Effects of supplementation with unsaturated fatty acids on plasma and membrane lipid composition and platelet function in patients with cirrhosis and defective aggregation.
OBJECTIVE
Defective platelet aggregation and reduced platelet production of thromboxane A2, a metabolite of arachidonic acid, are common findings in patients with cirrhosis. We evaluated the effects of dietary supplementation with two combinations of unsaturated fatty acids on platelet function and plasma and membrane fatty acids in patients 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/day of each fatty acid) or with oleic acid and linoleic acid (groups GLA and OA, respectively).


RESULTS
Under baseline conditions, patients showed elevated concentrations of monounsaturated fatty acids and a reduction in polyunsaturated fatty acids. The product/precursor ratios for delta6 and delta5 desaturases, two key enzymes in the pathway leading to arachidonic acid, were significantly reduced in the group of patients. In the GLA group, a significant increase in the levels of dihomo-gamma-linolenic acid (20:3omega6) was observed in plasma and membranes, together with a parallel decrease in the 20:4/20:3omega6 ratio after supplementation. No significant changes were observed in the OA group. The levels of arachidonic acid did not change significantly in either group of patients. Platelet aggregation to collagen was unchanged in the GLA group, but significantly improved in the OA group.


CONCLUSIONS
These results show that supplementation with precursors of arachidonic acid is ineffective in elevating plasma or membrane arachidonate levels and does not improve platelet aggregation, suggesting that synthesis of arachidonic acid through the delta5 desaturase cannot be correspondingly activated or that incorporation/retention of the produced fatty acid into lipids is impaired. The increased platelet aggregation in the OA group is likely to be explained by the effect of oleic acid contained in the diet, the effects of which may have been counteracted by the elevation in 20:3omega6, a source of anti-aggregatory prostanoids, in the GLA group.
Marra
F
F
Istituto di Medicina Interna, Università di Firenze, Florence, Italy.
Riccardi
D
D
Melani
L
L
Spadoni
S
S
Galli
C
C
Fabrizio
P
P
Tosti-Guerra
C
C
Carloni
V
V
Gentilini
P
P
Laffi
G
G
D000368:Aged; D001792:Blood Platelets / Q000502:physiology*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D008055:Lipids / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood / Q000178:diet therapy*; D008297:Male; D008563:Membrane Lipids / Q000032:analysis*; D008875:Middle Aged; D019301:Oleic Acid / Q000494:pharmacology; D010974:Platelet Aggregation / Q000502:physiology; D012016:Reference Values; D013928:Thromboxane A2 / Q000096:biosynthesis; D014810:Vitamin E / Q000097:blood; D017965:gamma-Linolenic Acid / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; D008055:Lipids; D008563:Membrane Lipids; D014810:Vitamin E; D019301:Oleic Acid; D013928:Thromboxane A2; D017965:gamma-Linolenic Acid; D019787:Linoleic Acid