Carl J. Lavie, MD, FACC, FACP, FCCP is the Medical Director of Cardiac Rehabilitation and Prevention and the Director of the Stress Testing Laboratory at Ochsner Heart and Vascular Institute in New Orleans, Louisiana. In this interview he speaks with EP Lab Digest about the potential benefits of omega-3 therapy on cardiovascular diseases, including its possible use for atrial fibrillation. Explain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). What are the differences between the two? Is one more beneficial than the other? EPA and DHA are the two main omega-3 fatty acids. Both are important, but DHA may be preferable to EPA as it has more beneficial effects on arrhythmias as well as more beneficial effects on vascular relaxation, blood pressure lowering, and triglycerides. How do long-chain fatty acids work in the body? These get incorporated into cell membranes as well as used for energy. Tell us about the research demonstrating a reduced risk of arrhythmias with omega-3 polyunsaturated fatty acid (w-3 PUFA). What effect does w-3 PUFA have on heart rate and arrhythmias? The most significant effects are to improve autonomic function or the balance between parasympathetic and sympathetic tone (typically one sees very small reductions in heart rate but better effects on heart rate variability). Omega-3 also has beneficial effects in the setting of reperfusion arrhythmias, which would decrease ventricular tachycardia and ventricular fibrillation (VT/VF) and the risk of sudden cardiac death. Is w-3 PUFA currently prescribed in patients with arrhythmia? Is a prescription needed for w-3 PUFA or is a supplement in the recommended dosage available over the counter (OTC)? In addition, is fish oil from food or from supplements better, or are the results comparable? I personally prescribe omega-3 for arrhythmia prevention. The only omega-3 that is available as a prescription is Lovaza (GlaxoSmithKline, Research Triangle Park, NC), which is officially on the market not to treat or prevent arrhythmias but only to lower high levels of triglycerides. Four Lovaza pills are needed to reduce triglycerides, but only one would be needed for arrhythmias (800-1000 mg per day of combined EPA/DHA, which could also be obtained by taking one, two or three OTC pills depending on the concentration). To obtain 800-1000 mg of EPA/DHA per day, four or five fatty fish meals per week would be needed, and few people eat this much fatty fish. Has w-3 PUFA been shown to be beneficial in patients with ICDs? There have been several fish oil trials in ICD patients; these are described in more detail in my paper.1 One of the trials actually showed an increase in arrhythmias, one a reduction, and others showed a slight trend toward reduction. I believe the overall results suggest a slight reduction. Discuss the research that has been done on w-3 PUFA use in patients with atrial fibrillation (AF). Several trials in AF have been published, and all are relatively small. These trials have concentrated on perioperative atrial fibrillation; the trial results have suggested that omega-3 pretreatment may reduce the risk of perioperative AF. What effect does w-3 PUFA have on the risk of sudden cardiac death? At what dosage(s) does w-3 PUFA have antiarrhythmic effects and/or a reduced risk for SCD? In the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell’ Infarto Miocardico)-Prevenzione study, one Lovaza (GlaxoSmithKline) or 800-1000 mg per day of combined EPA/DHA reduced the risk of sudden cardiac death. In primary prevention trials, eating more fish and having higher blood levels of EPA and DHA have also been associated with reduced risk. However, the risk of sudden cardiac death in heart failure (HF) patients, such as in GISSI-HF study, was not reduced by taking one Lovaza (GlaxoSmithKline). Tell us about your research2 on the use of EPA and DHA in heart failure patients. We showed in a small study of advanced heart failure patients that high doses of omega-3 reduced inflammatory biomarkers and improved the cachexia state in advanced HF. I personally believe that higher doses of Lovaza (2, 3, 4, maybe even 5 or 6 pills daily) would have produced a much more marked benefit than was noted with just one Lovaza in GISSI-HF. What other benefits can w-3 PUFA provide, in addition to the potential benefits listed above? Omega-3 may have benefits to reduce atherosclerosis, improve lipids (especially triglycerides), lower blood pressure, and may have benefits on many other factors such as arthritis, immune function, cancers, brain function, etc. What trial thus far would you say has been the most significant regarding w-3 PUFA research advancements? I believe that the most important trials were GISSI-Prevenzione and GISSI-HF. What is the recommended dosage of w-3 PUFA? Why is there a higher dosage for those patients who already have coronary heart disease (CAD)? Healthy people should consume at least 500 mg/day of combined EPA/DHA, which is equivalent to approximately two fish meals per week. For patients with heart disease, including CAD, HF, and I also include AF as well, I recommend 800-1000 mg/day of combined EPA/DHA. Has the usage of w-3 PUFA increased in recent years? If there has been an increase in the use of omega-3 in recent years, it probably has only been slight. I predict that my recent article and all the attention that it has received in the press may change this. What are the negative aspects of w-3 PUFA intake? In addition, describe some of the research that has shown unfavorable results in w-3 PUFA supplementation. The biggest negative of eating more fish would be contaminants, namely mercury. Since mercury is water soluble and not fat soluble, this could be in the muscle of the fish but should not be in the oil. Therefore, fish oil supplements, even the cheap ones, should not contain mercury to any meaningful degree. The other more significant problem with omega-3 supplements, particularly if these are taken at very high doses, is the caloric load. Each fish oil pill generally contains 9 or 10 calories, and in a society where we are experiencing an epidemic in overweightness/obesity, any excess calories are a potential problem. In addition, please see my recent obesity article in JACC,3 since obesity is also a major cause of sudden cardiac death and atrial fibrillation! How is w-3 PUFA research valuable to those in the electrophysiology field? Electrophysiologists certainly care about reducing the risk of SCD, major arrhythmias in ICD patients, and atrial fibrillation. Therapy with omega-3 could lead to reductions in the quantity and/or doses of some of the more toxic antiarrhythmic agents that are used in this field. What further research in this area is needed? We need more studies at various doses, as well as further study of the importance of the relative doses of DHA versus EPA for many different conditions. Regarding AF, numerous studies in various type of patients (with CAD, HF, valvular heart disease, etc.) using different doses is needed to assess primary AF and recurrences.