Special Issue "Iron Intake and Human Health"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (15 March 2019).

Special Issue Editor

Dr. Gladys Oluyemisi Latunde-Dada
Website
Guest Editor
Department of Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, UK
Interests: iron; nutrition; metabolism; absorption

Special Issue Information

Dear Colleagues,

Iron is an essential micronutrient that is important for cellular and physiological processes, such as respiration, energy metabolism, replication, and gene regulation. Dietary iron is absorbed principally from the proximal duodenum in a regulated process that modulates iron homeostasis since iron excretion is not regulated in humans. Iron in foods is present in two forms, heme (meat types) and non-heme (vegetables and cereals). Recent publications have revealed iron bioavailability data on novel food products, new oral iron supplements or iron biofortifed foods that are safe and less toxic to the gut. Moreover, food processing procedures such as micro-milling or food encapsulation are employed to influence luminal bioaccessibilty and iron absorption from foods. Furthermore, gut microflora have emerged as important entities that modify food matrices, metabolites and modulate iron absorption in distal gut region. While the mechanism of heme iron absorption is still not resolved, intake and absorption of non-heme iron involve a regulated interplay of an apical ferrireduction, ferrous ion absorption by DMT1 symporter, abluminal efflux by ferroportin and ferroxidation by haphaestin. This intestinal transit machinery is regulated by transcriptional Hif-2α activation, post-transcriptional IRP-IRE binding and the post-translational inhibitory mechanism by hepcidin. Emerging evidence in recent years is, however, alluding to the modulation of the transport machinery by luminal bioactive ingredients or dietary constituents. Moreover, disorders of the gastrointestinal tract are common in chronic diseases with increased inflammation and hepcidin levels that result in a reduced iron intake and subsequently systemic iron deficiency. In contrast, genetic diseases such as mutation in genes that regulate hepcidin and ferroportin expression lead to inappropriately low hepcidin levels that promote iron absorption and result in iron overload.

Dr. Gladys Oluyemisi Latunde-Dada
Guest Editor

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Keywords

  • Iron
  • Intake
  • Processing
  • Bioavailability

Published Papers (9 papers)

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Research

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Open AccessArticle
Is Iron Supplementation Influenced by Sub-Clinical Inflammation?: A Randomized Controlled Trial Among Adolescent Schoolgirls in Myanmar
Nutrients 2019, 11(4), 918; https://doi.org/10.3390/nu11040918 - 24 Apr 2019
Cited by 1
Abstract
Iron absorption was impaired in the presence of sub-clinical inflammation (SCI) and might hamper the effect of iron supplementation. The purpose of the study was to identify the influence of SCI on iron supplementation. A randomized, double-blinded, placebo-controlled experimental study was conducted among [...] Read more.
Iron absorption was impaired in the presence of sub-clinical inflammation (SCI) and might hamper the effect of iron supplementation. The purpose of the study was to identify the influence of SCI on iron supplementation. A randomized, double-blinded, placebo-controlled experimental study was conducted among anaemic adolescent schoolgirls in Ayeyarwady region, Myanmar. A total of 402 schoolgirls were recruited from six schools screened from 1269 girls who were assigned into one of four groups: Folate group (2.5 mg of folate), Vitamin A group (15,000 IU of vitamin), Iron folate group (60 mg elemental iron and folate) and Iron, and vitamin A and folate group. Supplementation was done once a week for 12 weeks. Iron, vitamin A and inflammation were measured at the baseline, middle and endline. Changes in serum ferritin and body iron were significantly higher in the IFA and IFA + vitA among those without SCI. There was interaction between vitamin A and SCI on Hb changes. Analysis of GLM repeated measure showed interactions between treatment and SCI for hemoglobin and serum transferrin receptor. Those treated with vitamin A had better outcomes when there was SCI. Inflammation accompanied a negative effect on iron supplementation and vitamin A improved efficacy of iron supplementation in the presence of SCI. Full article
(This article belongs to the Special Issue Iron Intake and Human Health)
Open AccessArticle
The Association of TMPRSS6 Gene Polymorphism and Iron Intake with Iron Status among Under-Two-Year-Old Children in Lombok, Indonesia
Nutrients 2019, 11(4), 878; https://doi.org/10.3390/nu11040878 - 19 Apr 2019
Abstract
Multiple common variants in transmembrane protease serine 6 (TMPRSS6) were associated with the plasma iron concentration in genome-wide association studies, but their effect in young children where anemia and iron deficiency (ID) were prevalent has not been reported, particularly taking account of iron [...] Read more.
Multiple common variants in transmembrane protease serine 6 (TMPRSS6) were associated with the plasma iron concentration in genome-wide association studies, but their effect in young children where anemia and iron deficiency (ID) were prevalent has not been reported, particularly taking account of iron intake. This study aims to investigate whether TMPRSS6 SNPs (rs855791 and rs4820268) and iron intake are associated with a low iron and hemoglobin concentration in under-two-year-old children. The study analyzed the baseline of a randomized trial (NUPICO, ClinicalTrials.gov NCT01504633) in East Lombok, Indonesia. Children aged 6–17 months (n = 121) were included in this study. The multiple linear regressions showed that TMPRSS6 decreased serum ferritin (SF) by 4.50 g/L per copy minor allele (A) of rs855791 (p = 0.08) and by 5.00 μg/L per copy minor allele (G) of rs4820268 (p = 0.044). There were no associations between rs855791 and rs4820268 with soluble transferrin receptor (sTfR) and hemoglobin (Hb) concentration (rs855791; p = 0.38 and p = 0.13, rs4820268; p = 0.17 and p = 0.33). The finding suggests the need for further studies to explore whether the nutrient recommendation for iron should be based on genetic characteristics, particularly for children who have mutation in TMPRSS6. Full article
(This article belongs to the Special Issue Iron Intake and Human Health)
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Open AccessFeature PaperArticle
Maternal and Early Life Iron Intake and Risk of Childhood Type 1 Diabetes: A Danish Case-Cohort Study
Nutrients 2019, 11(4), 734; https://doi.org/10.3390/nu11040734 - 29 Mar 2019
Abstract
Background: Iron overload has been associated with diabetes. Studies on iron exposure during pregnancy and in early life and risk of childhood type 1 diabetes (T1D) are sparse. We investigated whether iron supplementation during pregnancy and early in life were associated with risk [...] Read more.
Background: Iron overload has been associated with diabetes. Studies on iron exposure during pregnancy and in early life and risk of childhood type 1 diabetes (T1D) are sparse. We investigated whether iron supplementation during pregnancy and early in life were associated with risk of childhood T1D. Methods: In a case-cohort design, we identified up to 257 children with T1D (prevalence 0.37%) from the Danish National Birth Cohort through linkage with the Danish Childhood Diabetes Register. The primary exposure was maternal pure iron supplementation (yes/no) during pregnancy as reported in interview two at 30 weeks of gestation (n = 68,497 with iron supplement data). We estimated hazard ratios (HRs) using weighted Cox regression adjusting for multiple confounders. We also examined if offspring supplementation during the first 18 months of life was associated with later risk of T1D. Results: Maternal iron supplementation was not associated with later risk of T1D in the offspring HR 1.05 (95% CI: 0.76–1.45). Offspring intake of iron droplets during the first 18 months of life was inversely associated with risk of T1D HR 0.74 (95% CI: 0.55–1.00) (ptrend = 0.03). Conclusions: Our large-scale prospective study demonstrated no harmful effects of iron supplementation during pregnancy and in early life in regard to later risk of childhood T1D in the offspring. Full article
(This article belongs to the Special Issue Iron Intake and Human Health)
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Open AccessArticle
The Safety and Tolerability of a Potential Alginate-Based Iron Chelator; Results of A Healthy Participant Study
Nutrients 2019, 11(3), 674; https://doi.org/10.3390/nu11030674 - 21 Mar 2019
Cited by 1
Abstract
Evidence supporting the ferro-toxic nature of iron in the progression of inflammatory bowel disease (IBD) is becoming well established. A microbial dysbiosis is observed in IBD patients, and intra-luminal colonic-iron is able to support a more pathogenic community of bacteria; whether this is [...] Read more.
Evidence supporting the ferro-toxic nature of iron in the progression of inflammatory bowel disease (IBD) is becoming well established. A microbial dysbiosis is observed in IBD patients, and intra-luminal colonic-iron is able to support a more pathogenic community of bacteria; whether this is attributed to the development of IBD and how iron could be mediating these microbial changes is still unknown. Dietary fibres are commonly used in pre-biotic supplements to beneficially affect the host by improving the viability of bacterial communities within the colon. Alginates are a class of biopolymers considered as prebiotics due to their fibre-like composition and are able to bind metal cations, in particular, iron. Considering that iron excess is able to negatively alter the microbiome, the use of alginate as a food supplement could be useful in colonic-iron chelation. As such, this first-in-man study aimed to assess whether the use of alginate as a dietary iron chelator was both safe and well tolerated. In addition, the impact of alginate on the microbiome and iron levels was assessed by using an intestinal model SHIME (Simulation of the Human Intestinal Microbial Ecosystem). Alginate was supplemented into the diets (3 g/day) of healthy volunteers (n = 17) for 28 days. Results from this study suggest that daily ingestion of 3 g alginate was well tolerated with very minor side effects. There were no detrimental changes in a variety of haematological parameters or the intestinal microbiome. The bacterial communities within the SHIME model were also not influenced by iron and or alginate; it is possible that alginate may be susceptible to bacterial or enzymatic degradation within the gastro-intestinal tract. Full article
(This article belongs to the Special Issue Iron Intake and Human Health)
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Open AccessArticle
Iron Deficiency and Neuroendocrine Regulators of Basal Metabolism, Body Composition and Energy Expenditure in Rats
Nutrients 2019, 11(3), 631; https://doi.org/10.3390/nu11030631 - 15 Mar 2019
Cited by 4
Abstract
Although dietary iron is a determinant of iron status in animals, body fat mass has been reported to have an inverse association with iron status in human studies. The goal of this study was to determine the relationship between Fe homeostasis, body composition, [...] Read more.
Although dietary iron is a determinant of iron status in animals, body fat mass has been reported to have an inverse association with iron status in human studies. The goal of this study was to determine the relationship between Fe homeostasis, body composition, energy expenditure and neuroendocrine regulators for severe Fe-deficiency anaemia. Forty male Wistar albino rats recently weaned were divided at random into two groups: the control group was fed the basal diet, AIN-93G diet (normal-Fe) and the anaemic group received a low-Fe diet for 40 days. Neuroendocrine parameters that regulate basal metabolism and appetite (thyroid hormones, ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon, insulin, adrenocorticotropic hormone and corticosterone), body composition, respiratory volumes, energy expenditure, haematological and biochemical were assessed. Total body fat was lower, whereas lean mass, free and total water were higher in the anemic group. O2 consumption, CO2 production, energy expenditure (EE) and respiratory quotient (RQ) were lower in the Fe-deficient animals. Triiodothyronine and thyroxine hormones decreased, while thyroid-stimulating hormone increased in the anemic group. Circulating levels of ghrelin were lower in the anemic group, while GIP, glucagon, insulin, corticosterone and adrenocorticotropic hormone levels were higher. Fe-deficiency impairs weight gain in the rats, with marked reductions in lean mass and body fat, indicating lower energy stores. Full article
(This article belongs to the Special Issue Iron Intake and Human Health)
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Open AccessArticle
Iron Transport from Ferrous Bisglycinate and Ferrous Sulfate in DMT1-Knockout Human Intestinal Caco-2 Cells
Nutrients 2019, 11(3), 485; https://doi.org/10.3390/nu11030485 - 26 Feb 2019
Cited by 1
Abstract
This experiment was conducted to investigate the transport characteristics of iron from ferrous bisglycinate (Fe-Gly) in intestinal cells. The divalent metal transporter 1 (DMT1)-knockout Caco-2 cell line was developed by Crispr-Cas9, and then the cells were treated with ferrous sulfate (FeSO4) [...] Read more.
This experiment was conducted to investigate the transport characteristics of iron from ferrous bisglycinate (Fe-Gly) in intestinal cells. The divalent metal transporter 1 (DMT1)-knockout Caco-2 cell line was developed by Crispr-Cas9, and then the cells were treated with ferrous sulfate (FeSO4) or Fe-Gly to observe the labile iron pool and determine their iron transport. The results showed that the intracellular labile iron increased significantly with Fe-Gly or FeSO4 treatment, and this phenomenon was evident over a wide range of time and iron concentrations in the wild-type cells, whereas in the knockout cells it increased only after processing with high concentrations of iron for a long time (p < 0.05). DMT1-knockout suppressed the synthesis of ferritin and inhibited the response of iron regulatory protein 1 (IRP-1) and IRP-2 to these two iron sources. The expression of peptide transporter 1 (PepT1) was not altered by knockout or iron treatment. Interestingly, the expression of zinc-regulated transporter (ZRT) and iron-regulated transporter (IRT)-like protein 14 (Zip14) was elevated significantly by knockout and iron treatment in wild-type cells (p < 0.05). These results indicated that iron from Fe-Gly was probably mainly transported into enterocytes via DMT1 like FeSO4; Zip14 may play a certain role in the intestinal iron transport. Full article
(This article belongs to the Special Issue Iron Intake and Human Health)
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Open AccessArticle
Total and Nonheme Dietary Iron Intake Is Associated with Metabolic Syndrome and Its Components in Chinese Men and Women
Nutrients 2018, 10(11), 1663; https://doi.org/10.3390/nu10111663 - 04 Nov 2018
Cited by 10
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Iron Intake and Human Health)
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Open AccessArticle
Iron (II) Citrate Complex as a Food Supplement: Synthesis, Characterization and Complex Stability
Nutrients 2018, 10(11), 1647; https://doi.org/10.3390/nu10111647 - 03 Nov 2018
Cited by 1
Abstract
Iron deficiency represents a widespread problem for a large part of the population, especially for women, and has received increasing attention in food/supplement research. The contraindications of the iron supplements commercially available (e.g., imbalances in the levels of other essential nutrients, low bioavailability, [...] Read more.
Iron deficiency represents a widespread problem for a large part of the population, especially for women, and has received increasing attention in food/supplement research. The contraindications of the iron supplements commercially available (e.g., imbalances in the levels of other essential nutrients, low bioavailability, etc.) led us to search for a possible alternative. In the present work, a rapid and easy method to synthetize a solid iron (II) citrate complex from iron filings and citric acid was developed to serve, eventually, as a food supplement or additive. In order to state its atomic composition and purity, an assortment of analytical techniques was employed (e.g., combustion analysis, thermogravimetry, X-ray diffractometry, UV/Vis spectrophotometry, etc.). Results demonstrate that the synthesized crystalline solid corresponds to the formula FeC6H6O7∙H2O and, by consequence, contains exclusively iron (II), which is an advantage with respect to existing commercial products, because iron (II) is better absorbed than iron (III) (high bioavailability of iron). Full article
(This article belongs to the Special Issue Iron Intake and Human Health)
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Review

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Open AccessReview
Iron Deficiency and Iron Homeostasis in Low Birth Weight Preterm Infants: A Systematic Review
Nutrients 2019, 11(5), 1090; https://doi.org/10.3390/nu11051090 - 16 May 2019
Cited by 3
Abstract
Iron is an essential micronutrient that is involved in many functions in humans, as it plays a critical role in the growth and development of the central nervous system, among others. Premature and low birth weight infants have higher iron requirements due to [...] Read more.
Iron is an essential micronutrient that is involved in many functions in humans, as it plays a critical role in the growth and development of the central nervous system, among others. Premature and low birth weight infants have higher iron requirements due to increased postnatal growth compared to that of term infants and are, therefore, susceptible to a higher risk of developing iron deficiency or iron deficiency anemia. Notwithstanding, excess iron could affect organ development during the postnatal period, particularly in premature infants that have an immature and undeveloped antioxidant system. It is important, therefore, to perform a review and analyze the effects of iron status on the growth of premature infants. This is a transversal descriptive study of retrieved reports in the scientific literature by a systematic technique. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were adapted for the review strategy. The inclusion criteria for the studies were made using the PICO (population, intervention, comparison, outcome) model. Consequently, the systematic reviews that included studies published between 2008–2018 were evaluated based on the impact of iron status on parameters of growth and development in preterm infants. Full article
(This article belongs to the Special Issue Iron Intake and Human Health)
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