n−3 Fatty acids, cardiac arrhythmia and fatal coronary heart disease

Abstract

n−3 Polyunsaturated fatty acids (n−3 PUFA) are suggested to prevent cardiac death via inhibition of cardiac arrhythmia. In this review we discuss the results of human studies on intake of n−3 PUFAs and heart disease and, more specifically, on cardiac arrhythmia.

Observational studies indicate that intake of fish is associated with a lower incidence of fatal coronary heart disease in several populations. These studies are fairly consistent, but people that have a high intake of fatty fish might have a healthier lifestyle in general, and such confounding is difficult to remove completely with statistical adjustments and corrections. Evidence from trials is less clear. In two open label trials in patients with a previous myocardial infarction intake of fish or fish oil prevented fatal coronary heart disease. In contrast, a trial in patients with angina suggested a higher risk of sudden cardiac death in patients taking fish oil. Furthermore, results of trials in patients with an implantable cardioverter defibrillator (ICD) that investigated effects of fish oil on arrhythmia in patients already suffering from ventricular tachycardia are not consistent. Also, studies on relationships between intake of n−3 PUFA from fish and less life-threatening forms of arrhythmia, such as atrial fibrillation and premature ventricular complexes (PVCs) are equivocal. Thus, after 35 years of research the question whether fish prevents heart disease remains unanswered, and an anti-arrhythmic effect of fish oil remains unproven although the idea is still viable and is being actively tested in further trials.

Introduction

n−3 Polyunsaturated fatty acids (n−3 PUFA), also known as ω−3 fatty acids, are fatty acids with the first double bound at the third position from the methyl end. They occur in the diet as α-linolenic acid (ALA, C18:3n−3) from vegetable sources and nuts, and as very-long-chain ‘marine’ n−3 PUFA from fish and other seafood. The main forms of marine n−3 PUFA are eicosapentaenoic acid (EPA, C20:5n−3) and docosahexaenoic acid (DHA, C22:6n−3). Typical intake in Western populations is 1–2 g per day for ALA and 0–0.4 g per day for marine n−3 PUFA. n−3 PUFA are ‘essential’ nutrients; they cannot be synthesized by the body but are needed, particularly, for the formation of the retina and of the brain. The minimum dietary amount sufficient to prevent deficiencies is in the order of 0.2% of daily calorie intake (0.2 en%) which is equivalent to about 0.5 g per day. ALA can be converted to EPA and DHA in the human body. However, the extent of this conversion is not precisely known and, at best, very limited.

Evidence from observational studies and controlled trials indicates that, in addition to their effects as essential nutrients, intake of the marine very long-chain n−3 PUFA reduces the risk of fatal coronary heart disease and, in particular, of sudden cardiac death [1], [2], [3], [4], [5]. Sudden cardiac death forms a major part of mortality from cardiovascular disease and is, in most cases, a direct consequence of cardiac arrhythmia [6]. n−3 PUFA may exert their protective effects through reducing the susceptibility to cardiac arrhythmia. Here, we discuss the results of human studies on the effect of n−3 PUFAs on heart disease and, more specifically, on cardiac arrhythmia.