Vitamin body pool

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. 

Requirement. A daily intake of 1 pg should cover the daily loss of vitamin and maintain an adequate body pool. The RDA (34), however, has been estabHshed at 2 pg/day to cover metaboHc variation among individuals and to ensure normal semm concentrations and adequate pool sizes (Table 2). 

Approximately 0.05 to 0.2% of vitamin > 2 stores are turned over daily, amounting to 0.5—8.0 )J.g, depending on the body pool size. The half-life of the body pool is estimated to be between 480 and 1360 days with a daily loss of vitamin > 2 of about 1 )J.g. Consequentiy, the daily minimum requirement for vitamin B22 is 1 fig. Three micrograms (3.0 J.g) vitamin B22 are excreted in the bile each day, but an efficient enterohepatic circulation salvages the vitamin from the bile and other intestinal secretions. This effective recycling of the vitamin contributes to the long half-life. Absence of the intrinsic factor intermpts the enterohepatic circulation. Vitamin > 2 is not catabolized by the body and is, therefore, excreted unchanged. About one-half of the vitamin is excreted in the urine and the other half in the bile. 

The total body pool of vitamin B12 in humans ranges from 2 to 5 mg, most of which is stored in the liver. Daily losses of vitamin B12 are usu-... 

Replacement of Metabolic Losses An alternative approach to determining vitamin requirements is to measure the loss from the body pool in a steady state. This requires estimation of the total body pool, and measurement of the fractional rate of loss from that pool, generally using radioactive or stable isotope tracers. Three problems can arise in such studies. 

The measured total body pool may not be appropriate or desirable, because it win reflect the state of the subjects nutrition on a self-selected diet (see Section 13.7.3 for a discussion of the problem of the desirable body pool of vitamin C). 

There may be multiple metabolicpoolsofthe vitamin, with very different rates of turnover. In this case, short-term and long-term smdies will give very different estimates of the fractional rate of turnover of the total body pool. As discussed in Section 9.6.1, this is known to be a problem with vitamin Be, because some 80% of the total body pool is associated with muscle glycogen phosphorylase and has a much lower fractional turnover rate than the remaining 20%. 

The fractional rate of turnover of the body pool may well change with changes in intake as discussed in Section 13.7.3, this is known to be the case with vitamin C. 

Vitamin Be requirements have been estimated both by isotopic tracer studies to determine turnover of the body pool (Section 9.6.1) and also by depletion/ repletion studies using a variety of indices of status (Section 9.6.2). These studies have generally been conducted on young adults, and there is inadequate information to determine the requirements of elderly people, because apparent status assessed by a variety of indices declines with increasing age, despite intake as great as in younger people (Bates et al., 1999a). As discussed in Section 9.6.3, there is also inadequate information to estimate the requirements of infants. 

There is a variety of estimates of the body pool of vitamin Be. Short-term studies with isotopic tracers suggest a total body content of between 160 to 600 ixmo (40 to 150 mg), with a half-life of 33 days, suggesting a minimum requirement for replacement in the wide range between 0.6 to 2.27 mg per day. 

About 80% of the total body vitamin Bg is in skeletal muscle glycogen phos-phorylase, with a relatively slow turnover. Based on longer term tracer studies, Coburn (1990, 1996) has suggested a total body pool of 250 mg, or 15 nmol (3.7 /xg) per g of body weight, with a loss of about 0.13% per day, hence a... 

The total body pool of vitamin B12 is of the order of 1.8 /xmol (2.5 mg), with a minimum desirable body pool of about 0.3 /xmol (1 mg). 

The daily loss is about 0.1% of the body pool in subjects with normal intrinsic factor secretion and enterohepatic circulation of the vitamin (Section 10.7.2). On this basis, the requirement is 0.3 to 1.8 nmol (1 to 2.5 /xg) per day (Herbert, 1987b). This is probably a considerable overestimate of requirements, because parenteral administration of less than 0.3 nmol per day is adequate to maintain normal hematology in patients with pernicious anemia, in whom the enterohepatic recycling of the vitamin is grossly impaired. 

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. 

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. 

The daily loss is about 0.1% of the body pool in subjects with normal intrinsic factor secretion turd enterohepatic circulation of the vitamin (Section... 

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