LOW-DENSITY-LIPOPROTEIN OXIDATION CORRELATION BETWEEN DECREASED RESISTANCE IN-VITRO AND ENHANCED OXIDATION IN-VIVO

Objectives: The oxidation of low density lipoproteins has been recently proposed as one of the critical factors in promoting atherogenesis. This process results from the balance between the prooxidant stimuli and the endogenous antioxidants present in LDL and strictly depends on the concentration of oxidizable substrates, namely unsaturated fatty acids. Methods: Twelve male hypertriglyceridaemic patients were investigated before and after oral supplementation with omega-3 polyunsaturated fatty acids (PUFA) and compared with eighteen untreated healthy matched control subjects. The plasma lipid profile was measured in all patients. LDL oxidation was evaluated as both the susceptibility to in vitro oxidation and the presence of plasma anti-oxidized LDL antibodies (as a marker for in vivo oxidation). Results: Omega-3-fatty acid supplementation caused a significant reduction in plasma triglyceride level (267 +/- 38 vs 375 +/- 33 mg/dl, p < 0.01) and decreased the resistance of LDL to oxidation as revealed by an early and accelerated generation of conjugated dienes following exposure to CuSO4 (105.3 +/- 7 vs 133 +/- 9.3 min, p < 0.01). Moreover, the concentration of the antioxidant vitamin E in LDL was slightly but significantly decreased at the end of the treatment (2.59 +/- 0.19 vs 2.89 +/- 0.17 nmol/mg LDL, p < 0.05), but its efficiency in preventing LDL oxidation was unaltered. Furthermore, a marked increase of the plasma anti-oxidised LDL antibody titre was found in nearly all patients at the end of the treatment (2.08 +/- 0.48 vs 1.37 +/- 0.2 anti-oxidised/anti-native LDL antibody ratio, p < 0.001). Conclusion: These results indicate that PUPA supplementation decreases the resistance of LDL to in vitro oxidation and that this decreased resistance is accompanied by an enhanced LDL oxidation in vivo.