Iron absorption inhibitors

Inhibitors of non-haem iron absorption include polyphenols and phytates. The former, secondary plant metabolites rich in phenolic hydroxyl groups, are found... 

An increase in consumption of whole grain flour products is the nutritional aim in Norway. The high content of dietary fiber or factors associated with it, however, present in bran and whole grain flour, may interfere with the bioavailability of iron as indicated by several authors (2,3,4). Phosphate and especially phytic acid present in unrefined cereal products have frequently been said to be potent inhibitors of iron absorption (5,6). 

Phytate-bound iron may or may not constitute available forms of iron to the human as discussed in several other chapters of this book. Earlier work sugests that phytates inhibit iron absorption. Since phytates and oxalates are provided by cereal/ plant products, an Increase in the plant components of diet is likely to increase the intake of these inhibitors. 

Drug-Drug and Drug-Food Interactions. Drugs commonly used in the CKD population that may decrease absorption of oral iron include calcium preparations and antacids. Oral iron may also decrease the absorption of quinolone antibiotics. Medications that increase gastric pH such as H2-antagonists and proton pump inhibitors may also decrease iron absorption since iron absorption in the duodenum is maximized at an acidic pH. 

Ferric iron must be reduced to Fe for absorption by the mucosal cells in the proximal duodenum, the primary site of absorption. The most effective enhancer of iron absorption is ascorbic acid, especially with food of low iron bioavailability where a 10-fold, or greater, enhancement has been observed (8). Inhibitors of iron absorption include tea, soy protein, bran, and other fibers. Gastric and intestinal juices assist in solubilizing and releasing bound Fe in food. Absorbed Fe is reoxidized to Fe by ferroxidase(s) before it is bound by apotransferrin or apoferritin (storage). Ferroxidase activity has been demonstrated with xanthine oxidase and cemloplasmin [11-13]. 

Some recent observations on the role of the pancreas in iron absorption may be relevant to the pathogenesis of hemochromatosis. Iron absorption is increased four times in patients with repeated attacks of pancreatitis. A heat- and acid-stable ultrafiltrable inhibitor of iron absorption has been found in the pancreas its chemical composition is not known. 

Heme-iron, only present in animal foods, is more bioavailable compared to other sources contained in grains and vegetables. The consumption of animal products enhances iron absorption associated with grains. Another important enhancer of iron absorption is vitamin C because it chelates nonheme-iron under stomach acidic conditions, and keeps it soluble under the relatively neutral pH conditions of the duodenum. Vitamin C reduces ferric iron (Fe+ ) into ferrous iron (Fe+ ) in the stomach. The ferrous form is more efficiently absorbed by the duodenum epithelial cells. Heme-iron enters the epithelial cells complexed to porphyrin myoglobin and hemoglobin. The absorbed iron is stored in ferritin molecules located inside the intestinal cells and transported bound to transferrin. There are known inhibitors of iron absorption, the most important being phytates and fiber. 

Fig. 6. Difference spectra between xanthine oxidase inactivated with various pyra-zolo [3, 4-d] pyrimidines and the native enzyme. The spectra are believed to represent the increase in absorption occurring when Mo(VI) of native enzyme is converted to Mo(IV) complexed with the inhibitors. Spectra were obtained by treating the enzyme with inhibitors in the presence of xanthine, then admitting air, so as to re-oxidize the iron and flavin chromophores. The extinction coefficients, de, are expressed per mole of enzyme flavin. Since some inactivated enzyme was present, extinction coefficients per atom of molybdenum of active enzyme will be about 30% higher than these values. (Reproduced from Ref. 33, with the permission of Dr. V. Massey.)...

Iron-, copper-, and zinc complexes of rutin, dihydroquercetin, and green tea epicatechins were found to be much more efficient inhibitors than parent flavonoids of toxic effects of chrysotile asbestos fibers on peritoneal macrophages and erythrocytes [168], It was proposed that in this case the enhanced activity of metal-flavonoid complexes was increased by the absorption on chrysotile fibers. 

Proton pump inhibitors cause a profound and long-lasting inhibition of gastric acid secretion therefore, proton pump inhibitors may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, ampicillin, iron salts, digoxin, cyanocobalamin). 

Absorption of certain drugs, including those with neutral or cationic charge as well as anions, may be impaired by the resins. These include digitalis glycosides, thiazides, warfarin, tetracycline, thyroxine, iron salts, pravastatin, fluvastatin, folic acid, phenylbutazone, aspirin, and ascorbic acid. Any additional medication (except niacin) should be given 1 hour before or at least 2 hours after the resin to ensure adequate absorption. Colesevelam does not bind digoxin, warfarin, or reductase inhibitors. 

For the most part, adequate copper is received in diet and widespread human deficiencies do not occur, but deficiencies may arise because of antagonists. The metals Cd, Hg, Ag and Zn interfere with copper metabolism, probably by competing for copper-binding sites in proteins. Ascorbic acid depresses intestinal absorption of copper56 (in contrast to iron). Some proteins in the diet adversely affect utilization of copper. The sulfide ion is a well known inhibitor of copper absorption, since it forms copper(II) sulfide which is insoluble.56... 

Acid is important in releasing vitamin B12 from food. A minor reduction in oral cyanocobalamin absorption occurs during proton pump inhibition, potentially leading to subnormal Bi2 levels with prolonged therapy. Acid also promotes absorption of food-bound minerals (iron, calcium, zinc) however, no mineral deficiencies have been reported with proton pump inhibitor therapy. 

Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine), a photosynthetic inhibitor that is used in large quantities for weed control in com and sorghum, has been treated electrochemically in aqueous solution on reticulated vitreous carbon cathode in the presence of noble-metal catalysts (Stock and Bunce 2002). Elec-trocatalytic hydrogenolysis to 2-ethylamino-4-isopropylamino-s-triazine occurs in quantitative yield, and is most efficient with Pd-based catalysts. Current efficiency increases with increasing atrazine and catalyst concentration, and decreasing current density. The Authors observed a time lag between the start of the electrolysis and the appearance of the dechlorinated products, which was attributed to the absorption of hydrogen by the palladium lattice. As alternative to the electrochemical treatment, the degradation of chlorinated triazines by zero-valent-iron was already mentioned (Dombek et al. 2004). 

PROTON PUMP INHIBITORS IRON 1 plasma concentrations of iron Proton pump inhibitors inhibit the absorption of iron Consider use of parenteral iron in patients on proton pump inhibitors treatment... 

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