Iron Absorption In Man Research Articles

Investigation of the release of iron from ferritin by naturally occurring antioxidants

Ferritin is the main intracellular iron storage protein. The release of iron from ferritin in the presence of a number of phenolic based compounds of nutritional significance was studied at physiological pH. The release of iron was measured by monitoring the formation of the iron(II)–ferrozine complex. The kinetics of this process were studied in Hepes buffer (pH 7.00), at 37 °C. The order of ability to remove iron from ferritin is epigallocatechin>gallic acid methyl ester≈sinapic acid>ferulic acid. The presence of the oxyradical scavenger urea resulted in a slight inhibition in the release of iron from ferritin by both gallic acid methyl ester and epigallocatechin. The ability of each reagent to release iron is interpreted on the basis of their ability to (a) reduce the bound iron and (b) complex the iron with the oxidised form of the phenol, thus mobilising it from the protein. These studies indicate that some phenolic based compounds that have been epidemiologically associated with a negative effect on iron absorption in man, can individually mobilise and release iron from ferritin under suitable conditions.

Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages

The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20-50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50-70%, whereas beverages containing 100-400 mg total polyphenols/serving reduced Fe absorption by 60-90%. Inhibition by black tea was 79-94%, peppermint tea 84%, pennyroyal 73%, cocoa 71%, vervain 59%, lime flower 52% and camomile 47%. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.

Effect of oral iron chelator L1 on iron absorption in man.

Effect of oral iron chelator L1 on iron absorption in man.

Iron uptake by human upper small intestine microvillous membrane vesicles. Indication for a facilitated transport mechanism mediated by a membrane iron-binding protein.

To investigate the hypothesis that iron absorption in man involves a carrier-mediated cellular uptake mechanism, influx velocity (Vo) of 59Fe3+ by isolated human microvillous membrane (MVM) vesicles of the upper small intestine was examined. Vo revealed saturation kinetics (Km = 315 nM; Vmax = 361 pmol Fe3+ x min-1 x mg protein-1) was temperature dependent and inhibited by pronase pretreatment of MVM. In the presence of an inwardly directed Na(+)-gradient a typical overshoot phenomenon with maximal uptake at 30-40 s was observed. The suggestion of an active, carrier-mediated uptake mechanism for iron was pursued by isolation of a 160-kD iron-binding protein from solubilized human MVM proteins. This glycoprotein was assembled as a trimer composed of 54-kD monomers. A monospecific antibody against the 54-kD subunit inhibited vesicular influx of Fe3+ into MVM by greater than 50%. Immunofluorescence and immunoblot analysis confirmed the localization of the protein in brush border plasma membranes. It was detectable in human intestinal mucosa and liver, but not in esophagus. These data indicate that the translocation of Fe3+ across human MVM represents a facilitated transport mechanism which is, at least in part, mediated by a membrane iron-binding protein.

The influence of jamaican herb teas and other polyphenol-containing beverages on iron absorption in the rat

The content of total polyphenols in a series of Jamaican herb tea infusions ranged from 1.9–39.6 mg/100 ml and was lower than in infusions of black tea, green tea, coffee and cocoa (79.7–136.2 mg/100ml). The polyphenols of black tea and cocoa included a substantial quantity of tannins. All infusions contained substances which bound iron and either enhanced or prevented its passage through a 6000–8000 molecular weight cut-off dialysis membrane. When added to a cereal-milk meal however only black tea, green tea and cocoa reduced dialysable iron whereas the herb teas and coffee had no effect. When administered to rats at an identical polyphenol concentration either alone (4 mg/ml) or with a cereal meal (4 mg/g), absorption of 59-Fe was reduced by 0–45%. Assam tea and the herb teas, pepper elder and basil, were the most inhibitory, followed by coffee and cocoa. One herb tea, sour sop, had no effect. Some, but not all, reference polyphenols tested also reduced iron absorption in the rat. It was concluded that cocoa and some herb teas of high polyphenol content might, like black tea and coffee, also reduce iron absorption in man if consumed with a meal.

Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate

The dose-dependent inhibitory effect of sodium phytate on iron absorption was studied in man by serving wheat rolls containing no phytates and rolls to which various amounts (seven dose levels between 2 and 250 mg expressed as phytate phosphorus) were added just before serving. Fe in the two kinds of rolls was labeled with two radioisotopes of Fe (55Fe, 59Fe) and the rolls were served on alternate days. The inhibition of Fe absorption was strongly related to the amount of phytate added; 2 mg inhibited absorption by 18%, (p less than 0.001), 25 mg by 64% (p less than 0.001), and 250 mg by 82% (p less than 0.001). The addition of ascorbic acid significantly counteracted the inhibition whereas the corresponding effect of meat was less well defined and only seen at the highest phytate level. The marked inhibition of Fe absorption by phytates and the significant counteracting effect of ascorbic acid have wide nutritional implications.

Iron absorption in man calculated from erythrocyte incorporation of the stable isotope iron-54 determined by fast atom bombardment mass spectrometry

The methodology of precise isotope abundance determinations of erythrocyte iron by fast atom bombardment mass spectrometry and signal averaging is established. For the determination of the 54Fe/ 56Fe ratio a relative precision of 0.5% and an absolute precision of 0.03% is achieved. After oral loading with 54Fe-enriched samples in the range between 5 and 25 mg per subject, the 14-day erythrocyte incorporation of 54Fe has been determined in five individuals, namely, two adults, two children, and one infant. In the two adults, the oral dose of 54Fe was simultaneously labeled with a trace amount of carrier-free 59Fe. In these double-isotope loading tests, a good agreement was observed between the absorption data determined on the basis of whole body retention of 59Fe and on the basis of the 54Fe erythrocyte incorporation. The stable isotope methodology applied allows measurement of the iron absorption using highly enriched 54Fe at a dose of 25 mg for an adult or at a dose of 5 mg for infants of about 1 year of age.

Phytates and the inhibitory effect of bran on iron absorption in man

The cause of marked inhibitory effect of bran on absorption of dietary nonheme iron was studied in man by double-radioiron technique. Washing bran with hydrochloric acid but not with water removed inhibitory factor(s). Inhibition was almost restored by reconstituting phytate level. Removal of phytates in bran by endogenous phytase significantly increased absorption of iron. Removing, by washing with water, phosphates formed from phytates during enzymatic dephytinization led to a bran fraction with only a small remaining inhibitory effect on iron absorption. Half the iron in bran is in the form of monoferric phytate, which is well-absorbed. When potassium and magnesium phytates were added in amounts present in bran, the same inhibitory effect on iron absorption was seen. Although there appear to be other factors in bran that partly explain the inhibition, phytates are the main cause of the inhibitory effect of bran on iron absorption.

Effect of soy protein on nonheme iron absorption in man

The absorption of iron was measured from a hamburger in which half of the meat protein was substituted with various soy protein products (textured soy flour or defatted soy flour). Thge reduction of the meat content per se in the hamburgers reduced the percentage nonheme iron absorption by 25% from 11.2 to 8.4% The addition of defatted soy flour reduced the percentage absorption further from 8.4% to 5.2%. The amount of nonheme iron absorbed, however, was unchanged due to the high iron content of soy flour. A removal of phytates from soy flour did not increase the nonheme iron absorption. The total amount of iron absorbed, including the heme iron, is much lower when the content of meat was reduced by half in the soy-meat hamburgers. The addition of heme iron as blood to these hamburgers fully restored the total amount of iron absorbed to the level measured in hamburger meals prepared of meat only.

The inhibitory effect of soy products on nonheme iron absorption in man

Radioiron absorption studies were performed in male volunteer subjects to determine the effect on nonheme iron absorption of various semipurified proteins. When egg albumen and casein were substituted in protein-equivalent quantities in a semisynthetic meal, similar mean absorptions of 2.5 and 2.7% were observed. In contrast, isolated soy protein reduced absorption sharply, to an average of 0.5%. When egg albumen in the semisynthetic meal was replaced with full fat soy flour, textured soy flour, and isolated soy protein, absorption fell from 5.5 to 1.0, 1.9, and 0.4%, respectively, indicating an inhibitory effect by a wide range of soy products. The effect of substituting textured soy flour for meat in a meal containing a hamburger, french fries, and a milkshake was also evaluated. With 3:1 and 2.1 ratios of meat to unhydrated textured soy flour, absorption decreased by 61 and 53%, respectively. The soy products tested in this study have a pronounced inhibitory effect on the absorption of nonheme iron.

The inhibitory effect of bran on iron absorption in man

The effects of whole wheat bran and its components on the absorption of nonheme dietary iron were measured using a double isotope technique in human volunteers. When 12 g bran was added to a light meal, absorption decreased by 51 to 74%; this inhibitory effect of bran was shown for meals of both high and low iron availability. Inhibition was not explained by monoferric phytate, the major form of iron in bran, because labeled iron from monoferric phytate was absorbed at least as well as the common pool of nonheme dietary iron. Furthermore, removal of phytate from bran by endogenous phytase did not in itself alter the inhibitory effect of the bran on iron absorption. Studies in which dephytinized bran was separated into a soluble, phosphate-rich fraction and an insoluble, high-fiber fraction indicated that the soluble fraction was more inhibitory than the insoluble fraction.

Effect of cysteine on iron absorption in man

Cysteine significantly increases, about 2-fold, the absorption from nonheme iron present in vegetable foods, hemosiderin, and of a ferric salt, when this amino acid is administered during the ingestion of foods. No enhancing effect was obtained when the amino acid was mixed with the food before the final cooking. A slight but significant enhancement of heme iron absorption was observed when a large dose of cysteine was administered during the ingestion of hemoglobin. This amino acid mimics the enhancing effect from proteins present in animal foods such as beef, lamb, pork, fish, chicken, and liver. It could be possible that proteins and cysteine share the same mechanism by which they induce an increase of iron absorption.

The measurement of food iron absorption in man

1. The present study was considered as a first step to develop a method to measure food iron absorption from realistic common meals prepared and consumed by the subjects themselves in their own homes. The absorption of Fe from the meals was measured by means of the extrinsic-tag method modified to allow for a free choice of food items. 2. The mean Fe intake was 2.79 mg and the mean Fe absorption approximately 0.30 mg. The Fe status of the subjects corresponded to 31.5% absorption from a reference dose solution containing 3 mg elemental Fe as ferrous ascorbate. The variation in food Fe absorption obtained in this field study was found to be of the same magnitude as that obtained in studies performed under more controlled conditions as in the laboratory. 3. The conclusion was drawn that the proposed method could be used in realistic field studies aimed at, for example, explaining or preventing a high prevalence of deficiency. A suffciently long run-in period and a careful instruction of the subjects was considered essential for the design of future field studies.

Studies on the Control of Iron Absorption in Man

Studies on the Control of Iron Absorption in Man

Food iron absorption in man II. The effect of EDTA on absorption of dietary non-heme iron

One hundred and eighty iron absorption tests were performed in 45 normal men to determine the effect of EDTA on the absorption of dietary non-heme iron. The addition of 50 mg EDTA to test meals containing 4.1 mg iron reduced absorption by approximately one-half from meals of both high (standard meal) and low (semisynthetic meal) iron availability. Studies employing dual radioiron labels demonstrated complete isotopic exchange of ferric EDTA with dietary non-heme iron. Further studies were carried out to determine the decrease in food iron absorption at varying levels of EDTA. At a 1:1 molar ratio of EDTA to iron, absorption of non-heme iron was reduced to 72% and at a 2:1 molar ratio, to 50% of absorption without EDTA. These levels of EDTA are within the range believed to be present in the United States diet.

The effect of iron stores on iron absorption in the rat: the possible role of circulating ferritin.

Iron absorption in man is inversely related to body iron stores and serum ferritin concentration. A negative correlation between intestinal iron absorption and the amount of storage iron in the body has been confirmed in the rat and the hypothesis that absorption may be regulated through the mediation of ferritin has been tested. There was no difference in mucosal iron uptake or absorption between rats undergoing a jugular infusion of ferritin and those infused with saline despite a hundredfold difference in circulating ferritin concentration.

Inhibition of iron absorption in man by tetracycline (author's transl)

Inhibition of iron absorption in man by tetracycline (author's transl)

Effects of fructose on ferric and ferrous iron absorption in man.

Even at a molar ratio fructose:Fe = 106:1, fructose did not improve the poor bioavailability of ferric iron and had no effect on the better absorption of ferrous iron from therapeutic doses of 50 mg Fe. This was demonstrated for subjects with normal and depleted iron stores by intraindividual comparison of the whole-body retention of the absorbed <sup>59</sup> Fe. It is concluded that fructose complexes of ferric and ferrous iron are of no value in oral iron therapy.

Food iron absorption in man. II. Isotopic exchange of iron between labeled foods and between a food and an iron salt

Food iron absorption in man. II. Isotopic exchange of iron between labeled foods and between a food and an iron salt

Food iron absorption in man. 3. Effect of iron salt, ascorbic acid and desferrioxamine on the isotopic exchange between native food iron and an extrinsic inorganic iron tracer.

A new two pool extrinsic tag method to measure the dietary iron absorption has recently been proposed. One of the main prerequisites for this method is that a complete isotopic exchange takes place in the soluble ionized part of the common non‐haeme iron pool.The present investigation was carried out to test the validity of using this method to measure the effect of substances promoting or inhibiting dietary non‐haeme iron absorption.Normal subjects were served a meal prepared from biologically 55Fe labelled wheat or maize with added inorganic iron labelled with 59Fe. When served with added ferrous sulphate or ascorbic acid equal absorptions from the two tracers were found. When served with desferrioxamine there was a marked and almost equal reduction of the absorption from the two radioiron tracers. It is concluded that the rate or extent of isotopic exchange is not affected by compounds increasing (ferrous sulphate or ascorbic acid) or decreasing (desferrioxamine) the size of the ionized and/or soluble part of the common non‐heame iron pool.The extrinsic tag method can thus be used to study the effect of iron fortification or of substances promoting or inhibiting the absorption of dietary non‐haeme iron.