Although hepcidin synthesis is stimulated by inflammation and inhibited by Fe deficiency, the strength of their opposing effects on serum hepcidin (SHep) in humans remains unclear. It was recently shown that an inflammatory stimulus in anaemic women did not increase SHep or decrease Fe absorption. The enhancing effect of ascorbic acid on Fe absorption may not be effective during inflammation because of increased SHep. Our study aim was to test whether reducing inflammation in Fe-depleted overweight (OW) women with low-grade inflammation would lower SHep and improve Fe absorption with and without ascorbic acid, compared with normal-weight (NW) women without inflammation. Before and after 14 d of anti-inflammatory treatment (3 × 600 mg ibuprofen daily) in OW and NW women (n 36; 19–46 years of age), we measured SHep and fractional Fe absorption (FIA) (erythrocyte Fe incorporation) from 57Fe- and 58Fe-labelled test meals with and without ascorbic acid. There were significant group effects on IL-6, C-reactive protein, serum ferritin and SHep (for all, P < 0·05). There was a significant treatment effect on SHep (P < 0·05): in OW women, treatment decreased IL-6 by approximately 30 % and SHep by approximately 45 %. However, there were no significant treatment or group effects on FIA. Body Fe stores (BIS) were a significant positive predictor of SHep before and after treatment (P < 0·001), but IL-6 was not. Reducing chronic inflammation in OW women halved SHep but did not affect Fe absorption with or without ascorbic acid, and the main predictor of Fe absorption was BIS.

Fe and iodine deficiencies are among the common forms of nutritional deficiencies globally and cause detrimental effects on mother and child. In developing countries, strategies to address these problems rarely use preventative dietary approaches. This cross-sectional study aims to ascertain whether dietary diversity score (DDS) and dietary patterns (DP) can predict the associated risk (AR) of Fe and iodine deficiencies in mother–toddler dyads during the dry/lean season in northern Ghana. Data were collected from women (15–49 years; n 118) and their toddlers (6–23 months, n 121). Dyads DDS and DP were calculated from their food intake recall. Multivariable logistic regression models were used to examine whether DDS, DP and socio-demographic factors predict higher odds of Fe and iodine deficiencies in dyads. DDS and DP predicted Fe and iodine deficiencies AR. Compared with DDS ≥4, women with DDS <4 have higher odds of Fe deficiency (ID) (adjusted OR (AOR) 1·82, 95 % CI 1·03, 3·21) and iodine deficiency (AOR 9·73, 95 % CI 3·19, 29·67). Two DP emerged in principal component analyses, ‘rural elites diet’ predicted ID risk in mothers (AOR 8·65, 95 % CI 1·76, 42·39), while ‘indigenous diet’ predicted iodine deficiency risk (AOR 11·41, 95 % CI 1·36, 95·97) in mothers only. The AR of Fe and iodine deficiencies in vulnerable populations may be predicted by diet-based measures in northern Ghana. We recommend further research into DDS and DP to predict Fe and iodine status of mother–toddler dyads in Ghana.

Anaemia affects approximately 69 % of Indian children aged 6–12 months, with Fe deficiency (ID) being a common cause. The effectiveness of micronutrient-fortified infant cereal in improving Fe status and neurodevelopment was evaluated in non-anaemic and mildly anaemic Indian infants. An intervention group (IC) enrolled at age 6 months consumed 50 g/d of rice-based cereal providing 3·75 mg Fe/d as ferrous fumarate for 6 months (n 80) and was compared with a matched static cross-sectional control group (CG) without intervention enrolled at age 12 months (n 80). Mean Hb was higher in IC (118·1 (sd 10·2) g/l) v. CG (109·5 (sd 16·4) g/l) at age 12 months (adjusted mean difference: 9·7 g/l; 95 % CI 5·1, 14·3; P < 0·001), while geometric mean serum ferritin tended to be higher (27·0 (–1 sd 13·4, +1 sd 54·4) v. 20·3 (–1 sd 7·5, +1 sd 55·0) ng/ml); P = 0·085) and soluble transferrin receptor was lower (1·70 (–1 sd 1·19, +1 sd 2·43) v. 2·07 (–1 sd 1·29, +1 sd 3·33) mg/l; P = 0·014). Anaemia (23 v. 45 %; P = 0·007) and ID (17 v. 40 %; P = 0·003) were lower in IC v. CG. Bayley Scales of Infant and Toddler Development Third Edition scores for language (P = 0·003), motor development (P = 0·018), social-emotional (P = 0·004) and adaptive behaviour (P < 0·001), but not cognitive development (P = 0·980), were higher in IC v. CG. No significant difference in anthropometric Z-scores was observed between the groups. Consuming a micronutrient-fortified infant cereal daily for 6 months during complementary feeding promoted better Fe status while reducing the risk for anaemia and ID and was associated with superior neurodevelopmental scores.

Fe deficiency (ID) defined as plasma ferritin <12 µg/l is associated with delayed cognitive development in early childhood and increased incidence of infections; however, the longitudinal association between early-life factors and ID in 18-month-old children in Denmark is unknown. The present study aimed to determine the prevalence of ID and to describe risk factors associated with ID in healthy 18-month-old Danish children. Blood samples, anthropometric measurements and self-reported questionnaire data had been obtained in the birth cohort, Odense Child Cohort. The questionnaires were modified from those used in the Danish National Birth Cohort. Plasma ferritin and C-reactive protein in venous, non-fasting samples were analysed in the final sample size of 370 children after exclusion of seventy-nine children due to chronic disease, acute infection, C-reactive protein >10 mg/l, twin birth or prematurity. Associations with ID were analysed by logistic regression, adjusting for sex, maternal education, duration of partial breast-feeding and current intake of milk, fish and meat. Overall, fifty-six children had ID (15·1 %). Factors associated with increased risk were exclusive breast-feeding beyond 4 months (OR 5·97; 95 % CI 1·63, 21·86) and no intake of oral Fe supplements from 6 to 12 months (OR 3·99, 95 % CI 1·33, 11·97. Duration of partial breast-feeding and current diet was not associated with ID. In conclusion, the ID prevalence was 15·1 %, and both exclusive breast-feeding beyond 4 months and no intake of oral Fe supplements from 6 to 12 months were associated with increased risk of ID in 18-month-old children.

Fe therapy can be effective in heart failure patients both with and without anaemia. However, the role of Fe therapy in such patients is still uncertain. In this review, the aim was to evaluate the efficacy and safety of Fe therapy in adult patients with heart failure who have reduced ejection fraction (HFrEF). Multiple databases (PubMed, Medline, EMBASE, the Cochrane Library and Clinical Trials) were searched up to December 2017 and the reference lists of relevant articles obtained from the search were reviewed. Data extracted from randomised control trials (RCT) selected for the review were pooled using a fixed effects model or a random effects model, according to heterogeneity between trials. Nine RCT were included in this meta-analysis which included a total of 789 patients who received Fe therapy and who in turn were compared with 585 controls. There was significant improvement in the 6-min walk test (19·05 m, 95 % CI 10·48, 27·62) and peak VO2/kg (0·93 ml/kg per min, 95 % CI 0·16, 1·69) in the Fe supplementation arm. With Fe therapy, fewer patients were hospitalised for heart failure (OR: 0·42, 95 % CI 0·27, 0·65), but no relationship was found for total re-hospitalisation (OR: 0·70, 95 % CI 0·32, 1·51) or mortality (OR: 0·70, 95 % CI 0·38, 1·28). Fe therapy has the potential to improve exercise tolerance, reduce re-hospitalisations for patients with HFrEF having Fe deficiency. In addition, Fe supplementation was found to be safe, with no increased rate of adverse events.

Both maternal Fe deficiency (ID) and being overweight or obese (Ow/Ob, BMI≥25 kg/m2) may negatively affect offspring brain development. However, the two risk factors correlate and their independent effects on infant neurodevelopment are unclear. PREOBE is a prospective observational study that included 331 pregnant Spanish women, of whom 166 had pre-gestational Ow/Ob. Fe status was analysed at 34 weeks and at delivery, and babies were assessed using Bayley III scales of neurodevelopment at 18 months. In confounder-adjusted analyses, maternal ID at 34 weeks was associated with lower composite motor scores at 18 months (mean 113·3 (sd 9·9) v. 117·1 (sd 9·2), P=0·039). Further, the offspring of mothers with ID at delivery had lower cognitive scores (114·0 (sd 9·7) v. 121·5 (sd 10·9), P=0·039) and lower receptive, expressive and composite (99·5 (sd 8·6) v. 107·6 (sd 8·3), P=0·004) language scores. The negative associations between maternal ID at delivery and Bayley scores remained even when adjusting for maternal Ow/Ob and gestational diabetes. Similarly, maternal Ow/Ob correlated with lower gross motor scores in the offspring (12·3 (sd 2·0) v. 13·0 (sd 2·1), P=0·037), a correlation that remained when adjusting for maternal ID. In conclusion, maternal ID and pre-gestational Ow/Ob are both negatively associated with Bayley scores at 18 months, but independently and on different subscales. These results should be taken into account when considering Fe supplementation for pregnant women.

The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 μg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4·4 (sd 0·7) years and 50·5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (P<0·05). Moreover, the proportion of vitamin A deficiency, marginal vitamin A deficiency and Fe deficiency among children in group 3 were markedly lower compared with children in groups 1 and 2 (P<0·05). Albendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status.

Fe and n-3 long-chain PUFA (n-3 LCPUFA) have both been associated with cognition, but evidence remains inconclusive in well-nourished school-aged children. In the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet (OPUS) School Meal Study, the 3-month intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster-randomised cross-over trial comparing school meals with packed lunch (control). At baseline and after each treatment, we measured serum ferritin, whole-blood n-3 LCPUFA and Hb, and performance in reading, mathematics and d2-test of attention. Data were analysed using mixed models (n 726) and principal component analysis of test performances (n 644), which showed two main patterns: ‘school performance’ and ‘reading comprehension’. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved ‘school performance’ (P=0·015), ‘reading comprehension’ (P=0·043) and EPA+DHA status 0·21 (95 % CI 0·15, 0·27) w/w % (P<0·001), but it did not affect serum ferritin or Hb. At baseline, having small Fe stores was associated with poorer ‘school performance’ in girls, but with better ‘reading comprehension’ in both boys and girls. Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with ‘school performance’, suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect. These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study.

The object of the present study was to investigate the levels of serum transferrin receptor (sTfR) and its response to Fe supplementation in Fe-deficient children and the role of sTfR in detecting Fe deficiency and assessing the efficacy of Fe supplementation. According to the diagnostic standard, 1006 children, aged 6–14 years in Fangshan district, Beijing, Peoples Republic of China, were divided into four groups: normal; Fe store depletion (IDs); Fe deficiency erythropoiesis (IDE); Fe deficiency anaemia (IDA). sTfR was determined and transferrin receptor-ferritin (TfR-F) index was calculated in 238 children, sixty-four normal and 174 Fe deficient. Children were administered a NaFeEDTA capsule containing 60 mg Fe once per week for the IDs and IDE groups and three times per week for the IDA group for nine consecutive weeks. The parameters reflecting Fe status and sTfR were determined before and after Fe supplementation. The levels of sTfR and TfR-F index in Fe-deficient children were significantly higher than those in the normal group. The receiver operating characteristic curve showed that sTfR has proper diagnostic efficacy for functional Fe deficiency. After Fe supplementation, the level of sTfR was significantly decreased in children with IDs, but not in children with IDE and IDA, while TfR-F index was significantly decreased in Fe-deficient children. sTfR is a reliable indicator for detecting functional Fe deficiency, and TfR-F index is a sensitive parameter for assessing the efficacy of Fe supplementation.

Phytosiderophore (PS) release occurs under both iron and zinc deficiencies in representative Poaceae and has been speculated to be a general adaptive response to enhance the acquisition of micronutrient metals. We tested this hypothesis within an on-going study of the role of micronutrient metal nutrition for patterns of spontaneous vegetation in relation to soil pH and carbonate content. Hordelymus europaeus (L.) Harz, a negative grass species commonly found on soils rich in CaCO3 in Western Central Europe, was subjected to deficiencies of Fe, Zn, Mn and Cu using chelator-buffered nutrient solutions. PS release rates were determined at 3–5 d intervals during onset and development of deficiency symptoms. Plant dry matter yields and nutrient concentrations, measured at three time points were used to construct growth curves for calculation of PS release per unit root mass. In comparison with trace metal-sufficient control plants, dry matter production was markedly reduced in the Fe, Zn, Mn and Cu-deficiency treatments, with final relative yields of 6, 11, 15 and 31%, respectively. The phytosiderophore produced under Fe- and Cu-deficiency treatments was identified, using HPLC, as desoxymugineic acid. The highest rate of PS release (18 μmol g−1 root d. wt in 2 h) was measured in the Fe-deficiency treatment, and there was substantial release in the Cu-deficiency treatment (7·25 μmol g−1 root d. wt in 2 h). No PS release above control levels (2·6 μmol g−1 root d. wt in 2 h) was observed in the Zn- or Mn-deficiency treatments (1·5 and 2·6 μmol g−1 root d. wt in 2 h, respectively). It remains to be clarified whether PS release in response to Cu deficiency is a primary reaction to the deficiency, or is caused by a chain of events similar to that observed in Zn-deficient wheat, which involves internal Fe deficiency. Our results suggest that PS release in the native plant species H. europaeus is a specific response to Fe and Cu deficiency and is not significantly induced in response to deficiencies of Zn and Mn. Induction of the PS mechanism in different plant species might be more diverse than previously thought.