Vitamin erythrocyte concentrations

A cross-sectional study showed a 20% lower serum vitamin B12 concentration in patients taking lithium (n = 81) than in controls (n = 14) (serum and erythrocyte folate concentrations were normal) (346). 

Patients with renal dysfunction are known to have raised circulating vitamin A concentrations. In chronic dialysis patients, the concentration can rise steadily. The significantly increased osmotic fragility of erythrocytes observed in hemodialysed patients also seems to be related to high vitamin A concentrations. However, the similarity between uremic symptoms and those of vitamin A excess may explain why hypervitaminosis A in uremic patients is rarely reported as being associated with clinical toxicity (SEDA-12, 327). 

Erythrocyte and plasma folate concentrations are reduced in protein-calorie malnutrition, but the serum vitamin Bj2 concentration is unaffected or may even be slightly increased. The plasma concentrations of vitamins A and E are much reduced. Although the blood hemoglobin concentration is reduced, the serum iron concentration is initially little affected by malnutrition. 

Most of the folate abnormalities observed have been associated with active disease. Patients in remission usually have a normal serum folate provided their dietary intake is adequate. Folate depletion associated with active neoplastic disease is in the main due to a poor diet and this may be made worse by an increased demand due to rapidly growing tissue. Although up to 85% of patients with malignant disease have been found to have a low serum folate, most have had a normal erythrocyte concentration of the vitamin (M15). 

Patients with homozygous sickle cell disease (SS) had a mean serum folate of 5.8 JLg/liter compared with 7.2 p.g/liter in patients with sickle cell trait and 7.9 p.g/liter in healthy controls. However, there was no correlation between the serum folate and the hematocrit or reticulocyte count. Since reticulocytes may have a higher folate concentration than mature erythrocytes, Liu found that the erythrocyte folate, measured before and after removal of the reticulocytes, was a reliable indicator of the folate status in patients with sickle cell disease despite the variable degree of re-ticulocytosis. Using this technique only one of nine patients was found to have a low erythrocyte concentration of the vitamin. Treatment with fohc acid resulted in higher hematocrits in three of four patients with low serum and erythrocyte folate concentrations, but only one of 12 patients with a normal folate concentration showed any improvement when treated with folate. 

Other methods are also used for the determination of plasma/serum levels in vitro lipid peroxidation in erythrocytes (malondialdehyde test) determination of vitamin E concentration in platelets determination of tocopherols in fat tissue (needle biopsy). 

Whereas the measurement of B vitamin status has, in recent years, tended to focus on blood analysis, perhaps mainly because of the convenience of sample collection, the development of blood-based status analysis for niacin has lagged behind that of the other components of the B complex. Some studies have indeed suggested that the erythrocyte concentration of the niacin-derived coenzyme NAD may provide useful information about the niacin status of human subjects that a reduction in the ratio of NAD to NADP to below 1.0 in red cells may provide evidence of niacin deficiency and that a decline in plasma tryptophan levels may indicate a more severe deficiency than a decline in red cell NAD levels. These claims now need to be tested in naturally deficient human populations. The niacin coenzymes can be quantitated either by enzyme-linked reactions or by making use of their natural fluorescence in alkaline solution. 

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. 

Clearly this patient has both clinical and haematological symptoms of severe anaemia. The cause is too few red cells low RBC count and PCV but the erythrocytes which are present contain a higher than usual concentration of haemoglobin (MCHC result). Iron deficiency and vitamin B12 deficiency can be ruled out by the high serum ferritin and normal MCV results respectively. The negative HbS screen rules out sickle cell anaemia which is fairly common in Africans. 

In a case-control study in 106 heroin-dependent individuals undergoing an opioid detoxification program (n = 19) or a methadone maintenance treatment program (n = 87) there were large significant differences in the mean values of some vitamins and minerals between the heroin-dependent individuals and the healthy, non-dependent controls (37). Dependent individuals had higher white cell counts and transaminases and lower erythrocyte counts and cholesterol, albumin, tocopherol, folic acid, sodium, selenium, and copper concentrations. 

Because vitamin E is transported in lipoproteins secreted hy the liver, the plasma concentration depends to a great extent on total plasma lipids. Erythrocytes may also he important in transport, because there is a relatively large amount of the vitamin in erythrocyte membranes, and this is in rapid equilibrium with plasma vitamin E. There are two mechanisms for tissue uptake of the vitamin. Lipoprotein lipase releases the vitamin by hydrolyzing the tri-acylglycerol in chylomicrons and VLDL, whereas separately there is receptor-mediated uptake of LDL-bound vitamin E. Studies in knockout mice suggest that the main mechanism for tissue uptake of vitamin E from plasma lipoproteins is byway of the class B scavenger receptor (Mardones et al., 2002). 

As shown in Table 9.5, there are a number of indices of vitamin Be status available plasma concentrations of the vitamin, urinary excretion of 4-pyridoxic acid, activation of erythrocyte aminotransferases by pyridoxal phosphate added in vitro, and the ability to metabolize test doses of tryptophan and methionine. None is wholly satisfactory and where more than one index has been used in population studies, there is poor agreement between the different methods (Bender, 1989b Bates et al., 1999a). 

Early studies of vitamin Be requirements used the development of abnormalities of tryptophan or methionine metabolism during depletion, and normalization during repletion with graded intakes of the vitamin. Although tryptophan and methionine load tests are unreliable as indices of vitamin Be status in epidemiological studies (Section 9.5.4 and Section 9.5.5), under the controlled conditions of depletion/repletion studies they do give a useful indication of the state of vitamin Be nutrition. More recent studies have used more sensitive indices of status, including the plasma concentration of pyridoxal phosphate, urinary excretion of 4-pyridoxic acid, and erythrocyte transaminase activation coefficient. 

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. 

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. 

Pyridoxine phosphate oxidase is a flavoprotein, and activation of the erythrocyte apoenzyme hy riboflavin 5 -phosphate in vitro can he used as an index of riboflavin nutritional status (Section 7.4.3). However, even in riboflavin deficiency, there is sufficient residual activity of pyridoxine phosphate oxidase to permit normal metabolism of vitamin Bg (Lakshmi and Bamji, 1974). Pyridoxine phosphate oxidase is inhibited by its product, pyridoxal phosphate, which binds a specific lysine residue in the enzyme. In the brain, the K, of pyridoxal phosphate is of the order of 2 / mol per L - the same as the brain concentration of free and loosely bound pyridoxal phosphate, suggesting that this inhibition may be a physiologically important mechanism in the control of tissue pyridoxal phosphate (Choi et al., 1987). 

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