Dietary Iron Is Necessary to Support Proliferative Regeneration after Intestinal Injury.

BACKGROUND: Tissue repair and regeneration in the gastrointestinal system are crucial for maintaining homeostasis, with the process relying on intricate cellular interactions and affected by micro- and macro-nutrients. Iron, essential for various biological functions, plays a dual role in tissue healing by potentially causing oxidative damage and participating in anti-inflammatory mechanisms, underscoring its complex relationship with inflammation and tissue repair. OBJECTIVE: The study aimed to elucidate the role of low dietary iron in gastrointestinal tissue repair. METHODS: We utilized quantitative iron measurements to assess iron levels in inflamed regions of patients with ulcerative colitis and Crohn's disease. In addition, 3 mouse models of gastrointestinal injury/repair (dextran sulfate sodium-induced colitis, radiation injury, and wound biopsy) were used to assess the effects of low dietary iron on tissue repair. RESULTS: We found that levels of iron in inflamed regions of both patients with ulcerative colitis and Crohn's disease are elevated. Similarly, during gastrointestinal repair, iron levels were found to be heightened, specifically in intestinal epithelial cells across the 3 injury/repair models. Mice on a low-iron diet showed compromised tissue repair with reduced proliferation. In standard diet, epithelial cells and the stem cell compartment maintain adequate iron stores. However, during a period of iron deficiency, epithelial cells exhaust their iron reserves, whereas the stem cell compartments maintain their iron pools. During injury, when the stem compartment is disrupted, low iron levels impair proliferation and compromise repair mechanisms. CONCLUSIONS: Low dietary iron impairs intestinal repair through compromising the ability of epithelial cells to aid in intestinal proliferation.

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.

Long-term dietary iron intake and risk of non-fatal cardiovascular diseases in the China Health and Nutrition Survey.

AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: 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) 1989­2015, 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.

The Association between Dietary Iron Intake and Incidence of Dementia in Adults Aged 60 Years or over in the UK Biobank.

Background Several studies have investigated the association between dietary iron intake and cognitive impairment, but little is known about the relationship between iron intake and dementia incidence. Objectives This study explored the association between dietary iron intake and incident dementia in males and females. Whether this association was modified by factors such as age and medical diseases was also examined. Methods We included 41,213 males and 48,892 females aged 60 years or over, from the UK-Biobank cohort. Dietary iron intake was measured using a web-based 24-h dietary recall questionnaire from between 2009 and 2012. Incident dementia was ascertained using hospital inpatient records and death registers until April 2021. Cox proportional regression models examined the association between iron intake and incident dementia, and hazard ratio curves were constructed with knots from the analysis indicating insufficient or excessive iron intake. Results During a mean follow-up of 11.8 years, 560 males and 492 females developed dementia. A non-linear relationship between iron intake and incident dementia was observed in both males and females. The lowest incidence rates were observed in the higher iron intake quintile (Q4: ≥15.73, <17.57 mg/day) for males, and the intermediate iron intake quintile (Q3: ≥12.4, <13.71 mg/day) for females. Among those aged 60 and above, all-cause dementia in males was associated with deficient iron intake (Q1 versus Q4: Hazard ratio [HR]: 1.37, 95% Confidence interval [95%CI]: 1.01−1.86, p = 0.042) and excessive iron intake (Q5 versus Q4: HR: 1.49, 95%CI: 1.14−1.96, p = 0.003), whilst significant associations between all-cause dementia and deficient iron intake were only observed in females without hypertension. Smoking status was a significant moderator (p-value for trend = 0.017) for dementia in males only. Conclusions Excessive iron intake (≥17.57 mg/day) is associated with a higher incidence of all-cause dementia in males and smoking status modified this association amongst males. Deficient iron intake (<10.93 mg/day) was associated with a higher incidence of all-cause dementia in females without a history of hypertension.

Efficacy of intermittent iron supplementation in children with mild iron-deficiency anemia. / å„¿ç«¥è½»åº¦ç¼ºé“æ€§è´«è¡€é—´æ­‡è¡¥é“ç–—æ³•çš„æœ‰æ•ˆæ€§ç ”ç©¶.

OBJECTIVES: To study the efficacy of intermittent iron supplementation in children with mild iron-deficiency anemia. METHODS: A total of 147 children with mild iron-deficiency anemia were enrolled in this prospective study. They were divided into an intermittent iron supplementation group (n=83) and a conventional iron supplementation group (n=64). The levels of hemoglobin were measured before treatment and after 1 and 3 months of treatment. The treat response rate and the incidence rate of adverse drug reactions were compared between the two groups. RESULTS: Both groups had a significant increase in the level of hemoglobin after iron supplementation (P<0.05). After 1 month of treatment, the conventional iron supplementation group had a significantly higher treatment response rate than the intermittent iron supplementation group (61% vs 42%, P<0.05). After 3 months of treatment, there was no significant difference in the treatment response between the two groups (86% vs 78%, P>0.05). The incidence rate of adverse drug reactions in the conventional iron supplementation group was significantly higher than that in the intermittent iron supplementation group (25% vs 8%, P<0.05). CONCLUSIONS: For children with mild iron-deficiency anemia, although intermittent iron supplementation is inferior to conventional iron supplementation in the short-term efficacy, there is no significant difference in the long-term efficacy between the two methods, and compared with conventional iron supplementation, intermittent iron supplementation can reduce the incidence of adverse drug reactions, alleviate family financial burdens, and improve treatment compliance of children, thus holding promise for clinical application.

Efficacy of intermittent iron supplementation in children with mild iron-deficiency anemia / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy of intermittent iron supplementation in children with mild iron-deficiency anemia.@*METHODS@#A total of 147 children with mild iron-deficiency anemia were enrolled in this prospective study. They were divided into an intermittent iron supplementation group (n=83) and a conventional iron supplementation group (n=64). The levels of hemoglobin were measured before treatment and after 1 and 3 months of treatment. The treat response rate and the incidence rate of adverse drug reactions were compared between the two groups.@*RESULTS@#Both groups had a significant increase in the level of hemoglobin after iron supplementation (P<0.05). After 1 month of treatment, the conventional iron supplementation group had a significantly higher treatment response rate than the intermittent iron supplementation group (61% vs 42%, P<0.05). After 3 months of treatment, there was no significant difference in the treatment response between the two groups (86% vs 78%, P>0.05). The incidence rate of adverse drug reactions in the conventional iron supplementation group was significantly higher than that in the intermittent iron supplementation group (25% vs 8%, P<0.05).@*CONCLUSIONS@#For children with mild iron-deficiency anemia, although intermittent iron supplementation is inferior to conventional iron supplementation in the short-term efficacy, there is no significant difference in the long-term efficacy between the two methods, and compared with conventional iron supplementation, intermittent iron supplementation can reduce the incidence of adverse drug reactions, alleviate family financial burdens, and improve treatment compliance of children, thus holding promise for clinical application.

Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01-2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844-868) at birth in terms of weight (ß' = 0.078 (0.024-0.133); p = 0.005), head circumference (ß' = 0.060 (0.012-0.107); p = 0.02), body mass index (ß' = 0.067 (0.014-0.119); p = 0.01), and various skinfold thicknesses (ß' = 0.067-0.094; p = 0.03-0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM.

Long-Term Iron Deficiency and Dietary Iron Excess Exacerbate Acute Dextran Sodium Sulphate-Induced Colitis and Are Associated with Significant Dysbiosis.

BACKGROUND: Oral iron supplementation causes gastrointestinal side effects. Short-term alterations in dietary iron exacerbate inflammation and alter the gut microbiota, in murine models of colitis. Patients typically take supplements for months. We investigated the impact of long-term changes in dietary iron on colitis and the microbiome in mice. METHODS: We fed mice chow containing differing levels of iron, reflecting deficient (100 ppm), normal (200 ppm), and supplemented (400 ppm) intake for up to 9 weeks, both in absence and presence of dextran sodium sulphate (DSS)-induced chronic colitis. We also induced acute colitis in mice taking these diets for 8 weeks. Impact was assessed (i) clinically and histologically, and (ii) by sequencing the V4 region of 16S rRNA. RESULTS: In mice with long-term changes, the iron-deficient diet was associated with greater weight loss and histological inflammation in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a change in the microbiome in DSS-treated mice consuming 100 ppm and 400 ppm iron diets, and control mice consuming the 400 ppm iron diet. Proteobacteria levels increased significantly, and Bacteroidetes levels decreased, in the 400 ppm iron DSS group at day-63 compared to baseline. CONCLUSIONS: Long-term dietary iron alterations affect gut microbiota signatures but do not exacerbate chronic colitis, however acute colitis is exacerbated by such dietary changes. More work is needed to understand the impact of iron supplementation on IBD. The change in the microbiome, in patients with colitis, may arise from the increased luminal iron and not simply from colitis.

The effect of food and nutrients on iron overload: what do we know so far?

There has been no established food and nutrition guidance for diseases characterized by the presence of iron overload (IOL) yet. Hepcidin is a hormone that diminishes iron bioavailability. Its levels increase in response to increased iron stores. Hence, IOL conditions could hypothetically trigger a self-regulatory mechanism for the reduction of the intestinal absorption of iron. In addition, some food substances may modulate intestinal iron absorption and may be useful in the dietary management of patients with IOL. This scoping review aimed to systematize studies that support dietary prescriptions for IOL patients. It was carried out according to the method proposed by the Joanna Briggs Institute and the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Although the need to restrict iron in the diet of individuals with hemochromatosis is quite clear, there is a consensus that IOL diminishes the rate of iron absorption. Reduced iron absorption is also present and has been reported in some diseases with transfusion IOL, in which serum hepcidin is usually high. The consumption of polyphenols and 6-shogaol seems to reduce iron absorption or serum ferritin concentration, while procyanidins do not cause any changes. Vitamin C deficiency is often found in IOL patients. However, vitamin C supplementation and alcohol consumption should be avoided not only because they increase iron absorption, but also because they provoke toxic oxidative reactions when the iron is excessive. Dietary approaches must consider the differences in the pathophysiology and treatment of IOL diseases.

Loss of Cardiac Ferritin H Facilitates Cardiomyopathy via Slc7a11-Mediated Ferroptosis.

RATIONALE: Maintaining iron homeostasis is essential for proper cardiac function. Both iron deficiency and iron overload are associated with cardiomyopathy and heart failure via complex mechanisms. Although ferritin plays a central role in iron metabolism by storing excess cellular iron, the molecular function of ferritin in cardiomyocytes remains unknown. OBJECTIVE: To characterize the functional role of Fth (ferritin H) in mediating cardiac iron homeostasis and heart disease. METHODS AND RESULTS: Mice expressing a conditional Fth knockout allele were crossed with 2 distinct Cre recombinase-expressing mouse lines, resulting in offspring that lack Fth expression specifically in myocytes (MCK-Cre) or cardiomyocytes (Myh6-Cre). Mice lacking Fth in cardiomyocytes had decreased cardiac iron levels and increased oxidative stress, resulting in mild cardiac injury upon aging. However, feeding these mice a high-iron diet caused severe cardiac injury and hypertrophic cardiomyopathy, with molecular features typical of ferroptosis, including reduced glutathione (GSH) levels and increased lipid peroxidation. Ferrostatin-1, a specific inhibitor of ferroptosis, rescued this phenotype, supporting the notion that ferroptosis plays a pathophysiological role in the heart. Finally, we found that Fth-deficient cardiomyocytes have reduced expression of the ferroptosis regulator Slc7a11, and overexpressing Slc7a11 selectively in cardiomyocytes increased GSH levels and prevented cardiac ferroptosis. CONCLUSIONS: Our findings provide compelling evidence that ferritin plays a major role in protecting against cardiac ferroptosis and subsequent heart failure, thereby providing a possible new therapeutic target for patients at risk of developing cardiomyopathy.

Iron intake is positively associated with viral load in antiretroviral naïve Brazilian men living with HIV.

BACKGROUND: Iron homeostasis contribute for the human immunodeficiency virus (HIV) pathogenesis. OBJECTIVES: We assessed the iron intake pattern in antiretroviral naïve Brazilian men living with HIV correlating with clinical and nutritional parameters. METHODS: The iron consumption mean was estimated according to a food frequency questionnaire (FFQ), and a 3-day food record (3dFR) submitted to the patients. HIV viral load, CD4+ T cell counts, serum iron, haematological and anthropometrics parameters were recorded. FINDINGS: Fifty-one HIV-infected adult men naïve for antiretroviral therapy (ART) were enrolled. The mean age of participants was 35 (SEM ± 1.28) years old, with mean time of HIV-1 infection of 1.78 (0-16.36, min-max) years. Majority (41.18%) had complete secondary, and 21.57% had tertiary educational level. The income was around 1x (54.90%) to 2x (41.18%) minimum wage. Fifty-four percent showed normal weight, while 40% were overweight. The patients showed normal mean values of haematological parameters, and mean serum iron was 14.40 µM (SEM ± 0.83). The FFQ showed moderate correlation with the 3dFR (ρ = 0.5436, p = 0.0009), and the mean values of iron intake were 10.55(± 0.92) mg/day, recorded by FFQ, and 15.75(± 1.51) mg/day, recorded by 3dFR. The iron intake, recorded by FFQ, negatively correlated with serum iron (ρ = -0.3448, p = 0.0132), and did not have influence in the CD4+ T cell counts [e.B 0.99 (0.97-1.01, 95% confidence interval (CI), p = 0.2]. However, the iron intake showed a positive effect in HIV viral load [e.B 1.12 (1.02-1.25, 95%CI), p < 0.01]. MAIN CONCLUSIONS: This study draws attention for the importance of iron intake nutritional counseling in people living with HIV. However, more studies are required to clarify the association between high iron intake and HIV infection and outcome.

Effects of over-load iron on nutrient digestibility, haemato-biochemistry, rumen fermentation and bacterial communities in sheep.

There is a risk of iron overload in grazing livestock. However, the effects on nutrient absorption and rumen function induced by excessive iron have not been well understood. Therefore, the purpose of present study was to investigate the impact of over-load iron on growth performance, nutrient digestibility, blood biochemistry, rumen fermentation and bacterial communities in sheep. Twenty-four German Mutton Merino cross-bred sheep with weight (42.66 ± 2.34 kg BW) were randomly divided into 4 groups, each with 6 replicates and 1 sheep per replicate. The basal diet consisted of 60% Leymus chinensis hay and 40% concentrate. The sheep in 4 groups were fed the basal diets supplemented with 50 (Control), 500 (T1), 1,000 (T2) and 1,500 (T3) mg Fe/kg as ferrous sulphate monohydrate (FeSO4 ·H2 O) respectively. And the actual contents of iron in the diet were determined to be 457.68 (control), 816.42 (T1), 1,256.78 (T2) and 1,725.63 (T3) mg/kg respectively. The experiment lasted 62 days including a 7-day metabolism trial. During the whole experiment, the digestibility of dry matter, organic matter, neutral detergent fibre and acid detergent fibre showed a quadratic increase with increasing over-load iron levels (p < .05), and maximum responses were found with 500 mg/kg supplementation. However, the response of total VFA concentration showed a quadratic decrease, as did the concentrations of propionate, butyrate and valerate (p < .05). Serum total iron-binding capacity on day 30 showed a quadratic decrease with the increase in high-dose iron, while the serum iron content increased linearly at day 60 (p < .05). Excessive iron resulted in the change in bacterial communities. An increase in over-load iron linearly decreased the abundance of bacteria in the phylum Bacteroidetes (p < .05), but linearly increased the Firmicutes (p = .037) and Proteobacteria (p = .018). In addition, there was a quadratic effect (p = .003) on the Fibrobacteres, which was higher in the 500 and 1,000 mg/kg Fe-supplemented groups. At the genus level, there were quadratic effects on the abundances of Selenomonas_1 (p = .023) and Ruminococcaceae_UCG-014 (p = .016). Furthermore, feeding of iron linearly increased the relative abundances of Succiniclasticum and Succinivibrionaceae_UCG-002 (p < .05). These results indicate that increasing ferrous sulphate monohydrate in diets had no negative impact on the growth performance, but it changed nutrient digestibility, blood iron parameters, rumen fermentation and bacterial communities in sheep.

Excess Iron Enhances Purine Catabolism Through Activation of Xanthine Oxidase and Impairs Myelination in the Hippocampus of Nursing Piglets.

BACKGROUND: Few studies have addressed the risk of nutritional iron overexposure in infancy. We previously found that excess dietary iron in nursing piglets resulted in iron overload in the liver and hippocampus and diminished socialization with novel conspecifics in a test for social novelty preference. OBJECTIVES: This experiment aimed to identify metabolites and metabolic pathways affected by iron overload in the liver and hippocampus of nursing piglets. METHODS: Liver and hippocampal tissues collected from 22-d-old piglets (Hampshire × Yorkshire crossbreed; 5.28 ± 0.53 kg body weight; 50% male) that received orally 0 (NI group) or 50 mg iron/(d · kg body weight) (HI group) from postnatal day (PD) 2 to PD21 were analyzed for mRNA and protein expression and enzyme activity of xanthine oxidase (XO). Untargeted metabolomics was performed using GC-MS. Expression of myelin basic protein (MBP) in the hippocampus was determined using western blot. RESULTS: There were 108 and 126 metabolites identified in the hippocampus and liver, respectively. Compared with NI, HI altered 15 metabolites (P < 0.05, q < 0.2) in the hippocampus, including a reduction in myo-inositol (0.86-fold) and N-acetylaspartic acid (0.84-fold), 2 metabolites important for neuronal function and myelination. Seven metabolites involved in purine and pyrimidine metabolism (e.g., hypoxanthine, xanthine, and ß-alanine) were coordinately changed in the hippocampus (P < 0.05, q < 0.2), suggesting that iron excess enhanced purine catabolism. The mRNA expression (2.3-fold) (P < 0.05) and activity of XO, a rate-limiting enzyme in purine degradation, was increased. Excess iron increased hippocampal lipid peroxidation by 74% (P < 0.05) and decreased MBP by 44% (P = 0.053). The hepatic metabolome was unaffected. CONCLUSIONS: In nursing piglets, excess iron enhances hippocampal purine degradation through activation of XO, which may induce oxidative stress and alter energy metabolism in the developing brain.

Dietary and Sentinel Factors Leading to Hemochromatosis.

Although hereditary hemochromatosis is associated with the mutation of genes involved in iron transport and metabolism, secondary hemochromatosis is due to external factors, such as intended or unintended iron overload, hemolysis-linked iron exposure or other stress-impaired iron metabolism. The present review addresses diet-linked etiologies of hemochromatosis and their pathogenesis in the network of genes and nutrients. Although the mechanistic association to diet-linked etiologies can be complicated, the stress sentinels are pivotally involved in the pathological processes of secondary hemochromatosis in response to iron excess and other external stresses. Moreover, the mutations in these sentineling pathway-linked genes increase susceptibility to secondary hemochromatosis. Thus, the crosstalk between nutrients and genes would verify the complex procedures in the clinical outcomes of secondary hemochromatosis and chronic complications, such as malignancy. All of this evidence provides crucial insights into comprehensive clinical or nutritional interventions for hemochromatosis.

Update of pre- and postnatal iron supplementation in malaria endemic settings.

This review focuses on pre- and post-natal iron supplementation in malaria endemic settings. Although iron supplementation can reduce iron deficiency, malaria infection may counteract this effect by the increase of hepcidin, and iron supplementation may further worsen malaria infection by providing additional iron for the parasites. However, most iron supplementation intervention studies in pregnant women with malaria have not shown a negative impact, although malaria treatment with iron supplementation may be beneficial in terms of improving birth outcomes. In infants and young children in malaria endemic settings, the adverse effects of iron supplementation has been well documented and malaria prevention and treatment with iron supplementation is recommended. Besides fostering the growth of malaria parasites, iron may also promote potential pathogens in the gut and cause an inflammatory response in young children. Overall, iron supplementation is beneficial for treating iron deficiency, but needs to be considered in the context of malaria prevention and treatment in pregnant women, infants and young children for safety and effectiveness.

Association between dietary iron and zinc intake and development of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: The prevalence of ulcerative colitis (UC) has been increasing in Japan. Trace elements, such as iron, zinc, magnesium, and copper, can cause digestive symptoms where there is a deficiency or excess. We focused on the dietary intake of trace elements and their associations with UC development. METHODS: A multicenter, hospital-based case-control study was conducted in Japan. Cases were 127 newly diagnosed UC patients, and 171 age-matched and sex-matched hospital controls were recruited. We considered that UC patients had potentially changed their dietary habits due to disease symptoms. The dietary habits were investigated using a self-administered diet history questionnaire to analyze the dietary intakes and frequencies at two points, the previous 1 month and 1 year before. RESULTS: In the assessment of dietary habits 1 year before, the highest intake of iron showed an increased odds ratio (OR) for UC on multivariate analysis (OR = 4.05, 95% confidence interval, 1.46-11.2, P < 0.01). The highest intake of zinc 1 year before showed a decreased OR for UC (OR = 0.39, 95% confidence interval, 0.18-0.85, P = 0.01). Intakes of magnesium and copper had no significant association with UC. Because most UC cases had experienced the first symptom of UC within the previous 11 months, these intakes at 1 year before represented an association with pre-illness dietary habits. CONCLUSION: A high intake of iron has some effect on the development of UC. In contrast, a high intake of zinc has a protective effect on the development of UC.

Chronic use of oral iron supplements is associated with poor clinical outcomes in patients with gram-negative bacteremia.

An unabsorbed dietary iron supplementation can modify the colonic microbiota equilibrium and favor the growth of pathogenic strains over barrier strains. Nevertheless, the impact of oral iron supplements (OIS) use on the clinical outcomes of patients with gram-negative bacteremia (GNB) has not been evaluated. To explore the impact of OIS on the outcomes of patients with GNB. A retrospective study conducted in a tertiary hospital including patients with GNB during 2011-2016. The entire cohort was divided into chronic OIS users (study group) and nonusers (control group). The two groups were compared for the study outcomes, septic shock at presentation, length of hospital stay (LOS), and short-term mortality. The study cohort included 232 patients; 44 patients in the study group and 188 in the control one. There was no any significant difference in demographic and comorbidities characteristics between the two groups. Escherichia coli comprised the majority of bacteria (69%), while the urinary tract was the main source of the bacteremia. OIS alone and after adjustment was significantly associated with septic shock at presentation (OR = 2, CI95% [1.03-5], p = 0.04 and OR = 5, CI95% [1.4-15], p = 0.01, respectively). By multivariate analysis, OIS was significantly associated with 30-day mortality (OR = 3, CI95% [1.05-7], p = 0.04), but had no impact on LOS (16 + 23 vs. 12 + 15, p = 0.9). There is a significant association between chronic OIS exposure and increased adverse outcomes in patients with GNB. These findings might have important clinical implications.

High iron intake is associated with poor cognition among Chinese old adults and varied by weight status-a 15-y longitudinal study in 4852 adults.

Background: High body iron status has been shown to be associated with adverse health outcomes. However, the relation between high body iron status, body mass index (BMI), and cognition is still understudied. Objective: This study aimed to examine the association between iron intake and cognitive function in Chinese adults and tested the interaction effect of iron intake and BMI on cognition. Design: Longitudinal study data from a nationwide sample (n = 4852; age ≥55 y) from the China Health and Nutrition Survey during 1991-2006 were used. Of the participants, 3302 had completed cognitive screening tests in ≥2 surveys. Cognitive function was assessed in 1997, 2000, 2004, and 2006. Dietary iron intake was obtained from a 3-d food record during home visits in 1991, 1993, 1997, 2000, 2004, and 2006. Multivariable mixed linear regression and logistic regression were used. Results: The cumulative mean ± SD iron intake in 1997 of tested subjects was 23.7 ± 11.3 mg/d (25.4 mg/d in men and 22.2 mg/d in women). High iron intake was associated with poor cognition. In fully adjusted models, across the quartiles of iron intake the regression coefficients (95% CIs) were 0, -0.39 (-0.77, -0.01), -0.55 (-0.95, -0.15), and -0.90 (-1.33, -0.47), respectively. Comparing extreme quartiles of iron intake (high), the OR (95% CI) for poor cognitive function was 1.30 (1.04, 1.64). There was a significant interaction between iron intake and BMI. The association between high iron intake and poor cognition was stronger among those with a high BMI than those with a low BMI. Among those with a BMI (kg/m2) >24, across quartiles of iron intake the ORs (95% CIs) for poor cognitive function were 1.00, 1.27 (0.91, 1.78), 1.41 (0.97, 2.04), and 2.04 (1.38, 3.01), respectively. Conclusion: Higher iron intake is associated with poor cognition in Chinese adults, especially among those with a high BMI.

Iron Oversupplementation Causes Hippocampal Iron Overloading and Impairs Social Novelty Recognition in Nursing Piglets.

BACKGROUND: Iron oversupplementation in healthy term infants may adversely affect growth and cognitive development. OBJECTIVE: We hypothesized that early-life iron excess causes systemic and central nervous system iron overload, and compromises social behavior. METHODS: The nursing pig was used as a translational model in a completely randomized study. On postnatal day (PD) 1, 24 pigs (1.57 ± 0.28 kg mean ± standard deviation body wt) were assigned to the following treatment groups: 1) nonsupplemented iron-deficient group (NON); 2) control group (CON), intramuscularly injected with iron dextran (100 mg Fe) on PD2; 3) moderate iron group (MOD), orally administered ferrous sulfate at 10 mg Fe · kg body wt-1 · d-1; and 4) high iron group (HIG), orally administered ferrous sulfate at 50 mg Fe · kg-1 · d-1. Piglets were nursed by sows during the study from PD1 to PD21. Tissue iron was analyzed by atomic absorption spectrophotometry. Messenger RNA and protein expression of iron regulator and transporters were analyzed by quantitative reverse transcriptase-polymerase chain reaction and Western blot. A sociability test was performed on PD19-20. RESULTS: Both MOD and HIG treatments (5.51 and 9.85 µmol/g tissue), but not CON (0.54 µmol/g), increased hepatic iron as compared with NON (0.25 µmol/g, P < 0.05). Similarly, the hippocampal iron concentrations in the MOD and HIG groups were 14.9% and 31.8% higher than that of NON, respectively (P < 0.05). In comparison with NON, MOD and HIG treatment repressed DMT1 in duodenal mucosa by 4- and 46-fold, respectively (P < 0.05); HIG drastically induced HAMP in liver by 540-fold (P < 0.05); iron-supplemented groups reduced TFRC in the hippocampus by <1-fold (P < 0.05). However, duodenal expression of ferroportin, the predominant transporter in basal membrane, was not affected by treatment. Despite normal sociability, the MOD and HIG pigs displayed deficits in social novelty recognition (P = 0.004). CONCLUSIONS: Duodenal ferroportin was hyporesponsive to iron excess (MOD and HIG), which caused hippocampal iron overload and impaired social novelty recognition in nursing pigs.

Iron intake is positively associated with viral load in antiretroviral naïve Brazilian men living with HIV

BACKGROUND Iron homeostasis contribute for the human immunodeficiency virus (HIV) pathogenesis. OBJECTIVES We assessed the iron intake pattern in antiretroviral naïve Brazilian men living with HIV correlating with clinical and nutritional parameters. METHODS The iron consumption mean was estimated according to a food frequency questionnaire (FFQ), and a 3-day food record (3dFR) submitted to the patients. HIV viral load, CD4+ T cell counts, serum iron, haematological and anthropometrics parameters were recorded. FINDINGS Fifty-one HIV-infected adult men naïve for antiretroviral therapy (ART) were enrolled. The mean age of participants was 35 (SEM ± 1.28) years old, with mean time of HIV-1 infection of 1.78 (0-16.36, min-max) years. Majority (41.18%) had complete secondary, and 21.57% had tertiary educational level. The income was around 1x (54.90%) to 2x (41.18%) minimum wage. Fifty-four percent showed normal weight, while 40% were overweight. The patients showed normal mean values of haematological parameters, and mean serum iron was 14.40 µM (SEM ± 0.83). The FFQ showed moderate correlation with the 3dFR (ρ = 0.5436, p = 0.0009), and the mean values of iron intake were 10.55(± 0.92) mg/day, recorded by FFQ, and 15.75(± 1.51) mg/day, recorded by 3dFR. The iron intake, recorded by FFQ, negatively correlated with serum iron (ρ = -0.3448, p = 0.0132), and did not have influence in the CD4+ T cell counts [e.B 0.99 (0.97-1.01, 95% confidence interval (CI), p = 0.2]. However, the iron intake showed a positive effect in HIV viral load [e.B 1.12 (1.02-1.25, 95%CI), p < 0.01]. MAIN CONCLUSIONS This study draws attention for the importance of iron intake nutritional counseling in people living with HIV. However, more studies are required to clarify the association between high iron intake and HIV infection and outcome.