Decreased Iron Absorption Research Articles

The efficacy of diazepam in the treatment of acute iron overload in rats.

While conducting studies on the prevention of mortality from acute iron intoxication in rats, diazepam, given to prevent animal suffering, was observed to be associated with reduced mortality in a limited number of animals. The objective was to assess whether diazepam reduces mortality following acute iron intoxication in rats. Survival of rats was compared among groups receiving (i) orally 612 mg/kg iron alone (LD60), (ii) iron with a subcutaneous injection of 2.5 mg/kg diazepam (DZ), or (iii) iron, DZ with 800 mg/kg deferiprone intraperitoneal injections. The administration of DZ decreased mortality from 60 to 16% (p < 0.001). The addition of deferiprone to DZ resulted in zero mortality (p < 0.05 compared with the DZ group) over the study period. The administration of DZ was not associated with decreased iron absorption or increased urinary iron excretion, whereas the administration of deferiprone did result in urinary iron excretion. Microscopic examination suggests that diazepam administration may be associated with lower intracellular accumulation of iron. In conclusion, diazepam reduces mortality from iron overdose in rats through a yet unidentified mechanism, although the drug does not inhibit iron absorption or enhance urinary iron removal.

Defective Iron Supply for Erythropoiesis and Adequate Endogenous Erythropoietin Production in the Anemia Associated With Systemic-Onset Juvenile Chronic Arthritis

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = -.81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo-Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released.

Intestinal transferrin receptors and iron absorption in the neonatal rat

The transferrin receptor is a major protein found on the basolateral membranes of intestinal epithelial cells, yet its possible role in intestinal iron metabolism and also in iron absorption is unclear. We have studied intestinal transferrin receptor expression during the peri- and postnatal development of the small intestine of the rat using immunohistochemistry with a monoclonal antibody to the rat receptor. Two major changes in transferrin receptor expression in the developing small intestine were found, a decrease in receptor expression associated with birth, and an increase at the time of weaning. Around the time of weaning there was a large decrease in iron absorption, but there was no direct correlation between absorption and transferrin receptor expression. However, at both birth and weaning there were major changes in intestinal cell kinetics, and the distribution of receptor correlated well with the distribution of proliferating cell populations. In addition, as the intestinal epithelial cells differentiated and stopped dividing, there was a redistribution of transferrin receptors from the cell surface to intracellular sites. These data suggest that the most likely role of the transferrin receptor in the neonatal intestine is in the supply of iron to the developing epithelial cells in the crypts, and that the receptor does not play a direct role in iron transit across the intestinal epithelium.

Non-everted oxygenated rat intestinal segments as a measure of neutral detergent fiber effects on iron absorption

Iron absorption in the presence of varying amounts and sizes of dietary fiber was measured. A method using non-everted rat intestinal segments perfused in oxygen was refined. Neutral detergent fiber (NDF), a component of dietary fiber, was extracted from cooked pinto bean ( Phaseolus vulgaris). The NDF did not affect iron absorption in intestinal segments from iron replete rats. However, 4 and 6 mg of NDF/ml significantly decreased iron absorption in the intestinal segments from anemic rats. NDF with a smaller particle size of 0.125 mm increased iron absorption relative to that absorbed with 0.180 mm particles. Histological examination validated using non-everted intestinal segments perfused with oxygen as a method for studying dietary effects on iron absorption. Segments which are not everted are less prone to damage. Perfusion with oxygen maintained metabolic activity in the tissue during the experiment.

Anaemia in rheumatoid arthritis: the role of iron, vitamin B12, and folic acid deficiency, and erythropoietin responsiveness.

Thirty six patients with rheumatoid arthritis (RA) (25 with anaemia) were studied to establish the role of iron, vitamin B12, and folic acid deficiency, erythropoietin responsiveness, and iron absorption in the diagnosis and pathogenesis of anaemia in RA. Iron deficiency, assessed by stainable bone marrow iron content, occurred in 13/25 (52%), vitamin B12 deficiency in 7/24 (29%), and folic acid deficiency in 5/24 (21%) of the anaemic patients. Only 8/25 (32%) had just one type of anaemia. The iron deficiency of anaemia of chronic disease (ACD) was distinguished by ferritin concentration, which was higher in that group. Mean cell volume (MCV) and mean cell haemoglobin (MCH) were lower in both anaemic groups, but most pronounced in iron deficient patients. Folic acid, and especially vitamin B12 deficiency, masked iron deficiency by increasing the MCV and MCH. Iron absorption tended to be highest in iron deficiency and lowest in ACD, suggesting that decreased iron absorption is not a cause of ACD in RA. No specific causes were found for vitamin B12 or folic acid deficiency. Haemoglobin concentration was negatively correlated with erythrocyte sedimentation rate in the group with ACD. Erythropoietin response was lower in ACD than in iron deficient patients. It was concluded that generally more than one type of anaemia is present simultaneously in anaemic patients with RA. The diagnosis of each type may be masked by another. Studies on pathogenesis of the anaemia are difficult as deficiencies generally coexist with ACD. Disease activity and, possibly, erythropoietin responsiveness are major factors in ACD pathogenesis.

Anaemia in rheumatoid arthritis: pathogenesis, diagnosis and treatment

The pathogenesis, diagnosis and treatment of the anaemia of chronic disorders (ACD) in rheumatoid arthritis (RA) were reviewed. Causes of anaemia other than ACD frequently present in RA. Decreased iron absorption was shown to be the result of active RA rather than a cause of ACD or iron deficiency. It has been hypothesized that bone marrow iron availability decreases due to decreased iron release by the mononuclear phagocyte system or that the anaemia in ACD is due to ineffective erythropoiesis; these remain controversial theories. Studies considering a decreased erythropoietin responsiveness have not produced consistent results. Erythroid colony growth is suppressed in vitro by interleukins and tumour necrosis factor but their role in vivo in ACD is unknown. The diagnosis of ACD is made by exclusion. Iron deficiency is detected by transferrin, ferritin, and cellular indices after adaptation of their normal values. Treatment of the anaemia consists merely of antirheumatic treatment. Iron administration is counterproductive since iron chelators or exogenous erythropoietin administration might increase erythropoiesis.

Aqueous Ethanol Extraction of Dietary Soy Protein Isolate Improves 59Fe Absorption by the Rat from a Casein-Based Test Meal

A commercial soy protein isolate (SPI) was further processed in an attempt to understand how a diet based on SPI can cause decreased iron retention by the rat from a separately administered casein-based test meal. Groups of eight rats were fed either a casein-based diet or a diet based on SPI. The acid-precipitated SPI was incorporated into diets as such, after neutralization, after 60% (v/v) ethanol extraction and neutralization, or after 60% ethanol exposure and neutralization. All dietary SPI was heat-treated by exposure to steam at 108 degrees C for 30 min. Rats were fed their respective diets, each containing 25 mg Fe/kg, for 13 d, and then all rats were fed a 59Fe-radiolabeled 2.5-g casein test meal containing 64 micrograms of iron. Ingested radioactivity was determined following the meal, and retained radioactivity over the subsequent 10-d period. Absorption was not distinguishable for groups fed the casein-based (78.3 +/- 3.6%) and the ethanol-extracted, SPI-based diet (80.2 +/- 5.4%). Absorption was lower (P less than 0.01) for groups fed each of the other SPI-based diets: SPI as such (68.3 +/- 8.9%), neutralized SPI (69.8 +/- 5.0%) and ethanol-exposed SPI (67.6 +/- 4.8%). An ethanol-extractable component of SPI may be responsible for decreased iron absorption by animals fed SPI prior to a radiolabeled test meal.

Hepatic iron in the control of iron absorption in a rat liver transplantation model.

Rat liver transplantation was utilized to study the effect of hepatic iron on the control of iron absorption. Six iron-loaded and six normal livers were transplanted into normal or iron-loaded animals. Iron absorption was measured pretransplant and 10 days posttransplant by total-body counting (59Fe). The animals were loaded with oral carbonyl iron to produce a predominantly parenchymal hepatic iron distribution and with parenteral iron dextran to produce a predominantly reticuloendothelial iron distribution. The carbonyl iron-loaded livers contained 175 +/- 6.6, the iron dextran livers 180 +/- 41, and the normal livers 6.6 +/- 2.8 mumol FE/g dry wt. Iron absorption was unchanged by the insertion of normal livers into normal animals. The transplantation of carbonyl iron-loaded livers into normal animals caused a marked decrease in iron absorption posttransplant from 7.2 +/- 0.9% to 0.3 +/- 0.4% (P less than .001) posttransplant. Neither the transplantation of iron dextran-loaded livers into normal animals nor the transplantation of normal livers into iron-loaded animals significantly altered iron absorption at 10 days posttransplant. These results are consistent with the hypothesis that hepatocyte iron stores are a major determining factor controlling iron absorption.

Decreased iron absorption in patients with active rheumatoid arthritis, with and without iron deficiency.

Mucosal uptake, mucosal transfer, and retention of a physiological dose of ferrous iron were studied in women with active rheumatoid arthritis (RA): 19 with normal and 17 with depleted bone marrow iron stores. Control subjects were 26 normal women and 20 women with uncomplicated iron deficiency. Iron absorption was measured with 59Fe as a tracer and by whole body counting. Compared with controls, final iron retention was considerably decreased in both groups of patients with RA. Analysis of the two sequential steps of iron absorption showed that mucosal uptake was normal in iron replete patients with RA but was significantly lower in patients with RA with depleted iron stores compared with iron deficient controls. Mucosal transfer of iron was considerably decreased in patients with RA with normal iron stores. The impaired absorption of iron in patients with active RA may delay the correction of the haemoglobin concentration when anaemia of chronic disease is complicated by iron deficiency.

The Effect of Antacids on the Absorption of Simultaneously Ingested Iron

Most discussions of iron therapy include a statement about the ineffectiveness of iron ingested simultaneously with antacids. This study was designed to determine whether or not antacids inhibit iron absorption. A small-dose iron tolerance test was used to compare absorption of iron with and without various antacids. Liquid antacid containing aluminum hydroxide and magnesium hydroxide did not significantly decrease iron absorption. Sodium bicarbonate and calcium carbonate caused the plasma iron increase to be 50% and 67% less than the control values, respectively. However, when calcium carbonate was present in a multivitamin-plus-minerals tablet, the plasma iron change was not significantly different from control trials. Presumably the competitive binding of iron by ascorbic acid in the vitamin pill allowed uninhibited absorption of the iron. Our results suggest that certain antacids may be combined with iron therapy without reducing the efficacy of the iron.

Iron deficiency in infants: The influence of mild antecedent infection

In this study of 467 healthy term infants seen for routine 1-year health maintenance examination, we determined the influence of mild prior infection on the concentration of hemoglobin and other laboratory evidence of iron deficiency. In addition we studied the Hgb response in 261 infants randomized to receive a 3-month course of treatment with either iron or placebo. Infants who had had one or more clinic visits because of infection during the previous 3 months or who were reported as not being entirely well during the past month or who had an elevated sedimentation rate were more likely to have anemia or "low normal" Hgb, higher erythrocyte protoporphyrin and serum ferritin values, and lower serum iron concentration than infants who had been well. Hgb response greater than or equal to 1 gm/dl after iron treatment occurred more commonly in infants who had had prior visits because of infection. The results indicate that upper respiratory and other mild antecedent infections commonly predispose to iron deficiency (probably because of a decrease in iron absorption).

Inhibition of food iron absorption by coffee

Dual isotope studies were performed in iron replete human subjects to evaluate the effect of coffee on nonheme iron absorption. A cup of coffee reduced iron absorption from a hamburger meal by 39% as compared to a 64% decrease with tea, which is known to be a potent inhibitor of iron absorption. When a cup of drip coffee or instant coffee was ingested with a meal composed of semipurified ingredients, absorption was reduced from 5.88% to 1.64 and 0.97%, respectively, and when the strength of the instant coffee was doubled, percentage iron absorption fell to 0.53%. No decrease in iron absorption occurred when coffee was consumed 1 h before a meal, but the same degree of inhibition as with simultaneous ingestion was seen when coffee was taken 1 h later. In tests containing no food items, iron absorption from NaFeEDTA was diminished to the same extent as that from ferric chloride when each was added to a cup of coffee. These studies demonstrate that coffee inhibits iron absorption in a concentration-dependent fashion.

Components of fiber impair iron absorption in the dog

We have demonstrated previously that semipurified components of fiber bind ferrous iron in vitro. The present studies examined the possibility that these same fibers would decrease absorption of iron by the canine small bowel. Healthy and anemic dogs were studied chronically. Two preparations were needed; soluble components of fiber were tested by continuous perfusion of a duodenojejunal segment of approximately 100 cm, insoluble components were tested in Thiry-Vella fistulae of jejunum (25 cm). The results confirm that, 1) anemic dogs absorb iron more efficiently than do healthy animals, and 2) that there is a slight, but significant, decrease in iron absorption during the 4 to 6 h of an acute experiment. To obviate problems of interpretation because of the latter point, all studies featured a control period, before and after, the test period. Lignin and psyllium mucilage were potent inhibitors of iron absorption, pectin less so, and cellulose was without effect in this system. The results in vivo correlate well with the binding of iron in vitro.

Role of Gastric Acid in Food Iron Absorption

Radioiron absorption tests in human volunteers demonstrated a modest but significant 28% reduction in the absorption of dietary nonheme iron from a meal that was preceded by the administration of 300 mg cimetidine. More pronounced decreases of 42% and 65% were observed with 600 and 900 mg cimetidine, respectively. Antacid caused a 52% decrease in iron absorption whereas pentagastrin had no significant effect. Since 300 mg cimetidine reduces gastric acid secretion by 60%-80% but iron absorption by only 28%, it appears that under normal conditions more gastric acid is secreted than is required for optimal iron absorption; absorption falls only when acid secretion is markedly reduced. Cimetidine in the doses currently recommended would not be expected to have a major effect on iron nutrition, although the combination of high doses of cimetidine with antacids would impair nonheme iron absorption significantly.

Factors affecting iron balance.

The availability of radioisotopes of iron led to the performance of physiologic studies of the absorption, excretion, and kinetics of iron. The effects of dietary constituents and intestinal secretions upon iron absorption have been thoroughly explored and have permitted the development of tools for nutritional studies in various geographic areas of the world. The basic mechanisms for regulation of iron absorption are not fully understood. However, the isolation and characterization of newer iron-binding proteins, the existence of mucosal receptors in which there is competition for iron-binding sites with other metals, and the identification of a number of animal models with genetic abnormalities of iron absorption provide promise for development in the foreseeable future. The means by which the body informs the intestine to increase or decrease iron absorption is poorly understood, and the abnormality in hemochromatosis and iron overloading disorders remains unexplained. Much has been learned in recent years regarding the structure of iron-containing proteins and the variations that exist in different species. Similar problems remain to be solved with regard to the intermediary metabolism of iron in red blood cell precursors and other cells in the body. It is postulated that the combined usage of physiologic, biochemical, and immunologic investigations will provide the basic information required.

SOME EFFECTS OF DIFFERENT PHOSPHATE COMPOU NDS ON IRON AND CALCIUM ABSORPTION

ABSTRACTDifferent phosphates commonly used in food processing have been evaluated for their effects on iron and calcium absorption. In growing rats, addition of phosphates to diets caused decreased iron absorption, decreased hemoglobin concentrations and depressed liver iron values in both the control and achlorhydric animals. Liver iron values were somewhat depressed in the mature rats which was slightly more severe in the achlorhydric animals. Sodium pyrophosphate and sodium tripolyphosphate impaired iron metabolism more severely than dibasic sodium phosphate and sodium metaphosphate in both age groups; this effect tended to be greater in the achlorhydric animals. In the growing rats, addition of phosphates to the diets decreased calcium absorption and femur calcium content, the severity of which was greater in the achlorhydric animals. Sodium tripolyphosphate caused consistent decreases in bone calcium content. The phosphate effects were definitely more severe in the achlorhydric growing rats and tended to be more severe in the achlorhydric mature rats. The data presented indicate that the various phosphates have different effects on calcium and iron metabolism and that these effects are magnified by achlorhydria.

Iron absorption from wheat bread. Influence of various amounts of bran.

Bran is known to reduce iron absorption. There is, however, no information on the relationship between the amount of bran added and the decrease in iron absorption. In the present study a comparison was made of the iron absorption from a white wheat bread and a bread baked with different amounts of bran added (from 10 to 0.3%). There was a decrease in iron absorption from rolls baked with added bran in amounts equal to and greater than 3.3 %. A significant linear relationship was found between the ratio of absorption with/without added bran and the log amount of bran added. From the relationship observed it is concluded that addition of approximately 7% of bran to wheat bread decreases ironabsorption by a factor of two. It is considered reasonable to ascribe the marked reductionin iron absorption to the content of phytate in bran.

The absorption of 59Fe by the rat fetus.

&lt;sup&gt;59&lt;/sup&gt;Fe was given orally to fetal rats from day 18 to 21 to determine whether there was evidence for regulation of iron absorption prior to birth. The fetal rat was able to absorb &lt;sup&gt;59&lt;/sup&gt;Fe. The quantity absorbed, however, declined significantly towards term. We suggest that the decrease in iron absorption is due to the operation of a regulatory mechanism in the fetal intestine during this interval.

Effect of cobalt upon iron absorption.

SummaryThe addition of cobalt to oral test doses of radioiron decreases iron absorption. Studies were performed in rats to determine the site and mechanisms of this inhibition. Significantly less radioiron was observed in both the carcass and small intestine of rats fed cobalt with test doses of radioiron than in animals receiving iron alone. This indicates that cobalt diminished the mucosal uptake of iron from the intestinal lumen. Iron absorption studies in rats receiving various doses of iron with and without added cobalt suggested that cobalt was capable of saturating a common pathway in intestinal absorptive cells for the absorption of both metals.

Disorders associated with malabsorption of iron: A critical review.

Malabsorption is a disorder of the gastrointestinal tract that leads to defective digestion, absorption and transport of important nutrients across the intestinal wall. Small intestine is the major site where most of the nutrients are absorbed. There are three main mechanisms of malabsorption; premucosal, mucosal and postmucosal. Premucosal malabsorption is the inadequate digestion due to improper mixing of gastrointestinal enzymes and bile with chyme. This could be because of surgical resection of the small intestine or a congenital deficiency of the enzymes and bile responsible for digestion e.g. postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis etc. Mucosal malabsorption occurs in celiac disease, tropical sprue, Crohn’s disease etc. Postmucosal condition arises due to impaired nutrients transport e.g. intestinal lymphangiectasia, macroglobulinemia etc. Disorders of malabsorption lead to decreased iron absorption and produce iron deficiency anemia.Using the index terms malabsorption, postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis, celiac disease, tropical sprue, Crohn’s disease intestinal lymphangiectasia, macroglobulinemia and iron deficiency anemia the MEDLINE and EMBASE databases were searched. Additional data sources included bibliographies and references of identified articles.