Absorption of iron Fe-humate in nutrient solutions by plants

Humic substances have significant practical implications regarding the transport and availability of micronutrients to plants. Nutrient solution studies were conducted to evaluate Fe-humate complexes as a iron source to plants. A short term Fe-humate absorption study was conducted using excised barley roots, while long term absorption studies were conducted using sunflower andSpirodella intermedia. Humic acid was extracted with 0.5N NaOH from a Typic Argiudol, A horizon, and purified with exhange resins and EDTA. The Fe-humate was obtained by passing purified humic acid through a cation exhange resin saturated with iron using⁵⁹Fe as a tracer. In the short term, absorption studies, the absorption of iron by barley roots was insensitive to metabolic inhibitors, low temperature and anaerobiosis. This may be due to a strong adsorption or precipitation of Fe-humate in the root free spaces masking the absorption. However, long term studies indicated that Fe-humate was a good source of iron which was readily absorbed and transported to the shoot.     

Zinc inhibits nonheme iron bioavailability in humans

There is increasing concern about potential negative interactions in combined iron and zinc supplementation. The aim of the present study was to determine the dose-response effect of zinc, given as a solution, on iron bioavailability. Twenty-two healthy adult women were selected to participate in the study. Iron, with or without zinc was given as an aqueous solution on d 1,2,14, and 15 of the study. Iron bioavailability was measured on the basis of erythrocyte incorporation of⁵⁵Fe or⁵⁹Fe 14 d after administration. Subjects received 0.5 mg of iron together with graded zinc concentrations (0-11.71 mg). No significant effect of zinc on iron absorption was found at Zn : Fe molar ratios up to 2 :1. At 5:1,10:1, and 20 :1 molar ratios, a dose-dependent inhibitory effect on iron absorption was observed (28-40% of iron absorption inhibition; one-way repeated-measures ANOVA, F = 4.48,p = 0.02). In conclusion, zinc administration combined with iron in an aqueous solution leads to the inhibition of iron bioavailability, which occurs in a dose-dependent way. This negative interaction should be considered for supplementation programs with both microminerals.     

Effects of iron deficiency and iron overload on manganese uptake and deposition in the brain and other organs of the rat

Managanese (Mn) is an essential trace element at low concentrations, but at higher concentrations is neurotoxic. It has several chemical and biochemical properties similar to iron (Fe), and there is evidence of metabolic interaction between the two metals, particularly at the level of absorption from the intestine. The aim of this investigation was to determine whether Mn and Fe interact during the processes involved in uptake from the plasma by the brain and other organs of the rat. Dams were fed control (70 mg Fe/kg), Fe-deficient (5–10 mg Fe/kg), or Fe-loaded (20 g carbonyl Fe/kg) diets, with or without Mn-loaded drinking water (2 g Mn/L), from day 18–19 of pregnancy, and, after weaning the young rats, were continued on the same dietary regimens. Measurements of brain, liver, and kidney Mn and nonheme Fe levels, and the uptake of⁵⁴Mn and⁵⁹Fe from the plasma by these organs and the femurs, were made when the rats were aged 15 and 63 d. Organ nonheme Fe levels were much higher than Mn levels, and in the liver and kidney increased much more with Fe loading than did Mn levels with Mn loading. However, in the brain the increases were greater for Mn. Both Fe depletion and loading led to increased brain Mn concentrations in the 15-d/rats, while Fe loading also had this effect at 63 d. Mn loading did not have significant effects on the nonheme Fe concentrations.⁵⁴Mn, injected as MnCl₂ mixed with serum, was cleared more rapidly from the circulation than was⁵⁹Fe, injected in the form of diferric transferrin. In the 15-d-rats, the uptake of⁵⁴Mn by brain, liver, kidneys, and femurs was increased by Fe loading, but this was not seen in the 63-d rats. Mn supplementation led to increased⁵⁹Fe uptake by the brain, liver, and kidneys of the rats fed the control and Fe-deficient diets, but not in the Fe-loaded rats. It is concluded that Mn and Fe interact during transfer from the plasma to the brain and other organs and that this interaction is synergistic rather than competitive in nature. Hence, excessive intake of Fe plus Mn may accentuate the risk of tissue damage caused by one metal alone, particularly in the brain.     

Potential role of in vitro iron bioavailability studies in combatting iron deficiency: a study of the effects of phosvitin on iron mobilization from pinto beans

Iron deficiency and iron overload affect one billion people worldwide. Treatment of iron malnutrition can be enhanced by an understanding of iron bioavailability from the diet. We have focused on the development of in vitro methods for determining iron bioavailability in the hopes of providing both an understanding of the chemical basis leading to the inhibition or enhancement of iron absorption and the provision of methodologies which will allow nutritionists around the world to ascertain iron bioavailability of local foods and food combinations. The study reported here focuses on the effects of phosvitin, a suspected inhibitor of iron absorption found in egg yolks, on the chemistry of iron during the in vitro enzymatic digestion of pinto beans. Three basic types of information were obtained. First, the total soluble iron was determined during in vitro enzymatic digestion under simulated oral, gastric (pH 2) and duodenal (pH 6) conditions. Phosvitin was found to have a strong solubilizing effect at pH 6 and pH 2 when in the presence of ascorbate. Pyrophosphate also leads to high iron mobilization. A second approach is to determine the static Fe2+ and Fe3+ concentrations following in vitro enzymatic digestion of pinto beans at pH 2 and pH 6. Ascorbic acid enhanced the total soluble iron at both pH values, however, only at pH 2 was a large proportion of the iron found in the Fe2+ state and then only in the presence of phosvitin but not pyrophosphate. A third approach is to determine the amount of Fe2+ formed in the digestive supernatant during a 10-min incubation with ferrozine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is solubility in vitro a reliable predictor of iron bioavailability?

In this paper we have described physiological factors that are likely to influence iron bioavailability, reviewed chemical properties of iron important to its absorption, and addressed the question posed in the title. Intestinal transit times, luminal pH, and diffusion barriers resulting from gastrointestinal mucus may affect absorption. The tendency of iron to form large-molecular-weight species and to bind to macromolecules may limit its absorption. Iron solubility following in vitro gastrointestinal digestion is a reliable predictor of ascorbic acid effects on bioavailability but not of protein effects. Solubility of low-molecular-weight iron is better than simple solubility for predicting iron bioavailability.     

Investigation of the mechanisms affecting Cu and Fe bioavailability from legumes

Chemical composition and content in polyphenols, phytic acid, and dietary fiber of whole cooked common bean (Phaseolus vulgaris L.) and faba bean (Vicia faba L.) and of soluble and insoluble fractions separated from them were determined. Simultaneous determination of Cu, Fe, and protein bioavailability in the small intestine of rat was carried out in single-dose, short-term (1 h) experiments. After cooking, about 80% of seed components (on a weight basis) of either legume was recovered in the precipitate (insoluble fraction) after extraction with water. Protein, lipid, starch, dietary fiber, and polyphenols underwent the most severe insolubilization, together with more than 70% of total Cu and Fe. Cu, Fe, and protein bioavailability showed a similar trend (i.e., the lower the protein, the lower the Cu and Fe availability). Availability of proteins, Cu, and Fe in the insoluble fractions were the lowest, but Cu bioavailability was higher than that of Fe in all fractions. The results provide evidence that the heat-induced insolubilization process adversely affects not only protein but also Cu and Fe bioavailability from legumes and that polyphenols are likely to be a major inhibitor on absorption.     

Intestinal iron absorption in chickens

Intestinal iron absorption in chickens was studied in vivo, using an intestinal perfusion technique in closed circuit. The results obtained show that iron absorption, at 30 min intervals, is a linear function of test solution iron concentrations of up to 776 μg Fe/20 mL. At higher concentrations, iron saturation occurs. The mucosal epithelial cells seem to be less a limiting factor than in rats. However, in chickens, the binding capacity of plasma might play an important role in the regulation of iron absorption. Iron absorption versus time was analyzed in 15, 30, 60, and 120 min periods for the iron concentration of 14 μg Fe/20 mL. Intestinal iron absorption showed a linear relationship between these two parameters. A period of perfusion of either 30 or 60 min by a solution of 14 μg Fe/20 mL appears suitable since no interference by a saturation process can then occur.     

Effects of type of fat in the diet on iron bioavailability assessed in suckling and weanling rats

Differences in iron bioavailability from human milk and milk formulas may in part be due to differences in lipid composition. We investigated the short and long term effects of diets based on different fats [corn, coconut, olive, or soy oil, human milk fat (HMF) and a formula fat blend (FF)] on iron absorption in rats. Suckling rat pups dosed with 59Fe-labeled diets containing different fat sources were killed after 6 h, and blood and individual tissues were counted. Iron availability was estimated by % 59Fe in blood. Pups dosed with a more saturated fat (coconut oil) had a higher % 59Fe in blood than those fed other fat sources. Weanling rats were used to determine iron bioavailability from fat sources using both the hemoglobin repletion method and whole body counting. Hemoglobin regeneration was significantly higher for rats fed the HMF diet (8.4 +/- 0.5 g/dl) than from the FF diet (6.5+/-0.6 g/dl) or the corn oil diet (less saturated) (6.4 +/- 0.3 g/dl). Rats fed diets based on coconut oil (more saturated) had significantly higher % 59Fe retention (61.6 +/- 1.4) than rats fed diets based on FF (49.8 +/- 3.4). There was a significant positive association between oleic acid in the diet and oleic acid in the intestinal mucosa (r = 0.95, p < 0.05) and between linoleic acid in the diet and linoleic acid in the intestinal mucosa (r = 0.97, p < 0.05) suggesting that the dietary treatment altered the fatty acid composition of the brush border membrane. Our results suggest that saturated fats may increase iron absorption and that part of this may be achieved by changes in the fatty acid composition of the intestinal mucosa. Hemoglobin regeneration and % 59Fe retention data suggest that differences in iron absorption from infant diets may in part be due to differences in fat composition. Therefore, lipid composition of infant formulas should also be taken into consideration as a factor influencing iron bioavailability.     

Effects of dietary supplementation with aluminum and citrate on iron metabolism in the rat

The metabolism of iron (Fe) has been shown to interact with that of aluminum (Al) in relation to intestinal absorption, transport in the blood plasma, and the induction of lipid peroxidation and cellular damage. Also, dietary supplementation with citrate has been shown to increase the absorption of both metals and, in the presence of high intakes of Fe and Al, leads to excessive accumulation of both metals in the body. In this study, the likely interaction between Al and internal Fe metabolism was investigated using rats fed diets that were either deficient, sufficient, or loaded with Fe, with or without the addition of Al and sodium citrate. These diets commenced when the rats were 4 wk old and were continued for 9–11 wk. At that time, Fe metabolism as assessed by measurement of organ uptake of⁵⁹Fe and¹²⁵I-transferrin, after iv injection of transferrin labeled with both isotopes, plus measurement of tissue concentrations of nonheme Fe and Al. The Fedeficient diet and Fe-loaded diet led to states of Fe deficiency and Fe overload in the rats, and supplementation of the diet with Al increased Al levels in the kidneys, liver, and femurs, but, generally, only when the diet also contained citrate. Neither Al nor citrate supplementation of the diet had any effect on nonheme Fe concentrations in the liver, kidney, or brain, or on the uptake of⁵⁹Fe or¹²⁵I-transferrin by liver, kidney, brain, or spleen. Only with the femurs was a significant effect observed: increased⁵⁹Fe uptake in association with increased Al intake. Therefore, using this animal model, there was little evidence for interaction between Fe and Al metabolism, and no support was obtained for the hypothesis that dietary supplementation with Fe and citrate can lead to excessive Fe absorption and deposition in the tissues.     

Solubility and dissolution of iron oxides

In most soils, FeIII oxides (group name) are the common source of Fe for plant nutrition. Since this Fe has to be supplied via solution, the solubility and the dissolution rate of the Fe oxides are essential for the Fe supply. Hydrolysis constants and solubility products (K_sp) describing the effect of pH on FeIII ion concentration in solution are available for the well-known Fe oxides occurring in soils such as goethite, hematite, ferrihydrite. K_sp values are usually extremely low ((Fe³⁺)·(OH)³=10^–37–10^–44). However, for each mineral type, K_sp may increase by several orders of magnitude with decreasing crystal size and it decreases with increasing Al substitution assuming ideal solid solution between the pure end-members. Based on such calculations a poorly crystalline goethite with a crystal size of 5 nm may well reach the solubility of ferrihydrite. The variations in K_sp are of relevance for soils because crystal size and Al substitution of soil Fe oxides vary considerably and can now be determined relatively easily.The concentration of Fe²⁺ in soil solutions is often much higher than that of Fe(III) ions. Therefore, redox potential strongly influences the activity of FeII. At a given pH and E_h, the activity of FeII is higher the higher K_sp of the FeIII oxide and thus also varies with the type of Fe oxide present.Besides the solubility, it is the dissolution rate which governs the supply of soluble Fe to the plant roots. Dissolution of Fe oxides takes place either by protonation, complexation or, most important, by reduction. Numerous dissolution rate studies with various FeIII oxides were conducted in strong mineral acids (protonation) and they have shown that besides the Fe oxide species, crystal size and/or crystal order and substitution are important determinative factors. For example, in soils, small amounts of a more highly soluble meta- or instable Fe oxide such as ferrihydrite with a large specific surface (several hundred m²g^–1) may be essential for the Fe supply to the plant root. Its higher dissolution rate can also be used to quantify its amount in soils. Ferrihydrite can be an important component in soils with high amounts of organic matter and/or active redox dynamics, whereas highly aerated and strongly weathered soils are usually very low in ferrihydrite. On the other hand, dissolution rates of goethites decrease as their Al substitution increases.Much less information exists on the rate of reductive and chelative dissolution of Fe oxides which generally simulate soil conditions better than dissolution by protonation. Here again, type of oxide, crystal size and substitution are important factors. Organic anions such as oxalate, which are adsorbed at the surface, may weaken the Fe³⁺-O bonds and thereby increase reductive dissolution. As often observed in weathering, the dissolution features of the crystals appear to follow zones of weakness in the crystal.     

Long-term effects of iron: Zinc interactions on growth in rats

The influence of iron (Fe) on the bioavailability and functional status of zinc (Zn) was studied in young rats using metabolic balances and tissue dosages, which were compared to growth. Diets supplied adequate intakes of Fe (45 and 300 mg/kg diet) and Zn (14 and 45 mg/kg) for 2 mo. Two metabolic balance determinations were performed that were correlated for Zn and Fe during the first and the last weeks of the study. A significant effect of Fe supply, but not of Zn was displayed on Fe absorption; both Fe and Zn diet concentrations had a significant influence on Zn absorption. Fe and Zn organ contents were significantly correlated with the amount absorbed during the two metabolic balances. There was a positive correlation between liver and muscle Fe and Fe absorption, and Fe absorption and muscle Zn, as well as a negative one with liver Zn; a positive correlation was displayed between Zn absorption and Zn organ content. No correlation was found between Zn absorption and Fe tissue content. Growth was correlated with Zn, but not with Fe absorption during both balances. A positive correlation was displayed between growth and Zn liver content, and a negative one with Fe liver content. Care must be taken to give growing subjects balanced diets or supplementation, since the negative interactions between these trace elements are likely to persist as long as the diet is given.     

Voltage-clamp: a useful approach to study in vitro duodenal iron transport in the mouse

The mechanism(s) controlling iron absorption remain(s) uncertain despite the progress in the identification of genes selectively expressed in the duodenum. The availability of experimental models of iron absorption is critical to the clarification of such mechanism(s). In the present study, a simple method for studying in vitro iron absorption in mouse duodenum is described. Short circuit current, open circuit potentials and epithelial conductances were measured in mouse duodenal segments. Also, unidirectional ⁵⁵Fe fluxes at different pH conditions were measured in mice with varying iron status. The findings reinforce evidence for an adaptive response of the iron absorptive process according to the body iron status. Significant differences are demonstrated between iron fluxes measured in normal and parenterally iron loaded mice and at acidic compared to neutral pH environment. Also, a significant difference was observed between transepithelial potential measured in duodenum from iron-loaded compared to untreated mice. Advances in the understanding of the mechanism(s) of iron absorption can be brought by the application of voltage-clamp techniques to the electrophysiologic study of iron overload mouse models.     

Mechanisms and regulation of reduction-based iron uptake in plants

Despite the usually high abundance of iron (Fe) in soils, the low solubility of Fe-bearing minerals restricts the available Fe pools in most aerobic soils to levels that are far below those required for microbial or plant growth. To acquire the necessary amounts of Fe from the environment, organisms have evolved mechanisms that enhance the solubility and dissolution rate of Fe(iii) oxyhydroxides prevailing in aerobic soils. Chemically, these mechanisms are based on weakening of the Fe–O bond by reduction, chelation and protonation. Physiologically, two distinct and in all known cases mutually exclusive strategies can be distinguished: the excretion of siderophores capable of solubilizing external ferric Fe and subsequent uptake of the ferric siderophore complex; and reduction of Fe(iii) prior to uptake of the more soluble Fe²⁺ ion. With the exception of graminaceous species, in which Fe uptake is based on the former mechanism, the latter strategy is found in all cormophytes and certain algae, yeast and bacteria. In higher plants, the increase in their capacity to convert extracellular ferric to ferrous Fe is part of a series of physiological and morphological events that act in concert to achieve appropriate internal levels of Fe. It is this amalgam of features that determines the Fe efficiency of a species or cultivar that in turn affects the yield of economically important plants and the natural distribution of species. Adaptive changes to limited Fe availability have been studied at the molecular, physiological and whole-plant level. This review summarises current knowledge of the components of reduction-based Fe uptake in plants and presents an integrated view of the present understanding of mechanisms that control the rate and extent of Fe absorption by roots.     

Mechanisms of iron acquisition from siderophores by microorganisms and plants

Most bacteria, fungi, and some plants respond to Fe stress by the induction of high-affinity Fe transport systems that utilize biosyrthetic chelates called siderophores. To competitively acquire Fe, some microbes have transport systems that enable them to use other siderophore types in addition to their own. Bacteria such as Escherichia coli achieve this ability by using a combination of separate siderophore receptors and transporters, whereas other microbial species, such as Streptomyces pilosus, use a low specificity, high-affinity transport system that recognizes more than one siderophore type. By either strategy, such versatility may provide an advantage under Fe-limiting conditions; allowing use of siderophores produced at another organism's expense, or Fe acquisition from siderophores that could otherwise sequester Fe in an unavailable form.Plants that use microbial siderophores may also be more Fe efficient by virtue of their ability to use a variety of Fe sources under different soil conditions. Results of our research examining Fe transport by oat indicate parity in plant and microbial requirements for Fe and suggest that siderophores produced by root-colonizing microbes may provide Fe to plants that can use the predominant siderophore types. In conjunction with transport mechanisms, ecological and soil chemical factors can influence the efficacy of siderophores and phytosiderophores. A model presented here attempts to incorporate these factors to predict conditions that may govern competition for Fe in the plant rhizosphere. Possibly such competition has been a factor in the evolution of broad transport capabilities for different siderophores by microorganisms and plants.     

Improved absorption of caseinophosphopeptide-bound iron: role of alkaline phosphatase

Hydrolysis of proteins could lessen their inhibiting effect on the poor absorption of cow's milk iron (Fe), which is responsible for the high incidence of Fe deficiency worldwide. When bound to Fe, caseinophosphopeptides (CPP) derived from milk proteins resist luminal digestion, enhance Fe solubility and could improve its bioavailability; brush border enzyme alkaline phosphatase activity could influence iron absorption by releasing free Fe; this study assessed its role in the absorption of CPP-bound Fe. Rat duodenal loops were perfused with Fe gluconate or Fe bound to the CPP of beta casein [beta-CN (1-25)], with or without the addition of an inhibitor of alkaline phosphatase, Na2WO4. The uptake of Fe-beta-CN (1-25) was greater than Fe gluconate. Na2WO4 enhanced the uptake of Fe-beta-CN (1-25) and not of Fe gluconate. So the release of free, insoluble Fe, by alkaline phosphatase seems to be prevented by providing Fe in the Fe-beta-CN (1-25) complex form. Its good disappearance rate makes beta-CN (1-25)-bound Fe a candidate for food fortification.     

Soil and crop management strategies to prevent iron deficiency in crops

Plants and humans cannot easily acquire iron from their nutrient sources although it is abundant in nature. Thus, iron deficiency is one of the major limiting factors affecting crop yields, food quality and human nutrition. Therefore, approaches need to be developed to increase Fe uptake by roots, transfer to edible plant portions and absorption by humans from plant food sources. Integrated strategies for soil and crop management are attractive not only for improving growing conditions for crops but also for exploiting a plant??s potential for Fe mobilization and utilization. Recent research progress in soil and crop management has provided the means to resolve complex plant Fe nutritional problems through manipulating the rhizosphere (e.g., rhizosphere fertilization and water regulation), and crop management (includes managing cropping systems and screening for Fe efficient species and varieties). Some simple and effective soil management practices, termed ??rhizosphere fertilization?? (such as root feeding and bag fertilization) have been developed and widely used by local farmers in China to improve the Fe nutrition of fruit plants. Production practices for rice cultivation are shifting from paddy-rice to aerobic rice to make more efficient use of irrigation water. This shift has brought about increases in Fe deficiency in rice, a new challenge depressing iron availability in rice and reducing Fe supplies to humans. Current crop management strategies addressing Fe deficiency include Fe foliar application, trunk injection, plant breeding for enriched Fe crop species and varieties, and selection of cropping systems. Managing cropping systems, such as intercropping strategies may have numerous advantages in terms of increasing Fe availability to plants. Studies of intercropping systems on peanut/maize, wheat/chickpea and guava/sorghum or -maize increased Fe content of crops and their seed, which suggests that a reasonable intercropping system of iron-efficient species could prevent or mitigate Fe deficiency in Fe-inefficient plants. This review provides a comprehensive comparison of the strategies that have been developed to address Fe deficiency and discusses the most recent advance in soil and crop management to improve the Fe nutrition of crops. These proofs of concept studies will serve as the basis for future Fe research and for integrated and optimized management strategies to alleviate Fe deficiency in farmers?? fields.     

In vitro dialyzability using meal approach as an index for zinc and iron absorption in humans

With a standardized protocol under simulated gastrointestinal conditions,⁶⁵Zn and⁵⁹Fe dialyzability was measured for 38 diets from 7 different published studies on human absorption. The compositions of these diets were available in the form of the amounts of food ingredients used for breakfast, lunch, and dinner. Considering each of these types as a separate meal, percent dialyzability was measured. The weighted average of breakfast, lunch, dinner, and snacks, if any, was taken to represent the entire day’s bioavailability. The correlation between in vitro percent dialyzability and reported human absorption was 0.92 for zinc and 0.96 for iron and both were statistically significant (p = 0.0001). The prediction equations for zinc and iron were obtained asy = -0.7718 + 1.1038x andy = 0.3197 + 0.9084x, respectively. This indicated that in vitro dialyzability using the meal approach can be used as an index with good discriminating power for different levels of human absorption.     

PHYSIOLOGICAL CHARACTERIZATION OF A SYNECHOCOCCUS SP. (CYANOPHYCEAE) STRAIN PCC 7942 IRON‐DEPENDENT BIOREPORTER FOR FRESHWATER ENVIRONMENTS1

The complex chemical speciation of Fe in aquatic systems and the uncertainties associated with biological assimilation of Fe species make it difficult to assess the bioavailability of Fe to phytoplankton in relation to total dissolved Fe concentrations in natural waters. We developed a cyanobacterial Fe‐responsive bioreporter constructed in Synechococcus sp. strain PCC 7942 by fusing the Fe‐responsive isiAB promoter to Vibrio harveyi luxAB reporter genes. A comprehensive physiological characterization of the bioreporter has been made in defined Fraquil medium at free ferric ion concentrations ranging from pFe 21.6 to pFe 19.5. Whereas growth and physiological parameters are largely constrained over this range of Fe bioavailability, the bioreporter elicits a luminescent signal that varies in response to Fe deficiency. A dose‐response characterization of bioreporter luminescence made over this range of Fe^{3 +} bioavailability demonstrates a sigmoidal response with a dynamic linear range extending between pFe 21.1 and pFe 20.6. The applicability of using this Fe bioreporter to assess Fe availability in the natural environment has been tested using water samples from Lake Huron (Laurentian Great Lakes). Parallel assessment of dissolved Fe and bioreporter response from these samples reinforces the idea that measures of dissolved Fe should not be considered alone when assessing Fe availability to phytoplankton communities.     

Effects of dietary factors on iron uptake from ferritin by Caco-2 cells

Biofortification of staple foods with iron (Fe) in the form of ferritin (Ft) is now possible, both by conventional plant breeding methods and transgenic approaches. Ft-Fe from plants and animals is absorbed well (25-30%) by human subjects, but little is known about dietary factors affecting its absorption. We used human intestinal Caco-2 cells and compared Fe absorption from animal Ft and FeSO4 to determine the effects of inhibitors and enhancers, such as phytic acid, ascorbic acid, tannic acid, calcium and heme. When postconfluent cells were coincubated with 59Fe-labeled (1 microM) FeSO4 and dietary factors, at different molar ratios of dietary factor to Fe (phytic acid:Fe, 10:1; ascorbic acid:Fe, 50:1; tannic acid:Fe, 50:1; calcium:Fe, 10:1 and hemin:Fe, 10:1), all inhibited uptake from FeSO4, except ascorbate, confirming earlier studies. In contrast, these dietary factors had little or no effect on Fe uptake from undigested Ft or Ft digested in vitro at pH 4, except tannins. However, results after in vitro digestion of Ft at pH 2 were similar to those obtained for FeSO4. These results suggest that Fe uptake occurs from both undigested as well as digested Ft but, possibly, via different mechanisms. The Fe-Ft stability shown here could minimize Fe-induced oxidation of Fe-supplemented food products.