Effect of ascorbate supplementation on low density lipoprotein oxidation in smokers

The oxidative modification of low density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis. Furthermore, evidence of oxidized LDL (ox-LDL) has been found in vivo. Supplementation of some, animal models with antioxidants has been shown to retard the formation of aortic atherosclerosis. Ascorbate (vitamin C) is a highly potent aqueous-phase antioxidant in plasma, which has been shown in vitro to retard LDL oxidation. Cigarette smokers have reduced concentrations of ascorbate in their plasma, and their LDL may be more prone to oxidation. Hence, the objective of the present study was to examine the effect of ascorbate depletion and supplementation on the propensity of LDL to oxidize in smokers in a 6-week study. Nineteen healthy smokers followed a low ascorbate diet (less than or equal to 30 mg/day) for 2 weeks, then were randomly assigned to receive placebo or 1000 mg ascorbate per day for 4 weeks. Blood was taken at 0 and 4 weeks of supplementation for study of LDL oxidative susceptibility. LDL was oxidized with 5 mu mol/l copper. The ascorbate-supplemented group had significant increases in plasma ascorbate. The placebo group showed no change in the time course of LDL oxidation between 0 and 4 weeks. However, the ascorbate-supplemented group has a significant reduction in LDL oxidative susceptibility as measured by thiobarbituric acid-reactive substances (TEARS) and the formation of conjugated dienes. The ascorbate-supplemented group demonstrated significantly increased lag phase and decreased oxidation rate at 4 weeks compared to 0 weeks. No changes were found in the placebo group. The ascorbate-supplemented group showed no biochemical signs consistent with increased body iron stores. Supplementation of otherwise healthy smokers for 4 weeks with 1000 mg ascorbate per day resulted in increased plasma ascorbate and reduced LDL oxidative, susceptibility.