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. 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-1 both in crude analysis and after adjustment for age and body mass index (kg/m(2)). Furthermore, PAI-1 was associated with body mass index, apo-B100, serum triglycerides, and the concentration of n-6 polyunsaturated fatty acids 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.
Hansen
J
J
Department of Medicine, Institute of Clinical Medicine, University of Tromso, N-9037, Tromso, Norway. johnbh@fagmed.uit.no
Grimsgaard
S
S
Nordoy
A
A
Bonaa
K H
KH
D000328:Adult; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage* / Q000009:adverse effects; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D014280:Triglycerides / Q000097:blood
D004042:Dietary Fats, Unsaturated; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid