The importance of bioavailability of dietary iron in relation to the expected effect from iron fortification.

BACKGROUND: The most common method of combating iron deficiency is iron fortification, especially in developing countries. However, few studies have shown a significant effect on iron status following iron fortification of low bioavailability diets. OBJECTIVE: To investigate how iron fortification and dietary modifications affect iron absorption and rates of changes in iron stores. METHODS: Research has made it possible to predict both iron absorption and the effects of iron fortification and diet modifications on iron stores using recently developed algorithms. Iron absorption and rate of change in iron stores were calculated from nine diets representing a broad range of iron bioavailability and iron contents. The calculations were related to the main target group for iron fortification, that is, women of reproductive age having empty stores but normal haemoglobin concentrations. RESULTS: As the only measure, iron fortification has practically no effect on iron status if the original diet has low bioavailability. However, after dietary modifications such a diet shows a positive effect on iron stores. The combined action of fortification (6 mg/day) and modest bioavailability changes in a low bioavailability diet results approximately in 40 and 70% greater increases in iron stores than through iron fortification or dietary modification alone. CONCLUSIONS: It is difficult to achieve good effects on iron status from iron fortification as the only measure if the diet has low bioavailability. Both dietary modifications as well as iron fortification are required to improve effectively the iron status of a population.

Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron.

BACKGROUND: Dietary iron absorption from a meal is determined by iron status, heme- and nonheme-iron contents, and amounts of various dietary factors that influence iron absorption. Limited information is available about the net effect of these factors. OBJECTIVE: The objective was to develop an algorithm for predicting the effects of factors known to influence heme- and nonheme-iron absorption from meals and diets. DESIGN: The basis for the algorithm was the absorption of iron from a wheat roll (22.1 +/- 0.18%) containing no known inhibitors or enhancers of iron absorption and adjusted to a reference dose absorption of 40%. This basal absorption was multiplied by the expected effect of different amounts of dietary factors known to influence iron absorption: phytate, polyphenols, ascorbic acid, meat, fish and seafood, calcium, egg, soy protein, and alcohol. For each factor, an equation describing the dose-effect relation was developed. Special considerations were made for interactions between individual factors. RESULTS: Good agreement was seen when measurements of iron absorption from 24 complete meals were compared with results from use of the algorithm (r(2) = 0.987) and when mean iron absorption in 31 subjects served a varied whole diet labeled with heme- and nonheme-iron tracers over a period of 5 d was compared with the mean total iron absorption calculated by using the algorithm (P = 0.958). CONCLUSIONS: This algorithm has several applications. It can be used to predict iron absorption from various diets, to estimate the effects expected by dietary modification, and to translate physiologic into dietary iron requirements from different types of diets.

Iron balance in menstruating women.

OBJECTIVES: To study factors determining iron balance in menstruating women by examining the relationships between total iron requirements, based on menstrual iron losses and basal iron losses, and serum ferritin concentration, transferrin saturation, blood haemoglobin concentration, bone marrow haemosiderin and absorption of iron from a test dose of ferrous sulphate (0.56 mg Fe). SUBJECTS: The study was made in 203 women all aged 38 years, randomly selected from the census register of Göteborg. The study was originally made in 1968-69. Serum ferritin in frozen sera was first analysed in 1978. Reanalyses, calibrated to the International Standard 80/602, and studies on the effect of storage of sera, were made in 1992. This allowed a complete re-examination of the importance of different determinants of iron balance in women. RESULTS: With increasing iron requirements there was an increase in iron absorption, and a decrease in serum ferritin concentration and transferrin saturation. Above a certain level of iron requirement there was a rather sudden decrease in haemoglobin concentration and in stainable iron in bone marrow smears, indicating the critical level of iron requirements in these women that could be balanced by an increased iron absorption from the present diet. This level represents the maximal adaptation to maintain iron balance in an iron-replete state that can be achieved with this diet and corresponds to a prevalence of iron deficiency of about 25%. CONCLUSIONS: The continuous regulation of iron absorption from iron deficiency to iron repletion has a critical balance point determined by the properties of the diet.

Prevention of iron deficiency.

This chapter discusses different methods to prevent iron deficiency--to reduce iron losses (e.g. reducing menstrual iron losses by using a contraceptive pill or combating of hookworm infestation) or to increase iron absorption. Iron absorption can be increased (1) by modifying the composition of meals--increasing the content of dietary factors enhancing iron absorption (e.g. meat and ascorbic acid) or reducing the content of factors inhibiting iron absorption such as phytate and iron-binding phenolic compounds, (2) by increasing the iron content of the diet by fortification with iron, or by (3) supplementation with iron tablets. Several factors to consider in the choice of strategy are discussed such as the importance of the bioavailability of the diet for the efficacy of iron fortification, the choice of vehicle for iron fortification that is compatible with the iron compound used, the feasibility to increase the bioavailability of the dietary iron by modification of the composition of the diet and the short time available in pregnancy to ensure a sufficient supply of the extra iron needed limiting the effective measures available to supplementation with iron tablets.

Iron fortification of flour with a complex ferric orthophosphate.

The unexpectedly low bioavailability in humans of elemental iron powder prompted us to search for other Fe compounds suitable for Fe fortification of flour that fulfill the two requirements of insolubility in water (due to high water content of flour) and good bioavailability in humans. Systematic studies of compatibility, solubility, and bioavailability led to this study of a microcrystalline complex ferric orthophosphate (CFOP), Fe3H8(NH4)-(PO4)6.6H2O, a well-defined compound. This compound was labeled with 59Fe, and the native Fe in meals was labeled with 55FeCl3. The ratio of absorbed 59Fe to absorbed 55Fe is a direct measure of the fraction of CFOP that joins the nonheme Fe pool and that is made potentially available for absorption. The relative bioavailability of CFOP varied from 30% to 60% when labeled wheat rolls were served with different meals. The CFOP meets practical requirements of an Fe fortificant for flour well, with regard to both compatibility and bioavailability in humans.

Preventing and controlling iron deficiency anaemia through primary health care : a guide for health administrators and programme managers / E. M. DeMaeyer, with the collaboration of P. Dallman ... [et al.] / Prévenir et combattre l' anémie ferriprive dans le cadre des soins de santé primaire : guide à l' usage des administrateurs de la santé et des responsables de programme

A guide to the full range of technical and practical considerations required for the design of direct, inexpensive, and effective strategies to combat iron deficiency anaemia. Noting that this condition impairs the lives of over 700 million persons worldwide, the book makes a special effort to show how new knowledge about the technical means for prevention and control can be used to reach the largest numbers at the lowest possible costs. Throughout, emphasis is placed on problems and pitfalls, particularly in developing countries, that need to be considered when selecting the most appropriate measures for control. The opening chapters provide essential background information about the complex causes of iron deficiency anaemia, the many factors that influence its etiology, and the corresponding implications for assessment and treatment. A chapter devoted to etiology and epidemiology includes a thorough explanation of iron requirements, intake, and bioavailability useful in understanding why some individuals are at greater risk than others. Details range from a table indicating recommended daily iron intakes to examples of dietary combinations, commonly found in developing countries, that either enhance or inhibit iron absorption. Against this background, the book turns to the practical problems of assessment, treatment, and prevention. A chapter concerned with anaemia screening and the detection of iron deficiency critically compares available laboratory tests, pointing out advantages and drawbacks likely to be encountered under field conditions in developing countries. Readers are then given detailed information on treatment options using iron tablets, liquid preparations, or tablets including folate or ascorbic acid, on he recommended dosage and duration of therapy, and on side-effects associated with specific preparations and known to cause poor compliance. Information on prevention concentrates on four basic approaches involving supplementation with medicinal iron, education and associated measures to increase dietary iron intake, the control of parasitic and other infections, and the fortification of a staple food with iron. The book concludes with a discussion of the costs and benefits of prevention and a guide to the components, goals, and logistics of an anaemia control programme

Iron losses in sweat.

The losses of iron in whole body cell-free sweat were determined in eleven healthy men. A new experimental design was used with a very careful cleaning procedure of the skin and repeated consecutive sampling periods of sweat in a sauna. The purpose was to achieve a steady state of sweat iron losses with minimal influence from iron originating from desquamated cells and iron contaminating the skin. A steady state was reached in the third sauna period (second sweat sampling period). Iron loss was directly related to the volume of sweat lost and amounted to 22.5 micrograms iron/l sweat. The findings indicate that iron is a physiological constituent of sweat and derived not only from contamination. Present results imply that variations in the amount of sweat lost will have only a marginal effect on the variation in total body iron losses.

Low bioavailability of carbonyl iron in man: studies on iron fortification of wheat flour.

The bioavailability in man of commercially available elemental iron powders is unknown despite their extensive use for fortification of flour. Carbonyl iron, which is widely used in Europe, is considered as one of the best reduced iron powders based on studies both in vitro and in animals. In this study, a 55Fe labeled carbonyl iron was prepared by neutron irradiation and used to fortify wheat flour. The native iron of the wheat was extrinsically labeled by 59FeCl3. Doubly labeled wheat rolls were served with different meals. The ratio of absorbed 55Fe/59Fe is a direct measure of the fraction of carbonyl iron that joins the nonheme iron pool and is made potentially available for absorption. This relative bioavailability of carbonyl iron was unexpectedly low and varied from 20 to 5% when the iron fortified wheat rolls were served with different meals. The baking process did not change the relative bioavailability nor the addition of ascorbic acid. The low and variable bioavailability of carbonyl iron in man, makes it necessary to reconsider the rationale of using elemental iron powders for the fortification of foods for human consumption.

Improvement of iron nutrition in developing countries: comparison of adding meat, soy protein, ascorbic acid, citric acid, and ferrous sulphate on iron absorption from a simple Latin American-type of meal.

A study in 49 subjects compared different methods for increasing the absorption of iron from a simple Latin American-type meal composed of maize, rice, and black beans. The addition of meat (75 g) increased the nonheme iron absorption from 0.17 to 0.45 mg; soy protein in an amount corresponding to the protein content of the meat increased the absorption to 0.51 mg (due to the high iron content of soy flour); cauliflower as a source of ascorbic acid (65 mg) increased the absorption to 0.58 mg, pure ascorbic acid (50 mg) to 0.41 mg, and ferrous sulphate mixed into the meal in an amount (6 mg) corresponding to the iron content of the soy flour increased the absorption to 0.64 mg. The addition of citric acid (1 g) reduced the absorption to 0.06 mg (to about one-third). We conclude that several methods are available for increasing iron absorption from a Latin American meal and that the choice of method depends on several factors, particularly cost.

Iron metabolism and "sports anemia". II. A hematological comparison of elite runners and control subjects.

A hematological comparison was performed between 43 middle and long distance male runners and 119 male controls. The hematocrit, serum iron, transferrin saturation and serum ferritin values were significantly lower in the athletes. The amount of bone marrow hemosiderin was also lower in the athletes than in a group of non-athletic men of the same age. Even if these values were clearly lower than in the controls, they were not low enough to indicate iron deficiency. The observations that sideroblast counts in bone marrow smears were normal and that both red cell indices and red cell protoporphyrin were normal strongly support the conclusion that lack of iron had not limitated erythropoiesis or the formation of an optimal red cell mass. Low serum haptoglobin values in most athletes indicated an increased intravascular hemolysis. As the hemoglobin-haptoglobin complex formed is taken up by hepatocytes, this implies that there is a shift in the red cell catabolism in these athletes from the reticuloendothelial system to the hepatocytes. This shift may explain the paradoxical findings of low serum ferritin concentrations and reduced contents of bone marrow hemosiderin. This is consistent with the observed normal erythropoiesis. It was concluded that runners "anemia" is no true anemia and not caused by iron deficiency. "Sports anemia" is thus no indication for routine iron supplementation.

Effect of different drinks on the absorption of non-heme iron from composite meals.

A study was made on the effect of various drinks on the absorption on non-heme iron. The drinks were taken with standard meals composed of a hamburger, string beans and mashed potatoes. In each series identical meals were served to the same subject either with water or with the drink under study, labelling the meals with two different radio-iron isotopes. A reduction in iron absorption was seen when serving tea (62 per cent) or coffee (35 per cent) with the meals. Orange juice increased the iron absorption (85 per cent). Pure alcohol and wine increased only slightly the percentage absorbed. Wine often has a high iron content, which increased significantly the amount of iron absorbed (three times). Milk and beer have no significant effect. Coca-Cola increased only slightly the absorption. The present studies clearly shows that the choice of drink drunk with a meal can markedly affect the absorption of non-heme iron.