Dietary Iron

Iron metabolism differs from the metabolism of other metals in that there is no physiologic mechanism for iron excretion, it is unusual; approximately 90% of daily iron needs are obtained from an endogenous source, the breakdown of circulating RBCs. Additionally humans derive iron from their everyday diet, predominantly from plant foods and the rest from foods of animal origin. Iron is found in food as either haem or non-haem iron. Iron bioavailability has been estimated to be in the range of 14–18% for mixed diets and 5–12% for vegetarian diets in subjects with no iron stores. Iron absorption in humans is dependent on physiological requirements, but may be restricted by the quantity and availability of iron in the diet. Bioavailability of food iron is strongly influenced by enhancers and inhibitors in the diet. Iron absorption can vary from 1 to 40%. A range of iron bioavailability factors that depend on the consumption of meat, fruit, vegetables, processed foods, iron-fortified foods, and the prevalence of obesity. The methods of food preparation and processing influence the bioavailability of iron. Cooking, fermentation, or germination can, by thermal or enzymatic action, reduce the phytic acid and the hexa- and penta-inositol phosphate content. Thus improving bioavailability of non-haem iron. This chapter will elaborate the dietary iron sources and means of enhancing bioavailability.

Iron Deficiency Caused by Intestinal Iron Loss—Novel Candidate Genes for Severe Anemia

The adult human body contains about 4 g of iron. About 1–2 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g/dL and ferritin levels below 30 ng/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient.

Disorder of Iron Metabolism as a Universal Pathogenetic Factor in Damage to Organs and Systems in Covid-19

Relevance. The pathogenesis of COVID-19 remains one of the most pressing. The literature discusses the role of iron as a factor supporting inflammatory processes, hypercoagulability and microcirculation crisis in severe COVID-19.The aim of study. was to identify changes in iron metabolism in patients with severe COVID-19 and hyperferritinemia.Material and methods. In this study, we used a content analysis of available scientific publications and our own observations of the peculiarities of the clinical picture and laboratory parameters in patients with a severe course of COVID-19 who had hyperferretinemia at the height of the disease. The main group consisted of 30 patients hospitalized in the Department of Anesthesiology, Resuscitation and Intensive Care of N.A. Semashko City clinical Hospital No. 38 with the diagnosis COVID-19, bilateral polysegmental pneumonia, severe course and hyperferritinemia. The diagnosis of a new coronavirus infection was confirmed by visualization of bilateral viral lung lesions with chest CT-scan, positive PCR test for SARS-CoV-2 and the presence of immunoglobulins to SARS-CoV-2. The control group consisted of 20 healthy volunteers. The study evaluated the biochemical parameters of iron metabolism, fibrinolysis and markers of inflammation. Changes associated with impaired iron metabolism were assessed by the level of serum iron, transferrin, daily and induced iron excretion in the urine. Statistical processing was carried out using nonparametric methods.Results. All patients with severe COVID-19 and hyperferritinemia showed signs of impaired iron metabolism, inflammation and fibrinolysis — a decrease in the level of transferrin (p<0.001), serum iron (p><0.005), albumin (p><0.001), lymphocytes (p><0.001) and an increase in leukocytes (p><0.001), neutrophils (p><0.001), CRP (p><0.005), IL-6 (p><0.001), D-dimer (p><0.005), daily urinary iron excretion (p><0.005) and induced urinary iron excretion (p><0.001). Conclusions The study showed that in the pathogenesis of the severe course of COVID-19, there is a violation of iron metabolism and the presence of a free iron fraction. The appearance of free iron can be caused by damage to cells with the “release” of iron from cytochromes, myoglobin, hemoglobin, or violation of the binding of iron to transferrin, which may be the result of a change in the protein structure or violation of the oxidation of iron to the trivalent state. When assessing the degree of viral effect on the body, one should take into account the effect of various regulators of iron metabolism, as well as an assessment of the level of free iron not associated with transferrin. Keywords: new coronavirus infection, COVID-19, SARS-CoV-2, iron metabolism, free iron, ferritin, transferrin, NTBI, nontransferrin bound iron>˂0.001), serum iron (p˂0.005), albumin (p˂0.001), lymphocytes (p˂0.001) and an increase in leukocytes (p˂0.001), neutrophils (p˂0.001), CRP (p˂0.005), IL-6 (p˂0.001), D-dimer (p˂0.005), daily urinary iron excretion (p˂0.005) and induced urinary iron excretion (p˂0.001).Conclusions. The study showed that in the pathogenesis of the severe course of COVID-19, there is a violation of iron metabolism and the presence of a free iron fraction. The appearance of free iron can be caused by damage to cells with the “release” of iron from cytochromes, myoglobin, hemoglobin, or violation of the binding of iron to transferrin, which may be the result of a change in the protein structure or violation of the oxidation of iron to the trivalent state. When assessing the degree of viral effect on the body, one should take into account the effect of various regulators of iron metabolism, as well as an assessment of the level of free iron not associated with transferrin.

Chronic overload of concentration-dependent iron exerts different effects on ovarian function in C57BL/6J mice†

Overloaded iron can deposit in the reproductive system and impair ovarian function. But few studies have identified the exact effect of overloaded iron on the endocrine function and fertility capacity in female mice. Here, we established iron-overloaded mouse models by intraperitoneal injection of iron dextran to adult female C57BL/6J mice at 0.1 g/kg (LF group), 0.5 g/kg (MF group), and 1.0 g/kg (HF group) concentrations once a week for eight consecutive weeks. We found that overloaded iron resulted in smaller ovaries, as well as accumulated oxidative damages. The endocrine function and follicle development were also impeded in the MF and HF groups. The 10-month breeding trial indicated that (1) Low concentration of iron (0.1 g/kg) wasn’t detrimental to the ovary; (2) Middle concentration of iron (0.5 g/kg) impeded the childbearing process, though it could be recovered following the iron excretion; and (3) High concentration of iron (1.0 g/kg) damaged the fertility, even gave rise to sterility. Yet for those fertile mice, litter number and litter size were smaller and the ovarian reserve of their offspring was impaired. Transcriptome profiling results indicated that overloaded iron could compromise ovarian function by disrupting ovarian steroidogenesis, interfering with ovarian microenvironment, and inhibiting Wnt signaling. Taken together, we have demonstrated the effect that chronic concentration-dependent iron overload exerted on mouse ovarian function, which may act as a preliminary basis for further mechanism and intervention investigations.

97 The effects of excess iron on growth performance, intestinal and liver morphology and antioxidant capacity in weaned piglets

Iron is one of the essential trace elements for animals and involved in many important physiological processes, thus exogenous iron is often supplemented as feed additive. However, the addition of excess iron may have adverse effects on animals and the environment. To investigate the effects of excess iron on growth performance, intestinal and liver morphology and antioxidant capacity in weaned piglets, in this study, forty 23-day-old weaned piglets were allotted to 4 treatments，respectively received the basal diet containing 100, 400, 3000 or 10000 mg Fe/kg as FeSO4. The experiment lasted for 28 days and then the piglets were euthanized and sampled. Lower average daily gain and higher diarrhea rate were detected in the piglets received the diet with 3000 or 10000 mg Fe/kg. Iron excretion in piglets’ feces was dependent on the iron concentration in the diet. In addition, iron overload induced mitochondrial swelling and cell death in the duodenum and liver of piglets. Excessive iron also increased piglets’ serum malondialdehyde content and reduced glutathione peroxidase and superoxide dismutase activity. Furthermore, significant increase of malondialdehydecontent and protein carbonyl content in the intestine and decrease of total antioxidant capacity, glutathione peroxidase activity and superoxide dismutase activity in the liver were observed in the piglets received diet containing high concentrations of iron. In conclusion, the results indicated that excess iron would reduce the growth performance of weaned piglets and increase the iron excretion in feces which adversely affect the environment. It may also negatively affect intestine and liver morphology and reduce the antioxidant capacity of piglets.

Renal clearable nanochelators for iron overload therapy

Iron chelators have been widely used to remove excess toxic iron from patients with secondary iron overload. However, small molecule-based iron chelators can cause adverse side effects such as infection, gastrointestinal bleeding, kidney failure, and liver fibrosis. Here we report renal clearable nanochelators for iron overload disorders. First, after a singledose intravenous injection, the nanochelator shows favorable pharmacokinetic properties, such as kidney-specific biodistribution and rapid renal excretion (>80% injected dose in 4 h), compared to native deferoxamine (DFO). Second, subcutaneous (SC) administration of nanochelators improves pharmacodynamics, as evidenced by a 7-fold increase in efficiency of urinary iron excretion compared to intravenous injection. Third, daily SC injections of the nanochelator for 5 days to iron overload mice and rats decrease iron levels in serum and liver. Furthermore, the nanochelator significantly reduces kidney damage caused by iron overload without demonstrating DFO’s own nephrotoxicity. This renal clearable nanochelator provides enhanced efficacy and safety.