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 d eveloping 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 aut oantibodies to oxidised LDL (ox-LDL), an in vivo indicator of LDL oxidation , is unknown. Design This double-blind, placebo-controlled study investigated the suscept ibility of LDL to copper induced oxidation and malondialdehyde (MDA) deriva tized-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 = 1 7) received placebo in the same fashion. Blood samples were obtained at bas eline and each subsequent visit to measure vitamin E status and oxidation o f LDL. Results A significant increase in both alpha-tocopherol levels and the leng ths of lag phase was seen in the vitamin E group after first week of supple mentation (100 IU day(-1)). This continued to rise in a dose-dependent fash ion with a doubling of the lag phase on 1600 IU daily. However, the titre o f antibodies to MDA-LDL was not altered. Conclusions The results suggest, that although regarded as an in vivo marke r 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 pos sibly be attributable to a long half-life of the antibody or, once initiate d, a continuous immunological response to ox-LDL contained in atherosclerot ic lesions of the arterial wall.