Fe(III)-EDTA complex as iron fortification.

Fe(III)-EDTA as iron fortification presents several advantages over the other iron salts previously used including ferrous sulfate. This iron compound exchange completely with vegetable food iron in the lumen of the gut but with the characteristics that the absorption from both, extrinsic and intrinsic food iron, is higher than that expected from other iron salfs. The comparison between the iron absorption from Fe(III)-EDTA and ferrous sulfate as iron fortification indicates that the absorption form EDTA is about twice as high than that observed from ferrous sulfate. The data indicates that only 10 to 15 mg of iron as Fe(III)-EDTA as iron fortification would be necessary to prevent iron deficiency anemia in population relying their subsistence of vegetable food only and free of parastic infection producing blood loss.     

Sugar as a vehicle for iron fortification: further studies.

The data presented confirm the advantages of sugar as a vehicle for iron fortification over other vehicles used in the past. The absorption comparison between ferric and ferrous salts added to sugar demonstrated that Fe(III)-EDTA Complex and ferrous sulfate exhibited the highest absorption, while ferric ammonium citrate was poorly absorbed. It was also found that Fe(III)-EDTA reacts slowly with the tannin contained in tea; the color of the tea changes slightly in the first 2 hr after the addition of the fortified sugar. Iron absorption of sugar fortified with ferrous sulfate was tested in seven beverages. The mean absorption ratio from fortified sugar given with beverages to reference dose of iron ascorbate ranged between 0.42 and 0.70, that is, more than 4 times the absorption from fortified sugar when it is administered with a meal containing one or more vegetals. An absorption of between 0.25 and 0.80 mg of iron/soft drink sugar fortified with 3 mg of iron as ferrous sulfate can be expected in subjects with various degrees of iron deficiency. Thus, two soft drinks per day between meals would be enough to meet the iron requirement in more than 95% of menstruating women, even though the daily iron absorption from the diet is about 0.8 to 1.0 mg.     

Ferrous sulfate is more bioavailable among preschoolers than other forms of iron in a milk-based weaning food distributed by PROGRESA, a national program in Mexico

After 1 y of distributing a milk-based fortified weaning food provided by the Mexican social program PROGRESA, positive effects on physical growth, prevalence of anemia, and several vitamin deficiencies were observed. There was no effect on iron status, which we hypothesized was related to the poor bioavailability of the reduced iron used as a fortificant in PROGRESA. The objective of this study was to compare the iron bioavailability from different iron sources added as fortificants to the weaning food. Children (n = 54) aged 2-4 y were randomly assigned to receive 44 g of the weaning food fortified with ferrous sulfate, ferrous fumarate, or reduced iron + Na(2)EDTA. Iron absorption was measured using an established double-tracer isotopic methodology. Iron absorption from ferrous sulfate (7.9 +/- 9.8%) was greater than from either ferrous fumarate (2.43 +/- 2.3%) or reduced iron + Na(2)EDTA (1.4 +/- 1.3%) (P < 0.01). The absorption of log-(58)Fe sulfate given with the iron source correlated with serum ferritin (s-ferritin) concentration (n = 13, r = 0.63, P = 0.01) and log-(57)Fe absorption (reference dose) (n = 14, r = -0.52, P = 0.02). Absorption from ferrous fumarate and reduced iron + Na2EDTA did not correlate with s-ferritin or absorption of (57)Fe. The recommended daily portion of the fortified complementary food provides an average of 0.256, 0.096, 0.046 mmol (1.44, 0.54, and 0.26 mg) of absorbed iron, if fortified with sulfate, fumarate and reduced iron + Na(2)EDTA, respectively. Ferrous sulfate was more bioavailable than either ferrous fumarate or reduced iron + Na(2)EDTA when added to the milk-based fortified food and more readily met the average daily iron requirements for children 2-3 y of age.     

Iron absorption by human subjects from different iron fortification compounds added to Thai fish sauce

OBJECTIVES: (a) To measure iron absorption by human subjects from citric acid stabilized fish sauce fortified with ferrous sulfate, ferric ammonium citrate or ferrous lactate and (b) to identify the effect of added citric acid (3 g/l) on iron absorption from ferrous sulfate fortified fish sauce. DESIGN: Iron absorption from the intrinsically labeled compounds was determined via erythrocyte incorporation of isotopic labels ((57)Fe and (58)Fe) using a randomized crossover design. In three separate absorption studies, 10 adult women each consumed a basic test meal of rice and vegetable soup seasoned with isotopically labeled, iron fortified fish sauce. RESULTS: Iron absorption was significantly lower from ferrous lactate and from ferric ammonium citrate fortified fish sauce than from ferrous sulfate fortified fish sauce. Fractional iron absorption (geometric mean; -1s.d., +1s.d.) was 8.7(3.6; 21.4)% for ferrous lactate compared to 13.0(5.4; 31.4)% from ferrous sulfate, P = 0.003 (study 1) and 6.0(2.5; 14.3)% from ferric ammonium citrate relative to 11.7(4.4; 30.7)% from ferrous sulfate, P < 0.001, in study 2. Citric acid added at a molar ratio of approximately 2.5 to iron had no effect on iron absorption from ferrous sulfate (study 3). Iron absorption in the presence of citric acid was 14.1(6.4; 30.8)% compared to 12.0(5.8; 24.7)% in its absence (P = 0.26). CONCLUSIONS: Iron absorption was 50-100% higher from ferrous sulphate fortified fish sauce than from fish sauce fortified with ferric ammonium citrate or ferrous lactate. In the presence of citric acid as a chelator, ferrous sulfate would appear to be a useful fortificant for fish sauce. SPONSORSHIP: International Atomic Energy Agency (IAEA), Vienna, Austria.     

高铁营养酵母中铁吸收率的实验研究

用放射性~(56)铁掺入高铁酵母,普通酵母与硫酸亚铁加~(59)铁以及单纯硫酸亚铁加~(59)铁灌胃大鼠,测定铁的吸收率。大鼠灌胃后,分笼饲养,连续收集三天粪便,经灰化定容后,测定放射性强度。实验结果表明,高铁酵母中铁的吸收率为38.7％,硫酸亚铁吸收率为38.3％,表明掺入酵母中的铁吸收率较高,与硫酸亚铁相似。高铁营养酵母富含铁、蛋白质和B族维生素,用于强化儿童食品,对于提高营养价值和预防儿童缺铁性贫血具有实际意义。     

Iron absorption from NaFeEDTA is downregulated in iron-loaded rats

NaFeEDTA is a promising fortificant for use in plant foods, because it is less susceptible to iron absorption inhibitors and has fewer undesirable impacts on sensory quality than ferrous sulfate. However, the hypothesis that iron absorption from NaFeEDTA is effectively downregulated in iron-overload conditions has not been thoroughly tested. Therefore, the objective of this study was to compare downregulation of iron absorption from ferrous sulfate and NaFeEDTA in intact iron-loaded rats. Male Sprague-Dawley rats were fed diets containing either ferrous sulfate (35 mg Fe per 1 kg diet) or elemental iron (30,000 mg Fe per 1 kg diet) for 29 d to achieve basal or iron-loaded status. While body weights and hemoglobin concentrations were the same for basal and iron-loaded rats, nonheme-iron concentrations in liver, spleen, and kidney were all significantly higher in iron-loaded rats, indicating elevated iron status. Percentage of iron absorption from (59)Fe-labeled ferrous sulfate and NaFeEDTA, determined from whole-body retention of (59)Fe activity, was 64.7 and 49.4% in basal rats but decreased to 12.8 and 10.2% in iron-loaded rats, respectively. The reductions in percentage of iron absorption from both iron sources in rats as a result of iron loading were comparable (about -80% for both iron sources). Our results suggest that iron absorption from NaFeEDTA and ferrous sulfate is downregulated to a similar extent in iron-loaded rats. Hence, NaFeEDTA is no more likely than ferrous sulfate to exacerbate iron overload in subjects with adequate body iron stores.     

Absorption of iron from unmodified maize and genetically altered, low-phytate maize fortified with ferrous sulfate or sodium iron EDTA

BACKGROUND: Reducing the phytate content in grains by genetic manipulation is a novel approach to increasing nonheme-iron absorption from mixed diets. Fractional iron absorption from a genetically modified strain of low-phytate maize (LPM) increased significantly, by 50%. OBJECTIVE: We assessed iron absorption from porridges prepared from the same LPM (lpa-1-1 mutant) and unmodified wild-type maize (WTM), both of which were fortified with either ferrous sulfate or sodium iron EDTA. DESIGN: Porridges providing 3.4 mg Fe were fortified with either ferrous sulfate or sodium iron EDTA to provide an additional 1 mg Fe/serving. In 14 nonanemic women, iron absorption was measured as the amount of radioiron incorporated into red blood cells (extrinsic tag method) 12 d after consumption of the study diets. RESULTS: No significant effect of phytate content on iron absorption was found when porridge was fortified with either sodium iron EDTA or ferrous sulfate. Fractional absorption of iron from WTM porridge fortified with sodium iron EDTA (5.73%) was 3.39 times greater than that from the same porridge fortified with ferrous sulfate (1.69%). Fractional absorption of iron from the sodium iron EDTA-fortified LPM porridge (5.40%) was 2.82 times greater than that from LPM porridge fortified with ferrous sulfate (1.91%) (P<0.0001 for both comparisons, repeated-measures analysis of variance). Thus, the previously identified benefit of LPM was no longer detectable when maize porridge was fortified with additional iron. CONCLUSION: Iron was absorbed more efficiently when the fortificant was sodium iron EDTA rather than ferrous sulfate, regardless of the type of maize.     

Iron status and food matrix strongly affect the relative bioavailability of ferric pyrophosphate in humans

BACKGROUND: Although ferric pyrophosphate is a promising compound for iron fortification of foods, few data are available on the effect of food matrices, processing, and ascorbic acid on its bioavailability. OBJECTIVE: We compared the relative bioavailability (RBV) of ferrous sulfate in an experimental form of micronized dispersible ferric pyrophosphate (MDFP) in a wheat-milk infant cereal given with and without ascorbic acid with the RBV of MDFP from a processed and unprocessed rice meal. DESIGN: A crossover design was used to measure iron absorption in young women (n = 26) from test meals fortified with isotopically labeled [57Fe]-MDFP and [58Fe]-ferrous sulfate, based on erythrocyte incorporation of stable isotope labels 14 d later. RESULTS: Geometric mean iron absorption from the wheat-based meal fortified with MDFP was 2.0% and that from the meal fortified with ferrous sulfate was 3.2% (RBV = 62). The addition of ascorbic acid at a molar ratio of 4:1 to iron increased iron absorption from MDFP to 5.8% and that from ferrous sulfate to 14.8% (RBV = 39). In the rice meals, mean iron absorption from MDFP added to the rice at the time of feeding was 1.7%, and that from ferrous sulfate was 11.6% (RBV = 15). The mean iron absorption from MDFP extruded into artificial rice grains was 3.0% and that from ferrous sulfate in unprocessed rice was 12.6% (RBV = 24). Sixteen of 26 subjects were iron deficient. Iron status was a highly significant predictor of the RBV of MDFP (P < 0.001). CONCLUSION: RBV of the experimental MDFP varied markedly with food matrix and iron status. Assigning a single RBV value to poorly soluble compounds may be of limited value in evaluating their suitability for food fortification.     

Ascorbyl palmitate enhances iron bioavailability in iron-fortified bread

BACKGROUND: One of the strategies to control iron deficiency anemia is the fortification of food with iron. A mechanism for improving the bioavailability of iron is to add an iron absorption promoter. OBJECTIVE: The objective was to determine the effect of ascorbyl palmitate (AP) on the bioavailability of iron in fortified bread made from refined wheat flour. DESIGN: The iron bioavailability of wheat flour fortified with either ferrous sulfate alone or ferrous sulfate plus AP was studied with the use of double radio iron (55Fe and 59Fe) erythrocyte incorporation in 14 women. RESULTS: Geometric mean (+/- range of 1 SD) iron absorption from the bread fortified with ferrous sulfate was 10.5% (4.1-27.0%). The addition of AP at molar ratios of AP to Fe of 2:1 and 4:1 significantly increased iron absorption [14.6% (5.9-36.1%) and 20.2% (10.6-38.6%), respectively; P < 0.001]. CONCLUSION: AP is a strong promoter of iron absorption from fortified bread because of its thermoresistant properties.     

Iron bioavailability in humans from breakfasts enriched with iron bis-glycine chelate, phytates and polyphenols

This study was conducted to determine the bioavailability of iron amino acid chelate (ferrochel) added to fortify breads prepared from either precooked corn flour or white wheat flour + cheese and margarine compared with the same basal breakfast enriched with either ferrous sulfate or iron-EDTA. The inhibitory effect of phytate and polyphenols on iron absorption from ferrochel was also tested. A total of 74 subjects were studied in five experiments. Iron absorption from ferrochel was about twice the absorption from ferrous sulfate (P: < 0.05). When ferrous sulfate and ferrochel were administered together or in different meals, absorption from ferrochel was about twice the absorption from ferrous sulfate (P: < 0.05). Polyphenols present in coffee and tea inhibited iron absorption in a dose-dependent manner. American-type coffee did not modify iron absorption significantly, whereas both espresso-type coffee and tea reduced iron absorption from ferrochel by 50% (P: < 0. 05). Ferrochel partially prevented the inhibitory effect of phytates. Because of its high solubility in aqueous solutions even at pH 6, its low interactions with food and high absorption, ferrochel is a suitable compound for food fortification.     

Effects of dietary corn on hematological response of anemic rats to ferrous sulfate

Anemic rats were fed diets containing adequate quantities of all required nutrients, except iron, which was supplied by ferrous sulfate and/or corn grain. Diets were supplemented with the inorganic salt and corn in such a pattern that regression of hematological response on increments of ferrous sulfate intake could be calculated for 0, 25%, 50% and 75% dietary corn. Corn was added to the diets at the expense of starch which served only as a source of energy. Slopes of the regression lines for response (hemoglobin iron gain or final hemoglobin concentration) to ferrous sulfate intake were not altered significantly by inclusion of up to 75% corn in the diets. Results indicate that corn does not contain an inhibitor of iron absorption. Poor iron absorption from diets or meals in which corn provides a significant portion of the total food supply is probably due to a nutritional inadequacy of the corn, possibly its amino acid imbalance.     

The potential of encapsulated iron compounds in food fortification: a review

Iron (Fe) encapsulation has the potential to help overcome several major challenges in Fe fortification of foods. It may decrease unwanted sensory changes in fortified products and reduce interactions of Fe with food components that lower Fe bioavailability. However, the effect of encapsulation per se on Fe bioavailability is a concern. Rat studies comparing encapsulated ferrous sulfate, ferric ammonium citrate, and ferrous fumarate to non-encapsulated compounds indicate that a ratio of capsule:substrate of > or = 60:40 may decrease the relative bioavailability (RBV) of the Fe by approximately 20%. At a ratio of capsule:substrate of < or = 50:50, the RBV of encapsulated ferrous sulfate appears to be similar to ferrous sulfate. Even minor changes in capsule composition may influence Fe bioavailability. Encapsulated ferrous fumarate given with ascorbic acid as a complementary food supplement and encapsulated ferrous sulfate fortified into salt have been shown to be efficacious in anemic children. For salt fortification, further refinements in Fe capsule design are needed to increase resistance to moisture and abrasion, while maintaining bioavailability. Studies evaluating the potential efficacy of encapsulated Fe in staple cereals (wheat and maize flours) are needed. A potential barrier to use of encapsulated forms of Fe in staple food fortification is the relatively low melting point of the capsules, which may cause unwanted sensory changes during food preparation. Research and development efforts to improve the quality of coatings and their resistance to high temperatures are ongoing. Process costs for encapsulation can be high, and unless they can be reduced, may limit applications. Further research is needed to determine which encapsulation technologies are most effective in ensuring iron bioavailability from encapsulated compounds.     

Sodium iron NaFeEDTA as an iron fortification compound in Central America. Absorption studies.

Studies were performed in seven children and 98 adults to compare the proportion of iron absorbed when administered as ferric sulfate (Fe2(SO4)3), NaFeEDTA, hemoglobin (Hb), and ferrous ascorbate. Studies in children (mostly iron deficient) showed that when the compounds were given with a milk-rice-sugar formula totalling 5 mg Fe, iron from hemoglobin was absorbed best, followed by NaFeEDTA and by Fe2(SO4)3 (mean percent absorption +/-SD = 34.5 +/- 1.5, 8.6 +/- 1.9 and 3.3 +/- 1.5, respectively). Studies in normal or iron deficient adults also demonstrated a better absorption of iron from NaFeEDTA than from Fe2(SO4)3 whether these compounds were given in an aqueous solution (5 mg Fe) or with a standard meal consisting of beans, tortillas, bread, and coffee providing also a total of 5 mg Fe. Hb iron under the same conditions was absorbed in the same proportion to the reference iron ascorbate, always being higher than iron absorbed from the other compounds. Fe2(SO4)3 and NaFeEDTA mixed in the same meal were absorbed in the same proportion as when NaFeEDTA alone was added to the meal and 2 to 3 times better than when Fe2(SO4)3 alone was added to the meal. Addition of desferrioxamine depressed iron absorption from Fe2(SO4)3 and NaFeEDTA, the latter being less affected. Addition of ascorbic acid increased absorption from both. When the compounds were added to the meal to provide 50 mg of iron, percent absorption was depressed in relation to the smaller iron dose in the case of Fe2(SO4)3 and Hb but remained unaltered in the case of NaFeEDTA. Addition of 45 mg Fe as Fe2(SO4)3 or NaFeEDTA to 0.4 mg Fe from the Hb in the meal did not change Hb iron absorption. Addition of 45 mg Fe as Hb or NaFeEDTA to 0.4 mg Fe from Fe2(SO4)3 in the meal enhanced iron absorption from the latter in the same proportions. Addition of 45 mg Fe as Fe2(SO4)3 and Hb to 0.4 mg Fe as NaFeEDTA in the meal respectively depressed and enhanced iron absorption from NaFeEDTA. These studies indicate that NaFeEDTA, Fe2(SO4)3 and nonheme food iron from a common pool different from the heme pool but which is changed in its characteristics by the presence of NaFeEDTA, resulting in a better absorption of iron.     

Iron absorption from ferrous bisglycinate and ferric trisglycinate in whole maize is regulated by iron status

BACKGROUND: There is a need to determine whether iron absorption from iron amino acid chelates is protected from inhibition by dietary phytate and regulated normally by iron status. OBJECTIVE: The objective of this study was to compare iron absorption from ferrous sulfate, ferrous bisglycinate, and ferric trisglycinate in whole-maize meal; to determine whether iron from ferrous bisglycinate and ferrous sulfate exchanges in the intestinal pool; and to assess iron absorption from ferrous bisglycinate and ferric trisglycinate over a range of iron statuses. DESIGN: In study 1A, 10 iron-sufficient men consumed ferrous sulfate-fortified whole-maize meal porridge equilibrated with (59)Fe-sulfate on day 1 and (55)Fe-bisglycinate on day 2. In study 1B, these volunteers consumed ferrous sulfate-fortified porridge equilibrated with (59)Fe-sulfate and (55)Fe-bisglycinate simultaneously. In studies 2A and 2B, iron absorption from 3 mg Fe as (59)Fe-ascorbate, (55)Fe-bisglycinate, or (59)Fe-trisglycinate in water and in porridge was compared in 23 subjects with a range of iron statuses. Iron absorption was determined from blood radioactivity on day 16. RESULTS: In study 1A, geometric mean iron absorption from ferrous bisglycinate was 6.0% (range: 2.6-13.6%), 4 times higher than that from ferrous sulfate (1. 7%; range: 1.0-3.3%; P < 0.05). In study 1B, absorption from neither source was different from that in study 1A. In studies 2A and 2B, absorption from all sources was strongly inversely related to serum ferritin, with geometric means of 32.5% (iron ascorbate), 9.1% (bisglycinate), and 15.3% (trisglycinate). Iron from ferric trisglycinate was poorly absorbed (2.3%; range: 0.5-9.2%) from maize. CONCLUSION: In whole-maize meal, iron from ferrous bisglycinate is better absorbed than is iron from ferrous sulfate and does not exchange with iron from maize or ferrous sulfate in the intestinal pool. Absorption of iron from bisglycinate and trisglycinate is regulated normally by iron status.     

IRON ABSORPTION. IV. THE ABSORPTION OF HEMOGLOBIN IRON

The absorption of radioiron in rabbit hemoglobin, hemin, and ferritin has been compared to that of ferrous salt in healthy volunteers and in subjects with iron-deficiency anemia. At a dosage level of 5 mg elemental iron, hemoglobin iron was as well or better absorbed than ferrous salts in the normal subject. Absorption of hemoglobin iron increased less, however, in the iron-depleted or iron-deficient subject. In contrast to the absorption of ferrous salts, that of hemoglobin iron was not decreased by food or by phytate nor increased by ascorbic acid. The absorption of hemin iron was also not decreased by food. Iron absorbed from hemoglobin appeared in the plasma later than that from ferrous salts, but was found to be similarly dialyzable at acid pH with EDTA. These findings suggest that iron in heme complexes is absorbed as a porphyrin complex without conversion to the free ionized form. It is further apparent that there is less effective mucosal regulation of absorption of iron in this form. Finally, the present hypothesis of iron absorption based on the behavior of iron salts is not adequate for all types of food iron.     

Particle size reduction and encapsulation affect the bioavailability of ferric pyrophosphate in rats

Particle size is an important determinant of Fe absorption from poorly soluble Fe compounds in foods. Decreasing the particle size of elemental iron powders increases their absorption. The effect of a reduction in particle size on the bioavailability of ferric pyrophosphate (FePP) is unclear. Encapsulation of iron compounds for food fortification may protect against adverse sensory changes, but at the same time may reduce bioavailability. The hemoglobin (Hb) repletion method in weanling Sprague-Dawley rats (n = 100) was used to compare the relative bioavailability (RBV) of 4 forms of FePP: 1) regular FePP [mean particle size (MPS) approximately 21 microm]; 2) MPS approximately 2.5 microm; 3) MPS approximately 2.5 microm encapsulated in hydrogenated palm oil; and 4) MPS approximately 0.5 microm with emulsifiers. The RBV compared with ferrous sulfate was calculated by the slope-ratio technique. The RBV was 43% for encapsulated MPS approximately 2.5 microm, significantly lower than the other FePP compounds (P < 0.05), 59% for the regular FePP, and 69% for MPS approximately 2.5 microm, not different from each other but significantly lower than ferrous sulfate (P < 0.05), and 95% for emulsified MPS approximately 0.5 microm, comparable to ferrous sulfate. Encapsulation of FePP with hydrogenated palm oil at a capsule:substrate ratio of 60:40 decreased RBV. Particle size reduction increases the RBV of FePP and may make this compound more useful for food fortification.     

Utilization of iron from an animal-based iron source is greater than that of ferrous sulfate in pregnant and nonpregnant women

Heme iron absorption during pregnancy and the role of hepcidin in regulating dietary heme iron absorption remains largely unexplored. The objective of this research was to examine relative differences in heme (animal based) and nonheme (ferrous sulfate) iron utilization. This study was undertaken in 18 pregnant (ages 16-32 y; wk 32-35 of gestation) and 11 nonpregnant women (ages 18-27 y). Women were randomly assigned to receive both an animal-based heme meal (intrinsically labeled (58)Fe pork) and labeled ferrous sulfate ((57)Fe) fed on alternate days. Blood samples obtained 2 wk postdosing were used to assess iron status indicators and serum hepcidin and iron utilization based on RBC incorporation of iron isotopes. Heme iron utilization was significantly greater than nonheme iron utilization in the pregnant (47.7 ± 14.4 vs. 40.4 ± 13.2%) and nonpregnant women (50.1 ± 14.8 vs. 15.3 ± 9.7%). Among pregnant women, utilization of nonheme iron was associated with iron status, as assessed by the serum transferrin receptor concentration (P = 0.003; r(2) = 0.43). In contrast, heme iron utilization was not influenced by maternal iron status. In the group as a whole, women with undetectable serum hepcidin had greater nonheme iron utilization compared with women with detectable serum hepcidin (P = 0.02; n = 29); however, there were no significant differences in heme iron utilization. Our study suggests that iron utilization from an animal-based food provides a highly bioavailable source of dietary iron for pregnant and nonpregnant women that is not as sensitive to hepcidin concentrations or iron stores compared with ferrous sulfate.     

A micronised, dispersible ferric pyrophosphate with high relative bioavailability in man

Ferric pyrophosphate is a water-insoluble Fe compound used to fortify infant cereals and chocolate-drink powders as it causes no organoleptic changes to the food vehicle. However, it is only of low absorption in man. Recently, an innovative ferric pyrophosphate has been developed (Sunactive Fe trade mark ) based on small-particle-size ferric pyrophosphate (average size 0.3 microm) mixed with emulsifiers, so that it remains in suspension in liquid products. The aim of the present studies was to compare Fe absorption of micronised, dispersible ferric pyrophosphate (Sunactive Fe trade mark ) with that of ferrous sulfate in an infant cereal and a yoghurt drink. Two separate Fe absorption studies were made in adult women (ten women/study). Fe absorption was based on the erythrocyte incorporation of stable isotopes ((57)Fe and (58)Fe) 14 d after the intake of labelled test meals of infant cereal (study 1) or yoghurt drink (study 2). Each test meal was fortified with 5 mg Fe as ferrous sulfate or micronised, dispersible ferric pyrophosphate. Results are presented as geometric means. There was no statistically significant difference between Fe absorption from micronised, dispersible ferric pyrophosphate- and ferrous sulfate-fortified infant cereal (3.4 and 4.1 % respectively; P=0.24) and yoghurt drink (3.9 and 4.2 % respectively; P=0.72). The results of the present studies show that micronised, dispersible ferric pyrophosphate is as well absorbed as ferrous sulfate in adults. The high relative Fe bioavailability of micronised, dispersible ferric pyrophosphate indicates the potential usefulness of this compound for food fortification.     

Enhancers of iron absorption: ascorbic acid and other organic acids

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 AA: 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.     

The potential role of NaFeEDTA as an iron fortificant

Ethylene diamine tetraacetic acid (EDTA) is a hexadentate chelator, which can combine with virtually every metal in the periodic table. CaNa2EDTA and Na2EDTA (ADI 2.5 mg EDTA/kg body weight/day) are widely used as sequestering agents in canned products, while NaFeEDTA is a promising iron fortificant. Binding of EDTA with iron is favored in the acid milieu of the stomach, irrespective of whether the EDTA is administered as CaNa2EDTA, Na2EDTA, or NaFeEDTA, but in the more alkaline medium of the duodenum the iron is exchanged, in part, with other metals. The iron released from EDTA is absorbed by the normal physiological mechanisms. When NaFeEDTA is present in a meal, the iron moiety exchanges with the intrinsic food iron and the EDTA partially protects the iron in this common non-heme iron pool from the effects of inhibitors of iron absorption, such as phytates and polyphenols. When iron is added as NaFeEDTA to an inhibitory meal, it is two to three times better absorbed than is iron added as ferrous sulfate. It also has a similar effect on the intrinsic food iron in the meal. Fortification with NaFeEDTA is most efficacious when administered with cereal- and legume-based diets but offers no advantages over other fortificants when added to meals of high bioavailability. Its potential as a fortificant has been confirmed in five extended fortification trials carried out in developing countries. There is no evidence that NaFeEDTA in the dose range proposed for food fortificants (5 to 10 mg iron daily) will have any direct toxic effects. Na2EDTA and CaNa2EDTA have proved safe over a number of years, while the Joint FAO/WHO Expert Committee on Food Additives concluded in 1999 that NaFeEDTA "could be considered safe when used in supervised fortification programs". Animal and human studies, including the results of two fortification trials, suggest that NaFeEDTA has little or no effect on overall zinc metabolism. Indeed, if anything, it increases zinc and possibly copper absorption. Data on potentially toxic metals, such as lead mercury, aluminum, and manganese, are limited but the evidence that is available is uniformly negative thus far. Further studies in this field are desirable. The long-term potential of NaFeEDTA fortification to cause iron overload is conjectural but the available evidence suggests that homeostatic controls would prevent excess iron accumulation in the normal population. NaFeEDTA, which is pale yellow in color, causes fewer organoleptic changes in a number of stored vehicles, including cereals, than do other soluble iron salts. Other potential vehicles include condiments, several of which have been successfully used in fortification trials. What is currently lacking is a consolidated body of published evidence on the stability of NaFeEDTA during processing, storage, and household cooking in widely consumed food vehicles, coupled with standardized testing of consumer acceptance of each fortified vehicle. While NaFeEDTA seems to be an appropriate fortificant for developing countries, its cost is about six to eight times that of ferrous sulfate in terms of equivalent amounts of iron. Its better absorption (a factor of 2-3) might make it possible to halve the daily fortification level but, it still remains expensive and there is a pressing need for food grade NaFeEDTA at more affordable prices. Another possible option is the use of other salts of EDTA (Na2EDTA or Ca Na2EDTA) together with a soluble source of iron, such as ferrous sulfate. The combination has been shown to be as effective as NaFeEDTA when the EDTA:Fe molar ratio is between 1:2 and 1:1. This approach is, however, only feasible with vehicles that are stored for short periods because of ferrous sulfate's propensity to cause organoleptic changes. The search for an iron source that is more stable but at the same time available to combine with EDTA has been unsuccessful thus far. Target populations for fortification with NaFeEDTA include all those that subsist on cereal- and legume-based diets, with the most appropriate vehicles being cereal products and condiments. The fortification of infant milk and cereal formulas with NaFeEDTA does not seem appropriate, since the amounts of NaFeEDTA required for effective fortification would be close to the acceptable daily intake (ADI) of 2.5 mg EDTA/kg body weight/day.