Author + information
- Received December 1, 2010
- Revision received June 8, 2011
- Accepted June 16, 2011
- Published online November 8, 2011.
- ↵⁎Reprint requests and correspondence:
Dr. Dariush Mozaffarian, 665 Huntington Avenue, Building 2-319, Boston, Massachusetts 02115
We reviewed available evidence for cardiovascular effects of n-3 polyunsaturated fatty acid (PUFA) consumption, focusing on long chain (seafood) n-3 PUFA, including their principal dietary sources, effects on physiological risk factors, potential molecular pathways and bioactive metabolites, effects on specific clinical endpoints, and existing dietary guidelines. Major dietary sources include fatty fish and other seafood. n-3 PUFA consumption lowers plasma triglycerides, resting heart rate, and blood pressure and might also improve myocardial filling and efficiency, lower inflammation, and improve vascular function. Experimental studies demonstrate direct anti-arrhythmic effects, which have been challenging to document in humans. n-3 PUFA affect a myriad of molecular pathways, including alteration of physical and chemical properties of cellular membranes, direct interaction with and modulation of membrane channels and proteins, regulation of gene expression via nuclear receptors and transcription factors, changes in eicosanoid profiles, and conversion of n-3 PUFA to bioactive metabolites. In prospective observational studies and adequately powered randomized clinical trials, benefits of n-3 PUFA seem most consistent for coronary heart disease mortality and sudden cardiac death. Potential effects on other cardiovascular outcomes are less-well-established, including conflicting evidence from observational studies and/or randomized trials for effects on nonfatal myocardial infarction, ischemic stroke, atrial fibrillation, recurrent ventricular arrhythmias, and heart failure. Research gaps include the relative importance of different physiological and molecular mechanisms, precise dose-responses of physiological and clinical effects, whether fish oil provides all the benefits of fish consumption, and clinical effects of plant-derived n-3 PUFA. Overall, current data provide strong concordant evidence that n-3 PUFA are bioactive compounds that reduce risk of cardiac death. National and international guidelines have converged on consistent recommendations for the general population to consume at least 250 mg/day of long-chain n-3 PUFA or at least 2 servings/week of oily fish.
This work was supported by the National Heart, Lung, and Blood Institute (RC2-HL101816), National Institutes of Health, and a Research Fellowship for Dr. Wu from the National Heart Foundation of Australia. The supporting agencies had no role in the design of the study; interpretation of the data; or the preparation, review, or approval of the manuscript. Dr. Mozaffarian had received research grants from GlaxoSmithKline, Sigma Tau, Pronova, and the National Institutes of Health for an investigator-initiated, not-for-profit clinical trial of fish oil; travel reimbursement, honoraria, or consulting fees from the International Life Sciences Institute, Aramark, Unilever, SPRIM, and Nutrition Impact for topics related to diet and cardiovascular health; ad hoc consulting fees from Foodminds; and royalties from UpToDate for an online chapter on fish oil. Harvard University has filed a provisional patent application that has been assigned to Harvard and lists Dr. Mozaffarian as a co-inventor to the U.S. Patent and Trademark Office for use of trans-palmitoleic acid to prevent and treat insulin resistance, type-2 diabetes, and related conditions; however, no money has been paid to Dr. Mozaffarian. Dr. Wu reports that he has no relationships relevant to the contents of this paper to disclose. Drs. Mozaffarian and Wu contributed equally to this work.
- Received December 1, 2010.
- Revision received June 8, 2011.
- Accepted June 16, 2011.
- American College of Cardiology Foundation