The effects of omega-3 polyunsaturated fatty acids on cardiac rhythm: a critical reassessment

Pharmacol Ther. 2013 Oct;140(1):53-80. doi: 10.1016/j.pharmthera.2013.05.011. Epub 2013 Jun 2.


Although epidemiological studies provide strong evidence for an inverse relationship between omega-3 polyunsaturated fatty acids (n-3 PUFAs) and cardiac mortality, inconsistent and often conflicting results have been obtained from both animal studies and clinical prevention trials. Despite these heterogeneous results, some general conclusions can be drawn from these studies: 1) n-PUFAs have potent effects on ion channels and calcium regulatory proteins that vary depending on the route of administration. Circulating (acute administration) n-3 PUFAs affect ion channels directly while incorporation (long-term supplementation) of these lipids into cell membranes indirectly alter cardiac electrical activity via alteration of membrane properties. 2) n-3 PUFAs reduce baseline HR and increase HRV via alterations in intrinsic pacemaker rate rather than from changes in cardiac autonomic neural regulation. 3) n-3 PUFAs may be only effective if given before electrophysiological or structural remodeling has begun and have no efficacy against atrial fibrillation. 5) Despite initial encouraging results, more recent clinical prevention and animal studies have not only failed to reduce sudden cardiac death but actually increased mortality in angina patients and increased rather than decreased malignant arrhythmias in animal models of regional ischemia. 6) Given the inconsistent benefits reported in clinical and experimental studies and the potential adverse actions on cardiac rhythm noted during myocardial ischemia, n-3 PUFA must be prescribed with caution and generalized recommendations to increase fish intake or to take n-3 PUFA supplements need to be reconsidered.

Keywords: AF; AFL; ALA; APD; Atrial fibrillation; BP; CICR; Ca-ATs; DADs; DHA; DPA; Docosahexaenoic acid; EADs; EPA; ERP; Eicosapentaenoic acid; HR; HRV; Heart rate variability; ICDs; MI; MSNA; Omega-3 polyunsaturated fatty acids; RBC; RYRs; SR; VF; VT; Ventricular fibrillation; action potential duration; alpha-linolenic acid; atrial fibrillation; atrial flutter; blood pressure; calcium aftertransients; calcium induced calcium release; delayed afterdepolarizations; docosahexaenoic acid; docosapentaenoic acid; early afterdepolarizations; effective refractory period; eicosapentaenoic acid; heart rate; heart rate variability; implantable cardioverter defibrillators; muscle sympathetic nerve activity; myocardial infarction; n−3 PUFAs; n−6 PUFAs; omega-3 polyunsaturated fatty acids; omega-6 polyunsaturated fatty acids; red blood cell; ryanodine receptors; sarcoplasmic reticulum; ventricular fibrillation; ventricular tachycardia.

Publication types

  • Review

MeSH terms

  • Animals
  • Atrial Fibrillation / drug therapy
  • Fatty Acids, Omega-3 / pharmacology*
  • Fatty Acids, Omega-3 / therapeutic use
  • Heart / drug effects*
  • Heart / physiology
  • Heart Rate / drug effects
  • Humans
  • Ventricular Fibrillation / drug therapy


  • Fatty Acids, Omega-3