Dietary fish oil decreases superoxide generation by human neutrophils: relation to cyclooxygenase pathway and lysosomal enzyme release.

12 volunteers with slightly elevated serum triglyceride levels were given 30 ml fish oil (5.4 g eicosapentaenoic acid and 3.2 g docosahexaenoic acid) daily for 4 weeks. The percentage of eicosapentaenoic acid increased (P < 0.01) and the percentage of linoleic (P < 0.05) and arachidonic acid (P < 0.01) decreased in neutrophil phospholipids. Superoxide generation by neutrophils initiated by phorbol myristate acetate decreased significantly from 48.6 +/- 8.8 to 34.7 +/- 11.1 nmol/10 min/400,000 cells (means +/- SD, P < 0.01, n = 11). Treatment of the cells with the cyclooxygenase inhibitor indomethacin had no significant influence on the decrease in superoxide generation, indicating that cyclooxygenase products were not involved in this effect of fish oil. Neutrophil elastase release did not change significantly, suggesting that neutrophil lysosomal enzyme release and superoxide generation may be under separate control. In conclusion, dietary fish oil decreased superoxide generation by human neutrophils without involvement of the cyclooxygenase pathway and without altering neutrophil lysosomal enzyme release. Dietary fish oil could have beneficial effects in pathological conditions with activated neutrophils, such as ischaemic heart disease.

Whole blood production of thromboxane, prostacyclin and leukotriene B4 after dietary fish oil supplementation in man: effect of vitamin E.

12 subjects were given 30 ml/day of a fish oil already stabilized with vitamin E (1.5 IU/g) and other natural antioxidants (fish oil, FO), and the same fish oil supplemented with extra vitamin E (to total 4.5 IU/g) (FO+E), in a randomized double-blind cross-over study. The whole blood production of thromboxane B2, measured in serum, was reduced after 4 weeks of ingestion of both FO+E (by 47%, P < 0.01) and of FO (by 40%, P < 0.05) whereas 6-keto-PGF1 alpha increased slightly in both cases, by 4% and 5% respectively, both NS. Leukotriene B4 production decreased on both FO+E (by 20%, NS) and FO (by 17%, P < 0.05). This study thus showed that a stabilized fish oil had marked effects on eicosanoid production, which may be important for its cardiovascular effect. Further supplementation with vitamin E had no additional effect, indicating that the vitamin E content (1.5 IU/g) in this stabilized fish oil might have been optimal.

Fatty acid composition in total phospholipids of human coronary arteries in sudden cardiac death.

A study was made of the fatty acid composition of the total phospholipid fraction of human coronary arteries in 30 cases of sudden cardiac death due to ischaemic heart disease (aged 40 +/- 5 years, mean +/- S.D.) and in 29 controls (mostly traffic accident victims, aged 45 +/- 6 years). The coronary arteries from cases of sudden cardiac death showed more atherosclerotic lesions than those of controls (P < 0.001). The percentages of palmitic acid (16:0) and linoleic acid (18:2(n-6)) were significantly higher and the percentage of arachidonic acid (20:4(n-6)) and of all the other major polyunsaturated fatty acids, both n-6 and n-3, was significantly lower in cases of sudden cardiac death than in controls. In conclusion, this study showed increased percentages of saturated and reduced percentages of polyunsaturated fatty acids, except linoleic acid, in total phospholipids of human coronary arteries in cases of sudden cardiac death. The results suggest an impaired metabolism of linoleic acid, possibly due to a decreased delta-6-desaturase activity in the coronary artery wall in cases of sudden cardiac death.

Leukocyte elastase inhibition and t-PA-induced coronary artery thrombolysis in dogs: beneficial effects on myocardial histology.

Leukocyte-derived elastase is released following coronary artery occlusion and reperfusion and may contribute to reperfusion-related myocardial injury. Leukocyte infiltration into the reperfused myocardium may also contribute to ischemic injury following reflow. In the present study, we examined the effects of tissue-plasminogen activator (t-PA, 1 mg/kg over 20 minutes) given intravenously with either saline or a leukocyte elastase inhibitor (ICI 200,880, 5 mg/kg) in dogs with electrically-induced coronary artery thrombosis. ICI 200,880 administration increased elastase inhibitory activity without affecting t-PA and plasminogen activator inhibitor (PAI-1) activities. Time to reflow, magnitude of peak coronary blood flow, and duration of reflow were not different in dogs given t-PA with saline or with the elastase inhibitor. However, administration of the elastase inhibitor decreased the histologically-determined leukocyte infiltration and severity of myocardial injury in dogs subjected to coronary artery thrombosis and subsequent thrombolysis. These early observations suggest that elastase release during reperfusion may be an important mediator of anoxia-reoxygenation-mediated tissue injury.

The effects of fish oil on triglycerides, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E.

The effects of fish oils supplemented with 0.3 IU/g and 1.5 IU/g of vitamin E were compared in a double-blind, cross-over study. Twelve healthy volunteers were given 30 mL/day of either oil for 3 wk. Intake of the vitamin E-rich fish oil resulted in a marked decrease in serum triglycerides (48%) and in fibrinogen (11%). After administration of the low vitamin E-containing oil there was a considerably smaller reduction of serum triglycerides and no significant reduction of fibrinogen. Both oils caused an increase in high density lipoprotein cholesterol and a decrease in the atherogenic index, but neither oil altered the total cholesterol level. Serum vitamin E was decreased by 9% and plasma malondialdehyde was increased by 122% after intake of the low vitamin E-containing oil, but both remained normal after intake of the other oil. The effect of vitamin E may be due to inhibition of fatty acid peroxidation with less formation of malondialdehyde and a larger amount of active (n-3) fatty acids in their sites of action in the liver, resulting in a greater decrease in the synthesis of triglycerides and fibrinogen.

Effects of dietary supplementation with vitamin E on human neutrophil chemotaxis and generation of LTB4.

Three weeks' dietary supplementation with a moderate dose of vitamin E (45 IU DL-alpha-tocopherol acetate daily), in eight healthy volunteers significantly increased the serum vitamin E level from 12.3 +/- 3.3 to 16.2 +/- 3.7 mg/L (means +/- SD) and significantly decreased neutrophil chemotaxis from 15 +/- 3 to 4 +/- 1 micron/h (means +/- standard error of the means). Generation of leukotriene B4 was not influenced by vitamin E, suggesting that the decrease in neutrophil chemotaxis was not due to blockage of the lipoxygenase pathway. Neither was the plasma malondialdehyde concentration influenced by vitamin E, contradicting the possibility of an antioxidant effect of vitamin E. As one early event in neutrophil chemotaxis is an increase in intracellular calcium concentration resulting from increased membrane permeability, it is possible that vitamin E influenced chemotaxis by a stabilizing effect on the neutrophil membrane, rather than by its antioxidant effect. Vitamin E supplementation could thus be beneficial in pathological conditions with activated neutrophils, such as ischaemic heart disease.

Effects of a new fluid fish oil concentrate, ESKIMO-3, on triglycerides, cholesterol, fibrinogen and blood pressure.

Eskimos have a very low incidence of cardiovascular disease, at least in part due to a high intake of n-3 fatty acids. ESKIMO-3 is a new stabilized (insensitive to oxidation) fluid fish oil concentrate, 30 ml of which contains an amount of eicosapentaenoic acid and total n-3 fatty acids equivalent to the daily intake among Eskimos. Thirty-three volunteers, healthy or with coronary artery disease, were given ESKIMO-3, at a dose of 15 or 30 ml d-1, corresponding to 2.7 or 5.4 g of eicosapentaenoic acid d-1, or placebo oil, for a period of up to 6 months. ESKIMO-3 had a pronounced dose-dependent effect on several risk factors for coronary artery disease. Intake of one tablespoon (15 ml) daily for 6 months significantly reduced levels of triglycerides (-64%), total cholesterol (-8%), plasma fibrinogen (-23%) and diastolic blood pressure (-9%). Bleeding time was unchanged. Intake of two tablespoons daily for 4 weeks increased plasma eicosapentaenoic acid levels by 490%, and decreased arachidonic acid by 20%. The HDL concentration increased by 21%. No change in the above mentioned variables was observed after intake of placebo oil.