Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification invitro

Aims The aim of this study was to investigate the effect of policosanol on the susceptibility of LDL-C to in vitro lipid peroxidation in human healthy volunteers. Methods The effect of policosanol (5 and 10 mg day(-1)) on LDL-C oxidation was studied in a double-blind, randomized, placebo-controlled trial conduct ed in 69 subjects. LDL-C samples isolated at baseline and after 8 weeks wer e subjected to in vitro tests of LDL-C oxidation. We tested the susceptibil ity of LDL-C to lipid peroxidation in a cell-free system by the addition of copper ions as well as in a more physiological system, macrophage-mediated oxidation. Results At baseline all groups were well matched regarding all variables. A fter 8 weeks of therapy policosanol administered at 5 and 10 mg, significan tly and in a dose-dependent manner increased the lag phase of conjugated di ene generation (mean +/- s.d.) from 83.79 +/- 29.16 min to 94.90 +/- 25.50 min (5 mg day(-1)) and from 82.74 +/- 17.16 min to 129.89 +/- 35.71 min (10 mg day(-1)), while in the placebo group LDL-C oxidation did not change sig nificantly. Policosanol (10 mg day(-1)), but not placebo, significantly dec reased the rate of conjugated diene generation. Comparison with placebo aft er therapy also showed significant differences. Macrophage mediated-oxidati on was also inhibited by policosanol as evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol (10 mg day(-1)) significantl y lowered malondialdehyde (MDA) generation from 8.50 +/- 0.91 to 5.76 +/- 1 .01 nmol mg(-1) protein. Comparison with placebo after 5 and 10 mg day(-1) showed significant differences. Policosanol significantly lowered total cho lesterol by 10.5% (5 mg day(-1)) and 12.4% (10 mg day(-1)) and LDL-C by 16. 7% and 2-0.2%, respectively. Also, policosanol (10 mg day(-1)) increased HD L-C by 15.2%. Five subjects withdrew from the study, none because of advers e experiences. No clinical or blood biochemical drug-related disturbances w ere found. Conclusions The present study demonstrated that policosanol administered wi thin its therapeutic dosage for lowering cholesterol (5 and 10 mg day(-1)), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.