Electrophysiological Mechanisms of the Anti-arrhythmic Effects of Omega-3 Fatty Acids
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Heart rhythm disorders, or arrhythmias, are a leading cause of morbidity and mortality worldwide. Omega-3 polyunsaturated fatty acids (ω3PUFAs), commonly found in fish oils and plant seeds, have recently emerged as potential anti-arrhythmic agents. The purpose of this review is to summarize the electrophysiological basis of the anti-arrhythmic properties of ω3PUFAs from clinical, animal, and cellular research. Evidence of the anti-arrhythmic effects of ω3PUFAs originated from epidemiological studies that correlated a low incidence of sudden cardiac death with high dietary ω3PUFA intake. Subsequently, multiple clinical trials have confirmed the therapeutic effects of ω3PUFAs in preventing sudden cardiac death and multiple other arrhythmia-related disorders. This has led basic scientists to investigate the effects of ω3PUFAs on several ion channels including sodium, potassium, and calcium channels, as well as Na/Ca exchangers. Therefore, ω3PUFAs may hold promise as safe and effective anti-arrhythmic agents. Nevertheless, further research is needed in areas such as: (1) identifying which form(s) of ω3PUFAs (i.e., phospholipid, triglyceride, or free) is (are) responsible for anti-arrhythmic actions; and (2) developing reproducible methods for delivery so that the appropriate form and concentration may be present at the target site to prevent and treat arrhythmias.
KeywordsOmega-3 polyunsaturated fatty acids Anti-arrhythmic agent Heart rhythm disorder Sudden cardiac death
We acknowledge funding from the GAANN (Graduate Assistance in Areas of National Need) Program, US Department of Education; the Institute for Engineering in Medicine at the University of Minnesota; and the Qwest Program of Medtronic, Inc.
Eric Richardson was the recipient of GAANN funding for his graduate program at the University of Minnesota and is currently an employee of Medtronic, Inc.; Yong-Fu Xiao is employed by Medtronic, Inc.; Paul Iaizzo has a research agreement with Medtronic, Inc.
- 2.“Sudden cardiac death:” Available at: http://www.americanheart.org/presenter.jhtml?identifier=4741 Accessed 6 March 2009.
- 3.Lip, G. Y., & Godtfredsen, J. (2003). Cardiac arrhythmias. New York: Elsevier.Google Scholar
- 6.Pawlowsky, R. J., Hibbeln, J. R., Novotny, J. A., & Salem, N., Jr. (2001). Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. Journal of Lipid Research, 42, 1257–1265.Google Scholar
- 13.Brouwer, I. A., Zock, P. L., Camm, A. J., et al. (2006). Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the study on omega-3 fatty acids and ventricular arrhythmia (SOFA) randomized trial. Journal of the American Medical Association, 295, 2613–2619.CrossRefPubMedGoogle Scholar
- 20.Raitt, M. H., Connor, W. E., Morris, C., et al. (2005). Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: A randomized controlled trial. Journal of the American Medical Association, 293, 2884–2291.CrossRefPubMedGoogle Scholar
- 22.NIH. (2004). Working group report on future of clinical research directions on omega-3 fatty acids and cardiovascular disease.Google Scholar
- 24.“The Vitamin D and Omega-3 Trial (VITAL):” Available at: http://www.vitalstudy.org. Accessed on: 16 July 2010.
- 29.Billman, G. E., Nishijima, Y., Belevych, A. E., et al. (2010). Effects of dietary omega-3 fatty acids on ventricular function in dogs with healed myocardial infarctions: in vivo and in vitro studies. American Journal of Physiology. Heart and Circulatory Physiology, 298, H1219–H1228.CrossRefPubMedGoogle Scholar
- 46.Xiao, Y. F., Gomez, A. M., Morgan, J. P., Lederer, W. J., & Leaf, A. (1997). Suppression of voltage-gated L-type Ca2+ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes. Proceedings of the National Academy of Sciences of the United States of America, 94, 4182–4187.CrossRefPubMedGoogle Scholar
- 54.(1999). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-prevenzione trial. Gruppo italiano per lo studio della sopravvivenza nell’infarto miocardico. Lancet, 7(354):447–455.Google Scholar