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As precursors of eicosanoids, PUFAs found in fish oils exert a wide influence over many important physiological processes. CARDIOVASCULAR EFFECTS

Fish oils exert myriad different effects on the heart and vessels, which have been demonstrated in both experimental models and human studies. It is suspected that the summation of many small protective risk factor effects of omega-3 fatty acids adds up to a larger protective effect on mortality and/or cardiovascular events. Prevent malignant cardiac arrhythmias Dietary fish or fish oil intake has been shown to prevent cardiac arrhythmias and associated sudden death in numerous animal studies (Billman et al 1999, 1997, Kang & Leaf 1996, 2000, McLennan et al © 2007 Elsevier Australia

1988, 1990). This has been achieved using intakes below those required to alter plasma lipids or blood pressure. It appears that the myocardial membrane phospholipid content of DHA increases with fish intake, but not always EPA. The preferential accumulation of DHA affords protection against ventricular fibrillation induced under a variety of conditions such as ischaemia and reperfusion (McLennan 2001).

Inadequate DHA in myocyte membranes have been reported to be associated with altered sodium, calcium and potassium ion channel functions, mitochondrial function and increased arrhythmia susceptibility with an increased prevalence of sudden cardiac death (Siscovick et al 2003). One in vivo study suggests fish oils electrically stabilise myocytes, increasing the electrical impulse required to produce an action potential by approximately 50% and prolonging the refractory time by 1 50% (Kang & Leaf 2000).

Triglyceride-lowering activity Human studies have revealed the potent ability of EPA and DHA to reduce circulating levels of blood triglyceride levels significantly, which is of interest because only moderate elevations in triglyceride levels have been associated with a progressively increased risk of ischaemic heart disease, independent of other major risk factors including HDL-cholesterol (Jeppesen et al 1998). Lipoprotein effects Concerns raised previously about increased levels of the long-chain PUFAs in lipoproteins increasing the susceptibility to oxidation of the LDLs have recently been moderated, with a demonstrable difference between EPA and DHA on this outcome. While increased levels of EPA (4.8 g/day) did increase the LDL susceptibility to damage, DHA supplementation (4.9 g/day) had no effect on the oxidation process (Mesa et al 2004).

Improved endothelial function Studies have indicated that fish oils can improve endothelial relaxation by enhancing NO- and non-NO-induced vasodilatation (Holub 2002).

A double-blind study conducted by Mori et al (2000) showed that relative to placebo, DHA, but not EPA, enhances vasodilator mechanisms and attenuates constrictor responses in the forearm microcirculation.

Reduce blood pressure Two meta-analyses have concluded that fish oils exert a significant blood pressure-lowering effect in hypertensive people; however, the effects can only be described as modest, between 2 and 5 mmHg (Geleijnse et al 2002, Morris et al 1993). Hypotensive activity appears to be dose-dependent and DHA may have greater effect than EPA. Alternately, a 2006 Cochrane review found no significant changes to SBP or DBP with n-3 EFA consumption (Hooper et al 2006). The

review assessed studies that used both plant-and fish-based n-3 fatty acids, dietary sources and supplements.

The mechanism responsible is unknown; however, current theories include EPA stimulation of prostacyclin synthesis and increased NO production, both vasodilators. An additional action may be improved autonomic nervous system function, and inhibition of the adrenal activation (Din et al 2004, Ross 2005). Of the n-3 EFAs, hypotensive activity is attributed to DHA.

Reduce and possibly reverse atherogenesis Omega-3 fatty acids alter eicosanoid synthesis and inhibit smooth muscle cell proliferation, suggesting a role in reducing atherosclerotic development (Holub 2002). One controlled study demonstrated that fish oil ingestion had a clinically significant influence on atherosclerosis (von Schacky et al 2001). This randomised double-blind study of 223 patients found that a dose of 1.5 g n-3 fatty acids reduced progression and increased regression of established coronary artery disease as assessed by coronary angiography.

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