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Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity

      Abstract

      There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. Evidence that antioxidant therapy decreases mortality is, however, inconclusive. We have examined the effects of vitamin E on the susceptibility of LDL and high density lipoprotein (HDL) to oxidation, and on cholesteryl ester heteroexchange in an in vitro system using autologous serum lipoproteins. Vitamin E in doses of 200 and 400 mg/day were administered orally to 21 healthy volunteers (12 females and nine males) aged between 23 and 50 years, and to 16 healthy volunteers (eight females and eight males) aged between 22 and 51 years for 50 days, respectively. Fasting serum lipoproteins, susceptibility of lipoproteins to oxidation and cholesteryl ester transfer activity (CETA) were measured before and after vitamin E supplementation. Serum lipoprotein and lipid concentrations did not change significantly in either group. The LDL-conjugated diene (CD) lag phase during incubation with Cu2+ was increased by 157% (110–232%) (median (interquartile range)) (P<0.05) on vitamin E (200 mg/day) and by 235% (185–259%) (P<0.0001) on 400 mg/day. The lag phases for LDL-lipid peroxide (LPO) generation were also significantly increased by 146% (122–192%) (P<0.005) and 177% (101–267%) (P<0.005), respectively. The HDL-CD lag phase also increased on both doses 140% (115–169%) (P<0.005) and 171% (122–192%) (P<0.005), as did the HDL-LPO lag phase by 123% (104–153%) (P<0.05) on 200 mg/day and 240% (97–360%) (P<0.005) on 400 mg daily. Cholesteryl ester transfer activity from HDL to very low and low density lipoproteins significantly increased from 12.7±2.6 (mean±SEM) to 16±3.4 nmol/ml/h (P<0.05) on 200 mg/daily and 10.4±2.0 to 19.2±3.3 nmol/ml/h (P<0.005) on vitamin E, 400mg day. Thus, vitamin E (200 and 400mg daily) significantly decreased the susceptibility of LDL and HDL to oxidation in vitro. However, the increase in CETA resembled that reported with another antioxidant, probucol. Some evidence has suggested that increased CETA is potentially deleterious and it might therefore counteract beneficial effects of vitamin E or probucol on the susceptibility of lipoproteins to oxidation.

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