Iron deficiency (ID) in early life is associated with morbidities. Most fetal iron required for infant growth is acquired in the third trimester from maternal iron store. However, how prenatal iron level affects ferritin level in early infancy remains controversial. This study aimed to examine the associations between maternal ferritin levels and cord blood serum ferritin (CBSF) and to compare the ferritin levels between different feeding practices in early infancy. Healthy Chinese mothers with uncomplicated pregnancy and their infants were followed up at 3 months post-delivery for questionnaire completion and infant blood collection. Infants who were predominantly breastfed and those who were predominantly formula fed were included in this analysis. Serum ferritin levels were measured in maternal blood samples collected upon delivery, cord blood and infant blood samples at 3 months of age. Ninety-seven mother–baby dyads were included. Maternal ID is common (56 %) while the CBSF levels were significantly higher than maternal ferritin levels. Only three infants (3 %) had ID at 3 months of age. There were no significant correlations between maternal ferritin levels with CBSF (r 0·168, P = 0·108) nor with infant ferritin levels at 3 months of age (r 0·023, P = 0·828). Infant ferritin levels at 3 months were significantly and independently associated with CBSF (P = 0·007) and birth weight (P < 0·001) after adjusting for maternal age, parity, maternal education, infant sex and feeding practice. In conclusion, maternal ID was common upon delivery. However, maternal ferritin levels were not significantly associated with CBSF concentrations nor infant ferritin concentrations at 3 months of age.

We aim to determine the association between Fe status and the metabolic syndrome (MetS) during menopause. Records of 1069 premenopausal and 703 postmenopausal Korean women were retrieved from the database of the fifth Korean National Health and Nutrition Examination Survey (KNHANES V 2012) and analysed. The association between the MetS and Fe status was performed using multivariable-adjusted analyses, subsequently develop a prediction model for the MetS by margin effects. We found that the risk of Fe depletion among postmenopausal women was lower than premenopausal women (PR = 0·813, 95 % CI 0·668, 0·998, P = 0·038). The risk of the MetS was 2·562-fold lower among premenopausal women with than without Fe depletion (PR = 0·390, 95 % CI 0·266, 0·571, P < 0·001). In contrast, the risk of the MetS tended to be higher among postmenopausal women with than without Fe depletion (PR = 1·849, 95 % CI 1·406, 2·432, P < 0·001). When the serum ferritin levels increased, the risk of the MetS increased in both premenopausal women and postmenopausal women. The margin effects showed that an increase in serum Hb and ferritin was associated with an increase in the risk of the MetS according to menopausal status and age group. Therefore, ferritin is the most validated and widely used Fe marker, could be a potential clinical value in predicting and monitoring the MetS during menopause. Further prospective or longitudinal studies, especially, clinically related studies on menopause and Fe status, are needed to clarify the causality between serum ferritin levels and the MetS that could offer novel treatments for the MetS.

The present study reports the effects of a high-fat (HF) diet of over 8 weeks on the Fe status of growing rats. Tissue Fe levels were analysed by atomic absorption spectrophotometry, and whole-body adiposity was measured by dual-energy X-ray absorptiometry. Histopathology and morphometry of adipose tissue were performed. Liver homogenates were used for measuring ferroportin-1 protein levels by immunoblotting, and transcript levels were used for Fe genes measured by real-time PCR. Tissue Fe pools were fit to a compartmental biokinetic model in which Fe was assessed using fourteen compartments and twenty-seven transfer constants (kj,i from tissue ‘i’ to tissue ‘j’) adapted from the International Commission on Radiological Protection (ICRP) 69. Ten kj,i were calculated from the experimental data using non-linear regression, and seventeen were estimated by allometry according to the formula ${k_{i,j}} = a \times {M^b}$. Validation of the model was carried out by comparing predicted and analysed Fe pool sizes in erythrocytes, the liver and the spleen. Body adiposity was negatively associated with serum Fe levels and positively associated with liver Fe stores. An inferred increase in Fe transfer from bone marrow to the liver paralleled higher hepatic Fe concentrations and ferritin heavy-chain mRNA levels in the HF diet-fed animals, suggesting that liver Fe accumulation occurred at least in part due to a favoured liver erythrocyte uptake. If this feeding condition was to be prolonged, impaired Fe decompartmentalisation may occur, ultimately resulting in dysmetabolic Fe overload.

Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6–23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (–1·93 (95 % CI –1·88, –1·97)) v. placebo (–1·88 (95 % CI –1·83, –1·92)), and the opposite occurred among initially anaemic children (final mean LAZ –1·90 (95 % CI –1·86, –1·94) in MNP v. –1·92 (95 % CI –1·88, –1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.

The effect of 38 µg (1500 IU) daily vitamin D3 supplementation, consumed with an Fe-fortified breakfast cereal for 8 weeks, on haematological indicators in Fe-deficient female subjects was investigated. Fifty Fe-deficient subjects (plasma ferritin concentration <20 µg/l; mean age: 27·4 (sd 9·4) years) were randomised to consume an Fe-fortified breakfast cereal containing 9 mg of Fe daily, with either a vitamin D3 supplement or placebo. Blood samples were collected at baseline, interim (4 weeks) and post-intervention (8 weeks) for measurement of Fe and vitamin D status biomarkers. The effect of intervention was analysed using mixed-model repeated-measures ANOVA. Significant increases were observed in two main haematological indices: Hb concentration and haematocrit level from baseline to post-intervention in the vitamin D group but not in the placebo group. The increase from baseline to post-intervention in Hb concentration in the vitamin D group (135 (sd 11) to 138 (sd 10) g/l) was significantly higher compared with the placebo group (131 (sd 15) to 128 (sd 13) g/l) (P=0·037). The increase in haematocrit level from baseline to post-intervention was also significantly higher in the vitamin D group (42·0 (sd 3·0) to 43·8 (sd 3·4) %) compared with the placebo group (41·2 (sd 4·3) to 40·7 (sd 3·6) %) (P=0·032). Despite the non-significant changes in plasma ferritin concentration, this study demonstrates that 38 µg supplemental vitamin D, consumed daily, with Fe-fortified breakfast cereal led to improvement in Hb concentration and haematocrit levels in women with low Fe stores. These findings may have therapeutic implications in the recovery of Fe status in Fe-deficient populations at a healthcare level.

Fe deficiency is relatively common in pregnancy and has both short- and long-term consequences. However, little is known about the effect on the metabolism of other micronutrients. A total of fifty-four female rats were fed control (50 mg Fe/kg) or Fe-deficient diets (7·5 mg/kg) before and during pregnancy. Maternal liver, placenta and fetal liver were collected at day 21 of pregnancy for Cu and Zn analysis and to measure expression of the major genes of Cu and Zn metabolism. Cu levels increased in the maternal liver (P=0·002) and placenta (P=0·018) of Fe-deficient rats. Zn increased (P<0·0001) and Cu decreased (P=0·006) in the fetal liver. Hepatic expression of the Cu chaperones antioxidant 1 Cu chaperone (P=0·042) and cytochrome c oxidase Cu chaperone (COX17, P=0·020) decreased in the Fe-deficient dams, while the expression of the genes of Zn metabolism was unaltered. In the placenta, Fe deficiency reduced the expression of the chaperone for superoxide dismutase 1, Cu chaperone for superoxide dismutase (P=0·030), ceruloplasmin (P=0·042) and Zn transport genes, ZRT/IRT-like protein 4 (ZIP4, P=0·047) and Zn transporter 1 (ZnT1, P=0·012). In fetal liver, Fe deficiency increased COX17 (P=0·020), ZRT/IRT-like protein 14 (P=0·036) and ZnT1 (P=0·0003) and decreased ZIP4 (P=0·004). The results demonstrate that Fe deficiency during pregnancy has opposite effects on Cu and Zn levels in the fetal liver. This may, in turn, alter metabolism of these nutrients, with consequences for development in the fetus and the neonate.

Iron-deficiency anemia is a public health concern that frequently occurs in pregnant mammals and neonatal offspring. Ferrous N-carbamylglycinate chelate (Fe-CGly) is a newly designed iron fortifier with proven effects in iron-deficient rats and weanling piglets. However, the effects of this new compound on pregnant mammals are unknown. Therefore, this experiment was conducted to evaluate the effects of Fe-CGly on sow reproductive performance and iron status of both sows and neonatal piglets. A total of 40 large-white sows after second parity were randomly assigned to two groups (n=20). They were receiving a diet including 80 mg Fe/kg as FeSO4 or Fe-CGly, respectively, from day 85 of gestation to parturition. The serum (day 110 of pregnancy) and placentas of sows were sampled. Litter size, mean weight of live born piglets, birth (live) litter weight, number of live born piglets, and the number of still-born piglets, mummies, and weak-born piglets were recorded. Once delivered, eight litters were randomly selected from the 20 litters per treatment, and one new-born male piglet (1.503±0.142 kg) from each selected litter was slaughtered within 3 h after birth from the selected litters, without colostrum ingestion. The serum, longissimus muscle, liver and kidneys of the piglets were collected. The iron status of the serum samples and the messenger RNA level of iron-related genes in the placenta, liver and kidney were analyzed. The results showed that litter weight of live born piglets was higher (P=0.030) in the Fe-CGly group (19.86 kg) than in the FeSO4 group (17.34 kg). Fe-CGly significantly increased placental iron concentration (P<0.05) of sows. It also significantly increased iron saturation and reduced the total iron-binding capacity of piglets (P<0.05) at birth. However, the results revealed that supplementation of Fe-CGly in sows reduced liver and kidney iron concentration of neonatal piglets (P<0.05), indicating decreased iron storage. In addition, the concentration of iron in the colostrum was not significantly changed. Therefore, the present results suggested that replacement of maternal FeSO4 supplement with Fe-CGly in the late-gestating period for sows could improve litter birth weight, probably via enhanced iron transportation in the placenta.

There are limited data on the association between Fe overload and leucocyte telomere length (LTL), known as a useful biomarker of the replicative ageing of cells. The aim of the study was to evaluate associations between Fe-status biomarkers and LTL. A cross-sectional study included 1174 men and women aged 50–79 years who provided blood samples for assays of Fe-status biomarkers including ferritin, transferrin saturation (TSAT), total Fe-binding capacity (TIBC) and relative LTL. They were free of hepatitis, potential infection or Fe deficiency. In multiple linear regression analysis adjusted for potential confounding variables, log-transformed LTL was positively associated with TIBC (adjusted coefficient estimate for its highest quartile: 0·17 (se 0·03), P<0·001) and inversely associated with TSAT (adjusted coefficient estimate for its third and fourth quartiles: −0·09 (se 0·03), P<0·01). These associations were consistent after additional adjustment for serum concentrations of high-sensitivity C-reactive protein, alanine transaminase and aspartate transaminase. In particular, participants with not only abnormally high concentrations (>45 %) but also with high-normal concentrations (35–45 %) of TSAT had shorter LTL compared with those with low-normal concentrations (<30 %) (P<0·05). We also observed that less-active or obese persons with high TSAT concentrations had shorter LTL than others. Our findings that cellular ageing is influenced not only by Fe overload but also by high-normal concentrations of TSAT support the hypothesis regarding the detrimental effects of labile Fe, which has a potent pro-oxidant activity in the body.

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.

While prenatal Fe supplementation prevents maternal Fe deficiency and anaemia, it is uncertain whether it improves infant health outcomes, at least when taken by Fe-replete women. Inflammation as well as physiological changes complicates the assessment of Fe status during pregnancy. In the present study, we measured the concentrations of serum ferritin and soluble transferrin receptors (sTfR), Hb and the acute-phase proteins C-reactive protein (CRP) and α1-antichymotrypsin (ACT) in a cross-sectional study among 738 pregnant women attending antenatal care in Guinea-Bissau, West Africa. Multiple linear regression analysis was used to identify the predictors of Fe status markers. The mean gestational age was 23 (sd 7) weeks. Serum ferritin values were lower with progressing gestation, from 27 % lower during weeks 16–20 of gestation up to 59 % lower after 29 weeks of gestation compared with early pregnancy. Using cut-off values for Fe deficiency as established in non-pregnant individuals, 52 % of the women had sTfR levels >2·3 mg/l, while only 25 % had serum ferritin levels < 12 μg/l. Serum ferritin but also sTfR levels were elevated at increased serum CRP and ACT levels. The proportion of sTfR >2·3 mg/l decreased to 47 % after adjustment for elevated serum CRP and ACT levels. On the contrary, the proportion of serum ferritin < 12 μg/l increased to 33 % after adjustment for ACT and CRP. The high proportion of elevated serum sTfR calls for pregnancy-specific cut-offs since increased erythropoiesis is expected in response to increased plasma volume of pregnancy. The present study further underlines the need to adjust for inflammation when serum sTfR and serum ferritin are used to assess Fe status in pregnancy.

Fe deficiency and Fe-deficiency anaemia are common in patients with inflammatory bowel disease (IBD). Traditional clinical markers of Fe status can be skewed in the presence of inflammation, meaning that a patient's Fe status can be misinterpreted. Additionally, Fe absorption is known to be down-regulated in patients with active IBD. However, whether this is the case for quiescent or mildly active disease has not been formally assessed. The present study aimed to investigate the relationship between Fe absorption, Fe requirements and standard haematological indices in IBD patients without active disease. A group of twenty-nine patients with quiescent or mildly active IBD and twenty-eight control subjects undertook an Fe absorption test that measured sequential rises in serum Fe over 4 h following ingestion of 200 mg ferrous sulphate. At baseline, serum Fe, transferrin saturation, non-transferrin-bound Fe (NTBI), ferritin and soluble transferrin receptor were all measured. Thereafter (30–240 min), only serum Fe and NTBI were measured. Fe absorption did not differ between the two groups (P = 0·9; repeated-measures ANOVA). In control subjects, baseline haematological parameters predicted Fe absorption (i.e. Fe requirements), but this was not the case for patients with IBD. Fe absorption is normal in quiescent or mildly active IBD patients but standard haematological parameters do not accurately predict Fe requirements.