EPA and DHA possess different metabolic properties.

Abstract

It is generally accepted that high levels of plasma cholesterol represent an important risk factor for coronary artery disease. However, more resent research suggests that high serum levels of triglyceride (TG)-rich lipoproteins, i.e, very low density lipoprotein (VLDL) and its remnants are also important risk factors.1,2 Serum lipids can be lowered either by dietary treatment with fish oil or by pharmacological treatment with drugs of the fibrate class.5 Fibrate action has been partly ascribed to increased fatty acid oxidation, decreased TG synthesis and secretion, and enhanced clearance of VLDL from serum due to a down-regulation of hepatic apoC-III gene-expression.6,7 Besides lowering plasma lipids and the apparent protection in thrombosis, dietary supplements enriched in omega-3 fatty acids have proved to lower blood pressure, alter lipoprotein metabolism and dampen platelet aggregation among other beneficial effects in humans.8–10 The two components of fish oil attracting the most attention, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are still often referred to as omega-3, or n-3 fatty acids without any further distinction. Nearly all studies that have been conducted have used a mixture of EPA and DHA. It has, however, been reported that DHA are retroconverted to EPA in cultured hepatocytes,11 rat12 and man13 and it is, therefore, conceivable that EPA and DHA possess different metabolic properties. The availability of TG is a major driving force in the secretion of VLDL by the liver. Evidently, factors influencing the balance between TG biosynthesis and/ or fatty acid oxidation may ultimately influence plasma lipoprotein levels and metabolism.15 We have demonstrated this mechanism of action with sulfur-substituted fatty acids (3thia fatty acids). In rats, the TG-lowering effect of the 3-thia fatty acid tetradecylthioacetic acid (C14-S-acetic acid), was established within hours of feeding and this was mainly due to stimulated mitochondrial fatty acid oxidation, thereby reducing hepatic TG synthesis and secretion. The mechanism has been further evaluated using cell cultures. Treatment of rats with the peroxisomaland mitochondrialproliferating C14-S-acetic acid, caused a drop in the hepatic content of ERA. Conversion of EPA to