Search

Forty LW × L pigs (20 boars and 20 gilts) (51.1 ± 0.41 kg) were allocated to a 2 × 2 × 2 factorial design with the respective factors being supplemental organic iron (Fe, 0 and 500 mg/kg), inulin (In, 0 and 50 g/kg) and sex (boars and gilts). After 5 weeks the animals were transported to an abattoir before slaughter and collection of samples. Serum iron was increased by supplemental Fe (28.4 v. 30.9 μmol/L, P = 0.05), although there was an interaction (P = 0.03) such that pigs fed diets with In had lower serum Fe concentrations than those without In (26.8 v. 32.3 μmol/L). Boars had lower (P < 0.01) haemoglobin (116 vs 125), haematocrit (36.7 v. 39.7%) and erythrocyte (6.6 v. 7.1 × 10 6 /mL) concentrations than gilts. Dietary In increased liveweight gain (795 v. 869 g/d, P < 0.02) and carcass weight (62.9 v. 65.2 kg, P < 0.02). Dietary Fe or In supplementation did not improve muscle Longissimus thoracis et lumborum (LTL) total Fe concentration (P > 0.05). Muscle non-heme Fe concentration was higher in Fe-supplemented pigs (P < 0.04) and gilts (P < 0.05) than their counterparts. Muscle heme Fe concentration was greater (3.04 vs 2.51, P < 0.05) in boars than in gilts. The LTL marbling score was greater (P < 0.01) for In-supplemented pigs, and the response was more notable when Fe and In were fed together. These data show that dietary supplementation of Fe increased serum Fe and muscle non-heme Fe concentrations. Supplementation of In at 5% in the diet of finisher pigs improved liveweight gain and the marbling score of pork., Competing Interests: Declaration of competing interest “Dietary iron or inulin supplementation alters iron status, growth performance, intramuscular fat and meat quality in finisher pigs” by F. R. Dunshea, J.R. Pluske and EN Ponnampalam. None of the authors have any actual or potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Anemia in pregnancy is an important global public health problem. It is estimated that 38% of pregnant women worldwide are anemic. In Africa, literature from observational studies show 20% of maternal deaths are attributed to anemia. In Uganda, 50% of pregnant women have iron deficiency anaemia. The proportion of pregnant women receiving Iron-Folic acid (IFA) supplementation has improved. However, the number of IFA pills consumed is still low. We carried out a randomized controlled trial to determine the effect of dispensing blister and loose packaged IFA pills on adherence measured by count on next return visit and hemoglobin levels among pregnant women at two National Referral Hospitals in Kampala, Uganda., Methods: This trial was conducted between April and October 2016. Nine hundred fifty pregnant women at ≤28 weeks were randomized to either the blister (intervention arm) or loose (control arm) packaged IFA. The participants completed the baseline measurements and received 30 pills of IFA at enrolment to swallow one pill per day. We assessed adherence by pill count and measured hemoglobin at four and 8 weeks. The results were presented using both intention-to-treat and per-protocol analysis., Results: There were 474 participants in the control and 478 in the intervention arms. Adherence to IFA intake was similar in the two groups at 4th week (40.6 and 39.0%, p = 0.624) and 8th week (51.9 and 46.8%, p = 0.119). The mean hemoglobin level at 4 weeks was higher in the blister than in the loose packaging arms (11.9 + 1.1 g/dl and 11.8 + 1.3 g/dl, respectively; p = 0.02), however, similar at week 8 (12.1 + 1.2 and 12.0 + 1.3, respectively; p = 0.23). However, over the 8-week period blister packaging arm had a higher change in hemoglobin level compared to loose package (blister package 0.6 ± 1.0; loose packaging 0.2 ± 1.1; difference: 0.4 g/dL (95% CI: 0.24-0.51 g/dL); p = 0.001. There were no serious adverse events., Conclusions: Our results showed no effect of blister packaging on IFA adherence among pregnant women. However, our findings showed that blister packaged group had a higher hemoglobin increase compared to loose iron group., Trial Registration: No. PACTR201707002436264 (20 /07/ 2017)., (© 2022. The Author(s).)

Exome sequencing has identified the glyceronephosphate O-acyltransferase (GNPAT) gene as a genetic modifier of iron overload in hereditary hemochromatosis (HH). Subjects with HFE (Homeostatic Iron Regulator) p.C282Y mutations and the GNPAT p.D519G variant had more iron loading compared with subjects without the GNPAT variant. In response to an oral iron challenge, women with GNPAT polymorphisms loaded more iron as compared with women without polymorphisms, reinforcing a role for GNPAT in iron homeostasis. The aim of the present study was to develop and characterize an animal model of disease to further our understanding of genetic modifiers, and in particular the role of GNPAT in iron homeostasis. We generated an Hfe/Gnpat mouse model reminiscent of the patients previously studied and studied these mice for up to 26 weeks. We also examined the effect of dietary iron loading on mice with reduced Gnpat expression. Gnpat heterozygosity in Hfe knockout mice does not play a role in systemic iron homeostasis; Gnpat+/- mice fed a high-iron diet, however, had lower hepatic hepcidin (HAMP) mRNA expression, whereas they have significantly higher serum iron levels and transferrin saturation compared with wildtype (WT) littermates on a similar diet. These results reinforce an independent role of GNPAT in systemic iron homeostasis, reproducing in an animal model, the observations in women with GNPAT polymorphisms subjected to an iron tolerance test., (© 2020 The Author(s).)

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today's knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal., Competing Interests: The authors declare no conflict of interest.

Solanum torvum (STO) and edible insects are potential dietary approaches to prevent malnutrition. Hence, we determined the effect of STO and insect powders on improving nutritional status in malnourished rats. Malnutrition was induced in rats by feeding 5% protein, ~2 ppm Fe (LPI) diet for 21 days. During the 14 day repletion, five groups of rats ( n = 8) were fed diets supplemented with Acheta domesticus (cricket, ADO), Rhynchophorus phoenicis fabricius (palm weevil larvae, RFA), STO, ADO + STO (TAD), and casein + ferrous sulfate (PIS, positive control), as well as a non-supplemented group (negative control, LPI). A normal (NOM) group was fed protein-Fe sufficient (PIS) diet throughout the study. Body composition was measured by Dual-energy X-ray absorptiometry. The hemoglobin (Hb) repletion method was used to assess relative biological value (RBV, compared to PIS) of the supplemented groups. No differences were found in weight gain, bone mineral content, lean and fat mass, and organ weights among the edible insects and PIS groups, but these results differed from STO and the LPI groups. An increase in Hb Fe and RBV with ADO and RFA was comparable to PIS. ADO and RFA could be excellent sources of protein and bioavailable Fe, making it a sustainable, low-cost food source to prevent malnutrition in humans.

High tissue iron levels are a risk factor for multiple chronic diseases including type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). To investigate causal relationships and underlying mechanisms, we used an established NAFLD model-mice fed a high fat diet with supplemental fructose in the water ("fast food", FF). Iron did not affect excess hepatic triglyceride accumulation in the mice on FF, and FF did not affect iron accumulation compared to normal chow. Mice on low iron are protected from worsening of markers for non-alcoholic steatohepatitis (NASH), including serum transaminases and fibrotic gene transcript levels. These occurred prior to the onset of significant insulin resistance or changes in adipokines. Transcriptome sequencing revealed the major effects of iron to be on signaling by the transforming growth factor beta (TGF-β) pathway, a known mechanistic factor in NASH. High iron increased fibrotic gene expression in vitro, demonstrating that the effect of dietary iron on NASH is direct. Conclusion: A lower tissue iron level prevents accelerated progression of NAFLD to NASH, suggesting a possible therapeutic strategy in humans with the disease.

The common dry bean ( Phaseolus vulgaris L.) is a globally produced pulse crop and an important source of micronutrients for millions of people across Latin America and Africa. Many of the preferred black and red seed types in these regions have seed coat polyphenols that inhibit the absorption of iron. Yellow beans are distinct from other market classes because they accumulate the antioxidant kaempferol 3-glucoside in their seed coats. Due to their fast cooking tendencies, yellow beans are often marketed at premium prices in the same geographical regions where dietary iron deficiency is a major health concern. Hence, this study compared the iron bioavailability of three faster cooking yellow beans with contrasting seed coat colors from Africa (Manteca, Amarillo, and Njano) to slower cooking white and red kidney commercial varieties. Iron status and iron bioavailability was assessed by the capacity of a bean based diet to generate and maintain total body hemoglobin iron (Hb-Fe) during a 6 week in vivo ( Gallus gallus ) feeding trial. Over the course of the experiment, animals fed yellow bean diets had significantly ( p ≤ 0.05) higher Hb-Fe than animals fed the white or red kidney bean diet. This study shows that the Manteca yellow bean possess a rare combination of biochemical traits that result in faster cooking times and improved iron bioavailability. The Manteca yellow bean is worthy of germplasm enhancement to address iron deficiency in regions where beans are consumed as a dietary staple.

Background: Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding., Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 416,746 individuals from 10 countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident lung cancer (n = 3731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1489 matched controls for whom serum cotinine was available., Results: Haem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00-1.07), and in the highest versus lowest quintile (HR 1.16, 95% CI 1.02-1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case-control subset., Conclusions: Greater haem iron intake may be modestly associated with lung cancer risk.

Purpose: Elemental deficiencies are highly prevalent and have a significant impact on health. However, clinical monitoring of plasma elemental responses to foods remains largely unexplored. Data from in vitro studies show that red meat (beef) is a highly bioavailable source of several key elements, but cooking method may influence this bioavailability. We therefore studied the postprandial responses to beef steak, and the effects of two different cooking methods, in healthy young males., Methods: In a randomized cross-over controlled trial, healthy males (n = 12, 18-25 years) were fed a breakfast of beef steak (270 ± 20 g) in which the meat was either pan-fried (PF) or sous-vide (SV) cooked. Baseline and postprandial blood samples were collected and the plasma concentrations of 15 elements measured by inductively coupled plasma-mass spectrometry (ICP-MS)., Results: Concentrations of Fe and Zn changed after meal ingestion, with plasma Fe increasing (p < 0.001) and plasma Zn decreasing (p < 0.05) in response to both cooking methods. The only potential treatment effect was seen for Zn, where the postprandial area under the curve was lower in response to the SV meal (2965 ± 357) compared to the PF meal (3190 ± 310; p < 0.05)., Conclusions: This multi-element approach demonstrated postprandial responsiveness to a steak meal, and an effect of the cooking method used. This suggests the method would provide insight in future elemental metabolic studies to evaluate responses to meat-based meals, including longer-term interventions in more specifically defined cohorts to clearly establish the role of red meat as an important source of elements.

The causal relationship between serum ferritin and metabolic syndrome (MetS) remains inconclusive. Dietary iron intake increases serum ferritin. The objective of this study was to evaluate associations of total, heme, and nonheme dietary iron intake with MetS and its components in men and women in metropolitan China. Data from 3099 participants in the Shanghai Diet and Health Survey (SDHS) obtained during 2012⁻2013 were included in this analysis. Dietary intake was assessed by 24-h diet records from 3 consecutive days. Multivariate generalized linear mixed models were used to evaluate the associations of dietary iron intake with MetS and its components. After adjustment for potential confounders as age, sex, income, physical exercise, smoking status, alcohol use, and energy intake, a positive trend was observed across quartiles of total iron intake and risk of MetS ( p for trend = 0.022). Compared with the lowest quartile of total iron intake (<12.72 mg/day), the highest quartile (≥21.88 mg/day) had an odds ratio (95% confidence interval), OR (95% CI), of 1.59 (1.15,2.20). In addition, the highest quartile of nonheme iron intake (≥20.10 mg/day) had a 1.44-fold higher risk of MetS compared with the lowest quartile (<11.62 mg/day), and higher risks of MetS components were associated with the third quartiles of total and nonheme iron intake. There was no association between heme iron intake and risk of MetS ( p for trend = 0.895). Associations for total and nonheme iron intake with MetS risk were found in men but not in women. Total and nonheme dietary iron intake was found to be positively associated with MetS and its components in the adult population in metropolitan China. This research also revealed a gender difference in the association between dietary iron intake and MetS.

Salmonella and the host battle for iron (Fe), due to its importance for fundamental cellular processes. To investigate Fe redistribution of Salmonella-infected hens and the effects of high dietary Fe on it, Salmonella-free hens were randomly assigned to 1 of 4 treatments in 2 (two dietary Fe level) × 2 (Salmonella-inoculation or -noninoculation) factorial assignment. After feeding a basal diet supplemented with 60 (adequate, control) or 300 mg Fe/kg (high-Fe) for 4 weeks, 59-week-old Salmonella-free hens were orally inoculated with 5 × 10 7 colony-forming units of Salmonella Typhimurium (infection) or PBS (vehicle). Blood, spleen, and liver samples (n = 8) were collected at 14 days post-inoculation to determine Fe concentration and Fe transporters expression. Salmonella infection decreased (P < 0.05) hematocrit, serum Fe concentration, and splenic Fe concentration regardless of high-Fe or control hens, whereas increased (P < 0.05) Fe centration in the livers of high-Fe-treated hens. High dietary Fe increased hematocrit and serum Fe concentration, but did not affect (P = 0.11) splenic Fe concentration in Salmonella-infected hens. Salmonella infection did not influence (P = 0.31) liver Fe centration in control hens, but increased (P = 0.04) it in high-Fe-treated hens. High dietary Fe decreased (P < 0.01) the mRNA abundance of divalent metal transporter 1 and transferrin receptor, but increased (P < 0.02) ferroportin-1 (FPN1) mRNA and protein in the spleens and the livers regardless of Salmonella-infected or vehicle hens. Salmonella infection increased (P < 0.02) FPN1 mRNA and protein expression in the spleens, but did not influence its expression in the livers. These results suggested Salmonella infection and high dietary Fe differently influence the Fe distribution in the spleen and the liver of Salmonella-infected hens.

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.

Predictive iron bioavailability (FeBio) methods aimed at evaluating the association between diet and body iron have been proposed, but few studies explored their validity and practical usefulness in epidemiological studies. In this cross-sectional study involving 127 women (18⁻42 years) with presumably steady-state body iron balance, correlations were checked among various FeBio estimates (probabilistic approach and meal-based and diet-based algorithms) and serum ferritin (SF) concentrations. Iron deficiency was defined as SF < 15 &micro;g/L. Pearson correlation, Friedman test, and linear regression were employed. Iron intake and prevalence of iron deficiency were 10.9 mg/day and 12.6%. Algorithm estimates were strongly correlated (0.69&le; r &ge;0.85; p < 0.001), although diet-based models (8.5⁻8.9%) diverged from meal-based models (11.6⁻12.8%; p < 0.001). Still, all algorithms underestimated the probabilistic approach (17.2%). No significant association was found between SF and FeBio from Monsen (1978), Reddy (2000), and Armah (2013) algorithms. Nevertheless, there was a 30⁻37% difference in SF concentrations between women stratified at extreme tertiles of FeBio from Hallberg and Hulth&eacute;n (2000) and Collings&rsquo; (2013) models. The results demonstrate discordance of FeBio from probabilistic approach and algorithm methods while suggesting two models with best performances to rank individuals according to their bioavailable iron intakes.

The role of hepcidin in iron homeostasis in preeclamptic pregnant women is unclear. To test the hypothesis that increased serum iron in women diagnosed with preeclampsia results from decreased production of hepcidin, we performed an observational case-control study in which serum hepcidin concentration, dietary iron intake, hematological indices, iron status, liver function, and inflammatory markers in 18 preeclamptic women and 18 healthy normotensive pregnant women of similar age range were evaluated. Iron intake was established via a food frequency questionnaire, whereas hematological indices, iron status, liver function, and inflammatory markers were assessed using standard protocols. Hematocrit was significantly higher (P = .031) in the preeclamptic group compared with the control, whereas erythropoietin level was significantly lower (P = .003). The pronounced inflammatory status of preeclamptic women was confirmed by significantly higher concentrations of interleukin-6 (P = .001), tumor necrosis factor-α (P < .001), and ferritin (P < .001). Nonetheless, the preeclamptic group exhibited significantly higher serum iron (P = .012) and transferrin saturation (P = .006), and these alterations were accompanied by lower hepcidin levels (P = .047). No significant correlations between hepcidin concentration and iron status parameters were observed in either group. However, a positive and significant correlation between hepcidin concentration and C-reactive protein was observed in the preeclamptic group (r = 0.474; P = .047). We conclude that high serum iron in preeclamptic women is likely caused by low production of hepcidin, thus supporting the hypothesis originally stated., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Whey proteins possess antioxidant properties, and probiotics have various health-promoting effects. We investigated the effects of whey protein hydrolysates (WPHs) and probiotics in rats exposed to oxidative stress induced by iron-overload diet (IOL). Rats were divided into control (CTRL), IOL (0.2% ferrous sulphate), WPH (10%), probiotic (PB) mixture (Lactococcus lactis NK34 and B. polyfermenticus SCD), and WPH + PB group for 6 weeks. Average leukocytes and colonocytes tail moments were increased in IOL compared to CTRL but decreased in other groups. Conjugated diene was lower in WPH, PB, and WPH + PB than in IOL. Only WPH + PB group could recover glutathione S-transferase (GST) levels. SOD levels were recovered by WPH and PB. PB and WPH + PB increased α-tocopherol and only WPH + PB increased γ-tocopherol. Thus, our data demonstrated that WPH and PB exhibit antioxidant properties in a rat model of high-iron diet-induced oxidative stress and combination of them may provide an enhanced effect.

During pregnancy, iron needs to increase substantially to support fetoplacental development and maternal adaptation to pregnancy. To meet these iron requirements, both dietary iron absorption and the mobilization of iron from stores increase, a mechanism that is in large part dependent on the iron-regulatory hormone hepcidin. In healthy human pregnancies, maternal hepcidin concentrations are suppressed in the second and third trimesters, thereby facilitating an increased supply of iron into the circulation. The mechanism of maternal hepcidin suppression in pregnancy is unknown, but hepcidin regulation by the known stimuli (i.e., iron, erythropoietic activity, and inflammation) appears to be preserved during pregnancy. Inappropriately increased maternal hepcidin during pregnancy can compromise the iron availability for placental transfer and impair the efficacy of iron supplementation. The role of fetal hepcidin in the regulation of placental iron transfer still remains to be characterized. This review summarizes the current understanding and addresses the gaps in knowledge about gestational changes in hematologic and iron variables and regulatory aspects of maternal, fetal, and placental iron homeostasis., (© 2017 American Society for Nutrition.)

Background: Tea has been shown to be a potent inhibitor of nonheme iron absorption, but it remains unclear whether the timing of tea consumption relative to a meal influences iron bioavailability. Objective: The aim of the study was to investigate the effect of a 1-h time interval of tea consumption on nonheme iron absorption in an iron-containing meal in a cohort of iron-replete, nonanemic female subjects with the use of a stable isotope ( 57 Fe). Design: Twelve women (mean ± SD age: 24.8 ± 6.9 y) were administered a standardized porridge meal extrinsically labeled with 4 mg 57 Fe as FeSO 4 on 3 separate occasions, with a 14-d time interval between each test meal (TM). The TM was administered with water (TM-1), with tea administered simultaneously (TM-2), and with tea administered 1 h postmeal (TM-3). Fasted venous blood samples were collected for iron isotopic analysis and measurement of iron status biomarkers. Fractional iron absorption was estimated by the erythrocyte iron incorporation method. Results: Iron absorption was 5.7% ± 8.5% (TM-1), 3.6% ± 4.2% (TM-2), and 5.7% ± 5.4% (TM-3). Mean fractional iron absorption was found to be significantly higher (2.2%) when tea was administered 1 h postmeal (TM-3) than when tea was administered simultaneously with the meal (TM-2) ( P = 0.046). An ∼50% reduction in the inhibitory effect of tea (relative to water) was observed, from 37.2% (TM-2) to 18.1% (TM-3). Conclusions: This study shows that tea consumed simultaneously with an iron-containing porridge meal leads to decreased nonheme iron absorption and that a 1-h time interval between a meal and tea consumption attenuates the inhibitory effect, resulting in increased nonheme iron absorption. These findings are not only important in relation to the management of iron deficiency but should also inform dietary advice, especially that given to those at risk of deficiency. This trial was registered at clinicaltrials.gov as NCT02365103., (© 2017 American Society for Nutrition.)

Background: Evidence shows that iron deficiency in adulthood may affect cognitive performance, possibly by disrupting neurotransmitter regulation or brain energy metabolism. Women of reproductive age (WRA) are among those who are most vulnerable to iron deficiency; however, they have been largely ignored in the literature relating iron status to cognition. Objective: Our aim was to determine the efficacy of iron-biofortified beans in improving cognition in WRA compared with control beans. Methods: A double-blind, randomized intervention study was conducted in 150 women aged 18-27 y with low iron status (ferritin <20 μg/L). Women were randomly assigned to consume iron-biofortified beans (86.1 ppm iron) or control beans (50.1 ppm iron) daily for 18 wk. Iron status was assessed based on hemoglobin, ferritin, transferrin receptor, and body iron values and on cognitive performance on 5 computerized tasks at baseline and endline. Results: Groups did not differ on any variables at baseline. Per protocol analyses revealed that consumption of the biofortified beans resulted in a 17% larger improvement in the speed of spatial selective attention; a nearly 7-fold larger improvement in the speed, a 68% greater improvement in the efficiency, and a >2-fold greater improvement in the specificity of memory retrieval; and a >2-fold larger improvement in the speed and a >3-fold larger improvement in the efficiency of memory search-all of which are relative to consumption of the control beans ( P < 0.01 for all comparisons). Conclusions: Cognitive performance is sensitive to iron status, and consumption of iron-biofortified beans for 18 wk improved cognitive performance, especially the efficiency of search and the speed of retrieval on memory tasks, in young adult women. This trial was registered at clinicaltrials.gov as NCT01594359., Competing Interests: Author disclosures: LEM-K, MJW, SPS, SER, MGL, and JDH, no conflicts of interest. MJW and JDH served as paid technical consultants for HarvestPlus/International Food Policy Research Institute. The funders of this study had no role in the study design and implementation; data collection, analysis, and interpretation; or writing of the manuscript.

Background: Special Operations Forces (SOF) Soldiers deploy frequently and require high levels of physical and cognitive performance. Nutritional status is linked to cognitive and physical performance. Studies evaluating dietary intake and nutritional status in deployed environments are lacking. Therefore, this study assessed the effects of combat deployment on diet quality and serum concentrations of nutritional status markers, including iron, vitamin D, parathyroid hormone (PTH), glucose, and lipids, among elite United States (U.S.) Army SOF Soldiers., Methods: Changes from baseline to post-deployment were determined with a repeated measure within-subjects design for Healthy Eating Index-2010 (HEI-2010) scores, intake of foods, food groups, key nutrients, and serum nutritional status markers. Dietary intake was assessed with a Block Food Frequency Questionnaire. The association between post-deployment serum 25-hydroxy vitamin D (25-OH vitamin D) and PTH was determined. Analyses of serum markers were completed on 50 participants and analyses of dietary intake were completed on 33 participants., Results: In response to deployment, HEI-2010 scores decreased for total HEI-2010 (70.3 ± 9.1 vs. 62.9 ± 11.1), total fruit (4.4 ± 1.1 vs. 3.7 ± 1.5), whole fruit (4.6 ± 1.0 vs. 4.2 ± 1.4), dairy (6.2 ± 2.7 vs. 4.8 ± 2.4), and empty calories (14.3 ± 3.2 vs. 11.1 ± 4.5) (P ≤ 0.05). Average daily intakes of foods and food groups that decreased included total dairy (P < 0.01), milk (P < 0.01), and non-juice fruit (P = 0.03). Dietary intake of calcium (P = 0.05) and vitamin D (P = 0.03) decreased. PTH increased from baseline (3.4 ± 1.6 vs. 3.8 ± 1.4 pmol/L, P = 0.04), while there was no change in 25-OH vitamin D. Ferritin decreased (385 ± 173 vs. 354 ± 161 pmol/L, P = 0.03) and soluble transferrin receptor increased (16.3 ± 3.7 vs. 17.1 ± 3.5 nmol/L, P = 0.01). There were no changes in glucose or lipids. Post-deployment, serum 25-OH vitamin D was inversely associated with PTH (r = -0.43, P < 0.01)., Conclusions: HEI-2010 scores and dietary intake of milk, calcium, and vitamin D decreased following deployment. Serum PTH increased and iron stores were degraded. No Soldiers were iron deficient. Personnel that deploy frequently should maintain a high diet quality in the U.S. and while deployed by avoiding empty calories and consuming fruits, vegetables, and adequate sources of calcium, vitamin D, and iron. Improving availability and quality of perishable food during deployment may improve diet quality.

Young children are at risk of iron deficiency and subsequent anaemia, resulting in long-term consequences for cognitive, motor and behavioural development. This study aimed to describe the iron intakes, status and determinants of status in 2-year-old children. Data were collected prospectively in the mother-child Cork BASELINE Birth Cohort Study from 15 weeks' gestation throughout early childhood. At the 24-month assessment, serum ferritin, haemoglobin and mean corpuscular volume were measured, and food/nutrient intake data were collected using a 2-day weighed food diary. Iron status was assessed in 729 children (median [IQR] age: 2.1 [2.1, 2.2] years) and 468 completed a food diary. From the food diary, mean (SD) iron intakes were 6.8 (2.6) mg/day and 30% had intakes < UK Estimated Average Requirement (5.3 mg/day). Using WHO definitions, iron deficiency was observed in 4.6% (n = 31) and iron deficiency anaemia in five children (1.0%). Following an iron series workup, five more children were diagnosed with iron deficiency anaemia. Twenty-one per cent had ferritin concentrations <15 µg/L. Inadequate iron intakes (OR [95% CI]: 1.94 [1.09, 3.48]) and unmodified cows' milk intakes ≥ 400 mL/day (1.95 [1.07, 3.56]) increased the risk of low iron status. Iron-fortified formula consumption was associated with decreased risk (0.21 [0.11, 0.41] P < 0.05). In this, the largest study in toddlers in Europe, a lower prevalence of low iron status was observed than in previous reports. Compliance with dietary recommendations to limit cows' milk intakes in young children and consumption of iron-fortified products appears to have contributed to improved iron status at two years., (© 2016 John Wiley & Sons Ltd.)

Objective: To determine the associations between haemoconcentration at the end of pregnancy (third trimester and delivery) and neonatal behaviour in healthy pregnant women supplemented with moderate doses of Fe., Design: A prospective longitudinal study in which obstetric and clinical history, maternal toxic habits, maternal anxiety and Hb levels were recorded at the third trimester and delivery. Neonatal behaviour was assessed at 48-72 h of age using the Neonatal Behavioral Assessment Scale., Setting: Unit of Obstetrics and Gynaecology of the Sant Joan University Hospital in Reus, Tarragona (Spain)., Subjects: A total of 210 healthy and well-nourished pregnant women and their full-term, normal-weight newborns., Results: The results showed that, after adjusting for confounders, in the third trimester the risk of haemoconcentration (6·2 % of pregnant women) was related to decreased neonatal state regulation (B=-1·273, P=0·006) and alertness (B=-1·848, P=0·006) scores. In addition, the risk of haemoconcentration at delivery (12·0 % of pregnant women) was also related to decreased neonatal state regulation (B=-0·796, P=0·021) and poor robustness and endurance (B=-0·921, P=0·005) scores., Conclusions: Our results show that the risk of haemoconcentration at the end of pregnancy is related to the neonate's neurodevelopment (and self-regulation capabilities), suggesting that Fe supplementation patterns and maternal Fe status during pregnancy are important factors for neurodevelopment which may be carefully controlled.

Background: Values for dietary iron bioavailability are required for setting dietary reference values. These are estimated from predictive algorithms, nonheme iron absorption from meals, and models of iron intake, serum ferritin concentration, and iron requirements. Objective: We developed a new interactive tool to predict dietary iron bioavailability. Design: Iron intake and serum ferritin, a quantitative marker of body iron stores, from 2 nationally representative studies of adults in the United Kingdom and Ireland and a trial in elderly people in Norfolk, United Kingdom, were used to develop a model to predict dietary iron absorption at different serum ferritin concentrations. Individuals who had raised inflammatory markers or were taking iron-containing supplements were excluded. Results: Mean iron intakes were 13.6, 10.3, and 10.9 mg/d and mean serum ferritin concentrations were 140.7, 49.4, and 96.7 mg/L in men, premenopausal women, and postmenopausal women, respectively. The model predicted that at serum ferritin concentrations of 15, 30, and 60 mg/L, mean dietary iron absorption would be 22.3%, 16.3%, and 11.6%, respectively, in men; 27.2%, 17.2%, and 10.6%, respectively, in premenopausal women; and 18.4%, 12.7%, and 10.5%, respectively, in postmenopausal women. Conclusions: An interactive program for calculating dietary iron absorption at any concentration of serum ferritin is presented. Differences in iron status are partly explained by age but also by diet, with meat being a key determinant. The effect of the diet is more marked at lower serum ferritin concentrations. The model can be applied to any adult population in whom representative, good-quality data on iron intake and iron status have been collected. Values for dietary iron bioavailability can be derived for any target concentration of serum ferritin, thereby giving risk managers and public health professionals a flexible and transparent basis on which to base their dietary recommendations. This trial was registered at clinicaltrials.gov as NCT01754012., (© 2017 American Society for Nutrition.)

Background: Ready-to-use-therapeutic foods (RUTFs) high in lipid, protein, and iron are used to treat malnutrition. Lipids increase gastric residence time, which could increase iron absorption, particularly from poorly soluble iron compounds and in combination with phytase. Objectives: The objectives were to 1 ) assess the effect on iron absorption of a lipid emulsion given 20 min before or together with an iron-fortified maize meal and 2 ) assess iron absorption from a micronutrient powder (MNP) given with a nutrient-dense RUTF and/or a microbial phytase. Design: A total of 41 women participated in 3 studies. They consumed a maize meal fortified with isotopically labeled ferrous sulfate (FeSO 4 ; study 1) or ferric pyrophosphate (FePP; study 2). In studies 1 and 2, a lipid emulsion was given with or 20 min before the meal. In study 3, with the use of a 2 × 2 factorial design, subjects consumed a maize meal fortified with an MNP containing labeled FeSO 4 (MNP) given with an RUTF (MNP+RUTF), with a phytase (MNP+phytase), or both (MNP+RUTF+phytase). Iron absorption was assessed by isotope incorporation in erythrocytes 14 d after the test meals. Results: The lipid emulsion given either before or with the meal significantly increased iron absorption from FePP by 2.55-fold (95% CI: 1.48-, 4.37-fold; P = 0.001) but not from FeSO 4 There was a trend to increase iron absorption with the MNP+RUTF meal, which did not reach significance (1.21-fold; 95% CI: 0.92-, 1.61-fold; P = 0.060). The addition of phytase to MNP and MNP+RUTF significantly increased iron absorption by 1.85-fold (95% CI: 1.49-, 2.29-fold; P < 0.001), with no interaction between phytase and RUTF. Conclusions: In iron-fortified maize-based meals, the addition of lipids more than doubles iron absorption from FePP. Our results suggest the possibility of an enhancing effect on iron absorption of lipid-rich RUTFs, but more research is needed to determine this. This trial was registered at clinicaltrials.gov as NCT01991626., (© 2017 American Society for Nutrition.)

Multivitamin/mineral supplements (MVMs) are widely used in many populations. MVMs, together with iron and folic acid, are recommended for pregnant women to improve birth outcome and to reduce low-birthweight and rates of miscarriage. However, MVM use is common in the general population as well. The aim of the present review was to evaluate the safety of long-term use of these supplements. To examine the safety of MVM use, we performed a literature search for randomized controlled studies involving supplementation with a combination of at least nine vitamins and three minerals at a maximum concentration of 100% of the Recommended Dietary Allowance. We found nine studies evaluating the use and efficacy of MVMs in pregnant women and healthy adults and six studies in the elderly where adverse effects were explicitly addressed. Only minor adverse events (e.g., unspecific gastrointestinal symptoms) were reported in all studies. In particular, there were no significant differences between treatment and placebo groups. MVM use within the range of the Dietary Reference Intake will not result in excess intake, even when including the effect of food and fortified food, and does not increase mortality. Taken together, these findings indicate that MVMs can be safe for long-term use (>10 y)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the influence of oral iron supplementation, in the form of fortified breads, on the growth performance, health, iron status parameters, and fecal metabolome of anemic piglets. A study was conducted on 24 hybrid (Large White × Landrace × Duroc) piglets. From day 44, the post-natal 12 piglets were supplemented with 100 g of one of two experimental breads, each fortified with 21 mg of ferrous sulphate, either encapsulated or not. After one week of oral supplementation, hematological parameters (hematocrit value, hemoglobin, and red blood cells) showed statistically significant differences ( p ≤ 0.05). Piglets fed with the fortified breads had higher iron concentrations in the heart, liver, and intestinal mucosa compared to anemic piglets fed with control bread. Gene expression of hepcidin, iron exporter ferroportin (IREG1), and divalent metal transporter 1 (DMT1), together with concentrations of plasma ferritin, showed no significant statistical differences between groups. Both fortified breads could be used as sources of bioavailable iron. The seven-day intervention trial showed microencapsulation to have only a mild effect on the effectiveness of iron supplementation in the form of fortified bread.

Anaemia is prevalent in developing countries and is commonly Fe deficiency related. We aimed to assess the association between Fe status, Fe intake and mortality among Chinese adults. We prospectively studied 8291 adults aged 20-98 years with a mean follow-up of 9·9 years. All participants were measured for Hb at baseline in 2002. Food intake, measured by 3-d weighed food record (n 2832), and fasting serum ferritin were measured. We documented 491 deaths (including 192 CVD and 165 cancer deaths) during 81 527 person-years of follow-up. There was a U-shaped association between Hb levels and all-cause mortality. Compared with the second quartile of Hb (121 g/l), the first (105) and fourth quartile (144) had hazard ratios (HR) of 2·29 (95 % CI 1·51, 3·48) and 2·31 (95 % CI 1·46, 3·64) for all-cause mortality in women. In men, compared with third quartile of Hb (143 g/l), first (122) and fourth quartiles (154) had 61 and 65 % increased risk of all-cause mortality. Anaemia was associated with an increased risk of all-cause and CVD mortality in men but not in women after adjusting for potential confounders. Low and high Fe intake as percentage of Chinese recommended nutrient intake (RNI) were positively associated with all-cause mortality in women but not in men. In women, across quartiles of relative Fe intake, HR for all-cause mortality were 2·55 (95 % CI 0·99, 6·57), 1·00, 3·12 (95 % CI 1·35, 7·18) and 2·78 (95 % CI 1·02, 7·58). Both low and high Hb levels are related to increased risk of all-cause mortality. Both low and high intake of Fe as percentage of RNI was positively associated with mortality in women.

In light of evidence that high-dose iron supplements lead to a range of adverse events in low-income settings, the safety and efficacy of lower doses of iron provided through biological or industrial fortification of foodstuffs is reviewed. First, strategies for point-of-manufacture chemical fortification are compared with biofortification achieved through plant breeding. Recent insights into the mechanisms of human iron absorption and regulation, the mechanisms by which iron can promote malaria and bacterial infections, and the role of iron in modifying the gut microbiota are summarized. There is strong evidence that supplemental iron given in nonphysiological amounts can increase the risk of bacterial and protozoal infections (especially malaria), but the use of lower quantities of iron provided within a food matrix, ie, fortified food, should be safer in most cases and represents a more logical strategy for a sustained reduction of the risk of deficiency by providing the best balance of risk and benefits. Further research into iron compounds that would minimize the availability of unabsorbed iron to the gut microbiota is warranted., (© The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Background: In the monitoring of infant and young child feeding, dietary diversity is used as an indicator of micronutrient adequacy; however, their relation may have weakened with the increasing use of fortified complementary foods., Objective: The objectives were to assess the relation between dietary diversity and micronutrient adequacy in an urban infant population with a high consumption of fortified foods and to investigate whether dietary diversity and micronutrient adequacy were independently associated with subsequent growth., Methods: We used longitudinal data on 811 infants in the Chilenje Infant Growth, Nutrition, and Infection Study conducted in Lusaka, Zambia. The relation between mean micronutrient adequacies and dietary diversity scores derived from 24-h diet recalls at 6 mo of age was investigated with the use of Spearman rank correlation. Multiple linear regression was used to assess the association between micronutrient adequacy, dietary diversity, and subsequent growth to 18 mo of age., Results: Overall mean micronutrient density adequacy (MMDA) and MMDA of "problem micronutrients," defined as those micronutrients (calcium, iron, zinc) with mean density adequacies less than half of estimated needs, were correlated with dietary diversity scores (ρ = 0.36 and 0.30, respectively, both P < 0.0001). Consumption of "sentinel foods" (iron rich, fortified, animal source, dairy) showed better correlation with MMDA than with dietary diversity (ρ = 0.58-0.69, all P < 0.0001). In fully adjusted analyses, MMDA calcium, iron, zinc, and dietary diversity, but not overall MMDA, were associated with linear growth to 18 mo (both P ≤ 0.028)., Conclusions: Micronutrient adequacy in infants consuming fortified foods may be more accurately assessed using locally specific sentinel food indicators rather than dietary diversity scores. Nonetheless, dietary diversity has a positive effect on subsequent linear growth apart from that of micronutrient adequacy, warranting its continued monitoring and further investigation into the mechanisms underlying this finding. This trial was registered at www.controlled-trials.com as ISRCTN37460449., (© 2016 American Society for Nutrition.)

The relationship between dietary intake, circulating hepcidin and iron status in free-living premenopausal women has not been explored. This cross-sectional study aimed to identify dietary determinants of iron stores after accounting for blood loss and to determine whether iron intake predicts iron stores independently of hepcidin in a sample of Australian women. Three hundred thirty eight women aged 18-50 years were recruited. Total intake and food sources of iron were determined via food frequency questionnaire; the magnitude of menstrual losses was estimated by self-report; and blood donation volume was quantified using blood donation records and self-reported donation frequency. Serum samples were analysed for ferritin, hepcidin and C-reactive protein concentrations. Linear regression was used to investigate associations. Accounting for blood loss, each 1 mg/day increase in dietary iron was associated with a 3% increase in iron stores (p = 0.027); this association was not independent of hepcidin. Hepcidin was a more influential determinant of iron stores than blood loss and dietary factors combined (R² of model including hepcidin = 0.65; R² of model excluding hepcidin = 0.17, p for difference <0.001), and increased hepcidin diminished the positive association between iron intake and iron stores. Despite not being the biggest contributor to dietary iron intake, unprocessed meat was positively associated with iron stores, and each 10% increase in consumption was associated with a 1% increase in iron stores (p = 0.006). No other dietary factors were associated with iron stores. Interventions that reduce hepcidin production combined with dietary strategies to increase iron intake may be important means of improving iron status in women with depleted iron stores., Competing Interests: C.A.N. is a member of World Action on Salt and Health and the Australian division of World Action on Salt and Health and does not receive any financial support from these organizations. C.A.N. has received remuneration from Meat and Livestock Australia Ltd., Nestle Health Science and the Dairy Health Consortium. These payments are unrelated to the submitted work. The remaining authors, K.H.C.L., A.O.B, E.A.S.-G., D.O.I. and L.J.R., declare no conflict of interest.

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.)

Background: Children prenatally exposed to inadequate iron have poorer motor and neurocognitive development. No prior study to our knowledge has assessed the influence of maternal prenatal iron intake on newborn brain tissue organization in full-term infants., Methods: Third trimester daily iron intake was obtained using the Automated Self-Administered 24-h Dietary Recall with n = 40 healthy pregnant adolescents (aged 14-19 y). Cord blood ferritin was collected in a subsample (n = 16). Newborn (mean = 39 gestational weeks at birth; range 37-41) magnetic resonance imaging scans were acquired on a 3.0 Tesla MR Scanner. Diffusion Tensor Imaging (DTI) slices were acquired to measure the directional diffusion of water indexed by fractional anisotropy (FA)., Results: Reported iron intake was inversely associated with newborn FA values (P ≤ 0.0001) predominantly in cortical gray matter. FA findings were similar using cord blood ferritin values., Conclusion: Higher maternal prenatal iron intake accentuates, and lower intake attenuates, the normal age-related decline in FA values in gray matter, perhaps representing increasing dendritic arborization and synapse formation with higher iron intake. These DTI results suggest that typical variation in maternal iron outside the scope of standard clinical surveillance exerts subtle effects on infant brain development.

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.)

Background: Previous trials of iron supplementation in infancy did not consider maternal iron supplementation., Objective: This study assessed effects of iron supplementation in infancy and/or pregnancy on infant iron status, illnesses, and growth at 9 mo., Methods: Enrollment occurred from December 2009 to June 2012 in Hebei, China. Infants born to women in a pregnancy iron supplementation trial were randomly assigned 1:1 to iron [∼1 mg Fe/(kg · d) as oral iron proteinsuccynilate] or placebo from 6 wk to 9 mo, excluding infants with cord ferritin <35 μg/L. Study groups were pregnancy placebo/infancy placebo (placebo/placebo), pregnancy placebo/infancy iron (placebo/iron), pregnancy iron/infancy placebo (iron/placebo), and pregnancy iron/infancy iron (iron/iron). The primary outcome was 9-mo iron status: iron deficiency (ID) by cutoff (≥2 abnormal iron measures) or body iron <0 mg/kg and ID + anemia (hemoglobin <110 g/L). Secondary outcomes were doctor visits or hospitalizations and weight or length gain from birth to 9 mo. Statistical analysis by intention to treat and dose-response (between number of iron bottles received and outcome) used logistic regression with concomitant RRs and general linear models, with covariate control as applicable., Results: Of 1482 infants randomly allocated, 1276 had 9-mo data (n = 312-327/group). Iron supplementation in infancy, but not pregnancy, reduced ID risk: RRs (95% CIs) were 0.89 (0.79, 0.998) for placebo/iron compared to placebo/placebo, 0.79 (0.63, 0.98) for placebo/iron compared to iron/placebo, 0.87 (0.77, 0.98) for iron/iron compared to placebo/placebo, and 0.86 (0.77, 0.97) for iron/iron compared to iron/placebo. However, >60% of infants still had ID at 9 mo. Receiving more bottles of iron in infancy was associated with better infant iron status at 9 mo but only among iron-supplemented infants whose mothers were also iron supplemented (i.e., the iron/iron group). There were no group differences in hospitalizations or illnesses and no adverse effects on growth overall or among infants who were iron sufficient at birth., Conclusions: Iron supplementation in Chinese infants reduced ID at 9 mo without adverse effects on growth or illness. Effects of iron supplementation in pregnancy were observed only when higher amounts of iron were distributed in infancy. This trial was registered at clinicaltrials.gov as NCT00613717., (© 2016 American Society for Nutrition.)

Multiple micronutrient deficiencies exist in school going children in India and bridging the gap between nutrient intake and requirements is an effective way to combat the deficiencies. This study aimed to test the effect of a multi-micronutrient fortified malt and cocoa based milk beverage on the micronutrient status, cognition, physical performance and nutritional deficiencies of 7-10 years old south Indian children. A randomized, double blind placebo controlled study design was used with normal healthy children from low to middle income families, aged 7-10 years randomly assigned to receive either a multi-micronutrient fortified or an unfortified milk based control drink. The drinks were provided 6 days/week for 5 months. Assessments included anthropometry, blood biochemistry, physical performance and cognition at baseline and endline. The baseline characteristics of the study groups were similar. The changes in body weight and height were similar between the groups at the end of the study. Levels of vitamin B12, red cell folate and vitamin B2 significantly improved in the intervention group, while vitamin D, selenium and body iron showed no difference. The Hemoglobin (Hb) and serum ferritin levels of the control group decreased at endline, while those in the intervention group maintained their levels. The serum transferrin receptor levels increased in both the groups. The prevalence of iron deficiency and Vitamin B2 deficiency were significantly lower in the intervention group at endline. Overall improvement in cognitive and physical performance was seen in both the groups at endline, with no significant differences between the groups. The micronutrient fortified milk based drink was efficacious in improving the micronutrient status of Vitamin B2, Vitamin B12 and red cell folate and in preventing a decline in Hb level compared to an unfortified milk based drink. It also reduced anemia and the risk of deficiencies of iron, and B12, in apparently healthy children. ClinicalTrials.gov IdentifierNCT01415557. Clinical Trial RegistryIndia - REF/2012/12/004332., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Iron is needed for oxygen transport, muscle activity, mitochondrial function, DNA synthesis, and sensing of hypoxia. The hierarchical master determinant of dietary iron absorption and iron distribution within the body is the peptide hormone hepcidin. Hepcidin itself is regulated by a combination of signals derived from iron stores, inflammation, and erythropoietic expansion. Iron deficiency and iron deficiency anemia are common and important conditions that can be treated with iron preparations. However, other factors besides iron deficiency can cause anemia, especially inflammation, which responds poorly to iron treatment, and inherited disorders of red blood cells, which are associated with accumulation of excess pathogenic iron. Assessment of iron status is challenging, and indices such as serum ferritin, soluble transferrin receptor, and zinc protoporphyrin have specific weaknesses. Moreover, a diagnosis of iron deficiency or iron deficiency anemia is most useful if the diagnosis also leads to effective treatment. Low levels of hepcidin allow iron absorption and effective iron incorporation into red blood cells. The best 'biomarker' to guide treatment may therefore be the physiological 'determinant' of iron utilization. Iron is also important in transplantation medicine and influences clinical outcome of arterial pulmonary hypertension; here too, biomarkers including hepcidin may be useful to actively and beneficially manage iron status., (© 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Iron deficiency, one of the most widespread nutritional disorders, affects millions of people in emerging economies and, increasingly, in industrialized countries. Due to the high iron requirements during growth and development, infants and young children are among those most severely affected by iron deficiency. Iron deficiency that occurs during the critical phases of early life development has long-lasting health consequences that are reflected in increased risk of disease, reduced economic productivity and premature death, underscoring the importance of infants and young children as a key target group for addressing iron deficiency. This chapter focuses on the use of fortified foods as a cost-effective mechanism to address iron deficiency in this particularly vulnerable subpopulation. Nutritional policies that include food fortification need to be implemented within the context of effective public-private partnerships in order to address the fundamental mechanisms of accessibility, affordability and availability of nutritious food items for those in the lowest socio-economic strata., (© 2016 S. Karger AG, Basel.)

The egg is a nutrient-dense food and contains a number of antioxidants. The consumption of eggs has been considered to improve the balance of diets, although its impact on serum cholesterol levels has been a matter of concern in many countries. Here, we conducted a pilot study to investigate whether daily additional consumption of an egg might affect serum lipid profiles and also antioxidant status in healthy subjects. Fourteen male subjects were provided with breakfasts including a boiled egg for 4 wk. At the end of intervention, serum concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were unchanged, despite the significant increase in the intake of dietary cholesterol. In contrast, a significant increase in high-density lipoprotein cholesterol (HDL-C) and a reduction of the LDL-C/HDL-C ratio were observed. Interestingly, the malondialdehyde modified-LDL (MDA-LDL)/LDL-C ratio and the oxidizability of LDL were significantly reduced. Serum total antioxidant capacity value after the intervention period was higher than at baseline. These data indicate that consuming one egg per day for 4 wk as breakfast in addition to a normal diet does not affect serum lipids, and suggests that it may improve serum antioxidant status in healthy males.

A quick-cooking rice, produced from broken rice, is a convenient ingredient for complementary foods in Thailand. The rice is fortified with micronutrients including iron during the processing procedure, which can cause unacceptable sensory changes. A quick-cooking rice fortified with ferric ammonium citrate (FAC) or a mixture of ferrous sulphate (FeSO4 ) and ferric sodium ethylenediaminetetraacetic acid (NaFeEDTA), with a 2:1 molar ratio of iron from FeSO4  : iron from NaFeEDTA (FeSO4  + NaFeEDTA), gave a product that was organoleptically acceptable. The study compared iron absorption by infants and young children fed with micronutrient-fortified quick-cooking rice containing the test iron compounds or FeSO4 . Micronutrient-fortified quick-cooking rice prepared as a traditional Thai dessert was fed to two groups of 15 8-24-month healthy Thai children. The iron fortificants were isotopically labelled with (57) Fe for the reference FeSO4 or (58) Fe for the tested fortificants, and iron absorption was quantified based on erythrocyte incorporation of the iron isotopes 14 days after feeding. The relative bioavailability of FAC and of the FeSO4  + NaFeEDTA was obtained by comparing their iron absorption with that of FeSO4 . Mean fractional iron absorption was 5.8% [±standard error (SE) 1.9] from FAC and 10.3% (±SE 1.9) from FeSO4  + NaFeEDTA. The relative bioavailability of FAC was 83% (P = 0.02). The relative bioavailability of FeSO4  + NaFeEDTA was 145% (P = 0.001). Iron absorption from the rice containing FAC or FeSO4  + NaFeEDTA was sufficiently high to be used in its formulation, although iron absorption from FeSO4  + NaFeEDTA was significantly higher (P < 0.00001)., (© 2015 John Wiley & Sons Ltd.)

Food fortification is a cost-effective and sustainable strategy to prevent or correct micronutrient deficiencies. A double-blind cluster (bari) randomised controlled trial was conducted in a rural community in Bangladesh to evaluate the impact of consumption of chapatti made of micronutrient-fortified wheat flour for 6 months by school-aged children on their vitamin A, haemoglobin and iron status. A total of 43 baris (group of households) were randomly selected. The baris were randomly assigned to either intervention or control group. The intervention group received wheat flour fortified with added micronutrients (including 66 mg hydrogen-reduced elemental iron and 3030 μg retinol equivalent as retinyl palmitate per kilogram of flour), while the control group received wheat flour without added micronutrients. A total of 352 children were enrolled in the trial, 203 in the intervention group and 149 in the control group. Analyses were carried out on children who completed the study (191 in the intervention group and 143 in the control group). Micronutrient-fortified wheat flour chapatti significantly increased serum retinol concentration at 6 months by 0.12 μmol L(-1) [95% confidence interval (CI): 0.06, 0.19; P < 0.01]. The odds of vitamin A deficiency was significantly lower for children in the intervention group at 3 months [odds ratio (OR) = 0.26; 95% confidence interval (CI): 0.07, 0.89; P < 0.05] and 6 months (OR = 0.21; 95% CI: 0.06, 0.68; P < 0.01). No demonstrable effect of fortified chapatti consumption on iron status, haemoglobin levels or anaemia was observed. Consumption of fortified chapattis demonstrated a significant improvement in the vitamin A status, but not in iron, haemoglobin or anaemia status., (© 2013 John Wiley & Sons Ltd.)

Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS1-infected INS-GAS mice will be an appropriate animal model for further study of the effects of concurrent H. pylori infection and anemia on iron homeostasis and adult iron-dependent brain gene expression.

Background: Total (heme and nonheme) iron bioavailability from the US diet has been estimated to be 18% based on a single human absorption study. New data, however, suggest that it may be time to revisit this estimate., Objective: We estimated total iron bioavailability from the US diet with the use of our recently reported algorithm that estimates nonheme iron absorption and a conservative value for heme iron absorption., Methods: We used dietary intake and biomarker information from the NHANES 2001-2002, MyPyramid Equivalents Database, and Food and Nutrient Database for Dietary Studies. The survey package in R software was used to estimate means and CIs, taking into account the strata, primary sampling units, and appropriate survey weight. We implemented 2 different approaches to estimate total iron absorption. In the first approach, we included all survey participants but adjusted the geometric mean of nonheme iron absorption to 15 μg ferritin/L serum to mimic values of individuals with no iron stores; in the second approach, absorption was estimated for only nonanemic subjects with no iron stores. A total sample size of 6631 was used based on availability of dietary and iron status biomarker data and C-reactive protein concentration ≤ 6 mg/L., Results: The geometric mean (95% CI) of unadjusted nonheme iron absorption for all subjects was 3.7% (3.6%, 3.8%), higher in female subjects [5.6% (5.4%, 5.7%)] than male subjects [2.6% (2.5%, 2.7%)] (P < 0.0001). Nonheme iron absorption was lower in non-Hispanic whites [3.5% (3.4%, 3.6%)] than Mexican Americans [4.5% (4.2%, 4.8%)] and non-Hispanic blacks [4.4% (4.1%, 4.7%)]. Estimated total iron absorption was 15.5% or 15.1%, depending on which approach was used to carry out the calculations., Conclusion: This study provides useful data for evaluating the current value of iron bioavailability from the US diet., (© 2015 American Society for Nutrition.)

Background: Fortification of milk formulas with iron is a strategy widely used, but the absorption of non-heme iron is low. The purpose of this study was to measure the bioavailability of two iron fortified milk formulas designed to cover toddlers´ nutritional needs. These milks were fortified with iron sulfate stabilized with maltodextrin and citric acid., Methods: 15 women (33-47 years old) participated in study. They received on different days, after an overnight fast, 200 mL of Formula A; 200 mL of Formula B; 30 mL of a solution of iron and ascorbic acid as reference dose and 200 mL of full fat cow's milk fortified with iron as ferrous sulfate. Milk formulas and reference dose were labeled with radioisotopes (59)Fe or (55)Fe, and the absorption of iron measured by erythrocyte incorporation of radioactive Fe., Results: The geometric mean iron absorption corrected to 40% of the reference dose was 20.6% for Formula A and 20.7% for Formula B, versus 7.5% of iron fortified cow's milk (p < 0.001). The post hoc Sheffé indeed differences between the milk formulas and the cow's milk (p < 0.001)., Conclusion: Formulas A and B contain highly bioavailable iron, which contributes to covering toddlers´ requirements of this micronutrient.

Iron deficiency is common, especially among young women. Adding probiotics to foods could be one way to increase iron absorption. The aim of this study was to test the hypothesis that non-haem iron absorption from a fruit drink is improved by adding Lactobacillus plantarum 299v (Lp299v). Iron absorption was studied in healthy women of reproductive age using a single-blind cross-over design in two trials applying the double-isotope (55Fe and 59Fe) technique. In Trial 1, iron absorption from a fruit drink containing 109 colony-forming units (CFU) Lp299v was compared with that from a control drink without Lp299v. Trial 2 had the same design but 1010 CFU were used. The test and control drinks contained approximately 5 mg of iron as ferrous lactate and were labelled with 59Fe (B) and 55Fe (A), respectively, and consumed on 4 consecutive days in the order AABB. Retention of the isotopes was measured with whole-body counting and in blood. Mean iron absorption from the drink containing 109 CFU Lp299v (28·6(sd 12·5) %) was significantly higher than from the control drink (18·5(sd 5·8) %), n 10, P<0·028). The fruit drink with 1010 CFU Lp299v gave a mean iron absorption of 29·1(sd 17·0) %, whereas the control drink gave an absorption of (20·1(sd 6·4) %) (n 11, P<0·080). The difference in iron absorption between the 109 CFU Lp299v and the 1010 CFU Lp299v drinks was not significant (P=0·941). In conclusion, intake of probiotics can increase iron absorption by approximately 50 % from a fruit drink having an already relatively high iron bioavailability.

Iron is a functional component of oxygen transport and energy production in humans and therefore is a critically important micronutrient for sport and exercise performance. Athletes, particularly female athletes participating in endurance sport, are at increased risk of compromised iron status due to heightened iron losses through menstruation and exercise-induced mechanisms associated with endurance activity. Conventionally oral iron supplementation is used in prevention or/and treatment of iron deficiency. However, this approach has been criticised because of the side effects and increased risk of iron toxicity associated with the use of supplements. Thus, more recently there has been a growing interest in using dietary modification rather than the use of supplements to improve iron status of athletes. Dietary iron treatment methods include the prescription of an iron-rich diet, or/and haem iron-based diet, dietary advice counselling and inclusion of novel iron-rich products into the daily diet. Although studies using dietary modification are still scarce, current literature suggests that dietary iron interventions can assist in maintaining iron status in female athletes, especially during intensive training and competition. Future research should focus on the most efficient method(s) of dietary modification for improvement of iron status and whether these approaches can have a favourable impact on sports and exercise performance.

Background: Despite a World Health Organization recommendation for exclusive breastfeeding of all full-term infants to 6 months of age, it is not clear what the health implications may be. Breast milk alone may not meet the nutrition needs for all growing infants, leaving them at risk for deficiencies. The objective of this study was to investigate the relationship between moderate (4 months) versus late (6 months) introduction of complementary foods to the full-term breastfed infant on iron status and growth., Methods: An electronic search of peer-reviewed and gray-literature was conducted for randomized control trials (RCTs) and observational studies related to the timing of introduction of complementary foods. Iron status and growth data from the relevant RCTs were analyzed using RevMan 5.2.11., Results: Three RCTs and one observational study met the inclusion criteria. Meta-analysis showed significantly higher hemoglobin levels in infants fed solids at 4 months versus those fed solids at 6 months in developing countries [mean difference [MD]: 5.0 g/L; 95% CI: 1.5, 8.5 g/L; P = 0.005]. Meta-analysis also showed higher serum ferritin levels in the 4-month group in both developed and developing countries [MD: 26.0 μg/L; 95% CI: -0.1, 52.1 μg/L, P = 0.050], [MD: 18.9 μg/L; 95% CI: 0.7, 37.1 μg/L, P = 0.040]. Short follow-up periods and small sample sizes of the included studies were the major limitations., Conclusions: RCT evidence suggests the rate of iron deficiency anemia in breastfed infants could be positively altered by introduction of solids at 4 months.

Objective: To understand the level of the dietary iron intake of Harbin people, and explore the relation between dietary iron intake and nonalcoholic fatty liver disease (NAFLD)., Methods: Total of 215 NAFLD patients and 215 control population were selected in Harbin and a dietary survey was performed with a food frequency questionnaire (FFQ). Then the dietary iron intake was calculated and the risk of iron for NAFLD was analyzed by logistic regression., Results: The levels of the dietary intake of iron, heme iron and nonheme iron in patientswith NAFLD (30.76 ± 17.11 mg/d, 5.03 ± 5.99 mg/d and 25.73 ± 12.99 mg/d, respectively) , were significantly higher than those in normal control (22.33 ± 10.96 mg/d, 2.63 ± 3.52 mg/d mg/d and 19.70 ± 9.08 mg/ d, respectively, P < 0.05). The results from logistic analysis showed that high dietary intakesof iron and heme iron were risk factors for NAFLD (iron: OR = 5.5, 95% CI 2.061-14.45, P = 0.001; heme iron: OR = 6.1, 95% CI 2.562-14.63, P < 0.001). But dietary intake of nonheme iron was not a risk factor for NAFLD., Conclusion: The high dietary iron intake was a risk factor for NAFLD, so iron intake, especially the dietary heme iron intake, for the patients with NAFLD should be appropriate.

Background: Iron deficiency is the most widespread nutritional deficiency in the world., Objective: The objective of this randomized efficacy trial was to determine the effects of iron-biofortified pearl millet (Fe-PM) on iron status compared with control pearl millet (Control-PM)., Methods: A randomized trial of biofortified pearl millet (Pennisetum glaucum), bred to enhance iron content, was conducted in 246 children (12-16 y) for 6 mo in Maharashtra, India. Iron status [hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), and total body iron (TBI)], inflammation (C-reactive protein and α-1 acid glycoprotein), and anthropometric indices were evaluated at enrollment and after 4 and 6 mo. Hodges-Lehmann-Sen 95% CIs were used to examine the effect of the Fe-PM on iron status compared with commercially available Control-PM. Linear and binomial regression models were used to evaluate the effects of Fe-PM on iron status and incidence of anemia and iron deficiency, compared with Control-PM., Results: At baseline, 41% of children were iron deficient (SF <15 μg/L) and 28% were anemic (hemoglobin <12.0 g/dL). Fe-PM significantly increased SF concentrations and TBI after 4 mo compared with Control-PM. Among children who were iron deficient at baseline, those who received Fe-PM were 1.64 times more likely to become iron replete by 6 mo than were those receiving Control-PM (RR: 1.64, 95% CI: 1.07, 2.49, P = 0.02). The effects of Fe-PM on iron status were greater among children who were iron deficient at baseline than among children who were not iron deficient at baseline., Conclusions: Fe-PM significantly improved iron status in children by 4 mo compared with Control-PM. This study demonstrated that feeding Fe-PM is an efficacious approach to improve iron status in school-age children and it should be further evaluated for effectiveness in a broader population context. This trial was registered at clinicaltrials.gov as NCT02152150., (© 2015 American Society for Nutrition.)

We re-evaluated the old hypothesis that gastritis-induced achlorhydria is a cause of iron deficiency anemia (IDA) in humans. First, we analyzed the currently available research on the association between achlorhydria and IDA. When gastric acid secretion was measured after maximal stimulation, the frequency of achlorhydria (or severe hypochlorhydria) was 44% in patients with idiopathic IDA and 1.8% in healthy controls. In some patients with pernicious anemia, presumed achlorhydria preceded the development of IDA in time. However, we found no credible evidence that IDA caused gastritis or that IDA preceded the development of achlorhydria. Thus, correlational results favor achlorhydria as the causal factor in the association between achlorhydria and IDA. Second, we sought to determine whether gastritis and achlorhydria cause negative iron balance. When biosynthetic methods were used to isotopically label iron in food, achlorhydric patients were found to have severe malabsorption of nonheme iron, which persisted after the development of IDA. In 1 study, achlorhydria reduced the normal increase in heme-iron absorption from hemoglobin in response to iron deficiency. After an injection of isotopic iron into normal men, the physiologic loss of iron from the body was found to be 1 mg/d. Patients with chronic gastritis had excess fecal loss of isotopically tagged plasma iron. Calculations based on these results indicate that the absorption of iron from a typical Western diet by achlorhydric patients would be less than physiologic iron losses, creating a negative iron balance that could not be overcome by the adaptive increase in duodenal iron absorptive capacity that occurs in response to iron deficiency. The combination of results from these correlational and pathophysiologic studies supports the hypothesis that gastritis-induced achlorhydria can be an independent cause of IDA., (© 2015 American Society for Nutrition.)