Ascorbic acid, iron absorption

Ascorbic acid. Iron absorption, 144 Atom percent excess, definition, 187 Atomic absorption... 

Ascorbic acid increases absorption (see above) but its use (200 mg/day) is not clinically important in routine therapy desferrioxamine binds iron and reduces absorption (see Poisoning, below) tea (tannins) and bran reduce absorption. 

Using an isolated loop technique, a twofold increase in iron-59 uptake in rat intestine in the presence of ascorbic acid was demonstrated (5), and a similar eflFect was noted in isolated, perfused gut segments of mice (6). Using an everted intestinal sac technique, equivalent enhancement of mucosal uptake of both ferric and ferrous ions in the presence of 8 X 10 mM ascorbate concentration in the buffer was shown (7). The uptake of iron-59 by everted sacs of rat intestine was linear through a 0.5-3.0 mM concentration of ascorbic acid experiments on isolated intestinal loops of rats also have demonstrated a dose-dependent enhancement of iron absorption by ascorbic acid through an ascorbic acid iron molar ratio of 1 1 to 4 1 (49). 

Table I. Effects of Ascorbic Acid on Absorption of Therapeutic Doses of Iron in Humans Using the Radioiron Method...

Mechanistic Aspects of the Ascorbic Acid—Iron Interaction in the Intestine. Studies of the mechanism of the interaction of ascorbic acid and iron at the molecular and cellular levels have yielded a variety of theories. An acidic pH in the lumen of the intestine favors the absorption... 

In vitro experiments (38) showed that iron could form soluble chelates with ascorbic acid at the pH of the normal intestinal lumen. Soluble ascorbic acid-iron chelates formed at an acidic pH remained in solution even after the alkalinization of the medium (39). Intraintestinal installation of the pH-adjusted chelates into the rat enhanced the absorption of iron. The authors also suggest that the ascorbic acid normally present in mammalian bile has a physiologically important role in the absorption of nonheme iron from the diet. Whether the whole ascorbic acid-iron chelate is taken up intact into the mucosal cell under these conditions has not been established. Iron is, at the same time, more soluble, reduced, and more absorbable at intestinal pH in the presence of ascorbic acid those factors, with or without direct mucosal uptake of ascorbic acid-iron complexes, explain the contribution of ascorbic acid to the enhancement of iron availability. 

Effect of Heat Processing on Bioavailability of Added Iron. Several studies in Table III measured directly the effect of heat processing on added iron. These studies compared processed foods to a control group of identical unprocessed food. Studies in Table 111 utilizing unprocessed controls include 15, 19, and 23. Other studies did not employ an unprocessed control, but used a reference dose to enable comparisons from study to study. Reference doses of ferrous sulfate (most animal assays) or ferrous ascorbate (most human tests) were frequently used. Preparation of ferrous ascorbate, usually a 2 1 molar ascorbic acid iron solution, has been detailed by Layrisse et al. (25). These controls enabled measurement of variation in iron absorption from subject to subject, important in view of greater absorption of an iron deficient versus an iron replete subject. When a reference dose was fed as a radiolabeled salt (55Fe), and on alternate times the test diet was fed with a different radiolabel (59Fe), errors due to variation in subject absorption were eliminated, as each subject served as its own control. The different availabilities of various iron sources from baked enriched rolls were established in this manner (17). 

Ascorbic acid has also been shown to interact with therapeutic iron. Derman, et al., have reported that ascorbic acid increases absorption of various iron fortification compounds in infant formulas in cereals this three-fold increase in iron absorption induced by ascorbic acid was observed in multiparous women (16). El-Hawary, et al., studied 97 infants and young children and observed that ascorbic acid increased absorption from a four mg iron supplement as ferrous sulfate (17). 

Recent studies of Moore and Dubach have shown that normal subjects absorb about 10 % of iron from foodstuffs. Ascorbic acid enhanced absorption, but administration of hydrochloric acid and antacids were without effect. Subjects with iron-deficiency anemia showed no increased efficiency of iron absorption from foods. This finding is in contrast to studies of absorption of inorganic iron salts, in which subjects with iron deficiency showed greater absorption than normal subjects. 

Iron Absorption. A very important effect of ascorbic acid is the enhancement of absorption of nonheme iron from foods. Ascorbic acid also enhances the reduction of ferric iron to ferrous iron. This is important both in increasing iron absorption and in its function in many hydroxylation reactions (140,141). In addition, ascorbic acid is involved in iron metaboHsm. It serves to transfer iron to the Hver and to incorporate it into ferritin. 

The absorption of oral iron is decreased when tlie agent is administered with antacids, tetracyclines, penicillamine, and the fluoroquinolones. When iron is administered with levothyroxine, there may be a decrease in tlie effectiveness of levothyroxine When administered orally, iron deceases the absoqition of lev-odopa. Ascorbic acid increases tlie absoqition of oral iron. Iron dextran administered concurrently with chloramphenicol increases serum iron levels. 

C Ascorbic acid Coenzyme in hydroxylation of proline and lysine in collagen synthesis antioxidant enhances absorption of iron Scurvy—impaired wound healing, loss of dental cement, subcutaneous hemorrhage... 

Camire (2002) showed that texturization does not seem to have a great effect on mineral retention and bioavailability. Others have reported increased retention of ascorbic acid in rice- and maize-based snacks (Hazell and Johnson, 1989 Plunkett and Ainsworth, 2007), increased iron diffusibility and absorption of iron-complexed protein (Poltronieri et al, 2000 Watzke, 1998), and no difference in iron and zinc absorption in human subjects fed textured bran-flour (Fairweather-Tait et al, 1989). 

The iron absorption is enhanced when soluble monomeric complexes are formed (in the presence of e.g. proteins, aminoacids, ascorbic acid, EDTA, citric acid etc.) [13]. 

Absorptions of non-heme iron were (50) 0.56 and 3.20, (soy isolate, isolate + ascorbic acid), 5.05 and 10.19 (albumen, albumen + ascorbic acid)... 

An extractive spectrophotometric procedure based on the complexation of reduced Iron(II) with 5-Chloro-7-iodo-8-hydroxyquinoline (CIHQ) for the estimation of micro amounts of vitamin C. The resulting brown colored complex was extracted into chloroform to give a reddish brown extract which shows an absorption band at 485 nm. This chelate was formed immediately and the apparent molar absorptivity and Sandell s sensitivity for vitamin C was found to be 8.5 x 105 dm3 mol"1 cm 1 and 2.072xl0 4g cm 2. Linear relationship between absorbance and concentration of ascorbic acid is observed up to 0.8 pg ml"1. Interference studies of different substances including sugars, vitamins and amino acids, metal ions and organic acids were carried out. The utility of the method was tested by analysing some of the marketed products of vitamin C... 

Interactions. Antacids inhibit iron absorption. Combination with ascorbic acid (Vitamin C), for protecting Fe + from oxidation to Fe +, is theoretically sound, but practically is not needed. 

In the Mehansho et al. experiment, the potential for ascorbic acid to solubilize Fe was reported to be limited to low pH environments. Other investigators have reported that ascorbic acid facilitates iron absorption by forming a chelate with ferric iron at an acidic pH that remains soluble at the alkaline pH of the duodenum (Lynch and Cook, 1980). Salovaara... 

Gastric acid and ascorbic acid facilitate the absorption of iron. Therefore, bioavailability of iron ingested with food is considerably decreased and also enteric-coated iron preparations are absorbed to a lesser extend. Fixed combinations with ascorbic acid increase the absorption of iron by at least 30%. However such increased uptake seems to have little advantage over a modest increase of dose. 

Ascorbic acid or vitamin C is found in fruits, especially citrus fruits, and in fresh vegetables. Man is one of the few mammals unable to manufacture vitamin C in the liver. It is essential for the formation of collagen as it is a cofactor for the conversion of proline and lysine residues to hydroxyproline and hydroxylysine. It is also a cofactor for carnitine synthesis, for the conversion of folic acid to folinic acid and for the hydroxylation of dopamine to form norepinephrine. Being a lactone with two hydroxyl groups which can be oxidized to two keto groups forming dehydroascorbic acid, ascorbic acid is also an anti-oxidant. By reducing ferric iron to the ferrous state in the stomach, ascorbic acid promotes iron absorption. 

Iron absorption occurs predominantly in the duodenum and upper jejunum. The physical state of iron entering the duodenum greatly influences its absorption. At physiological pH, ferrous iron is rapidly oxidized to the insoluble ferric form. Gastric acid lowers the pH in the proximal duodenum, enhancing the solubility and uptake of ferric iron. When gastric acid production is impaired, iron absorption is reduced substantially. Ascorbic acid enhances iron absorption. Ascorbic acid mobilizes iron from iron-binding proteins in vivo, which in turn could catalyze lipid peroxidation. Iron absorption is inhibited by antacids, phytates, phosphates and tetracyclines. 

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. 

As noted, vitamin C is needed for the production of collagen in the body, but it is also essential in the production of certain hormones such as dopamine and adrenaline. Ascorbic acid is also essential in the metabolism of some amino acids. It helps protect cells from free radical damage, helps iron absorption, and is essential for many metabolic processes. The dietary need of vitamin C is not clearly established, but the U.S. National Academy of Science has established a recommended dietary allowance (RDA) of 60 mg per day. Some groups and individuals, notably Linus Pauling in the 1980s, recommend dosages as high as... 

In the presence of a large amount ol ascorbic acid (vuamin C l. (he absorption of iron is appreciably enhanced, because of the reduction of F c11 to the Fc t form. In the presence of phosphates, carbonates, and phyiutes. insoluble iron compounds arc formed, thus reducing absorption... 

The richest dietary sources of total iron are organ meats (liver and kidney), egg yolk, dried legumes, com, molasses and parsley. Liver is particularly valuable because of the high absorbability of its iron. However, only about 10% of dietary iron is absorbed. Iron deficiency anemia can be treated with soluble iron(II) compounds providing 200 mg in three or four daily divided doses. Oral iron(II) sulfate is the least expensive and is in wide use. Ascorbic acid increases the absorption efficiency of iron(II) sulfate. Parenteral administration of iron is used when oral iron is ineffective. Iron-dextran, a colloid formed from iron(III) chloride and an alkali-modified dextran, is one of several preparations available which has found extensive clinical use. It contains up to 28% Fe by weight and has a structural similarity to ferritin. Transfusion therapy may also be used in severe chronic anemia or acute hemorrhage. 

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... 

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... 

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