Tissue Uptake of Vitamin C

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Ascorbate and dehydroascorbate are taken up into tissues by separate mechanisms, and there is little or no competition between them (Welch et al., 1995):

1. Ascorbate enters cells byway of sodium-dependent transporters.

2. Dehydroascorbate enters cells byway of the (insulin-dependent) glucose transporters (GLUT), and is reduced to ascorbate intracellularly.

The relative importance of uptake of dehydroascorbate and dehydroascor-bate by tissues is unclear. It has been suggested that normal physiological concentrations of glucose will inhibit uptake of dehydroascorbate (Liang et al., 2001). Functional signs of deficiency may develop in poorly controlled diabetes mellitus, despite an adequate intake and adequate plasma concentrations, suggesting that hyperglycemia and insulin insensitivity - and thus uptake of dehydroascorbate in competition with glucose - are important. Some of the adverse effects of poor glycemic control in diabetes mellitus (especially the development of cataract) may be related to this impairment of vitamin C

uptake, and supplements ofvitamin C maybe beneficial (Cunningham, 1998a, 1998b).

With cells in culture, high concentrations of flavonoids (Section 14.7.2) inhibit the uptake of both ascorbate and dehydroascorbate, although it is not clear whether inhibitory concentrations of flavonoids occur in vivo (Park and Levine, 2000).

About 70% of blood ascorbate is in plasma and erythrocytes (which do not concentrate the vitamin from plasma). The remainder is in white cells, which have a marked ability to concentrate ascorbate: mononuclear leukocytes achieve 80-fold, platelets 40-fold, and granulocytes 25-fold concentration, compared with plasma concentration. In adequately nourished subjects, and those receiving supplements, the ascorbate concentration in erythrocytes, platelets, and granulocytes, but not in mononuclear leukocytes, is correlated with plasma concentration. Mononuclear leukocytes concentrate ascorbate independently of plasma concentration (Evans et al., 1982). In deficiency, as plasma concentrations of ascorbate fall, mononuclear leukocyte, granulocyte, and platelet concentrations of ascorbate are protected to a considerable extent. As discussed in Section 13.5.2, the leukocyte content of ascorbate is used as an index of vitamin C nutritional status, but in view of the differing capacity of different cell types to accumulate the vitamin, differential white cell counts are essential to interpret the results.

There is no specific storage organ for ascorbate; apart from leukocytes (which account for only 10% of total blood ascorbate), the only tissues showing a significant concentration of the vitamin are the adrenal and pituitary glands. Although the concentration of ascorbate in muscle is relatively low, skeletal muscle contains much of the body pool of 5 to 8.5 mmol (900 to 1,500 mg) of ascorbate.

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