Omega-3 Fatty Acids in Cardiovascular Disease

Re-assessing the Evidence

Alan Begg; Susan Connolly; Julian Halcox; Agnes Kaba; Linda Main; Kausik Ray; Henry Purcell; Helen Williams; Derek Yellon

Disclosures

Br J Cardiol. 2012;19(2):79-84. 

In This Article

How Do Fish Oils Work?

Omega-3 PUFAs are essential dietary components and have a number of biological actions. It is not known exactly how they exert their clinical benefits but they have a multitude of effects (Table 2), reviewed in detail by Mozaffarian and Wu.[13] These include lowering blood pressure, serum triglycerides, inflammatory markers and coagulability; reducing heart rate and increasing heart rate variability; enhancing insulin sensitivity and endothelial function; and anti-arrhythmic and plaque-stabilising effects, which have the potential to improve cardiovascular health and reduce the risk of clinical events. There is also indirect evidence that, by reducing the rate of telomere shortening, omega-3 PUFAs may slow biological ageing.

Triglyceride Lowering

The well-recognised effect of omega-3 PUFAs on triglyceride lowering shows this to be a linear and dose-dependent effect, but with variable individual dose responses. Doses of at least 2 g/day are required to achieve a meaningful reduction, and greater absolute reductions are seen in those with higher baseline triglyceride levels.[13]

Antithrombotic Effects

Omega-3 PUFAs are considered to have antithrombotic effects based on observation of increased bleeding times at very high doses (e.g. 15 g/day) but in clinical trials they have shown no consistent effects on platelet aggregation or coagulation factors.[13]

The panel felt that at doses of up to 4 g/day, antithrombotic effects are unlikely to be a major pathway for lower cardiovascular risk, but subtle effects cannot be excluded.[13]

Endothelial Function

Omega-3 consumption increases nitric oxide (NO) bioavailability with several trials demonstrating improved flow-mediated arterial dilatation, a measure of improved endothelial function. Autonomic function, as a consequence of augmentation of vagal tone may also be improved.[13]

Heart Failure

Increases in cardiac ejection fraction have been observed in heart failure patients taking omega-3 PUFAs.[14,15]

Insulin Resistance/anti-inflammatory

The biological effects of omega-3 PUFAs on insulin resistance (marginally adverse or otherwise) are currently unclear. Similarly, it is not known whether their well-recognised anti-inflammatory effects are clinically meaningful.[13]

Anti-arrhythmic Effects

The anti-arrhythmic activity of omega-3 PUFAs has been challenging to document in human studies.[13] Animal experiments suggest that omega-3 PUFAs directly influence atrial and ventricular electrophysiology, and that, by altering the function of membrane ion channels (e.g. L-type Ca2+ channels, Na+/Ca2+ exchanger) or 'cell–cell conexins', they may contribute to reduced myocyte excitability, potentially reducing arrhythmia triggering (Figure 1).

Figure 1.

Diagram to show possible mechanisms of anti-arrhythmic effects that may be associated with omega-3 polyunsaturated fatty acids

The panel concluded that the clinically relevant mechanisms by which omega-3 PUFAs influence arrhythmia are unknown. They noted the data showing a dose-effect with a fish-enriched diet and a reduction in arrhythmias. They agreed there was evidence of health benefits in randomised clinical trials with omega-3 PUFA supplementation, but noted many trials were not conducted on top of a background of contemporary therapy. In addition, the panel noted the use of a wide range of supplement preparations and dietary interventions which had provided variable doses of omega-3 intake, making the clinical relevance of their effects difficult to interpret, not only for patients, but also for some healthcare professionals.

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