Body pool, ascorbate

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). 

Mobilization and Metabolism. The total ascorbic acid body pool in healthy adults has been estimated to be approximately 1.5 g, which increases to 2.3—2.8 g with intakes of 200 mg/d (151—158). Depletion of the body pool to 600 mg initiates physiological changes, and signs of clinical scurvy are reported when the body pool falls below 300 mg (149). Approximately 3—4% of the body pool turns over daily, representing 40—60 mg/d of metabolized, or consumed, vitamin C. Smokers have a higher metaboHc turnover rate of vitamin C (approximately 100 mg/d) and a lower body pool than nonsmokers, unless compensated through increased daily intakes of vitamin C (159). The metaboHsm of ascorbic acid varies among different species. 

Moreau, R. Dabrowski, K. (1998) Body pool and synthesis of ascorbic acid in adult sea lamprey (Petromyzon marinus) an agnatan fish with gulonolactmie oxidase activity. Proc. Natl. Acad. Sci. USA, 95,10279-82. 

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. 

There have been two major studies of ascorbate requirements in deple-tion/repletion studies, one in Sheffield during the 1940s (Medical Research Council, 1948) and the other in Iowa during the 1960s (Baker et al., 1969,1971 Hodges etal., 1969,1971). In addition, Kallnerand coworkers (1979,1981) have determined the body pool of ascorbate and the fractional rate of turnover under various conditions. Levine and coworkers (1995, 1996, 1999) have measured plasma and leukocyte ascorbate in studies of subjects maintained on more than minimally adequate amounts of vitamin C for relatively prolonged periods of time to determine optimum, rather than minimum, requirements. 

The midpoint of the steep region of the curve, where the plasma concentration increases linearly with increasing intake, represents a state in which tissue reserves are adequate and plasma ascorbate is available for transfer between tissues. This corresponds to an intake of 40 mg per day, and is the basis of the U.K., European Union, and Food and Agriculture Organization/World Health Organization figures shown in Table 13.3. At this level of intake, the total body pool is about 900 mg (5.1 mmol). 

Requirements Estimated from Maintenance of the Body Pool of Ascorbate... 

A priori, the best means of determining vitamin C requirement would seem to be determination of the total body pool and its fractional rate of loss or catabolism. An appropriate intake would then be that to replace losses and maintain the body pool. Clinical signs of scurvy are seen when the total body pool of ascorbate is below 1.7 mmol (300 mg). The pool increases with intake, reaching a maximum of about 8.5 mmol (1,500 mg) in adults -114 /rmol (20 mg) per kg of body weight. The fractional turnover rate of ascorbate is 3% to 4% daily, suggesting a need for 45 to 60 mg per day for replacement. The basis for the 1989 U.S. Recommended Daily Allowance (RDA) of 60 mg (National Research Council, 1989) was the observed mean fractional turnover rate of 3.2% of a body pool of 20 mg per kg of body weight per day, with allowances for incomplete absorption of dietary ascorbate and individual variation. 

The rate of ascorbate catabolism is not constant. If it were, more or less complete depletion of the body pool would be expected within 25 to 33 days yet, in the Sheffield study, in which the subjects were initially maintained on 70 mg of ascorbate per day, they received a diet essentially free from the vitamin no changes were apparent for 17 weeks (Medical Research Council, 1948). In the Iowa study, the subjects were not initially saturated with vitamin C the first skin lesions did not develop for 5 to 6 weeks after the depletion period (Baker etal., 1969,1971 Hodges etal., 1969,1971). Kallner and coworkers (1979) showed that the turnover time of body ascorbate varied between 56 days at low intake (about 15 mg per day) and 14 days (at intakes of 80 mg per day). It is thus apparent that the rate of ascorbate catabolism is affected markedly by the intake, and the requirement to maintain the body pool cannot be estimated as an absolute value. A habitual low intake, with a consequent low rate of catabolism, will maintain the same body pool as a habitual higher intake with a higher rate of catabolism. 

Kallner A, Hartmann D, and Hornig D (1979) Steady-state turnover and body pool of ascorbic acid in man. American Journal of Clinical Nutrition 32, 530-9. 

The course of carbon-14-radioactivity derived from oral (l- C)ascorbic acid in plasma and several tissues was studied in male guinea pigs up to 320 h after intake. The excretion of label was followed in respiratory carbon dioxide, urine, and feces. The evaluation by pharmacokinetic principles yielded an overall half-life of 61 h and a body pool of 21 mg with a total turnover of about 10 mg/d. The total turnover of ascorbate is lower than the daily intake (16 mg/d), indicating incomplete absorption. Ascorbic acid seemed to be bound in several tissues (adrenals, testes) to a higher percentage than in plasma. The maximum rate of excretion as carbon dioxide occurred at 0.5 h, whereas peak concentration of radioactivity in plasma was reached at 1.5 h. Therefore, presystemic metabolism must be considered. 

Relevant kinetic parameters (half-life, body pool, and mean transit time in organs) can be calculated. According to Equation 1 the specific activity in plasma shows a triphasic decay with half-lives of ti = 1.1 h, t2 == 22 h, and 3 == 61 h. The half-lives ti and 2 essentially describe the distribution of the compound into the system. The third half-life of 61 h (2.5 d) is valid for all tissues after attainment of the distribution equilibrium and represents the overall half-life of elimination from the body under the special conditions of the study (ascorbate status of the animals). 

The amount of ascorbic acid in the body (body pool) can be obtained by multiplying the volume of distribution (Vss) by the averaged steady state concentration [Css (Table II)] of ascorbic acid in plasma. This calculation yields a body pool of 21 mg. Unfortunately, the estimated body pool cannot be compared with an experimental value since the total pool was not accessible experimentally. 

Under the experimental conditions, the overall half-life (biological half-life) of ascorbic acid elimination from the body was calculated at about 61 h (2.5 d). This value has been evaluated from the slope of the log linear phase ( -phase), indicating equilibration of the labeled ascorbic acid with the exchangeable body pool. The observed half-life compares well with data obtained in earlier studies— mainly calculated from the time dependence of the logarithm of radioactivity remaining in the body, and with the assumption that metabolites of ascorbic acid are rapidly eliminated. Thus, biological half-lives for ascorbic acid of GO-MO h (3), 85-115 h (36), 48-72 h (2), or 127 h (22) are reported. In one study (22) the half-life was determined from the plasma specific activity to be only 39 h. 

The model used allows the calculation of the total body pool. As shown in Table I, the total body pool varies with ascorbate intake and ranges between about 10 and 20 mg/kg body weight. 

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