Purified Eicosapentaenoic Acid Reduces Small Dense LDL, Remnant Lipoprotein Particles, and C-Reactive Protein in Metabolic Syndrome

  1. Noriko Satoh, MD, PHD1,
  2. Akira Shimatsu, MD, PHD1,
  3. Kazuhiko Kotani, MD, PHD1,
  4. Naoki Sakane, MD, PHD1,
  5. Kazunori Yamada, MD, PHD2,
  6. Takayoshi Suganami, MD, PHD3,
  7. Hideshi Kuzuya, MD, PHD2 and
  8. Yoshihiro Ogawa, MD, PHD34
  1. 1Clinical Research Institute for Endocrine Metabolic Diseases, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
  2. 2Diabetes Center, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
  3. 3Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
  4. 4Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstitution of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan
  1. Address correspondence and reprint requests to Noriko Satoh MD, PhD, Clinical Research Institute for Endocrine Metabolic Diseases, National Hospital Organization, Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto 612-8555, Japan. E-mail: nsato{at}

Eicosapentaenoic acid (EPA), one representative of n-3 unsaturated fatty acids (n-3 PUFAs), is clinically used for its lipid-lowering effects (1). n-3 PUFAs were shown to exert various physiological functions such as antiplatelet actions (by antagonizing effects of arachidonic acid) and plaque stabilization (2,3). Several epidemiological studies have explored antiatherogenic and cardioprotective effects of n-3 PUFA that are abundantly contained in fish oil (4). Dyslipidemia accompanying the metabolic syndrome is often associated with elevated levels of remnant lipoprotein particles and small dense LDL (sdLDL), which are newly recognized risk factors for cardiovascular disease (CVD) (5). It was reported that fish oil improved lipoprotein subclass profiles in subjects with an atherogenic lipoprotein phenotype (6). Besides EPA, docosahexaenoic acid and cholesterol are present in fish oil (7), but it is not clear whether purified EPA independently affects lipoprotein subclass profiles. Therefore, we used purified EPA ethyl ester and examined effects of EPA on atherogenic sdLDL particles and remnant lipoprotein particles in the metabolic syndrome, a precursor of CVD. Furthermore, sdLDL has been reported to synergistically interact with inflammation in pathophysiologic processes leading to CVD (8). Therefore, we simultaneously measured effects of EPA on C-reactive protein (CRP), a marker of inflammation, and examined how alteration of lipoprotein profiles by EPA affects systemic inflammation.


A total of 44 Japanese obese type 2 diabetic patients were recruited in our clinics (Table 1). All patients satisfied the definition and diagnostic criteria of the metabolic syndrome proposed by the National Metabolic Syndrome Criteria Study Group of Japan in 2005 (9). Accordingly, an individual is diagnosed with metabolic syndrome if he or she has central adiposity plus two or more of the following three factors: 1) raised concentration of triglycerides …

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