Fish oil and ischemic heart disease.

Fish oil products are available with or without prescription and are widely used by patients with ischaemic heart disease (IHD). The interest in fish oils, rich in the long chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (n-3 20:5) and docosahexaenoic acid (n-3 22:6), originates primarily from the pioneering work of Dyerberg and Bang.' Prompted by the low incidence of acute myocardial infarction in Eskimos in Greenland they suggested that a very high dietary intake of n-3 PUFA's from marine food offered protection against IHD. They showed that the Eskimos had a beneficial lipid pattern and that their balance between pro-aggregatory thromboxanes and anti-aggregatory prostacyclins was shifted towards an anti-thrombotic state compared with Danes.' There is also evidence from Japan and Holland that dietary intake of fishprotects against IHD.2 In the American MRFIT study the daily intake of n-3 PUFA was inversely related to IHD mortality in middle-aged men.3 However, no such relation was found in the American Physicians' Health Study.4 Experimental studies of atherogenesis and arterial thrombogenesis in various animal species lend some support to the hypothesis that dietary intake of n-3 PUFA's may play a part in primary or secondary prevention of IHD or both.5 but probably also because of increased synthesis of prostacyclins.59 Studies in pigs indicated that n-3 PUFAs can stimulate the synthesis of endothelium-derived relaxing factor.'0 This may contribute to the favourable change in the interaction between platelets and the vessel wall and may also be partly responsible for the reduction in blood pressure shown after dietary supplementation with n-3 PUFA in patients with mild hypertension." 12 The risk of clinically significant episodes of bleeding is very low2 13-probably lower than after a low dose of aspirin. The synthetic activity of leucocytes is reduced after intake of fish oil mainly because the production of bioactive leukotrienes is decreased.'4 Both synthesis of interleukin-l and tumour necrosis factor by mononuclear cells'5 and of platelet-derived growth-factorlike protein by endothelial cells'6 are inhibited after intake of n-3 PUFA. There is evidence that n-3 PUFAs reduce blood viscosity.'7 Fish oil may impair fibrinolysis by increasing the plasma concentration of plasminogen activator inhibitor. This has also been shown for patients with IHD7 and is a potentially negative effect of fish oil supplements. The modulation of inflammatory responses could theoretically increase the risk of infection and cancer, but there are no clinical data to support this.