PEROXIDATION OF LDL FROM COMBINED-HYPERLIPIDEMIC MALE SMOKERS SUPPLIED WITH (OMEGA)OVER-BAR-3 FATTY-ACIDS AND ANTIOXIDANTS

The effects of marine (omega)over-bar-3 polyunsaturated fatty acids (F As) and antioxidants on the oxidative modification of LDL were studied in a randomized, double-blind, placebo controlled trial. Male smokers (n = 41) with combined hyperlipidemia were allocated to one of four g roups receiving supplementation with (omega)over-bar-3 FAs (5 g eicosa pentaenoic acid and docosahexaenoic acid per day), antioxidants (75 mg vitamin E, 150 mg vitamin C, 15 mg beta-carotene, and 30 mg coenzyme Q(10) per day), both (omega)over-bar-3 FAs and antioxidants, or contro l oils. LDL and human mononuclear cells were isolated from the patient s at baseline and after 6 weeks of supplementation. LDL was subjected to cell-mediated oxidation by the patients' own mononuclear cells, as well as to Cu2+-catalyzed and 2,2'-azobis(2-amidinopropane hydrochlori de) (AAPH)-initiated oxidation. Extent of LDL modification was measure d as lag time, the formation rate of conjugated dienes (CDs), the maxi mum amount of CDs formed, formation of lipid peroxides, and the relati ve electrophoretic mobility of LDL on agarose gels. Dietary supplement ation with (omega)over-bar-3 FAs increased the concentration of total (omega)over-bar-3 FAs in LDL and reduced the concentration of vitamin E in serum. The (omega)over-bar-3 FA-enriched LDL particles were not m ore susceptible to Cu2+-catalyzed, AAPH-initiated, or autologous cell- mediated oxidation than control LDL. In fact, enrichment with (omega)o ver-bar-3 FAs significantly reduced the formation rate of CDs when LDL was subjected to AAPH-induced oxidation. Supplementation with moderat e amounts of antioxidants significantly increased the concentration of vitamin E in serum and increased the resistance of LDL to undergo Cu2 +-catalyzed oxidation, measured as increased lag time, reduced formati on of lipid peroxides, and reduced relative electrophoretic mobility c ompared with control LDL. Supplementation with (omega)over-bar-3 FAs/a ntioxidants showed oxidizability of LDL similar to that of control LDL and (omega)over-bar-3 FA-enriched LDL. In conclusion, (omega)over-bar -3 FAs neither rendered the LDL particles more susceptible to undergo in vitro oxidation nor influenced mononuclear cells' ability to oxidiz e autologous LDL, whereas moderate amounts of antioxidants protected L DL against oxidative modification.