A. Palomaki et al., Effects of lovastatin therapy on susceptibility of LDL to oxidation duringalpha-tocopherol supplementation, ART THROM V, 19(6), 1999, pp. 1541-1548
A randomized, double-masked, crossover clinical trial was carried out to ev
aluate whether lovastatin therapy (60 mg daily) affects the initiation of o
xidation of low density lipoprotein (LDL) in cardiac patients on alpha-toco
pherol supplementation therapy (450 IU daily). Twenty-eight men with verifi
ed coronary heart disease and hypercholesterolemia received alpha-tocophero
l with lovastatin or with dummy tablets in random order. The two 6-week, ac
tive-treatment periods were preceded by a washout period of at least 8 week
s. The oxidizabilty of LDL was determined by 2 methods ex vivo. The depleti
on times for LDL ubiquinol and LDL alpha-tocopherol were determined in time
d samples taken during oxidation induced by 2,2-azobis(2,4-dimethylvaleroni
trile). Copper-mediated oxidation of LDL isolated by rapid density-gradient
ultracentrifugation was used to measure the lag time to the propagation ph
ase of conjugated-diene formation. alpha-Tocopherol supplementation led to
a 1.9-fold concentration of reduced alpha-tocopherol in LDL (P<0.0001) and
to a 2.0-fold longer depletion time (P<0.0001) of cr-tocopherol compared wi
th determinations after the washout period. A 43% prolongation (P<0.0001) w
as seen in the lag time of conjugated-diene formation. Lovastatin decreased
the depletion time of reduced alpha-tocopherol in metal ion-independent ox
idation by 44% and shortened the lag time of conjugated-diene formation in
metal ion-dependent oxidation by 7%. In conclusion alpha-tocopherol supplem
entation significantly increased the antioxidative capacity of LDL when mea
sured ex vivo, which was partially abolished by concomitant lovastatin ther
apy.