Enhancers of Iron Absorption: Ascorbic Acid and other Organic Acids

2004 ◽  
Vol 74 (6) ◽  
pp. 403-419 ◽  
Author(s):  
Teucher ◽  
Olivares ◽  
Cori

Ascorbic acid (AA), with its reducing and chelating properties, is the most efficient enhancer of non-heme iron absorption when its stability in the food vehicle is ensured. The number of studies investigating the effect of AA on ferrous sulfate absorption far outweighs that of other iron fortificants. The promotion of iron absorption in the presence of AA is more pronounced in meals containing inhibitors of iron absorption. Meals containing low to medium levels of inhibitors require the addition of AA at a molar ratio of 2:1 (e.g., 20 mg 3 mg iron). To promote absorption in the presence of high levels of inhibitors, AA needs to be added at a molar ratio in excess of 4:1, which may be impractical. The effectiveness of AA in promoting absorption from less soluble compounds, such as ferrous fumarate and elemental iron, requires further investigation. The instability of AA during food processing, storage, and cooking, and the possibility of unwanted sensory changes limits the number of suitable food vehicles for AA, whether used as vitamin fortificant or as an iron enhancer. Suitable vehicles include dry-blended foods, such as complementary, precooked cereal-based infant foods, powdered milk, and other dry beverage products made for reconstitution that are packaged, stored, and prepared in a way that maximizes retention of this vitamin. The consumption of natural sources of Vitamin C (fruits and vegetables) with iron-fortified dry blended foods is also recommended. Encapsulation can mitigate some of the AA losses during processing and storage, but these interventions will also add cost. In addition, the bioavailability of encapsulated iron in the presence/absence of AA will need careful assessment in human clinical trials. The long-term effect of high AA intake on iron status may be less than predicted from single meal studies. The hypothesis that an overall increase of dietary AA intake, or fortification of some foods commonly consumed with the main meal with AA alone, may be as effective as the fortification of the same food vehicle with AA and iron, merits further investigation. This must involve the consideration of practicalities of implementation. To date, programs based on iron and AA fortification of infant formulas and cow's milk provide the strongest evidence for the efficacy of AA fortification. Present results suggest that the effect of organic acids, as measured by in vitro and in vivo methods, is dependent on the source of iron, the type and concentration of organic acid, pH, processing methods, and the food matrix. The iron absorption-enhancing effect of AA is more potent than that of other organic acids due to its ability to reduce ferric to ferrous iron. Based on the limited data available, other organic acids may only be effective at ratios of acid to iron in excess of 100 molar. This would translate into the minimum presence/addition of 1 g citric acid to a meal containing 3 mg iron. Further characterization of the effectiveness of various organic acids in promoting iron absorption is required, in particular with respect to the optimal molar ratio of organic acid to iron, and associated feasibility for food application purposes. The suggested amount of any organic acid required to produce a nutritional benefit will result in unwanted organoleptic changes in most foods, thus limiting its application to a small number of food vehicles (e.g., condiments, beverages). However, fermented foods that already contain high levels of organic acid may be suitable iron fortification vehicles.

2001 ◽  
Vol 71 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Susan J. Fairweather-Tait ◽  
Gary M. Wortley ◽  
Birgit Teucher ◽  
Jack Dainty

Sodium iron ethylenediaminetetracetic acid (NaFeEDTA) has been recommended for food fortification programmes to improve iron status but its performance in commercial products has not been evaluated. The effect of EDTA on iron absorption from fortified cornflakes, given as part of a typical Western breakfast, was determined in a double-blind randomised study with 20 non-anaemic female volunteers, using experimentally prepared iron compounds, enriched with 58Fe, and faecal monitoring. Five meals were compared: hydrogen reduced iron, hydrogen reduced iron plus Na2EDTA (molar ratio EDTA:Fe 1:2), hydrogen reduced iron plus NaFe(III)EDTA at two different molar ratios (EDTA:total Fe 1:3 and 1:2), and hydrogen reduced iron plus 15 mg ascorbic acid (ascorbic acid:Fe 1.3:1). The iron and EDTA compounds were accurately weighed into gelatine capsules and taken with unfortified cornflakes, semi-skimmed milk and tea on two consecutive days; the iron dose per meal was 3.75 mg. Iron absorption from all five test meals was measured in each volunteer with a minimum wash-out period of 2 weeks between tests. Geometric mean iron absorption (%) from the 5 tests was 14.1, 17.6, 20.6, 24.4 and 17.5 respectively (equivalent to 0.5–0.9 mg absorbed iron). There was a significantly higher iron absorption from the mixture of reduced iron and NaFe(III)EDTA (EDTA:Fe 1:2) than from reduced iron alone (p = 0.014). It is not known whether the higher absorption was from reduced iron or NaFeEDTA or both. Absorption was not increased significantly with NaFe(III)EDTA (EDTA:Fe 1:3), Na2EDTA (EDTA:Fe 1:2) or ascorbic acid (15 mg).


1992 ◽  
Vol 55 (11) ◽  
pp. 893-898 ◽  
Author(s):  
TAKESHI SUZUKI ◽  
FERGUS M. CLYDESDALE ◽  
TIRA PANDOLF

The effect of six organic acids, ascorbic, citric, fumaric, lactic, malic, and succinic, alone and in combination, at a 1:1.9 molar ratio (Fe+2:ligand) on the solubility of iron was evaluated in the presence of lignin under simulated gastrointestinal pH conditions. The enhancing effect, evaluated under two systems of preparation at two pH values, was in the following order: citric>malic>ascorbic>lactic,fumaric>succinic. Citric acid solubilized 80 and 81% of iron under both pH conditions. When ascorbic acid was mixed with fumaric, lactic, and succinic acids, a higher percentage of soluble iron was retained than with these three acids alone. In the case of citric and malic acids, the addition of ascorbic acid reduced the soluble iron. The percentage of soluble iron obtained when prepared at the endogenous pH (2.5–3.1) was higher than that at pH 5.5. These results indicated that ascorbate bound less iron in a soluble form than citrate or malate but more than fumarate, lactate, or succinate. Also, combinations of citric with malic acid did not demonstrate a synergistic effect.


Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2187-2193 ◽  
Author(s):  
SR Lynch ◽  
BS Skikne ◽  
JD Cook

Abstract The relationship between iron status and food iron absorption was evaluated in 75 normal volunteers, 15 patients with idiopathic hemochromatosis, and 22 heterozygotes by using double extrinsic radioiron tags to label independently the nonheme and heme iron components of a hamburger meal. In normal subjects, absorption from each of these pools was inversely correlated with storage iron, as measured by the serum ferritin concentration. In patients with hemochromatosis, absorption of both forms of iron was far greater than would be predicted from the relationship between absorption and serum ferritin observed in normal volunteers. Nevertheless, there was still a modest but statistically significant reduction in absorption of nonheme iron with increasing serum ferritin. This relationship could not be demonstrated in the case of heme iron absorption. In heterozygotes, nonheme iron absorption from a hamburger meal containing no supplementary iron did not differ significantly from that observed in normal volunteers. However, when this meal was both modified to promote bioavailability and supplemented with iron, absorption of nonheme iron was significantly elevated. These studies confirm the presence of excessive nonheme iron absorption even from unfortified meals in patients with idiopathic hemochromatosis and suggest in addition that they are particularly susceptible to iron loading from diets containing a high proportion of heme iron. Impaired regulation of nonheme iron absorption was also observed in heterozygous individuals, but a statistically significant abnormality was demonstrable only when the test meal contained a large highly bioavailable iron supplement.


2002 ◽  
Vol 283 (5) ◽  
pp. G1125-G1131 ◽  
Author(s):  
Jennifer R. Follett ◽  
Yasushi A. Suzuki ◽  
Bo Lönnerdal

Heme-Fe is an important source of dietary iron in humans. Caco-2 cells have been used extensively to study human iron absorption with an emphasis on factors affecting nonheme iron absorption. Therefore, we examined several factors known to affect heme iron absorption. Cells grown in bicameral chambers were incubated with high specific activity [59Fe]heme alone or with 1% globin, BSA, or fatty acid-free BSA (BSA-FA) to examine the effect of protein source on absorption. Heme iron absorption was enhanced by globin and inhibited by BSA and BSA-FA. Absorption of heme iron in cells pretreated for 7 days with serum-free medium containing 1, 25, 50, or 100 μM Fe was higher in the 1-μM-Fe pretreatment group than in all other groups ( P < 0.05), showing an effect of iron status. Increased heme concentrations resulted in decreased percent absorbed but increased total heme iron absorption and increased transport rate across the basolateral membrane. Finally, cells treated with 10 μM CdCl2, which induces heme oxygenase, demonstrated higher absorption of [59Fe]heme than control cells ( P < 0.05). Our results from Caco-2 cells are in agreement with human studies and make this a promising model for examining intestinal heme iron absorption.


2010 ◽  
Vol 82 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Bo Lönnerdal

Iron is known to be absorbed from foods in two major forms, heme iron and non-heme iron. Iron status as well as dietary factors known to affect iron absorption has limited effect on heme iron absorption, whereas inhibitors and enhancers of iron absorption have pronounced effects on non-heme iron absorption. The enterocyte transporter for non-heme iron, DMT1, is strongly up-regulated during iron deficiency and down-regulated during iron overload. A transporter for heme iron, HCP1, was recently characterized and is present on the apical membrane of enterocytes. Two other pathways for iron absorption have been discovered and may serve to facilitate uptake of iron from two unique iron-binding proteins, lactoferrin and ferritin. Lactoferrin is an iron-binding protein in human milk and known to survive proteolytic digestion. It mediates iron uptake in breast-fed infants through endocytosis via a specific lactoferrin receptor (LfR). Recently, lactoferrin has become popular as a food additive and may enhance iron status in several age groups. Ferritin is present in meat, but also in plants. The ferritin content of plants can be enhanced by conventional breeding or genetic engineering, and thereby increase iron intake of populations consuming plant-based diets. Ferritin is a bioavailable source of iron, as shown in recent human studies. Ferritin can be taken up by intestinal cells via endocytosis, suggesting a receptor-mediated mechanism.


2004 ◽  
Vol 74 (6) ◽  
pp. 445-452 ◽  
Author(s):  
Hurrell

Phytic acid is a potent inhibitor of native and fortification iron absorption and low absorption of iron from cereal- and/or legume-based complementary foods is a major factor in the etiology of iron deficiency in infants. Dephytinization of complementary foods or soy-based infant formulas is technically possible but, as phytic acid is strongly inhibitory at low concentrations, complete enzymatic degradation is recommended. If this is not possible, the phytic acid to iron molar ratio should be decreased to below 1:1 and preferably below 0.4:1. Complete dephytinization of cereal- and legume-based complementary foods has been shown to increase the percentage of iron absorption by as much as 12-fold (0.99% to 11.54%) in a single-meal study when the foods were reconstituted with water. The addition of milk, however, inhibits iron absorption and overcomes the enhancing effect of phytic acid degradation. Dephytinization can therefore be strongly recommended only for cereal/legume mixtures reconstituted with water, especially low-cost complementary foods destined for infants in developing countries. In countries where infant cereals are consumed with milk, ascorbic acid addition can more easily be used to overcome the negative effect of phytic acid on iron absorption. Similarly with soy-based infant formulas, especially if manufactured from low-phytate isolates, ascorbic acid can be used to ensure adequate iron absorption.


2004 ◽  
Vol 74 (4) ◽  
pp. 294-300 ◽  
Author(s):  
Fidler ◽  
Davidsson ◽  
Zeder ◽  
Walczyk ◽  
Marti ◽  
...  

The effects of added ascorbic acid and particle size on iron absorption from ferric pyrophosphate were evaluated in adult women (9–10 women/study) based on erythrocyte incorporation of iron stable isotopes (57Fe or 58Fe) 14 days after administration. Three separate studies were made with test meals of iron-fortified infant cereal (5 mg iron/meal) and the results are presented as geometric means and relative bioavailability values (RBV, FeSO4 = 100%). The results of study 1 showed that iron absorption was significantly lower from ferric pyrophosphate (mean particle size 8.5 mum) than from FeSO4 in meals without ascorbic acid (0.9 vs. 2.6%, p < 0.0001, RBV 36%) and in the same meals with ascorbic acid added at a 4:1 molar ratio relative to fortification iron (2.3 vs. 9.7%, p < 0.0001, RBV 23%). Ascorbic acid increased iron absorption from ferric pyrophosphate slightly less (2.6-fold) than from FeSO4 (3.7-fold) (p < 0.05). In studies 2 and 3, RBV of ferric pyrophosphate with an average particle size of 6.7 mum and 12.5 mum was not significantly different at 52 and 42% (p > 0.05), respectively. In conclusion, the addition of ascorbic acid increased fractional iron absorption from ferric pyrophosphate significantly, but to a lesser extent than from FeSO4. Decreasing the mean particle size to 6.7 mum did not significantly increase iron absorption from ferric pyrophosphate.


2001 ◽  
Vol 7 (3) ◽  
pp. 191-198 ◽  
Author(s):  
M. Jovaní ◽  
R. Barberá ◽  
R. Farré

Infants’ high nutritional needs are fulfilled by mother’s milk or infant formulas to provide all the necessary nutrients, among them minerals. Minerals uptake depends not only on mineral content but also on their bioavailability which, in turn, is affected by the different components of the infant formulas. An understanding of these effects would help to improve mineral bioavailability. This work reviews the influence of endogenous (proteins and phytates) and added (ascorbic and citric acid) components in infant formulas on the bioavailability of nutritionally important mineral elements (calcium, zinc, iron and copper) and their interactions. Special attention is given to the influence of protein, which is positive for calcium and negative for iron absorption. The marked negative effect of phytates on iron and zinc absorption can be counteracted by a dephytinization process. Of the added compounds, ascorbic acid has a positive effect on iron absorption that depends on the molar ratio between ascorbic acid and iron. In fact, adding ascorbic acid can counteract the negative effect of phytic acid on iron absorption but does not alter the effect of phytic acid on zinc absorption. The null effect of an increase in citric acid content can be ascribed to the fact that the citrate contents of infant formulas are already high. One of the most important element interactions is the negative effect of calcium on zinc and iron intestinal absorption and also the interaction between zinc and iron. These interactions deserve our attention because these minerals are essential to infants’ growth and development.


2015 ◽  
Vol 9 (5) ◽  
pp. 41-44 ◽  
Author(s):  
Fereshteh Khosravi ◽  
Nahid Rastakhiz ◽  
Behzad Iranmanesh ◽  
Seyyed Sina Seyyed Jafari Olia

A reversed phase UPLC method for separation and quantification of organic acids (oxalic, citric, tartaric, malic and ascorbic and lactic acids) in fruit juices was developed. The chromatographic separation was performed with a Surveyor Thermo Electron system at 10°C by using a potassium dihydrogen orthophosphate buffer (pH3.1) as mobile phase, an Hypersil Gold a Q Analytical Column and diode array detection at λ=254 nm for ascorbic acid and λ=214 nm for the other organic acids. Organic acid profiles of seven species of fruits: sweet orange, white and red apple, lemon, lime, white and pink grape fruit were established. Species significantly affect the organic acid distribution of fruit juices. In all juices, the most abundant organic acid was citric acid, ranging from 5.22 to 62.42g/l. Fruit juices are good sources of ascorbic acid (0.137-0.625g/l). The average ascorbic acid was the highest in lemon juice followed by sweet orange juice, sweetie and white grapefruit.DOI: http://dx.doi.org/10.3126/ijls.v9i5.12690


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