Plasma and Leukocyte Concentrations of Ascorbate

The plasma concentration of vitamin C falls relatively rapidly during depletion studies, to undetectably low levels within 4 weeks of initiating a vitamin C-free diet, although clinical signs of scurvy may not develop for a further 3 to 

4 months and tissue concentrations of the vitamin may he as high as 50% of saturation. In field studies and surveys, subjects with plasma ascorbate below 11 yit mol per L are considered to be at risk of developing scurvy (see Table 13.2), whereas anyone with a plasma concentration below 6 //mol per L would be expected to show clinical signs. At intakes above about 100 mg per day, the plasma concentration of ascorbate reaches a plateau around 70 to 80 //mol per L, because of quantitative excretion of the vitamin as the renal threshold is exceeded (Section 13.2.4). 

The concentration of ascorbate in leukocytes is well correlated with the concentrations in other tissues and falls more slowly than plasma concentration in depletion studies. The reference range of leukocyte ascorbate is 1.1 to 2.8 pmol per 10 cells a significant loss of leukocyte ascorbate coincides with the development of clear clinical signs of scurvy. Predictably, at high levels of ascorbate intake, although the plasma concentration continues to increase with intake, the leukocyte content does not, because the cells, like othertissues, are saturated. 

The concentration of ascorbate in leukocytes is well correlated with the concentrations in other tissues and falls more slowly than plasma concentration in depletion studies. The reference range of leukocyte ascorbate is 1.1 to 

---

Requirements Estimated from the Plasma and Leukocyte Concentrations of Ascorbate... 

The Effect of Smoking on Vitamin C Requirements There is evidence that smokers have a higher requirement for vitamin C than nonsmokers. A number of studies have shown lower plasma and leukocyte concentrations of vitamin C in smokers, but many also report lower intake of the vitamin by smokers. The rate of catabolism of ascorbate is up to 40% greater in smokers than nonsmokers (Kallner et al., 1981), and therefore their vitamin C requirement may be almost twice that of nonsmokers. 

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 independendy 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 ofvitamin 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. 

The adrenal glands and pituitary glands have the highest tissue concentration of ascorbic acid. The brain, Hver, and spleen, however, represent the largest contribution to the body pool. Plasma and leukocyte ascorbic acid levels decrease with increasing age (152). Elderly people require higher ascorbic acid intakes than children to reach the same plasma and tissue concentration (153). 

Table 13.2 Plasma and Leukocyte Ascorbate Concentrations as Criteria of Vitamin C Nutritional Status...

With regard to the concentration of ascorbic acid in leukocytes, Briggs and Briggs (B13) reported a control value of 39 28 (SD) jug per 10 cells. On the assumption that the average diameter of the white cells is 12 jum (W9) and that the cell is spherical, the value of Briggs and Briggs (B13) can be calculated to be about 45 mg/100 ml. The mean normal values obtained by Butler and Cushman (B24), Lowry et al. (L8), and Bodansky et al. (B9) were about 30 mg/100 ml. The administration of oral contraceptives leads to significant decreases in the plasma, leukocytes, and platelet concentrations (Table 2). 

Table 2 Plasma and leukocyte ascorbate concentrations as criteria of vitamin C nutritional status...

With adequate intake of vitamin C, plasma concentrations of total vitamin (ascorbic acid plus dehydroascorbic acid) are between 0.4 and 1.5mg/dL (23 to 85 jimol/L). The lower limit value may be seen in some cases with subclinical vitamin C deficiency and in older individuals. A value lower than 0.2mg/dL (llpmol/L) is considered deficient. The guidance reference interval for vitamin C levels in leukocytes is 20 to 53p,g/10 leukocytes (1.14 to 3.01 finol/leukocyte). A value in leukocytes of less than lOpg/10 leukocytes (0.57fmol/leukocyte) is considered deficient. ... 

About 70% of blood-borne 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 concentration, platelets 40-fold, and granulocytes 25-fold, compared with the plasma concentration. 

Absorption, Transport, and Excretion. The vitamin is absorbed through the mouth, the stomach, and predominantly through the distal portion of the small intestine, and hence, penetrates into the bloodstream. Ascorbic acid is widely distributed to the cells of the body and is mainly present in the white blood cells (leukocytes). The ascorbic acid concentration in these cells is about 150 times its concentration in the plasma (150,151). Dehydroascorbic acid is the main form in the red blood cells (erythrocytes). White blood cells are involved in the destmction of bacteria. 

The effects of oral contraceptive agents on ascorbate levels in plasma, leukocytes, and platelets of African women living in the Republic of Zambia have been studied in some detail by Briggs and Briggs (B13-B15). The mean value for the plasma concentration in 15 Zambian women of apparently good health was given as 7.5 2.0 (SD) /ig/liter (B14). The jug is, however, a misprint (M. Briggs, personal communication and should be 7.5 2.0 (SD) mg/liter, or 0.75 0.2 mg per 100 ml, essentially the same value obtained by Lowry (L8), Roe (R5), and Bodansky et al. (B9). 

---