Longitudinal and Transverse Relaxivity Analysis of Native Ferritin and Magnetoferritin at 7 T MRI.

Magnetite mineralization in human tissue is associated with various pathological processes, especially neurodegenerative disorders. Ferritin's mineral core is believed to be a precursor of magnetite mineralization. Magnetoferritin (MF) was prepared with different iron loading factors (LFs) as a model system for pathological ferritin to analyze its MRI relaxivity properties compared to those of native ferritin (NF). The results revealed that MF differs statistically significantly from NF, with the same LF, for all studied relaxation parameters at 7 T: r1, r2, r2*, r2/r1, r2*/r1. Distinguishability of MF from NF may be useful in non-invasive MRI diagnosis of pathological processes associated with iron accumulation and magnetite mineralization (e.g., neurodegenerative disorders, cancer, and diseases of the heart, lung and liver). In addition, it was found that MF samples possess very strong correlation and MF's relaxivity is linearly dependent on the LF, and the transverse and longitudinal ratios r2/r1 and r2*/r1 possess complementary information. This is useful in eliminating false-positive hypointensive artefacts and diagnosis of the different stages of pathology. These findings could contribute to the exploitation of MRI techniques in the non-invasive diagnosis of iron-related pathological processes in human tissue.

Iron-dependent apoptosis causes embryotoxicity in inflamed and obese pregnancy.

Iron is essential for a healthy pregnancy, and iron supplementation is nearly universally recommended, regardless of maternal iron status. A signal of potential harm is the U-shaped association between maternal ferritin, a marker of iron stores, and risk of adverse pregnancy outcomes. However, ferritin is also induced by inflammation and may overestimate iron stores during inflammation or infection. In this study, we use mouse models to determine whether maternal iron loading, inflammation, or their interaction cause poor pregnancy outcomes. Only maternal exposure to both iron excess and inflammation, but not either condition alone, causes embryo malformations and demise. Maternal iron excess potentiates embryo injury during both LPS-induced acute inflammation and obesity-induced chronic mild inflammation. The adverse interaction depends on TNFα signaling, causes apoptosis of placental and embryo endothelium, and is prevented by anti-TNFα or antioxidant treatment. Our findings raise important questions about the safety of indiscriminate iron supplementation during pregnancy.

Multiple micronutrient supplementation improves micronutrient status in primary school children in Hai Phong City, Vietnam: a randomised controlled trial.

We aimed to determine the efficacy of multiple micronutrient supplementation on the biomarkers of iron, zinc, and vitamin A status across anthropometric status categories in Vietnamese school children. In this 22-week randomised controlled trial, 347 undernourished, normal weight, or overweight/obese children aged 6-9 years were allocated to receive every school day a multiple micronutrient supplement (10 mg iron, 10 mg zinc, 400 µg vitamin A) or a placebo. Haematological indices; circulating ferritin, zinc, and retinol (corrected for inflammation); and C-reactive protein were measured at baseline and 22 weeks. At week 22, linear mixed models showed that mean corpuscular volume increased by 0.3 fL, serum ferritin by 9.1 µg/L, plasma zinc by 0.9 µmol/L, and plasma retinol by 15%, and the prevalence of zinc deficiency decreased by 17.3% points in the intervention group compared to placebo. No intervention effects were found for other haematological indices, or the prevalence of anaemia. Multiple micronutrient supplementation for 22 weeks improved the biomarkers of zinc and vitamin A status and some biomarkers of iron status, and reduced the prevalence of zinc deficiency in Vietnamese school children.Trial registration: This trial was registered on 06/09/2016 at www.anzctr.org.au as ACTRN12616001245482.

The effect of curcumin on serum copper, zinc, and zinc/copper ratio in patients with ß-thalassemia intermedia: a randomized double-blind clinical trial.

Thalassemia intermedia is a subgroup of ß-thalassemia which originates from mutations in the beta-globin gene. Zinc and copper play important roles in the metabolism. Due to its significant therapeutic effects, curcumin has led many studies to focus on curcumin. In a double-blind clinical trial study, 30 patients with beta-thalassemia intermedia with an age range of 20 to 35 years were randomly selected 1:1 to receive either curcumin or placebo for 3 months. Before and after the intervention period, 5 ml of blood was taken to determine the serum levels of zinc and copper. The laboratory tests were checked at baseline and at the end of the treatment. While the serum levels of zinc and zinc/copper significantly increased, the serum levels of copper decreased after 3 months of curcumin intake. In addition, on the basis of baseline characteristics, a negative correlation was found between zinc and body mass index and positive correlations were identified between copper with triglyceride and high-density lipoprotein. Also, the level of ferritin protein in the curcumin group compared to the placebo group showed a significant decrease after 3 months of curcumin use. Therefore, it could be concluded that curcumin might exert a net protective effect on copper toxicity in thalassemia intermedia patients. The investigation also implicated that curcumin represents an approach to regulating zinc homeostasis and may be useful as a complementary treatment of patients with thalassemia intermedia, especially in patients with zinc deficiency or low serum zinc/copper ratio. Clinical Trial Registration Number: IRCT20190902044668N1.

A biomathematical model of human erythropoiesis and iron metabolism.

Anaemia therapy or perisurgical support of erythropoiesis often require both, EPO and iron medication. However, excessive iron medication can result in iron overload and it is challenging to control haemoglobin levels in a desired range. To support this task, we develop a biomathematical model to simulate EPO- and iron medication in humans. We combine our previously established model of human erythropoiesis including comprehensive pharmacokinetic models of EPO applications with a newly developed model of iron metabolism including iron supplementation. Equations were derived by translating known biological mechanisms into ordinary differential equations. Qualitative model behaviour is studied in detail considering a variety of interventions such as bleeding, iron malnutrition and medication. The model can explain time courses of erythrocytes, reticulocytes, haemoglobin, haematocrit, red blood cells, EPO, serum iron, ferritin, transferrin saturation, and transferrin under a variety of scenarios including EPO and iron application into healthy volunteers or chemotherapy patients. Unknown model parameters were determined by fitting the predictions of the model to time series data from literature. We demonstrate how the model can be used to make predictions of untested therapy options such as cytotoxic chemotherapy supported by iron and EPO. Following our ultimate goal of establishing a model of anaemia treatment in chronic kidney disease, we aim at translating our model to this pathological condition in the near future.

Cultivars of biofortified cowpea and sweet potato: Bioavailability of iron and interaction with vitamin A in vivo and in vitro.

The objective of this study was to evaluate the interaction of pro-vitamin A-rich sweet potato on iron bioavailability of biofortified cowpeas, using in vitro Caco-2 cells and in vivo depletion-repletion rat model. Mixtures of conventional rice with cultivars of iron-biofortified (Aracê, Xiquexique, and Tumucumaque) or conventional (Guariba) cowpeas with or without sweet potato biofortified with pro-vitamin A carotenoids were evaluated. The ratio of ferritin/total protein in Caco-2 cells was used as the index of cellular Fe uptake in the in vitro assay. The animal study evaluated the hemoglobin gain, the relative biological value, and the gene expression of transferrin and ferritin proteins by reverse transcription polymerase chain reaction. In the in vitro study, Xiquexique cowpea presented higher bioavailability of iron in the absence of sweet potato, and no difference was observed between the other cultivars of cowpea with and without sweet potato. The in vivo bioavailability (relative biological value of hemoglobin regeneration efficiency) differed statistically only between Guariba groups added to sweet potato and Tumucumaque. Ferritin mRNA expression did not differ between the test and control (ferrous sulfate) groups. Regarding the transferrin mRNA expression, there was a difference between the test and control groups except for the Xiquexique group. The association of rice and beans with sweet potato rich in carotenoids favored the gene expression of proteins involved in the iron metabolism, as well as its bioavailability, corroborating beneficial effects of this mixture. Xiquexique cowpea was shown to be the most promising compared to the other cultivars, exhibiting higher iron content in the digestible fraction, better in vitro bioavailability of iron, and transferrin gene expression. PRACTICAL APPLICATION: Data from the study indicated greater in vitro bioavailability of iron for Xiquexique cowpea and sweet potato mixtures, in addition to the greater regeneration efficiency of hemoglobin in vivo as the bioavailability of iron among biofortified beans, highlighting the promising benefits of biofortification.

In Vitro and In Vivo Evaluations of Mesoporous Iron Particles for Iron Bioavailability.

Chronic renal failure involving hemodialysis results in blood loss during filtration. Iron deficiency and iron deficiency anemia can result. A compensatory increase in iron dosage has many side effects including discomfort. Elemental iron is a highly-pure iron source, which reduces the frequency of dosages; the solubility decreases with increased particle size or pore size. In this study, synthesized mesoporous iron particles (MIPs) were used to relieve iron deficiency anemia. Their bioavailability was measured in vitro by a Caco-2 cell model and in vivo in iron-deficient rats. In vitro bioavailability of MIPs was examined by measuring ferritin content in the Caco-2 cell model. Iron uptake of MIPs was significantly higher than commercial iron particles, which were less porous. In vivo bioavailability of MIPs was examined by measuring body weight gain and red blood cell-related parameters, compared with the bioavailability of standard drug ferrous sulfate in iron-deficient anemic rats. Finally, average hemoglobin content and hemoglobin regeneration efficiency were significantly higher in anemic rats supplemented with commercial iron particles, compared to anemic controls. In the 28-day oral toxicity test, MIPs were not significantly toxic to rat physiology or tissue histopathology. Thus, MIPs may allow effective recovery of hemoglobin in iron deficiency anemia.

Síndrome de piernas inquietas en niños: caracterización clínica / Characterization of restless leg syndrome in children

El Síndrome de piernas inquietas (SPI) o Enfermedad de Willis­Ekbom, es una condición neurológica que afecta al 2-4% de los niños en edad escolar. Etiológicamente se ha relacionado al metabolismo del hierro y a factores genéticos entre otros. En niños aun es una patología poco diagnosticada. Trabajo observacional descriptivo, en el cual se realiza caracterización clínica, según criterios internacionales, en 14 pacientes menores de 18 años, 9 varones. Edad promedio 8 años. Sintomatología inicial variada, desde resistencia a ir a la cama, hasta dibujar sus molestias. En 10 se comprobó déficit de hierro. En 11 pacientes se realizó un polisomnograma, 10 de ellos con un índice elevado de movimientos periódicos de extremidades. El uso de pregabalina y aporte de hierro fue el tratamiento más utilizado. Dos pacientes tenían padres diagnosticados con SPI.

Abstract. The Restless Legs Syndrome (RLS) or Willis-Ekbom Disease is a neurological condition that affects 2-4% of school-age children. Its etiology has been related to the metabolism of iron and genetic factors among others. In children it is still a frequently undiagnosed disorder. This is a descriptive observational report, in which clinical characterization is carried out according to international criteria in 14 patients under 18 years old, 9 boys. Average age is 8 years old. The initial symptomatology was varied, from resistance to comply with bedtime, to drawing their discomfort. In 9, iron deficiency was found. A polysomnogram was performed in 11 patients, 10 of which had a high periodic limb movements index. The use of pregabalin and supplementary iron were the most used treatments. Two patients had parents diagnosed with RLS.

Iron Supplements Containing Lactobacillus plantarum 299v Increase Ferric Iron and Up-regulate the Ferric Reductase DCYTB in Human Caco-2/HT29 MTX Co-Cultures.

Several human interventions have indicated that Lactobacillus plantarum 299v (L. plantarum 299v) increases intestinal iron absorption. The aim of the present study was to investigate possible effects of L. plantarum 299v on the mechanisms of iron absorption on the cellular level. We have previously shown that lactic fermentation of vegetables increased iron absorption in humans. It was revealed that the level of ferric iron [Fe (H2O)5]2+ was increased after fermentation. Therefore, we used voltammetry to measure the oxidation state of iron in simulated gastrointestinal digested oat and mango drinks and capsule meals containing L. plantarum 299v. We also exposed human intestinal co-cultures of enterocytes and goblet cells (Caco-2/HT29 MTX) to the supplements in order to study the effect on proteins possibly involved (MUC5AC, DCYTB, DMT1, and ferritin). We detected an increase in ferric iron in the digested meals and drinks containing L. plantarum 299v. In the intestinal cell model, we observed that the ferric reductase DCYTB increased in the presence of L. plantarum 299v, while the production of mucin (MUC5AC) decreased independently of L. plantarum 299v. In conclusion, the data suggest that the effect of L. plantarum 299v on iron metabolism is mediated through driving the Fe3+/DCYTB axis.

Iron monitoring of male and female rugby sevens players over an international season.

BACKGROUND: Given the likely influence that high training loads, contact-induced hemolysis and female-specific requirements have on the incidence of iron deficiency, characterizing the direction and magnitude of fluctuations in iron status over an international season is important for managing player health and physical performance in rugby sevens. METHODS: Australian national male (N.=27) and female (N.=23) rugby sevens players undertook blood tests at pre-season, mid-season, and end-season. Hemoglobin (Hb), hematocrit (Hct), ferritin, transferrin and transferrin saturation were quantified. Female athletes also reported oral contraceptive use and a subset (N.=7) provided 7-day food diaries to quantify iron intake. RESULTS: Male players typically had a three-fold higher ferritin concentration than females. Pre-season ferritin concentrations in male (151±66 µg/L) and female (51±24 µg/L) players declined substantially (~20%) by mid-season but recovered by end-season. Over the season 23% of female players were classified as iron deficient (ferritin <30 µg/L) and prescribed supplementation. The greatest incidence of iron deficiency in female players occurred mid-season (30%). Oral contraception and dietary iron intake had an unclear influence on female players' ferritin concentration, while age was largely positively correlated (r=0.66±~0.33). CONCLUSIONS: Given the relatively low ferritin concentrations evident in female rugby sevens players, and the potential for a further decline midway through a season when physical load may be at its highest, 6-monthly hematological reviews are suggested in combination with dietary management. Annual screening may be beneficial for male players, with further monitoring only when clinically indicated.

[Siwu decoction improves iron deficiency anemia in infant rats and regulates iron metabolism].

To investigate the effect of Siwu decoction on improving iron deficiency anemia in infant rats and observe its regulatory effects on iron metabolism. SD rats were fed with low iron fodder for 2 weeks, and then the rats with hemoglobin level less than 75 g•L ⁻¹ were screened out and randomly divided into model group, Ferrous succinate 50 mg•kg ⁻¹ group, Siwu decoction 4 g•kg ⁻¹, 8 g•kg ⁻¹ and 16 g•kg ⁻¹ groups. After 4 weeks' gavage administration, Wright-Giemsa's staining of blood smear and HE staining of the livers were conducted, and all rats were tested for blood routine, serum iron, total iron binding capacity, serum ferritin, serum hepcidin and liver hepcidin. The expression levels of liver ferritin, transferrin and transferrin receptor 1 were also detected. The results showed that as compared with normal group, the activity level of model group was decreased, and the color and lustre of auricles and toes were pale white; the number of red blood cells was decreased; the volume was smaller, with an increased zone of central pallor; the body weight and blood routine parameters were decreased significantly; the livers were pale red, and the hepatic cords around thecentral veins were unclear and misaligned; the serum iron, serum ferritin, liver iron levels and the expression of liver ferritin were decreased significantly; the total iron binding capacity, serum hepcidin, liver hepcidin, the expression levels of liver transferrin and transferrin receptor 1 were significantly increased, indicating successful establishment of models. As compared with the model group, activity was increased in Siwu decoction group; the color and lustre of auricles and toes were ruddy; the number of red blood cells was increased; the volume was larger, with a decreased zone of central pallor; the body weight and blood routine parameters were increased significantly; the livers were red, hepatic cords around the central veins were clear and aligned;the serum iron, serum ferritin, liver iron levels and the expression of liver ferritin were significantly increased, the total iron binding capacity, serum hepcidin, liver hepcidin, the expression of liver transferrin and transferrin receptor 1 were decreased significantly. The results demonstrated that Siwu decoction had a certain effect on improving iron deficiency anemia in infant rats, and the mechanism may be associated with the regulatory effect of hepcidin iron metabolism.

Dysregulation of serum NADPH oxidase1 and ferritin levels provides insights into diagnosis of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a common neurodegenerative disease. Oxidative stress is considered as a key modulator in the development of PD. This study aimed to investigate associations between serum NOX1 (NADPH oxidase1), ferritin, selenium (Se), and uric acid (UA) levels and clinical parameters in patients with PD. DESIGN AND METHODS: Serum levels of NOX1, ferritin, Se, and UA were measured in 40 PD patients and 40 healthy individuals. Receiver operating characteristic (ROC) analysis was performed to investigate incremental diagnostic value of each factor in the study groups. RESULTS: Mean serum NOX1 levels were markedly higher in patient group (22.36±5.80ng/mL) versus healthy individuals (8.89±2.37ng/mL) (p<0.001). Significant differences were also observed in the serum concentrations of ferritin (p=0.005) and Se (p=0.001) between patients with PD and healthy individuals. However, the serum concentrations of UA were not statistically significant between the study groups (p=0.560). ROC analysis revealed a diagnostic ability of serum NOX1 and ferritin levels for PD with an area under ROC curve of ≥0.7 (p<0.05) and relatively high sensitivity and specificity. Combination of serum NOX1 and Se along with ferritin and UA levels increased the sensitivity up to 85%, specificity up to 97% and area under the ROC curve up to 0.94 (95% confidence interval (95% CI): 0.89 to 0.99, p<0.001). CONCLUSION: Our findings indicated that serum concentrations of NOX1, ferritin, and Se are significantly higher in the patients with PD. Therefore, these factors can be considered as potential diagnostic biomarkers for diagnosis and monitoring of PD patients. Further studies are required with larger sample size to provide more detailed information about the cognitive profile of participants and the outcome measures.

Management of iron overload in hemoglobinopathies.

Hemoglobinopathies, thalassemia and sickle cell disease are among the most frequent monogenic diseases in the world. Transfusion has improved dramatically their prognosis, but provokes iron overload, which induces multiple organ damages. Iron overload is related to accumulation of iron released from hemolysis and transfused red cell, but also, in thalassemic patients, secondary to ineffective erythropoiesis, which increases intestinal iron absorption via decreased hepcidin production. Transfusion-related cardiac iron overload remains a main cause of death in thalassemia in well-resourced countries, and is responsible for severe hepatic damages in sickle cell disease. Regular monitoring by Magnetic Resonance Imaging (MRI) using myocardial T2* (ms) and Liver Iron Content (LIC) (mg of iron/g dry weight) are now standards of care in chronically transfused patients. Serum ferritin level measurements and record of the total number of transfused erythrocyte concentrates are also helpful tools. Three iron chelators are currently available, deferoxamine, which must be injected subcutaneously or intravenously, and two oral chelators, deferiprone and deferasirox. We will review the main characteristics of these drugs and their indications.

[Prevention of anemia in blood donors]. / Prévention de l'anémie chez les donneurs de sang.

The prevention of anemia of blood donor is a main issue for donor safety and self-supplying. This prevention is done in one hand by donor deferral whose haemoglobin level is under defined threshold and in other hand by preventing iron deficiency. Some subgroups of donors are at increased risk for developing iron deficiency and adverse effects of iron deficiency: premenopausal females; donors with haemoglobin values near the minimum for eligibility and frequent donors. Different interventions could be used: lengthening the inter-donational interval and/or decreasing the number of donations per year; donor ferritin testing to evaluate iron store and at least donor iron supplementation.

Sustained effectiveness of weekly iron-folic acid supplementation and regular deworming over 6 years in women in rural Vietnam.

BACKGROUND: Weekly iron-folic acid (IFA) supplementation and regular deworming is effective for the prevention of iron deficiency and anaemia in women of child-bearing age. Between 2006 and 2013, a program of weekly IFA and biannual deworming was implemented in Yen Bai province, Vietnam. In this study we aimed to determine the effectiveness of the program in reducing anaemia and the prevalence of hookworm infection after 72 months (six years). METHODS: This prospective cohort study followed up a cohort of 389 women of child-bearing age from baseline until six years after the introduction of the weekly IFA (one tablet containing 200 mg ferrous sulphate, 0.4mg folic acid) and deworming (one 400mg tablet of albendazole given twice yearly) program (May 2006 to 2012). In each of the six surveys (baseline and five follow-up surveys) we measured haemoglobin and ferritin, and the burden of soil transmitted helminth (STH) infections, and in the 72 month survey we also administered a questionnaire to assess adherence and possible impediments to participating in the program. RESULTS: Two hundred and fifty six (65.8%) of the original 389 women enrolled in the cohort attended the final 72 month survey. Haemoglobin levels were 122 g/L [95% C.I. 120, 124] at baseline and increased to 135g/L [95% C.I. 133, 138] after 72 months. The prevalence of anaemia was 37.8% [95% C.I. 31.0, 44.7] at baseline and reduced to 14.3% [95% C.I. 9.5, 19.1]. Hookworm infection prevalence, 75.9% [95% C.I. 68.1, 83.8] at baseline, reduced to 10.2% [95% C.I. 5.4, 15.0] with no moderate or heavy intensity infections. Seventy-two percent of participants reported still taking at least 75% of the weekly supplements, and 85.0% had taken the most recent deworming treatment. DISCUSSION: Anaemia rates fell significantly during the six-year program, and STH infections were eliminated as a public health risk. Adherence was well maintained but long-term sustainability is challenging in the absence of ongoing external support.

Impact of Oxidative Stress in Premature Aging and Iron Overload in Hemodialysis Patients.

Background. Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening. Methods. A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR. Results. Patients in Group B had significantly higher plasma TBARS (p = 0.008), carbonyls (p = 0.0004), and urea (p = 0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A (p = 0.0017). We observed a statistically significant association between relative telomere length and ferritin levels (r = -0.37, p = 0.001). Relative telomere length was inversely related to time on hemodialysis (r = -0.27, p = 0.02). Conclusions. Our findings demonstrate that iron overload was associated with increased levels of oxidative stress and shorter relative telomere length.

Impact of Sorghum Supplementation on Growth and Micronutrient Status of School Going Children in Southern India - A Randomized Trial.

OBJECTIVES: To study the impact of sorghum diet on growth, and micronutrient status of school going children for a period of 8 mo. METHODS: Children (n = 160 boys and n = 160 girls) aged between 9 to 12 y were randomly allocated into two groups (n = 80 in the control and n = 80 in the experimental group) to receive 60% sorghum diet and 40% of rice diet (Exp G) and regular rice diet (100%; CG). Anthropometric indices and biochemical parameters were measured at baseline and at 8 mo using standardized methods. RESULTS: The growth rate was significantly higher (p < 0.01) in the Exp G of girls, whereas in boys it was in the CG. Hemoglobin (Hb), serum ferritin, albumin, retinol binding protein (RBP) and iron levels were significantly improved (p < 0.05) in the Exp G of both the genders and in boys, serum folic acid and calcium levels were also improved with sorghum diet. CONCLUSIONS: Serum micronutrient status, in terms of hemoglobin, serum folic acid, albumin, RBP, ferritin, calcium and iron can be improved with sorghum supplementation in school going children.

[Management of anemia in patients with inflammatory bowel disease].

Anemia is one of the commonest extraintestinal manifestations of inflammatory bowel disease (IBD). The pathogenesis of anemia in IBD is complex but iron deficiency combined with inflammation is the most common factor related to the development of anemia. However, other causes such as vitamin B12 and folate deficiency, hemolysis, myelosuppression and drug also should not be overlooked. In addition to ferritin, inflammatory markers and new biochemical parameters such as hepcidin and ferritin index are being tested as diagnostic a tool. First step for treatment is disease activity control and iron supplementation. Although oral iron is widely used, intravenous iron therapy should be considered in patients who are intolerant to oral iron therapy, have severe and refractory anemia or are in active disease state. Recently, new intravenous iron formulations have been introduced and due to their safety and easy usage, they have become the standard treatment modality for managing anemia in IBD. Erythropoietin and transfusion can be considered in specific situations. Vitamin B12 and folate supplementation is also important in patients who are deficient of these micronutrients. Since anemia in IBD patients could significantly influence the disease outcome, further studies and standard guideline for IBD are needed.

Higher iron pearl millet (Pennisetum glaucum L.) provides more absorbable iron that is limited by increased polyphenolic content.

BACKGROUND: Our objective was to compare the capacity of iron (Fe) biofortified and standard pearl millet (Pennisetum glaucum L.) to deliver Fe for hemoglobin (Hb)-synthesis. Pearl millet (PM) is common in West-Africa and India, and is well adapted to growing areas characterized by drought, low-soil fertility, and high-temperature. Because of its tolerance to difficult growing conditions, it can be grown in areas where other cereal crops, such as maize, would not survive. It accounts for approximately 50% of the total world-production of millet. Given the widespread use of PM in areas of the world affected by Fe-deficiency, it is important to establish whether biofortified-PM can improve Fe-nutriture. METHODS: Two isolines of PM, a low-Fe-control ("DG-9444", Low-Fe) and biofortified ("ICTP-8203 Fe",High-Fe) in Fe (26 µg and 85 µg-Fe/g, respectively) were used. PM-based diets were formulated to meet the nutrient requirements for the broiler (Gallus-gallus) except for Fe (Fe concentrations were 22.1±0.52 and 78.6±0.51 µg-Fe/g for the Low-Fe and High-Fe diets, respectively). For 6-weeks, Hb, feed-consumption and body-weight were measured (n = 12). RESULTS: Improved Fe-status was observed in the High-Fe group, as suggested by total-Hb-Fe values (15.5±0.8 and 26.7±1.4 mg, Low-Fe and High-Fe respectively, P<0.05). DMT-1, DcytB, and ferroportin mRNA-expression was higher (P<0.05) and liver-ferritin was lower (P>0.05) in the Low-Fe group versus High-Fe group. In-vitro comparisons indicated that the High-Fe PM should provide more absorbable-Fe; however, the cell-ferritin values of the in-vitro bioassay were very low. Such low in-vitro values, and as previously demonstrated, indicate the presence of high-levels of polyphenolic-compounds or/and phytic-acid that inhibit Fe-absorption. LC/MS-analysis yielded 15 unique parent aglycone polyphenolic-compounds elevated in the High-Fe line, corresponding to m/z = 431.09. CONCLUSIONS: The High-Fe diet appeared to deliver more absorbable-Fe as evidenced by the increased Hb and Hb-Fe status. Results suggest that some PM varieties with higher Fe contents also contain elevated polyphenolic concentrations, which inhibit Fe-bioavailability. Our observations are important as these polyphenols-compounds represent potential targets which can perhaps be manipulated during the breeding process to yield improved dietary Fe-bioavailability. Therefore, the polyphenolic and phytate profiles of PM must be carefully evaluated in order to further improve the nutritional benefit of this crop.

Effect of supplementation with iron fortified biscuits on the hemoglobin status of children in rural areas of Shimoga, Karnataka.

OBJECTIVE: To assess the efficacy of iron fortified biscuits, in high and low dosages, on the hemoglobin levels of anemic school going children aged 6 to 12 y. METHODS: The nutrition intervention was conducted in primary schools located in villages at Shimoga district, Karnataka. School children aged 6 to 12 y who were anemic, with hemoglobin level <11.5 g/dl were considered for the nutrition intervention. The sampling design undertaken was quasi experimental with pre and post stages of outcome. The children enrolled were divided into two groups. One group received high dosage of iron fortified biscuits (30 mg of elemental iron/6 biscuits) and the second group received a relatively lower dosage of iron fortified biscuits (1.8 mg of elemental iron/6 biscuits) for a period of 120 d. The hemoglobin levels were estimated pre and post fortified biscuit supplementation by cyanomethemoglobin method. RESULTS: There was an increase in the mean hemoglobin level of children which was found to be higher in group I (high iron fortified biscuits) (1.06 g/dl) compared to group II (low iron fortified biscuits) (0.41 g/dl), significant at 0.01 level (t = 3.84**). CONCLUSIONS: In the current nutrition intervention, both high and low iron fortified biscuits led to a significant enhancement in the body weight and hemoglobin status of anemic school children in a rural setup. The nutrition intervention clearly highlights biscuits as an ideal fortification vehicle for addressing anemia.