The effect of change in pH on the solubility of iron bis-glycinate chelate and other iron compounds.

The effect of a pH change from 2 to 6 was tested on the solubility of ferrous sulfate, ferrous fumarate, iron bis-glycine chelate (Ferrochel) and sodium-iron ethylenediaminetetraacetic acid (NaFeEDTA). It was found that at pH 2 ferrous sulfate, Ferrochel and NaFeEDTA were completely soluble and only 75% of iron from ferrous fumarate was soluble. When pH was raised to 6, iron from amino acid chelate and NaFeEDTA remained completely soluble while solubility from ferrous sulfate and ferrous fumarate decreased 64 and 74%, respectively compared to the amount of iron initially soluble at pH 2. These results suggest that iron solubility from iron bis-glycine chelate and NaFeEDTA is not affected by pH changes within the ranges tested, probably because iron remained associated to the respective compounds.

Iron bioavailability in humans from breakfasts enriched with iron bis-glycine chelate, phytates and polyphenols.

This study was conducted to determine the bioavailability of iron amino acid chelate (ferrochel) added to fortify breads prepared from either precooked corn flour or white wheat flour + cheese and margarine compared with the same basal breakfast enriched with either ferrous sulfate or iron-EDTA. The inhibitory effect of phytate and polyphenols on iron absorption from ferrochel was also tested. A total of 74 subjects were studied in five experiments. Iron absorption from ferrochel was about twice the absorption from ferrous sulfate (P: < 0.05). When ferrous sulfate and ferrochel were administered together or in different meals, absorption from ferrochel was about twice the absorption from ferrous sulfate (P: < 0.05). Polyphenols present in coffee and tea inhibited iron absorption in a dose-dependent manner. American-type coffee did not modify iron absorption significantly, whereas both espresso-type coffee and tea reduced iron absorption from ferrochel by 50% (P: < 0. 05). Ferrochel partially prevented the inhibitory effect of phytates. Because of its high solubility in aqueous solutions even at pH 6, its low interactions with food and high absorption, ferrochel is a suitable compound for food fortification.

New property of vitamin A and beta-carotene on human iron absorption: effect on phytate and polyphenols as inhibitors of iron absorption.

One hundred and seventy four human subjects were studied to find out the interaction of vitamin A or beta-carotene with the inhibitors of iron absorption, from a basal breakfast containing bread from either 100 g of precooked corn flour or 100 g of white wheat flour, 50 g of cheese and 10 g of margarine. Bread was labeled with either 55Fe or 59Fe. This bread was made from commercially flours fortified with iron as ferrous fumarate and vitamins. It was noticed that the percentage of iron absorption from the breakfast prepared with precooked corn flour given alone and with different concentrations of coffee was practically the same, while the iron absorption from the breakfast prepared from wheat flour decreased from 6% when the breakfast was given alone, to less than 2% when it was given with different concentrations of coffee. The only ingredient present in precooked corn flour and not in wheat flour was vitamin A. This difference encouraged the authors to perform further experiments using precooked corn and wheat flours fortified only with ferrous fumarate. These studies demonstrated that vitamin A inhibits the effect of the polyphenol and partially inhibits the effect phytate on iron absorption. HPLC and spectrophotometric studies demonstrated an interaction between vitamin A and iron. Other experiments, which included 100 volunteers, were performed to test the effect of vitamin A and beta-carotene on iron absorption from corn, wheat and rice. The presence of vitamin A increased iron absorption up to 3 times for rice, 2.4 times for wheat and 1.8 times for corn. beta-carotene increased absorption almost 3 times for the three cereals tested, showing that both compounds were capable of preventing the inhibitory effect of phytates on iron absorption. This information suggest that vitamin A and beta-carotene form a complex with iron keeping it soluble in the intestinal lumen and preventing the inhibitory effect of phytates and polyphenols on iron absorption.

Beta-carotene and inhibitors of iron absorption modify iron uptake by Caco-2 cells.

A National fortification program instituted in Venezuela in 1993 reduced iron deficiency and anemia by half in only 1 y. The fortification mixture contained ferrous fumarate, vitamin A and other vitamins. We conducted experiments to characterize ferrous fumarate uptake by Caco-2 cells. Increasing amounts of ferrous fumarate, vitamin A, phytate, tannic acid and beta-carotene were added to incubation mixtures using a range of concentrations that included the molar ratios used in the Venezuelan fortification program. Cells were incubated for 1 h at 37 degrees C with 37 kBq (59)Fe and the compound to be evaluated. They were then rinsed, trypsinized and counted to measure uptake. Effects of ascorbic acid, days in culture and use of flasks or inserts were also evaluated. Optimal conditions for uptake experiments were pH 5.5, in the presence of ascorbic acid and at 16 d in culture. Use of flasks or inserts did not affect uptake. Vitamin A did not significantly increase iron uptake under the experimental conditions employed. However, beta-carotene (6 micromol/L) significantly increased iron uptake compared to no beta-carotene addition (114.9 +/- 6.3 and 47.2 +/- 5.9 pmol/mg cell protein, respectively). Moreover, in the presence of phytates or tannic acid, beta-carotene generally overcame the inhibitory effects of both compounds depending on their concentrations. We conclude that beta-carotene improves iron uptake and overcomes the inhibition by potent inhibitors of iron absorption. These experiments also validated the usefulness of Caco-2 cell model system to evaluate iron metabolism.

[Anemia in indigenous population of the West of Venezuela]. / Anemia en poblaciones indígenas del occidente de Venezuela.

The purpose of the study was to investigate the frequency of nutritional anemia among western venezuelan indians. Three hundred and ninety nine Yucpa indians from the communities of Aroy, Marewa and Peraya were studied. The concentrations of hemoglobin, serum iron, total iron binding capacity, serum ferritin, serum folate and serum vitamin B12 and the frequency of anemia and nutrient deficiency were determined. Anemia was found in 71.7% of people from Aroy, 52.25 from Marewa and in 74.4% from Peraya. No nutrient deficiencies were found in 48.1% of cases with anemia, while iron deficiency anemia was present in 39% of the population studied, and folate and or vitamin B12 deficiency were associated with anemia in only 12.9% of cases. The high frequency of anemia, unrelated to nutrient deficiency, among the Yucpa indians, is attributed to the prevalence of chronic infectious diseases such as hepatitis and parasitic infections, as well as skin and respiratory infectious processes.

[Iron deficiency towards the year 2000]. / Deficiencia de hierro hacia el año 2000.

This is a non-comprehensive overview of the latest 50 years about the evolution of iron metabolism and the methodology we currently have for the diagnosis of iron deficiency and its effects on human health. In the 40's iron absorption was determined by chemistry. The amount of iron absorbed was calculated as the difference between dietary iron and excreted iron. The other methods used to measure dietary iron was hemoglobin repletion. In the 70's the measurement of plasmatic ferritin was an important contribution to iron metabolism to assess iron deficiency and iron overload. In the same decade the extrinsic and intrinsic labelled methodology was an important advancement. The 70's and 80's were years where scientists aimed at finding iron absorption inhibitors, namely coffee, calcium, tea, zinc and fiber. The 80's and 90's were characterized for the emerging knowledge an iron absorption from a food, a meal and a complete diet and for the favorable effect of food iron fortification in developing countries. Also for the effect of iron excess in overall health and myocardial infarction in developed countries were studied.

Vitamin A and beta-carotene can improve nonheme iron absorption from rice, wheat and corn by humans.

After the rapid decrease in the prevalence of iron deficiency and iron-deficiency anemia in the Venezuelan population when a national program for fortification of flours with iron and vitamins was instituted, we studied micronutrient interactions in Venezuelan diets. One hundred human adults were fed three cereal-based diets, labelled with either 59Fe or 55Fe in six studies. Each diet contained different concentrations of vitamin A (from 0.37 to 2.78 micromol/100 g cereal) or beta-carotene (from 0.58 to 2.06 micromol/100 g cereal). The presence of vitamin A increased iron absorption up to twofold for rice, 0.8-fold for wheat and 1.4-fold for corn. beta-carotene increased absorption more than threefold for rice and 1.8-fold for wheat and corn, suggesting that both compounds prevented the inhibitory effect of phytates on iron absorption. Increasing the doses of vitamin A or beta-carotene did not further significantly increase iron absorption. We measured the iron remaining in solution performing in vitro studies in which the pH of solutions was adjusted from 2 to 6 in the presence of vitamin A or beta-carotene. All of the iron from ferrous fumarate was soluble after changing the pH of the solution containing 3.4 micromol of beta-carotene to 6.0. Vitamin A was less effective. However, 78 +/- 18% of iron was soluble in the presence of 3.3 micromol of vitamin A, whereas with no vitamin addition, only 26 +/- 13% of iron was soluble (<0.05). Vitamin A and beta-carotene may form a complex with iron, keeping it soluble in the intestinal lumen and preventing the inhibitory effect of phytates and polyphenols on iron absorption.

[Dietary iron absorption. Role of vitamin A]. / Absorción del hierro de los alimentos. Papel de la vitamina A.

Iron and vitamin A are essential nutrients for human growing, development and maintenance. Deficiency of these elements is a public health problem especially in developing countries. Recently it has been reported that vitamin A has a favorable effect on iron absorption, probably due to the formation of an iron-vitamin A chelate, that keeps iron soluble and available for absorption. This vitamin establishes a competence with other iron-binding molecules (phytates and polyphenols) that are not absorbed and render insoluble iron. Food enrichment programs with both iron and vitamin A, will provide these two essential nutrients and also an enhanced iron absorption even from diets with a high content of inhibitors.

Strategies for the prevention of iron deficiency through foods in the household.

Iron deficiency can be caused not only by diets deficient in iron but by poor absorption of available dietary iron. Extrinsically tagging foods with radioiron allows the exact measurement of iron absorbed from heme and nonheme iron foods. It has furthered the study of the effect of enhancers and inhibitors of iron absorption. As a result, we have a greater understanding of why iron deficiency and iron deficiency anemia are prevalent in populations of low socioeconomic status and of which food vehicles and iron compounds are most suitable for iron fortification.

Prevalence of anemia, iron, folic acid and vitamin B12 deficiency in two Bari Indian communities from western Venezuela.

The hematological status of 406 Bari indians from two communities was studied. One hundred and seventy nine individuals were from Campo Rosario a village located in a low arid plain south to the Perijá mountain range and 287 were from Saimadoyi, a fertile valley in the heart of the mountain. Anemia was found in 54% and 31% of the people from Campo Rosario and Saimadoyi respectively. Low serum iron was present in 28% of the population in both communities while low serum ferritin levels were encountered in 20% of the population from Campo Rosario and 5% of the people from Saimadoyi. A high prevalence of serum folate and vitamin B12 deficiency (91% and 64% respectively) was found in Campo Rosario, in contrast only 5% of the population from Saimadoyi had low folate and none were vitamin B12 deficient. While there was a positive significant correlation between hemoglobin and serum iron concentrations (r = 0.517, p < 0.001), no significative correlation was found between the other parameters studied. The high prevalence of anemia and nutrient deficiency among the Bari indians, can be attributed to inadequate diets and the varied diseases encountered in the population.

Early response to the effect of iron fortification in the Venezuelan population.

In Venezuela a severe economic crisis beginning in 1983 provoked a progressive reduction of the quality and quantity of food consumed by the low socioeconomic strata of the population. In these strata, which represent > or = 80% of the Venezuelan population, we had seen a continuous increase in the prevalence of iron deficiency during that recent decade. As a result, in 1993 the Venezuela Government created the Special Commission for Enrichment of Foods. That same year a fortification program began in which precooked yellow and white maize and wheat flours were enriched with 20 and 50 mg Fe (as ferrous fumarate)/kg flour, respectively. The corn flour was also enriched with vitamin A, thiamine, riboflavin, and niacin, whereas the wheat flour was enriched with these same vitamins, except vitamin A. These two cereals represent 45% of the total energy consumed daily by the low socioeconomic strata of the population. A preliminary survey carried out in Caracas in 1994 in a population of 307 children aged 7, 11, and 15 y showed that the prevalence of iron deficiency determined by measuring the serum ferritin concentration and the prevalence of anemia were reduced from 37% and 19%, respectively, in 1992 to 15% and 10%, respectively in 1994.

Fortification of precooked maize flour with coarse defatted maize germ.

The possibility of improving the dietary value of precooked maize flour through fortification with 11% coarse defatted maize germ was investigated. The results of tests in humans presented here show that the total iron absorption from the fortified preparation is similar to that from the precooked maize alone, but with the advantage of being richer in several nutrients: protein (25%), zinc (61%), potassium (47%) and magnesium (112%), as well as fiber (34%). Fortification lowers (by 20%) rather than raises the cost of the flour, and may be an important contribution to the diet of those populations where maize bread is a major component of the diet.

The relationship between iron deficiency and anemia in Venezuelan children.

The iron status of 3228 subjects from the nutrition survey Proyecto Venezuela was studied. The sample included children from 1 to 16 y of age grouped by age and sex. Values for three indicators of iron status were compared: hemoglobin concentration, serum ferritin concentration, and percentage saturation of serum transferrin. In all groups there was a strong overlap in the hemoglobin concentration distribution curves for non-iron-deficient and iron-deficient subjects classified as such according to the other two indexes. The prevalence of iron deficiency ranged from 35% in 1-3 y olds to 10% in adolescent males, the values being almost identical in the nonanemic group compared with the total population. In the different groups, 80-97% of the subjects with abnormal values of at least one of these two indexes were not anemic. The difficulties involved in establishing a state of iron deficiency according to these indexes are discussed.

Relationships among iron absorption, percent saturation of plasma transferrin and serum ferritin concentration in humans.

The percent absorption of iron from four dietary sources was compared in 2018 human subjects with three indicators of iron status, serum ferritin concentration, percent saturation of plasma transferrin and iron absorption from a reference dose of ferrous sulfate. Higher correlation coefficients (r) were obtained by comparing dietary iron absorption with the reference dose absorption rather than with serum ferritin; for example, r = +0.61 and r = -0.38, respectively, for a meat and vegetable meal. However, in practice serum ferritin is almost as efficient as the reference dose absorption in estimating dietary iron absorption, because the 95% confidence limits calculated from the regression equations were very similar. The values of r calculated for iron absorption versus transferrin saturation were comparable to those obtained with the other indicators only in the range of transferrin saturation values below 25%, whereas in more iron-replete subjects (transferrin saturation greater than 25%), this correlation virtually disappeared. This indicates that, although both serum ferritin and transferrin saturation reflect iron status in iron-depleted subjects, the control of iron absorption in iron-replete subjects is more dependent on iron stores as reflected in the serum ferritin concentration than the percent saturation of transferrin.

[Requirements of nutrients which participate in erythropoiesis]. / Requerimientos de nutrientes que participan en la eritropoyesis.

Proteins, some minerals and vitamins, play important roles in erythropoiesis and the survival of the red blood cell. This article deals specifically with the physiological requirements and recommended intakes of iron, folate and vitamin B12. A comparison of the physiologic iron requirements according to age and sex, and the amount of iron which is actually absorbed from the diets consumed by the lower socioeconomic strata of the Venezuelan population; indicates that these diets do not satisfy the requirements at all ages. Such disparity is most marked in children below three years of age, in adolescents and in women during their reproductive age. Failure to do so leads to varying degrees of iron deficiency. This low bioavailability of the Venezuelan diet is also observed in other Latin American diets consumed by the same low socioeconomic strata, which explains the high prevalence of iron-deficiency anemia in the vulnerable groups. The low intake of fruits and vegetables by the lower socioeconomic strata of the Latin American population prevents these sectors from consuming an adequate intake of folate, failing to fulfill the daily recommended intake (3.3 - 3.6 micrograms/kg body weight). This situation is aggravated in pregnant and lactating women who require an additional intake of 300 micrograms and 100 micrograms, respectively. Prevalence of folate deficiency in the first stage may be in the order of 30% in some regions. In the second stage of deficiency, characterized by megaloblastic changes in the bone marrow and an erythrocyte folate concentration of less than 50 micrograms/lt, it could be as high as 40% in pregnant women. Nutritional vitamin B12 deficiency does not constitute a health problem in Latin America. Various surveys in the lower socioeconomic strata have reported normal or higher than normal serum B12 concentrations, compared to well-nourished populations.

Daily physiological iron requirements in children.

Median daily iron absorption was determined in iron-replete males and females between 2 and 19 years of age from the upper and lower socioeconomic strata of the Venezuelan population. A comparison was made with iron absorption of well-nourished children, on the basis of hematological and anthropometric reference values from the U.S. The median absorption level, which was calculated from the increase in total body iron due to growth and the daily losses through exfoliation and menstruation, was also used to estimate the requirements of 95% of the population. When the requirements were expressed in terms of body weight, no significant difference in iron absorption was observed between the three Venezuelan and one U.S. groups, ranging from about 30 to 38 micrograms/kg/day in both sexes between 4 and 16 years of age. However, when the requirements were expressed without division by the weight factor, the requirements of the better nourished groups were somewhat higher than those of the Venezuelan lower socioeconomic population with, in addition, a threefold variation over the 5 to 16 year age range. These findings suggest that the total iron requirements of children at a certain age may be most adequately expressed in terms of the optimal body weight for that age.

Iron and transferrin uptake by phytohemagglutinin-stimulated human peripheral blood lymphocytes.

Iron (Fe) and transferrin (TF) uptake by human peripheral blood lymphocytes stimulated in vitro with phytohemagglutinin was measured. Pulses of 59FeTF or 125I-TF were added to the cultures either at time 0 or 8 hr before the end of a 72-hr incubation. In time-course experiments, peak iron and transferrin uptake coincided with the peak of tritiated thymidine uptake taken as a measure of cellular activation. Iron, but not transferrin, was accumulated by the cells. Non-linear relationships existed between both iron and transferrin uptake and the degree of activation. Both rose markedly above basal levels only at a level of activation at least 50% of the maximum observed. The results suggest that although iron utilization is related to cellular activity, the uptake mechanism is only activated when an increased iron metabolism has exhausted internal stores.

Lymphocyte activation, iron uptake and release by human mononuclear leukocytes in the presence of desferrioxamine.

Desferrioxamine (DFO), an iron chelating drug, has been shown to inhibit the proliferative response of leukocytes to mitogen. In the present study we investigated the effect of DFO on different aspects of human mononuclear leukocyte (MNL) function in vitro. DFO, added at the beginning of the culture period, inhibited both tritiated thymidine and radioiron uptake by phytohemagglutinin-stimulated MNL and the degree of inhibition correlated with the degree of cellular activation, to the extent that in the absence of mitogen a significant stimulatory effect of DFO was observed, especially when iron supplement was present in the culture medium. However DFO was not found to inhibit iron uptake directly, and relatively low concentrations of iron as iron-transferrin totally reversed the inhibitory action of DFO on thymidine uptake. Although the release of iron from preloaded MNL in the presence of DFO was only 15% greater than the spontaneous release of control cultures, we conclude that the site of action of DFO is an intracellular iron pool, that increases in importance when the supply of iron to the cellular iron metabolism become limiting as in optimally activated MNL.