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Iron deficiency anemia (IDA) is probably the most ignored situation in the world of malnutrition-largely due to its slow progression. Multiple reasons can be attributed as the cause of IDA, which is not limited to any specific region or population; therefore, making it a matter of global concern. Despite the human body's ability to absorb and conserve iron stores, the gradual loss due to various physiological conditions leads to net deficiency of iron. Countless commercial iron supplements are available, but at given physiological conditions, almost all of these "Bio-not-available" iron forms quite often become ineffective. World Health Organization and other government bodies have jointly developed health advisories and tried to developed nutrition supplements several times in the last two decades. IDA, when combined with other disease conditions, becomes a life-threatening situation. At the same time, an overdose of iron could also be very harmful to the body. Therefore, it is important to deal with this situation with caution. This article covers iron metabolism, available options for iron supplementation, regulatory aspects and strategies to prevent IDA.

Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder caused by genetic mutations on TMPRSS6 gene which encodes Matriptase2 (MT2). An altered MT2 cannot appropriately suppress hepatic BMP6/SMAD signaling in case of low iron, hence hepcidin excess blocks dietary iron absorption, leading to a form of anemia resistant to oral iron supplementation. In this study, using the IRIDA mouse model Mask, we characterized homozygous (msk/msk) compared to asymptomatic heterozygous (msk/wt) mice, assessing the major parameters of iron status in different organs, at different ages in both sexes. The effect of carbonyl iron diet was analyzed as control iron supplementation being used for many studies in mice. It resulted effective in both anemic control and msk/msk mice, as expected, even if there is no information about its mechanism of absorption. Then, we mainly compared two forms of oral iron supplement, largely used for humans: ferrous sulfate and Sucrosomial iron. In anemic control mice, the two oral formulations corrected hemoglobin levels from 11.40 ± 0.60 to 15.38 ± 1.71 g/dl in 2-4 weeks. Interestingly, in msk/msk mice, ferrous sulfate did not increase hemoglobin likely due to ferroportin/hepcidin-dependent absorption, whereas Sucrosomial iron increased it from 11.50 ± 0.60 to 13.53 ± 0.64 g/dl mainly in the first week followed by a minor increase at 4 weeks with a stable level of 13.30 ± 0.80 g/dl, probably because of alternative absorption. Thus, Sucrosomial iron, already used in other conditions of iron deficiency, may represent a promising option for oral iron supplementation in IRIDA patients., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Anemia, iron deficiency, and iodine deficiency are problems of important public health concern in many parts of the world, with consequences for the health, development, and work capacity of populations. Several countries are beginning to implement double fortified salt (DFS) programs to simultaneously address iodine and iron deficiencies., Objective: Our objective was to summarize the evidence for efficacy and effectiveness of DFS on the full range of status and functional outcomes and across different implementation and evaluation designs essential to successful interventions., Methods: We conducted a systematic review and meta-analysis of published and gray literature examining the effects of DFS on nutritional status, cognition, work productivity, development, and morbidity of all population groups. We searched for articles in Medline, Embase, CINAHL, Cochrane Central Register, and ProQuest for randomized trials, quasi-randomized trials, and program effectiveness evaluations., Results: A total of 22 studies (N individuals = 52,758) were included. Efficacy studies indicated a significant overall positive effect on hemoglobin concentration [standardized mean difference (95% CI): 0.33 (0.18, 0.48)], ferritin [0.42 (0.08, 0.76)], anemia [risk ratio (95% CI): 0.80 (0.70, 0.92)], and iron deficiency anemia [0.36 (0.24, 0.55)]. Effects on urinary iodine concentration were not significantly different between DFS and iodized salt. The impact on functional outcomes was mixed. Only 2 effectiveness studies were identified. They reported programmatic challenges including low coverage, suboptimal DFS quality, and storage constraints., Conclusions: Given the biological benefits of DFS across several populations in efficacy research, additional evaluations of robust DFS programs delivered at scale, which consider effective implementation and measure appropriate biomarkers, are needed., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2021.)

Iron plays an essential role in preventing iron deficiency anemia and ensuring the healthy growth of animals. The special physiological condition of piglets is the main cause of iron deficiency. Iron metabolism in the intestine is the basis for understanding the effects of iron on the health of piglets. In order to scientifically evaluate dietary iron supplementation doses, it is necessary to recognize the effects of iron deficiency and iron overload on piglet intestinal health. Besides, iron as a cofactor is essential for the growth of microorganisms, and microorganisms compete with the host to absorb iron. Under the stress of iron deficiency and iron overload, various control schemes (such as precise nutrition, element balance, elimination of oxidation, etc.) are effective measures to eliminate adverse effects. In this review, we comprehensively review recent findings on the effects of iron deficiency and iron overload on intestinal health. This review will provide a rational design strategy to achieve a reasonable iron supplement, which will guide the use of iron in animal husbandry.

Background: Universal home fortification of complementary foods with iron-containing multiple micronutrient powders (MNPs) is a key intervention to prevent anaemia in young children in low-income and middle-income countries. However, evidence that MNPs might promote infection raises uncertainty about whether MNPs give net health benefits and are cost-effective. We aimed to determined country-specific net benefit or harm and cost-effectiveness of universal provision of MNPs to children aged 6 months., Methods: We developed a microsimulation model to estimate net country-specific disability-adjusted life-years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) due to anaemia, malaria, and diarrhoea averted (or increased) by provision of a 6-month course of MNPs to children aged 6 months, compared with no intervention, who would be followed up for an additional 6 months (ie, to age 18 months). Anaemia prevalence was derived from Demographic and Health Surveys or similar national surveys, and malaria and diarrhoea incidence were sourced from the Global Burden of Disease Study. Programme and health-care costs were modelled to determine cost per DALY averted (US$). Additionally, we explored the effects of reduced MNP coverage in a sensitivity analysis., Findings: 78 countries (46 countries in Africa, 20 in Asia or the Middle East, and 12 in Latin America) were included in the analysis, and we simulated 5 million children per country. 6 months of universal distribution of daily MNPs, assuming 100% coverage, produced a net benefit (DALYs averted) in 54 countries (24 in Africa, 19 in Asia and the Middle East, 11 in Latin America) and net harm in 24 countries (22 in Africa, one in Asia, and one in Latin America). MNP intervention provided a benefit on YLDs associated with anaemia, but these gains were attenuated and sometimes reversed by increases in YLLs associated with malaria and diarrhoea, reducing the benefits seen for DALYs. In the 54 countries where MNP provision was beneficial, the median benefit was 28·1 DALYs averted per 10 000 children receiving MNPs (IQR 20·6-40·4), and median cost per DALY averted was $3576 (IQR 2474-4918). DALY effects positively correlated with moderate and severe anaemia prevalence in Asia, the Middle East, and Latin America, but correlated inversely in Africa. Suboptimal coverage markedly reduced DALYs averted and cost-effectiveness., Interpretation: Net health benefits of MNPs vary between countries, are highest where prevalence of moderate and severe anaemia is greatest but infection prevalence is smallest, and are ameliorated when coverage of the intervention is poor. Our data provide country-specific guidance to national policy makers., Funding: International Union of Nutrition Sciences., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

To develop a novel delivery scheme to bridge the Mexican health system with highly isolated indigenous communities by involving naturally occurring social links: households and boarding schools. This was a school-based placebo-controlled trial with a follow-up period of 16 weeks. Children whose mothers fulfilled the inclusion criteria for anemia acted as iron supplement carriers between schools and homes. Adherence was measured based on teachers' and mothers' records. An effectiveness sub-analysis assessed changes in biochemical profiles according to random allocation to either supplementation or placebo groups. There was an overall high adherence in both groups. Analyses revealed that schooling years, literacy, and walking times played a role in high adherence. Logistic regression showed that women had higher adherence odds on the basis of household size, walking times, and previous inclusion in supplement distributions. Adherence significantly decreased the proportion of anemia by 48.2% in the intervention group. The difference at baseline and endpoint significantly reduced the number of iron-deficient anemic women by 67.7% in the supplementation group. This delivery method is a valid alternative to the conventional efforts used to reach Tarahumara indigenous communities, and could also have the potential to be piloted to tackle other health issues hindering these marginalized communities.

Background: The study aimed to analyze anemia management in non-pregnant, and non-menopausal women aged from 18 to 50 years old, in a French primary care setting., Methods: An observational descriptive prospective study was conducted between November 2018 and February 2019. Inclusion criteria were as followed: anemia diagnosed in women aged from 18 to 50, not pregnant and not menopausal. Quantitative and qualitative data were anonymized and collected through an electronic survey. Investigating general practitioners completed the questionnaire for each newly diagnosed woman. Mean values and medians were calculated for the quantitative data. Answers to the open questions were encoded manually and proportions of the different modalities have been calculated., Results: Altogether, 43 women with anemia were ascertained. Moderate microcytic anemia, due to an iron deficiency in a context of menorrhagia, was the most observed anemia profile. The mean value of hemoglobin was 10.5 ± 1 g/dl. Among these women: 32 (74%) presented an iron deficiency, 17 (53%) had inappropriate intakes, and 9 (28%) reported menorrhagia. For 17 (40%) women, unnecessary or inappropriate exams were prescribed. The investigations did not allow to establish a differential diagnosis for 12 women (28%). Even for similar clinical situations, anemia management was variable. Among the women who presented iron deficiency, 15 (47%) were informed about an iron-rich diet and received a daily iron supplementation of ferrous sulfate between 80 mg and 160 mg., Conclusions: Our study highlights that, in the absence of specific national guidelines for anemia management in non-pregnant, non-menopausal women in primary care settings, French GPs undergo various clinical management strategies leading to a heterogeneous, sometimes inappropriate follow-up. Women with iron deficiency were prescribed higher daily iron supplementation than recommended, according to new evidence, suggesting a maximal daily dose of 50 mg of elementary iron in a context of Hepcidin up-regulation in the case of an iron overload. Additional longitudinal studies with a bigger sample size and randomized controlled trials are needed to confirm our results and to elaborate national guidelines.

Background: It has been the impression of pediatricians at the Terem Clinic for African asylum seekers in Tel Aviv that they encounter large numbers of anemic children. The objectives of this study were 1) to quantify the prevalence of anemia among African African asylum seeking children treated in the Terem Clinic for refugees in Tel Aviv; 2) to compare it to the rates among Jewish Israeli children; 3) and to correlate it with their nutritional iron intake. Overall, this effort aims at informing changes in policies and practices that will ensure healthy development of African asylum seeking children in Israel., Methods: The prevalence of anemia was calculated for all toddlers and children under the age of twelve years visiting the refugee clinic and compared to the recently reported rates of anemia among urban Jewish Israeli children of similar ages; Nutritional iron intake was calculated in a subgroup by a food frequency questionnaire translated to Amharic and Tigrinya., Results: Mean age of the children (SD) was 2.96 yr. (SD 2.77) and mean hemoglobin 10.88 g/dl (1.47). Out of 386 eligible children, 131(34%) were anemic, fourfold more prevalent than reported among 263 Jewish toddlers and young children of the same age group [(11%), OR 4.15(95% ci 2.67-6.43)]. In a subgroup (n = 26) investigated for amount of daily iron intake, 46.2% did not receive the recommended daily allowance for their age. Nine of them had received iron supplements., Conclusions: Low hemoglobin levels are four-fold more prevalent among the African asylum seeking children. The dietary data suggest iron deficiency as a major cause, although other etiologies need to be ruled out. Because of the adverse long term impact of early anemia on child development, new policies need to be developed to ensure that refugee children develop in a healthy manner. These should include routine mandatory supplements of iron for all refugee children, in parallel to developing an educational program for parents how to achieve iron-sufficient diets for their children. Further research is needed to guide public health action for these children.

This review focuses on pre- and post-natal iron supplementation in malaria endemic settings. Although iron supplementation can reduce iron deficiency, malaria infection may counteract this effect by the increase of hepcidin, and iron supplementation may further worsen malaria infection by providing additional iron for the parasites. However, most iron supplementation intervention studies in pregnant women with malaria have not shown a negative impact, although malaria treatment with iron supplementation may be beneficial in terms of improving birth outcomes. In infants and young children in malaria endemic settings, the adverse effects of iron supplementation has been well documented and malaria prevention and treatment with iron supplementation is recommended. Besides fostering the growth of malaria parasites, iron may also promote potential pathogens in the gut and cause an inflammatory response in young children. Overall, iron supplementation is beneficial for treating iron deficiency, but needs to be considered in the context of malaria prevention and treatment in pregnant women, infants and young children for safety and effectiveness., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Anemia prevalence in India remains high despite preventive iron supplementation programs. Consequently, concurrent national policies of iron fortification of staple foods have been initiated., Objectives: This study evaluated the relation between dietary iron intake and anemia (hemoglobin <12 g/dL) in women of reproductive age (WRA; 15-49 y) with respect to iron fortification in India., Methods: Data from 2 national surveys were used. Data on hemoglobin in WRA were sourced from the National Family Health Survey-4, whereas dietary intakes were sourced from the National Sample Survey. Adjusted odds for anemia with increasing iron intake were estimated, along with the effect of modulating nutrients such as vitamins B-12 and C, from statistically matched household data from the 2 surveys. The risks of inadequate (less than the Estimated Average Requirement for WRA) and excess (more than the tolerable upper limit for WRA) intakes of iron were estimated by the probability approach., Results: The relation between iron intake and the odds of anemia was weak (OR: 0.992; 95% CI: 0.991, 0.994); increasing iron intake by 10 mg/d reduced the odds of anemia by 8%. Phytate and vitamin B-12 and C intakes modified this relation by reducing the odds by 1.5% when vitamin B-12 and C intakes were set at 2 μg/d and 40 mg/d, respectively. The additional intake of 10 mg/d of fortified iron reduced the risk of dietary iron inadequacy from 24-94% to 9-39% across states, with no risk of excess iron intake. Approximately doubling this additional iron intake reduced the risk of inadequacy to 2-12%, but the risk of excess intake reached 22%., Conclusions: Providing fortified iron alone may not result in substantial anemia reduction among WRA in India and could have variable benefits and risks across states. Geographically nuanced dietary strategies that include limited fortification and the intake of other beneficial nutrients should be carefully considered., (Copyright © American Society for Nutrition 2019.)

Objective: To use quantitative electroencephalography (qEEG) to assess the impact of iron-deficiency anemia on central nervous system maturation in the first year of life., Method: Twenty-five infants (3-12 months old) presenting ferropenic anemia (IDA) and 25 healthy controls (CTL1), matched by age/gender with the former, were studied in two stages. Electroencephalogram during spontaneous sleep was recorded from all participants; the fast Fourier transform was calculated to obtain absolute power (AP) and relative power (RP) qEEG measures. In the first stage, a qEEG comparison between CTL1 and IDA was performed. Second stage consisted in comparing qEEG of the IDA infants before and after supplementation with iron (IDA-IS group), and comparing qEEG of the IDA-IS group with another control age-matched group (CTL2). Non-parametric multivariate permutation tests (NPT) were applied to assess differences between CTL1 and IDA groups, as well as IDA vs. IDA-IS, and IDA-IS vs. CTL2., Results: More power in slow frequency bands and less power in fast frequency bands in 64% of IDA babies were observed. NPT evinced higher alpha AP and RP (P < 0.001), less theta AP, and less delta and theta RP in CTL1 than in IDA. After iron-restoration therapy, alpha AP and RP increased while theta AP and theta and delta RP decreased, reaching almost normal values., Discussion: This work reveals CNS developmental delay through the study of qEEG (less rapid and more slow frequencies) which recovered significantly with iron supplementation. It is concluded that IDA constitutes a high risk factor for a lag of CNS maturation.

Competing Interests: Competing interests: None declared.

Introduction: Here, we investigated inflammatory signs of peripheral nerves in leptin-deficient obese ob/ob mice and the modulating effects of the exogenous iron load., Methods: Ob/ob and ob/+ control mice were fed with high, standard, or low iron diet for four months., Results: We found intraepidermal nerve fiber degeneration in foot skin and low-grade neuropathic abnormalities including mildly slowed motor and compound sensory nerve conduction velocities and low-grade macrophage and T-cell infiltration without overt neuropathology in sciatic nerves of all ob/ob mice. Low dietary iron load caused more pronounced abnormalities than high iron load in ob/ob mice., Discussion: Our data suggest that dietary non-heme iron deficiency may be a modulating factor in the pathogenesis of peripheral neuropathy in obese ob/ob mice with metabolic syndrome. Once the mechanisms can be further elucidated, how low dietary iron augments peripheral nerve degeneration and dysfunction via pro-inflammatory pathways and new therapeutic strategies could be developed., Abbreviations: CMAP: compound muscle action potential; cSNCV: compound sensory nerve conduction velocity; IENFD: intraepidermal nerve fiber density; LDL: low-density lipoprotein; MetS: metabolic syndrome; MNCV: motor conduction velocity; NCV: nerve conduction velocity; PN: peripheral neuropathy; PNS: peripheral nervous system; STZ: streptozotocin; T2D: type 2 diabetes mellitus; TNF alpha: tumor necrosis factor alpha; WHO: World Health Organization.

Microalgae are potential iron supplements for improving iron deficiency through an unknown mechanism. To analyze the increase in non-heme iron absorption caused by microalgae, six different microalgal feeds were prepared from Spirulina, Chlorella and Synechococcus sp. PCC 7002 as the main source of dietary iron (25 mg kg-1; denoted as H-Sp, H-Ch, and H-Sy, respectively) or as a partial source of dietary iron (5 mg kg-1; denoted as L-Sp, L-Ch, and L-Sy, respectively) to suppress iron-deficiency anemia in rats. The hemoglobin regeneration efficiencies in anemic rats were in the order ferric citrate (34.7 ± 1.8%) < H-Ch (49.9 ± 4.1%) ≈ H-Sy (50.6 ± 5.3%) ≈ L-Sp (46.9 ± 6.2%) ≈ L-Ch (43.1 ± 6.9%) ≈ L-Sy (43.5 ± 2.4%) ≈ FeSO4 (47.2 ± 4.9%) < H-Sp (54.8 ± 5.5%). The percentage content of intestinal nanosized iron in the H-Sp, H-Ch, and H-Sy treatment groups was significantly higher than that in the L-Sp, L-Ch, and L-Sy groups, and was significantly higher in the microalgal diet groups than in the ferric citrate group, providing strong evidence for nanosized iron supplementation from microalgae. Overall, microalgae, especially Spirulina, are functional iron nutritive fortifiers that can supply intestinal nanosized iron.

Several epidemiological studies investigated the relationship between dietary intake of essential trace elements and the risk of esophageal cancer (EC), yielding inconsistent results. We therefore conducted a systematic meta-analysis to investigate and quantify the putative association between the intake of various essential trace elements and the risk of EC. We searched Embase, PubMed, and Web of Science for eligible articles published through April 2018 reporting the odds ratio (OR) with 95% confidence interval (95% CI). Pooled results were then calculated using fixed and random effect models. A total of 20 articles containing 4855 cases from 1 387 482 participants were included in our analysis. We found a significant inverse correlation between total iron intake and the risk of EC (OR = 0.81, 95% CI: 0.70-0.94), particularly in Asian populations. A dose-response analysis revealed that each 5 mg/day increase in total iron intake was associated with a 15% reduction in EC risk (OR = 0.85, 95% CI: 0.79-0.92). In contrast, each 1 mg/day increase in heme iron intake was associated with a 21% increase in EC risk (OR = 1.21, 95% CI: 1.02-1.45). Lastly, a pooled risk estimate revealed that each 5 mg/day increase in zinc intake was associated with a 15% reduction in EC risk (OR = 0.85, 95% CI: 0.77-0.93). Taken together, our analysis indicates that increased dietary intake of total iron and zinc, as well as decreased heme iron intake, may be associated with a lower risk of developing esophageal cancer. These findings have important public health implications with respect to preventing this relatively common form of cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Iron deficiency (ID) and vitamin D deficiency (VDD) are significant pediatric health issues in New Zealand and Australia and remain prevalent micronutrient deficiencies in young children globally., Objective: We aimed to investigate the effect of a micronutrient-fortified, reduced-energy growing-up milk (GUMLi) compared with cow milk (CM) consumed for 1 y on dietary iron and vitamin D intakes and the status of New Zealand and Australian children at 2 y of age., Methods: The GUMLi Trial was a multicenter, double-blind, randomized controlled trial in 160 healthy 1-y-old New Zealand and Australian children conducted in 2015-2017. Participants were randomly assigned 1:1 to receive GUMLi (1.7 mg Fe/100 mL; 1.3 µg cholecalciferol/100 mL) or CM (0.02 mg Fe/100 mL; 0.06 µg cholecalciferol/100 mL) for 12 mo. Secondary outcomes, reported here, included change in dietary iron and vitamin D intakes, iron status, and 25-hydroxyvitamin D [25(OH)D] concentrations from blood samples at age 2 y. All regression models were adjusted for baseline outcome and study center., Results: GUMLi was a large contributor to dietary intakes of iron and vitamin D after 12 mo when compared with intakes from food and CM. The adjusted mean difference between groups for serum ferritin concentrations was 17.8 µg/L (95% CI: 13.6, 22.0 µg/L; P < 0.0001), and for 25(OH)D it was 16.6 nmol/L (95% CI: 9.9, 23.3 nmol/L; P < 0.0001). After 12 mo, ID was present in 16 (24%) participants in the CM group and 5 (7%) participants in the GUMLi group (P = 0.009), and the prevalence of VDD in the CM group increased to 14% (n = 10) and decreased to 3% (n = 2) (P = 0.03) in the GUMLi group., Conclusion: In comparison with CM, GUMLi significantly improved dietary iron and vitamin D intakes and the iron and vitamin D status of healthy children at 2 y of age. This trial was registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12614000918628.

This study aimed to investigate the validity of patient-reported anemia and therapeutic use of iron supplements, compared to hemoglobin values recorded on the patient's prenatal card. The study used data from the 2015 Pelotas (Brazil) birth cohort. For validation of self-reported anemia, we included all mothers with hemoglobin values recorded on their prenatal card (N = 3,419), while validation of self-reported therapeutic use of iron supplements included those who had hemoglobin values recorded on their prenatal care and who reported having used medicines containing ferrous sulfate during pregnancy. Anemia was defined as at least one record of hemoglobin ≤ 11g/dL on the prenatal card (gold standard). Prevalence of anemia according to the gold standard was 35.9% (34.3-37.5), while patient-reported anemia was 42.2% (40.8-43.7), and patient-reported therapeutic use of iron supplements was 43.2% (41.3-45.1). Sensitivity of patient-reported anemia was 75.2% (72.8-77.6) and specificity was 75.1% (73.3-76.9). For patient-reported therapeutic use of iron supplements, sensitivity was 66.4% (63.5-69.2) and specificity was 71.9% (69.7-74.0). Specificity of patient-reported anemia and patient-reported therapeutic use of iron supplements in mothers with ≥ 12 years of schooling was 78.4% (75.4-81.4) and 79.5% (76.1-82.9), respectively. In the study population, for every five postpartum women that reported anemia or therapeutic use of iron supplements, three were telling the truth. The specificity of both self-reports was high in mothers with ≥ 12 years of schooling.

Double-fortified salt (DFS) containing iron and iodine has been proposed as a feasible and cost-effective alternative for iron fortification in low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis from randomized and quasi-randomized controlled trials to 1) assess the effect of DFS on biomarkers of iron status and the risk of anemia and iron deficiency anemia (IDA) and 2) evaluate differential effects of DFS by study type (efficacy or effectiveness), population subgroups, iron formulation (ferrous sulfate, ferrous fumarate, and ferric pyrophosphate), iron concentration, duration of intervention, and study quality. A systematic search with the use of MEDLINE, EMBASE, Cochrane, Web of Science, and other sources identified 221 articles. Twelve efficacy and 2 effectiveness studies met prespecified inclusion criteria. All studies were conducted in LMICs: 10 in India, 2 in Morocco, and 1 each in Côte d'Ivoire and Ghana. In efficacy studies, DFS increased hemoglobin concentrations [standardized mean difference (SMD): 0.28; 95% CI: 0.11, 0.44; P < 0.001] and reduced the risk of anemia (RR: 0.59; 95% CI: 0.46, 0.77; P < 0.001) and IDA (RR 0.37; 95% CI: 0.25, 0.54; P < 0.001). In effectiveness studies, the effect size for hemoglobin was smaller but significant (SMD: 0.03; 95% CI: 0.01, 0.05; P < 0.01). Stratified analyses of efficacy studies by population subgroups indicated positive effects of DFS among women and school-age children. For the latter, DFS increased hemoglobin concentrations (SMD: 0.32; 95% CI: 0.03, 0.60; P < 0.05) and reduced the risk of anemia (SMD: 0.48; 95% CI: 0.34, 0.67; P < 0.001) and IDA (SMD: 0.37; 95% CI: 0.25, 0.54; P < 0.001). Hemoglobin concentrations, anemia prevalence and deworming at baseline, sample size, and study duration were not associated with effect sizes. The results indicate that DFS is efficacious in increasing hemoglobin concentrations and reducing the risk of anemia and IDA in LMIC populations. More effectiveness studies are needed.

Nearly two thirds of young children are anaemic in Bihar, India. Paediatric iron and folic acid syrup (IFAS) and multiple micronutrient powders (MNPs) are two evidence-based interventions to prevent anaemia. Using a randomized crossover design, we examined the acceptability of IFAS versus MNPs for children 6-23 months. In a catchment area of 2 health centres in Bihar, health front-line workers (FLWs) delivered either (a) IFAS twice weekly or (b) MNPs for 1 month followed by the other supplementation strategy for 1 month to the same families (NCT02610881). Household surveys were conducted at baseline (N = 100), 1 month after receiving the first intervention (1 month; N = 95), and 1 month after the second intervention (2 months; N = 93). Focus group discussions (10 FLWs) and in-depth interviews (20 mothers) were held at 1 and 2 months. We used chi-square and Fisher exact tests to test mothers' product preferences. Qualitative data were analysed using MaxQDA and Excel employing a thematic analysis approach. There was high adherence and acceptability for both products (>80%). There was no significant difference in preference (p < .05) on perceived benefits (39% MNPs, 40% IFAS), side effects (30% MNPs, 30% IFAS), ease of use (42% IFAS, 31% MNPs), child preference (45% IFAS, 37% MNPs), and maternal preference (44% IFAS, 34% MNPs). Mothers and FLWs indicated that the direct administration of IFAS ensured that children consumed the full dose, and MNPs intake depended on the quantity of food consumed, especially among younger children, which emphasizes the need to integrate supplementation with the promotion of optimal child feeding practices., (© 2017 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.)

Background: Iron deficiency remains a prevalent adolescent health problem in low income countries. Iron supplementation is recommended but improvement of iron status requires good adherence., Objectives: We explored factors affecting adolescent adherence to weekly iron and/or folic acid supplements in a setting of low secondary school attendance., Methods: Taped in-depth interviews were conducted with participants in a randomised, controlled, periconceptional iron supplementation trial for young nulliparous women living in a rural, malaria endemic region of Burkina Faso. Participants with good, medium or poor adherence were selected. Interviews were transcribed and analysed thematically., Results: Thirty-nine interviews were conducted. The community initially thought supplements were contraceptives. The potential benefits of giving iron supplementation to unmarried "girls" ahead of pregnancy were not recognised. Trial participation, which required parental consent, remained high but was not openly admitted because iron supplements were thought to be contraceptives. Unmarried non-school attenders, being mobile, were often sent to provide domestic labour in varied locations. This interrupted adherence - as did movement of school girls during vacations and at marriage. Field workers tracked participants and trial provision of free treatment encouraged adherence. Most interviewees did not identify health benefits from taking supplements., Conclusions: For success, communities must be convinced of the value of an adolescent intervention. During this safety trial, benefits not routinely available in iron supplementation programmes were important to this low income community, ensuring adolescent participation. Nevertheless, adolescents were obliged to fulfil cultural duties and roles that interfered with regular adherence to the iron supplementation regime., Trial Registration: Trial Registration at clinicaltrials.gov : NCT01210040.

Purpose: Considering the low content in breast milk breastfed infants might be at particular risk for depleted iron stores after the first months of life. This study evaluates the association of the mode of milk feeding and the timing of complementary food (CF) introduction with parameters of iron status in term healthy infants in Germany., Methods: In this secondary analysis of a randomized controlled trial, parents recorded all foods consumed by their infants from the age of 8 weeks onwards. Mothers were advised on the German food-based dietary guidelines for infants. Accordingly, CF was introduced between the fifth and seventh month of age. Blood samples were taken at 4 and at 10 months of age for analyses of iron status parameters. Iron depletion was defined as serum ferritin <12 ng/mL., Results: The iron intake was lower in breastfed infants (n = 50) than in formula fed (n = 23) with decreasing differences during the course of infancy. At 10 months of age, most iron parameters were not associated with the mode of milk feeding or the timing of CF introduction. At this age, the iron depletion prevalence was >34% without general differences according to the mode of milk feeding or the timing of CF introduction., Conclusion: The high prevalence of depleted iron stores observed in both breastfed and formula-fed infants illustrates the need for further studies to improve our understanding of the optimal iron intake and sensitive parameters of iron status in infancy.

Background & Aims: The main objective of this report is to measure to what extent folate or vitamin B12 given daily for 6 months to young North Indian Children improves hemoglobin (Hb) concentration., Methods: In a randomized placebo controlled trial in low-to-middle income neighborhoods in New Delhi, India, children were randomized into four groups in a 1:1:1:1 ratio and supplemented daily for 6 months with 2 RDAs of vitamin B12, folic acid, both, or placebo. All children with anemia at baseline were given iron supplementation daily for 2 months. We measured the plasma concentrations of soluble transferrin receptor (sTfR), folate, vitamin B12, total homocysteine (tHcy) and Hb in 262 children., Results: Mean Hb concentration decreased in all four study groups during the six months of follow up and supplementation of either or both of the vitamins did not improve the Hb concentration. Iron supplements for the initial 2 mo had limited effect on anemia at 6 mo as almost 90% were still anemic at study end., Conclusion: Supplementation of folic acid and/or vitamin B12 for 6 months does not improve Hb concentration in young children. Our findings do not argue for widespread vitamin B12 or folic acid supplementation to combat anemia. Our results also call for alternative strategies to improve iron status and treat iron deficiency anemia., Clinical Trial Registry: NCT00717730 at www.clinicaltrials.gov, CTRI No.: CTRI/2010/091/001090 at www.ctri.nic.in., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Low birth weight (LBW) (≤2500 g) is associated with iron deficiency in infancy and high blood pressure (BP) later in life. Objective: We investigated the effect of iron supplementation that was given to LBW infants on midchildhood BP. Design: The study was a randomized, double-blind, controlled trial that included 285 marginally LBW (2000-2500-g) infants at 2 Swedish centers between May 2004 and November 2007. The infants were randomly assigned to receive a placebo or 1 or 2 mg Fe · kg -1 · d -1 from 6 wk to 6 mo of age. In secondary analyses at the age of 7 y, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the prevalence of children with BP within the hypertensive range (>90th percentile) were compared between the groups. Results: BP was analyzed via intention to treat in 189 children (66%). The mean ± SD SBP was 103 ± 8.1, 101 ± 7.5, and 101 ± 7.8 mm Hg in children who had received the placebo ( n = 70), 1 mg Fe · kg -1 · d -1 ( n = 54), or 2 mg Fe · kg -1 · d -1 ( n = 65), respectively. When the iron-supplemented groups were combined in covariate-adjusted analyses, the mean SBP in LBW children who had received iron supplementation in infancy was 2.2 mm Hg (95% CI: 0.3, 4.2 mm Hg) lower than in those who were unsupplemented ( P = 0.026). Multivariate logistic regression showed that iron supplementation in infancy reduced the odds of having an SBP within the hypertensive range at 7 y of age (OR: 0.32; 95% CI: 0.11, 0.96). For DBP, there were no significant differences between the intervention groups. Conclusions: LBW children who receive iron supplementation (1 or 2 mg Fe · kg -1 · d -1 ) in infancy have lower SBP at 7 y. This (to our knowledge) novel observation suggests that the increased risk of hypertension that is observed in children and adults who are born small might be reduced with early micronutrient interventions. This trial was registered at clinicaltrials.gov as NCT00558454., (© 2017 American Society for Nutrition.)

Background: Maternal health and nutrition play a crucial role in early child growth and development. However, little is known about the benefits of preconception micronutrient interventions beyond the role of folic acid (FA) and neural tube defects. Objective: We evaluated the impact of weekly preconception multiple micronutrient (MM) or iron and folic acid (IFA) supplementation on child growth and development through the age of 2 y compared with FA alone. Methods: We followed 1599 offspring born to women who participated in a randomized controlled trial of preconception supplementation in Vietnam. Women received weekly supplements that contained either 2800 μg FA, 60 mg Fe and 2800 μg FA, or 15 MMs including IFA, from baseline until conception followed by daily prenatal IFA supplements until delivery. Child anthropometry was measured at birth and at 3, 6, 12, 18, and 24 mo. Child development was measured with the use of the Bayley Scales for Infant Development III at 24 mo. Results: The groups were similar for baseline maternal and offspring birth characteristics. At 24 mo of age, the offspring in the IFA group had significantly higher length-for-age z scores (LAZs) (0.14; 95% CI: 0.03, 0.26), reduced risk of being stunted (0.87; 95% CI: 0.76, 0.99), and smaller yearly decline in LAZs (0.10; 95% CI: 0.04, 0.15) than the offspring in the FA group. Similar trends were found for the offspring in the MM group compared with the FA group for LAZs (0.10; 95% CI: -0.02, 0.22) and the risk of being stunted (0.88; 95% CI: 0.77, 1.01). Offspring in the IFA group had improved motor development ( P = 0.03), especially fine motor development (0.41; 95% CI: 0.05, 0.77), at the age of 24 mo, but there were no differences for measures of cognition or language. Conclusions: Preconception supplementation with IFA improved linear growth and fine motor development at 2 y of age compared with FA. Future studies should examine whether these effects persist and improve child health and schooling. The trial was registered at clinicaltrials.gov as NCT01665378., Competing Interests: Author disclosures: PHN, IG-C, MFY, TVT, HH, HN, SN, AMD, RM, and UR, no conflicts of interest., (© 2017 American Society for Nutrition.)

Iron deficiency anemia is the most common nutritional deficiency in humans. Not all dietary ingested iron, heme or nonheme, will be available to absorption and negative imbalance between iron requirements and absorption leads to iron deficiency and/or anemia. The recommended iron values usually are based on the genetic and on diet iron-bioavailability, which can be considered as the principal factor that change among the cultures and influences the distinct levels of recommendation among countries. Dietary changes present practical limitations due to be difficult to change food habits. The iron food fortification is considered more cost effective and economically more attractive than iron supplementation. There are many iron compounds available to be used in iron fortification. Cereals represent a target food group to iron fortification programs due to high consumption and the in vitro studies can be useful to estimate the relative iron bioavailability in large number of products in short time and with a low cost. Wheat flour baked into bread or not was the main product tested in in vitro bioavailability studies and ferrous sulfate was the principal iron compound used in the fortification studies. However, iron bioavailability from ferrous sulfate is lower than from other compounds, such FeNaEDTA or ferric pyrophosphate. The variables level of fortification, storage, level of extraction, baking and also the association or not with other chemical compound seems to influence the results obtained.

Iron deficiency is the most prevalent nutritional deficiency, affecting more than 30% of the total world's population. It is a major public health problem in many countries around the world. Over the years various methods have been used with an effort to try and control iron-deficiency anemia. However, there has only been a marginal reduction in the global prevalence of anemia. Why is this so? Iron and zinc are essential trace elements for humans. These metals influence the transport and absorption of one another across the enterocytes and hepatocytes, due to similar ionic properties. This paper describes the structure and roles of major iron and zinc transport proteins, clarifies iron-zinc interactions at these sites, and provides a model for the mechanism of these interactions both at the local and systemic level. This review provides evidence that much of the massive extent of iron deficiency anemia in the world may be due to an underlying deficiency of zinc. It explains the reasons for predominance of cellular zinc status in determination of iron/zinc interactions and for the first time thoroughly explains mechanisms by which zinc brings about these changes.

Background: Despite a high prevalence of anemia among nonpregnant Cambodian women, current reports suggest that iron deficiency (ID) prevalence is low. If true, iron supplementation will not be an effective anemia reduction strategy. Objective: We measured the effect of daily oral iron with or without multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant Cambodian women screened as anemic. Design: In this 2 × 2 factorial, double-blind, randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations ≤117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs (14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo capsules. A 2 × 2 factorial intention-to-treat analysis with the use of a generalized mixed-effects model was used to assess the effects of iron and MMNs and the interaction between these factors. Results: In July 2015, 809 women were recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58% (venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN, Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123), and 116 (116, 117) g/L, with no iron × MMN interaction ( P = 0.66). Mean (95% CI) increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) ( P < 0.001) among women who received iron ( n = 407) and 1.2 g/L (-0.6, 3.0 g/L) ( P = 0.18) among women who received MMNs ( n = 407). The predicted proportions (95% CIs) of women with a hemoglobin response (≥10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30% (24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups, respectively. Conclusions: Daily iron supplementation for 12 wk increased hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer additional significant benefit. Overall, ∼24% of women who received iron responded after 12 wk; even fewer would be likely to respond in the wider population. This trial was registered at clinicaltrials.gov as NCT02481375., (© 2017 American Society for Nutrition.)

Purpose: Evaluating early iron supplementation in non-anemic mothers with postpartum depression (PPD)., Methods: This randomized, double-blind, placebo-controlled trial evaluated 70 mothers with PPD. One week after delivery, the mothers were randomly allocated in the iron-treated (50 mg elemental iron/daily) and placebo-treated groups. After 6 weeks, the improvement of PPD symptoms was compared between the groups., Results: Ferritin significantly increased in the iron-treated group (p < 0.001), but not in the placebo group (p = 0.09). After intervention, ferritin was higher in the iron-treated group (medians: 78.2 vs. 37 mg/dl, p = 0.01). The rate of iron deficiency significantly decreased in the iron-treated group (p = 0.009), but not in the placebo group (p = 0.4). After intervention, the rate of iron deficiency was higher in the placebo group (31.4 vs. 8.5 %, p = 0.01). The Edinburgh Postnatal Depression Scale (EPDS) score significantly decreased in the iron-treated group (p < 0.001), but not in the placebo group (p = 0.13). After intervention, the EPDS score was lower in the iron-treated group (medians 9 vs. 12, p = 0.01). The improvement rate for PPD was significantly higher in the iron-treated group (42.8 vs. 20 %, p = 0.03). After intervention, mothers with continued PPD had lower ferritin than the improved mothers (41.8 vs. 67 mg/dl, p = 0.03). Mothers with continued depression had higher rate of iron deficiency compared to the improved mothers (27.1 vs. 4.5 %, p = 0.02)., Conclusions: Early iron supplementation in mothers with PPD significantly improves the iron stores and causes a significant improvement in PPD with a 42.8 % improvement rate during 6 weeks. Continued PPD might be related to the lower postpartum ferritin levels in untreated mothers.

Strategies for preventing Fe deficiency include Fe supplementation and Fe fortification of foods. The absorption, metabolism and chemical characteristics of Fe multi-amino acid chelate (IMAAC) are not known. Absorption of IMAAC was compared with FeSO4 in Fe-depleted mice and in vitro chemical studies of the Fe supplement was performed in HuTu 80 cells. Hb repletion study was carried out in Fe-deficient CD1 mice that were fed for 10 d a diet supplemented with ferrous IMAAC or FeSO4. A control group of Fe-replete mice was fed a diet with adequate Fe concentrations throughout the study. Tissues were collected from the mice, and the expression of Fe-related genes was determined by quantitative PCR. Ferric reductase and Fe uptake were evaluated in HuTu 80 cells. Supplementation of the diet with FeSO4 or IMAAC significantly increased Hb levels (P<0·001) in Fe-deficient mice from initial 93·9 (SD 10·8) or 116·2 (SD 9·1) to 191 (SD 0·7) or 200 (SD 0·5) g/l, respectively. Initial and final Hb for the Fe-deficient control group were 87·4 (SD 6·7) and 111 (SD 11·7) g/l, respectively. Furthermore, the liver non-haem Fe of both supplement groups increased significantly (P<0·001). IMAAC was more effective at restoring Fe in the spleen compared with FeSO4 (P<0·005). Gene expression showed the IMAAC supplement absorption is regulated by the body's Fe status as it significantly up-regulated hepcidin (P<0·001) and down-regulated duodenal cytochrome b mRNA (P<0·005), similar to the effects seen with FeSO4. A significant proportion of Fe in IMAAC is reduced by ascorbic acid. Fe absorption in mice and cells was similar for both IMAAC and FeSO4 and both compounds induce and regulate Fe metabolism genes similarly in the maintenance of homeostasis in mice.

Background: India's high prevalence of iron-deficiency anemia has largely been attributed to the local diet consisting of nonheme iron, which has lower absorption than that of heme iron. Objective: We assessed the efficacy of the consumption of iron-supplement bars in raising hemoglobin concentrations and hematocrit percentages in anemic (hemoglobin concentration <12 g/dL) Indian women of reproductive age. Design: The Let's be Well Red study was a 90-d, pair-matched, cluster-randomized controlled trial. A total of 361 nonpregnant women (age 18-35 y) were recruited from 10 sites within Mumbai and Navi Mumbai, India. All participants received anemia education and a complete blood count (CBC). Random assignment of anemic participants to intervention and control arms occurred within 5 matched site-pairs. Intervention participants received 1 iron-supplement bar (containing 14 mg Fe)/d for 90 d, whereas control subjects received nothing. CBC tests were given at days 15, 45, and 90. Primary outcomes were 90-d changes from baseline in hemoglobin concentrations and hematocrit percentages. Linear mixed models and generalized estimating equations were used to model continuous and binary outcomes, respectively. Results: Of 179 anemic participants, 136 (76.0%) completed all follow-up assessments (65 intervention and 71 control participants). Baseline characteristics were comparable by arm. Mean hemoglobin and hematocrit increases after 90 d were greater for intervention than for control participants [1.4 g/dL (95% CI: 1.3, 1.6 g/dL) and 2.7% (95% CI: 2.2%, 3.2%), respectively]. The anemia prevalence at 90 d was lower for intervention (29.2%) than for control participants (98.6%) (OR: 0.007; 95% CI: 0.001, 0.04). Conclusions: The daily consumption of an iron-supplement bar leads to increased hemoglobin concentrations and hematocrit percentages and to a lower anemia prevalence in the target population with no reported side effects. This intervention is an attractive option to combat anemia in India. This trial was registered at clinicaltrials.gov as NCT02032615., (© 2017 American Society for Nutrition.)

Previous studies have yielded conflicting results on the associations of maternal Fe intake with birth outcomes. This study aimed to investigate the associations between maternal Fe intake (total Fe from diet and supplements, dietary total Fe, haeme Fe, non-haeme Fe and Fe supplements use) and adverse birth outcomes in Shaanxi Province of Northwest China. In all, 7375 women were recruited using a stratified multistage random sampling method at 0-12 months (median 3; 10th-90th percentile 0-7) after delivery. Diets were collected by a validated FFQ and maternal characteristics were obtained via a standard questionnaire. The highest tertile of haeme Fe intake compared with the lowest tertile was negatively associated with low birth weight (LBW) (OR 0·68; 95 % CI 0·49, 0·94), small for gestational age (SGA) (OR 0·76; 95 % CI 0·62, 0·94) and birth defects (OR 0·55; 95 % CI 0·32, 0·89). Maternal haeme Fe intake was associated with a lower risk of intra-uterine growth retardation (IUGR) (medium tertile v. lowest tertile: OR 0·78; 95 % CI 0·61, 0·95; highest tertile v. lowest tertile: OR 0·76; 95 % CI 0·59, 0·93; P trend=0·045). The OR of LBW associated with Fe supplements use were as follows: during pregnancy: 0·72 (95 % CI 0·50, 0·95); in the second trimester: 0·67 (95 % CI 0·42, 0·98); in the third trimester: 0·47 (95 % CI 0·24, 0·93). We observed no associations of total Fe, dietary total Fe or non-haeme Fe intake with birth outcomes. The results suggest that maternal haeme Fe intake is associated with a reduced risk of LBW, SGA, IUGR and birth defects, and Fe supplements use during pregnancy reduces LBW risk.

Iron is a trace element and a structural part of antioxidant enzymes, and its requirements vary according to age and gender. We hypothesized that iron deficiency (ID) leads to an increase in free radicals which mainly affect the brain, and the severity of damage would therefore be dependent on age and gender. Two groups of Wistar rats were evaluated evolutionarily: 100 rats (50 males; 50 females) with ID diet and 100 rats (50 males; 50 females) with standard diet. Both groups were offspring from mothers who were previously under the same dietary intervention. The ages studied roughly correspond to stages of human development: birth (0 postnatal day "PND" in rats), childhood (21 PND), early adolescence (42 PND), late adolescence (56 PND), and adulthood (70 PND). The following biomarkers in the brain, blood, and liver were analyzed: lipid peroxidation products (LPO), protein carbonyl content and activity of the antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. It was demonstrated that ID subjects are born with high levels of LPO in the brain and low antioxidant activity, the damage being more severe in males. After birth, antioxidant defense focuses on the central level (brain) in ID females and on the peripheral level (blood and liver) in ID males. In two critical stages of development, birth and late adolescence, antioxidant protection is insufficient to counteract oxidative damage in ID subjects. Moreover, we observed that the variability of results in the literature on oxidative stress and ID comes from gender and age of the subjects under study. With this, we can establish patterns and exact moments to carry out studies or treatments.

Objectives: We previously demonstrated that a mild pre-natal/early post-natal iron-deficient anaemic (IDA) diet devoid of long-chain polyunsaturated fatty acids (LC-PUFA) affected development, neurophysiology, and cerebral lipid biochemistry of the guinea pigs' progeny. Impacts of dietary LC-PUFA on altered cerebral development resulting from pre-natal IDA are unknown. To address this health issue, impacts of mild gestational IDA in the presence of dietary LC-PUFA on the offsprings' neural maturation were studied in guinea pigs using auditory brainstem responses (ABRs) and assessments of brain fatty acids (FAs)., Methods: Female guinea pigs (n = 10/group) were fed an iron sufficient (IS) or IDA diet (146 and 12.7 mg iron/kg, respectively) with physiological amounts of LC-PUFA, during the gestation and lactation periods. From post-natal day (PNd) 9 onwards, the IS + PUFA diet was given to both groups of weaned offspring. Cerebral tissue and offsprings' ABR were collected on PNd24., Results: There was no difference in peripheral and brainstem transmission times (BTTs) between IS + PUFA and IDA + PUFA siblings (n = 10/group); the neural synchrony was also similar in both groups. Despite the absence of differences in auditory thresholds, IDA + PUFA siblings demonstrated a sensorineural hearing loss in the extreme range of frequencies (32, 4, and 2 kHz), as well as modified brain FA profiles compared to the IS + PUFA siblings., Discussion: The present study reveals that siblings born from dams exposed to a moderate IDA diet including balanced physiological LC-PUFA levels during pregnancy and lactation demonstrate minor impairments of ABR compared to the control siblings, particularly on the auditory acuity, but not on neural synchrony, auditory nerve velocity and BTT.

Current evidence of the relationship between diets and Fe status is mostly derived from studies in developed countries with Western diets, which may not be translatable to Chinese with a predominantly plant-based diet. We extracted data that were nationally sampled from the 2009 wave of China Health and Nutrition Survey; dietary information was collected using 24-h recalls combined with a food inventory for 3 consecutive days. Blood samples were collected to quantify Fe status, and log-ferritin, transferrin receptor and Hb were used as Fe status indicators. In total, 2905 (1360 males and 1545 females) adults aged 18-50 years were included for multiple linear regression and stratified analyses. The rates of Fe deficiency and Fe-deficiency anaemia were 1·6 and 0·7 % for males and 28·4 and 10·7 % for females, respectively. As red meat and haem Fe consumption differed about fifteen to twenty times throughout the five groups, divided by quintiles of animal protein intake per 4·2 MJ/d, only Fe status as indicated by log-ferritin (P=0·019) and transferrin receptor (P=0·024) concentrations in males was shown to be higher as intakes of animal foods increased. Log-ferritin was positively associated with intakes of red meat (B=0·3 %, P=0·01) and haem Fe (B=12·3 %, P=0·010) in males and with intake of non-haem Fe in females (B=2·2 %, P=0·024). We conclude that diet has a very limited association with Fe status in Chinese adults consuming a traditional Chinese diet, and a predominantly plant-based diet may not be necessarily responsible for poor Fe status.

Background: Iron is an essential micronutrient required for normal growth and development of the body. Infants are more vulnerable to develop iron-deficiency anaemia due to inadequate iron supply in early stages. The objective of the study was in vivo assessment of iron bioavailability from pearl millet based weaning food fortified with iron and vitamin A, and to investigate the role of vitamin A in iron absorption in animal models., Results: Results revealed that anaemic group showed significantly (P < 0.05) higher bioavailability than that of normal rat models. Animals fed vitamin A supplemented pearl-millet diet exhibited comparable results with a sub-group provided commercially available weaning diet in both normal and anaemic groups, but significantly (P < 0.05) higher values for studied biological indices than that of a sub-group provided iron fortified pearl-millet or synthetic diet. When the anaemic rats were provided iron + vitamin A fortified diet, iron bioavailability increased and liver iron stores returned to the normal levels after 30 days, indicating a promoter role of vitamin A in intestinal iron absorption., Conclusions: Overall, bioavailability of electrolytic iron could be improved by supplementation of vitamin A, and this mixture can be considered as a useful fortificant for pearl millet based complementary foods fortification designed to prevent iron deficiency. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Introduction: Nutritional intervention in pre-school children using cookies prepared with wheat flour enriched with iron and folic acid (CWFFeFA) and cookies prepared with cowpea (Vigna unguiculata (L.) Walp) flour fortified with iron and zinc and wheat flour enriched with iron and folic acid (CCFFeZn + WFFeFA)., Objective: To assess the impact of the ingestion of CWFFeFA and CCFFeZn + WFFeFA by pre-school children, using the cowpea variety BRS-Xiquexique, to control iron-deficiency anaemia., Methods: Nutritional intervention was conducted in municipal day care centres selected at random (n = 262) involving pre-school children aged 2 to 5 years living in Teresina, state of Piauí, Brazil. To assess the socioeconomic data, BMI-for-age, haemoglobin levels before and after intervention, and dietary intake, the children were divided into group 1 (G1), which received CWFFeFA (30 g), and group 2 (G2), which received CCFFeZn + WFFeFA (30 g). Food acceptance was evaluated daily., Results: The prevalence of anaemia in G1 and G2 before the nutritional intervention was 12.2% (n = 18) and 11.5% (n = 30), respectively. After intervention, the prevalence decreased to 1.4% in G1 (n = 2) and to 4.2% in G2 (n = 11). Food acceptance by pre-school children in G1 and G2 was 97.4% and 94.3%, respectively., Conclusion: The use of both types of cookie formulations decreased the prevalence of anaemia among pre-school children, and CCFFeZn + WFFeFA yielded the greatest decrease.

Aim: High iron measured using dietary intake and biomarkers is associated with Type 2 diabetes. It is uncertain whether a similar association exists for gestational diabetes mellitus. The aim of this systematic review was to conduct a cohort study examining first trimester body iron stores and subsequent risk of gestational diabetes, and to include these findings in a systematic review of all studies examining the association between maternal iron status, iron intake (dietary and supplemental) and the risk of gestational diabetes., Methods: Serum samples from women with first trimester screening were linked to birth and hospital records for data on maternal characteristics and gestational diabetes diagnosis. Blood was analysed for ferritin, soluble transferrin receptor and C-reactive protein. Associations between iron biomarkers and gestational diabetes were assessed using multivariate logistic regression. A systematic review and meta-analysis, registered with PROSPERO (CRD42014013663) included studies of all designs published in English from January 1995 to July 2015 that examined the association between iron and gestational diabetes and included an appropriate comparison group., Results: Of 3776 women, 3.4% subsequently developed gestational diabetes. Adjusted analyses found increased odds of gestational diabetes for ferritin (OR 1.41; 95% CI 1.11, 1.78), but not for soluble transferrin receptor (OR 1.00; 95% CI 0.97, 1.03) per unit increase of the biomarker. Two trials of iron supplementation found no association with gestational diabetes. Increased risk of gestational diabetes was associated with higher levels of ferritin and serum iron and dietary haem iron intakes., Conclusions: Increased risk of gestational diabetes among women with high serum ferritin and iron levels and dietary haem iron intakes warrants further investigation., (© 2015 Diabetes UK.)

Childhood cancer incidence increases and although rare, it is a leading cause of mortality. Leukemia and lymphoma comprise 40% of all cancers in children but little is known of their etiology. In this study, we examined the associations of breastfeeding and other early life exposures with childhood leukemia and lymphoma. A population-based case-control study carried out in 2011-2013 comprised mothers of 190 incidents (2005-2013) of leukemia/lymphoma cases aged 1-19 yr at diagnosis and 384 population-based controls. Interviews based on a computerized structured questionnaire were conducted with the mothers. Multivariate logistic regression models adjusted for potential confounders assessed the association between breastfeeding patterns and childhood leukemia/lymphoma. Ever breastfeeding category was associated with a 64% decreased risk for childhood leukemia/lymphoma lsqb;odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.22, 0.60lrqb; and similar trends, with a dose-response effect, were observed for any breastfeeding (exclusive and/or partial) category for 6, 12, and 18+ mo. Other infant exposures associated with cancer risk were child iron supplementation (OR = 0.39, 95% CI: 0.26, 0.59), pet ownership (OR = 0.50, 95% CI: 0.33, 0.78), paternal smoking (OR = 1.93, 95% CI: 1.18, 3.15), and having older siblings (OR = 1.18, 95% CI: 1.05, 1.33). Breastfeeding-a controllable and modifiable exposure-is inversely associated with risk for childhood leukemia and lymphoma with a dose-response effect.

Background: Food-based strategies to reduce nutritional iron deficiency have not been universally successful. Biofortification has the potential to become a sustainable, inexpensive, and effective solution., Objective: This randomized controlled trial was conducted to determine the efficacy of iron-biofortified beans (Fe-Beans) to improve iron status in Rwandan women., Methods: A total of 195 women (aged 18-27 y) with serum ferritin <20 μg/L were randomly assigned to receive either Fe-Beans, with 86 mg Fe/kg, or standard unfortified beans (Control-Beans), with 50 mg Fe/kg, 2 times/d for 128 d in Huye, Rwanda. Iron status was assessed by hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), and body iron (BI); inflammation was assessed by serum C-reactive protein (CRP) and serum α1-acid glycoprotein (AGP). Anthropometric measurements were performed at baseline and at end line. Random weekly serial sampling was used to collect blood during the middle 8 wk of the feeding trial. Mixed-effects regression analysis with repeated measurements was used to evaluate the effect of Fe-Beans compared with Control-Beans on iron biomarkers throughout the course of the study., Results: At baseline, 86% of subjects were iron-deficient (serum ferritin <15 μg/L) and 37% were anemic (hemoglobin <120 g/L). Both groups consumed an average of 336 g wet beans/d. The Fe-Beans group consumed 14.5 ± 1.6 mg Fe/d from biofortified beans, whereas the Control-Beans group consumed 8.6 ± 0.8 mg Fe/d from standard beans (P < 0.05). Repeated-measures analyses showed significant time-by-treatment interactions for hemoglobin, log serum ferritin, and BI (P < 0.05). The Fe-Beans group had significantly greater increases in hemoglobin (3.8 g/L), log serum ferritin (0.1 log μg/L), and BI (0.5 mg/kg) than did controls after 128 d. For every 1 g Fe consumed from beans over the 128 study days, there was a significant 4.2-g/L increase in hemoglobin (P < 0.05)., Conclusion: The consumption of iron-biofortified beans significantly improved iron status in Rwandan women. This trial was registered at clinicaltrials.gov as NCT01594359., (© 2016 American Society for Nutrition.)

We evaluated the role of iron deficiency (ID) without anemia on hearing function and cochlear pathophysiology of young rats before and after noise exposure. We used rats at developmental stages as an animal model to induce ID without anemia by dietary iron restriction. We have established this dietary restriction model in the rat that should enable us to study the effects of iron deficiency in the absence of severe anemia on hearing and ribbon synapses. Hearing function was measured on Postnatal Day (PND) 21 after induction of ID using auditory brainstem response (ABR). Then, the young rats were exposed to loud noise on PND 21. After noise exposure, hearing function was again measured. We observed the morphology of ribbon synapses, hair cells and spiral ganglion cells (SGCs), and assessed the expression of myosin VIIa, vesicular glutamate transporter 3 and prestin in the cochlea. ID without anemia did not elevate ABR threshold shifts, but reduced ABR wave I peak amplitude of young rats. At 70, 80, and 90 dB SPL, amplitudes of wave I (3.11 ± 0.96 µV, 3.52 ± 1.31 µV, and 4.37 ± 1.08 µV, respectively) in pups from the ID group were decreased compared to the control (5.92 ± 1.67 µV, 6.53 ± 1.70 µV, and 6.90 ± 1.76 µV, respectively) (p < 0.05). Moreover, ID without anemia did not impair the morphology hair cells and SGCs, but decreased the number of ribbon synapses. Before noise exposure, the mean number of ribbon synapses per inner hair cell (IHC) was significantly lower in the ID group (8.44 ± 1.21) compared to that seen in the control (13.08 ± 1.36) (p < 0.05). In addition, the numbers of ribbon synapses per IHC of young rats in the control (ID group) were 6.61 ± 1.59, 3.07 ± 0.83, 5.85 ± 1.63 and 12.25 ± 1.97 (3.75 ± 1.45, 2.03 ± 1.08, 3.81 ± 1.70 and 4.01 ± 1.65) at 1, 4, 7 and 14 days after noise exposure, respectively. Moreover, ABR thresholds at 4 and 8 kHz in young rats from the ID group were significantly elevated at 7 and 14 days after noise exposure compared to control (p < 0.05). The average number of young rat SGCs from the ID group were significantly decreased in the basal turn of the cochlea compared to the control (p < 0.05). Therefore, ID without anemia delayed the recovery from noise-induced hearing loss and ribbon synapses damage, increased SGCs loss, and upregulated prestin after noise exposure. Thus, the cochleae in rat pups with ID without anemia were potentially susceptible to loud noise exposure, and this deficit may be attributed to the reduction of ribbon synapses and SGCs.

Dietary advice is the cornerstone in first-line treatment of metabolic diseases. Nutritional interventions directed at these clinical conditions mainly aim to (a) improve insulin resistance by reducing energy-dense macronutrient intake to obtain weight loss and (b) reduce fluctuations in insulin secretion through avoidance of rapidly absorbable carbohydrates. However, even in the majority of motivated patients selected for clinical trials, massive efforts using this approach have failed to achieve lasting efficacy. Less attention has been given to the role of micronutrients in metabolic diseases. Here, we review the evidence that highlights (a) the importance of iron in pancreatic beta-cell function and dysfunction in diabetes and (b) the integrative pathophysiological effects of tissue iron levels in the interactions among the beta cell, gut microbiome, hypothalamus, innate and adaptive immune systems, and insulin-sensitive tissues. We propose that clinical trials are warranted to clarify the impact of dietary or pharmacological iron reduction on the development of metabolic disorders.

Purpose of Review: Iron is essential for normal cellular function and many diseases result from disturbances in iron homeostasis. This review describes some of the recent key advances in iron transport and its regulation, how this relates to iron-related disorders, and emerging therapies for these diseases., Recent Findings: The iron-regulatory hormone hepcidin and its target, the iron exporter ferroportin (FPN), play central roles in iron homeostasis. Recent studies have expanded our understanding of how hepcidin is regulated in response to stimulated erythropoiesis and have added some new players to the complex network of factors that influences hepcidin expression. Novel structural insights into how FPN transports iron have been an important addition to the field, as has the recognition that some zinc transporters such as ZIP14 can transport iron. Investigations into cardiac iron homeostasis have revealed a key role for FPN, and transferrin receptor 1, which is essential for cellular iron uptake, has been shown to be critical for normal immune function., Summary: The increased understanding of mechanisms of iron homeostasis that has resulted from recent research has greatly improved our ability to diagnose and manage iron-related disorders, and has offered new therapies for this important class of human diseases.

Anemia is a common diagnosis in the geriatric population, especially in institutionalized and hospitalized elderly. Most common etiologies for anemia in elderly people admitted to a geriatric ward are iron-deficiency anemia and anemia associated with chronic disease. Determination of serum ferritin is the most used assay in the differential diagnosis, despite low sensitivity and moderate specificity. New insights into iron homeostasis lead to new diagnostic assays such as serum hepcidin, serum transferrin receptor and reticulocyte hemoglobin equivalent.Importance of proper diagnosis and treatment for this population is large since there is a correlation between anemia and morbidity - mortality. Anemia is usually defined as hemoglobin less than 12 g/dl for women and less than 13 g/dl for men. There is no consensus for which hemoglobinvalue an investigation into underlying pathology is obligatory. This needs to be evaluated depending on functional condition of the patient.

Objectives: To examine the prevalence and determinants of iron supplement use and the amount of iron consumed from iron-containing supplements., Methods: A cross-sectional survey was performed in antenatal clinics in two tertiary hospitals in Sydney, Australia between January and March 2014., Results: Of 612 (91% response rate) pregnant women, 589 with complete data were analysed. Overall iron-containing supplement use was 88.0%, of which 70.1% was multivitamin (MV) only, 7.2% was iron-only and 22.2% was both. Use of iron-containing supplements was associated with increased gestational age, a diagnosis of anaemia or iron deficiency (ID) in the current pregnancy and pre-pregnancy use of an iron-containing supplement. Several risk factors for ID or anaemia such as non-red meat eating and previous miscarriage were not associated with current iron supplement use. About 65% of women diagnosed with ID, and 62.3% of women diagnosed with anaemia were taking an iron-only supplement, with or without a MV. The proportion of women consuming low (<30), preventative (30-99) and treatment (≥100) mg/day doses were 36.8%, 45.4%, and 17.8%, respectively. Only 46.7% of women diagnosed with ID were taking ≥100 mg/day iron from supplements, while 23.3% were taking <30 mg/day., Conclusion: Women are consuming varying doses of iron and some high-risk women are taking inadequate doses of iron to prevent or treat ID or iron deficiency anaemia. Healthcare professionals are best positioned to advise women on iron supplement use in pregnancy and should educate women individually about the type and dose of supplement best suited to their needs., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Phytic acid (PA) is a major inhibitor of iron bioavailability from beans, and high PA concentrations might limit the positive effect of biofortified beans (BBs) on iron status. Low-phytic acid (lpa) bean varieties could increase iron bioavailability., Objective: We set out to test whether lpa beans provide more bioavailable iron than a BB variety when served as part of a composite meal in a bean-consuming population with low iron status., Methods: Dietary iron absorption from lpa, iron-biofortified, and control beans (CBs) (regular iron and PA concentrations) was compared in 25 nonpregnant young women with low iron status with the use of a multiple-meal crossover design. Iron absorption was measured with stable iron isotopes., Results: PA concentration in lpa beans was ∼10% of BBs and CBs, and iron concentration in BBs was ∼2- and 1.5-fold compared with CBs and lpa beans, respectively. Fractional iron absorption from lpa beans [8.6% (95% CI: 4.8%, 15.5%)], BBs [7.3% (95% CI: 4.0%, 13.4%)], and CBs [8.0% (95% CI: 4.4%, 14.6%)] did not significantly differ. The total amount of iron absorbed from lpa beans and BBs was 421 μg (95% CI: 234, 756 μg) and 431 μg (95% CI: 237, 786 μg), respectively, and did not significantly differ, but was >50% higher (P < 0.005) than from CBs (278 μg; 95% CI: 150, 499 μg). In our trial, the lpa beans were hard to cook, and their consumption caused transient adverse digestive side effects in ∼95% of participants. Gel electrophoresis analysis showed phytohemagglutinin L (PHA-L) residues in cooked lpa beans., Conclusion: BBs and lpa beans provided more bioavailable iron than control beans and could reduce dietary iron deficiency. Digestive side effects of lpa beans were likely caused by PHA-L, but it is unclear to what extent the associated digestive problems reduced iron bioavailability. This trial was registered at clinicaltrials.gov as NCT02215278., (© 2016 American Society for Nutrition.)

Iron is often initiated for children with low hemoglobin values in the absence of other indicators of iron deficiency in low-resource settings. Unfortunately, there are few reports describing outcomes from such an approach outside of clinical trials. This study examined outcomes of an anemia screening and treatment service in a low-resource community in the Dominican Republic. Complete blood counts (CBC) and receipt of iron supplementation were extracted from health records of young children participating in a well-baby clinic in the targeted community. Of the 265 children screened, 68.7% had hemoglobin values <11.0 g/dl; 61.5% of these anemic children had follow-up CBCs. While 72.3% of those with follow-up CBCs picked-up some iron supplements, only 21.4% had a follow-up hemoglobin ≥11.0 g/dl. Amount of iron given was not related to change in hemoglobin at follow-up. More follow-up monitoring of quality and impact of community care is required with associated evidence-informed benchmark targets., (© The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation., Objectives: We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment.., Design: Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations ≥80 μmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron., Results: At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 μmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 μg/L (95% CI: 84.2, 121.0 μg/L) compared with 152.9 μg/L (128.8, 181.6 μg/L), respectively; P ≤ 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P < 0.011]., Conclusions: Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration. This trial was registered at clinicaltrials.gov as NCT01093989., (© 2016 American Society for Nutrition.)