N-ACETYLCYSTEINE TREATMENT LOWERS PLASMA HOMOCYSTEINE BUT NOT SERUM LIPOPROTEIN(A) LEVELS

High levels of lipoprotein(a) (Lp(a)) or homocysteine in plasma have b oth been associated with an increased risk for premature cardiovascula r disease. For both components, the plasma levels are primarily geneti cally determined, and they have been very restintant to therapeutic ap proaches. It has been suggested that N-acetylcysteine (NAG) breaks dis ulphide bonds in Lp(a) as well as between homocysteine and plasma prot eins. In the present study we analyze if this mechanism, in vivo, coul d be used to lower plasma concentrations of Lp(a) and homocysteine. Tr eatment with NAC and placebo was performed in a double blind cross ove r design with 2 weeks wash-out between treatments. Eleven subjects wit h high plasma Lp(a) ( > 0.3 g/l) were recruited from the Lipid Clinic at Sahlgren's Hospital, Goteborg, Sweden. Main outcome measures were t reatment effects on plasma Lp(a) and plasma amino thiols (homocysteine , cysteine and cysteinyl glycine), There was no significant effect on plasma Lp(a) levels. Plasma thiols were significantly reduced during t reatment with NAG: homocysteine by 45% (P < 0.0001), cysteinyl glycine by 24% (P < 0.0001) and cysteine by 11% (P = 0.0002). The high dose o f NAC was well tolerated. In conclusion NAC has no effect on plasma Lp (a) levels while the reduction in homocysteine is considerable and mig ht be of clinical significance in cases with high plasma homocysteine levels.