N-acetylcysteine and serum concentrations of lipoprotein(a)

A high plasma concentration of lipoprotein(a) [Lp(a)], a complex of low-density lipoprotein linked by disulphide bridges to apoprotein(a), is correlated with premature atherosclerosis. We determined whether the serum Lp(a) concentration could be decreased in vitro and in vivo by the reducing agent N-acetylcysteine (NAC), a drug used as a mucolytic agent, which acts by cleaving disulphide bonds. High concentrations of NAC (greater than or equal to 8 mg ml-1) resulted in dissociation of the Lp(a) antigen in vitro. However, the plasma level of Lp(a) was not changed by administration of NAC 1.2 g d-1 for 4 weeks in 7 subjects with a median Lp(a) concentration of 14.3 mg dl-1 (range 2.1-21.0 mg dl-1) or by doubling the dose to 2.4 g d-1 for a further 2 weeks. In 12 subjects with a high plasma level of Lp(a), median 87.0 mg dl-1 (range 42.0-201.6 mg dl-1), a small but significant decrease in Lp(a) concentration of 7% (P = 0.02) was observed after administration of NAC in a dose of 1.2 g d-1 for 6 weeks. These results indicate that NAC has only a limited capacity to reduce the concentration of Lp(a), which is not clinically significant.