n Ondersoek na die moontlike meganismes waardeur 'n visoliekonsentraat plasmafibrinogeenvlakke beïnvloed

Abstract

Fish oil contains eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), which may have beneficial effects in the prevention and treatment of coronary heart disease and atherosclerosis through effects on serum lipids and lipoproteins, eicosanoid production, blood pressure, carbohydrate metabolism, haematological variables and on the haemostatic system. It appears as if high levels of plasma fibrinogen are associated with an increased risk for coronary heart disease. The main objective of this study was to examine the influence of a fish oil concentrate on plasma fibrinogen concentrations, as well as possible mechanisms by which fish oil could affect fibrinogen levels. Possible mechanisms that were examined in this study were: the effects of circulating free fatty acids (FF A) and of fibrinolytic factors, especially tissue plasminogen activator (tPA) antigen and plasminogen activator inhibitor (PAI) activity, on plasma fibrinogen. The influence of a fish oil concentrate on some other coagulation and fibrinolytic factors were also investigated. Twenty healthy volunteers (10 women, 10 men) participated in a double-blind, placebo controlled, cross-over study. Subjects were randomly assigned to receive either 6 g/day of fish oil concentrate (1.14 g EPA, 0.44 g DHA) or 6 g of olive oil/day as placebo, for 6 weeks. A washout period of 3 weeks followed, after which cross-over took place for a further 6 weeks. Fasting venous blood samples were collected at baseline and completion of each period before and after standardized venous occlusion was performed. Effects on serum lipids and lipoproteins, free fatty acids (FFA), insulin, glucose, proteins, enzymes, excretion products, minerals, electrolytes, plasma fibrinogen, factors V, VII, VIII, X and plasminogen activities, tP A antigen, and PAI activity, plasma fatty acid profiles, as well as erythrocyte membrane deformability and haematocrit were determined with standardized methodology. Anthropometric measurements of subjects were also monitored. Significant differences between groups and between baseline and end values were calculated with analysis of variance and paired Student t-tests, using the SAS ® package. The expected decrease in serum triglycerides with intake of fish oil was observed, even though mean baseline levels were low (from 0.69±0.27 to 0.49±0.16 mmol/L). Olive oil supplementation resulted in a significant decrease in serum total cholesterol (TC), (from 4.98±0.88 to 4.44±0.81 mmol/L). This decrease was due to decreases in both high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). No significant changes with fish oil supplementation were observed on serum TC, HDL-C, LDL-C, FFA, haematocrit, erythrocyte membrane deformability, body mass index and waist/hip ratio. Both fish oil and olive oil caused a decrease in plasma fibrinogen, but only significantly in the women (from 3.23±0.98 to 2.64±0.55 and from 3.19±0.72 to 2.66±0.49 g/L, respectively). A possible reason for this may have been that the women had higher initial plasma fibrinogen levels than the men. Fish oil significantly lowered plasma factor VII activity (from 86.73±25.43 to 57.67±27.25 %), again mainly because of effects in the women. Both fish oil and olive oil resulted in lower plasma factor X levels in the women (from 93.63± 17.30 to 60.33±24.59 % and from 85.0±23.78 to 58.3±23.98 %, respectively). Plasma factor V levels were also decreased in women who received fish oil (from 74.13± 15.30 to 48.0±23.11 %). Olive oil supplementation caused a decrease in insulin sensitivity, especially in the women, and fish oil supplementation showed a tendency towards lowering of insulin sensitivity in the women (from 287.26±91. 73 to 152.32±51.47 and from 211.11 ±97.13 to 158.12±53.19 for women, respectively). Both fish oil and olive oil significantly increased PAI-1 activity (from 3.87±7.15 to 13.57±9.36 U/mL and 6.16±8.77 to 11.30±7.12 U/mL, respectively), but had no effect on tPA or plasminogen levels. Levels of serum proteins, minerals and enzymes showed that oxidative haemolysis of red blood cells possibly did not occur. It is concluded that in subjects with high initial plasma fibrinogen levels, fish oil and olive oil may lower plasma fibrinogen. The mechanisms by which fish oil could lower plasma fibrinogen was not due to changes in circulating FF A's. Also, it seems that an increased fibrinolytic activity was not responsible, because no changes in tPA antigen and PAI activity levels were observed. The mechanisms need further investigation. The results indicated that intake of fish oil and olive oil may also lower activities of some other enzymes in the coagulation cascade, especially in the women, and that it may cause a detrimental effect on PAI activity. The mechanism for this detrimental effect, which may be a result of effects on insulin sensitivity, deserves serious attention.