IMPAIRED RESISTANCE TO OXIDATION OF LOW-DENSITY-LIPOPROTEIN IN CYSTIC-FIBROSIS - IMPROVEMENT DURING VITAMIN-E SUPPLEMENTATION

Antioxidants such as vitamin E protect unsaturated fatty acids of LDL against oxidation. In the ex vivo model used, LDL was exposed to Cu2ions, a potent prooxidant capable of initiating the oxidation of LDL. The lag time, indicating the delay of conjugated diene formation in LD L due to antioxidant protection, was measured in 54 cystic fibrosis (C F) patients with plasma alpha-tocopherol levels below (Group A, n = 30 ) or above (Group B, n = 24) 15.9 mu mol/L (mean - 2 SD of Swiss popul ation). Patients were reevaluated after 2 months on 400 IU/d of oral R RR-alpha-tocopherol. In group A, alpha-tocopherol concentrations in LD L increased significantly from 3.2 +/- 1.6 mol/mol LDL to 8.2 +/- 2.8 mol/mol (P < 0.001) and lag times increased from 79 +/- 33 min to 126 +/- 48 min (P < 0.001), whereas in the vitamin E sufficient group B no further increase neither in LDL alpha-tocopherol concentrations or in lag times was observed. LDL oleic acid concentrations were higher, an d linoleic acid concentrations were lower in patients than in controls . After efficient vitamin E supplementation, lag times were positively related to LDL alpha-tocopherol (P < 0.01) and negatively to LDL lino leic and arachidonic acid content (P < 0.001). The maximum rate of oxi dation correlated positively with linoleic and arachidonic acid concen trations, as did the maximum conjugated diene absorbance, These result s indicate that LDL resistance to oxidation is impaired in vitamin E d eficient CF patients but can be normalized within 2 months when alpha- tocopherol is given in sufficient amounts. Linoleic and arachidonic ac id content exhibit a major influence on the LDL resistance to oxidatio n.