REVIEWOmega-3 Fatty Acids for Cardioprotection
Section snippets
Background
During the past 3 decades, thousands of epidemiologic, observational, experimental, and randomized controlled studies have been published on the CV effects of omega-3 fatty acids. In the aggregate, these studies document clear CV protective effects.2 The 2 specific omega-3 fatty acids that have been associated with CV benefit and triglyceride lowering are those from fish oils, DHA and EPA. In contrast, ALA, which is found in abundance in flaxseed and to a lesser extent in walnuts and other tree
MECHANISMS OF ACTION
Omega-3 fatty acids appear to confer CV benefits largely through DHA and EPA enrichment of membrane phospholipids.9 Via this mechanism, omega-3 fatty acids can ultimately increase arrhythmic thresholds,10 reduce blood pressure,11, 12 improve arterial and endothelial function,13 reduce platelet aggregation,14 and favorably affect autonomic tone11, 15 (Table 2). In a meta-regression analysis of 22double-blind studies, Geleijnse et al16 reported that consumption of approximately 4.0 g/d of omega-3
OPTIMAL OMEGA-3 FATTY ACID MIX: DHA VS EPA
Both DHA and EPA are present in all oily fish, although at variable ratios (Table 3).27 Most commonly consumed fish, such as salmon, contain DHA and EPA in a ratio of approximately 2:1, whereas standard fish oil (usually derived from menhaden, an oily fish of the herring family) contains DHA and EPA in a 2:3 ratio. To a small extent, DHA can be retroconverted to EPA28; however, EPA supplementation does not increase tissue or blood levels of DHA.29 In vitro studies have shown both fatty acids to
ADVERSE EFFECTS
In prospective placebo-controlled trials, no adverse effects were observed to occur at a frequency of more than 5%, and no difference in frequency was noted between the placebo and omega-3 fatty acid groups.24, 40 The most commonly observed adverse effects are nausea, gastrointestinal upset, and a “fishy burp.” Steps to reduce burping and improve adherence include taking the omega-3 fatty acid at bedtime or with meals, keeping the fish oil capsules in the freezer, or using enteric-coated
PRIMARY AND SECONDARY PREVENTION OF CAD
To date, no randomized controlled trial has shown that omega-3 fatty acids reduce the risk of CV events and mortality in a primary prevention population. The evidence supporting a benefit in primary prevention comes instead from an observed 18% decrease in CV events in the 80% of patients in the JELIS trial without documented CAD (P=.13); this effect size was essentially the same as that observed in the secondary prevention cohort (19%, P<.05). In addition, prospective observational cohort
RECOMMENDATIONS FOR ADMINISTRATION
The correct dosage of any fish oil product can be calculated simply by adding up the amount of DHA and EPA per capsule and dividing this number into the target daily doses for triglyceride lowering or primary or secondary prevention. For example, the standard fish oil concentrate contains 120 mg of DHA and 180 mg of EPA per 1-g capsule. Thus, 1 to 2 capsules of standard over-the-counter fish oil per day (300-600 mg of DHA and EPA) would meet the recommendations for primary prevention; 3 to 4
CONCLUSION
Current data suggest that patients with known CAD should consume at least 1.0 g/d of long-chain omega-3 fatty acids; people without disease, at least 250 to 500 mg/d. Both DHA and EPA should be consumed. Regardless of statinuse, patients with hypertriglyceridemia benefit from treatment with 3.0 to 4.0 g/d of DHA and EPA.
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2019, Chemico-Biological InteractionsCitation Excerpt :It was hypothesized that these differences were due to the higher dietary intake of food sources rich in n-3 PUFAs in the Greenland Inuit population [160,161]. Since then, numerous studies have suggested a role of n-3 PUFA for the prevention of secondary cardiovascular events in patients with documented CAD [162–168] and showed higher intake of n-3 PUFAs lowers the number of mortalities related to cardiovascular diseases (CVD) [169–174]. For example, in a prospective cohort study, Mozaffarian et al. demonstrated higher plasma levels of n-3 PUFA were associated with lower total mortality rates with fewer cardiovascular compared to non-cardiovascular deaths in older adults [175].
Dr O'Keefe has received research grants from and is a consultant for CardioTabs. Dr Lavie has been a speaker and consultant for Reliant Pharmaceuticals. Dr Marchioli is a member of the steering committee of the Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial sponsored by Astra-Zeneca and Società Prodotti Antibiotici (SPA), a member of the steering committee of the Rischio & Prevenzione trial sponsored by SPA, and a speaker for SPA, Sigma-Tau, Solvay Pharmaceuticals, and Pronova BioPharma. Dr Harris is a consultant for and has received research grants from both Reliant Pharmaceuticals and Monsanto and is a speaker for the former.