There is increasing evidence that oxidative modification of
low-density lipoprotein (
LDL) plays an important role in the pathogenesis of
atherosclerosis. Homozygous familial hypercholesterolaemia (HFH) is characterized by premature, severe
atherosclerosis. Drugs available at present are ineffective in lowering the markedly elevated
LDL levels in this condition;
antioxidant therapy to protect the
LDL against oxidation may be of benefit.
Probucol, the only
drug shown to induce
xanthoma regression in HFH, is a potent
antioxidant, but it also lowers
high-density lipoprotein cholesterol (HDL-C) levels, causing some concern.
Vitamin E is a naturally occurring
antioxidant that does not affect HDL-C levels. We have therefore evaluated the effect of long-term high dose
vitamin E on
xanthoma regression in HFH. Ten subjects with HFH, mean age 17 years (range 4-34), received
vitamin E (400-1000 mg/dl
alpha-tocopherol acetate/day) for a period of 23 months (range 12-27). There was a 4.2-fold increase in the mean serum
vitamin E level (mean (S.D.) 49.7 (19.9) to 177.9 (45.6) mumol/l; P < 0.005), but no change in serum
lipid or
lipoprotein concentrations. Although there was an increase in the in vitro resistance of
LDL to oxidation as determined by the duration of the lag phase during
copper-mediated oxidation (116 (8.34) vs. 141.5 (9.23) min; P < 0.005) there was no
xanthoma regression; in fact they progressed in 4 subjects. Unlike
probucol, high dose long-term
vitamin E has no demonstrable effect on
xanthoma regression in HFH.