Efficiency Of Iron Absorption Research Articles

In situ implantable DNA hydrogel for diagnosis and therapy of postoperative rehemorrhage following intracerebral hemorrhage surgery.

Postoperative rehemorrhage following intracerebral hemorrhage surgery is intricately associated with a high mortality rate, yet there is now no effective clinical treatment. In this study, we developed a hemoglobin (Hb)-responsive in situ implantable DNA hydrogel comprising Hb aptamers cross-linked with two complementary chains and encapsulating deferoxamine mesylate (DFO). Functionally, the hydrogel generates signals upon postoperative rehemorrhage by capturing Hb, demonstrating a distinctive "self-diagnosis" capability. In addition, the ongoing capture of Hb mediates the gradual disintegration of the hydrogel, enabling the on-demand release of DFO without compromising physiological iron-dependent functions. This process achieves self-treatment by inhibiting the ferroptosis of neurocytes. In a collagenase and autologous blood injection model-induced mimic postoperative rehemorrhage model, the hydrogel exhibited a 5.58-fold increase in iron absorption efficiency, reducing hematoma size significantly (from 8.674 to 4.768 cubic millimeters). This innovative Hb-responsive DNA hydrogel not only offers a therapeutic intervention for postoperative rehemorrhage but also provides self-diagnosis feedback, holding notable promise for enhancing clinical outcomes.

Iron deficiency anemia: a critical review on iron absorption, supplementation and its influence on gut microbiota.

Iron deficiency anemia (IDA) caused by micronutrient iron deficiency has attracted global attention due to its adverse health effects. The regulation of iron uptake and metabolism is finely controlled by various transporters and hormones in the body. Dietary iron intake and regulation are essential in maintaining human health and iron requirements. The review aims to investigate literature concerning dietary iron intake and systemic regulation. Besides, recent IDA treatment and dietary iron supplementation are discussed. Considering the importance of the gut microbiome, the interaction between bacteria and micronutrient iron in the gut is also a focus of this review. The iron absorption efficiency varies considerably according to iron type and dietary factors. Iron fortification remains the cost-effective strategy, although challenges exist in developing suitable iron fortificants and food vehicles regarding bioavailability and acceptability. Iron deficiency may alter the microbiome structure and promote the growth of pathogenic bacteria in the gut, affecting immune balance and human health.

Effects of salinity and iron deficiency on growth and physiological attributes of Avicennia marina (Forssk.) Vierh

ABSTRACT The grey mangrove, Avicennia marina, grows in coastal zones in which salinity is frequently associated with iron deficiency. Its response to these combined stresses has not yet explored. The current study aims to assess the physiological and biochemical effects of iron deficiency (ID), salt stress (SS) and their combination (ID + SS) on A. marina seedlings. Iron deficiency reduced growth at non-saline treated plants by 27% while its deleterious effect was mitigated by the supply of 600 mM NaCl, mainly through the increase of photosynthetic pigment contents, iron accumulation in leaves, and intrinsic water use efficiency (iWUE), and the maintain of iron use efficiency (FeUE). Iron deficiency restricted iron accumulation in leaves (31%), iron absorption efficiency (FeAE) (38%), photosynthetic activity and pigment contents, and enhanced FeUE (48%) at saline treated plants. Otherwise, salinity enhanced growth (47%), root volume (20%), Fe accumulation in leaves (8%), and pigment contents at Fe-deficient plants. However, it reduced their FeAE (18%), transpiration rate (77%) and stomatal conductance (86%). Equally, it increased Na and Cl accumulation, the net photosynthetic assimilation rate and iWUE at Fe-deficient. Interestingly, the combined stresses had no additive effects and stressed plants (ID +SS) had comparable biomass to that of the control.

Purification, immunological, and functional characterization of MxFIT in Malus xiaojinensis

MxFIT is a FER-like iron deficiency induced transcriptional factor in Malus xiaojinensis. Here, we described the heterologous expression of MxFIT in Escherichia coli BL21 (DE3) host cells. The E. coli harboring the recombinant construct pET-MxFIT was efficiently induced to express the MxFIT protein at a high level and the optimal profile for MxFIT expression was investigated. By inoculating a New Zealand rabbit with purified MxFIT-His fusion protein, a high specific anti-MxFIT antiserum was achieved. Western blot analysis showed MxFIT protein expression was induced in roots when iron supply was limiting and was inhibited when iron supply was excessive. In leaves, there was almost no expression irrespective of iron supply. The localization of MxFIT on transverse section of root indicated that MxFIT participated in iron deficiency response. Over-expression of MxFIT in transgenic tobacco suspension cells showed that MxFIT increased iron absorption under insufficient iron supply. This study provides a basis for further investigating the underlying mechanism of high iron absorption efficiency in M. xiaojinensis.

Intravenous Iron Infusion Administration Schedule and Hematologic Response; A Single-Center Retrospective Cohort Study

Background: Clinical trials studying the efficacy of intravenous (IV) iron replacement have used a variety of dosing schedules, even for the same iron formulations and there isn't a clear standard for how IV iron replacement should be scheduled. Differences in iron absorption efficiency have been observed with different oral iron supplementation schedules but it is not known if the same is true for IV iron. The objective of this study was to evaluate the association between iron administration schedule and hemoglobin response in patients treated at a tertiary care center. Methods: Data was collected retrospectively using The Ottawa Hospital Data Warehouse (OHDW) capturing all iron infusions given at 3 local institutions between January 2007 and December 2018. Patients that received at least 2 intravenous iron infusions within 180 days of each other were included. A 'course' of iron replacement was defined as consecutive infusions with ≤180 days between doses. Patients transfused red blood cells within 90 days of the last iron infusion in each course were excluded. Patient age, sex, dose and formulation of administered, date of each iron infusion, and laboratory parameters from the period starting 3 months before the first infusion to 6 months after the last infusion were extracted for analysis. Patients were categorized into 4 groups based on the mean time between iron infusions in each course: 1-10 days, 11-20 days, 21-30 days, and >30 days. Achieving a maximum hemoglobin (Hb) 10 g/L or higher than the pre-infusion Hb was defined as a 'good' response. A logistic regression model was used to evaluate the association between interval between infusions and achieving a 'good' Hb response. The model was adjusted for sex, age, presence of chronic kidney disease (CKD), dose of iron per course, number of infusions per course, and number of courses. CKD was defined as having a serum creatinine >177 µmol/L. Iron sucrose, iron gluconate, and iron dextran were available for administration during the study period. Results: A total of 4350 patients were included in the analysis. These patients received a total of 6409 courses of iron replacement, with a median of 2 courses (interquartile range [IQR] 1-3) per patient, and 4 infusions (IQR 3-6) per replacement course. Infusions were given a median of 21.9 days (IQR 12-34) apart in each course, with a range of 1-179 days. Iron sucrose was given in most courses (81.6%), followed by iron gluconate (18.2%) and iron dextran (0.1%). Patient characteristics are summarized in Table 1 and laboratory values prior to the first infusion of each course are summarized in Table 2. The interval between iron infusions was associated with Hb response. Results of the logistic regression are summarized Table 3. Compared with patients receiving infusions every 10-20 days, patients receiving infusions more frequently or less frequently were less likely to achieve a good Hb response. Male sex was associated with increased odds of response, while increasing age, having CKD, and receiving more courses of iron were associated with decreased odds of response. Conclusions: In this single-center retrospective cohort analysis, an association between interval of iron infusions and hematologic response was observed. Patients given iron every 10-20 days more likely to achieve a good response compared with more, or less frequent dosing intervals. Strengths of this study include the large sample size, adjustment for sex, age, presence of CKD, and number of iron infusions and courses given. Transfused patients were excluded, so the hemoglobin response is attributable to iron replacement. The study has several important limitations. The clinical decision-making for the infusion schedule was not known and factors that went into this decision are a possible source of confounding (for example, ongoing bleeding). The suspected cause of iron deficiency was not known. Additionally, concomitant oral iron supplementation and iron infusions or transfusions occurring outside the study institution are unknowns and may influence to outcome. The hypothesis-generating findings suggest that the schedule of iron administration may play an important role in hematologic response to iron infusions. Disclosures No relevant conflicts of interest to declare.

Hepcidin Status at 2 Months in Infants Fed Breast Milk Compared with Formula

Introduction: The basis for the superior absorption of iron from breast milk compared with infant formulas is unclear. The hormone hepcidin downregulates dietary iron absorption. Hepcidin production increases with increased body iron status (reflected in serum ferritin levels). We hypothesized that serum hepcidin levels are suppressed relative to iron status in infants fed breast milk compared with formula. Methods: Subjects were healthy infants presenting for routine 2-month clinic visit and strictly fed either breast milk or standard infant formula. Urinary hepcidin and ferritin levels (reflective of serum levels) were analyzed and compared across the breast milk- and formula-fed groups. The relationship between urinary hepcidin and ferritin levels within each group was analyzed by linear regression. Results: Twenty-four subjects were enrolled in each group. The median urinary hepcidin level in the group fed breast milk was lower than in formula (130 vs. 359 ng hepcidin/mg creatinine, p < 0.05). However, the median ferritin levels were similar (2.1 vs. 1.9 ng/mL). Within each group, urinary hepcidin correlated with urinary ferritin (r = 0.5, p < 0.05 for each group); however, the slope of the regression line was lower in the group fed breast milk compared with formula (p < 0.005). Conclusion: Despite similar urinary ferritin levels, urinary hepcidin levels are lower at 2 months in infants fed breast milk compared with infants fed formula. Hepcidin levels correlate with iron status in each group; however, this relationship is relatively dampened in infants fed breast milk. We speculate that relatively lower infant hepcidin contributes to the superior efficiency of iron absorption from breast milk.

Effect of fulvic and humic acids on iron and manganese homeostasis in rats.

The objective of this study was to investigate the effects of fulvic acid (FA) and humic acid (HA) as the two main compounds of humic substances, separately on Fe and Mn homeostasis. Seventy-two male Wistar rats were randomly divided into 9 experimental groups. The control diet (AIN-93G formula) and diets supplemented with 0.1%, 0.2%, 0.4% and 0.8% HA or FA were fed for 26 days. Fe and Mn concentrations of the large intestinal content, liver, kidney, femur and hair were determined. No significant differences were observed in the production parameters. The effects of FA and HA on iron homeostasis were significantly different. FA proved to be a good iron source, and slightly increased the iron content of liver and kidney, but - up to a dietary iron level of 52.7 mg/kg - it did not influence the efficiency of iron absorption. Above a dietary iron level of 52.7 mg/kg down-regulation of Fe absorption can be assumed. HA significantly stimulated the iron uptake and there was no down-regulation of Fe absorption up to 0.8% dietary HA supplementation level (61.5 mg Fe/kg diet). In the HA groups the iron content of the liver and kidney decreased significantly, suggesting that in spite of the better Fe absorption, the HA-Fe complex does not provide iron to the investigated organs. Neither FA nor HA supplementation influenced the Fe content of the femur and hair and slightly decreased the Mn concentration in the large intestinal content. This effect was significant (with a 22.7% Mn concentration decrease) only at the HA supplementation rate of 0.8%. Neither FA nor HA influenced significantly the Mn concentrations of the liver, kidney and femur. The Mn concentration of the hair in rats receiving FA- or HA-supplemented diets was higher than in the control rats; however, this result needs further confirmation.

Natural iron isotopic composition of blood is an indicator of dietary iron absorption efficiency in humans

Persistent impairments in the regulation of intestinal iron absorption result in iron deficiency or iron accumulation in the long term. Diagnosis remains difficult unless pathological symptoms develop as iron absorption varies strongly between meals and days. Variations in the natural iron isotopic composition of whole blood have recently been suggested as a novel parameter to assess long-term differences in intestinal absorption efficiency between individuals. In this study, baseline blood samples collected in two previous conventional iron absorption studies in Swiss and Thai women using stable isotope tracers were reanalyzed by multicollector inductively coupled plasma mass spectrometry. The natural iron isotopic compositions obtained were compared with fractional absorption from the test meals observed in these earlier trials. Correlations of natural blood iron isotopic composition and fractional absorption from the test meals were found to be highly significant in both cohorts (for Swiss women, r = 0.40, P = 0.01, n = 38; for Thai women, r = 0.57, P < 0.01, n = 24), with the blood of both ethnicities clearly differing in iron isotopic composition (P < 0.001). Combining the findings of this study and those of recent animal and human studies confirms that blood iron isotopic patterns may serve as a novel compound biomarker of iron metabolism to assess impairments in regulation of intestinal iron absorption in individuals or population groups.

Mobilization of storage iron is reflected in the iron isotopic composition of blood in humans

We recently showed in an animal model that iron isotopic composition varies substantially between different organs. For instance, iron in ferritin-rich organs--such as the major storage tissues liver, spleen, and bone marrow--contain a larger fraction of the heavy iron isotopes compared with other tissues, including blood. As a consequence, partitioning of body iron into red blood cells and storage compartments should be reflected in the isotopic pattern of blood iron. To confirm this hypothesis, we monitored blood iron isotope patterns in iron-overloaded subjects undergoing phlebotomy treatment by multicollector inductively coupled plasma mass spectrometry. We found that bloodletting and consequential replacement of lost blood iron by storage iron led to a substantial increase of the heavy isotope fraction in the blood. The progress of iron depletion therapy and blood loss was quantitatively traceable by isotopic shifts of as much as +1‰ in δ((56)Fe). These results show that--together with iron absorption efficiency--partitioning of iron between blood and iron storage tissues is an important determinant of blood iron isotopic patterns, which could make blood iron isotopic composition the first composite measure of iron metabolism in humans.

Isotopic signatures of iron in body tissues as a potential biomarker for iron metabolism

Previous studies using MC-ICP-MS for high precision isotope ratio analysis revealed that human blood is enriched in light iron isotopes relative to dietary iron. Moreover, distinct differences in blood iron isotopic patterns between individual subjects can be observed. Discrimination of heavy iron isotopes during uptake of dietary iron in the gastrointestinal tract may explain this observation. This hypothesis was now tested in the pig model. Samples of tissues relevant to iron metabolism were screened for iron isotopic patterns using MC-ICP-MS, revealing considerable isotope fractionation during intestinal uptake on one hand and during distribution between body tissues on the other hand. Light iron isotopes are enriched in the gastrointestinal mucosa relative to feed, with isotopic patterns reflecting major iron absorption sites in mammals along the gut. While heavy iron isotopes are enriched in the liver, spleen and bone marrow, light isotopes are enriched in red blood cells. Well-established links between iron absorption efficiency and iron distribution between functional compartments and stores point to blood iron isotope signatures as a novel type of compound biomarker of element metabolism.

Synthesis and Iron(III)-Chelating Properties of Novel 3-Hydroxypyridin-4-one Hexadentate Ligand-Containing Copolymers

Iron overload is a critical clinical problem that can be prevented by the use of iron-specific chelating agents. An alternative method of relieving iron overload is to reduce the efficiency of iron absorption from the intestine by administering iron chelators, which can bind iron irreversibly to form nontoxic, kinetically inert complexes that are not absorbed and are therefore excreted in the feces. A series of polymeric chelators with various iron binding capacities were therefore prepared as nonabsorbable iron-selective additives. A novel 3-hydroxypyridin-4-one hexadentate ligand CP254 has been synthesized and incorporated into polymers by copolymerisation with N, N-dimethylacrylamide (DMAA), and N, N'-ethylene-bis-acrylamide (EBAA) using (NH4)2S2O8 as the initiator. The physicochemical properties of CP254 were determined, namely, log K = 33.2 and pFe(3+) = 27.24. The chelating capacity of the CP254-DMAA copolymers was determined at physiological pH. The iron(III) chelation was found to achieve 80% capacity after 1 h and was virtually complete after 5 h, which is much quicker than that of the commercially available chelating resin Chelex100. The chelating copolymers were found to be readily regenerated and reusable. The copolymers possess a high selectivity for iron(III). The conditional affinity (log K') for iron(III) at pH 7.46 was determined to be 26.55, which is not significantly different to that of the hexadentate ligand CP254 (log K' = 26.47). In vitro perfusion studies indicate that the polymeric chelators described in this study can reduce iron absorption from the intestine.

Iron Absorption Prediction Equations Lack Agreement and Underestimate Iron Absorption

A number of algorithms have been developed to predict the bioavailability of iron from mixed meals and diets, but their direct validity in predicting change in iron status remains questionable. Throughout the course of conducting a large feeding trial in 10 convents in Manila, we collected weighed food intake data (n = 317) and directly compared the performance of these prediction equations to each other and to the change in serum ferritin (SF). Dietary weighed food intakes were measured on d 3 every 2 wk for each woman and iron status determined at baseline, 4.5 mo, and 9 mo. The Monsen and Balintfy equation predicted higher median absorption efficiency (7.3%) than did the equations of Hallberg and Hulthen (6.1%) and Reddy et al. (5.8%). In contrast, the predictions that used the equations of Bhargava et al. (3.8%), Tseng et al. (2.9%), and Du et al. (2.6%) were significantly lower. The iron absorption efficiencies calculated using the Monsen and Balintfy equation correlated with those using the Hallberg and Hulthen equation (r = 0.91, P < 0.001). This slope did not differ from unity, whereas all other equations underestimated iron absorption efficiency relative to Monsen and Balintfy’s equation. The median efficiency of absorption, based on change in SF in 114 subjects, was 17.2%, suggesting that these equations underestimate iron absorption. The inhibitory and enhancing factors in the published prediction equations were quantitatively either too large or perhaps too small to correctly predict apparent iron bioavailability over a 9-mo period. The causes of the lack of agreement between change in iron status estimated by SF change and absorption predicted by algorithms are open to discussion and will need to be resolved.

Iron Absorption: Comparison of Prediction Equations and Reality. Results from a Feeding Trial in the Philippines

A number of algorithms have been developed that seek to predict the bioavailability of iron from mixed meals and diets, but their direct validity in predicting change in iron status remains questionable. Throughout the course of conducting a large feeding trial in convents in Manila, we collected weighed food-intake data and have the opportunity to directly compare the performance of these prediction equations. The specific aims of this particular analysis are as follows: (a) to determine habitual intakes of macro- and micronutrients in religious sisters in Manila, (b) to determine the predicted efficiency of iron absorption from each of the published bioavailability algorithms (Monsen, Hallberg, Reddy, Tseng, Barghava, and Du), and (c) to determine which of these equations best predicts the actual "gain" in iron in religious sisters over the duration of the trial. The efficacy of consuming high-iron rice was tested during a nine-month feeding trial with a double-blinded dietary intervention; these results have been published [7]. Religious sisters living in 10 convents around metropolitan Manila, the Philippines were randomly assigned to consume either high-iron rice (3.21 mg/kg Fe) or a local variety of control rice (0.57 mg/kg Fe) within each convent. Religious sisters in convents consumed a diet that appeared to be typical of habitual intakes of macro-and micronutrients in this part of the Philippines. The analysis of the six equations revealed highly significant differences in predicted efficiency of iron absorption. The Hallberg, Monsen, and Reddy equations all predicted similar median efficiency (6.88, 7.92, and 6.42%). In contrast, Bhargava (4.68%), Tseng (3.23%), and Du (2.92%) were significantly lower. The correlation (r = 0.98) of Monsen to Hallberg was highly significant and the slope was not different than unity. The median efficiency of absorption based on the gain in body iron in 114 subjects over nine months, combined with an estimate of daily iron requirements, was 17.2%. Thus, none of these equations approximated the computed iron absorption based on improvement in serum ferritin and suggests alternative approaches to predicting iron accumulation from diet need to be formulated. Inhibitory factors in the prediction equations either had little effect or had too large of an effect on apparent bioavailability as compared to median absorption over a nine-month period. The causes of the lack of agreement between computed iron gain and predicted absorption are open to discussion and will need to be resolved.

Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women

Hepcidin plays a major role in iron homeostasis, but understanding its role has been hampered by the absence of analytical methods for quantification in blood. A commercial ELISA has been developed for serum prohepcidin, a hepcidin precursor, and there is interest in its potential use in the clinical and research arena. We investigated the association between serum prohepcidin concentration and iron absorption in healthy men, and its relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients, and pregnant women. Iron absorption was determined in thirty healthy men (fifteen wild-type, fifteen C282Y heterozygote) using the stable isotope red cell incorporation technique. Iron status was measured in 138 healthy men (ninety-one wild-type, forty-seven C282Y heterozygote), six hereditary haemochromatosis patients, and thirteen pregnant women. Mean serum prohepcidin concentrations were 214 (SD 118) ng/ml [208 (SD 122) ng/ml in wild-type and 225 (SD 109) ng/ml in C282Y heterozygotes] in healthy men, 177 (SD 36) ng/ml in haemochromatosis patients, and 159 (SD 59) ng/ml in pregnant women. There was no relationship between serum prohepcidin concentration and serum ferritin in any subject groups, nor was it associated with efficiency of iron absorption. Serum prohepcidin is not a useful biomarker for clinical or research purposes.

Mechanisms and Regulation of Intestinal Iron Absorption

ABSTRACT Iron absorption from the small intestine is regulated according to the body's needs, increasing in iron deficiency and decreasing in iron overload. It has been proposed that the efficiency of absorption is determined by the amount of iron acquired by developing enterocytes when they are in the crypts of Lieberkůhn and that this regulates expression of iron transporters such as DMT1 in mature enterocytes of the intestinal villi. In the crypts the cells take up iron from plasma transferrin by receptor-mediated endocytosis, a process that is influenced by the hemochromatosis protein, HFE. Hence, the availability of plasma transferrin-bound iron and the expression and function of transferrin receptors (TfR1), HFE and DMT1 should all contribute to the absorptive capacity of villus enterocytes. These aspects of the regulation and mechanism of iron absorption were investigated in genetically normal rats and mice, and in Belgrade anemic ( b/b) rats and HFE knockout mice. In most experiments the function of the TfR1 was assessed by the uptake of radiolabeled transferrin-bound iron given intravenously. Absorption of non-heme iron was measured using closed in situ duodenal loops. The expression and cellular distribution of DMT1 and TfR1 were determined by in situ hybridisation and immunohistochemistry. The uptake of transferrin-bound iron and expression of functional TfR1 was shown to occur mainly in crypt cells and to be proportional to the plasma concentration of iron. It was not impaired by the mutation of DMT1 that occurs in b/b rats but was impaired in HFE knockout mice. Iron absorption was increased in these mice but was still influenced by the level of iron stores, as in normal mice. These results are in accordance with the proposed regulation of iron absorption and suggest that DMT1 is not the only iron transporter operating within endosomes of crypt cells. This view was supported by the failure to detect DMT1 mRNA or protein in crypt cells. Expression of DMT1 mRNA and protein started at the crypt-villus junction and increased to reach highest levels in the mid-villus region. Greater expression was found in iron deficiency and less in iron loaded animals than in controls and in the iron deficient rats most of the protein was present on the brush border membrane. In normal rats the efficiency of iron absorption parallelled the level of DMT1 expression, but in b/b rats absorption was very low and independent of dietary iron content even though DMT1 was present in villus enterocytes. The results confirm the essential role of DMT1 in the uptake phase of non-heme iron absorption. When normal rats previously fed a low iron diet were given a bolus of iron by stomach tube, the subsequent absorption of iron from a test dose placed in the duodenum diminished in parallel with the expression of DMT1 mRNA and protein, commencing within 1hour and reaching low levels by 7 hours. The margination of DMT1 to the brush border membrane disappeared. These results show the level of expression and intracellular distribution and function of DMT1 respond very quickly to the iron content of the diet as well as being affected by storage iron levels.

Iron Treatment Downregulates DMT1 and IREG1 mRNA Expression in Caco-2 Cells

Iron deficiency is the most common nutritional disorder worldwide, whereas pathologic elevations of body iron stores can occur under certain circumstances due to genetic abnormalities or in association with other diseases. The intestine is the exclusive locus of homeostatic regulation of body iron stores, which is accomplished by changes in iron absorption efficiency by largely unknown molecular mechanisms in response to alterations in body iron stores. Recently, a number of novel genes involved in iron metabolism, such as the iron uptake transporter DMT1/DCT1/Nramp2 and the iron export transporter IREG1/ferroportin1/MTP1, have been identified, providing important insights about molecular aspects of intestinal iron absorption and its regulation. The aim of this study was to investigate the effects of iron treatment on DMT1 and IREG1 mRNA expression in Caco-2 cells, a human intestinal cell line. Exposure of the cells to iron (200 micromol/L ferric nitrilotriacetic acid for 72 h) significantly decreased transferrin receptor mRNA (80%), DMT1 mRNA (57%) and IREG1 mRNA (52%). These observations are consistent with the notion of parallel regulation of these iron-responsive genes in vivo to protect the enterocyte from iron toxicity and mediate a decreased efficiency of intestinal iron absorption to prevent iron overload.

Iron

The most useful and appropriate methods for assessing the bioavailability of (nonheme) iron supplements are described. When the supplement can be labeled isotopically, the best method for measuring bioavailability is hemoglobin incorporation, followed by fecal monitoring. Caco-2 cell in vitro systems can be used for rapid screening to predict potential availability for absorption. If the compound cannot be labeled, then the plasma appearance/disappearance of oral iron given together with an intravenous dose of iron isotope can be used to quantify absorption. With oral doses in excess of 25 mg, the 4- to 6-h plasma concentration can provide a qualitative assessment of bioavailability. Approaches for normalizing results to minimize intraindividual and interindividual variability in efficiency of iron absorption are discussed.

Calcium supplementation and iron status of females

Iron balance is regulated in part by the level of iron absorption, which is influenced by iron stores and the level of erythropoietic activity. In short-term absorption studies, dietary calcium and supplemental doses of calcium chloride or calcium carbonate inhibited iron absorption from concomitantly consumed meals. In contrast, several long-term intervention studies of the effect of calcium supplementation on iron status in populations at potentially high risk for compromised iron status failed to show reductions in various indicators of iron status including serum ferritin levels. The evidence suggests that long-term consumption of calcium supplements does not affect overall iron status. An adaptive response, possibly involving an upregulation in the efficiency of iron absorption, has been suggested as a possible explanation for the disparity between the results from short- and long-term studies.

Iron needs during pregnancy: do we need to rethink our targets?

This paper argues that current estimates of the need for absorbed iron, estimates of iron absorption, and hence estimates of iron requirements for pregnant women greatly depend on what is determined as the desirable or target hemoglobin concentration (goal). The existing goal appears to be based on the maximal hemoglobin concentration that can be achieved with iron supplementation of well-nourished women; this is a situation that can be expected to minimize iron absorption efficiency. I am unaware of attempts to define hemoglobin or anemia goals based on functional criteria (health of infant or mother). The current approach may seriously overestimate iron need and discourage food-based programs; furthermore, it may declare operational iron supplementation programs to be failures when, in fact, many programs may be successful in preventing functional effects of iron deficiency anemia. This is illustrated with data from a completed comparative study of daily and weekly iron supplementation. The final plea is to set aside existing traditions and, instead, attempt to develop functional criteria for anemia and establish functional goals of hemoglobin concentrations to be achieved during pregnancy.

Nonheme-iron absorption, fecal ferritin excretion, and blood indexes of iron status in women consuming controlled lactoovovegetarian diets for 8 wk

The characteristics of vegetarian diets suggest that these diets would have lower dietary iron bioavailability than nonvegetarian diets, but there is no evidence of iron deficiency in vegetarians. We evaluated the responsiveness of serum and fecal ferritin to differences in iron absorption from controlled lactoovovegetarian and nonvegetarian diets. Twenty-one women aged 20-42 y with serum ferritin concentrations from 6 to 149 microg/L consumed lactoovovegetarian and nonvegetarian weighed diets for 8 wk each (crossover design). The diets differed substantially in meat and phytic acid contents. Nonheme-iron absorption was measured from the whole diets after 4 wk by using extrinsic 59Fe and whole-body counting. Ferritin in extracts of fecal composites and in serum was measured by enzyme-linked immunosorbent assay the last 2 wk of each diet. Nonheme-iron absorption was less from the lactoovovegetarian diet than from the nonvegetarian diet (1.1% compared with 3.8%; P < 0.01; n = 10). Diet did not affect hemoglobin, transferrin saturation, erythrocyte protoporphyrin, or serum ferritin. Substantially less fecal ferritin was excreted with the lactoovovegetarian diet than with the nonvegetarian diet (1.1 compared with 6.0 microg/d, respectively; P < 0.01; n = 21). This research indicates 1) 70% lower nonheme-iron absorption from a lactoovovegetarian diet than from a nonvegetarian diet; 2) an associated decrease in fecal ferritin excretion, suggesting partial physiologic adaptation to increase the efficiency of iron absorption; and 3) an insensitivity of blood iron indexes, including serum ferritin, to substantial differences in dietary iron absorption for 8 wk.