Dietary supplementation with highly purified eicosapentaenoic acid and docosahexaenoic acid does not influence PAI-1 activity

Impaired fibrinolysis due to elevated levels of plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for atherothrombotic disease. Many studies have reported a positive correlation between serum triglycerides and PAI-1 activity. Dietary intervention with very long n-3 fatty acids from marine sources is known to decrease serum triglycerides, but an adverse increase in PAI-1 activity has been reported in some studies. A double blind, placebo controlled study was conducted among 224 middle-aged (ages 36-56), healthy, non-smoking men in which the participants were randomly assigned to daily supplementation with 3.8 g eicosapentaenoic acid/d, 3.6 g docosahexaenoic acid/d, or 4.0 g corn oil/d (placebo) for 7 weeks. PAI-1 activity increased by 2.35 +/- 6.24 U/ml (28%), 1.15 +/- 6.74 U/ml (14%), and 1.33 +/- 5.64 U/ml (22 %) during dietary supplementation with eicosapentaenoic acid, docosahexaenoic acid, and corn oil, respectively, but the changes were not significantly different between groups (p = 0.43). There was no relationship between change in concentrations of serum triglycerides or phospholipid n-3 fatty acids and change in PAI-1 activity. At baseline, analysis was performed to investigate the influence of dietary lipids, blood lipids, and serum fatty acids on plasma concentrations of PAI-1 activity. Dietary intake of saturated fat correlated directly with PAI-I both in crude analysis (r = 0.14, p < 0.05) and after adjustment for age and body mass index (kg/m(2)) (r = 0.20, p < 0.01). Furthermore, PAI-1 was associated with body mass index (r = 0.32, p < 0.001), apo-B100 (r = 0.27, p < 0.001), serum triglycerides (r = 0.31, p < 0.001), and the concentration of n-6 polyunsaturated fatty acids (r = 0.22, p < 0.01) in serum. In a multiple regression analysis, 21% of the variation in PAI-1 activity could be explained by these variables. Plasma PAI-1 activity did not correlate with dietary intake or serum concentrations of n-3 polyunsaturated fatty acids. In a review of 17 trials, including 935 subjects that assessed the effect of n-3 fatty acids on PAI-1 activity, an overall 17.7% increase in PAI-1 activity was estimated by n-3 supplementation. However, only two studies were able to demonstrate a significant increase in PAI-1 attributable to n-3 fatty acid supplementation. We conclude that there is no strong evidence for an unfavourable, clinically relevant effect of n-3 fatty acids on PAI-1 activity in plasma. (C) 2000 Elsevier Science Ltd. All rights reserved.