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PubMed2001

Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload.

BACKGROUND & AIMS: Imbalances of iron homeostasis are accompanied by alterations of intestinal iron absorption. The identification of divalent-metal transporter 1 (DMT1) and ferroportin 1 (FP1) has improved our understanding of transmembrane iron trafficking. To gain insight into the regulatory properties of these transporters in the duodenum, we studied their expression in patients with hereditary hemochromatosis (HFE-associated and non-HFE-associated), secondary iron overload, and iron deficiency. METHODS: DMT1, FP1 messenger RNA (mRNA), and protein expression were analyzed in duodenal biopsy specimens from patients by means of TaqMan real-time polymerase chain reaction, Western blotting technique, and immunohistochemistry. RESULTS: DMT1 and FP1 mRNA levels are positively correlated with each other in all patient groups (P < 0.001). Moreover, DMT1 and FP1 mRNA levels were significantly increased in patients with iron deficiency, HFE and non-HFE hemochromatosis, whereas they were unchanged in patients with secondary iron overload. Alterations in DMT1 and FP1 mRNA levels were paralleled by comparable changes in the duodenal expression of these proteins. In patients with normal iron status or iron deficiency, significant negative correlations between DMT1, FP1 mRNA, and serum iron parameters were found, which were absent in subjects with primary hemochromatosis. CONCLUSIONS: DMT1 and FP1 are centrally involved in iron uptake/transfer in the duodenum and in the adaptive changes of iron homeostasis to iron deficiency and overload.

Adult↗
PubMed1993

[Teenage iron deficiency].

Iron deficiency is common in adolescents. This age-group needs more iron owing to the spurt of growth in puberty, and, in girls, because of menstrual losses, and in the event of pregnancy. In boys there is a normal rise in haemoglobin level from about 13 to about 15 g/100 ml, and in myoglobin (muscular mass). Physical training increases the need of iron (21). In addition, poor eating habits are quite common in adolescents. There are few data in the literature on the iron status of Norwegian adolescents, but large studies from USA, Canada and Sweden have disclosed iron depletion (s-ferritin below 16 micrograms/l) with or without anaemia in 40% of adolescent girls and 15% of adolescent boys. Screening, including haemoglobin and s-ferritin determinations, is advocated.

Adolescent↗
PubMed2000

Iron metabolism: iron deficiency and iron overload.

Iron is an essential cofactor in a variety of cellular processes. Except for a few unusual bacterial species, iron is indispensable for living organisms. However, free iron is toxic because of its propensity to induce the formation of dangerous free radicals. Consequently, iron balance is tightly regulated. Disorders of iron homeostasis are among the most common afflictions of humans. This review discusses inherited iron deficiency and iron overload disorders and recent insights into their pathophysiology.

Anemia, Iron-Deficiency↗
PubMed1991

Prevalence of iron deficiency and iron overload in the adult Icelandic population.

The aim of this cross-sectional study was to estimate the prevalence of iron deficiency and overload in the adult population in Iceland, a developed Scandinavian country. The study population consisted of 4240 individuals aged 25-74 years randomly selected from the national roster. Basic hematological, S-iron, S-total iron binding capacity (TIBC), and S-ferritin measurements were obtained on 2588 individuals (61.0%). The results indicated unusually large iron stores in the adult Icelandic population and significantly larger iron stores in the rural compared to the urban population. Iron deficiency was rare except in urban premenopausal women, where 1 in 4 showed evidence of iron deficiency and 3.2% had iron deficiency anemia. Seven patients with hereditary hemochromatosis were identified from a subgroup of 1887 subjects, resulting in a prevalence of 0.37%. Two of the hereditary hemochromatosis patients had been gastrectomized. Measures to improve the iron balance in urban premenopausal women cannot therefore include increased iron fortification of food but must be more directed towards the target group.

Adult↗
PubMed1972

An immunoradiometric assay for ferritin in the serum of normal subjects and patients with iron deficiency and iron overload.

An immunoradiometric assay for human ferritin has been developed. Concentrations of ferritin in the serum of male and female controls and patients with iron deficiency and iron overload were measured.Male controls were found to have a significantly higher mean concentration of serum ferritin than females. Patients with iron deficiency had significantly lower levels than normals of either sex and patients with iron overload had greatly elevated serum ferritin concentrations. It is thought that the serum ferritin concentration may reflect the iron stores of the body.

Anemia, Hypochromic↗
PubMed1989

Reevaluation of the utility of mean cell hemoglobin (MCH) screening in infants for iron deficiency.

Iron deficiency (ID) at the stage of latent deficiency (LID) or frank anemia (IDA) is still common in pediatric practice. We have assessed the prevalence of LID and IDA in an infant population with an age range of 9-11 months, in Paris. Red cell indices, hemoglobin level, serum iron, transferrin saturation and serum ferritin levels were assayed. There was considerable prevalence of ID as 82% of the children exhibited low levels in one of the above parameters. We found low mean cell hemoglobin (MCH) to be predictive of LID in one third of cases. Since MCH value is routinely available to the physician, it appears that a close examination of this red cell index should allow for the diagnosis of ID in a large number of children at risk, without the need to resort to more elaborate and expensive laboratory tests.

Anemia, Hypochromic↗
PubMedDate not supplied

Anemia: when is it iron deficiency?

Iron deficiency anemia, the most common of childhood anemias, presents many challenges to the practitioner. Careful history taking that includes nutritional assessment may uncover this frequently subtle condition. In keeping with AAP recommendations, screening will aid in diagnosing this condition in populations at risk. Prompt treatment and conscientious follow-up will afford the most optimal outcome.

Adolescent↗
PubMed2003

Iron intake and regulation: implications for iron deficiency and iron overload.

Although iron deficiency anemia is the most common nutritional deficiency worldwide and in the United States, the health effects of iron overload merit increased attention. In the United States, public health interventions such as fortification and enrichment of foods with iron were undertaken to reduce the prevalence of iron deficiency anemia and improve health. These measures, along with iron supplementation, remain controversial, because additional exposure to dietary iron places some segments of the population at increased risk of iron excess. The health consequences of unmistakable iron excess are exemplified by hemochromatosis, an iron storage disease associated with liver damage further exacerbated by alcohol consumption. Progressive liver damage associated with this condition is generally attributed to increased oxidative stress. In otherwise healthy individuals, more modest levels of iron storage may occur if iron is provided by supplements or otherwise added to the food supply. Increased iron intake and storage have been linked to a variety of chronic diseases. The associations are not firmly established but are of considerable public health importance.

Absorption↗
PubMed1999

Iron status in Danes updated 1994. I: prevalence of iron deficiency and iron overload in 1332 men aged 40-70 years. Influence Of blood donation, alcohol intake, and iron supplementation.

Iron status, S-ferritin, and hemoglobin (Hb) were assessed in a population survey in 1994 (DAN-MONICA 10) comprising 1332 Caucasian Danish men equally distributed in age cohorts of 40, 50, 60 and 70 years. Blood donors (n=186) had lower S-ferritin, median 76 microg/l, than nondonors, median 169 microg/l (p<0.0001). S-ferritin in donors was inversely correlated with the number of phlebotomies (r(s)=-0.57, p<0.0001). S-ferritin in nondonors (n=1146) was similar in men 40-60 years of age, median 176 microg/l, and subsequently decreased at 70 years of age to a median of 146 microg/l (p=0.01). In the entire series, the prevalence of small iron stores (S-ferritin 16-32 microg/l) was 2.7%, that of depleted iron stores (S-ferritin <16 microg/l) 0.45%, and that of iron deficiency anemia (S-ferritin <13 microg/l and Hb <129 g/l) 0.15%. Among nondonors, the prevalence of iron overload (S-ferritin >300 microg/l) was 20%. S-ferritin in nondonors correlated with body mass index (r(s)=0.19, p=0.0001) and with alcohol intake (r(s)=0.26, p=0.0001). In the entire series, 28% of the subjects took supplemental iron (median 14 mg ferrous iron daily). Iron supplements had no influence on iron status. Nondonors (n=170) treated with acetylsalicylic acid had lower S-ferritin, median 136 microg/l, than nontreated, median 169 microg/l (p<0.001) and those treated with H(2)-receptor antagonists (n=30) had lower S-ferritin, median 142 microg/l, than nontreated, median 171 microg/l (p<0.04). Compared with the DAN-MONICA 1 iron status survey of Danish men in 1984, the prevalences of iron depletion and iron deficiency anemia are unchanged whereas the prevalence of iron overload has increased significantly. In Denmark, iron fortification of flour was abolished in 1987. This apparently had no negative effect on iron status in men.

Adult↗
PubMed1991

A study of changes in red cell volume and haemoglobin concentration during phlebotomy induced iron deficiency and iron repletion using the Technicon H1.

The recently introduced Technicon H1 analyser uses an improved optical principle to measure the size and haemoglobin concentration of erythrocytes. We have made a serial study of ten patients undergoing phlebotomy to induce mild iron deficiency. The instrument showed the early development of anisohypochromia with subsequent fall in the mean cell haemoglobin concentration (MCHC). Cell volume was preserved until relatively late and during early iron deficient erythropoiesis cell volume would appear to be maintained at the expense of haemoglobin concentration. The Technicon H6000 (conventional technology) used in parallel produced contrasting results indicating anisomicrocytosis with preservation of cell haemoglobin concentration until relatively late. Five cases of severe iron deficiency treated with iron were similarly studied and showed comparable changes on both instruments, with characteristically bimodal cell volume histograms and large increases in red cell distribution width. Our results indicate that the new generation of instruments will generate red cell data of additional clinical value.

Anemia, Hypochromic↗
PubMed1978

Ferritin in bone marrow and serum in iron deficiency and iron overload.

Nonheme iron and ferritin in the bone marrow and serum ferritin was investigated in patients with iron deficiency anaemia or iron overload. As controls served patients without any disturbance of the iron metabolism. There is a precise correlation between the nonheme iron and ferritin in the bone marrow of patients with and without disturbance of iron metabolism. A correlation was also found between the ferritin in the bone marrow and the serum. Nonheme iron and ferritin in the bone marrow and serum ferritin was decreased in patients with iron deficiency anaemia. Conversely, the same parameters were increased in patients with iron overload.

Anemia, Hypochromic↗
PubMed2001

Can dietary treatment of non-anemic iron deficiency improve iron status?

OBJECTIVE: To investigate the efficacy of, first, a dietary regimen involving increased consumption of iron-rich foods and enhancers of iron absorption and decreased consumption of inhibitors of iron absorption and, second, a low dose iron chelate iron supplement, for increasing iron stores in young adult New Zealand women with mild iron deficiency (MID). METHODS: The study was a 16 week randomized placebo-controlled intervention. Seventy-five women aged 18 to 40 years with MID (serum ferritin < 20 microg/L and hemoglobin > or = 120 g/L) were assigned to one of three groups: Placebo, Supplement (50 mg iron/day as amino acid chelate) or Diet. Participants in the Diet Group were given individual dietary counseling to increase the intake and bioavailability of dietary iron. Dietary changes were monitored by a previously validated computer-administered iron food frequency questionnaire. RESULTS: Diet Group members significantly increased their intake of flesh foods, heme iron, vitamin C and foods cooked using cast-iron cookware and significantly decreased their phytate and calcium intakes. Serum ferritin increased in the Supplement and Diet Groups by 59% (p=0.001) and 26% (p=0.068), respectively, in comparison to the Placebo Group. The serum transferrin receptor:serum ferritin ratio decreased by 51% in the Supplement Group (p=0.001), and there was a non-significant decrease of 22% (p=0.1232) in the Diet Group. CONCLUSIONS: This study is the first, to our knowledge, to demonstrate that an intensive dietary program has the potential to improve the iron status of women with iron deficiency.

Adolescent↗
PubMed2003

Iron deficiency alters iron regulatory protein and iron transport protein expression in the perinatal rat brain.

Iron plays an important role in numerous vital enzyme systems in the perinatal brain. The membrane proteins that mediate iron transport [transferrin receptor (TfR) and divalent metal transporter 1 (DMT-1)] and the iron regulatory proteins (IRP-1 and IRP-2) that stabilize their mRNAs undergo regional developmental changes in the iron-sufficient rat brain between postnatal day (P) 5 and 15. Perinatal iron deficiency (ID) affects developing brain regions nonhomogeneously, suggesting potential differences in regional iron transporter and regulatory protein expression. The objective of the study was to determine the effect of perinatal ID on regional expression of IRP-1, IRP-2, TfR, and DMT-1 in the developing rat brain. Gestationally iron-deficient Sprague Dawley rat pups were compared with iron-sufficient control pups at P10. Serial 12-mu coronal sections of fixed frozen brain from pups on P10 were assessed by light microscopy for IRP-1, IRP-2, DMT-1, and TfR localization. ID did not change the percentage of cells with positive staining for the four proteins in the choroid epithelium, ependyma, vascular endothelium, or neurons of the striatum. ID increased the percentage of neurons expressing the four proteins in the hippocampus and the cerebral cortex. Increased numbers of TfR- and DMT-1-positive cells were always associated with increased IRP-positive cells. The P10 rat responds to perinatal ID by selectively increasing the number of neurons expressing IRP-regulated transporters in brain regions that are rapidly developing, without any change at transport surfaces or in regions that are quiescent. Brain iron distribution during ID seems to be locally rather than globally regulated.

Anemia, Iron-Deficiency↗
PubMed1990

The effect of iron deficiency and iron overload on the evolution of Chagas disease produced by three strains of Trypanosoma cruzi in CFW mice.

1. CFW mice were fed either on control diet or on iron-deficient diet. 2. After 5 months the mice were infected with CL, Y or YuYu strain of Trypanosoma cruzi. 3. On the fifth day after the infection, the mice on control diet were divided in three groups: one group remained as controls, two groups were injected either with desferrioxamine or iron-dextran. 4. The severity of the disease was evaluated by parasitemia and mortality. 5. The experimental groups were compared with the infected group fed on the control diet. 6. In mice fed on the iron-deficient diet, the disease was more severe for CL strain and less severe for Y and YuYu strains. 7. Treatment with desferrioxamine produced a less severe disease with YuYu strain and no difference with the other strains. 8. On Treatment with iron-dextran, the disease became more severe with Y and CL strains; no effect was observed with YuYu strain. 9. These findings may be due to intraspecific differences among the strains.

Animals↗
PubMed1983

Effect of iron deficiency and iron restoration on ultrastructure of Anacystis nidulans.

The effects of iron deficiency and iron reconstitution on the ultrastructure of the unicellular cyanobacterium Anacystis nidulans R2 were studied by electron microscopy. Low-iron cells, grown with different amounts of aeration, were analyzed at 6, 12, and 24 h after the addition of iron. Low-iron cells had a decrease in the quantities of membranes, phycobilisomes, and carboxysomes and a large increase in glycogen storage granules. In cells aerated with gentle shaking, the addition of iron caused the number of carboxysomes to increase rapidly within 6 h. This was paralleled by a decrease in the quantity of glycogen storage granules. Carboxysomes were associated with the nucleoplasmic face of the inner photosynthetic membrane in normal, but not low-iron, cells; they once more contacted the membrane by 6 h after iron addition. Phycobilisome assembly was apparent by 6 h, and the number of phycobilisomes increased throughout reconstitution. Membrane restoration was accomplished in two stages: (i) components were added to preexisting membranes until about 12 h, and (ii) new membranes were synthesized beginning at 12 to 18 h. Low-iron cells grown by bubbling with air had only one to two concentric layers of membrane per cell. The addition of iron led to a pattern of reconstitution that was similar to that described above with two important exceptions. Under these conditions, the number of carboxysomes remained low and the carboxysomes rarely contacted the photosynthetic membranes. New membranes were not synthesized until the culture had reached the late-logarithmic growth phase and after all other morphological features had returned to normal.

Cell Membrane↗
PubMed2002

Iron status in Danish men 1984-94: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload.

BACKGROUND AND OBJECTIVES: From 1954 to 1987, flour in Denmark was fortified with 30 mg carbonyl iron per kg. This mandatory fortification was abolished in 1987. The aim of this study was to compare iron status in Danish men before and after abolition of iron fortification. METHODS: Iron status (serum ferritin, haemoglobin), was assessed in population surveys in Copenhagen County during 1983-84 comprising 1324 Caucasian men (1024 non-blood-donors, 300 blood donors) and in 1993-94 comprising 1288 Caucasian men (1103 non-blood-donors, 185 donors), equally distributed in age cohorts of 40, 50, 60 and 70 yr. RESULTS: In the 1984 survey median serum ferritin values in the four age cohorts in non-blood-donors were 136, 141, 133 and 111 microg/L, and in the 1994 survey 177, 173, 186 and 148 microg L(-1), respectively. The difference was significant in all age groups (P<0.001). There was no significant difference between the two surveys concerning the prevalence of small iron stores (ferritin 16-32 micro g L(-1)), depleted iron stores (ferritin <16 microg L(-1)) or iron-deficiency anaemia (ferritin <13 microg L(-1) and Hb <5th percentile for iron-replete men). However, from 1984 to 1994, the prevalence of iron overload (ferritin >300 microg L(-1)) increased from 11.3% to 18.9% (P<0.0001). During the study period there was an increase in body mass index (P<0.0001), alcohol consumption (P<0.03) and use of non-steroid anti-inflammatory drugs (NSAID) (P<0.0001), and a decrease in the use of vitamin-mineral supplements (P<0.04) and in the prevalence of tobacco smoking (P<0.0001). In contrast, median ferritin in blood donors showed a significant fall from 1984 to 1994 (103 vs. 74 micro g L(-1), P<0.02). CONCLUSION: Abolition of iron fortification reduced the iron content of the Danish diet by an average of 0.24 mg MJ(-1), and the median dietary iron intake in men from 17 to 12 mg d(-1). From 1984 to 1994, body iron stores and the prevalence of iron overload in Danish men increased significantly, despite the abolition of food iron fortification. The reason appears to be changes in dietary habits, with a lower consumption of dairy products and eggs, which inhibit iron absorption, and a higher consumption of alcohol, meat, and poultry, containing haem iron and enhancing iron absorption. The high prevalence of iron overload in men may constitute a health risk.

Adult↗
PubMed1985

Iron deficiency and iron overload.

An up to date review of our knowledge of human iron metabolism is given including problems of iron balance, internal transport, and intracellular mechanisms. Current knowledge of the iron proteins is summarized and this background is used in discussing the pathophysiology of iron deficiency and overload, together with the internal derangements such as sideroblastic anemia which form much of the clinical practice associated with disorders of iron metabolism. The therapeutic approach to these problems will be described.

Absorption↗