Vitamin E supplementation in hyperlipidaemic patients: effect of increasing doses on in vitro and in vivo low-density lipoprotein oxidation.
BACKGROUND
Vitamin E supplementation is associated with a reduced risk of developing atherosclerotic events; probably because it inhibits low-density lipoprotein (LDL) oxidation, an initial step in atherosclerosis. Metal ion-dependent LDL oxidation is a commonly used method to estimate oxidizability of LDL, but the effect of antioxidant supplementation on the levels of autoantibodies to oxidised LDL (ox-LDL), an in vivo indicator of LDL oxidation, is unknown.


METHODS
This double-blind, placebo-controlled study investigated the susceptibility of LDL to copper induced oxidation and malondialdehyde (MDA) derivatized-LDL (MDA-LDL) in hyperlipidaemic patients on supplements of vitamin E. The vitamin E group (n = 20) took vitamin E 100 IU daily and the dose was doubled at six-weekly intervals to 1600 IU daily. The control group (n = 17) received placebo in the same fashion. Blood samples were obtained at baseline and each subsequent visit to measure vitamin E status and oxidation of LDL.


RESULTS
A significant increase in both alpha-tocopherol levels and the lengths of lag phase was seen in the vitamin E group after first week of supplementation (100 IU day-1). This continued to rise in a dose-dependent fashion with a doubling of the lag phase on 1600 IU daily. However, the titre of antibodies to MDA-LDL was not altered.


CONCLUSIONS
The results suggest that although regarded as an in vivo marker of LDL oxidation, antibodies to MDA-LDL may not be a suitable measure to evaluate the effect of short-term antioxidant supplementation. The failure of autoantibody titres to fall despite reduced oxidizability of LDL may possibly be attributable to a long half-life of the antibody or, once initiated, a continuous immunological response to ox-LDL contained in atherosclerotic lesions of the arterial wall.
Wen
Y
Y
Department of Therapeutics, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland.
Killalea
S
S
Norris
L A
LA
Cooke
T
T
Feely
J
J
D000975:Antioxidants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D014810:Vitamin E / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000975:Antioxidants; D005609:Free Radicals; D008077:Lipoproteins, LDL; D014810:Vitamin E