Estimation of dietary iron bioavailability from food iron intake and iron status.

Currently there are no satisfactory methods for estimating dietary iron absorption (bioavailability) at a population level, but this is essential for deriving dietary reference values using the factorial approach. The aim of this work was to develop a novel approach for estimating dietary iron absorption using a population sample from a sub-section of the UK National Diet and Nutrition Survey (NDNS). Data were analyzed in 873 subjects from the 2000-2001 adult cohort of the NDNS, for whom both dietary intake data and hematological measures (hemoglobin and serum ferritin (SF) concentrations) were available. There were 495 men aged 19-64 y (mean age 42.7±12.1 y) and 378 pre-menopausal women (mean age 35.7±8.2 y). Individual dietary iron requirements were estimated using the Institute of Medicine calculations. A full probability approach was then applied to estimate the prevalence of dietary intakes that were insufficient to meet the needs of the men and women separately, based on their estimated daily iron intake and a series of absorption values ranging from 1-40%. The prevalence of SF concentrations below selected cut-off values (indicating that absorption was not high enough to maintain iron stores) was derived from individual SF concentrations. An estimate of dietary iron absorption required to maintain specified SF values was then calculated by matching the observed prevalence of insufficiency with the prevalence predicted for the series of absorption estimates. Mean daily dietary iron intakes were 13.5 mg for men and 9.8 mg for women. Mean calculated dietary absorption was 8% in men (50th percentile for SF 85 µg/L) and 17% in women (50th percentile for SF 38 µg/L). At a ferritin level of 45 µg/L estimated absorption was similar in men (14%) and women (13%). This new method can be used to calculate dietary iron absorption at a population level using data describing total iron intake and SF concentration.

Why nutritional iron deficiency persists as a worldwide problem.

The earliest studies of food iron absorption employing biosynthetically incorporated radioisotopes were published in the 1950s. Wheat flour has been fortified with iron in Canada, the United Kingdom, and the United States since the 1940s. However, half a century later, nutritional iron deficiency (ID) is estimated to affect 1.5-2 billion people worldwide. The reasons for the apparently limited impact of health and nutrition policies aimed at reducing the prevalence of ID in developing countries are complex. They include uncertainty about the actual prevalence of ID, particularly in regions where malaria and other infections are endemic, failure of policy makers to recognize the relationships between ID and both impaired productivity and increased morbidity, concerns about safety and the risks to iron-sufficient individuals if mass fortification is introduced, and technical obstacles that make it difficult to add bioavailable iron to the diets of those at greatest risk. It is, however, likely that the next decade will see a marked reduction in the prevalence of ID worldwide. More specific assessment tools are being standardized and applied to population surveys. The importance of preventing ID during critical periods of the life cycle is receiving increased attention. Innovative approaches to the delivery of bioavailable iron have been shown to be efficacious. The importance of integrating strategies to improve iron nutrition with other health measures, and economic and social policies addressing poverty as well as trade and agriculture, are receiving increasing consideration.

Assessment of iron deficiency in US preschool children and nonpregnant females of childbearing age: National Health and Nutrition Examination Survey 2003-2006.

BACKGROUND: A new index to determine body iron promises a simpler approach to monitoring iron deficiency (ID) prevalence. OBJECTIVE: Our objective was to compare ID defined as body iron <0 mg/kg and calculated from the log ratio of transferrin receptor to ferritin (the body iron model) to ID defined as >/=2 of 3 abnormal concentrations in ferritin, transferrin saturation, or erythrocyte protoporphyrin (the ferritin model). DESIGN: We used measures of iron status and inflammation from 486 children aged 1-2 y, 848 children aged 3-5 y, and 3742 nonpregnant females aged 12-49 y from the National Health and Nutrition Examination Survey 2003-2006. RESULTS: ID prevalences (+/-SE) based on the body iron model in children (1-2 and 3-5 y) and in females (12-19 and 20-49 y) were 14.4 +/- 1.9%, 3.7 +/- 0.8%, 9.3 +/- 1.0%, and 9.2 +/- 1.6%, respectively. ID prevalences based on the ferritin model in children (3-5 y) and females (12-19 and 20-49 y) were 4.5 +/- 0.9%, 15.6 +/- 1.2%, and 15.7 +/- 0.8%, respectively. The kappa statistics for agreement between the 2 models were 0.5-0.7. Among females (12-49 y) the positive predictive values of ID based on the body iron model and the ferritin model for identifying anemia were 43 +/- 3% and 30 +/- 2%, respectively, whereas negative predictive values did not differ. C-reactive protein was elevated in 28.8 +/- 3.1% of females with ID by the ferritin model but not by the body iron model and in 0% of persons with ID by the body iron model but not by the ferritin model. CONCLUSIONS: The agreement between the 2 indexes was fair to good. Among females, the body iron model produced lower estimates of ID prevalence, better predicted anemia, and appeared to be less affected by inflammation than the ferritin model.

A comparison of physical properties, screening procedures and a human efficacy trial for predicting the bioavailability of commercial elemental iron powders used for food fortification.

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.

Comparison of the efficacy of wheat-based snacks fortified with ferrous sulfate, electrolytic iron, or hydrogen-reduced elemental iron: randomized, double-blind, controlled trial in Thai women.

BACKGROUND: Although elemental iron powders are widely used to fortify cereal products, little data exist on their efficacy in humans. OBJECTIVE: We compared the efficacy of wheat-based snacks fortified with ferrous sulfate, electrolytic iron, or hydrogen-reduced iron in Thai women with low iron stores. DESIGN: A double-blind intervention was conducted in 18-50-y-old women (n = 330) randomly assigned into 4 groups to receive either no fortification iron or 12 mg Fe/d for 6 d/wk for 35 wk as ferrous sulfate, electrolytic iron, or hydrogen-reduced iron in a baked, wheat-flour-based snack. Snacks were not consumed with meals, and consumption was monitored. At baseline, 20 wk, and 35 wk, hemoglobin status and iron were measured and the groups were compared. RESULTS: Between baseline and 35 wk, geometric mean serum ferritin (SF) increased significantly in all 3 groups receiving iron (P < 0.01), and geometric mean serum transferrin receptor (TfR) decreased significantly in the groups receiving ferrous sulfate and electrolytic iron (P < 0.05). Calculated mean (+/-SD) body iron stores increased from 1.5 +/- 2.8 to 5.4 +/- 2.9 mg/kg in the ferrous sulfate group, from 1.5 +/- 3.5 to 4.4 +/- 3.6 mg/kg in the electrolytic iron group, and from 1.3 +/- 3.2 to 3.2 +/- 4.3 mg/kg in the hydrogen-reduced iron group (P < 0.01 for all 3 groups) but did not change significantly in the control group. CONCLUSIONS: Ferrous sulfate, electrolytic iron, and hydrogen-reduced iron, fortified into wheat-based snacks, significantly improved iron status. On the basis of the change in body iron stores during the 35-wk study, the relative efficacy of the electrolytic and hydrogen-reduced iron compared with ferrous sulfate was 77% and 49%, respectively.

The impact of iron fortification on nutritional anaemia.

Iron deficiency continues to be the most prevalent nutritional deficiency disorder in the world, affecting an estimated two billion people, most of whom live in developing countries. It has far-reaching effects on the health, well-being and productivity of those affected. Iron fortification of food is regarded as the most cost-effective method for reducing the prevalence of nutritional iron deficiency. In industrialized countries this has had an important beneficial effect; however, nutritional anaemia remains very prevalent in developing countries, and iron fortification appears until recently to have had little impact. Two important reasons for the latter situation are inadequate documentation of the magnitude of the iron deficiency component of anaemia in different regions of the world, and the use of iron compounds that are poorly bioavailable in fortification programmes. Several recent interventions using innovative approaches to dietary fortification that ensure the delivery of adequate quantities of bioavailable iron have demonstrated that iron fortification of food can be an effective and implementable strategy for controlling nutritional iron deficiency in non-industrialized countries.

Iron and ascorbic Acid: proposed fortification levels and recommended iron compounds.

An adequate supply of dietary iron during the 1st 24 mo of life is essential for preventing iron deficiency with its attendant negative effects on mental, motor and emotional development as well as later cognitive performance. Iron reserves and the small amount of highly bioavailable iron in human milk are adequate to satisfy the iron requirements of breast-fed infants of adequate birth weight for the 1st 6 mo of life. Thereafter, complementary foods, iron supplements or both are needed to meet this requirement. Complementary foods should not displace the consumption of human milk. The quantities eaten, particularly by younger infants, may therefore be quite small. As a consequence it is essential that the iron be supplied in a highly bioavailable form. This can be achieved by fortifying complementary foods with ferrous sulfate and ascorbic acid provided that the ascorbic acid is not lost during storage or meal preparation. Suggested fortification levels for ferrous sulfate and ascorbic acid for some types of complementary foods are given. The use of ferrous fumarate or an elemental iron powder instead of ferrous sulfate has not been evaluated adequately. There is a need to develop alternative strategies for improving iron bioavailability in complementary foods because it may not be possible to preserve ascorbic acid activity in many of them.