n3 PUFAs improved endothelial function and arterial stiffness with a parallel anti inflammatory effect in adults with metabolic syndrome

January 1, 2014 Human Health and Nutrition Data 0 Comments

n3 PUFAs improved endothelial function and arterial stiffness with a parallel anti inflammatory effect in adults with metabolic syndrome

Year: 2014
Authors: Tousoulis, D. Plastiras, A. Siasos, G. Oikonomou, E. Verveniotis, A. Kokkou, E. Maniatis, K. Gouliopoulos, N. Miliou, A. et al
Publication Name: Atherosclerosis
Publication Details: Volume 232; Pages 10-16


Objectives: Metabolic syndrome (MetS) is associated with adverse cardiovascular events, and impaired vascular function. In this study we evaluated the effects of omega 3 polyunsaturated fatty acids (PUFAs) supplementation on vascular function, inflammatory and fibrinolytic process in subjects with MetS. Methods: We studied the effect of a 12 weeks oral treatment with 2 g/day of  n3 PUFAs in 29 (15 male) subjects (mean age 44 to 12 years) with MetS on three occasions (day 0: baseline, day 28 and day 84). The study was carried out on two separate arms (PUFAs and placebo), according to a randomized, placebo to controlled, double to blind, cross to over design. The diagnosis of MetS was based on the guidelines of Adult Treatment Panel III definition. Endothelial function was evaluated by flow to mediated dilation (FMD) of the brachial artery. Carotid to femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Serum levels of interleukin 6 (IL  6) and plasminogen activator inhibitor 1(PAI 1) were measured by ELISA. Results: Treatment with PUFAs resulted in a significant improvement from day 0 to 28 and 84 in FMD and PWV (p less than   0.001 for all). Nevertheless, treatment with placebo resulted in no significant changes in FMD and PWV. Moreover, PUFAs treatment, compared to placebo, decreased  IL 6 levels and increased PAI  1 levels. Finally, treatment with PUFAs resulted in a significant decrease in fasting triglyceride levels from day 0 to 28 and 84 (p less than   0.001) and in serum total cholesterol levels (p less than   0.001). Conclusions: In subjects with MetS, treatment with  n3 PUFAs improved endothelial function and arterial stiffness with a parallel anti inflammatory effect. (Authors abstract)
The metabolic syndrome (MetS), a concurrence of impaired glucose and insulin metabolism, overweight and abdominal fat distribution, dyslipidemia, and hypertension, has gain awareness
and interest recently, as it is directly correlated with the development and progression of atherosclerotic cardiovascular disease and with type 2 diabetes mellitus and identifies people at
higher risk of cardiovascular disease than the general population. Importantly, the close relationship between MetS, endothelial dysfunction and impaired arterial wall properties is linked to cardiovascular risk, coronary artery disease and mortality.  The use of marine  n3 polyunsaturated fatty acids (omega 3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as presented either in oil fish or in concentrated pharmaceutical
preparations has demonstrate substantial cardiovascular benefits. The effects of  n3 PUFAs on vascular properties and inflammatory process remain unknown. Therefore in the present study the impact of  n3 PUFAs supplementation on the endothelial function, arterial wall properties, inflammatory and fibrinolytic process in subjects with MetS was examined.
In the present study a daily administration of  n3 PUFAs (2 g dose, 46 percent EPA and 38 percent DHA acid) resulted in an improvement in endothelial function, arterial stiffness, inflammatory and fibrinolytic status in MetS patients. n3 PUFAs treatment improved the metabolic profile of these subjects by reducing total cholesterol, LDL to cholesterol and triglycerides levels. These findings introduce the hypothesis that favorable effects of  n3 PUFAs on endothelial function and arterial stiffness in adults with MetS are partially mediated through modification of the metabolic profile and inflammatory process. It is known that  n3 PUFAs act via incorporation into cellular phospholipids partly at the expense of arachidonic acid. This incorporation results in a concomitant reduction of n6 PUFAs suggesting that a specific ratio of n 3 to n 6 fatty acids is important in improving endothelial function. The mechanistic basis for the improved endothelium to triggered relaxation with  n3 PUFAs includes the suppression of thromboxane A2 or cyclic endoperoxides, a reduced production of cytokines, the augmented
endothelial synthesis of nitric oxide, an improvement of vascular smooth muscle cell sensitivity to nitric oxide, and a reduced expression of endothelial adhesion molecules.  Further,
incorporation of  n3 PUFAs into advanced atherosclerotic plaques has a plaque stabilizing effect reducing number of macrophages in the plaque and stabilizing plaque morphology. It has also proposed that  n3 PUFAs reduce production of the vasoconstrictor thromboxane A2, improved vascular reactivity and compliance, and has a favorable effect on autonomic nerve function .
Metabolic syndrome and its components, dyslipidemia, glucose intolerance, diabetes mellitus, obesity, arterial hypertension are characterized by chronic inflammation and an imbalance between proinflammatory and anti to inflammatory cytokines .   n3 PUFAs compete with arachidonic acid as substrates for the formation of pro to inflammatory mediators, such as leukotrienes, prostaglandins, and cytokines. In addition to competitive inhibition of the n 6 fatty acid pathway, n 3 PUFAs may also inhibit production of inflammatory and fibrotic mediators including C reactive protein, interleukins, tumor necrosis factor alpha, matrix metalloproteinases 2 and 9, and tissue inhibitors of metalloproteinase. Treatment with  n3 PUFAs may favorably affect endothelial function and the elastic properties of the arterial tree in MetS subjects, with a parallel antiinflammatory effect. The effect of  n3 PUFAs on vascular endothelium and endothelial activation provides a novel mechanism by which  n3 PUFAs affects vascular compliance, which requires further investigation. (Editors comments)

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