During the past few years, there has been an increase in both scientific and public interest in the role of omega-3 fatty acids found in fish and fish oils in the prevention and management of cardiovascular disease.
EPA DHA Omega-3 Fatty Acids
The omega-3 fatty acids that are of particular interest for cardiovascular care include EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), which are found predominantly in fish and fish oils. The basis of this heightened interest in dietary intakes of EPA and DHA comes partly from epidemiological and population studies indicating: increased consumption of fish as a source of omega-3 fatty acids is often associated with decreased mortality (as well as morbidity) from cardiovascular disease.
Controlled trials in humans have indicated a favorable modifying effect of dietary fish oils on various risk factors for cardiovascular disease independent of their lowering ability to lower bad cholesterol.
ted omega-3 fish oil concentrates has shown the potential to reduce both the progression of cardiovascular disease and related mortality, including sudden cardiac death.
The typical North American diet provides about 1-3 g of ALA per day but only 0.10-0.15 g of EPA plus DHA per day. The very high intake of n-6 PUFA, mostly as linolenic acid (LA) in our diet (12-15 g/day) from common vegetable oils (corn, safflower, soybean) and other sources.
Intervention Studies And Risk Factor Modification Using EPA And DHA
Intervention studies using fish oil concentrates that provide EPA and DHA at intakes of up to 2-4g/day over a few weeks1,2,3 have shown that these fatty acids can favorably lower various risk factors for cardiovascular disease (independent of any blood cholesterol-lowering effect). These effects include an antithrombotic effect, lipid (triglyceride) lowering, reduced blood and plasma viscosity, and improvements in endothelial dysfunction.1,2,3,19
Omega-3 fatty acids accumulate to a considerable extent in various sites including circulating blood platelets, the heart and serum phospholipid. The accumulation of EPA and DHA in platelets is associated with decreased platelet adhesiveness and aggregation and an overall reduction in thrombogenicity. Antiatherogenic effects of omega-3 fatty acids have also been shown in animal studies.
Fish Oil Lowers Triglycerides
Human studies have revealed the potent ability of EPA and DHA to significantly reduce circulating levels of blood triglyceride,20 which is of interest because only moderate elevations in triglycerides have been associated with a progressively increased risk of ischemic heart disease.21
Within 2-3 weeks of EPA and DHA supplementation, significantly reduced blood triglyceride levels with an approximate reduction of 6%-8% (or more) per gram of EPA and DHA consumed are routinely observed. In a placebo-controlled, double-blind trial,22 – 26% lower levels of triglycerides were recently demonstrated in postmenopausal women receiving 4 g omega-3 (EPA and DHA) daily over 28 days.
Supplementation with omega-3 (EPA and DHA), as given in addition to statin therapy in patients with combined hyperlipidemia,23 was found to reduce levels of atherogenic lipoproteins while more effectively reducing the hemostatic risk profile.
Omega-3 Fatty Acids can Reduce Mortality Related to Cardiovascular Disease
The antiarrhythmic potential of EPA and DHA (upon accumulation in cardiac tissue) has been considered to be yet another important mechanism by which consumption of these fatty acids can reduce mortality related to cardiovascular disease (particularly sudden cardiac death). This last effect is considered to be exhibited at even lower intakes of omega-3 (EPA and DHA combined) of about 1 g/day.4
Because it appears that lower heart rate variability may be used to predict an increased risk of coronary heart disease,25 mortality and arrhythmic events, evidence that 4 g/day of EPA and DHA (about 1.5% of daily energy intake) may increase heart rate variability in survivors of myocardial infarction is of interest.26
Heart rate variability, a noninvasive marker of autonomic nervous system function, is reduced with sympathetic predominance and other factors (including reduced baroflex sensitivity) that may be favorably modified by omega-3 fatty acids. Dietary supplementation with fish oil, enriched with EPA and DHA (up to 3-4 g omega-3/day) has also been reported to enhance systemic large-artery endothelial functions as measured in male subjects with hyperlipidemia by ultrasonic vessel wall tracking.19
Consumption of EPA and DHA at levels approaching 2 g/day is similar to that seen in large sectors of the Japanese population and well below the intakes of the Greenland Inuit.
Clinical Trials With Fish Oil Supplements
Recent studies have focused upon the potential for fish oil supplements (enriched with EPA and DHA) to modify clinical end points in patients with respect to coronary atherosclerosis and myocardial infarctions.
A European study of the effect of dietary omega-3 fatty acids on coronary atherosclerosis (measured via coronary angiography) in patients with cardiovascular disease using a randomized, double-blind, placebo-controlled trial has been reported.33 This study revealed that patients with coronary artery disease given omega-3 (EPA and DHA) therapy (at levels of about 1.5 g/day) over 2 years had moderately less progression and more regression of coronary artery disease (discernible, modest mitigation of atherosclerosis) than did patients on placebo. Fewer cardiovascular events were noted in the omega-3 group.
The omega-3 supplementation was considered safe and well tolerated.
Very recently, the 1999 GISSI-Prevenzione trial results have been reported from Italy.6 In this study, 11,324 patients who had experienced a myocardial infarction were assigned to supplemental interventions following the introduction of a Mediterranean-type diet (which included moderate fish consumption), as well as aggressive treatment with various pharmaceutical agents for cardiovascular care.
About half the patients received an encapsulated omega-3 fish oil supplementation (providing 850-882 mg/day EPA plus DHA). Over the subsequent interval (3.5 years), the individuals who received omega-3 supplements were found to exhibit a significant reduction in overall cardiovascular deaths and a reduction in sudden cardiac death of about 45%.
Vitamin E (-tocopherol) supplementation, which was also studied in this trial, was without significant effect in this regard. These findings support the concept that, independent of blood cholesterol lowering, EPA and DHA intakes (including supplementation) can be favorable.
Target Intakes Of EPA And DHA For Cardiovascular Health
The mean current daily intake of EPA and DHA combined in a typical North American diet (which includes about one fish serving every 10 days) approaches 130 mg/day, which is about 0.15% of total dietary fat intake.
Most Dietary EPA And DHA is Consumed in The Form of Fish Or Seafood.
This dietary intake is markedly lower than Japanese intakes and only a small fraction of the EPA and DHA consumed by the Greenland and Nunavik Inuit. Fish consumed 2.5-3 times per week would provide a combined intake of about 500 mg EPA and DHA per day.
This intake is about 4 times that of current North American consumption rates. Epidemiological data from the Multiple Risk Factor Intervention Trial in the United States have indicated that progressively higher intakes of the fish-derived omega-3 fatty acids (up to about 665 mg/day) over 10.5 years were associated with a progressive reduction in mortality related to coronary heart disease, as well as total mortality with no associated increase in total cancer-related mortality.34
A recent review of the existing evidence indicated that an increase in the consumption of fish may contribute to lower colorectal cancer and breast cancer risks.35
In summary, there is evidence for the beneficial effect of regular fish consumption (up to 2-3 times/week) both in healthy subjects and in those at considerable risk for coronary artery disease or with established coronary artery disease.
Fried or processed fish containing partially hydrogenated fats ("trans" fatty acids) and salted or pickled fish should be avoided. A National Institutes of Health workshop held in 1999 resulted in the recommendation of a combined average EPA and DHA intake of 650 mg/day for healthy adults.
Newly Released American Heart Association Guidelines
The newly released American Heart Association guidelines37 included the following recommendations with respect to omega-3 fatty acid supplements: "Consumption of 1 fatty fish meal per day (or alternatively, a fish oil supplement) could result in an omega-3 fatty acid intake (ie, EPA and DHA) of ~900mg/d, an amount shown to beneficially affect coronary heart disease mortality rates in patients with coronary disease." Current mean intakes (adults) of EPA and DHA (combined) are about 130 mg/d or 14%-20% of these target intakes of 650 mg/d and 900 mg/d.
Future Perspectives In Cardiovascular Care
Future nutrition labeling and health claims should provide both listings for the omega-3 fatty acids of interest (ALA, EPA and DHA) and evidence-based health claims for EPA and DHA related to lowering of blood triglyceride levels, heart health and so on.
Omega-3-enriched supplements (nutraceuticals) and functional foods (e.g., EPA- and DHA-enriched eggs and other food products) with effective quantities of EPA and DHA in various forms will become increasingly available as complementary options to fish.
Significant blood triglyceride lowering has been recently reported in subjects fed 1000 kJ/day (240 kcal/day, that is about 10% of the total daily energy intake) of a commercial liquid scrambled egg-type product containing EPA and DHA. These and other such products will offer the possibility of an overall increase in the daily consumption of EPA and DHA, which are currently consumed only in moderate quantities in the form of fish and fish oil, thereby narrowing the current nutritional gap.
Omega-3 Therapeutics will offer alternatives as well as complementary options and strategies for the informed practitioner.
Clinicians and other health professionals will need to become fully educated about the evidence-based use of omega-3 fatty acids from fish oils (dose, duration, expected benefits, monitoring and so on) in the management of cardiovascular care. "Omega-3 therapeutics" will offer alternatives as well as complementary options and strategies for the informed practitioner.
Depending upon the patient’s preference, fish oil supplements (taken with meals) or functional food sources (e.g., liquid egg enriched in omega-3 PUFA) can serve as alternative dietary sources of the target 650-900 mg combined EPA and DHA average daily intake.
By Dr. Holub Professor, Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ont. ON N1G 2W1