Body pool, ascorbic acid

As mentioned above, ascorbic acid acts as a neuroprotective agent in in vitro models of scurvy. Therefore, it is a surprise that no symptoms of brain cell damage have been reported in conditions involving severe systemic ascorbic acid deficiency. This may be explained by the fact that the scorbutic state cannot be produced in the intact animal brain because of the brain s homeostatic mechanisms such as the highly specific ascorbic acid transport system in the choroid plexus (Spector, 1989) and the inability of ascorbic acid to cross the blood-brain barrier, which effectively isolate the ascorbic acid content of the intact brain from the rest of the body s ascorbic acid pool. The active transport of ascorbic acid from blood to cerebrospinal fluid (Spector and Eells, 1984), together with cellular uptake mechanisms, represents the base for homeostasis of brain ascorbic acid concentrations (see also Section 2). This is in agreement with the report about normal ascorbic acid concentrations in brains from patients with Parkinson s disease (Riederer et al., 1989), in which free radical damages are postulated to be involved (see below). 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

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. 

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. 

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. 

Kallner, A.B., Hartmann, D., Hornig, D.H. On the requirements of ascorbic acid in man Steady-state turnover and body pools in smokers. Am. J. Clin. Nutr. 1981 34 1347u55. 

C is rapidly excreted. About 4% of this pool is lost daily (fractional catabolic rate) after intermission of vitamin C supply. The biological half-time of the pool is therefore approximately 8-40 days (Homig, 1981). The first symptoms of scurvy occur upon reaching a total body pool of 300-400 mg. Table II shows data on the turnover rate of ascorbic acid for man and different species. Table III shows the ascorbic acid concentrations in organs and body fluids of the adult man. 

The minimum vitamin C requirement to prevent the development of scurvy has been found to be 10 mg/day (Hodges et al., 1971). This supply is not sufficient for the provision of acceptable reserves of the vitamin. The intake of 10 mg ascorbic acid per day reflects a plasma concentration of 7.6-14.1 p,mol/liter (0.13-0.24 mg/100 ml), a concentration that is far from tissue saturation. The renal clearance of ascorbic acid rises sharply at a point of 82 xmol/liter (1.4 mg/100 ml). An adequate plasma level of 44 p.mol/liter (0.75 mg/100 ml) can be maintained by a daily supply of 60-75 mg ascorbic acid. The daily amount of ascorbic acid, which is catabolized by the human body, can be calculated to be 60 mg based on a total body pool of ascorbic acid of approximately 1500 mg and a maximum turnover rate of 4%. These data are the scientific basis for the formulation of the above recommendations to meet the physiological needs. Table IV shows the recommended daily vitamin C intake for different population groups from the different societies that issue such recommendations. 

Early literature demonstrated that the administration of various drugs to rats stimulated ascorbic acid synthesis, as evidenced by the dramatic increases in urinary ascorbate (Longenecker et al., 1940) and the doubling of body pools (Conney et al., 1961). Drug-induced ascorbate synthesis appeared to proceed through the glu-... 

Epidemiological studies have shown the elfect of smoking in reducing ascorbic acid levels in blood (Pelletier, 1970). Exposure to ozone and nitrogen dioxide also reduces blood ascorbic acid content. Unusually low amounts of ascorbate in milk of lactating women smokers have also been reported (Kallner et aL, 1981). This is attributed to the increased need for reducing agents imposed by chemical oxidants contained in tobacco smoke and some metabolic properties of nicotine (Bucca et al., 1989). This explains why the daily intake of ascorbic acid of at least 140 mg is required for smokers to reach a body pool of ascorbic acid comparable to that of nonsmokers, for whom a daily intake of about 100 mg is sufficient (Kallner et aL, 1981). 

About 3% of the body s vitamin C pool, which is 20-50 mg/kg body weight, is excreted in the urine as ascorbic acid, dehydroascorbic acid (a combined total of 25%) and their metabolites, 2,3-diketo-L-gulonic acid (20%) and oxalic acid (55%). An increase in excreted oxalic acid occurs only with a very high intake of ascorbic acid. Scurvy is caused by a dietary deficiency of ascorbic acid. 

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