D. Hornig

Contribution of selected vitamins and trace elements to immune function.

Adequate intakes of vitamins and trace elements are required for the immune system to function efficiently. Micronutrient deficiency suppresses immune functions by affecting the innate T-cell-mediated immune response and adaptive antibody response, and leads to dysregulation of the balanced host response. This increases the susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (both active and passive), in individuals with chronic alcohol abuse, in patients with certain diseases, during pregnancy and lactation, and in the elderly. With aging a variety of changes are observed in the immune system, which translate into less effective innate and adaptive immune responses and increased susceptibility to infections. Antioxidant vitamins and trace elements (vitamins C, E, selenium, copper, and zinc) counteract potential damage caused by reactive oxygen species to cellular tissues and modulate immune cell function through regulation of redox-sensitive transcription factors and affect production of cytokines and prostaglandins. Adequate intake of vitamins B6, folate, B12, C, E, and of selenium, zinc, copper, and iron supports a Th1 cytokine-mediated immune response with sufficient production of proinflammatory cytokines, which maintains an effective immune response and avoids a shift to an anti-inflammatory Th2 cell-mediated immune response and an increased risk of extracellular infections. Supplementation with these micronutrients reverses the Th2 cell-mediated immune response to a proinflammatory Th1 cytokine-regulated response with enhanced innate immunity. Vitamins A and D play important roles in both cell-mediated and humoral antibody response and support a Th2-mediated anti-inflammatory cytokine profile. Vitamin A deficiency impairs both innate immunity (mucosal epithelial regeneration) and adaptive immune response to infection resulting in an impaired ability to counteract extracellular pathogens. Vitamin D deficiency is correlated with a higher susceptibility to infections due to impaired localized innate immunity and defects in antigen-specific cellular immune response. Overall, inadequate intake and status of these vitamins and minerals may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition.

Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses

Adequate intakes of micronutrients are required for the immune system to function efficiently. Micronutrient deficiency suppresses immunity by affecting innate, T cell mediated and adaptive antibody responses, leading to dysregulation of the balanced host response. This situation increases susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (active and passive), in individuals with chronic alcohol abuse, in certain diseases, during pregnancy and lactation, and in the elderly. This paper summarises the roles of selected vitamins and trace elements in immune function. Micronutrients contribute to the bodys natural defences on three levels by supporting physical barriers (skin/mucosa), cellular immunity and antibody production. Vitamins A, C, E and the trace element zinc assist in enhancing the skin barrier function. The vitamins A, B6, B12, C, D, E and folic acid and the trace elements iron, zinc, copper and selenium work in synergy to support the protective activities of the immune cells. Finally, all these micronutrients, with the exception of vitamin C and iron, are essential for antibody production. Overall, inadequate intake and status of these vitamins and trace elements may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition. Therefore, supplementation with these selected micronutrients can support the bodys natural defence system by enhancing all three levels of immunity.

Na+-dependent, potential-sensitive L-ascorbate transport across brush border membrane vesicles from kidney cortex.

l-Ascorbate is taken up into brush border vesicles from kidney cortex of rat, rabbit and guinea pig by an efficient, Na+-dependent and potential-sensitive transport process. This uptake shows saturation (Km:0.1–0.3 mM) and is strongly stimulated by low concentrations of N3−. Erythorbate (d-isoascorbate) seems to be another, but poorer, substrate of the same transporter.

Ascorbic acid and cholesterol: effect of graded oral intakes on cholesterol conversion to bile acids in guinea-pigs.

A significant correlation between liver ascorbic acid (AA) and total bile acids or liver bile acids has been established in guinea-pigs by direct determination of the bile acids, confirming an earlier hypothesis. The oxidation of cholesterol to bile acids is dependent on the AA status, but it cannot be further stimulated by AA when the animals are already on an adequate intake of the vitamin. This suggests that AA has a hypocholesterolaemic effect over a limited range of AA status.

The Role of Ascorbic Acid in Carcinogenesis

Vitamin C is an essential nutrient whose protective role in carcinogenesis has been discussed for more than 50 years. Epidemiologic studies suggest that the consumption of vitamin C-rich foods is associated with a lower risk of cancers of the esophagus and stomach. The observation that cancer patients have low leukocyte vitamin C levels led to therapeutic trials the results of which are controversial; the hypothesis that vitamin C acts like a drug must be questioned. On the other hand, ascorbic acid interacts with various tumor-inducing compounds, such as the precursors of N-nitroso compounds, to prevent the formation of tumors. Experiments with animals and cell cultures indicate that ascorbic acid can interfere with the metabolism of tumor promoters. It has also been postulated that ascorbic acid helps to prevent cancer by enhancing cellular immunity. In general, evidence suggests that vitamin C can inhibit the formation of some carcinogens.

Uptake and release of [1-14C]ascorbic acid and [1-14C]dehydroascorbic acid by erythrocytes of guinea pigs

Abstract The uptake and release of [1- 14 C] ascorbic acid and [1- 14 C]dehydroascorbic acid by erythrocytes of guinea pigs kept on a normal diet and of those on an ascorbic acid-deficient diet was studied in vitro . Results strongly suggest that the erythrocyte membrane is permeable to both ascorbic acid and dehydroascorbic acid in either direction. Mean ratios of the uptake of dehydroascorbic acid to ascorbic acid by the erythrocytes of normally fed guinea pigs (2.03 ± 0.69) and of vitamin C-deficient animals (2.49 ± 0.44) are given. After incubation with [1- 14 C]ascorbic acid, only ascorbic acid was found in the erythrocytes and only ascorbic acid was released during reincubation. In the case of [1- 14 C]dehydroascorbic acid, mainly dehydroascorbic acid was found to be present in the erythrocyte, but some ascorbic acid was always detectable. Both dehydroascorbic acid and ascorbic acid were released, mainly, however, dehydroascorbic acid.

Site of intestinal absorption of ascorbic acid in guinea pigs and rats

Abstract The site of absorption of ascorbic acid by the small intestine was studied in vivo in guinea pigs, normal and hypophysectomized rats after oral application of 14C-ascorbic acid. A species-specific difference was revealed. The site of absorption in the guinea pig was located in the duodenal and proximal small intestinal wall, whereas the rat showed highest absorption in the ileum. Hypophysectomy in rats caused a shift of the absorption site from the ileum to the jejunum. No absorption was observed in the duodenum and ileum. A regulatory role of the pituitary gland in the absorption of ascorbic acid by the small intestine is discussed.

Ethanol selectively affects Na+-gradient dependent intestinal transport systems

Moderate concentrations of ethanol reduce the velocity of uptake of three representative Na+‐symport systems (D‐glucose, L‐alanine, L‐ascorbate), whether electrogenic (the first two) or electroneutral (L‐ascorbate). This ‘inhibition’ is observed only if these transport systems are tested in the presence of an initial Na+ gradient (out > in); no inhibition is found in tracer‐equilibrium exchange measurements. A representative Na+‐independent system (D‐fructose) is not inhibited by ethanol. ‘Passive diffusion’ (measured as uptake of L‐glucose) is increased somewhat by alcohol. All these observations can be rationalized [as suggested by Tillotson et al. (1981) Arch. Biochem. Biophys. 207, 360–370] by an effect of ethanol on passive diffusion, which leads to a faster collapse of the Na+ gradient, with the resulting reduction of the uptake velocities of Na+‐dependent transport systems when tested with the added driving force of an Na+ out → in gradient.

A biliary metabolite of ascorbic acid in normal and hypophysectomized rats

Abstract 1. 1. A metabolite of ascorbic acid was studied in bile-duct cannulated normal and hypophysectomized rats. [1- 14 C]Ascorbic acid was given by gastric intubation either in an emulsion containing triolein, carbohydrates and proteins, or in an aqueous solution. 2. 2. The kinetics of the biliary excretion of radioactive material were followed. The rate of excretion was dependent upon the concomitant dietary components and on the nature of the solution infused in the upper part of the common bile-duct. 3. 3. Peak excretion occurred 4–7 h after administration of ascorbic acid in the emulsion and 2–3 h after giving the vitamin in water. 4. 4. Infusion of either rat bile or of a solution of taurocholate stimulated the excretion of the metabolite to a similar extent (0.75 and 0.65% of the dose excreted during the first 24 h, respectively). Infusion of an isotonic salt solution reduced the total excretion to 0.4%. The results after administration of ascorbic acid in water were as follows: 0.5, 0.45 and 0.25%, respectively. 5. 5. A lower excretion (0.04% of the given dose during the first 10 h) was observed in hypophysectomized rats after administration of [1- 14 C]ascorbic acid in the emulsion and during infusion of taurocholate solution. 6. 6. Electrophoretic as well as chromatographic data suggest that ascorbic acid-2-sulfate accounts for the radioactive material in the bile. No labelled ascorbic acid could be detected. 7. 7. The existence of an enterohepatic circulation for this metabolite is discussed. A role of taurocholate is postulated for the absorption of this metabolite from the intestinal tract.

Studies on the uptake of [1-14C]ascorbic acid and [1-14C]-dehydroascorbic acid by platelets of guinea pigs

Abstract Ascorbic acid as well as dehydroascorbic acid were shown to penetrate the platelet membrane in vitro. The percentage uptake by platelets of control guinea pigs (ascorbic acid 0.22 ± 0.014; dehydroascorbic acid 0.54 ± 0.033; p = 0.001) as well as of vitamin C-deficient animals (ascorbic acid 0.40 ± 0.026; dehydroascorbic acid 0.88 ± 0.060; p = 0.001 SEM given) were found to be significantly different. The uptake of ascorbic acid as well as of dehydroascorbic acid were significantly enhanced compared to control animals (p = 0.001). However, the ratios of uptake of dehydroascorbic acid to ascorbic acid were unaffected (control animals 2.30 ± 0.24; vitamin C-deficient animals (2.30 ± 0.17). The uptake of ascorbic acid was found to be fairly dependent on the concentration and was not influenced by ouabain. On the contrary, the uptake of dehydroascorbic acid did not show a linear dependency on the concentration and was inhibited by 10−3 M ouabain. These findings suggest an active transport mechanism for the uptake of dehydroascorbic acid whereas in case of ascorbic acid the facilitated diffusion mechanism is discussed. After incubation of platelets of control and vitamin C-deficient animals with [1-14C]ascorbic acid as well as with [1-14C]dehydroascorbic acid only [1-14C] ascorbic acid was detectable in the platelets and only [1-14C]ascorbic acid was released by the platelets.