Nutritional Iron Deficiency Research Articles

Chronic Iron‐deficiency Anemia Caused by a Jejunojejunal Intussusception on a Solitary Hamartomatous Polyp

Chronic Iron‐deficiency Anemia Caused by a Jejunojejunal Intussusception on a Solitary Hamartomatous Polyp

Perinatal Nutritional Iron Deficiency Impairs Noradrenergic-Mediated Synaptic Efficacy in the CA1 Area of Rat Hippocampus ,

Many studies have shown that perinatal nutritional iron deficiency (ID) produces learning impairments in children. Research has also shown that catecholamines like epinephrine and norepinephrine play a pivotal role in the consolidation of memories. In this study, we sought to determine if perinatal ID impairs the following: 1) noradrenergic synaptic function in the hippocampus; and 2) several forms of hippocampus-dependent fear learning. Electrophysiological brain slice methods were used to examine noradrenergic-mediated synaptic efficacy in the CA1-hippocampus of rats that were subjected to perinatal ID or control (CN) diets. Rats were fed ID (3 mg Fe/kg) or CN (45 mg Fe/kg) diets on gestational d 14. These diets were maintained until postnatal d (P) 12 after which all rats were switched to the CN diet. Hippocampal slices were prepared between P26 and P30. The noradrenergic agonist isoproterenol (ISO) (1, 2, or 4 μmol) was used to induce modulatory increases in synaptic efficacy in the hippocampal slices. CN slices showed a long-lasting increase in synaptic efficacy as the result of ISO perfusion in the slice bath, whereas ID slices did not show increases in synaptic efficacy as the result of ISO perfusion. ID and CN groups did not differ when ISO was perfused through slices from adult rats (P61). Both young and adult ID rats showed reduced levels of hippocampus-dependent fear learning compared with the young and adult CN rats. Together, these findings suggest that ID may impair early forms of noradrenergic-mediated synaptic plasticity, which may in turn play a role in adult learning deficits.

Iron content of the formulated East African indigenous vegetable recipes

Nutritional iron deficiency is the common cause of anaemia in developing world. However, Africa is endowed with African indigenous vegetables (AIVs) rich in micronutrients. Surveys within East Africa relate low AIV consumption to limited information on recipe preparation. The aim of this research is to determine iron content of various formulated indigenous vegetable recipes. Experimental research involved four randomly selected AIVs; African Nightshade (Solanum scabrum), Vegetable Amaranth (Amaranthus blitum), Slenderleaf (Crotalaria ochroleuca) and Cowpea (Vigna unguiculata). Four single and six vegetable combinations were boiled for ten minutes with and without traditional salt, then fried for five minutes using onions and tomatoes, giving rise to twenty recipes. Iron content was evaluated using Atomic Absorption Spectroscopy. Iron content of raw indigenous vegetables was significantly (P 0.05) lower compared to those fried without lye. Fried AIVs should be recommended in areas with high dietary iron deficiency; this could help alleviate anaemia. Key words: Iron content, recipes, lye, African indigenous vegetables

From pseudotumour cerebri to idiopathic intracranial hypertension

The terms “pseudotumour cerebri”1 and “benign intracranial hypertension”,2 respectively introduced by Nonne in 1904 and Foley in 1955, were originally applied to patients with raised intracranial pressure in whom no...

Geographic and Racial Patterns of Anemia Prevalence Among Low‐income Alaskan Children and Pregnant or Postpartum Women Limit Potential Etiologies

The etiology of the 10-fold increase in anemia and iron deficiency prevalence among Alaska Native individuals from the culturally traditional southwestern/northern Alaska regions remains unknown. The present study sought to determine anemia prevalence among people enrolled in the Alaska Women, Infant, and Children (WIC) program and reconcile results with etiological hypotheses, particularly nutritional iron deficiency and Helicobacter pylori infection. An analysis was conducted of 50,964 children 6 to 59 months of age and 30,154 pregnant or postpartum women enrolled in WIC during 1999 to 2006. Based on 3 regional groupings of residence and Alaska Native status, 6 strata were defined. Southwestern/northern Alaska Native children-who are known to have high nutritional iron intake based on subsistence diets-had the highest anemia prevalence (35%). However, southwestern/northern residence increased anemia risk similarly for Alaska Native (relative risk 1.6) and non-Native (relative risk 1.5) children. Anemia prevalence was highest among the youngest children and declined with increasing age at approximately the same rate regardless of race or residence. Alaska Native pregnant or postpartum women from all of the regions had higher anemia prevalences than non-Native women; southwestern/northern residence conferred additional risk to Alaska Native women. A region-specific environmental factor is supported by the increased risk seen among all of the children residing in the southwestern/northern regions. However, the observed patterns make nutritional iron deficiency or H pylori infection unlikely as the sole or major etiologies of the high anemia prevalences observed in some groups.

Age-related changes in iron homeostasis in mouse ferroxidase mutants

Disorders of iron metabolism are a significant problem primarily in young and old populations. In this study, We compared 1-year-old C57BL6/J mice on iron deficient, iron overload, or iron sufficient diets with two similarly aged genetic models of disturbed iron homeostasis, the sla (sex-linked anemia), and the ceruloplasmin knockout mice (Cp(-/-)) on iron sufficient diet. We found tissue specific changes in sla and nutritional iron deficiency including decreased liver Hamp1 expression and increased protein expression of the enterocyte basolateral iron transport components, hephaestin and ferroportin. In contrast, the Cp(-/-) mice did not show significantly increased Hamp1 expression despite increased liver iron suggesting that regulation is independent of liver iron levels. Together, these results suggest that older mice have a distinct response to alterations in iron metabolism and that age must be considered in future studies of iron metabolism.

Changes in hepatic gene expression in dogs with experimentally induced nutritional iron deficiency

We investigated hepatic gene expression in dogs with experimentally induced nutritional iron deficiency (ID). Our hypothesis was that ID would result in decreased hepcidin gene expression, and possibly in altered expression of other genes associated with iron metabolism. Liver biopsies were collected from each of 3 dogs before induction of ID, at the point of maximal ID, and after resolution of ID. Using Affymetrix microarray technology and analytical tools specifically designed for microarray data, we identified genes that had at least a 2-fold change in expression in response to ID. Four genes were selected for further analysis by reverse transcriptase PCR (RT-PCR). Dogs with ID had markedly decreased expression of the hepcidin gene (mean decrease of 40-fold for one probe and >100-fold for another probe) and increased expression of the transferrin receptor gene (mean increase of >7-fold). There was also mildly decreased expression of the "similar to calreticulin" gene and a gene of unknown function. Results of RT-PCR analysis were consistent with microarray findings. Changes in hepcidin and transferrin receptor gene expression were consistent with the known biology of iron metabolism. The decrease in expression of a gene identified as "similar to calreticulin," while not statistically significant, was consistent with the findings of other investigators that suggest iron plays a role in calreticulin expression.

Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis

Microcytic anemia is the most commonly encountered anemia in general medical practice. Nutritional iron deficiency and beta thalassemia trait are the primary causes in pediatrics, whereas bleeding disorders and anemia of chronic disease are common in adulthood. Microcytic hypochromic anemia can result from a defect in globin genes, in heme synthesis, in iron availability or in iron acquisition by the erythroid precursors. These microcytic anemia can be sideroblastic or not, a trait which reflects the implications of different gene abnormalities. Iron is a trace element that may act as a redox component and therefore is integral to vital biological processes that require the transfer of electrons as in oxygen transport, oxidative phosphorylation, DNA biosynthesis and xenobiotic metabolism. However, it can also be pro-oxidant and to avoid its toxicity, iron metabolism is strictly controlled and failure of these control systems could induce iron overload or iron deficient anemia. During the past few years, several new discoveries mostly arising from human patients or mouse models have highlighted the implication of iron metabolism components in hereditary microcytic anemia, from intestinal absorption to its final inclusion into heme. In this paper we will review the new information available on the iron acquisition pathway by developing erythrocytes and its regulation, and we will consider only inherited microcytosis due to heme synthesis or to iron metabolism defects. This information could be useful in the diagnosis and classification of these microcytic anemias.

Influence of nutritional iron deficiency anemia on DNA stability and lipid peroxidation in rats

Objective Oxidative stress results from an imbalance between the formation and neutralization of pro-oxidants. Disturbance of the pro-oxidant/antioxidant balance is also considered to be a causative factor underlying oxidative damage to cellular molecules, such as DNA, causing strand breaks. There is considerable controversy about the antioxidant status in iron-deficiency anemia (IDA), but scant information is available regarding DNA integrity. In the present study, we investigated the relation between DNA stability and hepatic antioxidant capacity in rats with induced IDA. Methods Peripheral DNA damage was assessed using an alkaline comet assay. Further, the hepatic antioxidant enzyme glutathione peroxidase and the production of thiobarbituric acid–reactive substances were measured in control rats and in those with induced IDA. Results Comparison of the control and anemic rats showed no differences in thiobarbituric acid–reactive substances production in the cytosolic fraction of hepatic cells. Nor were there any differences in liver glutathione peroxidase enzyme activity or DNA stability, as demonstrated by the percentage of DNA in the head (90.77 in control rats versus 88.23 in anemic rats), tail (9.23 in control rats versus 11.76 in anemic rats), and olive tail moment (0.155 in control rats versus 0.141 in anemic rats). Conclusion IDA does not affect DNA stability or lipid peroxidation in rats, suggesting that there is enough compensatory capacity to keep antioxidant defenses high.

Anemia Among Long-Term Renal Transplant Recipients

Background The effects of anemia on cardiovascular disease among the end-stage renal disease (ESRD) population suggest that it may be one of the major factors explaining this complication among kidney transplant recipients. Systematic investigation into the prevalence of posttransplantation anemia (PTA) is therefore of critical importance. Materials and Methods This cross-sectional study of data from 650 patients followed at a single outpatient transplant clinic utilized the guidelines of the American Society of Transplantation to define anemia as a hemoglobin (Hb) ≤130 g/L in men or ≤120 g/L in women. Results Among the 39% of patients who were anemic, the prevalence was greater in women than in men. Serum Hb concentrations significantly correlated with the glomerular filtration rate (GFR), serum transferrin, the use of angiotensin converting enzyme inhibitors and mycophenolate mofetil therapy. Upon multivariate analysis, the GFR, serum transferrin, potential nutritional markers, chronic inflammation, and iron deficiency were independently and significantly associated with the presence of anemia. Erythropoietin was administered to 15 (5.7%) anemic patients. Conclusions PTA is a prevalent, undertreated condition. Based on our results, we suggest that protein/energy malnutrition and/or chronic inflammation were independently associated with anemia.

DYSPLASIA AND DISORDER OF CELL MEMBRANE ENTIRETY IN IRON-DEFICIENCY ANEMIA

Peripheral blood smears of 43 patients (26 males, median age 18 months, range: 6–180 months) with nutritional iron-deficiency anemia (IDA) were examined for the presence of trilineage hematological dysplasia. Twelve patients were reexamined for dysplastic findings after achieving a normal Hb and hematocrit level for age by the end of 2–3 months of iron treatment. A control group of 17 age-matched healthy children were also included. Neutrophils with loss of membrane entirety and protrusions were remarkable in 34/43 (79%) in the IDA group versus 1/12 (8%) after iron treatment and none of the control group. Microspherocytes were seen in 9/43 (21%) of IDA patients. Additionally, trilienage dysplasia was observed in the bone marrow samples available in 3 of the patients. It has been shown that iron-deficiency results in cellular DNA and RNA alterations, cell-cycle G1/S phase arrest, and apoptosis. Rac GTPases have been shown to control actin cytoskeleton, influencing cell polarity, microtubule dynamics, and the cytoskeletal organization of hematopoietic cells. Thus, the findings described above in neutrophils and red cells suggest a plausible link between iron and the Rac GTPase gene family. It may be a new avenue for iron waiting for proof.

The Effect of Dietary Habits and Socioeconomic Status on the Prevalence of Iron Deficiency in Children of Northern Greece

Backround: Despite encouraging reports concerning the declining prevalence of iron deficiency, this easily preventable disorder is still an existing problem in presumably developed regions. Objective: To evaluate the prevalence of iron deficiency and relevant anemia in children residing in Northern Greece and to study possible associations. Design: 3,100 children aged 8 months to 15 years were evaluated. Socioeconomic status was determined based on the parents’ profession and place of residence. Nutrition habits were also evaluated. Results: The incidence of iron deficiency was found to be 14% and that of iron deficiency anemia was 2.9%, with a higher prevalence in children younger than 2 years of age. The place of residence was the most significant factor in relation to the development of iron depletion in the children studied. Additional independent factors were revealed to be breast-feeding, meat-containing meal consumption and the consumption of non-home-cooked meals. Conclusion: Iron deficiency remains prevalent in Northern Greece, mainly affecting the vulnerable toddler group. Nutritional iron deficiency is still a severe public health problem even in what are considered to be developed regions. An improvement of dietary habits and an upgrading of semiurban areas should contribute substantially to decreasing the prevalence of iron depletion in Greek children.

Prevalence, consequences and prevention of childhood nutritional iron deficiency: a child public health perspective

The true extent of nutritional iron deficiency (ID) in childhood is unclear because of uncertainty over its definition and the insensitivity of markers of ID. The major cause is likely to be the excessive and early use of cow's milk. Recent neurophysiological observations support the many field studies correlating ID with cognitive developmental delays. Prevention is best sought through supplementation of essential foods.

Reticulocyte indices in a canine model of nutritional iron deficiency

Reticulocyte indices, especially reticulocyte hemoglobin content (CH retic), have shown promise as markers of iron deficiency (ID), but there have been no prospective investigations of reticulocyte indices in experimental models of ID. The objective of this study was to compare reticulocyte indices with conventional hematologic and biochemical indices as markers of ID in dogs. Iron deficiency was induced in 7 dogs by feeding an iron-deficient diet, and corrected by restoring dietary iron and by giving iron parenterally. Blood samples were collected at weekly intervals. Results of hematologic and biochemical tests were compared using t-tests and receiver operator characteristic (ROC) curve analysis. Comparing mean values on days 0 and 35, by which time hemoglobin concentration decreased to 90% of baseline in all dogs, % Macro retic, % Hypo retic, % Low CH retic, and % High CH retic differed by greater than 3-fold, whereas no conventional hematologic or biochemical indices differed by as much as 2-fold. Comparing conventional hematologic and reticulocyte indices by ROC curve analysis using 4 different biochemical diagnostic criteria of ID, CH retic, % Hypo retic, % Low CH retic, and % High CH retic had higher areas under the curve (AUC) than either MCV conv or MCHC conv according to all 4 criteria, and % Macro retic and MCV retic had higher AUC values according to 3 of 4 criteria (differences were not always statistically significant). Results of this study support the value of reticulocyte indices in the diagnosis and monitoring of ID in dogs. Species similarities in the pathophysiology and hematologic manifestations of ID suggest these findings also may be relevant to ID in people.

Perinatal nutritional iron deficiency reduces hippocampal synaptic transmission but does not impair short- or long-term synaptic plasticity

Studies show that perinatal nutritional iron deficiency (ID) produces learning and memory impairments in humans and animals. This suggests that the functional physiology of learning and cognitive centers in the brain, such as the hippocampus, may be compromised by developmental ID. The present study used electrophysiological brain slice methods to examine multiple measures of hippocampal synaptic efficacy from rats that were subjected to perinatal ID diets or control (CN) diets. Measures of synaptic efficacy were obtained from the first and last synaptic regions of the hippocampal tri-synaptic loop (i.e. the dentate gyrus (DG) and CA1). Rats were placed on ID or CN diets on gestational day 11, and hippocampal brain slices were prepared between postnatal day 25 and 37. Results show that ID slices were not impaired in short-term (i.e. paired-pulse facilitation (PPF)) or long-term measures (i.e. long-term potentiation (LTP)) of synaptic plasticity in either the DG or CA1 areas. Input–output (IO) measures showed that synaptic transmission was reduced in both of these areas in the ID slices when compared with the CN slices. This suggests that ID-induced learning deficits may be the result of reductions in synaptic transmission throughout the hippocampus, and possibly in other learning and memory centers.

Prebiotics and Iron Bioavailability—Is There a Connection?

ABSTRACT: Poor bioavailability of dietary iron, especially from diets rich in cereals and legumes, is a major factor contributing to the high prevalence of nutritional iron deficiency in developing countries. Dietary modification to increase intake of components that promote iron absorption from low‐bioavailability meals is an effective strategy for combating nutritional iron deficiency. Prebiotics are nondigestible oligosaccharides that selectively stimulate the growth and activity of specific species of bacteria in the colon with benefits to human health. Common prebiotics such as inulin and fructooligosaccharides occur naturally in a wide variety of plant‐based foods and have recently been suggested to have an enhancing effect on iron absorption. The hypothesis that prebiotics enhance iron absorption is biologically plausible because fermentation of prebiotics by natural microflora present in the colon may decrease the pH of the luminal content, promote reduction of Fe(III) to Fe(II), stimulate proliferation of epithelial cells to expand the absorptive surface area, and potentially stimulate expression of mineral‐transport proteins in epithelial cells. However, data available in the literature characterizing the enhancing properties of prebiotics on iron absorption are inconsistent, and mechanisms of actions involved are poorly understood. The notion that the colon can function as a significant site of iron absorption in response to stimulation by prebiotics, and the effect of long‐term exposure to prebiotics on the iron status of iron‐deficient subjects remain to be clarified. This review discusses the functional properties of prebiotics as a promising dietary factor that enhances iron absorption. Keywords: prebiotics, iron, colon, oligosaccharides, inulin

Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency

AbstractHephaestin is a membrane-bound multicopper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation. Mice with sex-linked anemia (sla) have a mutant form of Hephaestin and a defect in intestinal basolateral iron transport, which results in iron deficiency and anemia. Ireg1 (SLC11A3, also known as Ferroportin1 or Mtp1) is the putative intestinal basolateral iron transporter. We compared iron levels and expression of genes involved in iron uptake and storage in sla mice and C57BL/6J mice fed iron-deficient, iron-overload, or control diets. Both iron-deficient wild-type mice and sla mice showed increased expression of Heph and Ireg1 mRNA, compared to controls, whereas only iron-deficient wild-type mice had increased expression of the brush border transporter Dmt1. Unlike iron-deficient mice, sla mouse enterocytes accumulated nonheme iron and ferritin. These results indicate that Dmt1 can be modulated by the enterocyte iron level, whereas Hephaestin and Ireg1 expression respond to systemic rather than local signals of iron status. Thus, the basolateral transport step appears to be the primary site at which the small intestine responds to alterations in body iron requirements.

Iron balance and iron nutrition in infancy.

At birth, the total body iron content is approximately 75 mg/kg, twice that of an adult man in relation to weight. During the first 6 mo of life, total iron body content increases slightly and exclusive breastfeeding is sufficient to maintain an optimal iron balance. Thereafter, iron body content substantially increases and the infant becomes critically dependent on dietary iron, provided by complementary foods. Numerous factors may contribute to nutritional iron deficiency in infancy, the most important being low body iron content at birth, blood loss, high postnatal growth rate, and a low amount and/or bioavailability of dietary iron. We have documented that the prevalence of iron deficiency declined in Italy as iron nutrition improved and that early feeding on fresh cow's milk is the single most important determinant of iron deficiency in infancy. Healthy full-term infants should maintain optimal iron balance by consuming a good diet, which can be summarized as follows: breastfeeding should be continued exclusively for at least 5 mo and then together with complementary foods containing highly bioavailable iron; infants who are not breastfed or are partially breastfed should receive an iron-fortified formula, containing between 4.0 and 8.0 mg/L iron, from birth to 12 mo of age; fresh cow's milk should be avoided before 12 mo of age.

Iron deficiency and cognition

Iron deficiency is the most prevalent nutritional disorder in the world. One of the most worrying consequences of iron deficiency in children is the alteration of behaviour and cognitive performance. In iron-deficient children, striking behavioural changes are observed, such as reduced attention span, reduced emotional responsiveness and low scores on tests of intelligence. Animal studies on nutritional iron deficiency show effects on learning ability that parallel the human studies. Despite the obvious confounding impact of socioeconomic factors, there is a wealth of clinical, biochemical and neuropathological research that shows that iron deficiency can exert a direct deleterious effect on learning and the brain, and that this can occur with normal haemoglobin levels. Nutritional iron replacement therapy readily corrects haematological iron status in iron-deficient children within 2-3 weeks, but behavioural problems persist for several months or years. This resi stance to iron-replacement therapy and its long-term consequences on learning are not quite understood. A recent study in infants showed that the cognitive deficits in iron deficiency was reversed with iron supplementation. This finding provides evidence that in some settings cognitive deficits are not always permanent. Although further research is required to address these issues, several studies support the theory that iron sufficiency throughout the course of brain development is critical to normal brain iron and behavioural outcome.

Iron balance and iron nutrition in infancy

At birth, the total body iron content is approximately 75 mg/kg, twice that of an adult man in relation to weight. During the first 6 mo of life, total iron body content increases slightly and exclusive breastfeeding is sufficient to maintain an optimal iron balance. Thereafter, iron body content substantially increases and the infant becomes critically dependent on dietary iron, provided by complementary foods. Numerous factors may contribute to nutritional iron deficiency in infancy, the most important being low body iron content at birth, blood loss, high postnatal growth rate, and a low amount and/or bioavailability of dietary iron. We have documented that the prevalence of iron deficiency declined in Italy as iron nutrition improved and that early feeding on fresh cow's milk is the single most important determinant of iron deficiency in infancy. Healthy full-term infants should maintain optimal iron balance by consuming a good diet, which can be summarized as follows: breastfeeding should be continued exclusively for at least 5 mo and then together with complementary foods containing highly bioavailable iron; infants who are not breastfed or are partially breastfed should receive an iron-fortified formula, containing between 4.0 and 8.0mg/L iron, from birth to 12 mo of age; fresh cow's milk should be avoided before 12 mo of age.