(HDL) was greater than that of α-tocopherol to low-density lipoprotein (LDL), or to VLDL and LDL combined, and α-tocopherol was associated with the protein component of the HDL particle. However, vitamin E is readily transferred to other lipoproteins in a process catalyzed by phospholipid transfer protein in human plasma. HDLs can play an important role in delivering vitamin E to circulating blood cells. LDLs appear to be important in supplying vitamin E to peripheral tissues, where it is rapidly exchanged with cell membranes.
Vitamin E turnover rates vary among tissues. Erythrocytes, liver, and spleen are in rapid equilibrium with the plasma α-tocopherol pool. The heart, muscle, and spinal cord have slower turnover rates and the brain is slowest of all.
More than 90% of the human body α-tocopherol pool has been found in adipose tissue, and over 90% of that is in fat droplets, not in cell membranes (Traber and Kayden, 1987). The turnover rate of this pool is quite low, and the relative bioavailability of α-tocopherol in human adipose tissue compared with that in other tissues is controversial (Traber, 1999).
The primary oxidation product of α-tocopherol is α-tocopheryl quinone, which, after reduction to the hydroquinone, can be conjugated to yield a glucuronate. The glucuronate can be excreted in the bile or can be degraded to α-tocopheronic acid in the kidneys and excreted in urine (Drevon, 1991), with possible further oxidation to dimers, trimers, or other adducts (Kamal-Eldin and Appleqvist, 1996). Vitamin E isomers that are not preferentially used, such as γ-tocopherol and some of the isomers in synthetic racemic mixtures, are probably excreted in bile.
Vitamin E functions as a chain-breaking antioxidant in biologic membranes. It is a potent peroxyl-radical scavenger that prevents free-radical damage to polyunsaturated fatty acids (PUFAs) in membrane phospholipids and plasma lipoproteins. Lipid hydroperoxides, oxidized to peroxyl radicals (ROO·), react much faster with vitamin E in its reduced state (vit E-OH) than with PUFAs to form the corresponding hydroperoxide (ROOH) and a tocopheroxyl radical (vit E-O·). The tocopheroxyl radical formed in the cell membrane emerges from the lipid bilayer into the aqueous medium, where hydrogen donors, such as vitamin C or glutathione, react with the tocopheroxyl radical to return it to its reduced state (vit E-OH). Thus, the antioxidant function of oxidized vitamin E can be restored if aqueous antioxidants are present in sufficient amounts (Halpner et al., 1998a, 1998b).
The relative order of peroxyl radical scavenging reactivity of α-, β-, γ-, and δ-tocopherol (100, 60, 25, and 27, respectively) is similar to their relative biologic activities (1.5, 0.75, 0.15, and 0.05 IU·mg−1, respectively) as determined by the rat fetal-resorption assay. However, the biologic activities of vitamin E isomers appear not to reside exclusively in their ability to function as antioxidants. For example, α-tocotrienol has antioxidant activity that is at least equivalent to that of α-tocopherol but has only about one-third of its ability to prevent fetal resorption. It has been suggested that α-tocopherol’s activity is associated with unique structural features that interact preferentially with stereospecific cellular ligands, such as the hepatic protein α-TTP. Some forms of vitamin E modulate the activity of enzymes (such as suppression of arachidonic acid metabolism via inhibition of phospholipase A2 by α-tocopherol), and γ-tocotrienol enhances degradation of an enzyme (3-hydroxy-3-methyl glutaryl coenzyme A reductase) that regulates rates of cholesterol biosynthesis (Traber, 1999).
Vitamin E status depends not only on vitamin E forms and concentrations in the diet, but also on dietary concentrations of PUFA, nutritional history, concentrations of other antioxidants, and the presence of xenobiotics and some clinical abnormalities, such as malabsorption (Machlin, 1991). Indeed, vitamin E deficiency was observed in Saguinus labiatus and Callithrix jacchus (Baskin et al., 1983; Chalmers et al., 1983) in association with malabsorption, but Gutteridge et al. (1986) found no increase in vitamin E deficiency among marmosets with wasting syndrome.
Mason and Telford (1947) were among the first to observe signs of vitamin E deficiency in monkeys (Macaca mulatta) fed diets containing 4% lard and 0.57% cod liver oil. After 5 months, the animals developed muscular dystrophy and brownish intracellular pigmentation in several organs and tissues, including striated and smooth muscle. During the late 1950s and into the late 1960s, several investigators conducted studies of vitamin E deficiency in rhesus monkeys. A profound deficiency state—characterized by anemia, muscular dystrophy, and increased urinary excretion of creatine and allantoin—was reported after 167-391 days (Dinning and Day, 1957; Marvin et al., 1960; Porter et al., 1962; Fitch et al., 1980; Fitch and Dinning, 1963). Fitch et al. (1965) showed that the anemia was cured by α-tocopherol in doses approximating 0.378 mg·BWkg−1·d−1. Remissions of shorter duration could also be achieved by coenzyme Q10 and hexohydrocoenzyme Q4, although their potencies with respect to curing the anemia were markedly lower (Dinning et al., 1962; Farley et al., 1967). It was demonstrated that the anemia was due both to ineffective erythropoiesis, because of defective α-amino-levulinic acid synthesis (Porter and Fitch, 1966), and to hemolysis and shortened red-cell life span as measured by chromium-51 labeling (Fitch 1968a,b). The ineffective