IntroductionHeightened awareness in recent years of the adverse consequences of iron deficiency has prompted renewed efforts to reduce the prevalence of this common micronutrient insufficiency. One of the main reasons for the limited success of programs to combat iron deficiency is the continuing uncertainty about the optimal epidemiologic approach for identifying it and for measuring its severity. The inadequacy of anemia surveys is reflected in the wide-ranging estimates by various expert committees of the global prevalence of iron deficiency. In a 1985 World Health Organization (WHO) report, it was estimated that 15% to 20% of the world's population had iron deficiency anemia. 1 Despite the lack of new prevalence data, estimates of the global prevalence of iron deficiency anemia have increased to more than two thirds of the world population. 2 More reliable methods to assess iron status are needed to determine the prevalence of iron deficiency and the impact of iron supplementation and fortification trials.In the present article, a new method is described for assessing iron status based on the quantitative measurement of body iron. The method has been used to examine the iron status in a consensus sample of adult men and women in the United States and of pregnant women in Jamaica. The usefulness of the method has been further evaluated by measuring the absorption of added iron in a supplementation trial in pregnant women and a food fortification trial in anemic women. Materials and methods Estimation of body ironMeasurements of body iron were based on a prior study in which serial measurements of serum ferritin and serum transferrin receptor (sTfR) were obtained during repeated phlebotomies in 14 healthy control subjects. 3 Phlebotomy was discontinued when the baseline hemoglobin concentration in each subject had fallen by 20 g/L and remained so for 3 weeks without further bleeding. The amount of storage iron at baseline was calculated from the amount of hemoglobin iron removed to reduce the serum ferritin concentration to less than 12 g/L. Body iron was then calculated from the hemoglobin iron removed at each bleeding after correction for the absorption of dietary iron. A close linear relationship was demonstrated between the logarithm of the concentrations in micrograms per liter, of serum transferrin receptor/serum ferritin (R/F ratio), and of body iron expressed as milligram per kilogram body weight (Figure 1). The latter is expressed as the iron surplus in stores (positive value) or the iron deficit in tissues (negative value). Body iron was calculated from the R/F ratio as follows: body iron (mg/kg) ϭ Ϫ[log(R/F ratio) Ϫ 2.8229]/0.1207. SurveysData from 3 published studies were used to evaluate quantitative measurements of body iron. The largest data set was a convenience sample collected in the third National Health and Nutrition Examination Survey (NHANES III) in the US population from 1988 to 1994. 4 The sample differed from the full NHANES III sample in that it was not selected to represent the US po...

This study was undertaken to evaluate the role of serum transferrin receptor measurements in the assessment of iron status. Repeated phlebotomies were performed in 14 normal volunteer subjects to obtain varying degrees of iron deficiency. Serial measurements of serum iron, total iron-binding capacity, mean cell volume (MCV), free erythrocyte protoporphyrin (FEP), red cell mean index, serum ferritin, and serum transferrin receptor were performed throughout the phlebotomy program. There was no change in receptor levels during the phase of storage iron depletion. When the serum ferritin level reached subnormal values there was an increase in serum receptor levels, which continued throughout the phlebotomy program. Functional iron deficiency was defined as a reduction in body iron beyond the point of depleted iron stores. The serum receptor level was a more sensitive and reliable guide to the degree of functional iron deficiency than either the FEP or MCV. Our studies indicate that the serum receptor measurement is of particular value in identifying mild iron deficiency of recent onset. The iron status of a population can be fully assessed by using serum ferritin as a measure of iron stores, serum receptor as a measure of mild tissue iron deficiency, and hemoglobin concentration as a measure of advanced iron deficiency.

The quantitative assessment of body iron based on measurements of the serum ferritin and transferrin receptor was used to examine iron status in 800 Bolivian mothers and one of their children younger than 5 years. The survey included populations living at altitudes between 156 to 3750 m. Body iron stores in the mothers averaged 3.88 ؎ 4.31 mg/kg (mean ؎ 1 SD) and 1.72 ؎ 4.53 mg/kg in children. No consistent effect of altitude on body iron was detected in children but body iron stores of 2.77 ؎ 0.70 mg/kg (mean ؎ 2 standard error [SE]) in women living above 3000 m was reduced by one-third compared with women living at lower altitudes (P < .001). One half of the children younger than 2 years were iron deficient, but iron stores then increased linearly to approach values in their mothers by 4 years of age. When body iron in mothers was compared with that of their children, a striking correlation was observed over the entire spectrum of maternal iron status (r ‫؍‬ 0.61, P < .001). This finding could provide the strongest evidence to date of the importance of dietary iron as a determinant of iron status in vulnerable segments of a population.

Extracellular iron, which is predominantly bound by transferrin, is present in low concentrations within alveolar structures, and concentrations are increased in various pulmonary disorders. Iron accumulation by cells can promote oxidative injury. However, the synthesis of ferritin stimulated by metal exposure for intracellular iron storage is normally protective. The cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β may alter iron metabolism by alveolar cells. In this study, we assessed the effects of TNF-α and IL-1β on iron metabolism with a cell line with properties of type 2 alveolar epithelial cells (A549) exposed to non-transferrin-bound (NTBI; FeSO4) or transferrin-bound (TBI) iron. In addition, we assessed the cytotoxicity of these exposures by measuring the cell accumulation of malondialdehyde (MDA), a product of lipid peroxidation, and cell death (MTT assay and lactate dehydrogenase release). A549 cells treated with NTBI or TBI in concentrations up to 40 μM accumulated iron and synthesized predominantly L-type ferritin without accumulation of MDA or cell death. Treatment of A549 cells with TNF-α (20 ng) or IL-1β (20 ng) decreased cell transferrin-receptor expression and induced synthesis of H-type ferritin. TNF-α and IL-1β decreased the uptake of TBI; however, the uptake of NTBI was increased. Both cytokines enhanced total ferritin synthesis (H plus L types) in response to iron treatments due to enhanced synthesis of H-type ferritin. Coexposure to TNF-α and NTBI, but not to TBI, induced MDA accumulation and greater cytotoxicity (MTT and lactate dehydrogenase release) than TNF-α alone. These findings indicate that TNF-α and IL-1β modulate iron uptake by A549 cells, with differing effects on TBI and NTBI, as well as on H-ferritin synthesis. Enhanced iron uptake induced by TNF-α and NTBI was also associated with increased cytotoxicity to A549 cells.