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The aim of these studies was to explore the possibility that enhanced triacylglycerol clearance may contribute to the hypotriacylglycerolemic effect of n -- 3 fatty acids in humans. Healthy subjects (n = 20) and hypertriacylglycerolemic patients (n = 6) were given a placebo (olive oil, OO) or a fish-oil concentrate (FOC; 41% eicosapentaenoic acid and 23% docosahexaenoic acid) in two, independent, randomized, blind trials. For the healthy subjects, the FOC treatment period was 3 wk long and FOC intakes were 5 g/d. For the patients, treatment periods were 4 wk long and dosages were 5 g [multiplied by] 70 kg body [wt.sup.-1] [multiplied by] [d.sup.-1]. Washout periods were 2-4 wk for both groups. Blood samples were drawn at the end of each phase and analyzed for plasma lipids, lipoproteins, and endogenous (nonheparin-stimulated) activities of lipoprotein lipase (LPL) and hepatic lipase (HL). In the healthy subjects the FOC decreased plasma triacylglycerol concentrations by 18% (P [is less than] 0.01), whereas in the patients concentrations were reduced by 35% (P [is less than] 0.05). Low-density-lipoprotein-cholesterol concentrations increased by 25% in the latter group (P = 0.06). FOC increased the endogenous activities of LPL and HL by 62% and 68%, respectively (P [is less than] 0.0001), in the healthy subjects, but only LPL in the patients (65%, P [is less than] 0.005). These data suggest that endogenous lipase activities may be altered by nutritional interventions, and further, that accelerated lipolysis could contribute, at least in part, to the observed effects of n -- 3 fatty acids on human lipoprotein metabolism. Am J Clin Nutr 1997;66:254-60.

Fish oils rich in n - 3 fatty acids have been shown to augment endothelium-dependent vasodilation in human peripheral and coronary arteries. This suggests that n - 3 fatty acids may enhance arterial nitric oxide production. To explore this hypothesis we measured total unnary nitrate output in healthy volunteers supplemented with a fish oil concentrate (FOC; n = 15) or purified eicosapentaenoic acid (EPA, n = 14) in a placebo-controlled, parallel-group study. The FOC contained 41% EPA and 23% docosahexacnoic acid (DHA) ethyl esters, whereas EPA was 91% pure; the placebo contained olive oil ethyl esters. Doses were 5 g placebo, 5 g FOC, and 3 g EPA to keep the total n - 3 fatty acid content equal in the latter two groups. The placebo period was 2 wk long and was followed by a 3-wk n - 3 fatty acid phase. At the end of each period, 24-h urine collections and fasting blood samples were obtained. Serum and urinary nitrate concentrations were measured in a blinded fashion. The FOC produced a 43% increase in daily, creatinine-adjusted, nitrate excretion rates (P [is less than] 0.029). Because serum nitrate concentrations were not different, these findings suggest that FOC supplementation may stimulate systemic nitric oxide synthesis. The lack of effect with EPA supplementation suggests that this component of the FOC is not likely to be an active component. If confirmed, these observations suggest another mechanism whereby n - 3 fatty acids may be antiatherogenic.

BackgroundSevere hypertriglyceridemia is a risk factor for acute pancreatitis, therefore decreasing serum triglyceride concentrations is an important component of risk management. Omega-3 fatty acids are well known hypotriglyceridemic agents, but their efficacy in severe forms of the disorder is not well documented. Our objective was to examine the effects of Omacor, a drug composed of 85% omega-3 fatty acid ethyl esters.MethodsForty-two patients with triglyceride concentrations between 5.65 and 22.60 mmol/l (500 and 2000 mg/dl) were studied in a prospective, double-blind, placebo-controlled trial of Omacor (4 g/day for 4 months).ResultsCompared with baseline values, Omacor significantly reduced mean triglyceride concentrations by 45% (P< 0.00001), cholesterol by 15% (P< 0.001), very-low-density lipoprotein cholesterol by 32% (P< 0.0001) and cholesterol: High density lipoprotein (HDL) cholesterol ratio by 20% (P= 0.0013), and increased HDL cholesterol by 13% (P= 0.014) and low-density lipoprotein cholesterol by 31% (P= 0.0014). The placebo had no effect on these parameters. Omacor was well tolerated and no patient discontinued medication because of side effects.ConclusionsFour capsules of Omacor per day markedly decreased triglyceride concentrations in patients with severe hypertriglyceridemia. The availability of a potent and safe omega-3 fatty acid preparation for this patient population should diminish the risk for acute pancreatitis, and may also reduce the long-term risk for cardiovascular disease.