An evaluation of EDTA compounds for iron fortification of cereal-based foods

Fe absorption was measured in adult human subjects consuming different cereal foods fortified with radiolabelled FeSO4, ferrous fumarate or NaFeEDTA, or with radiolabelled FeSO4 or ferric pyrophosphate in combination with different concentrations of Na2EDTA. Mean Fe absorption from wheat, wheat-soyabean and quinoa (Chenopodium quinoa) infant cereals fortified with FeSO4 or ferrous fumarate ranged from 0.6 to 2.2%. For each infant cereal, mean Fe absorption from ferrous fumarate was similar to that from FeSO4 (absorption ratio 0.91-1.28). Mean Fe absorption from FeSO4-fortified bread rolls was 1.0% when made from high-extraction wheat flour and 5.7% when made from low-extraction wheat flour. Fe absorption from infant cereals and bread rolls fortified with NaFeEDTA was 1.9-3.9 times greater than when the same product was fortified with FeSO4. Both high phytate content and consumption of tea decreased Fe absorption from the NaFeEDTA-fortified rolls. When Na2EDTA up to a 1:1 molar ratio (EDTA:Fe) was added to FeSO4-fortified wheat cereal and wheat-soyabean cereal mean Fe absorption from the wheat cereal increased from 1.0% to a maximum of 5.7% at a molar ratio of 0.67:1, and from the wheat-soyabean cereal from 0.7% to a maximum of 2.9% at a molar ratio of 1:1. Adding Na2EDTA to ferric pyrophosphate-fortified wheat cereal did not significantly increase absorption (P > 0.05). We conclude that Fe absorption is higher from cereal foods fortified with NaFeEDTA than when fortified with FeSO4 or ferrous fumarate, and that Na2EDTA can be added to cereal foods to enhance absorption of soluble Fe-fortification compounds such as FeSO4.     

Cofortification of iron-fortified flour with zinc sulfate,but not zinc oxide,decreases iron absorption in Indonesian children

BACKGROUND: Iron deficiency is a major nutritional concern in developing countries, and food fortification is a common strategy to treat it. In Indonesia wheat flour is fortified with 60 mg Fe/kg, but because of increasing concerns about marginal zinc status in at-risk populations, consideration is being given to cofortifying flour with zinc. However, little is known about the effect of zinc fortification of flour on iron bioavailability or about the optimum form of zinc supplementation. OBJECTIVE: We measured iron and zinc bioavailability from wheat-flour dumplings containing 25 g flour fortified with 60 mg Fe/kg, either alone or with 60 mg Zn/kg as zinc oxide or as zinc sulfate. DESIGN: Ninety children aged 4-8 y were recruited and assigned randomly to the 3 groups; 86 completed the study. Iron and zinc absorption were measured with established stable-isotope methods. RESULTS: Iron absorption from the flour fortified with iron only was good (15.9 +/- 6.8%), but when corrections were made for hemoglobin concentrations, it was significantly lower from the flour cofortified with zinc sulfate (11.5 +/- 4.9%; P < 0.05) but not from the flour cofortified with zinc oxide (14.0 +/- 8.9%). Zinc absorption was not significantly different between the zinc oxide and zinc sulfate cofortified flours (24.1 +/- 8.2% compared with 23.7 +/- 11.2%; P = 0.87). CONCLUSIONS: Iron and zinc appear to be highly bioavailable from foods made from fortified flour, but zinc sulfate cofortification may have a detrimental effect on iron absorption.     

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.     

Zinc absorption from zinc oxide, zinc sulfate, zinc oxide + EDTA, or sodium-zinc EDTA does not differ when added as fortificants to maize tortillas

The fortification of staple foods with zinc may play an important role in achieving adequate zinc intakes in countries at risk of zinc deficiency. However, little is known about the relative bioavailability of different zinc compounds that may be used in food fortification. The objective of this study was to measure and compare fractional zinc absorption from a test meal that included a maize tortilla fortified with zinc oxide, zinc sulfate, zinc oxide + EDTA, or sodium-zinc EDTA. A double isotopic tracer ratio method ((67)Zn as oral tracer and (70)Zn as intravenous tracer) was used to estimate zinc absorption in 42 Mexican women living in a periurban community of Puebla State, Mexico. The test meal consisted of maize tortillas, yellow beans, chili sauce, and milk with instant coffee; it contained 3.3 mg zinc and had a phytate:zinc molar ratio of 17. Fractional zinc absorption did not differ significantly between the test groups (ANOVA; P > 0.05). Percent absorptions were (mean +/- SD) zinc oxide, 10.8 +/- 0.9; zinc sulfate, 10.0 +/- 0.02; zinc oxide + EDTA, 12.7 +/- 1.5; and sodium-zinc EDTA, 11.1 +/- 0.7. We conclude that there was no difference in zinc absorption from ZnO and ZnSO(4) when added as fortificants to maize tortillas and consumed with beans and milk. The addition of EDTA with zinc oxide or the use of prechelated sodium-zinc EDTA as fortificants did not result in higher zinc absorption from the test meal.     

Effect of EDTA on the bioavailability to rats of fortification iron used in Egyptian balady bread

The effectiveness of EDTA compounds on iron fortificants for potential use in Egyptian balady bread was tested in sixty Sprague-Dawley weanling male rats by the haemoglobin regeneration efficiency (HRE) method. To confirm HRE-derived findings, eight groups of ten animals were repleted with a modified American Institute of Nutrition (1977; AIN) 76A diet, fortified with ferric phosphate, electrolytic Fe, carbonyl Fe or ferrous sulphate, with and without ascorbic acid. Results without ascorbic acid were comparable to findings of a human study by Forbes et al. (1989). Bioavailability of EDTA-enhanced fortificants, FeSO4 + Na2EDTA and NaFe(III)EDTA, was compared with that of FeSO4 in six groups of ten animals repleted with a ground Egyptian bread meal or a casein-based AIN diet fortified with one of the three compounds. Addition of either EDTA compound significantly increased bioavailability of Fe in Egyptian balady bread. When present in the less inhibitory casein meal, however, FeSO4 + Na2EDTA fortification was significantly less effective than NaFe(III)EDTA or the reference FeSO4. Results indicate that NaFe(III)EDTA may be the fortificant of choice in a mixed diet. Further study of EDTA-enhanced Fe fortificants is needed.     

Iron bioavailability from iron-fortified Guatemalan meals based on corn tortillas and black bean paste

BACKGROUND: Corn masa flour is widely consumed in Central America and is therefore a potentially useful vehicle for iron fortification. OBJECTIVE: The goal was to evaluate the bioavailability of iron from meals based on corn tortillas and black bean paste that were fortified with ferrous fumarate, ferrous sulfate, or NaFeEDTA and to investigate the potential of Na(2)EDTA to increase the bioavailability of iron from ferrous fumarate. DESIGN: With use of a crossover study design, iron bioavailability was measured in Guatemalan girls aged 12-13 y by a stable-isotope technique based on erythrocyte incorporation 14 d after intake. RESULTS: Geometric mean iron bioavailability from test meals fortified with ferrous fumarate was 5.5-6.2% and was not improved significantly by the addition of Na(2)EDTA at molar ratios of 1:1 relative to fortification iron or to the total iron content of the fortified corn masa flour. Geometric mean iron bioavailability from test meals fortified with ferrous sulfate was 5.5% and was significantly higher in test meals fortified with NaFeEDTA (9.0%; P = 0.009, paired t test). CONCLUSIONS: The bioavailability of iron from ferrous fumarate was not improved by the addition of Na(2)EDTA, contrary to what was previously shown for ferrous sulfate in other cereal-based meals. However, the bioavailability of iron from the test meal was significantly enhanced when NaFeEDTA replaced ferrous sulfate. These results support the use of NaFeEDTA in the fortification of inhibitory staple foods such as corn masa flour.     

Iron absorption from ferrous fumarate in adult women is influenced by ascorbic acid but not by Na2EDTA

Ascorbic acid and Na2EDTA enhance Fe absorption from the water-soluble Fe compound FeSO4 but their effect on poorly water-soluble Fe compounds such as ferrous fumarate is less well established. In the present study, the effects of ascorbic acid and Na2EDTA on Fe absorption from ferrous fumarate were evaluated in adult women (ten women/study) from the erythrocyte incorporation of Fe stable isotopes ((57)Fe or (58)Fe) 14 d after administration. Two separate studies were made with test meals of Fe-fortified infant cereal (5 mg Fe/meal). Data were evaluated by paired t tests and the results are presented as geometric means. In study 1a, the comparison between Fe absorption from ferrous fumarate- and FeSO4-fortified cereal showed that adult women absorb Fe as well from ferrous fumarate as from FeSO4 (3.0 and 3.1 % respectively, P=0.85). After addition of Na2EDTA (Na2EDTA:fortification Fe molar ratio of 1:1), Fe absorption from FeSO4 was significantly higher than from ferrous fumarate (5.3 v. 3.3 % respectively, P<0.01; study 1b). In study 2, Fe absorption was compared from ferrous fumarate-fortified meals with and without ascorbic acid added at a 4:1 molar ratio (relative to fortification Fe) and the results showed that ascorbic acid increased Fe absorption from ferrous fumarate significantly (6.3 v. 10.4 %, P=0.02). The results of the present studies show that Fe absorption from ferrous fumarate is enhanced by ascorbic acid but not by Na2EDTA, thus emphasising that not all findings from Fe absorption studies made with FeSO4 can be extrapolated to Fe compounds with different solubility properties.     

Iron absorption from fish sauce and soy sauce fortified with sodium iron EDTA

BACKGROUND: Fish sauce and soy sauce have been suggested as food vehicles for iron fortification in Asia. NaFeEDTA is a potentially useful fortificant because it can be added to these condiments without causing precipitation during storage. OBJECTIVES: The objectives were to evaluate iron absorption from NaFeEDTA-fortified fish sauce and soy sauce against a reference fortificant (FeSO(4)), to compare iron absorption from NaFeEDTA-fortified fish sauce and soy sauce, and to evaluate the influence of fish sauce and soy sauce per se on iron absorption. DESIGN: Five separate iron-absorption studies were made in adult women (10 women per study). Iron absorption was measured on the basis of erythrocyte incorporation of (57)Fe or (58)Fe 14 d after the intake of labeled meals of rice or rice and vegetables. Fish sauce or soy sauce (10 g) fortified with 5 mg Fe as NaFeEDTA or FeSO(4) was fed with selected meals. The results are presented as geometric means. RESULTS: Iron absorption from NaFeEDTA- and FeSO(4)-fortified fish sauce (3.3% and 3.1%, respectively) and soy sauce (6.1% and 5.6%, respectively) was not significantly different. No significant difference was observed when NaFeEDTA-fortified fish sauce and soy sauce were compared directly (6.7% and 7.9%, respectively). Soy sauce inhibited iron absorption from rice-based meals (8.5% without and 6.0% with soy sauce; P < 0.02), whereas fish sauce did not affect iron absorption significantly. CONCLUSION: The relatively high iron absorption from NaFeEDTA-fortified fish sauce and soy sauce and the acceptable organoleptic properties of NaFeEDTA indicate the potential usefulness of this iron fortificant in fish sauce and soy sauce fortification programs.     

The poor bioavailability of elemental iron in corn masa flour is not affected by disodium EDTA

The most sustainable way to eradicate iron deficiency is through food fortification. Elemental iron powders are commonly utilized as fortificants due to their low cost and few sensory problems. However, their bioavailability is unknown. Our goals were to measure the bioavailability of elemental iron in Mexican style corn masa flour tortillas and to evaluate the effects of Na(2)EDTA. We used a stable isotope of H(2)-reduced iron powder, with and without Na(2)EDTA in tortillas prepared with corn masa flour. Two groups of 5- to 7-y-old children (n = 12/group) were fed tortillas to which was added 3 mg/100 g of H(2)-reduced (58)Fe with a mean particle size of 15 micro m. In one group, Na(2)EDTA was incorporated at a ratio of 1:2 mol/mol. The next day, (57)Fe ascorbate was given as a reference dose. After 14 d, blood samples were analyzed for isotopic enrichment. When normalized to 40% absorption of the reference dose, the geometric mean (+/-range 1 SD) bioavailability of reduced iron in tortilla was 3.8% (2.7-5.3). The addition of Na(2)EDTA, tended to increase it (P = 0.18) to 5.1% (2.8-9.2). This observed low absorption was compounded by the use of iron isotopes with smaller particle size (mean diameter 15 micro m) than typical of commercial elemental iron powder (<45 micro m). We conclude that H(2)-reduced iron powder is an ineffective fortificant in corn tortillas.     

Improving iron absorption from a Peruvian school breakfast meal by adding ascorbic acid or Na2EDTA

BACKGROUND: Iron-fortified school breakfasts have been introduced in Peru to combat childhood iron deficiency. OBJECTIVE: We evaluated whether iron absorption from a school breakfast meal was improved by increasing the ascorbic acid content or by adding an alternative enhancer of iron absorption, Na2EDTA. DESIGN: In a crossover design, iron absorption from test meals was evaluated by erythrocyte incorporation of 58Fe and 57Fe. The test meals (wheat bread and a drink containing cereal, milk, and soy) contained 14 mg added Fe (as ferrous sulfate) including 2.0-2.6 mg 58Fe or 4.0-7.0 mg 57Fe. RESULTS: Geometric mean iron absorption increased significantly from 5.1% to 8.2% after the molar ratio of ascorbic acid to fortification iron was increased from 0.6:1 to 1.6:1 (P < 0.01; n = 9). Geometric mean iron absorption increased significantly from 2.9% to 3.8%, from 2.2% to 3.5%, and from 2.4% to 3.7% after addition of Na2EDTA at molar ratios relative to fortification iron of 0.3:1, 0.7:1, and 1:1, respectively, compared with test meals containing no added enhancers (P < 0.01; n = 10 for all). Iron absorption after addition of ascorbic acid (molar ratio 0.6:1) was not significantly different from that after addition of Na2EDTA (molar ratio 0.7:1). CONCLUSIONS: Ascorbic acid and Na2EDTA did not differ significantly in their enhancing effects on iron absorption at molar ratios of 0.6:1 to 0.7:1 relative to fortification iron. Additional ascorbic acid (molar ratio 1.6:1) increased iron absorption significantly. Increasing the molar ratio of Na2EDTA to fortification iron from 0.3:1 to 1:1 had no effect on iron absorption.     

Factors affecting the absorption of iron from Fe(III)EDTA

1. The modification of iron absorption from Fe(III)EDTA by agents known to promote or inhibit absorption was examined in 101 volunteer multiparous Indian women. Fe absorption from Fe(III)EDTA was compared with absorption of intrinsic food Fe in a further twenty-eight subjects. Finally the urinary excretion of radio-Fe after oral administration of 59Fe(III)EDTA was studied in twenty-four subjects and evidence of intraluminal exchange of Fe was examined. 2. Fe absorption from maize porridge fortified with Fe(III)EDTA was more than twice that from porridge fortified with FeSO4 . 7H2O. 3. Although bran decreased Fe absorption from FeSO4 . 7H2O approximately 11-fold, it had no significant effect on Fe absorption from Fe(III)EDTA. Nevertheless tea, which is a more potent inhibitor of Fe absorption, decreased absorption from Fe(III)EDTA 7-fold. 4. Fe absorption from Fe(III)EDTA given in water was only increased 40% by addition of 3 mol ascorbic acid/mol Fe but by 7-fold when the relative proportions were increased to 6:1. This enhancing effect was blunted when the Fe(III)EDTA was given with maize porridge. In these circumstances, an ascorbate:iron value of 3:1 (which doubles absorption from FeSO4 . 7H2O) produced no significant increase in Fe absorption, while a value of 6:1 produced only a 2 . 5-fold increase. 5. Fe absorption from Fe(III)EDTA was not altered by addition of maize porridge unless ascorbic acid was present. 6. Less than 1% of 59Fe administered as 59Fe(III)EDTA was excreted in the urine and there was no inverse relationship between Fe absorption and the amounts excreted (r 0 . 58, P less than 0 . 05). 7. Isotope exchange between 59Fe(III)EDTA and 59FeSO4 . 7H2O was demonstrated by finding a similar relative value for the two isotopes in urine and erythrocytes when the two labelled compounds were given together orally. This finding was confirmed by in vitro studies, which showed enhanced 59Fe solubilization from 59FeSO4 . 7H2O in maize porridge when unlabelled Fe(III)EDTA was added. 8. Although Fe absorption from Fe(III)EDTA was marginally higher it appeared to form a common pool with intrinsic food iron in most studies. It is postulated that the mechanism whereby Fe(III)EDTA forms a common pool with intrinsic food Fe differs from that occurring with simple Fe salts. When Fe is present in the chelated form it remains in solution and is relatively well absorbed because it is protected from inhibitory ligands. Simple Fe salts, however, are not similarly protected and are absorbed as poorly as the intrinsic food Fe. 9. It is concluded that Fe(III)EDTA may be a useful compound for food fortification of cereals because the Fe is well absorbed and utilized for haemoglobin synthesis. The substances in cereals which inhibit absorption of simple Fe salts do not appear to inhibit absorption of Fe from Fe(III)EDTA.     

Iron absorption from a breakfast cereal: effects of EDTA compounds and ascorbic acid

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).     

Zinc bioavailability from zinc-fortified foods

Zinc fortification is considered a potentially useful strategy for the control of zinc deficiency, but the success of such intervention programs depends on the population's access to and consumption of zinc-fortified foods and adequate absorption of zinc from these foods. The latter issue has been assessed by a variety of studies that applied zinc isotopic tracers to assess zinc uptake from zinc-fortified foods. These studies show that the additional zinc provided by zinc fortification decreases fractional absorption of zinc, but increases total zinc absorption from these foods. Available studies show no significant difference in zinc absorption from foods fortified with either zinc oxide or zinc sulfate, which are the two cheapest chemical forms of zinc that are generally recognized as safe for human consumption. It appears that high-phytate meals depress zinc absorption from zinc-fortified foods, although total zinc absorption from such foods is still likely to be greater than if the foods were not fortified with zinc. With the possible exception of Na2EDTA, putative enhancers of zinc absorption do not seem to confer major benefits for zinc absorption from zinc-fortified foods. There is little information on the effect of fortification with other micronutrients on zinc absorption from co-fortified foods, and zinc fortification does not seem to suppress iron absorption from iron-fortified foods in most studies.     

Fortification iron as ferrous sulfate plus ascorbic acid is more rapidly absorbed than as sodium iron EDTA but neither increases serum nontransferrin-bound iron in women

The absorption profile of iron fortificants may be a determinant of their ability to generate nontransferrin-bound iron (NTBI) and, thus, their potential safety. Ferrous iron may be absorbed more rapidly than chelated ferric iron, but differences at the fortification level cannot be distinguished with nonisotopically labeled serum iron curves. Using stable isotope appearance curves (SIAC) in serum, we measured iron absorption profiles from FeSO(4) with ascorbic acid (AA) and from NaFeEDTA, as well as the serum hepcidin and NTBI response following the meals. Healthy women (n = 16) were given 6 mg oral iron as labeled FeSO(4) and NaFeEDTA with a maize porridge using a crossover design. SIAC, NTBI, and serum hepcidin were measured over 8 h after the meal. Iron from FeSO(4) plus AA was more rapidly absorbed, resulting in a 35% greater relative AUC during the first 2 h than for NaFeEDTA (P < 0.001). Median (95% CI) fractional iron absorption from the FeSO(4)- and NaFeEDTA-fortified meals was 15.2% (11.0-19.5) and 6.0% (5.0-9.2), respectively (P < 0.001). In response to the FeSO(4)-fortified meal, there was an ~60% increase in median serum hepcidin (P < 0.05) but no significant change in NTBI. There was no significant change in serum hepcidin or NTBI after the NaFeEDTA-fortified meal. SIAC are a useful new tool to compare iron absorption profiles from different iron compounds in fortified foods. Even with the use of a very well absorbed ferrous iron compound, iron fortification in this population does not increase NTBI, suggesting a low risk for adverse health consequences.     

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.     

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.     

Absorption of zinc from wheat products fortified with iron and either zinc sulfate or zinc oxide

BACKGROUND: Several chemical forms of zinc have been proposed for food fortification, but information is needed on their absorption from common cereals having varied phytate content. OBJECTIVE: The goal was to measure zinc absorption from wheat products fortified with iron sulfate and either zinc sulfate or zinc oxide. DESIGN: Adult volunteers received either low-phytate bread (n = 11) or higher-phytate porridge (n = 11) once weekly on 2 or 3 occasions. The foods were fortified with 1 of the 2 zinc salts (60 mg elemental Zn/kg wheat flour) during week 1 and with the other during week 2, in random order. (65)Zn in the same chemical form as the fortificant was incorporated in each food to assess zinc absorption with the use of whole-body counting. The porridge group received an additional test meal fortified with zinc oxide during week 3, but the (65)Zn tracer was given as an oral solution of (65)ZnCl(2). RESULTS: Zinc absorption from bread (13.8%; 95% CI: 11.8%, 16.2%) was significantly (P < 0.001) greater than from porridge (6.4%; 5.5%, 7.6%), presumably because of the greater phytate content of the porridge. With control for food type, there were no significant differences in zinc absorption from meals fortified with zinc sulfate or zinc oxide (P = 0.24). When the porridge was fortified with zinc oxide and labeled with (65)ZnCl(2), absorption of the tracer (8.9%; 7.1%, 11.0%) was significantly (P = 0.007) greater than when (65)ZnO was incorporated in the porridge (5.6%; 4.5%, 6.9%). CONCLUSIONS: Either zinc oxide or zinc sulfate can be used to fortify wheat products consumed by presumably healthy persons. Isotopic tracers used to assess the absorption of mineral fortificants should have the same chemical form as the fortificant.     

Longitudinal measurements of zinc absorption in Peruvian children consuming wheat products fortified with iron only or iron and 1 of 2 amounts of zinc

BACKGROUND: Information is needed on the fractional absorption of zinc (FAZ) and absorbed zinc (AZ) during prolonged exposure to zinc-fortified foods. OBJECTIVE: The objective was to measure FAZ and AZ from diets fortified with different amounts of zinc and to determine whether zinc absorption changes over approximately 7 wk. DESIGN: Forty-one stunted, moderately anemic children received daily, at breakfast and lunch, 100 g wheat products fortified with 3 mg Fe (ferrous sulfate) and 0 (group Zn-0), 3 (group Zn-3), or 9 (group Zn-9) mg Zn (zinc sulfate) per 100 g flour. FAZ was measured on days 2-3 and 51-52; meal-specific AZs were calculated as the product of FAZ and zinc intake. RESULTS: For the breakfast and lunch meals combined, mean total zinc intakes were 2.14, 4.72, and 10.04 mg/d in groups Zn-0, Zn-3, and Zn-9, respectively, during the initial absorption studies; mean (+/-SD) FAZ values were 0.341 +/- 0.111, 0.237 +/- 0.052, and 0.133 +/- 0.041, respectively, on days 2-3 (P < 0.001) and did not change significantly on days 51-52 in the subset of 31 children studied twice. Mean initial AZ was positively related to zinc intake (0.71 +/- 0.18, 1.11 +/- 0.21, and 1.34 +/- 0.47 mg/d, respectively; P < 0.001); final values did not differ significantly from the initial values. CONCLUSIONS: AZ from meals containing zinc-fortified wheat products increases in young children relative to the level of fortification and changes only slightly during approximately 7-wk periods of consumption. Although consumption of zinc-fortified foods may reduce FAZ, zinc fortification at the levels studied positively affects total daily zinc absorption, even after nearly 2 mo of exposure to zinc-fortified diets.     

12～14岁男童体内强化去植酸豆粉中钙铁锌的吸收利用率研究

目的　为了解我国少年儿童对豆粉、去植酸豆粉和牛奶中钙、铁、锌的吸收利用率 ,通过普及饮用豆粉 ,改善我国居民蛋白质和矿物质的营养状况提供理论依据。方法　选择 57名 1 2～ 1 4岁男童 ,按年龄、身高、体重和血红蛋白含量匹配 ,分成 3组 ,分别给予强化豆粉、强化去植酸豆粉和强化牛奶 2 2 0ml,其中含钙 2 70mg、铁 4mg、锌 4mg。给予受试者用稳定性核素4 4Ca、58Fe和70 Zn标记的受试物 ,以亮蓝和镝标记粪便 ,收集粪便样品 ,测量强化去植酸豆粉、豆粉和强化牛奶中钙、铁、锌的吸收率 ;使用热离子化质谱法测定粪便中4 4Ca含量 ;应用感应耦合等离子质谱法测定粪便中58Fe和70 Zn的丰度及镝的含量 ,计算铁、锌的表观吸收率 ,并以镝的回收率进行校正。结果　豆粉组、牛奶组和去植酸豆粉组的铁吸收率分别为 (6 7± 3 8) %、(1 5 5± 9 2 ) %和 (2 0 6± 7 3) % ,钙吸收率分别为 (43 5±1 0 7) %、(64 2± 1 1 4) %和 (50 9± 6 6) % ,锌吸收率分别为 (1 1 3± 6 5) %、(31 2± 1 0 4) %和 (2 0 1±7 4) %。强化豆粉经去除植酸处理后 ,钙、铁、锌的吸收率显著高于未去植酸的豆粉 ;牛奶中钙和锌的吸收率高于去植酸强化豆粉 ;经去除植酸处理后的豆粉中铁吸收率高于牛奶 ,但差异无显著性。我国儿童由于     

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.