Are All Fish Equally Close to the Heart?–Reply
2008; Elsevier BV; Volume: 83; Issue: 6 Linguagem: Inglês
10.4065/83.6.724-a
ISSN1942-5546
AutoresJames H. O’Keefe, John H. Lee, Roberto Marchioli, Carl J. Lavie, William S. Harris,
Tópico(s)Diet, Metabolism, and Disease
ResumoWe appreciate the interest of Drs Gebska and Friedman in our observations about fish-oil supplementation. Dr Gebska raises several insightful questions regarding the clinical use of fish oil for omega-3 fatty acid supplementation. The species of fish caught for their oil, such as menhaden, anchovies, and sardines, are not among those generally favored as food (eg, salmon, tuna). Fish oil is a commodity and is purchased in bulk with prices dictated by supply and demand. Specific EPA and DHA contents of fish-oil capsules reflect both the fish used as the source of the raw oil, and, more importantly, the subsequent processing (purification and concentration) each undergoes. A variety of concentrations and ratios of omega-3 fatty acids can be achieved by the specific processing methods. Ounce for ounce, some fish are more cardioprotective than others because of varying quantities of omega-3 and mercury. Salmon, sardines, trout, and herring are excellent choices because they are much higher in DHA and EPA than catfish, cod, or tilapia and are lower in mercury than swordfish, shark, king mackerel, and tuna. For example, one can of sardines (approximately 4 ounces) provides 435 mg of EPA and 468 mg of DHA. The same quantity of combined EPA and DHA (about 900 mg total), when consumed daily in the form of purified fish-oil capsules in the GISSI-Prevenzione randomized controlled trial, lowered total mortality by 28% and sudden cardiac death by 45%.1Marchioli R Barzi F Bomba E GISSI-Prevenzione Investigators et al.Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.Circulation. 2002; 105: 1897-1903Crossref PubMed Scopus (1178) Google Scholar How the fish is prepared is also important. In the Cardiovascular Health Study, consumption of fried fish low in DHA and EPA was not associated with improved coronary artery disease (CAD) outcomes, whereas consumption of fish that was baked or not fried was cardioprotective.2Mozaffarian D Gottdiener JS Siscovick DS Intake of tuna or other broiled or baked fish versus fried fish and cardiac structure, function, and hemodynamics.Am J Cardiol. 2006; 97 (Epub 2005 Nov 21.): 216-222Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar, 3Mozaffarian D Lemaitre RN Kuller LH et al.Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study.Circulation. 2003; 107: 1372-1377Crossref PubMed Scopus (351) Google Scholar Wild catfish is relatively low in EPA and DHA, and farmed catfish (generally grain-fed) is even lower, making catfish (which is usually breaded and fried) a relatively poor source of omega-3 fatty acids. In contrast, farm-raised salmon, because they are fed fish meal, are generally even higher in EPA and DHA than their wild counterparts. Both wild and farmed salmon are low in mercury.4Kelly B Ikonomou M Higgs D Oakes J Dubetz C Mercury and other trace elements in farmed and wild salmon from British Columbia, Canada.Environ Toxicol Chem. 2008 Jan; 22 (Epub ahead of print.): 1Google Scholar Currently, it is impossible to make an evidence-based judgment regarding the optimal mix of EPA and DHA for conferring cardiovascular benefits. A pure EPA supplement was cardioprotective in the JELIS trial.5Yokoyama M Origasa H Matsuzaki M Japan EPA Lipid Intervention Study (JELIS) Investigators et al.Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis [published correction appears in Lancet. 2007;370(9583):220].Lancet. 2007; 369: 1090-1098Abstract Full Text Full Text PDF PubMed Scopus (1936) Google Scholar In the GISSI-Prevenzione trial1Marchioli R Barzi F Bomba E GISSI-Prevenzione Investigators et al.Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.Circulation. 2002; 105: 1897-1903Crossref PubMed Scopus (1178) Google Scholar and Diet and Reinfarction Trial (DART),6Burr ML Fehily AM Gilbert JF et al.Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and Reinfarction Trial (DART).Lancet. 1989; 2: 757-761Abstract PubMed Scopus (2320) Google Scholar consumption of fish oil or fish containing approximately equivalent amounts of EPA and DHA provided substantial cardio-protective benefits. A trial to test pure DHA supplements for hard cardiac end points has not been performed. The key to choosing and dosing an over-the-counter or prescription fish-oil supplement is the EPA and DHA content; the species of fish used as the source of the fish oil is largely irrelevant. Fish-oil capsules, even inexpensive over-the-counter brands, have been found to be virtually free of mercury.7Bays HE Safety considerations with omega-3 fatty acid therapy.Am J Cardiol. 2007; 99 (Epub 2006 Nov.): 35C-43CAbstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar The EPA and DHA content of each capsule and the target intake dictate the number of capsules that need to be taken daily. The goals for EPA and DHA intake are 500 mg/d for primary CAD prevention, 1000 mg/d for secondary CAD prevention, and 3000 to 4200 mg/d for triglyceride lowering. Both EPA and DHA should be consumed, in roughly equal amounts. Dietary sources are preferred for meeting the EPA and DHA goals for primary prevention, whereas fish-oil supplements are generally necessary to administer EPA and DHA doses greater than 500 mg/d. Prescription omega-3 supplements, which supply 85% EPA and DHA by weight, are the most practical and clinically tolerable means of achieving the triglyceride-lowering doses. Until further evidence is available, this appears to be the most reasonable approach. Dr Friedman questions whether omega-3 fatty acids would confer the same cardiovascular benefits in the setting of aggressive statin-based cholesterol-lowering therapy. Marchioli et al8Marchioli R Marfisi RM Borrelli G et al.Efficacy of n-3 polyunsaturated fatty acids according to clinical characteristics of patients with recent myocardial infarction: insights from the GISSI-Prevenzione trial.J Cardiovasc Med (Hagerstown). 2007; 8: S34-S37Crossref PubMed Scopus (32) Google Scholar found that omega-3 supplements produced similar reductions in mortality in the 11,323 patients of the GISSI-Prevenzione trial, regardless of statin use. Omega-3 fatty acids and statins are thought to improve cardiovascular prognosis through different mechanisms of action. Statins do so largely by lowering LDL-C levels, whereas omega-3 fatty acids have neutral to adverse effects on LDL-C levels.9Davidson MH Stein EA Bays HE COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators et al.Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study.Clin Ther. 2007; 29: 1354-1367Abstract Full Text PDF PubMed Scopus (370) Google Scholar Omega-3 fatty acids confer cardiovascular benefits via enrichment of the cell membranes with DHA and EPA, which increase arrhythmic thresholds, improve arterial health, reduce platelet aggregation, and favorably alter autonomic tone. Statins and omega-3 fatty acids each reduce both triglyceride levels and inflammation and provide additive improvements in these parameters when used in combination.9Davidson MH Stein EA Bays HE COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators et al.Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study.Clin Ther. 2007; 29: 1354-1367Abstract Full Text PDF PubMed Scopus (370) Google Scholar The question regarding additive cardiovascular benefit in the setting of current guideline-based cholesterol treatment holds true for any therapy introduced and widely adopted before the widespread use of statins. For instance, the benefits of aspirin and β-blockers after myocardial infarction cannot be considered irrelevant today simply because their confirmatory trials largely predated the use of statins. Are All Fish Equally Close to the Heart?–1Mayo Clinic ProceedingsVol. 83Issue 6PreviewTo the Editor: I read with great interest the recent article by Lee et al1 on the cardioprotective effect of omega-3 fatty acids. Supported by data from multiple clinical trials, the authors emphasized the beneficial effects of a mixture of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on cardiovascular outcomes and all-cause mortality. I was particularly impressed by the growing body of evidence showing the synergistic effect of fish oil and statins on lowering triglycerides. Full-Text PDF
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