The effect of low-dose marine n-3 fatty acids on the biosynthesis of pro-inflammatory 5-lipoxygenase pathway metabolites in overweight subjects: a randomized controlled trial.

INTRODUCTION: Marine n-3 polyunsaturated fatty acids (PUFA) have a variety of anti-inflammatory properties. This study evaluated the effect of n-3 PUFA in a low, but recommended cardioprotective dosage on the formation of 5-lipoxygenase pathway metabolites in overweight subjects. MATERIALS AND METHODS: Fifty subjects were randomized to 1.1g of n-3 PUFA or olive oil for 6 weeks. RESULTS: Leukotriene B(4) formation decreased by 14% in the n-3 PUFA group which proved to be significant within the group (p=0.005) but not between groups (p=0.25). The formation of 5-hydroxyeicosatetraenoic acid (5-HETE) did not differ significantly between the groups. In the n-3 PUFA group, both 5-hydroxyeicosapentaenoic (5-HEPE) acid and leukotriene B(5) increased significantly compared to the control group (p<0.001). CONCLUSION: In conclusion, we did not observe any significant net anti-inflammatory effect on the 5-lipoxygenase pathway from a daily supplement of 1.1g marine n-3 PUFA for 6 weeks.

The effect of n-3 polyunsaturated fatty acids on leukotriene B4 and leukotriene B5 production from stimulated neutrophil granulocytes in patients with chronic kidney disease.

The proinflammatory leukotriene B4 (LTB4) may be of importance in the progression of chronic kidney disease (CKD). We investigated whether n-3 polyunsaturated fatty acids (PUFA) decrease LTB4 and increase the formation of the less inflammatory leukotriene B5 (LTB5) in patients with CKD. Fifty-six patients with CKD stage 2-5 were randomised to 2.4 g n-3 PUFA or olive oil for 8 weeks. Compared to controls, n-3 PUFA significantly decreased release of LTB4 (p<0.001) and 5-hydroxyeicosatetraenoic acid (5-HETE) (p<0.01) and significantly increased release of LTB5 (p<0.001) and 5-hydroxyeicosapentaenoic acid (5-HEPE) (p<0.001) from stimulated neutrophil granulocytes. Kidney function evaluated by creatinine clearance and proteinuria did not improve. In conclusion, n-3 PUFA supplementation for 8 weeks in patients with CKD stage 2-5 significantly decreased LTB4 and 5-HETE and significantly increased LTB5 and 5-HEPE. No effect was seen on kidney function.

Bioavailability of marine n-3 fatty acid formulations.

The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations - ethyl esters, free fatty acids and re-esterified triglycerides - with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.

Fatty acid composition of the internal mammary artery in relation to dietary intake of marine n-3 polyunsaturated fatty acids and association with flow-mediated vasodilation.

Some evidence suggests that long-chain marine n-3 polyunsaturated fatty acids (n-3 PUFA) may increase production of vasodilatory nitric oxide from vascular endothelium. Fatty acids may therefore play a role for the left internal mammary artery (LIMA) graft function in coronary artery bypass grafting (CABG). However, little is known about the composition of fatty acids in the vessel wall of the LIMA. Using gas chromatography we investigated fatty acid composition in segments of the LIMA, in plasma nonesterified fatty acids (NEFA), in plasma phospholipid (PL) and in the pericardial adipose tissue (PAT) from 22 patients undergoing CABG. Furthermore, we investigated whether there was an association between the n-3 PUFA composition in LIMA and flow-mediated vasodilation (FMD). Self-reported fish consumption and supplementation of eicosapentaenoic acid and docosahexaenoic acids were reflected by the fatty acid composition in NEFA, PL and in PAT, but less so in the LIMA. There was no association between FMD and fatty acid composition of the LIMA.

Flow-mediated vasodilation and dietary intake of n-3 polyunsaturated acids in healthy subjects.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two major marine n-3 polyunsaturated fatty acids (PUFA), have been proposed to decrease the risk of atherosclerosis and coronary heart disease. An early event during atherogenesis is endothelial dysfunction. We studied the correlation between fish consumption, serum phospholipid (sPL) levels of DHA and EPA and flow-mediated vasodilation (FMD), a measure of endothelial function. Furthermore, subjects were classified according to whether they did (Fish+, n = 19) or did not (Fish-, n = 21) follow the Danish recommendations, consuming at least 300 g fish/week. Neither the fish intake, sPL EPA nor sPL DHA significantly correlated with FMD, -0.20 (p = 0.23), -0.23 (p = 0.15) and -0.06 (p = 0.72), respectively. Also, when comparing the Fish+ and the Fish- group we did not find any significant differences in FMD (p = 0.33). In conclusion, our results did not show any correlation between intake and sPL levels of marine n-3 PUFA and FMD in healthy subjects.

Marine n-3 fatty acids: basic features and background.

There is some evidence from epidemiology that intake of n-3 polyunsaturated fatty acids (PUFA) from seafood may protect against coronary artery disease (CAD). This hypothesis is further supported from animal data showing a beneficial effect of n-3 PUFA on thrombosis and atherosclerosis in animals fed fish oils in most, but not all, studies. There are several mechanisms by which an increased intake of marine n-3 PUFA may protect against CAD; the most universal finding is a reduction of plasma triglycerides. It is puzzling, however, that a very low amount of n-3 PUFA, with no known beneficial biochemical effects, seems to be cardioprotective. It has therefore been of paramount interest to perform clinical trials. Such evidence and trials are discussed in later chapters, and the results have been very encouraging.