Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications.
ABSTRACT Hypertriglyceridemia is a risk factor for atherosclerotic coronary heart disease. Very high triglyceride (TG) levels (> or =500 mg/dl [5.65 mmol/l]) increase the risk of pancreatitis. One therapeutic option to lower TG levels is omega-3 fatty acids, which are derived from the oil of fish and other seafood. The American Heart Association has acknowledged that fish oils may decrease dysrhythmias, decrease sudden death, decrease the rate of atherosclerosis and slightly lower blood pressure, and has recommended fish consumption or fish oil supplementation as a therapeutic strategy to reduce cardiovascular disease. A prescription omega-3-acid ethyl esters (P-OM3) preparation has been available in many European nations for at least a decade, and was approved by the US FDA in 2004 to reduce very high TG levels (> or =500 mg/dl [5.65 mmol/l]). Mechanistically, most evidence suggests that omega-3 fatty acids reduce the synthesis and secretion of very-low-density lipoprotein (VLDL) particles, and increase TG removal from VLDL and chylomicron particles through the upregulation of enzymes, such as lipoprotein lipase. Omega-3 fatty acids differ mechanistically from other lipid-altering drugs, which helps to explain why therapies such as P-OM3 have complementary mechanisms of action and, thus, complementary lipid benefits when administered with statins. Additional human studies are needed to define more clearly the cellular and molecular basis for the TG-lowering effects of omega-3 fatty acids and their favorable cardiovascular effects, particularly in patients with hypertriglyceridemia.
- SourceAvailable from: Soo Lim[Show abstract] [Hide abstract]
ABSTRACT: Background: Experimental studies demonstrate that higher intake of omega-3 fatty acids (n - 3 FA) improves insulin sensitivity, however, we reported that n - 3 FA 2 g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n - 3 FA in patients with hypertriglyceridemia. Methods: This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n - 3 FA 1 (01), 2 (02), or 4 g (04), respectively daily for 2 months. Results: n - 3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n - 3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. 01 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n - 3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. Conclusions: n - 3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n - 3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. (C) 2014 Published by Elsevier Ireland Ltd.International Journal of Cardiology 08/2014; 176(3). DOI:10.1016/j.ijcard.2014.07.075 · 6.18 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To evaluate the effects of probiotic (VSL#3) and omega-3 fatty acid on insulin sensitivity, blood lipids, and inflammation, we conducted a clinical trial in 60 overweight (BMI > 25), healthy adults, aged 40-60 years. After initial screening the subjects were randomized into four groups with 15 per group. The four groups received, respectively, placebo, omega-3 fatty acid, probiotic VSL#3, or both omega-3 and probiotic, for 6 weeks. Blood and fecal samples were collected at baseline and after 6 weeks. The probiotic (VSL#3) supplemented group had significant reduction in total cholesterol, triglyceride, LDL, and VLDL and had increased HDL (P < 0.05) value. VSL#3 improved insulin sensitivity (P < 0.01), decreased hsCRP, and favorably affected the composition of gut microbiota. Omega-3 had significant effect on insulin sensitivity and hsCRP but had no effect on gut microbiota. Addition of omega-3 fatty acid with VSL#3 had more pronounced effect on HDL, insulin sensitivity and hsCRP. Subjects with low HDL, insulin resistance, and high hsCRP had significantly lower total lactobacilli and bifidobacteria count and higher E. coli and bacteroides count.Mediators of Inflammation 03/2014; 2014:348959. DOI:10.1155/2014/348959 · 2.42 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Hypertriglyceridaemia (HTG) is an independent risk factor for cardiovascular disease; high-risk patients with HTG, such as those with metabolic syndrome or diabetes, may benefit from hypolipidaemic therapies. Several lipid-lowering drugs act by reducing triglyceride (TG) levels, including fibrates, nicotinic acid and omega-3 fatty acids. The omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) dose-dependently reduce plasma TG levels; the effect tends to be greater in patients with higher TG levels at baseline. Evidence from clinical trials suggests that EPA+DHA doses of ≥2g/day are required to achieve significant effects. The optimal TG-lowering doses of EPA+DHA are 3-4g/day, with little evidence to support lipid-altering efficacy of doses of EPA and DHA <1g/day. Predicted changes in fasting serum TG levels at the recommended dietary intakes of EPA and/or DHA of 200-500mg/day are -3.1% to -7.2%. Reductions of plasma TG levels at the optimal doses are from 25-35% up to 45% in the presence of severely elevated TG levels (≥500mg/dl; ≥5.65mmol/l), along with a reduction in non-high-density lipoprotein-cholesterol (non-HDL-C) and an increase in HDL-C. This observation has also been confirmed in statin-treated patients.International journal of cardiology 07/2013; DOI:10.1016/j.ijcard.2013.06.040 · 6.18 Impact Factor