n-3 Fatty acids and lipoproteins: Comparison of results from human and animal studies

The impact of n-3 fatty acids (FA) on blood lipoprotein levels has been examined in many studies over the last 15 yr in both animals and humans. Studies in humans first demonstrated the potent triglyceride-lowering effect of n-3 FA, and these were followed up with animal studies to unravel the mechanism of action. This paper reviews the reported effects of n-3 FA on blood lipoproteins in 72 placebo-controlled human trials, at least 2 wk in length and providing 7 or less g of n-3 FA/day. Trials in normolipidemic subjects (triglycerides <2.0 mM; 177 mg/dL) were compared to those in hypertriglyceridemic patients (triglycerides greater than or equal to 2.0 mM). In the healthy subjects, mean triglyceride levels decreased by 25% (P < 0.0001), and total cholesterol (C) levels increased by 2% (P < 0.009) due to the combined increases in low density lipoprotein (LDL)-C (4%, P < 0.02) and high density lipoprotein (HDL)-C (3%, P < 0.008). In the patients, triglyceride levels decreased by 28% (P < 0.0001), LDL-C rose by 7% (P < 0.0001), but neither total C nor HDL-C changed significantly. Although the effect on triglyceride levels is also observed in rats and swine, it is rarely seen in mice, rabbits, monkeys, dogs, and hamsters. Whereas n-3 FA have only a minor impact on lipoprotein C levels in humans, they often markedly lower both total C and HDL-C levels in animals, especially monkeys. These differences are not widely appreciated and must be taken into account when studying the effects of n-3 FA on lipoprotein metabolism.