A moderate in vivo vitamin E supplement counteracts the fish-oil-induced increase in in vitro oxidation of human low-density lipoproteins

Abstract

The atherogenicity of the low-density-lipoprotein (LDL) partide �5 increased by peroxidation of its polyunsaturated fatty acids (PUFAs). Thus, diets high in the plasma cholesterol-lowering PUFAs decrease the number of LDL particles but mayat the same time-increase the susceptibility of LDLs to oxidative modification. We therefore examined whether this potentially unbeneficial effect of PUFA on LDL oxidation could be counteracted by moderate amounts of vitamin E, a natural antioxidant. Eleven healthy normocholesterolemic men, aged 19-53 y, were studied. For 3 wk seven men received a daily supplement of 6 g fish oil (> 50% n-3 PUFAs). Four of these men also received a daily supplement of300 mg vitamin E. The remaining four men continued on their habitual diet and served as a control group. LDL (0.25 g/L) was oxidized with CuCl2 ( 1.66 �zmol/L) and peroxidation was measured weekly by monitoring the formation of conjugated dienes at 234 nm over a 5-h period at 37 #{176}C. The time needed to start oxidation (lag time) depends on the amounts of PUFAs and antioxidants incorporated into the LDL particle and reflects its oxidation resistance. The study was approved by the Medical Ethics Committee of the University of Limburg. After 3 wk the change in the maximum amount of dienes formed was significantly higher in the groups receiving fish oil than in the control group (P < 0.05; Kruskal-Wallis one-way analysis of variance). The increase in dienes over 5 h was 24.2 ± 8.6 �tmol dienes/g LDL (i ± SD) in the fish-oil group and 2 1.6 ± 4.3 �tmol dienes/g LDL in the fish-oil-vitamin E group. whereas the change in the control group was only 0.9 ± 10.7 ��mol/g LDL. The lag time decreased by 22.7 ± 8.4 mm in the fish-oil group, but it increased by 5.6 ± 14.6 mm in the fish-oilvitamin E group (P < 0.05). The lag time in the control group (change, -7.5 ± 6.8 mm) tended to be longer compared with the fish-oil group and shorter compared with the fish-oil vitamin E group. The maximum rate ofdiene formation during oxidation decreased by 0.57 ± 0.35 ��mol dienes#{149}min’#{149}g LDL’ in the fish-oil/vitamin E group. Mean changes were -0.25 ± 0.7 1 .tmol dienes . min ‘ . g in the control group and + 0.22 ± 0.30 �tmol dienes#{149} mm’’ -g LDL’ in the fish-oil group. This pilot study shows that a moderate in vivo vitamin E supplement counteracts the fish-oil-induced decrease in oxidation resistance of LDL. Surprisingly, our results suggest that the largest decrease in the maximum rate of oxidation occurred in the fish-oil-vitamin E group, even though most antioxidants are consumed during the lag time. Further work should clarify the practical and physiological implications of our findings. #{163}3