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.     

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.     

Iron bioavailability in corn-masa tortillas is improved by the addition of disodium EDTA

Corn-masa flour flat bread tortillas are the main staple of Mexican and Central American populations. Due to high concentrations of inhibitors of iron absorption, the bioavailability from this matrix is unknown. We wanted to determine the most suitable fortificant that would efficaciously improve iron bioavailability. In tortillas prepared with commercial precooked, lime-treated, corn-masa flour, we examined the in vitro solubility of the following forms of iron: native iron with and without Na2EDTA, elemental reduced iron plus Na2EDTA, ferrous fumarate with and without Na2EDTA, bisglycine iron, ferrous sulfate and NaFeEDTA. We also examined the in vivo bioavailability in humans with double radioiron erythrocyte incorporation of ferrous fumarate with and without Na2EDTA, bisglycine iron, NaFeEDTA and native iron plus Na2EDTA, beans and rice. In vitro, solubility ranged from 1% in iron forms without Na2EDTA to 19.4% for NaFeEDTA. Forms of iron with Na2EDTA had intermediate values. In vivo radioiron studies showed that iron forms without Na2EDTA also had low bioavailability (< or =1%). NaFeEDTA had the highest bioavailability (5.3%). The bioavailability of all iron forms improved significantly when tested with Na2EDTA (<0.05). Adding Na2EDTA to ferrous fumarate increased bioavailability from 0.87% to 2.9% (P < 0.001). We conclude that NaFeEDTA is the form of iron best absorbed, but alternatively, ferrous fumarate plus Na2EDTA comprises a feasible option as a fortificant.     

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 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 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).     

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.     

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.     

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.     

Na2EDTA enhances the absorption of iron and zinc from fortified rice flour in Sri Lankan children

Rice flour was proposed as a vehicle for iron and zinc fortification in Sri Lanka. Although widely consumed, rice flour has not been evaluated as a fortified food, and the absorption of minerals including iron and zinc from this flour is unknown. Determination of the bioavailability of these nutrients is a critical step before commencing a fortification program. We randomly divided 53 Sri Lankan schoolchildren ages 6-10 y into 4 groups that consumed a local dish prepared with 25 g of fortified rice flour labeled with one of the following: 1) (58)FeSO(4) 2) (58)FeSO(4) + Na(2)EDTA 3) (58)FeSO(4) + (67)ZnO or, 4) (58)FeSO(4) + Na(2)EDTA + (67)ZnO. The levels of iron and zinc were 60 mg/kg; the rice flour also contained folate at 2 mg/kg in each group. Na(2)EDTA was added at a Fe:Na(2)EDTA, 1:1 molar ratio. A total of 48 children completed the trial. Absorption of (58)Fe from a meal was significantly greater (P < 0.01) in the groups administered FeSO(4) + Na(2)EDTA (4.7 +/- 3.6%) than in those administered FeSO(4) without Na(2)EDTA (2.2 +/- 1.3%). Fractional absorption of zinc was 13.5 +/- 6.0% in the FeSO(4) + Na(2)EDTA group and 8.8 +/- 2.0% in the FeSO(4) group (P = 0.037). Although zinc absorption was low, our results demonstrated a benefit in using Na(2)EDTA to improve both iron and zinc absorption. We conclude that the fortification of rice flour is feasible, although additional strategies such as dephytinization or an increase in the level of iron and zinc fortification should be considered to obtain a higher proportion of the daily requirement of total absorbed iron and zinc.     

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.     

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.     

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.     

Bioavailability of Petit-Suisse cheese as food vehicle for iron fortification estimated by the prophylactic method

Microencapsulated ferrous sulfate (SFE-171) and ferric orthophosphate in Petit-Suisse cheese were examined for iron bioavailability by the prophylactic method. The iron sources were industrially added to different samples of Petit-Suisse cheese, which were mixed with other food components in our laboratory before use. A reference standard diet inclusive of nonmicroencapsulated ferrous sulfate and a control diet low in iron content were prepared in the laboratory. The final iron content in the fortified diets was approximately 15 mg Fe/kg diet. These diets were administered to weaning rats for 23 days. The iron bioavailability was evaluated as the ratio of iron incorporated into hemoglobin to oral iron intake, thereby being estimated as 62.6 +/- 8.8% for ferrous sulfate and 59.2 +/- 10.6% for SFE-171, which were significantly effective at p < 0.01 compared to 43.4 +/- 10.5% for ferric orthophosphate. It thus turned out that SFE-171 was stable through industrial processing with Petit-Suisse cheese as the food vehicle and served as an iron fortifier equal to ferrous sulfate in bioavailability.     

Iron fortification of infant cereals: a proposal for the use of ferrous fumarate or ferrous succinate

Hemoglobin-repletion tests in rats, organoleptic studies, and iron-absorption studies in humans were used to search for Fe sources with high bioavailability that could be added to infant cereals as alternatives to the Fe compounds currently used for fortification. From rat and organoleptic studies on 11 alternative Fe sources, ferrous fumarate, ferrous succinate, and ferric saccharate were selected as the most suitable for infant-cereal fortification and, by use of radioactive labels, absorption of those compounds from fortified cereal was measured in adult human volunteers. There was no difference in absorption between ferrous fumarate and ferrous sulfate whereas the values for ferrous succinate, ferrous saccharate (10% Fe), and ferric pyrophosphate were 92%, 74%, and 39% of the ferrous sulfate values, respectively. We conclude that ferrous fumarate and ferrous succinate are highly available Fe sources in man that can be used to fortify infant cereals without causing fat oxidation or discoloration.     

Bioavailability of microencapsulated ferrous sulfate in powdered milk produced from fortified fluid milk: a prophylactic study in rats

OBJECTIVE: We investigated the iron bioavailability of microencapsulated ferrous sulfate (SFE-171) in a diet based on powdered milk by using the prophylactic method in rats. METHODS: The SFE-171 was added into fluid milk and industrially processed into powdered milk, which was then mixed in our laboratory with a normalized diet (17.2 +/- 2.1 mg Fe/kg). A reference standard diet using ferrous sulfate as iron-fortifying source (19.8 p+/- 2.9 mg Fe/kg) and a control diet without added iron (4.6 +/- 0.8 mg Fe/kg) were prepared in the laboratory in a similar way. These diets were administered to different groups of weaning rats for 28 d as the only solid nourishment. The iron bioavailability of the different sources was calculated as the relation between the mass of iron incorporated into hemoglobin during the treatment and the total iron intake per animal. RESULTS: The iron bioavailability values of SFE-171 and ferrous sulfate in the fortified diets were 41.6 +/- 6.6% and 42.6 +/- 4.2%, respectively; these results were significantly higher (P < 0.01) than the iron bioavailability of the control diet (28.8 +/- 8.1%). CONCLUSION: These results showed that iron-fortified powdered milk can be produced from fluid milk fortified with SFE-171. The bioavailability of SFE-171 in this rat model was not altered by the manufacturing process.     

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.     

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.     

Helicobacter pylori infection, iron absorption, and gastric acid secretion in Bangladeshi children

BACKGROUND: Nonheme-iron absorption requires an acidic milieu. Reduced gastric acid output as a consequence of Helicobacter pylori infection could be an important limiting factor for iron absorption. OBJECTIVE: We measured gastric acid output and iron absorption from a non-water-soluble iron compound (ferrous fumarate) and a water-soluble iron compound (ferrous sulfate) in children with and without H. pylori infection. DESIGN: Gastric acid output was quantified before (basal acid output, or BAO) and after pentagastrin stimulation (stimulated acid output, or SAO) in 2-5-y-old children with iron deficiency anemia who were (n = 13) or were not (n = 12) infected with H. pylori. Iron absorption was measured by using a double-stable-isotope technique. H. pylori-infected children were studied before and after eradication therapy. RESULTS: BAO and SAO were significantly lower in the H. pylori-infected children (0.2 +/- 0.2 and 1.6 +/- 0.9 mmol/h, respectively) than in the uninfected children (0.9 +/- 0.7 and 3.1 +/- 0.9 mmol/h, respectively; P = 0.01 and P < 0.005). BAO and SAO improved to 0.8 +/- 1.3 and 3.3 +/- 2.4 mmol/h, respectively, after therapy. Iron absorption from ferrous sulfate was significantly greater than that from ferrous fumarate both before (geometric : 19.7% compared with 5.3%; P < 0.0001) and after (22.5% compared with 6.4%; P < 0.0001) treatment in H. pylori-infected children. Corresponding values for uninfected children were 15.6% and 5.4%, respectively (P < 0.001; n = 12). CONCLUSIONS: Iron absorption from ferrous fumarate was significantly lower than that from ferrous sulfate in both H. pylori-infected and uninfected Bangladeshi children. Treatment of H. pylori infection improved gastric acid output but did not significantly influence iron absorption. The efficacy of ferrous fumarate in iron fortification programs to prevent iron deficiency in young children should be evaluated.