Duodenal iron proteins in idiopathic hemochromatosis.

This study was undertaken to assess the relationship between iron absorption and the concentration of duodenal iron proteins in normal subjects and patients with idiopathic hemochromatosis (IH). Biopsies were obtained endoscopically from the duodenum in 17 normal subjects, 3 of whom were mildly iron deficient, and 7 patients with untreated IH. The absorption of both heme and nonheme iron was increased in IH despite a 20-fold elevation in serum ferritin. Immunoassays using MAb were used to measure transferrin, H-rich ferritin, and L-rich ferritin in mucosal samples. Mucosal transferrin concentrations in normal subjects did not correlate with either iron status or iron absorption, indicating that mucosal transferrin plays no physiological role in iron absorption. Mucosal transferrin was significantly lower in IH, presumably because of a decrease in mucosal transferrin receptors. Mucosal H and L ferritin concentrations were directly related to body iron stores and inversely related to iron absorption in normal subjects. In IH, mucosal H and L ferritin failed to increase in parallel with the serum ferritin, but were appropriate for the level of iron absorption. The relationship of mucosal H/L ferritin in IH did not differ from that observed in normal subjects. Our findings indicate that the major abnormality in duodenal iron proteins in IH is a parallel decrease in the concentration of H- and L-rich ferritin. It is not evident whether this is the result or the cause of the absorptive abnormality.     

Immunolocalization of duodenal cytochrome B: a relationship with circulating markers of iron status

BACKGROUND: The brush border ferric reductase (Dcytb) is critical for the absorption of dietary iron and appears to be expressed on the duodenal enterocyte brush border. The Dcytb expression is increased in severe iron-deficient anaemia, but the situation in a more typical mild iron deficiency is unclear. This study investigated Dcytb expression in patients with normal iron status or mild iron deficiency and its relationships with enterocyte iron status. MATERIALS AND METHODS: Duodenal biopsy specimens and blood samples were obtained from 32 patients undergoing routine upper gastrointestinal endoscopy. Twenty-three specimens (six iron-deficient and 17 iron-replete) were processed for light-microscopy (LM) and for immunohistochemistry with antibodies against Dcytb and heavy/light chain ferritin subunits. The nine remaining biopsies (three iron-deficient and six iron-replete) were processed for electron microscopy (EM). Immunolocalization of Dcytb and intracellular ferritin was performed with appropriate primary antibodies followed by 10-nm gold conjugate labels. RESULTS: The LM process showed a strong negative correlation between immunolabelling intensity of Dcytb on the enterocyte brush border and serum iron saturation (P < 0.001), but only a weak negative correlation between this antigen and haemoglobin (P = 0.08) or serum ferritin concentrations (P = 0.4). EM confirmed anti-Dcytb preferential labelling of microvilli rather than enterocyte cytoplasm (P = 0.001), but preferential antiferritin labelling of cytoplasm (P < 0.02). There was no correlation with enterocyte cytoplasmic ferritin labelling (i.e. enterocyte iron status and Dcytb expression). CONCLUSIONS: Enterocyte Dcytb brush border expression is increased even in mild iron deficiency and may be related to serum iron saturation. The lack of correlation with enterocyte ferritin expression deserves further study with direct measurement of intracellular iron.     

Small intestinal regulation of iron absorption in the rat

Ultrastructural, biochemical, and immunologic studies of the small intestinal mucosa of rats were undertaken to investigate factors associated with the regulation of iron absorption. The quantity of iron within mucosal cells was proportionate to the degree of iron repletion. Although the quantity of iron-binding substances was similar in iron-deficient and iron-loaded animals, the unsaturated iron-binding capacity of mucosal cells varied inversely with the state of iron repletion of animals in ultrastructural, biochemical, and immunologic observations. Although only certain mucosal cells contained iron-binding substances, their number was not increased in iron-deficient animals. Greater quantities of iron and iron-binding substances were observed in duodenal mucosa than in ileal mucosa. These findings are consistent with the hypothesis that the quantity of unsaturated iron-binding substances within intestinal mucosal cells regulates iron absorption. These findings are only partially explained by changes observed in the concentration of ferritin and transferrin within intestinal mucosa and suggest that other iron-binding substances may also participate in the regulation of iron absorption.     

The Control of Iron Absorption by the Gastrointestinal Mucosal Cell

Gastrointestinal mucosal factors controlling rates of iron absorption were studied utilizing an in vivo closed duodenal loop technique. Cellular distribution of newly absorbed radioiron was identified by molecular sieve and iron-exchange chromatography of the mucosal cell supernate. In the normal animal, iron rapidly appeared in ferritin, and this fraction accounted for greater than 90% of mucosal supernatant radioactivity after 60 min absorption time. The nonferritin radioiron appeared to be unbound iron salts. In the presence of increased iron absorption induced by iron depletion or hemolysis, the major difference from the normal distribution pattern was an increase in the proportion and quantity of the free iron salts. Incorporation of newly absorbed iron into ferritin did not correlate with the rate of iron absorption. No evidence was found for a specific soluble iron-chelating molecule within the mucosal cell. The nonheme iron content of the mucosal supernates from iron-deficient and hemolyzing animals were significantly lower than in the normal animal.The data are consistent with hypotheses which suggest that iron absorption rates may be controlled in part by the rate of initial iron uptake by the mucosal cell and that a membrane transport mechanism exists which is modulated by the nonheme iron content of the mucosal cell or some portion thereof.     

Iron binding proteins of iron-absorbing rat intestinal mucosa

The distribution and quantitation of the iron-binding proteins of rat small intestinal mucosa was studied, in iron-deficient and replete animals, to explore their role in the absorption of iron. Adsorption (mucosal uptake) of iron in in situ ligated loops of small intestinal mucosa was found to be uniform throughout the length of the small intestine whereas absorption (carcass uptake) showed a steep decreasing gradient from the duodenum to the ileum. The disrupted, in vivo labeled mucosal cells were fractionated by isopycnic centrifugation and transferrin and ferritin were quantitated by radioimmunoassay. Transferrin derived from mucosal cells was shown to have a higher affinity for the antibody than transferrin in serum. Of the transferrin present in the mucosal extract, only a portion could be accounted for by contamination from the serum; the proteolysis resistant and intrinsic transferrin may be mucosal cell specific. Transferrin was found in similar amounts in all regions of the small intestine, was not affected by iron loading but doubled in response to iron deficiency. Mucosal ferritin was found in greater amounts in the iron-absorbing areas of the intestine, increased in the duodenum of iron-loaded animals, and decreased in iron-deficient animals. The incorporation of newly absorbed radioiron into ferritin was only found in iron absorbing regions and was completely inhibited by colchicine and cytochalasin-B, suggesting that ferritin was loaded with iron at the point of iron absorption and that the process is associated with vesicle movement and not simple diffusion. Transferrin and ferritin-specific immunoabsorption and also gel filtration established that no other soluble iron binding proteins were involved in absorption.     

Mucosal transferrin and ferritin factors in the regulation of iron absorption

1. A standardized decompensation and recompensation of iron homeostasis has been produced by a change-over from normal to iron deficiency and back. 2. Under these conditions the 59Fe uptake into transferrin and ferritin of the mucosal "cytosol" and SDS treated "membrane" fraction has been measured together with the 59Fe amount transferred into the body. 3. The increase of the intestinal 59Fe absorption due to a progressive iron deficiency is associated with an increase of the 59Fe uptake into the mucosal transferrin of the "cytosol" and the "membrane" fraction; the reverse is observed with regard to mucosal ferritin. 4. Three days after the re-establishment of normal conditions the 59Fe absorption was lowered to normal values, while the 59Fe uptake into mucosal ferritin achieved again normally high values. 5. The high apparent rate of absorption in iron deficient animals decreased during the last 50 min after injection of the 59Fe labelled test dose. The 59Fe content in the ferritin fraction increased simultaneously, whereas the 59Fe content in the transferrin fraction remained the same. 6. The conclusion is drawn that the intestinal iron absorption is regulated by both mucosal iron binding proteins. Mucosal transferrin is responsible for the increase of absorption in iron deficiency while mucosal ferritin is responsible for the inhibition of iron absorption when the iron homeostasis recompensats.     

Relationship between serum ferritin,iron stores and disease activity in rheumatoid arthritis

Summary Bone marrow aspirate from the sternum of 40 patients with active or inactive rheumatoid arthritis (RA) was stained with Perls’ Prussian blue for iron determination. In these patients serum ferritin concentrations were correlated with other indices of iron stores and disease activity. In patients with active RA and without bone marrow iron stores, serum ferritin was significantly lower than in patients with either active or inactive RA and iron stores. In patients with bone marrow iron stores, serum ferritin was directly correlated with erythrocyte sedimentation rate (ESR), Ritchie index, α₁-antitrypsin, α₁-acid glycoprotein and desferrioxamine (DFO)-induced sideruria, while an inverse correlation of serum ferritin with hemoglobin and serum iron was observed. In all patients serum ferritin was significantly correlated only with DFO-induced sideruria and unsaturated iron-binding capacity (UIBC). Thus, serum ferritin is an index of iron stores also in rheumatoid arthritis. In active disease, higher than expected values of serum ferritin are probably due to a shifting of iron from the circulating pool to the reticuloendothelial cells of the synovial membrane.     

Intestinal Absorption of Hemoglobin Iron-Heme Cleavage by Mucosal Heme Oxygenase

Hemoglobin and myoglobin are a major source of dietary iron in man. Heme, separated from these hemoproteins by intraluminal proteolysis, is absorbed intact by the intestinal mucosa. The absorbed heme is cleaved in the mucosal cell releasing inorganic iron. Although this mucosal heme-splitting activity initially was ascribed to xanthine oxidase, we investigated the possibility that it is catalyzed by microsomal heme oxygenase, an enzyme which converts heme to bilirubin, CO, and inorganic iron.Microsomes prepared from rat intestinal mucosa contain enzymatic activity similar to that of heme oxygenase in liver and spleen. The intestinal enzyme requires NADPH; is completely inhibited by 50% CO; and produces bilirubin IX-alpha, identified spectrophotometrically and chromatographically. Moreover, duodenal heme oxygenase was shown to release inorganic (55)Fe from (55)Fe-heme. Along the intestinal tract, enzyme activity was found to be highest in the duodenum where hemoglobin iron absorption is reported to be most active. Furthermore, when rats were made iron deficient, duodenal heme oxygenase activity and hemoglobin-iron absorption rose to a comparable extent. Upon iron repletion of iron-deficient animals, duodenal enzyme activity returned towards control values. In contrast to heme oxygenase, duodenal xanthine oxidase activity fell sharply in iron deficiency and rose towards base line upon iron repletion.Our findings suggest that mucosal heme oxygenase catalyzes the cleavage of heme absorbed in the intestinal mucosa and thus plays an important role in the absorption of hemoglobin iron. The mechanisms controlling this intestinal enzyme activity and the enzyme's role in the overall regulation of hemoglobin-iron absorption remain to be defined.     

Regulation of intestinal iron absorption and mucosal iron kinetics in hereditary hemochromatosis

In hereditary hemochromatosis (HH), increased intestinal iron absorption leads to the development of iron overload. To examine the abnormal regulation of iron absorption in this disorder, we analyzed mucosal iron kinetics in six patients with HH and in five normal subjects by using a compartmental model of intestinal iron absorption and systemic ferrokinetics. Subjects were given simultaneous oral and intravenous tracer doses of iron 59-labeled citrate and iron 55-labeled transferrin, respectively. Plasma and whole-body radioactive iron levels were then monitored serially during the next 2 weeks, and mucosal iron transport rate constants were estimated by non-linear least-squares fit of the model to these data. Iron absorption was inversely related to serum ferritin concentration in both normal subjects and patients with HH but was higher in relation to serum ferritin level among the latter (p less than 0.0002). Analysis of mucosal iron kinetics demonstrated a similar inverse relationship between the rate constant for mucosal iron uptake and serum ferritin among all subjects combined, but the mean uptake rate constant in patients with HH did not differ from that of normal subjects (p = 0.71). The mean rate constant for incorporation of iron into the mucosal storage pool in patients with HH also was comparable to that of normal subjects (p = 0.94). In contrast, the rate constant for transfer of mucosal iron to the plasma was higher in patients with HH than in normal subjects for any given serum ferritin level (p less than 0.0001), and the transfer rate constant accounted for 87% of the variability in iron absorption among all subjects. We conclude that the increased iron absorption in HH is mediated primarily by an increase in the rate constant for transfer of mucosal iron to the plasma.     

Cellular mechanisms underlying the increased duodenal iron absorption in rats in response to phenylhydrazine-induced haemolytic anaemia

Abstract. Haemolytic anaemia induced by phenylhy-drazine (PZ) promotes iron absorption across rat small intestine. This present study investigates the role of the brush border potential difference ( V _m) and mucosal reducing activity in the response. In addition, quantitative autoradiography was used to assess PZ-induced changes in the villus localization of brush border iron uptake. Iron transfer from duodenum to blood was increased significantly 5 days after treatment with PZ. Autoradiography showed that most brush border iron uptake occurred at the upper villus region and the maximal rate was increased fourfold by PZ. Duodenal villus length was increased in PZ-treated rats. PZ treatment did not influence mucosal reducing activity but V _m, measured using duodenal sheets, increased from -50 to -57mV { P < 0.001) and this was due to a reduced brush border sodium permeability. Thus, an expanded absorptive surface and an enhanced electrical driving force for iron uptake across the duodenal brush border are important adaptations for increased iron absorption in PZ-induced haemolytic anaemia.     

Choice of conditions for the gradient flotation of serum lipoproteins in swing-out rotors

A method for the preparation of suspensions of isolated, viable intestinal cells has been modified to study the initial rapid phase of iron uptake and absorption by the cells. The technique permits precise timing of absorption studies and avoids contamination by plasma transferrin.Iron uptake by the cell suspensions showed an initial rapid phase in the first 2 min followed by a slower uptake to 30 min. Column chromatographic analysis of the 10000 g supernatant from the cell homogenates revealed 4 iron-containing fractions, one of which was ferritin. The others included a fraction of molecular weight higher than ferritin and another of molecular weight lower than 50000. The appearance of iron in these 2 peaks preceded iron incorporation into ferritin. The results suggest that these fractions represent cytoplasmic intermediates involved in the uptake and transport of iron by the mucosal cell.Ascorbic acid increased the uptake of iron by the cells and was necessary for the incorporation of iron into ferritin.     

Iron Induced Increase in Red Cell Size in Haemodialysis Patients

In a group of haemodialysis patients who were iron loaded secondaryto parenteral iron administration a slight but significant increasein red cell size was noted when compared to a normal population.This macrocytosis was not related to serum B₁₂ or folate levels,or to the reticulocyte count. On stopping iron therapy bothmean corpuscular volume (MCV) and mean corpuscular haemoglobin(MCH) values declined significantly as did serum ferritin andiron levels. Bone marrow smears were of normal or increasedcellularity. When iron therapy was discontinued there was asteady fall in serum ferritin levels without a drop in haemoglobinvalues suggesting that the excess iron was available for haemopolesis.These findings suggest that the increase in red cell size inthis group of patients may have been induced directly by ironoverload.     

Effect of epidural blockade on indicators of splanchnic perfusion and gut function in critically ill patients with peritonitis: a randomised comparison of epidural bupivacaine with systemic morphine

OBJECTIVES: (a) To measure gastric tonometry values in critically ill patients with peritonitis and to assess the impact of epidural analgesia on these values. (b) To assess the impact of epidural analgesia on gastro-intestinal motility by abdominal ultrasound and paracetamol absorption. (c) To observe any change in clinical outcome that may result from the use of epidural analgesia in such patients. DESIGN: A double-blinded, prospective, randomised and controlled study of general intensive therapy unit (ITU) patients. PATIENTS: Twenty-one patients admitted with peritonitis and adynamic small bowel following abdominal surgery were randomly allocated to receive either intravenous morphine or epidural bupivacaine for analgesia. MEASUREMENTS AND RESULTS: Gastric intramucosal pH (pHig) and the mucosal:arterial PCO2 gradient (Pg-PaCO2) were measured at admission and after 24 h of analgesia. Analysis of mean changes in tonometry values showed a rise in Pg-PaCO2 and a fall in pHig in the morphine group and a significant difference between groups in the Pg-PaCO2 trends (p = 0.024). Significant improvements in the ultrasound appearance of the small bowel were observed in the epidural group (p = 0.0037, Mann-Whitney U test of median changes in a locally developed scoring system). There were no significant differences between the groups in any of the variables derived from the paracetamol absorption test (n = 10); both groups showed persistently delayed gastric outflow throughout the study period. CONCLUSIONS: Epidural analgesia resulted in improvements in gastric mucosal perfusion and the ultrasound appearance of the small bowel, indicating potential clinical benefit in a group of patients in whom epidural catheterisation is traditionally contraindicated.     

Hereditary hemochromatosis: laboratory evaluation

The condition of hereditary hemochromatosis (HH) is caused by gene-dependent protein abnormalities involved in iron absorption, storage, or modulation of iron; these abnormalities result in iron overload. The clinical laboratory plays a significant role in case finding, diagnostic validation, and monitoring HH therapy. Elevated serum iron, transferrin saturation, and ferritin suggest HH, but results can also indicate other forms of hepatocyte injury such as alcoholic or viral hepatitis, or other inflammatory disorders involving the liver. In the context of elevated serum iron, transferrin saturation, and ferritin, and after ruling out secondary causes of iron overload, HFE gene evaluation is the preferred test to confirm the diagnosis of HH. However, 5% to 15% of patients with phenotypic HH do not have HFE gene mutations. In these cases, MRI evaluation or liver biopsy with iron quantification is indicated. The clinical role of hepcidin, the iron modulating protein, is undetermined at this time. Because hepcidin also plays a key role in antimicrobial and inflammatory activities, interpretation of hepcidin serum or urine concentration will require thorough understanding of its complex role in iron regulation.     

Three-year follow-up after withdrawal of iron therapy in uremic patients on regular dialytic treatment

Summary Iron supplementation is commonly recommended in uremic patients undergoing regular dialytic treatment in order to correct a presumed iron deficiency due to impaired absorption and dialytic losses. Serum ferritin levels show an iron overload in 83% of 136 patients on 1.25 g/year i.v. iron therapy. After the withdrawal of iron therapy, directly correlated ferritin levels and percentage transferrin saturation decreased slowly, except in carriers of HLA-A₃ antigens and in polytransfused patients. In these latter patients, desferrioxamine reduced but did not normalize the iron balance. The 16 patients who never received iron therapy showed a normal iron balance over a 3-year follow-up. Despite iron-ferritin therapy, 11 patients with baseline ferritin values at the lower normal limits showed a tendency toward further depletion. Orally administered bivalent iron seems to be more promising in normalizing iron-deficient patients without potentially harmful overloading.     

Ultrasound examination of the small bowel: comparison with enteroclysis in patients with Crohn disease

Background Screening for inflammatory small bowel disease has hereto relied on barium examination, usually performed after duodenal intubation. A noninvasive technique for imaging of the small bowel in such patients would be preferable.Methods A total of 59 patients were included in the study. A small bowel barium examination (SBE) was performed after duodenal intubation using a barium and air double-contrast technique. Ultrasound (US) of the right lower quadrant was performed with a 3.5- or 5-MHz transducer. The patients fasted overnight.Results In 37 of 39 patients with a normal SBE, US was also normal. In 20 patients, SBE showed lesions compatible with Crohn disease and in 18 of these the US study showed thickening of the bowel wall. One of these patients later tested positive for Yersinia enterocolitica. There were two false-positive and two false-negative US examinations.For detection of inflammatory disease of the small bowel, US was calculated to have a sensitivity of 0.95, specificity of 0.93, accuracy of 0.93, predictive value of a positive test was 0.90, and a predictive value of a negative test was 0.95.Conclusions US, therefore, seems to be a reliable method in the workup of patients suspected of having inflammatory small bowel disease. Thereby, US probably can select patients for SBE.     

The Ageing Gut: A Study of Intestinal Absorption in Relation to Nutrition in the Elderly

This study was designed to assess the functional efficiencyof the ageing small intestine and the possible role of malabsorptionin old people with nutritional deficiencies. Fifty subjects aged 65 to 92 years were studied, of whom 33presented with anaemia, chronic diarrhoea or bone pains, and17 were apparently healthy ‘controls’ with no relevantsymptoms. Tests of intestinal function included blood xyloseand iron absorption curves, a doable isotope Schilling test,faecal fat, urinary indican and small bowel radiology, withduodenal aspiration and jejunal biopsy in some cases. On the basis either of steatorrhoea or at least two other abnormalparameters of absorption, there were 15 cases of malabsorption.Thirteen of these had symptoms but two were ‘controls’.Four of these had duodenal diverticulosis, two had the post-gastrectomysyndrome, and one had calcific pancreatitis Malabsorption inthe remaining eight cases was not fully explained. The age rangeof this last group was 72–86 years; one of them had acontaminated small bowel and two showed some evidence of pancreaticinsufficiency. Malabsorption emerged as a significant cause of low levels ofserum iron, haemoglobin and calcium. The blood xylose test isa useful screening procedure for intestinal malabsorption inold age, but fun evaluation calls for investigation of pancreaticfunction.     

The non-immune inflammatory response: serial changes in plasma iron, iron-binding capacity, lactoferrin, ferritin and C-reactive protein

The interrelationships between various components of the non-immune inflammatory response (white cell count, plasma lactoferrin, C-reactive protein, ferritin, iron and iron-binding capacity), were studied serially in a variety of inflammatory conditions including acute lobar pneumonia, active pulmonary tuberculosis, rheumatoid arthritis on gold therapy and sepsis in the face of marrow hypoplasia induced by chemotherapy. Lactoferrin concentrations paralleled the white count in all groups. They were highest in pneumonia and tuberculosis, mildly elevated in rheumatoid arthritis and markedly decreased in neutropenic sepsis. Very high initial lactoferrin concentrations were associated with a poor prognosis in acute pneumonia. C-reactive protein and ferritin concentrations remained elevated through the period of study in acute pneumonia and neutropenic sepsis, while they gradually normalised over weeks in subjects with tuberculosis or rheumatoid arthritis on therapy. In pneumonia and tuberculosis moderate hypoferraemia and a reduced iron-binding capacity were evident. In contrast, a raised percentage saturation was present in neutropenic sepsis, probably related to erythroid marrow suppression. Comparisons between ferritin, lactoferrin and C-reactive protein in the various groups supported the concept that ferritin behaves in part as an acute phase reactant and that hypoferraemia in inflammation is due to deviation of iron into ferritin stores. The suggestion that lactoferrin is responsible for the hypoferraemia and hyperferritinaemia was not supported by the present data. Iron deficiency appeared to limit the hyperferritinaemic response in rheumatoid arthritis, while erythropoietic inhibition by chemotherapy dampened the hypoferraemic response in neutropenic sepsis.     

Bovine ferritin iron bioavailability in man

The bioavailability of ferritin iron was evaluated in human subjects using radiolabelled [⁵⁵Fe]ferritin isolated from bovine spleen and liver. Preliminary studies with bovine spleen ferritin labelled in vitro demonstrated an inappropriately high absorption compared with ferritin labelled in vivo , and the latter was therefore used in all subsequent absorption studies. In 10 subjects, geometric mean absorption from 5 mg of ferritin iron was 3.8% when taken without and 3.2% when taken with food ( P  >0.05). These values were significantly lower than absorption from the same dose of iron given as ferrous sulphate, which averaged 24.1% without and 8.2% with food. When the iron dose was increased 10-fold, absorption of ferritin iron averaged only 0.6–0.7% with or without food as compared with 7.9% without and 2.6% with food when the iron was given as ferrous sulphate. In a further study, mean absorption from bovine spleen ferritin of 4.0% did not differ significantly from the mean of 2.7% observed with bovine liver ferritin. These findings confirm previous studies indicating that ferritin iron is poorly absorbed. Furthermore, its use as a pharmaceutical iron preparation cannot be advocated.     

Bovine ferritin iron bioavailability in man

The bioavailability of ferritin iron was evaluated in human subjects using radiolabelled [⁵⁵Fe]ferritin isolated from bovine spleen and liver. Preliminary studies with bovine spleen ferritin labelled in vitro demonstrated an inappropriately high absorption compared with ferritin labelled in vivo, and the latter was therefore used in all subsequent absorption studies. In 10 subjects, geometric mean absorption from 5 mg of ferritin iron was 3.8% when taken without and 3.2% when taken with food (P >0.05). These values were significantly lower than absorption from the same dose of iron given as ferrous sulphate, which averaged 24.1% without and 8.2% with food. When the iron dose was increased 10-fold, absorption of ferritin iron averaged only 0.6–0.7% with or without food as compared with 7.9% without and 2.6% with food when the iron was given as ferrous sulphate. In a further study, mean absorption from bovine spleen ferritin of 4.0% did not differ significantly from the mean of 2.7% observed with bovine liver ferritin. These findings confirm previous studies indicating that ferritin iron is poorly absorbed. Furthermore, its use as a pharmaceutical iron preparation cannot be advocated.