RESUMEN
Elemental iron powders are widely used to fortify staple foods. Experimental evidence indicates that there is considerable variation in the bioavailability of different products. For some powders, it may be too low to permit a significant impact on iron status. This study was designed to evaluate possible approaches to screening commercial iron powders for predicted bioavailability, to identify products that have the potential to improve iron status, and to ascertain whether bioavailability is related to the method of manufacture. Nine commercial iron powders were allocated to one of five types based on the production process; carbonyl, electrolytic, hydrogen-reduced (H-reduced), carbon monoxide-reduced (CO-reduced), and other reduced. Structure by scanning electron microscopy and physical properties (pycnometric and apparent density, particle size distribution, Fisher subsieve size, and surface area) were determined on all samples. Selected samples (one or more of each type depending on the cost of the assay) were then subjected to five screening procedures that have previously been advocated for predicting bioavailability in humans--issolution rate in 0.1 mol/L HCl, dialyzability and Caco-2 cell iron uptake, both after simulated in vitro gastrointestinal digestion, relative bioavailability (RBV) with respect to ferrous sulfate by the AOAC rat hemoglobin repletion method, and plasma iron tolerance tests in human volunteers. The results for particle size distribution, surface area, Fisher subsieve size, dissolution rate in 0.1 mol/L HCl, and RBV in rats were significantly correlated and consistent for powders of the same type. However, values for different powder types were significantly different. There was no correlation between either dialyzability or Caco-2 cell uptake and the predicted bioavailability estimates based on the physical properties, dissolution rates, RBV in rats, or human efficacy data. Although human plasma iron tolerance tests were in general agreement with the other measures of predicted bioavailability, they did not provide information that would have improved the precision of bioavailability estimates based on physical properties, dissolution in HCl and/or RBV in rats. Our observations indicate that the dissolution rate in 0.1 mol/L HCI under standardized conditions is highly predictive of potential bioavailability and that it would be the most practical approach to developing a reliable and sensitive screening procedure for predicting and monitoring the bioavailability of commercial elemental iron powder products. Some, but not all, of the carbonyl and electrolytic iron powders had the highest predicted bioavailability values. The predicted bioavailability for the reduced iron products was lower and variable, with the lowest values being recorded for the carbon monoxide and other reduced iron products. Two powder types were selected for a human efficacy trial, electrolytic (because it is the iron powder type recommended by WHO) and hydrogen-reduced (because of its widespread use). Electrolytic/A131 and H-reduced/AC-325 had relative efficacies compared with ferrous sulfate monohydrate of 77% and 49%, respectively, based on the change in body iron stores in Thai women with low iron stores, who received an additional 12 mg iron per day, six days per week for 35 weeks in wheat-based snacks. We conclude that there is significant variability in the bioavailability of the commercial iron powders that we evaluated (those used for food fortification at the time that our studies were initiated), and that bioavailability is related in part to production method. The bioavailability of some carbonyl and electrolytic iron powders may be adequate for effective food fortification. The reduced iron powders that we tested are unlikely to have an adequate impact on iron nutrition at the fortification levels currently employed, although preliminary analysis of a new H-reduced product indicates that it may be possible to improve the bioavailability of individual powders of this type of product. We did find significant differences among products in both the electrolytic and carbonyl categories. Therefore, all products should be screened rigorously.
Asunto(s)
Alimentos Fortificados , Absorción Intestinal , Hierro de la Dieta/farmacocinética , Adolescente , Adulto , Animales , Disponibilidad Biológica , Células CACO-2/metabolismo , Fenómenos Químicos , Química Física , Femenino , Ferritinas/sangre , Humanos , Hierro de la Dieta/sangre , Masculino , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Tamaño de la Partícula , Polvos , Valor Predictivo de las Pruebas , Ratas , Ratas Sprague-Dawley , Receptores de Transferrina/sangre , Solubilidad , Propiedades de Superficie , Factores de TiempoRESUMEN
Iron deficiency remains a major global health problem affecting an estimated 2 billion people. The World Health Organization ranked it as the seventh most important preventable risk for disease, disability, and death in 2002. Since an important factor in its causation is the poor bioavailability of iron in the cereal-based diets of many developing countries, SUSTAIN set up a Task Force, consisting of nutritional, medical, industry, and government experts to consider strategies for enhancing the absorption of fortification iron. This paper summarizes the findings of this Task Force. Detailed reviews of each strategy follow this overview. Highly soluble compounds of iron like ferrous sulfate are desirable food fortificants but cannot be used in many food vehicles because of sensory issues. Thus, potentially less well-absorbed forms of iron commonly are used in food fortification. The bioavailability of iron fortificants can, however, be enhanced with innovative ingredient technologies. Ascorbic acid, NaFeEDTA, ferrous bisglycinate, and dephytinization all enhance the absorption of fortification iron, but add to the overall costs of fortification. While all strategies cannot be recommended for all food fortification vehicles, individual strategies can be recommended for specific foods. For example, the addition of ascorbic acid is appropriate for dry blended foods such as infant foods and other dry products made for reconstitution that are packaged, stored, and prepared in a way that maximizes retention of this vitamin. NaFeEDTA can be recommended for fortification of fish sauce and soy sauce, whereas amino acid chelates may be more useful in milk products and beverages. With further development, dephytinization may be possible for low-cost, cereal-based complementary foods in developing countries. Encapsulation of iron salts in lipid coatings, while not an iron absorption-enhancing strategy per se, can prevent soluble forms of iron from interacting undesirably with some food vehicles and hence broaden the application of some fortificants. Research relevant to each of these strategies for enhancing the bioavailability or utility of iron food fortificants is reviewed. Individual strategies are evaluated in terms of enhancing effect and stability, organoleptic qualities, cost, and regulatory issues of interest to the nutrition community, industry, and consumers. Recommendations are made on potential usages and further research needs. Effective fortification depends on the selection of technically feasible and efficacious strategies. Once suitable strategies have been identified, cost becomes very important in selecting the best approach to implement. However it is essential to calculate cost in relation to the amount of bioavailable iron delivered. An approach to the calculation of cost using a conservative estimate of the enhancing effects of the innovative technologies discussed in the supplement is given in the final section.
Asunto(s)
Alimentos Fortificados , Hierro/farmacocinética , Absorción , Aminoácidos , Ácido Ascórbico/administración & dosificación , Disponibilidad Biológica , Conferencias de Consenso como Asunto , Dieta , Interacciones Farmacológicas , Ácido Edético , Compuestos Ferrosos/administración & dosificación , Humanos , Quelantes del Hierro , Deficiencias de Hierro , Ácido Fítico/administración & dosificación , Ácido Fítico/efectos adversos , Ácido Fítico/metabolismoRESUMEN
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.
Asunto(s)
Ácido Edético/administración & dosificación , Compuestos Férricos/administración & dosificación , Alimentos Fortificados , Hierro/farmacocinética , Absorción , Disponibilidad Biológica , Ensayos Clínicos como Asunto , Costos y Análisis de Costo , Interacciones Farmacológicas , Ácido Edético/efectos adversos , Ácido Edético/química , Ácido Edético/economía , Grano Comestible , Fabaceae , Compuestos Férricos/efectos adversos , Compuestos Férricos/economía , Humanos , Hierro/administración & dosificación , Hierro/química , Deficiencias de Hierro , Sobrecarga de HierroAsunto(s)
Costos y Análisis de Costo , Alimentos Fortificados/economía , Hierro/farmacocinética , Absorción , Ácido Ascórbico/administración & dosificación , Disponibilidad Biológica , Cápsulas , Ácido Edético/administración & dosificación , Compuestos Férricos/administración & dosificación , Compuestos Ferrosos/administración & dosificación , Glicina , Humanos , Deficiencias de Hierro , Ácido Fítico/análisisRESUMEN
Fortification of cereal flours may be a useful public health strategy to combat iron deficiency. Cereal flours that are used shortly after production (e.g., baking flour) can be fortified with soluble iron compounds, such as ferrous sulfate, whereas the majority of flours stored for longer periods is usually fortified with elemental iron powders to avoid unacceptable sensory changes. Elemental iron powders are less well absorbed than soluble iron compounds and they vary widely in their absorption depending on manufacturing method and physicochemical characteristics. Costs vary with powder type, but elemental iron powders are generally less expensive than ferrous sulfate. This review evaluates the usefulness of the different elemental iron powders based on results from in vitro studies, rat assays, human bioavailability studies, and efficacy studies monitoring iron status in human subjects. It concludes that, at the present time, only electrolytic iron powder can be recommended as an iron fortificant. Because it is only approximately half as well absorbed as ferrous sulfate, it should be added to provide double the amount of iron.