Cardiology Q&A: Fish Oil Supplementation for Cardioprotection: How Much Is Enough? How Much Is Safe?

Q: How much fish oil should I recommend that my patients with heart disease take? A: Omega-3 fatty acids have been touted as a cure for a myriad of diseases. To date, the strongest evidence of benefit is in the area of cardiovascular health. The cardioprotective effects of omega-3 fatty acids have been demonstrated in a number of studies.1,2  Fish oils are efficient vehicles for the delivery of omega-3 fatty acids. The 2 omega-3 fatty acids most strongly associated with cardioprotection are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Both are unique to marine life; they are originally synthesized by ocean microorganisms and then make their way up the food chain. RECOMMENDED DOSAGE FOR PATIENTS WITH HEART DISEASE The amount of EPA+DHA recommended by the American Heart Association is “about 1 gram” per day.2  This is roughly the equivalent of a 3-oz serving of salmon or sardines or 4 oz of albacore (white) tuna (Table). Most fish oil capsules on the market today contain about 300 mg of EPA+DHA per 1-g capsule; thus, 3 such capsules provide the recommended amount of omega-3 fatty acids. Capsules that contain higher amounts of omega-3 fatty acids are also available in health food stores and online. Therefore, it is important to read the product label, determine the amount of EPA+DHA per capsule, and prescribe accordingly (see Table). DOSAGES FOR TREATMENT OF HYPERTRIGLYCERIDEMIA Fish oil is one of the most effective therapies for hypertriglyceridemia. A regimen of 2 to 4 grams of EPA+DHA per day lowers triglyceride levels in most patients by 20% to 40%.3  For mixed dyslipidemia, we often use omega-3 fatty acids together with a high-efficacy statin. The combination of a statin and omega-3 fatty acids normalizes both low-density lipoprotein cholesterol levels and triglyceride levels in most patients, and it obviates the need for other, more potentially toxic combination therapies, such as a statin plus high-dose niacin or fibrates. An effective dosage of EPA+DHA for the treatment of hypertriglyceridemia is about 3 g/d. This translates into about 10 standard fish oil capsules per day—probably a major reason why omega-3 therapy for hypertriglyceridemia has not yet been widely embraced by the medical community. However, higher-concentration products that contain up to 650 mg of EPA+DHA per gram are now available over-the-counter. Five such capsules per day effectively lower triglyceride levels. Later this year, a new FDA-approved omega-3 product that contains 850 mg of EPA+DHA per gram (Omacor, Reliant Pharmaceuticals) will be available by prescription in the United States. The product is indicated for severe hypertriglyceridemia. SAFETY OF HIGHER DOSAGES The FDA has determined that dosages up to 3 g/d of EPA+DHA are generally safe. This does not necessarily mean that higher dosages are unsafe. Rather, it means that regimens of more than 3 g/d should be undertaken in consultation with a physician, as recommended by the American Heart Association.2 The primary concern at these higher dosage levels—prompted by the fact that EPA acts somewhat like aspirin—is excess bleeding. EPA is an analog of arachidonic acid (AA) and, like AA, can be converted into eicosanoids (prostaglandins, thromboxanes, and prostacyclins). The eicosanoids made from EPA are generally less active than those made from AA; thus, when the EPA-to-AA balance in tissues shifts toward EPA, platelets become less prone to aggregate. However, aspirin is a more potent platelet inhibitor than omega-3 fatty acids; at this point, the concern about bleeding with high-dose omega-3 therapy is only theoretical and has not been substantiated in clinical trials. Clinically significant bleeding has not been observed in trials in which patients undergoing percutaneous transluminal coronary angioplasty or coronary artery bypass grafting were given up to 7 g of EPA+DHA.4,5  In these studies, omega-3 fatty acids did not increase the risk of bleeding, even though patients were also receiving aspirin or warfarin. HOW TO TAKE FISH OIL CAPSULES Capsules may be taken at any time of day, with or without food, together or in divided doses. Many patients experience a “fishy burp” after they take fish oil capsules. Typically, patients prefer to take all the capsules at once so that any problems with the burp are experienced, at most, once a day. Strategies for diminishing the burp include using high-potency products, using enteric-coated capsules, and freezing the capsules. Taking capsules with a meal or at bedtime can also help. Patients need to experiment to determine what works best for them. RELIABILITY AND SAFETY It is not difficult to find reliable omega-3 supplements. In July 2003, Consumers’ Union tested 16 different fish oil products for potency (“Did the capsules contain as much EPA+DHA as claimed?”) and purity (“Were the capsules contaminated with organic pollutants or mercury?”).6  All 16 products contained the amount of EPA+DHA claimed on the label, and none contained significant amounts of contaminants. This led to the recommendation that consumers choose their omega-3 product based on price. You may also want to point out to patients that because methylmercury (the toxic form of mercury) is water-soluble and not oil-soluble, fish oil capsules contain no mercury. When oil is extracted from fish, the mercury stays behind in the fish meal. FLAXSEED OIL VERSUS FISH OIL Flaxseed oil is a rich source of the plant omega-3 fatty acid, alpha-linolenic acid (ALA), a short-chain version of the marine omega-3 fatty acids. Although some data suggest that it, too, may help reduce the risk of heart disease, the evidence for ALA is considerably weaker than that for the longer-chain omega-3 fatty acids found in fish. Moreover, ALA does not lower triglyceride levels. Accordingly, current recommendations emphasize the consumption of standard vegetable oils (canola, soybean) and walnuts, which contain small amounts of ALA. However, ALA should not be considered an effective substitute for EPA and DHA. CLINICAL SIGNIFICANCE OF BLOOD LEVELS OF OMEGA-3 FATTY ACIDS We have recently proposed that low blood levels of omega-3 fatty acids be considered an “emerging” risk factor for death from coronary heart disease. Low levels (4% or less of EPA+DHA in red blood cell membranes) place patients at increased risk, and high levels (8% or more of EPA+DHA in red blood cell membranes) appear to be protective.7 Dr Harris is director of lipid and metabolic research at the Mid America Heart Institute in Kansas City, Mo. He coauthored the American Heart Association’s scientific statement on the cardioprotective effects of omega-3 fatty acids. Dr O’Keefe is a cardiologist and researcher at the Mid America Heart Institute. REFERENCES: 1. Leaf A, Kang JX, Xiao YF, Billman GE. Clinical prevention of sudden cardiac death by -3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by -3 fish oils. Circulation. 2003;107:2646-2652. 2. Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747-2757. 3. Harris WS. Ω-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997;65(suppl):1645S-1654S. 4. Leaf A, Jorgensen MB, Jacobs AK, et al. Do fish oils present restenosis after coronary angioplasty? Circulation. 1994;90:2248-2257. 5. Eritsland J, Arnesen H, Gronseth K, et al. Effect of dietary supplementation with -3 fatty acids on coronary artery bypass graft patency. Am J Cardiol. 1996; 77:31-36. 6. Consumers’ Union. Omega-3 oil: fish or pills? Consumer Rep. 2003;68:30-32. 7. Harris WS, von Schacky C. The Omega-3 Index: a new risk factor for sudden cardiac death? Prev Med. 2004;39:212-220. 8. US Department of Agriculture (USDA), Agricultural Research Service. USDA National Nutrient Database for Standard Reference, Release 17. 2004. Available at: http://www.nal.usda.gov/fnic/foodcomp/. Accessed March 31, 2005. FOR MORE INFORMATION: Harris WS. Fish oil supplementation: evidence for health benefits. Cleve Clin J Med. 2004;71:208.