also provides antioxidant protection indirectly by regenerating other biological antioxidants such as glutathione and α-tocopherol back to their active state (Jacob, 1995).

Ascorbic acid functions as a reducing agent for mixed-function oxidases in the microsomal drug-metabolizing system that inactivates a wide variety of substrates, such as endogenous hormones or xenobiotics (i.e., other chemical compounds such as drugs, pesticides, or carcinogens that are foreign to humans) (Tsao, 1997). The activity of both microsomal drug-metabolizing enzymes and cytochrome P-450 electron transport is lowered by ascorbate deficiency. The vitamin is involved in the biosynthesis of corticosteroids and aldosterone and in the microsomal hydroxylation of cholesterol in the conversion of cholesterol to bile acids. In reactions similar to the hydroxylation of proline for collagen synthesis, ascorbate is required along with iron at two steps in the pathway of carnitine biosynthesis. Ascorbic acid modulates iron absorption, transport, and storage (Gosiewska et al., 1996). Limited data suggest that ascorbate modulates prostaglandin synthesis and thus exerts bronchodilatory and vasodilatory as well as anticlotting effects (Horrobin, 1996).

Physiology of Absorption, Metabolism, and Excretion
Absorption and Transport

Intestinal absorption of ascorbic acid occurs through a sodium-dependent active transport process that is saturable and dose dependent (Rumsey and Levine, 1998; Tsao, 1997). At low gastrointestinal ascorbate concentrations, active transport predominates, while simple diffusion occurs at high concentrations. Some 70 to 90 percent of usual dietary intakes of ascorbic acid (30 to 180 mg/day) are absorbed; however, absorption falls to about 50 percent or less with increasing doses above 1 g/day (Kallner et al., 1979). The bioavailabilities of the vitamin from foods and supplements are not significantly different (Johnston and Luo, 1994; Mangels et al., 1993).

Cellular transport of ascorbic acid and DHA is mediated by transporters that vary by cell type (Jacob, 1999; Tsao, 1997). DHA is the form of the vitamin that primarily crosses the membranes of blood and intestinal cells, after which it is reduced intracellularly to ascorbic acid. Accumulation of ascorbate into neutrophils and lympho-



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