EFFECTS OF SUPPLEMENTATION WITH UNSATURATED FATTY-ACIDS ON PLASMA ANDMEMBRANE LIPID-COMPOSITION AND PLATELET-FUNCTION IN PATIENTS WITH CIRRHOSIS AND DEFECTIVE AGGREGATION

Background/Aims: Defective platelet aggregation and reduced platelet p roduction of thromboxane A(2), a metabolite of arachidonic acid, are c ommon findings in patients with cirrhosis. We evaluated the effects of dietary supplementation with two combinations of unsaturated fatty ac ids on platelet function and plasma and membrane fatty acids in patien ts with liver cirrhosis. Methods: In a double-blind study, 15 patients with cirrhosis and defective aggregation were randomized to receive a 6-week supplementation with gamma-linolenic and linoleic acid (1 g/da y of each fatty acid) or with oleic acid and linoleic acid (groups GLA and OA, respectively). Results: Under baseline conditions, patients s howed elevated concentrations of monounsaturated fatty acids and a red uction in polyunsaturated fatty acids. The product/precursor ratios fo r Delta 6 and Delta 5 desaturases, two key enzymes in the pathway lead ing to arachidonic acid, were significantly reduced in the group of pa tients. In the GLA group, a significant increase in the levels of diho mo-gamma-linolenic acid (20:3 omega 6) was observed in plasma and memb ranes, together with a parallel decrease in the 20:4/20:3 omega 6 rati o after supplementation. No significant changes were observed in the O A group. The levels of arachidonic acid did not change significantly i n either group of patients, Platelet aggregation to collagen was uncha nged in the GLA group, but significantly improved in the OA group. Con clusions: These results show that supplementation with precursors of a rachidonic acid is ineffective in elevating plasma or membrane arachid onate levels and does not improve platelet aggregation, suggesting tha t synthesis of arachidonic acid through the Delta 5 desaturase cannot be correspondingly activated or that incorporation/retention of the pr oduced fatty acid into lipids is impaired. The increased platelet aggr egation in the OA. group is likely to be explained by the effect of ol eic acid contained in the diet, the effects of which may have been cou nteracted by the elevation in 20:3 omega 6, a source of anti-aggregato ry prostanoids, in the GLA group.