Ascorbate, gastrointestinal

Amphotericin B is particularly effective against systemic infections caused by C. albicans and Cryptococcus neoformans. It is poorly absorbed from the gastrointestinal tract and is thus usually administered by intravenous injection under strict medical supervision. Amphotericin B methyl ester (Fig. 5.15C) is water-soluble, unlike amphotericin B itself, and can be administered intravenously as a solution. The two forms have equal antifungal activity but higher peak serum levels are obtained with the ester. Although the ester is claimed to be less toxic, neurological effects have been observed. An ascorbate salt has recently been described which is water-soluble, of similar activity and less toxic. 

In the enterocyte as it enters the absorptive zone near to the villus tips, dietary iron is absorbed either directly as Fe(II) after reduction in the gastrointestinal tract by reductants like ascorbate, or after reduction of Fe(III) by the apical membrane ferrireductase Dcytb, via the divalent transporter Nramp2 (DCT1). Alternatively, haem is taken up at the apical surface, perhaps via a receptor, and is degraded by haem oxygenase to release Fe(II) into the same intracellular pool. The setting of IRPs (which are assumed to act as iron biosensors) determines the amount of iron that is retained within the enterocyte as ferritin, and that which is transferred to the circulation. This latter process is presumed to involve IREG 1 (ferroportin) and the GPI-linked hephaestin at the basolateral membrane with incorporation of iron into apotransferrin. (b) A representation of iron absorption in HFE-related haemochromatosis. 

Methenamine mandelate is a salt of mandelic acid and methenamine and both of these possess property of urinary antiseptic. It is rapidly absorbed in gastrointestinal tract and excreted unchanged in urine, where it broken down in acidic pH (< 5) of urine and formaldehyde is released, which inhibits most of the bacteria. It is administered with sodium biphosphate, mandelic acid or ascorbic acid to keep the urinary pH below 6. Its use is restricted to chronic, resistant type of UTI. 

M Cohen, HN Bhagavan. Ascorbic acid and gastrointestinal cancer. J Am Coll Nutr 14 565 -578,1995. 

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 of iron by the individual varies with age, iron status, the amount and chemical form of the iron ingested, and with conditions in the gastrointestinal tract, only about 5—15% of iron in the diet being normally absorbed. Ferrous iron, as the sulphate, gluconate, fumarate or lactate or as ferrous ammonium sulphate, is appreciably taken up into the bloodstream from the duodenum, especially in the presence of ascorbic acid, a reducing agent. Little difference was found in the extent of their absorption between ferrous sulphate and the various chelates, but ferric ammonium citrate or polysaccharide complexes were only very poorly absorbed22)... 

Vitamin C [ascorbic acid) Men 90 mg/d Women 75 mg/d Cofactor for reactions requiring reduced copper or iron met-alloenzyme and as a protective antioxidant prevents scurvy Gastrointestinal disturbances, kidney stones, excess iron absorption... 

The ability to synthesise ascorbic acid from glucose is absent in a small group of animal species that include man, primates, the guinea pig and the fruit-bat this is due to the absence of the gene that codes for one of the enzymes required for ascorbate synthesis. These species are therefore dependent on an external source of the vitamin in their diet and it is needed as a cofactor for several hydroxylase enzymes, notably the iron-dependent proline and lysine hydroxylases and the copper-dependent dopamine-(3-hydroxylase the function of ascorbate in these enzymes is likely to be its ability to keep the metal in the reduced form which is necessary for hydroxylation. The ability of ascorbate to reduce Fe3+ to Fe2+ is important in promoting the gastrointestinal uptake of iron and for its release from the iron store ferritin. 

Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminium absorption. Lancet I99I 338(8780) I467. 

Because ascorbic acid in the gastrointestinal tract can reduce the vitamin B12 content of food, patients with vitamin B12 deficiency should always be questioned about their intake of ascorbic acid (40). 

The body can absorb about 500 mg of ascorbic acid daily with any excess immediately excreted by the kidneys. Large doses may cause diarrhea or other gastrointestinal disturbances. Damage to the teeth has also been reported. However, no adverse effects have been reported at the levels employed as an antioxidant in foods and pharmaceuticals. The WHO has set an acceptable daily intake of ascorbic acid, potassium ascorbate, and sodium ascorbate, as antioxidants in food, at up to 15mg/kg body-weight in addition to that naturally present in food. ... 

The gastrointestinal absorption of ascorbate should be considered before summarizing this study. In no case did we achieve a complete recovery of the administered radioactively labeled ascorbic acid. In a separate set of experiments (7), the subjects were equilibrated on a limited intake of ascorbate and given a small oral dose of labeled ascorbate together with about 30 mg of carrier ascorbate (7). After a few hours this intake was followed by large intakes of unlabeled... 

The probable mechanism of the synergetic effect of L-ascorbic acid and substances capable of binding bile acids in the gastrointestinal tract is shown in Scheme 1. An increased intake of L-ascorbic acid accelerates the formation of 7a-hydroxycholesterol and thereby also accelerates the overall rate of cholesterol transformation into bile acids. Bile acids excreted from the liver into the gastrointestinal tract become bound and thus are prevented from affecting 7 -hydroxylation of cholesterol through a feedback mechanism. In this way, a permanent disequilibrium occurs between cholesterol and bile acids with increased cholesterol transformation to bile acids and enhanced irreversible output of the products of this reaction, which results in a decline of cholesterol levels in the blood and tissues. 

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