title: Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro.
abstract: OBJECTIVE
  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 conducted in 69 subjects. LDL-C samples isolated at baseline and after 8 weeks were subjected to in vitro tests of LDL-C oxidation. We tested the susceptibility 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. After 8 weeks of therapy policosanol administered at 5 and 10 mg, significantly and in a dose-dependent manner increased the lag phase of conjugated diene 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 significantly. Policosanol (10 mg day(-1)), but not placebo, significantly decreased the rate of conjugated diene generation. Comparison with placebo after therapy also showed significant differences. Macrophage mediated-oxidation was also inhibited by policosanol as evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol (10 mg day(-1)) significantly 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 cholesterol by 10.5% (5 mg day(-1)) and 12.4% (10 mg day(-1)) and LDL-C by 16.7% and 20.2%, respectively. Also, policosanol (10 mg day(-1)) increased HDL-C by 15.2%. Five subjects withdrew from the study, none because of adverse experiences. No clinical or blood biochemical drug-related disturbances were found.
  
  
  CONCLUSIONS
  The present study demonstrated that policosanol administered within its therapeutic dosage for lowering cholesterol (5 and 10 mg day(-1)), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.
authors.affiliation: Center of Natural Products, National Center for Scientific Research, PO Box 6880, Havana, Cuba.
authors.forename: R
authors.initials: R
authors.lastname: Menéndez
authors.forename: R
authors.initials: R
authors.lastname: Más
authors.forename: A M
authors.initials: AM
authors.lastname: Amor
authors.forename: R M
authors.initials: RM
authors.lastname: González
authors.forename: J C
authors.initials: JC
authors.lastname: Fernández
authors.forename: I
authors.initials: I
authors.lastname: Rodeiro
authors.forename: M
authors.initials: M
authors.lastname: Zayas
authors.forename: S
authors.initials: S
authors.lastname: Jiménez
mesh_terms: D000328:Adult; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D008078:Cholesterol, LDL / Q000097:blood / Q000737:chemistry / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D005233:Fatty Alcohols / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000187:drug effects* / Q000302:isolation & purification; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010084:Oxidation-Reduction
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D005233:Fatty Alcohols; D008077:Lipoproteins, LDL; C080710:policosanol; D003300:Copper