Abstract
A century ago a fat-soluble vitamin from leafy vegetables, later named vitamin E, was discovered to enhance fertility in animals. Vitamin E consists of 8 isomers of tocopherols and tocotrienols, each containing chromanol groups that confer antioxidant properties and differ only in the 15-carbon saturated phytyl poly-isoprenoid side chain of tocopherols and the 15-carbon unsaturated farnesyl poly-isoprenoid side chain of tocotrienols. Although tocotrienol was first isolated from rubber plants in 1964, its importance in multiple disease processes was not recognized until two decades later, when the cholesterol-lowering and anti-cancer effects were first reported. Tocotrienol (T3) protects against radiation injury and mitochondrial dysfunction by preventing opening of the mitochondrial permeability transition pore, thereby inhibiting loss of the active site for oxidative phosphorylation, thioretinaco ozonide oxygen ATP, from mitochondria by complex formation with the active site, TR2CoO3O2NAD+H2PO4 –T3. The preventive effects of tocotrienol on vascular disease, cancer, neurodegeneration and aging are attributed to its effects on cellular apoptosis and senescence. Geranylgeraniol is an important intermediate in the biosynthesis of cholesterol, and cholesterol auxotrophy of lymphoma cell lines and primary tumors is attributed to loss of squalene monooxygenase and accumulation of intracellular squalene. Geranylgeraniol and tocotrienol have synergistic inhibitory effects on growth and HMG CoA reductase activity, accompanied by reduction of membrane KRAS protein of cultured human prostate carcinoma cells. Since cholesterol inhibits opening of the mPTP pore of mitochondria, inhibition of cholesterol biosynthesis by these effects of tocotrienol and geranylgeraniol produces increased mitochondrial dysfunction and apoptosis from loss of the active site of oxidative phosphorylation from mitochondria.