Omega-3 Fatty Acids and Cardiovascular Disease Effects on Risk Factors, Molecular Pathways, and Clinical Events
Omega-3 Fatty Acids and Cardiovascular Disease Effects on Risk Factors, Molecular Pathways, and Clinical Events
Year: 2011
Authors: Mozaffarian, D. Wu, J.H.Y.
Publication Name: Journal of the American College of Cardiology
Publication Details: Volume 58; Number 20; Pages 2047 – 2067.
Abstract:
We reviewed available evidence for cardiovascular effects of n3 polyunsaturated fatty acid (PUFA) consumption, focusing on long chain (seafood) n3 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. n3 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 antiarrhythmic effects, which have been challenging to document in humans. N3 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 n3 PUFA to bioactive metabolites. In prospective observational studies and adequately powered randomized clinical trials, benefits of n3 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 n3 PUFA. Overall, current data provide strong concordant evidence that n3 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 n3 PUFA or at least 2 servings/week of oily fish (Authors abstracts).
This review article describes in vitro studies, animal experiments, observational studies, and randomized clinical trials (RCTs) that have examined the cardiovascular effects of seafood consumption and long chain n3 polyunsaturated fatty acids (PUFAs). Several questions remain, including the precise physiological effects and molecular mechanisms that account for the observed benefits, the magnitudes and dose-responses of effects on specific clinical outcomes, and the potential heterogeneity in different populations. Several recent clinical trials of n3 PUFA have also had mixed findings, raising concern about the consistency of the evidence. We reviewed the current evidence for cardiovascular disease (CVD) effects of seafood and n3 PUFA consumption, including the principal dietary sources; effects on physiological risk factors; potential molecular pathways of effects; and scientific evidence, including conflicting evidence, for effects on specific clinical endpoints. Promising but more limited evidence for plant-derived n3 fatty acids is briefly discussed. The authors conclude that PUFA consumption improves vascular and cardiac hemodynamics, triglycerides, and possibly endothelial function, autonomic control, inflammation, thrombosis, and arrhythmia. Experimental studies confirm multiple relevant molecular effects, including on membrane structure and associated functions, ion channel properties, genetic regulation, eicosanoid synthesis, and production of novel inflammation-resolving mediators. n3 PUFA are bioactive nutrients that play an important role in cardiovascular health, in particular for reducing risk of cardiac mortality. Additional appropriately designed and powered clinical trials are needed to assess effects of n3 PUFA on other cardiovascular endpoints, including nonfatal coronary events, ischemic stroke, recurrent ventricular arrhythmias, AF, and heart failure. As part of achieving a healthier overall dietary pattern, physicians should recommend fish consumption for their patients, and government and public health agencies should implement strategies to improve attainment of the recommended levels of fish and n3 PUFA consumption to reduce population burdens of CHD mortality and sudden cardiac death (Editors comments).
