Failure of N-acetylcysteine to reduce low-density lipoprotein oxidizability in healthy subjects.

We have studied the effects of N-acetylcysteine, which is thought to have antioxidant properties, on the susceptibility of low-density lipoprotein to oxidation and on whole-blood glutathione concentrations in six healthy volunteers. N-acetylcysteine was given orally in a dosage of at 1.2 g per day for 4 weeks, followed by 2.4 g per day for a further two weeks. The susceptibility of low-density lipoprotein to in vitro Cu(2+)-oxidation was determined by continuously measuring the formation of conjugated dienes. Whole-blood concentrations of reduced and oxidized glutathione were also determined. N-acetylcysteine had no effect on the susceptibility of LDL to oxidation. Concentrations of vitamin E in the serum and in low-density lipoprotein were not changed. Compared with controls the concentration of glutathione in N-acetylcysteine treated subjects was reduced (-48%) and the concentration of oxidized glutathione was higher (+80%). The GSH/GSSG-ratio, a marker of oxidative stress was 83% lower. The results do not support the supposed antioxidative action of N-acetylcysteine. It seems more likely that N-acetylcysteine acts as a pro-oxidant in the dosage used.