Curriculum in Cardiology
Understanding omega-3's

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Omega-3 fatty acids are a subset of polyunsaturated fatty acids found in marine sources as eicosapentaenoic acid and docosahexaenoic acid and in some leafy vegetables, nuts, and oils as α-linolenic acid (ALA). The metabolism of omega-3's may explain the cardioprotective effects observed in epidemiologic and experimental studies. Although most data for cardioprotective effects come from studies of marine sources, vegetable sources of omega-3 fatty acids (α-linolenic acid) may have similar effects through in vivo conversion to eicosapentaenoic acid and docosahexaenoic acid. This document will provide an overview of omega-3 fatty acids with a focus on specific sources, metabolism, safety issues, and their potential indication for cardiovascular prevention.

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What are omega-3's?

There are 3 types of naturally occurring fats classified by the number of double bonds present in their fatty acid side chains: saturated, monounsaturated, and polyunsaturated (Figure 1). The food industry created a fourth class, trans fats, by adding hydrogen ions to polyunsaturated fats through a process called hydrogenation (Figure 1). Polyunsaturated fats can be further classified into 2 groups based on the position of the first double bond site: omega-3 fatty acids and omega-6 fatty acids (

Where are omega-3's?

Dietary intake of omega-3 and omega-6 fatty acids varies within and between different populations. NHANES III, the largest database of nutrient consumption of Americans, reports a median intake of EPA + DHA of 0 and <1 g/d of ALA.5 The ratio of omega-6 to omega-3 intake is estimated to be 20 to 1 in a modern Western diet, compared with that of our Paleolithic ancestors who ate a diet much richer in omega-3's (estimated omega-3/omega-6 ratio of 1-2:1) (Figure 3).6, 7 This dramatic dietary shift

The metabolism of omega-3's

A dietary shift toward less omega-3's and more omega-6's may significantly impact one's health because of their different metabolic pathways. Eicosanoids are a class of bioactive molecules derived from omega-3's and omega-6's that include leukotrienes, prostaglandins, and thromboxanes (Figure 2). Eicosanoids derived from omega-6's are generally proinflammatory and proaggretory, whereas those derived from omega-3's are predominantly anti-inflammatory and inhibit platelet aggregation.6 This

Epidemiologic data

Several important observational studies have concluded that omega-3 consumption is inversely related to CVD, especially cardiac death.18, 19, 20, 21, 22 In a study of 22 071 male American physicians, those who consumed fish once a week had a 52% reduction of sudden cardiac death compared with those who ate fish less than once a month (P = .04).20 There was no additional protective effect for men eating fish in amounts greater than once a week. Although a reduction in sudden cardiac death and

Prospective randomized trials

The impact of omega-3's on cardiovascular end points has been evaluated in 4 well-designed secondary prevention trials. These trials evaluated omega-3's either as part of a comprehensive diet plan or as a capsule supplement, and although these trials differed in many respects, their findings were consistent and compelling—omega-3's are effective for secondary prevention of cardiovascular events.

The DART26 randomized 2033 post–myocardial infarction Welsh men to one of the following groups: (1)

Clinical use

In addition to being useful in the secondary prevention of CVD events, a prescription formulation of omega-3 fatty acids, Omacor, has gained Food and Drug Administration (FDA) approval as an adjunct to diet to reduce very high (>500 mg/dL) triglycerides in adults. Two studies of 4 g/d of Omacor demonstrated a 50% reduction in triglycerides and a 44.5% increase in low-density lipoprotein (LDL) cholesterol in 84 adults with primary hypertriglyceridemia.32 A review of 10 trials in 606 subjects

Safety

The US Department of Health and Human Services Agency for Healthcare Research and Quality identified 148 omega-3 fatty acid studies that reported on adverse events in >20 000 subjects.5 In summary, gastrointestinal complaints were reported in 6.6% of the subjects taking omega-3's versus 4.3% in the placebo groups. An increased incidence of bleeding was not observed, and only 1 of the 148 studies reviewed reported such an association in patients randomized to 6 g/d of omega-3. There are no

Conclusion

Omega-3's are a unique group of polyunsaturated fats that can be found most abundantly in fatty fish, flaxseed, walnuts, soy, and canola oil (Table II). The metabolism of omega-3's from fish (EPA + DHA) and vegetables (ALA) results in the production of the same eicosanoids (thromboxane, leukotrienes, prostaglandins); however, it is unclear as to what extent ALA is metabolized into these eicosanoids and if this metabolism is directly related to its effect on CVD. It does seem clear from the 4

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