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Biomedical subjects

R W Charlton

Publications and source records attributed to R W Charlton.

At least 19 recordsLinked to original sources

Factors affecting the absorption of iron from cereals.

Non-haem-iron absorption from a variety of cereal and fibre meals was measured in parous Indian women, using the erythrocyte utilization of radioactive Fe method. The present study was undertaken to establish whether alteration of the phytate and polyphenol contents of sorghum (Sorghum vulgare) affected Fe absorption from sorghum meals, and to assess the influence of fibre on Fe absorption. Removing the outer layers of sorghum grain by pearling reduced the polyphenol and phytate contents by 96 and 92% respectively. This treatment significantly increased the geometric mean Fe absorption from 0.017 to 0.035 (t 3.9, P less than 0.005). The geometric mean Fe absorption from a sorghum cultivar that lacked polyphenols (albino sorghum) was 0.043, which was significantly greater than the 0.019 absorbed from bird-proof sorghum, a cultivar with a high polyphenol content (t 2.83, P less than 0.05). Fe was less well absorbed from the phytate-rich pearlings of the albino sorghum than from the pearled albino sorghum (0.015 v. 0.035 (t 8.4, P less than 0.0005]. Addition of sodium phytate to a highly Fe-bioavailable broccoli (Brassica oleracea) meal reduced Fe absorption from 0.185 to 0.037. The geometric mean Fe absorption from malted sorghum porridge was 0.024 when 9.5 mg ascorbic acid were added and 0.094 when the ascorbic acid was increased to 50 mg (t 3.33, P less than 0.005). This enhancing effect of 50 mg ascorbic acid was significantly depressed to 0.04 by tea (t 38.1, P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic Acid

The relative dietary importance of haem and non-haem iron.

A study was undertaken to find out the relative amounts of haem and non-haem iron absorbed from meals in which varying amounts of these substances were present. Four meals, each containing 6 mg of iron but with varying ratios of haem and non-haem iron, were fed to two groups of subjects, each group receiving two meals. The geometric mean percentage absorption of non-haem iron decreased from 18.0% (SD range 14.6-22.3%) to 6.4% (SD range 3.4-11.8%) as the non-haem iron content of the meal increased from 1.52 mg to 5.72 mg--there was therefore little variation in the actual amounts of non-haem iron absorbed from the different meals. In contrast, the geometric mean absorption of haem iron was approximately 20% from all four meals, although the haem iron content varied between 0.28 mg and 4.48 mg. The amount of haem iron absorbed was thus a linear function of the amount of haem iron in the meal. Two points emerged from the study. Firstly, the relative importance of haem iron in overall iron nutrition was confirmed. Secondly, the fact that the pattern of absorption in relation to dosage was so different for haem iron and non-haem iron suggested that a controlling mechanism for non-haem iron absorption may be located at the mucosal surface. This conclusion is based on the fact that haem iron, the percentage absorption of which was found to be independent of the size of the dose, is absorbed into the mucosal cell when still contained within the porphyrin ring and the iron thus bypasses some controlling mechanism at the mucosal border.

Diet

Iron absorption.

The rate of absorption of iron is adjusted according to body iron requirements, but the virtual absence of heme and the poor bioavailability of the nonheme iron in the diets of many people, especially in developing countries, means that the amount that can be absorbed is limited. Those whose requirements are increased by growth, menstruation, or pregnancy frequently cannot absorb enough. Sufficient is now known about the factors in food that increase or diminish the bioavailability of nonheme iron to permit the effective fortification of dietary staples, although the application of this information has proved difficult particularly in the Third World where nutritional iron deficiency is most prevalent. Effective fortification may lead to iron overload in those whose control of iron absorption is genetically defective, and recent evidence that the HLA-linked recessive gene for idiopathic hemochromatosis may occur much more commonly than hitherto suspected makes it imperative that an effective monitoring system should form a part of every fortification program.

Adult

Iron absorption from ferritin and ferric hydroxide.

Ferritin and ferric hydroxide represent two forms of iron which are less available for absorption than that present in the 'common pool' of non-haem dietary iron. In the present study the absorption of iron from these two compounds was compared in 35 multiparous women when fed in water, in maize porridge and in maize porridge containing 100 mg ascorbic acid. The geometric mean absorption for 3 mg ferritin iron was 0.7% and for ferric hydroxide, 2.4%. Comparable figures when fed with maize porridge were 0.4% and 0.4% respectively. When 100 mg ascorbic acid was present in the porridge, absorption was enhanced from both sources, being 12.1% for ferritin and 10.5% for ferric hydroxide. These results indicate that the fraction of iron in ferritin and ferric hydroxide that enters the 'common pool' of non-haem dietary iron is profoundly influenced by the nature of the diet. The greater the concentration of enhancing ligands, the closer does the absorption of iron from these compounds approximate that of the non-haem dietary iron pool.

Adult

Iron nutrition in Indian women at different ages.

The iron status of 320 Indian women living in Chatsworth, Durban, who had volunteered for iron absorption studies, was assessed using a number of measurements. These included: radio-iron absorption, the transferrin saturation, the serum ferritin concentration and the haemoglobin concentration. In the sample as a whole, the prevalence of iron deficiency anaemia (haemoglobin concentration less than 12 g/dl, with two or more abnormal measurements of iron status) was 14,4%. A further 26% had depleted iron stores (serum ferritin less than 12 micrograms/l) and 8,4% also had evidence of iron-deficient erythropoiesis (serum ferritin less than 12 micrograms/l and transferrin saturation below 16%). A profile of iron status based on the cumulative frequency distribution of iron stores showed that the sample, with calculated median iron stores of 150 mg and lower and upper 10 percentiles of -355 mg and 655 mg respectively, was significantly more iron deficient than a sample of women studied in Washington State, USA. Of interest was the observation that all measurements of iron status were better in the older age groups, presumably as a result of the cessation of menstruation. In addition, there was evidence that the duration of menstruation, as volunteered in a brief history, had a significant effect on several measurements of iron status. This was particularly true of the serum ferritin concentration and radio-iron absorption, both of which reflect the size of the iron stores.

Adult

Effect of diet on the rate of iron accumulation in idiopathic haemochromatosis.

There is still controversy concerning the effects of increasing the dietary intake of iron on iron nutrition. This debate has not only centered on the question of efficacy but also on that of safety. At particular potential risk are those individuals with disorders such as idiopathic haemochromatosis, who absorb iron excessively from the diet. Data obtained in the present study and in several other investigations suggest that subjects homozygous for the mutant gene responsible for the disorder would develop clinical features of the disease at a younger age were the dietary iron intake to be increased. Iron stores in affected heterozygotes would increase but the size of the stores would probably equilibrate long before they had reached massive proportions. While these conclusions are drawn from a number of studies, there are enough unanswered questions to make it mandatory for any future fortification programmes, whether they be directed at the entire population or only at certain segments of it, to be carefully monitored. This can currently be achieved with serial plasma ferritin measurements, since the concentrations mirror the size of iron stores in the body.

Absorption

Factors affecting the absorption of iron from Fe(III)EDTA.

1. The modification of iron absorption from Fe(III)EDTA by agents known to promote or inhibit absorption was examined in 101 volunteer multiparous Indian women. Fe absorption from Fe(III)EDTA was compared with absorption of intrinsic food Fe in a further twenty-eight subjects. Finally the urinary excretion of radio-Fe after oral administration of 59Fe(III)EDTA was studied in twenty-four subjects and evidence of intraluminal exchange of Fe was examined. 2. Fe absorption from maize porridge fortified with Fe(III)EDTA was more than twice that from porridge fortified with FeSO4 . 7H2O. 3. Although bran decreased Fe absorption from FeSO4 . 7H2O approximately 11-fold, it had no significant effect on Fe absorption from Fe(III)EDTA. Nevertheless tea, which is a more potent inhibitor of Fe absorption, decreased absorption from Fe(III)EDTA 7-fold. 4. Fe absorption from Fe(III)EDTA given in water was only increased 40% by addition of 3 mol ascorbic acid/mol Fe but by 7-fold when the relative proportions were increased to 6:1. This enhancing effect was blunted when the Fe(III)EDTA was given with maize porridge. In these circumstances, an ascorbate:iron value of 3:1 (which doubles absorption from FeSO4 . 7H2O) produced no significant increase in Fe absorption, while a value of 6:1 produced only a 2 . 5-fold increase. 5. Fe absorption from Fe(III)EDTA was not altered by addition of maize porridge unless ascorbic acid was present. 6. Less than 1% of 59Fe administered as 59Fe(III)EDTA was excreted in the urine and there was no inverse relationship between Fe absorption and the amounts excreted (r 0 . 58, P less than 0 . 05). 7. Isotope exchange between 59Fe(III)EDTA and 59FeSO4 . 7H2O was demonstrated by finding a similar relative value for the two isotopes in urine and erythrocytes when the two labelled compounds were given together orally. This finding was confirmed by in vitro studies, which showed enhanced 59Fe solubilization from 59FeSO4 . 7H2O in maize porridge when unlabelled Fe(III)EDTA was added. 8. Although Fe absorption from Fe(III)EDTA was marginally higher it appeared to form a common pool with intrinsic food iron in most studies. It is postulated that the mechanism whereby Fe(III)EDTA forms a common pool with intrinsic food Fe differs from that occurring with simple Fe salts. When Fe is present in the chelated form it remains in solution and is relatively well absorbed because it is protected from inhibitory ligands. Simple Fe salts, however, are not similarly protected and are absorbed as poorly as the intrinsic food Fe. 9. It is concluded that Fe(III)EDTA may be a useful compound for food fortification of cereals because the Fe is well absorbed and utilized for haemoglobin synthesis. The substances in cereals which inhibit absorption of simple Fe salts do not appear to inhibit absorption of Fe from Fe(III)EDTA.

Adult

Mobilisation of iron from peritoneal rat macrophages by desferrioxamine.

The amount of radioiron released from rat peritoneal macrophages after phagocytosis of 59Fe labelled erythrocytes can be enhanced by addition of desferrioxamine. The effect is dose dependent and the iron chelated by desferrioxamine appears to be at the expense of ferritin. However, desferrioxamine does not appear to chelate iron already incorporated into ferritin. It seems likely that the iron comes from a labile chelatable pool through which the iron from haemoglobin catabolism passes before being incorporated into ferritin. The desferrioxamine appears to enter the macrophage and chelate iron to form ferrioxamine which subsequently leaves the macrophage. In vivo it was not possible to show substantial iron chelaton by desferrioxamine in rats when 59Fe labelled non-viable red cells were injected intravenously. This suggests that in vivo mobilization of reticuloendothelial iron by desferrioxamine may be of limited significance.

Animals

Equilibration of tracer radioiron with body iron.

1. The degree to which a tracer quantity of 55Fe bound to transferrin and introduced into the plasma 36 months previously had equilibrated with the body iron was studied in a subject who was phlebotomized repeatedly until iron-deficiency anaemia developed. 2. Analysis of the results with two mathematical models showed that equilibration with haemoglobin iron and storage iron was complete. 3. Estimates of the quantity of iron initially stored in the body by three different methods yielded values of 37.3, 33.1 and 34.8 mmol. 4. Since the previously determined mean initial plasma ferritin concentration was 185 micrograms/1 (462 pmol/1), there was 0.179-0.197 mmol of stored iron per 1 microgram of plasma ferritin/1. 5. The study suggests that the assumption on which currently accepted values for daily body iron loss were calculated is valid.

Anemia, Hypochromic

Iron absorption from maize (Zea mays) and sorghum (Sorghum vulgare) beer.

1. Iron absorption from maize (Zea mays) and sorghum (Sorghum vulgare) beer was more than twelve-fold greater than from a gruel made from the constituents used to prepare the beer. 2. The effect of changes occurring during brewing were investigated. These changes include a decrease in the solid content, and the formation of 30 ml ethanol/1 and 5 ml lactic acid/1. 3. The presence of solid material was found to inhibit Fe absorption markedly, especially when the solid content was 100 g/l or more. 4. The presence of ethanol potentiated Fe absorption but the effect was only modest in gruels with a high solid content. 5. Fe absorption from a 2 ml lactic acid/l solution was four-fold greater than from a hydrochloric acid solution of the same pH. When lactic acid was added to a gruel containing 200 g solids/l the mean absorbtion rose from 0.4 to 1.2 %. 6. In a direct comparison, Fe absorption from beer was significantly better than from a gruel of similar pH containing lactic acid. 7. The results suggest that at least three factors are responsible for the enhanced Fe absorption from maize and sorghum beer. These include the removal of solids during fermentation and the presence of ethanol and of lactic acid in the final brew. 8. In order to reproduce the way in which beer is brewed domestically in Fe containers, a study was done in which beer was prepared in the presence of Fe wire. Under such circumstances Fe was rapidly dissolved and the final Fe concentration of the brew was 89 mg/l. However, the nature of the Fe-containing compound or compounds was not elucidated.

Beer

The relationship between maternal and infant iron status.

Serum ferritin, iron and haemoglobin (Hb) concentrations were determined in 103 pregnant women and in the cord of their normal full-term offspring. In 50 of the cases the placental non-haem iron was also measured. The correlations between serum ferritin concentration and other measurements of iron status were similar in both maternal and cord blood suggesting that cord serum ferritin concentration may, as in adults, reflect neonatal iron stores. The inverse relationship found between cord serum ferritin and hb concentrations (r = -0.35, P less than 0.001) suggests that the amount of iron in foetal stores is influenced by that required for Hb. When Hb levels are elevated, as was demonstrated in babies of older mothers, significantly lower serum ferritin were found. Thus a low cord serum ferritin concentration does not necessarily indicate that less iron was transferred to the foetus. Maternal iron reserve, as reflected by serum ferritin concentration, was shown to be related to the amount of non-haem iron in the placenta (r = 0.41, P less than 0.005), but this iron does not seem to form part of foetal iron stores as it does not correlate with measurements of foetal iron status. A week correlation between cord and maternal serum ferritin concentrations was demonstrated (r = 0.21, P less than 0.05) but its biological significance is questionable.

Adolescent

Importance of ascorbic acid in the absorption of iron from infant foods.

The absorption of fortification iron from an infant milk formula and from 3 infant cereals was studied in 121 multiparous women. The mean absorption was less than 3.2% when no added ascorbic acid was present. The nature of the iron compound added to infant cereals did not seem to influence the amount absorbed. Absorption was significantly improved when ascorbic acid was added, the mean increase being threefold with an iron:ascorbic ratio of 1:1.5 molar and more than sixfold with a ratio of 1:3 molar (about 10 mg ascorbic acid per mg iron).

Adult

Serum ferritin concentrations in black miners.

Serum ferritin concentrations were measured in 651 Black male miners who originated from rural areas throughout southern Africa and who were aged between 17 and 57 years. The mean serum ferritin concentration of 229 microgram/l was above the normal range reported for White subjects, and in 52,8% of the subjects the values were greater than 200 microgram/l. The serum ferritin concentration rose with age, as did the proportion of subjects in each age group who exhibited high values (more than 200 microgram/l). The lowest mean ferritin concentration (112 microgram/l) as well as the lowest proportion of high values (22,9%) were found in subjects from the most northerly area studied. Similarly, the highest mean proportion of high values (66,3%) was seen in the most southerly group studied. Calculations from the present data suggest that the degree of iron overload is currently greater in rural than in urban Black male subjects.

Adult