Long-chain n-3 fatty acids specifically affect rat coagulation factors dependent on vitamin K: relation to peroxidative stress.

Fatty acids of marine origin have been shown to affect blood coagulation in the rat. In an attempt to gain insight into the mechanisms of this phenomenon, we studied the effects of dietary linseed and fish oils on the liver antioxidant status and plasma coagulation parameters in rats on a time-course basis. Dietary enrichment in eicosapentaenoic and docosahexaenoic acids resulted in strong hypocoagulation after only 1 week and a concomitant increase in liver lipid peroxidation and tocopherolquinone content. Enrichment in linolenic acid induced similar increases in lipid peroxidation and tocopherol catabolism but negligible alteration of coagulation. A significant correlation between plasma factor II coagulant activity and liver tocopherolquinone was found in fish oil- but not in linseed oil-fed rats. Although ingestion of tocopherolquinone led to high levels of this compound in the liver, it had only marginal effects on coagulation factors. Thus, it seems unlikely that this vitamin E metabolite could be involved in the lowering of vitamin K-dependent clotting factors through inhibition of gamma-glutamylcarboxylase. Rather, our results indicate that the effects of the n-3 fatty acids of fish oil on vitamin K-dependent coagulation factors are specific and independent of liver tocopherolquinone levels.