Cooperative Metabolic Adaptations in the Host Can Favor Asymptomatic Infection and Select for Attenuated Virulence in an Enteric Pathogen.

Pathogen virulence exists on a continuum. The strategies that drive symptomatic or asymptomatic infections remain largely unknown. We took advantage of the concept of lethal dose 50 (LD50) to ask which component of individual non-genetic variation between hosts defines whether they survive or succumb to infection. Using the enteric pathogen Citrobacter, we found no difference in pathogen burdens between healthy and symptomatic populations. Iron metabolism-related genes were induced in asymptomatic hosts compared to symptomatic or naive mice. Dietary iron conferred complete protection without influencing pathogen burdens, even at 1000× the lethal dose of Citrobacter. Dietary iron induced insulin resistance, increasing glucose levels in the intestine that were necessary and sufficient to suppress pathogen virulence. A short course of dietary iron drove the selection of attenuated Citrobacter strains that can transmit and asymptomatically colonize naive hosts, demonstrating that environmental factors and cooperative metabolic strategies can drive conversion of pathogens toward commensalism.

A Large Proportion of the Neonatal Iron Pool Is Acquired from the Gestational Diet in a Murine Model.

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. OBJECTIVES: 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.

Dietary Iron Restriction Protects against Aneurysm Rupture in a Mouse Model of Intracranial Aneurysm.

INTRODUCTION: Iron accumulation in vessel walls induces oxidative stress and inflammation, which can cause cerebrovascular damage, vascular wall degeneration, and intracranial aneurysmal formation, growth, and rupture. Subarachnoid hemorrhage from intracranial aneurysm rupture results in significant morbidity and mortality. This study used a mouse model of intracranial aneurysm to evaluate the effect of dietary iron restriction on aneurysm formation and rupture. METHODS: Intracranial aneurysms were induced using deoxycorticosterone acetate-salt-induced hypertension and a single injection of elastase into the cerebrospinal fluid of the basal cistern. Mice were fed an iron-restricted diet (n = 23) or a normal diet (n = 25). Aneurysm rupture was detected by neurological symptoms, while the presence of intracranial aneurysm with subarachnoid hemorrhage was confirmed by post-mortem examination. RESULTS: The aneurysmal rupture rate was significantly lower in iron-restricted diet mice (37%) compared with normal diet mice (76%; p < 0.05). Serum oxidative stress, iron accumulation, macrophage infiltration, and 8-hydroxy-2'-deoxyguanosine in the vascular wall were lower in iron-restricted diet mice (p < 0.01). The areas of iron positivity were similar to the areas of CD68 positivity and 8-hydroxy-2'-deoxyguanosine in both normal diet and iron-restricted diet mouse aneurysms. CONCLUSIONS: These findings suggest that iron is involved in intracranial aneurysm rupture via vascular inflammation and oxidative stress. Dietary iron restriction may have a promising role in preventing intracranial aneurysm rupture.

Excessive dietary iron exposure increases the susceptibility of largemouth bass (Micropterus salmoides) to Aeromonas hydrophila by interfering with immune response, oxidative stress, and intestinal homeostasis.

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.

Relationship between trajectories of dietary iron intake and risk of type 2 diabetes mellitus: evidence from a prospective cohort study.

BACKGROUND: The association between dietary iron intake and the risk of type 2 diabetes mellitus (T2DM) remains inconsistent. In this study, we aimed to investigate the relationship between trajectories of dietary iron intake and risk of T2DM. METHODS: This study comprised a total of 61,115 participants without a prior T2DM from the UK Biobank database. We used the group-based trajectory model (GBTM) to identify different dietary iron intake trajectories. Cox proportional hazards models were used to evaluate the relationship between trajectories of dietary iron intake and risk of T2DM. RESULTS: During a mean follow-up of 4.8 years, a total of 677 T2DM events were observed. Four trajectory groups of dietary iron intake were characterized by the GBTM: trajectory group 1 (with a mean dietary iron intake of 10.9 mg/day), 2 (12.3 mg/day), 3 (14.1 mg/day) and 4 (17.6 mg/day). Trajectory group 3 was significantly associated with a 38% decreased risk of T2DM when compared with trajectory group 1 (hazard ratio [HR] = 0.62, 95% confidence interval [CI]: 0.49-0.79), while group 4 was significantly related with a 30% risk reduction (HR = 0.70, 95% CI: 0.54-0.91). Significant effect modifications by obesity (p = 0.04) and history of cardiovascular disease (p < 0.01) were found to the relationship between trajectories of dietary iron intake and the risk of T2DM. CONCLUSIONS: We found that trajectories of dietary iron intake were significantly associated with the risk of T2DM, where the lowest T2DM risk was observed in trajectory group 3 with a mean iron intake of 14.1 mg/day. These findings may highlight the importance of adequate dietary iron intake to the T2DM prevention from a public health perspective. Further studies to assess the relationship between dietary iron intake and risk of T2DM are needed, as well as intervention studies to mitigate the risks of T2DM associated with dietary iron changes.

Dietary intakes of iron, folate, and vitamin B12 during pregnancy and correlation with maternal hemoglobin and fetal growth: findings from the ROLO longitudinal birth cohort study.

PURPOSE: Dietary micronutrient intakes of iron, folate and vitamin B12 are known to influence hemoglobin. Low maternal hemoglobin (maternal anemia) has been linked to low birthweight and other adverse health outcomes in the fetus and infant. Our primary aim was to explore relationships between maternal dietary micronutrient intakes, maternal full blood count (FBC) parameters and fetal abdominal circumference (AC) and estimated fetal weight (EFW) growth trajectories. Secondarily, we aimed to assess relationships between maternal dietary micronutrient intakes, maternal hemoglobin values and placental weight and birthweight. METHODS: Mother-child pairs (n = 759) recruited for the ROLO study were included in this analysis. Maternal dietary micronutrient intakes were calculated from food diaries completed during each trimester of pregnancy. FBC samples were collected at 13- and 28-weeks' gestation. Fetal ultrasound measurements were recorded at 20- and 34-weeks' gestation. Growth trajectories for AC and EFW were estimated using latent class trajectory mixture models. RESULTS: Dietary intakes of iron and folate were deficient for all trimesters. Mean maternal hemoglobin levels were replete at 13- and 28-weeks' gestation. Dietary iron, folate and vitamin B12 intakes showed no associations with fetal growth trajectories, placental weight or birthweight. Lower maternal hemoglobin concentrations at 28 weeks' gestation were associated with faster rates of fetal growth and larger placental weights and birthweights. CONCLUSION: The negative association between maternal hemoglobin at 28 weeks' gestation and accelerated fetal and placental growth may be due to greater consumption of maternal iron and hemoglobin by fetuses' on faster growth trajectories in addition to placental biochemical responses to lower oxygen states.

High Dietary Iron in Western Diet-Fed Male Rats Causes Pancreatic Islet Injury and Acute Pancreatitis.

BACKGROUND: High dietary iron has been linked to an increased type 2 diabetes risk. We have previously shown that intrauterine growth restriction (IUGR) and feeding a Western diet (WD) to male Sprague-Dawley rats independently, as well as together, cause pancreatic islet inflammation, fibrosis, and hemosiderosis. OBJECTIVES: To investigate whether iron has a role in the pathogenesis of this inflammatory islet injury caused by IUGR and WD intake. METHODS: Male Sprague-Dawley offspring of bilateral uterine artery ligated (IUGR) and sham-operated (Sham) dams, fostered to nonoperated dams, were fed a WD [45% sucrose, 19.4% protein and 23% fat (w/w)] containing low iron (LI, 20 mg/kg) or high iron (HI, 500 mg/kg) from weaning. Four groups were studied: Sham-LI, Sham-HI, IUGR-LI, and IUGR-HI. Serial measurements of rat body weight, blood glucose, lipids and insulin, an intraperitoneal glucose tolerance test (age 13 wk), and histological analysis of pancreas and liver (age 14 wk) were recorded. The effects of iron, IUGR, and their interaction, on these measurements have been analyzed. RESULTS: WD with HI compared with LI caused an 11% greater weight gain by age 14 wk (P < 0.001), impaired glucose tolerance [AUC for glucose (G-AUC) 17% higher; P < 0.001), acute pancreatitis (17/18, HI; 6/17, LI; P < 0.001), pancreas-associated fat necrosis and saponification (7/18, HI; 0/17 LI; P < 0.01), and a trend to islet fibrotic injury (7/18, HI; 1/17 LI; P = 0.051). Although pancreatic and hepatic steatosis was evident in almost all WD-fed rats, pancreatic and hepatic iron accumulation was prevalent only in HI-fed rats (P < 0.0001 for both), being only mild in the livers. IUGR, independent of dietary iron, also caused impairment in glucose tolerance (G-AUC: 17% higher; P < 0.05). CONCLUSIONS: A postweaning WD containing HI, independent of IUGR, causes acute pancreatitis and islet injury in Sprague-Dawley rats suggesting a role of dietary iron in the development of steatopancreatitis.

Estimation of the availability of iron in the school meals of Municipal Centers for Early Childhood Education of a capital city in northeastern Brazil.

The final stage of Fe deficiency is Fe deficiency anaemia, with repercussions for human health, especially in children under 5 years of age. Studies conducted in Brazilian public daycare centres show high prevalence of anaemia. The present study aims to evaluate the availability of Fe in the meals of the Municipal Centers of Early Childhood Education in Maceió. The experimental design comprises selection of algorithms, menu evaluation, calculation of the estimates, comparison between the estimates obtained and the recommendations, and analysis of correlation between meal constituents, and of the concordance between the absorbable Fe estimates. Four algorithms were selected and a monthly menu consisting of 22 d. The correlation analysis showed a moderate positive correlation to animal tissue (AT) v. non-heme iron (r = 0·42; P = 0·04), and negative to AT v. Ca (r = -0·54; P = 0·09) and Ca v. phytates (r = -0·46, P = 0·03). Estimates of absorbable Fe ranged from 0·23 to 0·44 mg/d. The amount of Fe available, unlike the total amount of Fe offered, does not meet the nutritional recommendations on most school days. The Bland-Altman analysis indicated that the Monsen and Balinfty and Rickard et al. showed greater agreement. The results confirm the need to adopt strategies to increase the availability of Fe in school meals.

Dietary intakes of total, nonheme, and heme iron and hypertension risk: a longitudinal study from the China Health and Nutrition Survey.

AIMS: Evidence is limited regarding the long-term impact of dietary iron intake on the development of hypertension. We investigated the association between dietary intakes of total, nonheme, and heme iron and hypertension risk in a large prospective cohort of Chinese populations over 26 years. METHODS: A total of 16,122 adults (7810 men and 8312 women) who participated in the China Health and Nutrition Survey (1989-2015) were included. Dietary intake was repeatedly assessed by combining three consecutive 24­h individual dietary recalls with household food inventory weighing at each survey round. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, diagnosis by physicians, or current use of anti-hypertensive drugs. RESULTS: During a median follow­up of 11.1 years, 2863 men and 2532 women developed hypertension. After adjustment for non-dietary and dietary factors, a lower risk of hypertension was found in men and women with higher intakes of total, nonheme, or heme iron. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest vs. lowest quartiles were 0.76 (0.67, 0.87) in men and 0.85 (0.74, 0.97) in women for total iron intake, 0.77 (0.67, 0.87) in men and 0.85 (0.74, 0.98) in women for nonheme iron intake, and 0.73 (0.62, 0.87) in men and 0.69 (0.58, 0.82) in women for heme iron intake. Dose-response analyses further revealed a U-shaped association of total and nonheme iron intake and an L-shaped association of heme iron intake with hypertension risk in both men and women (all P for non-linearity < 0.001). CONCLUSIONS: Our findings emphasize the importance of maintaining moderate iron intake in the prevention of hypertension. Both insufficient and excess intake of iron might increase the risk of hypertension.

Dietary iron intake and its impact on osteopenia/osteoporosis.

BACKGROUND: Osteoporosis is a prevalent condition characterized by low bone density and increased risk of fractures, resulting in a significant healthcare burden. Previous research has suggested that serum ferritin levels may be related to the risk of developing osteoporosis. The aim of this study was to investigate the relationship between dietary iron intake and the development of osteoporosis. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018, a total of 11,690 adults aged over 20 were evaluated. Bone mineral density (BMD) measurements of the femoral neck and lumbar spine were used to assess osteoporosis and osteopenia. Dietary iron intake was determined using food intake interviews and the Food and Nutrient Database for Dietary Studies. Logistic regression models were applied to investigate the association between dietary iron consumption and osteopenia and osteoporosis. RESULTS: After adjusting for sociodemographic factors, compared with those who had the first quartile (Q1) of dietary iron intake, the odds ratio (OR) for osteopenia across the quartiles of dietary iron intake levels was 0.88 (95%CI: 0.79-0.98), 0.80 (95%CI: 0.72-0.89), and 0.74 (95%CI: 0.67-0.83) for Q2, Q3, and Q4, respectively. And the OR for osteoporosis across the quartiles of dietary iron intake levels was 1.00, 0.77 (95%CI: 0.50-1.19), 0.54 (95%CI: 0.34-0.89), and 0.83 (95%CI: 0.54-1.29) for Q1, Q2, Q3, and Q4, respectively. Notably, the observed association was significant among females but not males. CONCLUSION: The risk of osteopenia/osteoporosis in females decreases with a moderate increase in dietary iron consumption. For females to preserve bone health, moderately increasing their dietary iron intake without overindulging should be seen as a key approach. Our study provides useful insights for developing dietary strategies to prevent and manage osteoporosis in vulnerable populations.

Toddlers may be getting enough iron in long day-care services after all.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Dietary iron and the risk of lung cancer.

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.

A Prolonged Bout of Running Increases Hepcidin and Decreases Dietary Iron Absorption in Trained Female and Male Runners.

BACKGROUND: Declines in iron status are frequently reported in those who regularly engage in strenuous physical activity. A possible reason is increases in the iron regulatory hormone hepcidin, which functions to inhibit dietary iron absorption and can be induced by the inflammatory cytokine interleukin-6 (IL-6). OBJECTIVES: The current study aimed to determine the impact of a prolonged bout of running on hepcidin and dietary iron absorption in trained female and male runners. METHODS: Trained female and male collegiate cross country runners (n = 28, age: 19.7 ± 1.2 y, maximal oxygen uptake: 66.1 ± 6.1 mL $\cdot$ kg -1$\cdot$ min-2, serum ferritin: 21.9 ± 13.3 ng/mL) performed a prolonged run (98.8 ± 14.7 min, 21.2 ± 3.8 km, 4.7 ± 0.3 min/km) during a team practice. Participants consumed a stable iron isotope with a standardized meal 2 h postrun and blood was collected 1 h later. The protocol was repeated 2 wk later except participants abstained from exercise (rest). RBCs were collected 15 d after exercise and rest to determine isotope enrichment. Differences between exercise and rest were assessed by paired t tests and Wilcoxon matched-pairs signed rank tests. Data are means ± SDs. RESULTS: Plasma hepcidin increased 51% after exercise (45.8 ± 34.4 ng/mL) compared with rest (30.3 ± 27.2 ng/mL, P = 0.0010). Fractional iron absorption was reduced by 36% after exercise (11.8 ± 14.6 %) compared with rest (18.5 ± 14.4 %, P = 0.025). Plasma IL-6 was greater after exercise (0.660 ± 0.354 pg/mL) than after rest (0.457 ± 0.212 pg/mL, P < 0.0001). Exploratory analyses revealed that the increase in hepcidin with exercise may be driven by a response in males but not females. CONCLUSIONS: A prolonged bout of running increases hepcidin and decreases dietary iron absorption compared with rest in trained runners with low iron stores. The current study supports that IL-6 contributes to the increase in hepcidin with prolonged physical activity, although future studies should explore potential sex differences in the hepcidin response.This trial was registered at Clinicaltrials.gov as NCT04079322.

An overview on mechanism, cause, prevention and multi-nation policy level interventions of dietary iron deficiency.

Iron deficiency anemia (IDA) is probably the most ignored situation in the world of malnutrition-largely due to its slow progression. Multiple reasons can be attributed as the cause of IDA, which is not limited to any specific region or population; therefore, making it a matter of global concern. Despite the human body's ability to absorb and conserve iron stores, the gradual loss due to various physiological conditions leads to net deficiency of iron. Countless commercial iron supplements are available, but at given physiological conditions, almost all of these "Bio-not-available" iron forms quite often become ineffective. World Health Organization and other government bodies have jointly developed health advisories and tried to developed nutrition supplements several times in the last two decades. IDA, when combined with other disease conditions, becomes a life-threatening situation. At the same time, an overdose of iron could also be very harmful to the body. Therefore, it is important to deal with this situation with caution. This article covers iron metabolism, available options for iron supplementation, regulatory aspects and strategies to prevent IDA.

The effect of a natural polyphenol supplement on iron absorption in adults with hereditary hemochromatosis.

OBJECTIVES: We developed a natural polyphenol supplement that strongly chelates iron in vitro and assessed its effect on non-heme iron absorption in patients with hereditary hemochromatosis (HH). METHODS: We performed in vitro iron digestion experiments to determine iron precipitation by 12 polyphenol-rich dietary sources, and formulated a polyphenol supplement (PPS) containing black tea powder, cocoa powder and grape juice extract. In a multi-center, single-blind, placebo-controlled cross-over study, we assessed the effect of the PPS on iron absorption from an extrinsically labelled test meal and test drink in patients (n = 14) with HH homozygous for the p.C282Y variant in the HFE gene. We measured fractional iron absorption (FIA) as stable iron isotope incorporation into erythrocytes. RESULTS: Black tea powder, cocoa powder and grape juice extract most effectively precipitated iron in vitro. A PPS mixture of these three extracts precipitated ~ 80% of iron when 2 g was added to a 500 g iron solution containing 20 µg Fe/g. In the iron absorption study, the PPS reduced FIA by ~ 40%: FIA from the meal consumed with the PPS was lower (3.01% (1.60, 5.64)) than with placebo (5.21% (3.92, 6.92)) (p = 0.026)), and FIA from the test drink with the PPS was lower (10.3% (7.29 14.6)) than with placebo (16.9% (12.8 22.2)) (p = 0.002). CONCLUSION: Our results indicate that when taken with meals, this natural PPS can decrease dietary iron absorption, and might thereby reduce body iron accumulation and the frequency of phlebotomy in patients with HH. TRIAL REGISTRY: clinicaltrials.gov (registration date: 9.6.2019, NCT03990181).

High Dietary Iron Has a Greater Impact on Brain Iron Homeostasis and Cognitive Function in Old Compared with Young C57BL/6J Male Mice.

BACKGROUND: Brain iron accumulation is a feature of Alzheimer disease (AD) but whether a chronic dietary iron overload contributes to AD induction is unknown. We previously showed that young mice fed a high iron diet did not display cognitive impairment despite the AD pathological markers in hippocampus. OBJECTIVES: We aim to compare the impact of high dietary iron on brain pathologic changes and cognitive function in young and old mice. METHODS: Male C57BL/6J mice at 1 mo and 13 mo of age were fed with either a control diet (66 mg Fe/kg; Young-Ctrl and Old-Ctrl) or a high iron diet (14 g Fe/kg; Young-High Fe and Old-High Fe) for 7 mo, and outcomes were evaluated at 8 mo and 20 mo of age. Iron concentrations in brain regions were measured by atomic absorption spectrophotometry. Perls's Prussian blue staining and amyloid-ß (Aß) immunostaining were performed. Protein expression in the cerebral cortex and hippocampus was determined by immunoblotting. Superoxide dismutase activity and malondialdehyde concentration were examined. Cognitive functions were tested with the Morris water maze system. Two-factor ANOVA was used to analyze most data. RESULTS: Compared with Old-Ctrl mice, Old-High Fe mice showed significantly higher iron concentrations in cerebral cortex (60% higher), cerebellum (60% higher), and hippocampus (90% higher), paralleled by lower superoxide dismutase activity and greater malondialdehyde concentration in cerebral cortex and hippocampus and worse cognitive function. In contrast, these variables did not significantly differ between the 2 young groups. Nevertheless, ferritin, phospho-tau, and Aß1-42 expression in hippocampus and ferritin and Aß1-42 expression in cerebral cortex were induced by the high iron diet irrespective of the age of mice (40-200% greater). CONCLUSIONS: High dietary iron induced cognitive defects in old mice but not young mice, suggesting that elderly people should avoid consuming abnormally high concentrations of iron.

Dietary iron intake and the risk of type 2 diabetes mellitus in middle-aged and older adults in urban China: a prospective cohort study.

The association between dietary Fe intake and diabetes risk remains inconsistent. We aimed to explore the association between dietary Fe intake and type 2 diabetes mellitus (T2DM) risk in middle-aged and older adults in urban China. This study used data from the Guangzhou Nutrition and Health Study, an on-going community-based prospective cohort study. Participants were recruited from 2008 to 2013 in Guangzhou community. A total of 2696 participants aged 40-75 years without T2DM at baseline were included in data analyses, with a median of 5·6 (interquartile range 4·1-5·9) years of follow-up. T2DM was identified by self-reported diagnosis, fasting glucose ≥ 7·0 mmol/l or glycosylated Hb ≥ 6·5 %. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95 % CI. We ascertained 205 incident T2DM cases during 13 476 person-years. The adjusted HR for T2DM risk in the fourth quartile of haem Fe intake was 1·92 (95 % CI 1·07, 3·46; Ptrend = 0·010), compared with the first quartile intake. These significant associations were found in haem Fe intake from total meat (HR 2·74; 95 % CI 1·22, 6·15; Ptrend = 0·011) and haem Fe intake from red meat (HR 1·86; 95 % CI 1·01, 3·44; Ptrend = 0·034), but not haem Fe intake from processed meat, poultry or fish/shellfish. The association between dietary intake of total Fe or non-haem Fe with T2DM risk had no significance. Our findings suggested that higher dietary intake of haem Fe (especially from red meat), but not total Fe or non-haem Fe, was associated with greater T2DM risk in middle-aged and older adults.

Non-anaemic iron deficiency.

Iron deficiency without anaemia is common. Patients may present with unexplained, non-specific symptoms. Iron studies will usually show a low ferritin and low transferrin saturation with a normal haemoglobin concentration. The cause of the iron deficiency should be identified and managed. There is limited evidence about the benefits of giving iron to people who do not have anaemia. If there is iron deficiency, most people can be given oral iron supplements. Iron studies are repeated after 60-90 days of oral iron supplements. Further investigations are needed if the iron deficiency has not been corrected. Some patients, including those who have not responsed to oral supplements may benefit from intravenous iron. There is no role for intramuscular injections of iron.

High Prevalence of Poor Iron Status Among 8- to 16-Year-Old Youth Athletes: Interactions Among Biomarkers of Iron, Dietary Intakes, and Biological Maturity.

Objective: The purpose of this study was to determine the prevalence of poor iron status in young athletes throughout the stages of iron deficiency and assess sex differences with iron deficiency in relation to growth and development and dietary intake.Methods: A cross-sectional analysis evaluated young male and female athletes (n = 91) between the ages 8 and 16 years. Anthropometric assessments, body composition, dietary intakes, and blood samples measuring ferritin, soluble transferrin receptor (sTfR), and hemoglobin (Hb) were examined. Prevalence was calculated as percentages, and independent samples t tests examined sex differences. Pearson product-moment correlation coefficient analyses quantified relationships among variables for the composite sample and each sex separately.Results: Iron depletion (low ferritin) was present in 65% and 86%, low iron levels (sTfR) in 51% and 68%, and anemia (low Hb) in 46% and 53% of the males and females, respectively. As iron deficiency progressed from low ferritin to high sTfR to anemia, prevalence decreased in both sexes, but always remained higher in females. Males were greater than females for weight, arm muscle size, and ferritin concentrations, while females were greater than males for biological maturity (p ≤ 0.05). Dietary iron intake was moderately to highly correlated (r = 0.543-0.723, p ≤ 0.05) with growth and development in females, but not males.Conclusions: Prevalence of poor iron status was higher than expected, particularly in adolescent females. Since rapid growth combined with sports participation may create high demands for iron bioavailability, emphasis may need to be placed on dietary iron intake for young athletes, particularly females.

Evaluation of promotion of iron-rich foods for the prevention of nutritional anemia in India.

BACKGROUND: Nutritional anemia due to iron deficiency is the most common cause of anemia in India. The average diet in India is low in iron and mostly of vegetable origin. This can be improved by increasing awareness of foodstuffs that are rich in iron and ensuring their availability. OBJECTIVE: The objective of the study was to assess the quality of information available on iron-rich foods and to assess their production and consumption in India. METHODS: This was a review of common textbooks for medical, nursing, and home science students; related policy and program documents; and government publications on production and consumption of various foodstuffs in India. RESULTS: Details of specific foods that are rich in iron have not been provided. Instead, food groups such as pulses, cereals, nuts, and green leafy vegetables (GLVs) have been mentioned that are good sources of non-heme iron. This is in spite of the fact that all the foodstuffs in these groups are not uniformly iron rich. Among cereals and pulses, rice and red gram dal (arhar) are the most commonly produced and consumed, though they have the lowest iron content. Spinach and mustard leaves believed to be iron rich and commonly consumed are among those GLVs having lowest iron content. CONCLUSION: Details of 5-10 foodstuffs which have the highest iron content within each food group should be available in relevant books and documents meant for education, production, and consumption data.