence and mortality, but tumour size was decreased by diets supplying omega-3 fatty acids: in the EL4 mice tumour weight was markedly depressed by linseed oil, compared to soya-bean oil, whereas thymoma tumour weight was lowest in mice receiving fish oil and highest in the soya-bean oil group. Both types of tumour caused pronounced hypoglycaemia and hyperinsulinaemia in the hosts, and the effect was modulated by the diets in the EL4 but not in the thymoma animals: the plasma glucose level was especially low in the linseed oil group and relatively highest in the soya-bean oil treatment. The degree of hyperinsulinaemia depended on the diet only in the thymoma-bearing mice, with linseed and fish oils producing higher insulin levels than soya-bean oil. A slight hyperinsulinaemia was also observed in linseed and fish oil-fed control mice. Serum triglycerides were elevated in tumour-bearing animals, without consistent differences between dietary treatments. Although no clear pattern emerged concerning total cholesterol and LDL levels, HDL values were strongly affected by the type of oil: in the control animals linseed oil caused an increase in HDL-cholesterol compared to the other two oils. The thymoma-bearing mice responded to the linseed and fish oil diets with greatly elevated HDL-cholesterol levels. The results point to important differences in the responses of the two implanted tumours and hosts not only to the omega-6 and omega-3 fatty acids, but also to the type of dietary omega-3 fatty acids, namely alpha-linolenic acid and long chain fish oil polyunsaturated fatty acids.

Guinea pig epidermis generates putative anti‐inflammatory metabolites from fish oil polyunsaturated fatty acids

Clinical studies have indicated that dietary fish oil may have therapeutic value in the treatment of psoriasis, a hyperproliferative, inflammatory skin disorder characterized by elevated LTB4. To evolve a possible mechanism for these beneficial effects, we determined the metabolic fate of fish oil derived n-3 fatty acids in the skin. Specifically, we incubated guinea pig epidermal enzyme preparations with [3H]eicosapentaenoic acid (20:5 n-3) and [14C]docosahexaenoic acid (22:6 n-3). Analyses of the radiometabolites revealed the transformation of these n-3 fatty acids into n-6 lipoxygenase (arachidonate 15-lipoxygenase) products: 15-hydroxyeicosapentaenoic acid (15-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDHE), respectively. Since 15-lipoxygenase products have been suggested as possible endogenous inhibitors of 5-lipoxygenase (an enzyme which catalyzes the formation of LTB4) we tested the ability of 15-HEPE and 17-HDHE in vitro to inhibit the activity of the 5-lipoxygenase. Incubations of these metabolites with enzyme preparations from rat basophilic leukemia (RBL-1) cells demonstrated that 15-HEPE (IC50 = 28 microM) and 17-HDHE (IC50 = 25 microM) are respectively potent inhibitors of RBL-I-5-lipoxygenase. The inhibitory potential of these fish oil metabolites provides a possible mechanism by which fish oil might act to decrease local cutaneous levels of LTB4, and thereby alleviate psoriatic symptoms.