Prevention of Cardiovascular Events with Omega-3 Polyunsaturated Fatty Acids and the Mechanism Involved

Yasuhiro Watanabe and Ichiro Tatsuno

Center for Diabetes, Metabolism and Endocrinology, Toho University Sakura Medical Center, Chiba, Japan

An epidemiological study of Greenlandic Inuit suggested that fish oil, or omega-3 polyunsaturated fatty acids (PUFA), was important in preventing atherosclerotic disease. After this landmark study, many large-scale epidemiological studies and meta-analyses have examined the health benefits of omega-3 PUFA as part of a fatty acid-rich diet to demonstrate its beneficial roles in the prevention of cardiovascular diseases. Recent research has also focused attention on the anti inflammatory effects of omega-3 PUFA and on specialized pro-resolving mediators. Findings of these studies have led to the development of omega-3 PUFA preparations for the treatment of dyslipidemia, including a highly purified eicosapentaenoic acid (EPA)-ethyl ester product (Epadel®) in Japan and an EPA/docosahexaenoic acid (DHA) preparation (Lotriga®) in the United States and Europe. Although various large-scale clinical trials on the cardiovascular preventive effect of omega-3 PUFA were conducted and reported, the results were not always consistent. The issues of not targeting subjects with hypertriglyceridemia and using low dose of omega-3 PUFA have been suggested to contribute to the failure of demonstrating the preventive effect of omega-3 PUFA in these clinical trials. Taking into account the above issues, the REDUCE-IT trial evaluated a highly purified EPA preparation at a high dose of 4 g/day in patients with hypertriglyceridemia and high cardiovascular risk, and demonstrated an extraordinary outcome of 25% relative reduction in cardiovascular events. This article reviews studies on omega-3 fatty acids during the last 50 years, including the progress in elucidating molecular mechanisms and recent large-scale clinical studie

Omega-3 polyunsaturated fatty acids, Cardiovascular disease, Fatty acid metabolism, Large-scale clinical trial