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Fish Oil Supplementation & Coronary Artery Disease: Does It Help?

By Subrata Kar, DO^a & Richard Webel, MD^a 

^aDivision of Cardiovascular Medicine, University of Missouri-Columbia School of Medicine

Abstract

Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to decrease the risk of cardiovascular disease. They reduce fatal and non-fatal myocardial infarction, stroke, coronary artery disease (CAD), sudden cardiac death, and all-cause mortality.  They are well tolerated and cause minimal adverse effects.  In this review, we sought to provide an overview of the current literature on the use of Omega-3 fatty acids for the treatment of CAD and discuss the possible benefits.

Introduction

Omega-3 polyunsaturated fatty acids (PUFAs) found in fish oil have been reported to reduce the risk of cardiovascular disease, primarily eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), which have been the most widely available and most studied.  A number of studies have shown a reduction in cardiovascular endpoints including fatal and non-fatal myocardial infarction (MI), stroke, coronary artery disease (CAD), sudden cardiac death (SCD), and all-cause mortality¹. PUFAs promote atherosclerotic plaque stability and decrease ischemia related cardiac arrhythmias.^2-5  PUFAs also have beneficial effects in mortality reduction following  myocardial infarction.² 

Daily consumption of PUFAs from either fish or fish oil supplements may be beneficial in patients with CAD.^6,7  Oily fish, such as salmon, tuna, sardines, herring, and mackerel provide natural source of PUFAs.¹¹   However, consumption of oily fish may be preferable because it provides Vitamin D, selenium, and naturally occurring antioxidants which are not found in purified fish oil supplements.⁶  In this article, we sought to review the literature and explore the potential benefits of PUFAs in the treatment of CAD.

Fish Oil Use for Cardiovascular Disease

PUFAs are fish oil extracts which have been shown to have beneficial effects in cardiovascular disease.  Figure 1 displays fish oil capsules.  PUFAs may reduce total mortality by as much as 20-50%, and  sudden death in doses of 0.85 to 4.0 grams/day after a duration of 12 to 42 months.²  Larger doses of 3 to 4 grams daily decrease triglycerides and inflammation while increasing vascular reactivity.  The Food and Drug Administration has approved Lovaza (formerly Omacor), a highly purified form of PUFAs, for severe hyperlipidemia at a dose of 4 grams/daily.⁶  Doses of 6 grams daily may decrease platelet function.⁸  PUFAs can also stabilize myocardial membranes which may decrease the incidence of ventricular arrhythmias and SCD.^3,4,9 

Figure 1. Fish oil supplements contain omega 3 fatty acids with the specific concentrations of EPA and DHA on the label 

PUFAs are essential fatty acids and cannot be synthesized in man.  Thus, it must be acquired from dietary sources.¹⁰  PUFAs may lower triglycerides by 20 to 50% through reduction of hepatic triglyceride synthesis by a reduction in the release of triglyceride rich VLDL particles, and increase HDL by 9%. ^{3, 11,12}  PUFAs also increase hepatic fatty acid beta-oxidation.^11,13 

PUFAs may be safely used in combination with statins to enhance triglyceride reduction or used in patients with severe hypertriglyceridemia unresponsive to statins.¹⁴  They may also be of benefit in patients after myocardial infarction.¹⁵ 

Effects on Atherosclerosis

PUFAs have been shown to reduce atherogenesis.¹⁷  In post-MI patients, PUFAs have been shown to decrease total mortality, cardiovascular mortality, and sudden cardiac death.⁷  PUFAs also decrease the production of pro-atherosclerotic mediators such as adhesion molecules, vascular smooth muscle cell growth factor, and chemoattractant molecules.⁴  Consequently, atherosclerotic plaque formation is diminished through a reduction in the destructive process of cell migration into the vessel intima which causes atherosclerotic plaques.⁴ PUFAs may also incorporate into atherosclerotic plaques to provide stability by decreasing the proportion of macrophages  which may prevent plaque rupture .¹⁸  The randomized Omacor Carotid Endarterectomy Intervention (OCEAN) studyof carotid endarterectomy patients showed that EPA incorporation into atherosclerotic plaque reduces foam cells and T cells which were associated with decreased inflammation and more stable atherosclerotic plaques.¹⁹ Moreover, PUFAs also display antioxidant properties which improve endothelial function and may contribute to the anti-atherosclerotic benefits. 

PUFA Associated Side Effects

PUFAs are overall a safe medication and well tolerated.  Common adverse effects include nausea, gastrointestinal distress, and belching.⁷  Other less frequent effects include eructation, dyspepsia, worsening of glycemic control, taste perversion, and bleeding from inhibition of platelet aggregation.^14,20  These adverse effects may be experienced at doses greater than 2 grams/day.⁴  PUFAs have not been shown to interact with statins to induce rhabdomyolysis, which has been seen with fibrates.²¹  PUFAs have no known combination effects with statins to induce myopathy, myositis, or rhabdomyolysis. Combination of PUFAs with fibrates is also not known to induce rhabdomyolysis.  Therefore, PUFAs can be used as combination therapy with statins, niacin, or fibrates to augment lipid control.  See Figure 2.

Figure 2 Artist’s rendering of a blood clot. PUFAs can be used as combination therapy with statins, niacin, or fibrates to augment lipid metabolism.

No known liver, muscle, or renal toxicity has been reported.  Currently, no clinical contraindication exists, although increased bleeding risk may occur with higher doses.

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