Electrophysiological Mechanisms of the Anti-arrhythmic Effects of Omega-3 Fatty Acids

Abstract

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.

Omega-3 fatty acid supplementation and cardiovascular disease

“…The consumption of EPA and DHA from fi sh oil increases atrial and ventricular EPA and DHA in membrane phospholipids ( 24,25,174 ). Several clinical trials have reported that 3 PUFA were able to i ) prevent SCD, ii ) prevent ventricular arrhythmia in patients with implantable cardioverter, iii ) lower occurrences of premature ventricular contractions, iv ) reduce heart rate, and v ) prevent atrial fi brillation ( 174,175 ). Studies in dogs showed anti-arrhythmic effects of EPA or DHA when administered during ischemia ( 176 ).…”

“…Approximately 80-90% of sudden cardiac deaths are linked to ventricular arrhythmias, and arrhythmias are linked to control of heart contraction, a process involving electrophysiological mechanisms controlling muscle contraction ( 174,175,177,178 ). As such, studies with cardiomyocytes have focused on 3 PUFA regulation of Na + -, Ca +2 -, K + -channels, ion pumps, and the Na + /Ca +2 exchangers ( 173,175 ).…”

“…As such, studies with cardiomyocytes have focused on 3 PUFA regulation of Na + -, Ca +2 -, K + -channels, ion pumps, and the Na + /Ca +2 exchangers ( 173,175 ). The impact on intracellular calcium handling is particularly noteworthy.…”

Omega-3 fatty acids: antiarrhythmic, proarrhythmic or both?

“…Experiments on ion channels in cultured cells, on cardiac tissue in vitro, Langendorff preparations of explanted hearts, or using similar techniques investigating acute effects of EPA and/or DHA are reviewed elsewhere (De Caterina, 2011;Mozaffarian and Wu, 2011;Richardson et al, 2011;Savelieva et al, 2011). Of note, in such studies biologically active metabolites of EPA and DHA were defined, making the developments of more effective compounds a distinct possibility (e.g., Falck et al, 2011).…”

“…Underlying mechanisms have recently been reviewed (Richardson et al, 2011). The impression that EPA + DHA are primarily antiarrhythmic has been challenged by results of clinical studies, reporting that EPA and DHA did not reduce sudden cardiac death (SCD; Rauch et al, 2010).…”