ABSTRACT
The 2.4× increase in degradation of the reductase enzyme reduces the T 1/2 from 3.73-1.59 h. There is a 57%–76% decreased ef•ciency of translation of the reductase mRNA and a 23%–76% decrease in reductase protein mass levels. In addition, the LDL receptor protein is augmented, increasing the number of LDL receptors and LDL removal as well as stimulation of apolipoprotein B degradation clearance (Pearce et al. 1992, 1994; Parker et al. 1993). There is a dose-dependent cholesterol reduction associated with tocotrienols. As the dose of tocotrienols increases, additional conversion to alpha-tocopherol may occur, which will limit the antilipid effects (Qureshi et al. 2002). If the alpha-tocopherol concentration is >20%, it will inhibit the tocotrienol lipid-lowering effects (Qureshi et al. 1986, 1996; Hosomi and Arita 1997). Alpha-tocopherol may compete for binding with the alpha-tocopherol transfer protein (TTP), and thus interfere with the transport of tocotrienols in the circulation (Hosomi and Arita 1997). In addition, alpha-tocopherol attenuates the inhibitory effects of tocotrienols on HMG-CoA reductase and actually induces enzymatic activity (Qureshi et al. 1996, 2002). This increase in HMG-CoA reductase activity with alpha-tocopherol may be one of the reasons that moderate to high dose alpha-tocopherol-as has been used exclusively in clinical trials-has not consistently reduced cardiovascular events in human prospective clinical trials. It is estimated that about 40% of the plasma tocotrienols are carried in LDL (O’Byrne et al. 2000).
