Prescription omega-3 fatty acids and their lipid effects: Physiologic mechanisms of action and clinical implications

Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA.
Expert Review of Cardiovascular Therapy 04/2008; 6(3):391-409. DOI: 10.1586/14779072.6.3.391
Source: PubMed


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.

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    • "Hence, the American Heart Association (AHA) has recommended the consumption of fatty fish (≥2 portions/week) or fish oil as a complimentary therapeutic strategy to reduce cardiovascular diseases [9] [11]. n-3 reduces serum triglycerides levels (TG); therefore, it is not known how much of the cardiovascular benefits are a result of the TG-lowering effects caused by the n-3, and how much of it is related to TG-independent effects [12]. Another possible benefit of the intake of FAs lies on the prevention of atrial fibrillation. "
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    ABSTRACT: Linoleic (LA) and α-linolenic acids (ALA) are considered essential fatty acids (EFA) because they are not produced by the human body. This way, EFAs sources must come from the diet. The primary dietary source of n-3 fatty acids is ALA, found in seeds and seed oils. Other important sources are fish oils such as tuna, salmon and herring. Currently, numerous studies suggest possible benefits of essential fatty acids in human health, such as in cardiovascular, cognitive and eye health, and also during pregnancy and childhood. This paper also discusses the impact of fatty acids in human metabolism, and the available evidence regarding its risks. It addresses the relevant debate regarding a general ban of trans fatty acids (TFA) from the world food market, because of the cardiovascular risks associated with its consumption.
    Full-text · Article · Jul 2015 · Open Journal of Endocrine and Metabolic Diseases
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    • "Thus, consumption of fish or fish-oil may help prevent adverse consequences of coronary artery disease, especially fatal myocardial infarction and sudden cardiac death. Consumption of omega-3 fatty acids causes improvement in many relevant cardiovascular biomarkers including those represented by hypertriglyceridemia [4], vascular dysfunction [5] [6], and inflammation [6]. However, recently, the reported beneficial effects of omega-3 fatty acids remain debated. "
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    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 2g 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 (O1), 2 (O2), or 4 g (O4), 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. O1 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.
    Full-text · Article · Aug 2014 · International Journal of Cardiology
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    • "Omega-3 has also been found to improve obesity-induced metabolic syndrome through regulating chronic inflammation [17] [18] [19]. Therefore in the present study, we compared the effects of probiotics with omega-3 fatty acid, which is well known for its anti-inflammatory properties and cholesterol lowering effect [20]. Thus, this study investigated whether VSL#3 alone or with omega-3 as adjunct improved lipid profile, insulin sensitivity, and inflammatory responses which are indicators of risk for metabolic syndrome and, ultimately, heart disease, diabetes, and stroke, in a healthy overweight population. "
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    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.
    Full-text · Article · Mar 2014 · Mediators of Inflammation
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