BACKGROUND: Iron is crucial for growth and development, but excess iron is harmful. Neonatal mice have elevated concentrations of circulating iron, but the source of this iron is unclear. This lack of understanding makes it difficult to optimize early life iron balance.
OBJECTIVE: Identify the origins of neonatal tissue-specific iron pools using dietary manipulation and cross-fostering murine models.
METHODS: To determine whether tissue-specific neonatal iron was primarily acquired during gestation or after birth, pups born to iron-sufficient or iron-deficient dams were cross-fostered, and tissues were harvested at postnatal days 3-5 to measure iron content. A separate set of female mice were fed a diet enriched with the stable iron isotope 57 (57Fe) for 4 generations to replace naturally abundant liver iron isotope 56 (56Fe) stores with 57Fe. To quantify the proportions of neonatal iron acquired during gestation, pups born to dams with 56Fe or 57Fe stores were cross-fostered, and tissues were harvested at postnatal day 3-5 to determine 56Fe:57Fe ratios by inductively coupled plasma mass spectrometry. Finally, to quantify the proportion of neonatal iron acquired from the maternal diet, female mice with 56Fe or 57Fe stores switched diets upon mating, and pup tissues were harvested on P0 to determine 56Fe:57Fe ratios by inductively coupled plasma mass spectrometry.
RESULTS: Perinatal iron deficiency resulted in smaller pups, and gestational iron deficiency resulted in lower neonatal serum and liver iron. Cross-fostering between dams with 56Fe and 57Fe stores demonstrated that ≤70% of neonatal serum, liver, and brain iron were acquired during gestation. Dietary manipulation experiments using dams with 56Fe and 57Fe stores showed that over half of neonatal serum, liver, and brain iron were from the dam\'s gestational diet rather than preconception iron stores.
CONCLUSIONS: This study provides quantitative values for the sources of neonatal iron, which may inform approaches to optimize neonatal iron status.

The objective of this study was to investigate the potential associations between serum iron levels, dietary iron intake, and iron supplementation, and the prevalence of metabolic syndrome (MetS) in adolescents A cross-sectional analysis was conducted, utilizing data from adolescents participating in the 2003-2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) pertaining to serum iron, dietary iron, and iron supplementation were derived through multivariate logistic regression models. Additionally, a restricted cubic spline (RCS) regression model was applied to explore the nonlinear relationship between dietary iron and serum iron concerning MetS. The study encompassed 4858 American adolescents aged 12 to 19, among whom 413 (8.5%) manifested MetS. The study cohort exhibited an average age of 15.52 years, comprising 2551 males (52.51%) and 2307 females (47.49%). Relative to individuals in the lowest serum iron quartile, those in the highest quartile for serum iron (OR = 0.33, 95% CI 0.21-0.50), the highest quartile for dietary iron (OR = 0.53, 95% CI 0.32-0.89), and those utilizing iron supplements (OR = 0.61, 95% CI 0.37-0.99) evinced a diminished prevalence of MetS, even post adjustment for potential confounding variables. A non-linear relationship was discerned between serum iron and MetS, exhibiting a statistically significant negative correlation when serum iron concentrations exceeded the inflection point (serum iron = 8.66 µmol/L, P for nonlinear < 0.001). This investigation reveals that higher levels of serum iron, increased dietary iron intake, and the use of iron supplements are linked to a lower prevalence of MetS in US adolescents. These findings suggest that dietary modifications could play a role in promoting the health of adolescents.

Millets are recognized for their health and nutritional values, and the United Nations declared 2023 the International Year of Millets. Among the several health and nutritional benefits of millets, their impact on hemoglobin concentration is important since anemia is a major public health issue in many countries. To investigate the effect of millet (including sorghum) consumption on hemoglobin concentration in the blood, a systematic review and meta-analysis were conducted. Thirteen published studies featuring randomized control trials involving 590 individuals in the intervention group and 549 control individuals were eligible for the meta-analysis. The difference-in-differences analysis revealed highly significant (p < 0.01) positive effects of millet consumption on hemoglobin concentration, with an effect size of +0.68 standardized mean difference units. The change in hemoglobin concentration observed in the intervention group was +13.6%, which is statistically significant (p < 0.0005), compared to that in the control group, which was +4.8% and not statistically significant (p = 0.1362). In four studies, the consumption of millets in the intervention group demonstrated a change from mild anemia to normal status among children, whereas there was no change in the control group. The findings provide evidence that the consumption of millets can improve blood hemoglobin concentration, likely resulting from increased iron intake. Further research is needed involving the assessment of iron content and bioavailability to better understand the effect variation among millet types and the mechanisms involved.

Iron is an essential cofactor in the fundamental metabolic pathways of organisms. Moderate iron intake can enhance animal growth performance, while iron overload increases the risk of pathogen infection. Although the impact of iron on the pathogen-host relationship has been confirmed in higher vertebrates, research in fish is extremely limited. The effects and mechanisms of different levels of iron exposure on the infection of Aeromonas hydrophila in largemouth bass (Micropterus salmoides) remain unclear. In this study, experimental diets were prepared by adding 0, 800, 1600, and 3200 mg/kg of FeSO4∙7H2O to the basal feed, and the impact of a 56-day feeding period on the mortality rate of largemouth bass infected with A. hydrophila was analyzed. Additionally, the relationships between mortality rate and tissue iron content, immune regulation, oxidative stress, iron homeostasis, gut microbiota, and tissue morphology were investigated. The results showed that the survival rate of largemouth bass infected with A. hydrophila decreased with increasing iron exposure levels. Excessive dietary iron intake significantly increased iron deposition in the tissues of largemouth bass, reduced the expression and activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, increased the content of lipid peroxidation product malondialdehyde, and thereby induced oxidative stress. Excessive iron supplementation could influence the immune response of largemouth bass by upregulating the expression of pro-inflammatory cytokines in the intestine and liver, while downregulating the expression of anti-inflammatory cytokines. Additionally, excessive iron intake could also affect iron metabolism by inducing the expression of hepcidin, disrupt intestinal homeostasis by interfering with the composition and function of the gut microbiota, and induce damage in the intestinal and hepatic tissues. These research findings provide a partial theoretical basis for deciphering the molecular mechanisms underlying the influence of excessive iron exposure on the susceptibility of largemouth bass to pathogenic bacteria.

Iron is an essential element involved in a multitude of bodily processes. It is tightly regulated, as elevated deposition in tissues is associated with diseases such as multiple sclerosis (MS). Iron accumulation in the central nervous system (CNS) of MS patients is linked to neurotoxicity through mechanisms including oxidative stress, glutamate excitotoxicity, misfolding of proteins, and ferroptosis. In the past decade, the combination of MRI and histopathology has enhanced our understanding of iron deposition in MS pathophysiology, including in the pro-inflammatory and neurotoxicity of iron-laden rims of chronic active lesions. In this regard, iron accumulation may not only have an impact on different CNS-resident cells but may also promote the innate and adaptive immune dysfunctions in MS. Although there are discordant results, most studies indicate lower levels of iron but higher amounts of the iron storage molecule ferritin in the circulation of people with MS. Considering the importance of iron, there is a need for evidence-guided recommendation for dietary intake in people living with MS. Potential novel therapeutic approaches include the regulation of iron levels using next generation iron chelators, as well as therapies to interfere with toxic consequences of iron overload including antioxidants in MS.

Nutritional intake can influence major adverse cardiovascular events (MACE). Dietary iron is found in two forms: haem-iron (HI) only found in animal sources and non-haem iron (NHI) present mostly in plant sources.
We evaluated the associations between dietary iron intakes with MACE and iron status biomarkers.
Prospective cohort study.
The Concord Health and Ageing in Men Project, Sydney, Australia.
539 community-dwelling older Australian men aged 75 years and older.
Men underwent nutritional assessment using a validated diet history questionnaire. Entries were converted to food groups and nutrients. The dietary calculation was used to derive HI and NHI intakes from total iron intakes. Analyses of iron intakes with iron status biomarkers were conducted using linear regression, and with MACE and individual endpoints were conducted using Cox regression. Five-point MACE comprised of all-cause mortality, myocardial infarction (MI), congestive cardiac failure (CCF), coronary revascularisation, and/or ischaemic stroke. Four-point MACE included the four endpoints of MI, CCF, coronary revascularisation, and/or ischaemic stroke, and excluded all-cause mortality.
At a median of 5.3 (4.6 - 6.3) years follow-up, the incidences were: 31.2% (n = 168) five-point MACE, 17.8% (n = 96) four-point MACE excluding all-cause mortality, 20.1% (n = 111) all-cause mortality, 11.3% (n = 61) CCF, and 3.1% (n = 15) coronary revascularisation. In adjusted analyses, higher HI intake (per 1mg increment) was associated with increased five-point MACE (HR: 1.45 [95% CI: 1.16, 1.80, P = .001]), four-point MACE excluding all-cause mortality (HR: 1.64 [95% CI: 1.26, 2.15, P <.001]), all-cause mortality (HR: 1.51 [95% CI: 1.15, 1.99, P = .003]), CCF (HR: 2.08 [95% CI: 1.45, 2.98, P <.001]), and coronary revascularisation (HR: 1.89 [95% CI: 1.15, 3.10, P = .012]). Compared with the bottom tertile of NHI intake, the middle tertile of NHI intake was associated with reduced risk of all-cause mortality (HR: 0.56 [95% CI: 0.33, 0.96, P = .035]). Total iron intake was not associated with MACE and individual endpoints. Dietary iron intakes were not associated with serum iron and haemoglobin.
Higher haem iron intake was independently associated with increased risks of five-point MACE, four-point MACE excluding all-cause mortality, all-cause mortality, CCF, and coronary revascularisation in older men over 5 years.

We aimed to investigate the association of long-term dietary iron intake with the risk of non-fatal cardiovascular diseases (CVDs), myocardial infarction (MI), and stroke in Chinese populations with predominantly plant-based diets by sex.
A total of 17 107 participants (8569 men and 8538 women) aged 18-80 years in the China Health and Nutrition Survey (CHNS) 1989-2015 were included. Dietary intake was assessed repeatedly by three consecutive 24-h dietary recalls. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 11.1 years, the adjusted HRs (95% CIs) for non-fatal CVDs risk across quintiles of total iron intake in men were 1.00, 0.65 (0.46-0.93), 0.54 (0.37-0.78), 0.66 (0.46-0.94), 0.69 (0.47-1.03), but no significant association in women. Similar associations were found for stroke risk, but not for MI risk. The dose-response curves for the association of total iron and non-heme iron intake with the risk of non-fatal CVDs and stroke followed a reverse J-shape only in men and similar reverse J-shaped association of heme iron intake with non-fatal CVDs and stroke risk in both men and women (P-non-linearity <0.05).
Moderate dietary iron intake may protect against non-fatal CVDs and stroke, especially in Chinese men consuming plant-based diets. Both quantity and quality of dietary iron intake should be considered in the prevention of non-fatal CVDs due to differences in dietary patterns among diverse populations.
This prospective cohort study, using data from 8569 men and 8538 women who participated in the China Health and Nutrition Survey (CHNS) 1989–2015, suggests that moderate intake of dietary iron may protect against non-fatal cardiovascular diseases (CVDs) and stroke, especially in men consuming predominantly plant-based diets. Key findings In men, the association of dietary intake of total iron, heme iron, and non-heme iron with the risk of non-fatal CVDs and stroke followed a reverse J-shape, with the lowest risk at ∼26 mg/d of total iron intake, ∼2 mg/d of heme iron intake, and ∼24 mg/d of non-heme iron intake. In women, a J-shaped association between dietary heme iron intake and the risk of non-fatal CVDs and stroke were observed, with the lowest risk at ∼1.8 mg/d of heme iron intake; while higher dietary intakes of total iron and non-heme iron tended to be associated with a lower risk of non-fatal stroke.

Animal models have suggested the carcinogenic effect of iron due to its oxidative potential. The lung is particularly vulnerable to oxidative stress. However, epidemiological studies investigating the association between dietary iron and the risk of lung cancer have reported inconclusive results. In this systematic review and meta-analysis, we aimed to clarify this association. Methods: We searched PubMed, Web of Science, Scopus and Google scholar for eligible articles published through May 2023 reporting the Relative Risk (RR), Hazard Ratio (HR) or Odds Ratio (OR) with 95% confidence interval (95% CI). Case-control and cohort studies that examined the relationship between dietary iron and lung cancer risk were included and review and meta-analyses articles, experimental studies, abstracts, letters to editor and studies with insufficient data were excluded. Finally, three case-control studies and 6 cohort studies were included. Random effect models were used to calculate the pooled results. Results: Nine studies (cases n=21,943, participants n=1,542,993) were included. There were no significant associations between the highest dietary total iron (heme and non-heme) (RR: 1.09, 95% CI: 0.78 to 1.51) or heme iron (RR: 1.01, 95% CI: 0.73 to 1.38) intake compared to the lowest intake with lung cancer risk. Null-associations were also observed in the subgroup analysis based on smoking status and lung cancer histology. However, in the subgroup of women (cases n=5074), heme iron was associated with a 14% increase in the risk of lung cancer (RR: 1.14, 95% CI: 1.01 to 1.29). Conclusions: The current results demonstrated that there is no significant relationship between dietary iron intake and the risk of lung cancer. However, a positive association was observed between dietary heme iron and the risk of lung cancer in women, which may require further investigation.

Previous research has suggested that toddlers are not provided with adequate dietary iron in long-day care (LDC) services. However, the iron bioavailability provided is unknown. The present study aimed to investigate the amount and bioavailability of iron provided to toddlers aged 2-3 years at LDC services.
A cross-sectional audit was conducted using a 2-day weighed food record of 30 LDC services. Iron provision (not child intake) in LDC services across Perth, Australia was compared with the estimated average requirements (EAR) and LDC services provision guidelines (50% of EAR = 2 mg/day based on a 14% bioavailability factor). Bioavailability was estimated per mealtime using haem and non-haem iron, ascorbic acid, animal protein, calcium, soy, eggs and phytates using two pre-existing algorithms (by A. P. Rickard and colleagues and H. Hallberg and H. Hulten).
Median iron supplied (2.52 mg/day, interquartile range [IQR] = 2.43-3.17) was above the 50% of EAR of 2.0 mg/day (p < 0.001). Median bioavailable iron was 0.6 mg/day (IQR = 0.54-0.8) using the method of Rickard et al. and 0.51 mg/day (IQR = 0.43, 0.76 using that of Hallberg and Hulthen). The top three foods contributing to iron provision were bread, breakfast cereals and beef.
Our results suggest that LDC services in Perth are meeting the minimum recommendation of provision of 50% of the iron EAR, and also that toddlers are provided with sufficient bioavailable iron. Future strategies should focus on promoting food combinations to maintain the iron bioavailability in meals currently served at LDC services.

Type 2 diabetes is associated with both dietary iron intake and single-nucleotide polymorphism (SNP) of intronic rs10830963 in melatonin receptor 1B (MTNR1B); however, it is unclear whether they interact. The aim of this study was to examine the associations between dietary iron intake, SNP of rs10830963, and glucose metabolism. Data were obtained from the Shanghai Diet and Health Survey (SDHS) during 2012-2018. Standardized questionnaires were carried out through face-to-face interviews. A 3-day 24 h dietary recall was used to evaluate dietary iron intake. Anthropometric and laboratory measurements were applied. Logistic regression and general line models were used to evaluate the association between dietary iron intake, SNP of the MTNR1B rs10830963, and glucose metabolism. In total, 2951 participants were included in this study. After adjusting for age, sex, region, years of education, physical activity level, intentional physical exercise, smoking status, alcohol use, and total energy, among G allele carriers, dietary iron intake was associated with a risk of elevated fasting glucose, higher fasting glucose, and higher HbA1c, while no significant results were observed among G allele non-carriers. The G allele of intronic rs10830963 in MTNR1B potentially exacerbated unfavorable glucose metabolism with the increasing dietary iron intake, and it was possibly a risk for glucose metabolism homeostasis in the Chinese population.