The effect of dietary proteins on iron bioavailability in man.
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Animals↗
Biomedical subjects
J D Cook
Publications and source records attributed to J D Cook.
Gastrostomy and Nissen fundoplication in neurologically impaired children.
We report our experience with 90 neurologically impaired children treated with gastrostomy and Nissen fundoplication. Malnutrition was the main problem, followed by aspiration, recurrent pneumonia, and vomiting. The symptomatology was caused by swallowing incoordination and gastroesophageal reflux. The diagnosis of gastroesophageal reflux was confirmed by upper gastrointestinal series and pH probe. Nissen fundoplication was performed following a standard technique with preservation of the vagus nerves and its branches, repair of the diaphragmatic crura, reconstruction of the angle of His, and a 360 degree wrap. A gastrostomy and pyloroplasty or pyloric dilatation were part of the operative procedure. There were no deaths and few complications related to the surgical procedure. Marked nutritional improvement was seen in most cases with an average weight gain of 3.2 kg/patient 3 months following surgery. There was also improvement in milestones and seizure control. The majority of parents were very satisfied and would recommend the procedure to other parents with similar problems.
Adolescent↗
Comparison of in vitro, animal, and clinical determinations of iron bioavailability: International Nutritional Anemia Consultative Group Task Force report on iron bioavailability.
Relative bioavailability of two iron fortificants, electrolytic Fe and ferric orthophosphate, was related to that of the reference ferrous sulfate with in vitro and rat model depletion-repletion methods in four laboratories to compare values directly with those obtained in a parallel human study. In vitro testing was performed on Fe compounds with both solubility and dialysis in a simulated in vitro gastrointestinal digestion system. Two depletion-repletion techniques, hemoglobin-regeneration efficiency (HRE) and an official method of the Association of Official Analytical Chemists (AOAC), were examined. AOAC relative biological values (RBV) of electrolytic Fe were 0.66 and 0.78 and of FePO4 were 0.25 and 0.34. HRE values were 0.78 and 0.58 for electrolytic Fe and FePO4, respectively. When compared with FeSO4 in a radiolabeled farina-based meal fed to humans, the RBV of FePO4 was 0.25 and electrolytic Fe 0.75. Results obtained with the AOAC method serve as the most reliable prediction of Fe bioavailability in the human although in vitro dialysis is a promising screening technique.
Animals↗
Iron absorption in humans as influenced by bovine milk proteins.
The effect of the two major bovine milk protein fractions on the dialyzability of iron in vitro under simulated gastrointestinal conditions and on the absorption of Fe by humans was studied. Liquid-formula meals were prepared from hydrolyzed maize starch, corn oil, and either spray-dried egg white or a milk-protein product. In meals containing egg white, 3.32% of the Fe was dialyzable. The substitution of casein and whey protein products reduced the dialyzable fraction to 0.19-0.56% and 0.86-1.60%, respectively. Percentage Fe absorption was also reduced by the substitution of casein or whey protein for egg white. Mean absorption values fell from 6.67 to 3.65% and 2.53 to 0.98%, respectively. When the intact milk-protein products were replaced by enzyme- or acid-hydrolyzed preparations, the dialyzable fraction increased markedly and in proportion to the extent of hydrolysis. A similar but much smaller effect on absorption was observed. These studies suggest that bovine casein and whey proteins are responsible at least in part for the poor bioavailability of the Fe in some infant formulas.
Adult↗
Iron fortification of infant cereals: a proposal for the use of ferrous fumarate or ferrous succinate.
Hemoglobin-repletion tests in rats, organoleptic studies, and iron-absorption studies in humans were used to search for Fe sources with high bioavailability that could be added to infant cereals as alternatives to the Fe compounds currently used for fortification. From rat and organoleptic studies on 11 alternative Fe sources, ferrous fumarate, ferrous succinate, and ferric saccharate were selected as the most suitable for infant-cereal fortification and, by use of radioactive labels, absorption of those compounds from fortified cereal was measured in adult human volunteers. There was no difference in absorption between ferrous fumarate and ferrous sulfate whereas the values for ferrous succinate, ferrous saccharate (10% Fe), and ferric pyrophosphate were 92%, 74%, and 39% of the ferrous sulfate values, respectively. We conclude that ferrous fumarate and ferrous succinate are highly available Fe sources in man that can be used to fortify infant cereals without causing fat oxidation or discoloration.
Absorption↗
Iron deficiency: definition and diagnosis.
There has been a continuous refinement over the past several decades of methods to detect iron deficiency and assess its magnitude. The optimal combination of measurements differs for clinical and epidemiological assessment. Clinically, the major problem is to distinguish true iron deficiency from other causes of iron-deficient erythropoiesis, such as the anaemia of chronic disease. Epidemiologically, techniques that provide quantified estimates of body iron are preferable. For both purposes, the serum ferritin is the focal point of the laboratory detection of iron deficiency. Serum ferritin measurements provide a reliable index of body iron stores in healthy individuals, a cost-effective method of screening for iron deficiency, and a useful alternative to bone marrow examinations in the evaluation of anaemic patients. Preliminary studies indicate that measurement of the serum transferrin receptor may be the most reliable way to assess deficits in tissue iron supply.
Anemia, Hypochromic↗
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.
Adult↗
The clinical measurement of serum transferrin receptor.
Monoclonal antibody reagents were used to develop a sensitive enzyme-linked immunoassay for clinical measurement of circulating transferrin receptor. By using transferrin-bound receptor for the preparation of the immunologic reagents, we developed an assay that gives an identical dose-response curve with either free or transferrin-bound receptor. The mean concentration of circulating receptor in 82 normal male and female volunteers was 5.63 +/- 1.42 mg/L. The level was reduced significantly in patients with primary aplastic anemia and post-transplant aplasia (2.58 +/- 1.07 mg/L and 2.32 +/- 0.48 mg/L, respectively) and was sharply elevated in patients with hemolytic anemia and iron deficiency anemia (33.1 +/- 17 and 18.0 +/- 11.4 mg/L, respectively). Our assay values are approximately 20-fold higher than results published previously in a study that used an immunoradiometric assay. The disparity apparently relates to a difference in sensitivity of the latter assay for free and transferrin-bound receptor. Measurements of serum transferrin receptor provide a useful clinical index of either total or iron-deficiency erythropoiesis.
Adult↗
Inaccuracies in digoxin measurement.
Six commercial digoxin immunoassay kits were evaluated for their accuracy of calibration and their extent of interference by digoxin-like immunoreactive substance (DLIS). Calibration accuracy was investigated with digoxin reference standards in pooled human serum. The Abbott and Becton Dickinson kits underestimate while the other kits overestimate digoxin concentration. The magnitude of this bias generally increases with increasing concentration of digoxin. Sera from digoxin-free patient populations with potential DLIS interference--pregnant women, newborns, hypertensives, and uremics--were analyzed with each kit. Healthy subjects not on digoxin therapy served as controls. Groups with DLIS interference, as exemplified by a significant difference of p less than 0.05 from controls, are: Abbott--newborns and pregnant women; Becton Dickinson--newborns and pregnant women; Dade--no difference; Dupont--newborns, uremics, pregnant women, and hypertensives; Kallestad--newborns; and Syva--newborns. The limitations of each individual digoxin method should be realized for DLIS interference and bias, and patient results from that method should be interpreted accordingly.
Adult↗
Iron absorption from fortified flat breads.
1. Radio-iron absorption measurements were performed in healthy volunteer subjects to assess the availability of fortification Fe added to various bread products. 2. When ferrous sulphate was used as a fortifier, Fe absorption from a traditional Egyptian flat bread (Baladi) averaged only 16% of that observed with European bread. This difference was attributed to the high extraction flour used to prepare Baladi bread. 3. The inhibiting effect of Baladi bread was largely eliminated by adding EDTA to the flour before baking.
Adult↗
Iron absorption in humans: bovine serum albumin compared with beef muscle and egg white.
We studied the influence of bovine serum albumin and beef meat on nonheme iron absorption in humans and on dialyzable iron in vitro. The addition of serum albumin to a maize gruel had no significant effect on nonheme Fe absorption whereas the addition of beef meat caused a threefold increase. When added to a bread meal, serum albumin caused a modest 60% increase in nonheme Fe absorption and beef meat had no effect. When added to a protein-free meal, serum albumin reduced Fe absorption by 47% compared with a 72% reduction on addition of egg white. The bioavailability of nonheme Fe from meals containing serum albumin was consistently overestimated by the in vitro technique. We conclude that the facilitation of nonheme Fe absorption by meat is not a general property of all animal protein but is better explained by the action of one or more specific animal tissues.
Adult↗
An immunoassay for human transferrin.
The laboratory measurement of serum transferrin is a valuable adjunct in the assessment of both iron and protein nutritional status. Conventional assays based on the Fe-binding properties of this protein are tedious to perform, susceptible to Fe contamination, and require volumes of serum that can only be obtained by venous sampling. We describe in this report a two-site enzyme immunoassay (EIA) developed with the use of monoclonal antibodies. Ten microliters serum is diluted 1:20,000 before assay, reflecting a high degree of sensitivity. The variability of this EIA is comparable to conventional colorimetric assays for total iron-binding capacity (TIBC), and excellent correspondence was observed between these methods over a range in TIBC of 150-500 micrograms/dL (27-90 mumol/L). No consistent difference was observed with the EIA when performed on venous and capillary specimens obtained simultaneously. This method will facilitate the evaluation of Fe and protein status in nutritional surveys.
Animals↗
Interaction of acidic isoferritins with human promyelocytic HL60 cells.
We have used undifferentiated human promyelocytic HL60 cells to study the binding of radioiodinated human ferritin in vitro. Specific binding of human heart ferritin could be demonstrated at 37 degrees C, whereas no binding of liver ferritin could be found. The uptake of labelled heart ferritin was abolished by incubation at 4 degrees C, by prior treatment of the HL60 cells with pronase and by the addition of human plasma to the medium. On the other hand, the addition of excess unlabelled human liver or rat liver ferritin had no effect on the uptake of labelled human heart ferritin. Dissociation studies showed that about 55% of the bound heart ferritin radioactivity could be released by incubation with medium alone and at least 90% with excess unlabelled heart ferritin. Over 70% of the dissociated ferritin could be precipitated with polyclonal anti-ferritin serum or trichloroacetic acid. More than two-thirds of the radioactivity which could not be released after washing in medium alone was recovered in the soluble intracellular fraction following cell lysis. Almost all of the soluble radioactivity could be precipitated with the polyclonal antiserum, indicating that very little lysosomal degradation of internalized heart ferritin had occurred. The present studies demonstrate a protein-mediated binding mechanism for acidic isoferritins on HL60 cells. These observations agree with published evidence that ferritin is often associated with cell membranes and are consistent with a possible role for the protein in the regulation of haematopoiesis or in iron transfer.
Cell Line↗
Erroneous electrolyte results caused by catheters.
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Blood Specimen Collection↗
Stability of radioiodinated ferritin.
Ferritin which had been radioiodinated using chloramine T exhibited marked instability on storage at 4 degrees C. Both [125I]human liver and heart ferritins showed a similar rate of decline in immunoreactivity (t 1/2 = 20-23 days) indicating that deterioration with storage was not a function of isoferritin composition. The decrease in radioactivity associated with ferritin was due not only to loss of 125I from the molecule but also to protein degradation as shown by enzyme-linked immunoassay and gel filtration. The degradation products had an Mr of at least 69,000 although low Mr material could be identified by gel filtration when a marked reduction in immunoreactivity had occurred. Ferritin instability was much more pronounced than when other proteins such as immunoglobulin and albumin were radioiodinated with chloramine T. These observations indicate that when performing in vivo and in vitro studies with labeled ferritin, degradation of the protein during storage should be carefully monitored and the protein repurified before use.
Antibodies↗
Mammalian folylpoly-gamma-glutamate synthetase. 4. In vitro and in vivo metabolism of folates and analogues and regulation of folate homeostasis.
The regulation of folate and folate analogue metabolism was studied in vitro by using purified hog liver folylpolyglutamate synthetase as a model system and in vivo in cultured mammalian cells. The types of folylpolyglutamates that accumulate in vivo in hog liver, and changes in cellular folate levels and folylpolyglutamate distributions caused by physiological and nutritional factors such as changes in growth rates and methionine, folate, and vitamin B12 status, can be mimicked in vitro by using purified enzyme. Folylpolyglutamate distributions can be explained solely in terms of the substrate specificity of folylpolyglutamate synthetase and can be modeled by using kinetic parameters obtained with purified enzyme. Low levels of folylpolyglutamate synthetase activity are normally required for the cellular metabolism of folates to retainable polyglutamate forms, and consequently folate retention and concentration, while higher levels of activity are required for the synthesis of the long chain length derivatives that are found in mammalian tissues. The synthesis of very long chain derivatives, which requires tetrahydrofolate polyglutamates as substrates, is a very slow process in vivo. The slow metabolism of 5-methyltetrahydrofolate to retainable polyglutamate forms causes the decreased tissue retention of folate in B12 deficiency. Although cellular folylpolyglutamate distributions change in response to nutritional and physiological modulations, it is unlikely that these changes play a regulatory role in one-carbon metabolism as folate distributions respond only slowly. 4-Aminofolates are metabolized to retainable forms at a slow rate compared to folates. Although folate accumulation by cells is not very responsive to changes in folylpolyglutamate synthetase levels and cellular glutamate concentrations, cellular accumulation of anti-folate agents would be highly responsive to any factor that changes the expression of folylpolyglutamate synthetase activity.
Animals↗
Use of capillary blood for the evaluation of iron status.
The accuracy and precision of measurements of iron status made on the capillary blood from a single 75 X 1-mm microhematocrit tube were evaluated in 301 normal volunteers. After recording the hematocrit value, a hematofluorometer was used to assay erythrocyte protoporphyrin directly on the packed red cell fraction. Values in the low normal range were 50-100% higher than assays by an extraction technique in simultaneously collected venous blood. However, measurements in the iron deficient range were only 12% greater. Plasma ferritin concentration was determined by using an enzyme-linked immunoassay on 10-microliters plasma retrieved after measuring the hematocrit. Capillary values were approximately 7% higher than venous concentrations, the proportional difference being consistent throughout the measured range. When the individual measurements were combined to calculate the iron storage status of each individual, the frequency distribution of iron stores in 141 female volunteers between 18 and 36 years of age was approximately Gaussian and paralleled that calculated for women aged 18-44 years in NHANES II. These studies demonstrate that iron status can be determined accurately from the measurement of hematocrit, erythrocyte protoporphyrin, and ferritin on a single microhematocrit tube of capillary blood.
Adolescent↗
Intestinal regulation of body iron.
A significant proportion of the world's population suffers from iron deficiency or iron overload. These disorders arise primarily from defects in the gastrointestinal absorption of iron. The intestinal mucosal cell plays a key role in this process because it lies at the interface between the gastrointestinal lumen which supplies its iron and body compartments which control its behaviour. The concentration of mucosal ferritin is closely linked to absorption, but it is still not clear whether it plays an active or a passive role. Transferrin also has been detected in the mucosal cell, but firm evidence that it participates in the absorptive process is lacking. Deficiencies in the luminal phase are responsible for the high global prevalence of iron deficiency which is predominantly dietary in origin. Much information has accumulated in recent years on dietary factors that enhance or impair iron absorption but their quantitative importance as determinants of iron status remains to be determined.
Humans↗