n-3 Polyunsaturated Fatty Acids: Promising Nutrients for Preventing Cardiovascular Disease

Shusuke Yagi, Daiju Fukuda, Ken-Ichi Aihara, Masashi Akaike, Michio Shimabukuro, Masataka Sata, Shusuke Yagi, Daiju Fukuda, Ken-Ichi Aihara, Masashi Akaike, Michio Shimabukuro, Masataka Sata

Abstract

The adoption of the Western-style diet, with decreased fish intake and lack of exercise, has increased the prevalence of cardiovascular disease (CVD) in Japan. Statin treatment has been established to reduce the risk of cardiovascular events; however, 60%-70% of these events occur despite its use. Thus, the residual risk for CVD should be identified and resolved to reduce further cardiovascular events. The serum levels of n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid and docosahexaenoic acid, are reportedly associated with an increased incidence of cardiovascular events and mortality, whereas the addition of n-3 PUFA treatment to the statin treatment decreases cardiovascular events. Similar to statins, n-3 PUFAs have pleiotropic effects in addition to lipid-modifying effects. Pre-clinical and clinical studies have shown that n-3 PUFAs prevent cardiovascular events by ameliorating endothelial function and attenuating lipid accumulation, vascular inflammation, and macrophage recruitment, thereby causing coronary plaque development and rupture. Taken together, n-3 PUFAs are comprehensively able to attenuate the atherogenic response. Therefore, n-3 PUFA intake is recommended to prevent cardiovascular events, particularly in patients with multiple cardiovascular risk factors.

Keywords: Cardiovascular disease; Docosahexaenoic acid; Eicosapentaenoic acid; Residual risk.

Conflict of interest statement

M. Sata received research funding from Tanabe-Mitsubishi, Takeda, Astellas, Byer Healthcare, Daiichi-Sankyo, MSD, and Ono and lecture fees from Astellas, Boehringer Ingelheim, Byer Healthcare, Mochida, Takeda, Tanabe-Mitsubishi, Novartis, AstraZeneca, MSD, and Shionogi. The Department of Cardio-Diabetes Medicine, Tokushima University Graduate School is supported in part by unrestricted research grants from Actelion, Boehringer Ingelheim, Kowa, and Tanabe-Mitsubishi. The others declare that they have no conflicts of interest to disclose.

Figures

Fig. 1.
Fig. 1.
The metabolism of PUFAs. AA, arachidonic acids; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid (https://pubchem.ncbi.nlm.nih.gov/compound)15)
Fig. 2.
Fig. 2.
The effects of n-3 PUFAs on the progression of atherosclerosis in Apoe−/− mice. En face Sudan IV staining of the aorta. The high-dose EPA+DHA group, which received an additional dose of DHA to the same dose of EPA as that in the EPA group, demonstrated a greater reduction in atherogenesis compared with the EPA group. The low-dose EPA+DHA group, in which half the amount of EPA in the EPA group was replaced with a similar amount of DHA, demonstrated similar suppression of atherogenesis as that in the EPA group30).
Fig. 3.
Fig. 3.
The presumed mechanism of the anti-inflammatory effect of n-3 PUFAs. A: Unsaturated fatty acids-poor membrane B: Unsaturated fatty acids-rich membrane
Fig. 4.
Fig. 4.
n-3 PUFAs attenuate all components of atherosclerosis.

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