Ascorbic acid vitamin plasma concentration

Ascorbic acid (vitamin C) is extensively sulfated in the gastrointestinal mucosa and competes with ethinylestra-diol, which is also extensively sulfated. Plasma ethinyles-tradiol concentrations are increased by ascorbic acid in women, both after a single dose of ethinylestradiol and during long-term oral contraceptive use, but the results are not consistent. On one occasion it was claimed that this effectively transformed a low-dose oral contraceptive into a high-dose formulation (333). It seems very dubious whether ascorbic acid in fact interferes significantly with the effects of oral contraceptives. 

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 possible involvement of free radicals in the development of hypertension has been suspected for a long time. In 1988, Salonen et al. [73] demonstrated the marked elevation of blood pressure for persons with the lowest levels of plasma ascorbic acid and serum selenium concentrations. In subsequent studies these authors confirmed their first observations and showed that the supplementation with antioxidant combination of ascorbic acid, selenium, vitamin E, and carotene resulted in a significant decrease in diastonic blood pressure [74] and enhanced the resistance of atherogenic lipoproteins in human plasma to oxidative stress [75]. Kristal et al. [76] demonstrated that hypertention is accompanied by priming of PMNs although the enhancement of superoxide release was not correlated with the levels of blood pressure. Russo et al. [77] showed that essential hypertension patients are characterized by higher MDA levels and decreased SOD activities. 

Another important field of application concerns food and beverages, especially wine, juices, and tea (A2, A11, A17, B4, K12, V7, Yl). The antioxidant components of food include vitamin E (a-tocopherol), vitamin A (retinoids), vitamin C (ascorbic acid), and also fi-carotene (provitamin A), other carotenoids (of which more than 600 compounds have been identified), flavonoids, simple phenols, and glucobrasicins (H3). Unfortunately, the TAC value of a food is not informative on the bioavailability of its antioxidants. It has been estimated that polyphenols are normally present in blood plasma at concentrations of 0.2-2 //M (PI). However, it has been demonstrated that feeding rats a quercetin-augmented diet can increase their plasma levels of quercetin and its metabolites up to 10-100 //M (M27), and transient increases in the concentration of plant-derived phenolic compounds can take place after ingestion of food and beverages, which may affect blood plasma TAC (see later). 

Blood plasma of children with cystic fibrosis was found to have decreased TAC (by 16%) in spite of increased concentrations of ascorbic acid, uric acid, and thiol groups (L4). In another study TAC of children with cystic fibrosis was normal, but these children received vitamin supplementation in doses prescribed in international guidelines (a-tocopherol <10 years, 100 mg daily, and >10 years, 200 mg daily retinol 2.5 mg daily ascorbic acid 100-200 mg daily) (M2). Other authors found TAC values for nonhospitalized patients (1.40 0.20 mM) not different from laboratory control values (1.35 0.11 mM), but greater than values for hospitalized patients (1.09 0.17 mM). TAC in CF children correlated positively with anthropometric values (height, weight, body mass index) and pulmonary function (forced expiratory volume in 1 sec), but not with age (L3). 

Disposition in the Body. Readily absorbed after oral administration the proportion of a dose absorbed tends to decrease with increasing dose it is widely distributed in the body tissues. The concentration of ascorbic acid is higher in leucocytes and platelets than in erythrocytes and plasma. Ascorbic acid is metabolised to dehydroascorbic acid, 2,3-diketogulonic acid, oxalate, and carbon dioxide some conjugation with sulphate occurs to form ascorbate-3-sulphate. Ascorbic acid in excess of the body s requirements is rapidly eliminated in the urine. About 85% of an intravenous dose, given to subjects previously saturated with the vitamin, is excreted in the urine in 24 hours, with about 70% of the dose excreted unchanged and 15% as dehydroascorbic acid and diketogulonic acid. The amount normally present in the body is in excess of 1.5 g. 

Blood and Animal Tissues. The most commonly used and practical procedure for evaluating vitamin C nutritional status is the measurement of serum (plasma) levels of ascorbic acid (87). Low plasma levels of ascorbic acid do not necessarily indicate scurvy, although scorbutic patients invariably have low or no plasma ascorbic acid, but continued low levels of plasma ascorbate of less than 0.10 mg/100 mL would eventually lead to signs and symptoms of scurvy. In general, serum ascorbic acid concentrations are usually more reflective of recent intakes rather than of total body stores (88). 

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. ... 

The concentration of ascorbate in the human plasma is 25 pM and above. Cells take up ascorbate by a Na -coupled uptake mechanism against a concentration gradient. A marked stereo-selectivity for L-ascorbic acid relative to D-isoascorbic acid in their cellular transport has been shown by Franceschi et al. [12]. The same transport is also important in the intestine. The nutritional supply of ascorbic acid is the only source for this vitamin in humans, primates, and guinea pigs. Other mammals are able to produce ascorbic acid. There exists sufficient evidence for an active role of ascorbate as an antioxidant in vivo. Decreased ascorbic acid will increase lipid peroxidation and decrease vitamin E and is connected with oxidative DNA damage. The supply of ascorbate in some cases will reduce the amount of oxidative damage in diseases that... 

Little information is available concerning alterations in vitamin requirements in ARF. Reduced plasma concentrations of vitamin A, ascorbate, vitamin D, and vitamin E have been reported in patients with ARF, whereas vitamin K concentrations are relatively increased. Losses of vitamins via dialysis also must be considered. Traditional HD clears several water-soluble vitamins such as folic acid, vitamins C and B12, and pyridoxine, but not the highly protein-bound vitamins A and D. The clinical significance of these findings in ARF is unknown. Currently, it seems prudent to administer vitamins at least daily in doses recommended by the Nutrition Advisory Group of the American Medical Association for patients receiving PN (see Chap. 137)." Administration of ascorbic acid should be restricted to under 200 mg/day to avoid secondary oxalosis which may worsen renal function." If the enteral route is used for nutritional support, vitamin administration should at least meet the recommended daily allowances (RDAs). 

As would be expected from the very high concentrations of ascorbic acid maintained in the tissues, and as was found for the guinea pig, the intake of ascorbic acid per kilogram of body weight is more closely correlated with the plasma levels of children than the total intake of the vitamin (R15). Another study did not show this relationship (H4). 

Vitamin C status can be assessed by measuring plasma levels or urinary excretion. However, due to practical disadvantages, e.g., quantitative sampling of urine and instability of vitamin C, determination of vitamin C in urine has been mainly replaced by determination of plasma levels. Methods include direct determination by FIPLC, or automated assays based on a derivatization of ascorbic acid forming colored or fluorescent derivatives. While a plasma concentration <11.4p.molH is widely used to characterize deficiency, literature data signifying adequate status vary from >17 to 28.4p.moll. ... 

Steady-State plasma concentration increases only from about 12 to 15 mg/1 (from 68 to 85 pmol/l). In other words, no matter how high a dose of vitamin C you take orally, there is a limit to the plasma concentration that can be reached. Furthermore, the uptake of ascorbic acid by the tissues is also saturable. All these imply that high doses of ascorbic acid are unhkely to have greater beneficial effects than ordinary doses but are more hkely to cause adverse reactions, associated with high concentrations of ascorbic acid in the gut and urine. 

Ascorbic acid in blood is transported by a reversible complex with serum albumin (Moloy et al., 1980). The main transport form of vitamin C seems to be the reduced molecule. The concentration of dehydroascorbic acid can, however, exceed that of ascorbic acid in vitamin C deficiency and certain diseases (Stone, 1977). The relation of ascorbic acid/dehydroascorbic acid in human plasma decreases also with age (Sasaki et al., 1983). Since the typical screening methods for the determination of vitamin C status in blood are not able to distinguish between the different circulating forms of vitamin C, it has to be clearly stated that the detailed interpretation of vitamin C status and its relation to certain disorders must reflect on both ascorbic acid and dehydroascorbic acid concentration in blood. 

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