Mónica Orozco

Oral Administration of Ferrous Sulfate, but not of Iron Polymaltose or Sodium Iron Ethylenediaminetetraacetic Acid (NaFeEDTA), Results in a Substantial Increase of Non-Transferrin-Bound Iron in Healthy Iron-Adequate Men:

Background Oral iron supplementation with ferrous sulfate (FeSO4) at dosage levels suggested by the international guidelines poses a safety hazard to young children with malaria. Exposure to loosely bound iron in the circulation has been advanced as a potential factor. Objective To evaluate the kinetics of circulating concentrations of plasma iron and non-transferrin-bound iron (NTBI) in response to oral iron administration in healthy adults. Methods Plasma samples were collected at 90-minute intervals over a period of 270 minutes from 10 healthy Guatemalan men after oral administration of water or 100 mg of iron from each of three iron compounds: FeSO4, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), and iron polymaltose. The four tests were administered in an individually randomized sequence. Serum iron concentration was measured spectrophotometrically by the ferrozine method, and NTBI concentration was measured by a fluorometric competitive binding assay. The kinetic response and the maximal and cumulative changes in circulating concentrations of the biomarkers of interest were compared. Results Serum iron and NTBI responses to oral administration of FeSO4 were significantly greater than responses to plain water or the other two iron compounds. NTBI concentrations after NaFeEDTA or iron polymaltose ingestion were not different from those determined after water intake. Conclusions Administration of two iron compounds of proven bioavailability, but with complex absorption characteristics, is associated with a negligible NTBI response, potentially mitigating the safety concerns associated with iron supplementation in malarial areas.

Antioxidant-rich oral supplements attenuate the effects of oral iron on in situ oxidation susceptibility of human feces.

Prophylactic doses of 120 mg of iron (Fe) are commonly used to prevent Fe-deficiency anemia in vulnerable populations, especially in developing countries. Evidence shows that residual Fe in the large bowel may alter the normal antioxidant capacity of the fecal stream. Our objective was to evaluate the effect of dietary antioxidants from the Carotino Tocotrienol-Carotene Mixed Concentrate (CTCMC) on the depletion of fecal antioxidant capacity by oral Fe supplementation. In total, 17 healthy male adults participated in the 2 phases of the study, 5 in the pilot study and 12 in the definitive intervention trial. Participants received different treatments, separated by washout periods. These included: 120 mg Fe; 120 mg Fe and refined palm oil (FeOil); and 120 mg Fe in refined palm oil combined with 1 of 2 dosages (0.4 g and 0.8 g) of CTCMC/5 mL of refined palm oil (CTCB and CTCA treatments, respectively). Fecal samples were collected and analyzed to quantify the products of hydroxyl radical attack on salicylic acid (2,5 dihydroxybenzoic acid, 2,3-dihydrobenzoic acid, and catechol) at baseline and after active supplementation. Fe supplementation in either form (Fe or FeOil treatments) increased the concentrations of hydroxylated compounds in fecal samples. The production of hydroxylated compounds was significantly lower in treatments CTCB and CTCA than in the FeOil reference. Baseline antioxidant capacity state was virtually restored with dietary carotenoids and tocotrienols from the CTCMC. In conclusion, dietary antioxidants can reverse the depletion of fecal antioxidant capacity induced by oral Fe supplements.

Iron metabolism in obesity: How interaction between homoeostatic mechanisms can interfere with their original purpose. Part I: Underlying homoeostatic mechanisms of energy storage and iron metabolisms and their interaction

Adipose tissue plasticity mediated by inflammation is an important evolutionary achievement to survive seasonal climate changes. It permits to store excessive calories and to release them if required, using inflammatory cells to remove the debris. This process is regulated by a complex interaction of cytokines (TNF-α, IL-6), adipokines (adiponectin, apelin, liptin), adhesion molecules (ICAM-1, VCAM-1, E-selectin) and transcription factors (NF-κB, HIF-1α). Iron mediates electron transfer as an essential component of e.g. myeloperoxidase, hemoglobin, cytochrome C and ribonucleotide reductase. Conversely, unbound iron can catalyze oxidation of lipids, proteins, and DNA. To balance the essential with the potentially toxic function requires an efficient iron homoeostasis. This is mediated by hepcidins interaction with the iron-exporter ferroportin, to adapt intestinal iron absorption and body iron-sequestration to changes in demand. In addition, the interaction of iron-responsive elements (IRE) and iron-responsive proteins (IRP), the IRE/IRP-mechanism, regulates cellular iron homoeostasis. Obesity-induced inflammation interacts with both these mechanisms and disturbs iron availability by impairing its absorption, and by sequestering it in the reticuloendothelial system. Both mechanisms lead to anemia and reduce physical fitness which, in a vicious cycle, can support the development of pathological obesity. Thus, interaction between these two sets of beneficial regulatory mechanisms can become detrimental in situations of ample calorie supply.

Differences in circulating non-transferrin-bound iron after oral administration of ferrous sulfate, sodium iron EDTA, or iron polymaltose in women with marginal iron stores.

Background The adverse interactions between iron supplements and malaria have driven the assessment of new therapeutic options for anemia prophylaxis in areas holoendemic for falciparum malaria. Objective To determine the responses of circulating non-transferrin-bound iron (NTBI) and plasma iron to three different oral iron compounds—ferrous sulfate, sodium iron ethylenediaminetetraacetate (NaFeEDTA), and iron polymaltose (IPM)—in women with marginal iron stores. Methods Serum samples from 10 Guatemalan women with marginal iron stores were collected every 90 minutes over a period of 270 minutes, after the individually randomized administration of 100 mg of iron from each of the three studied iron compounds or water alone. Serum iron concentration was quantified by the ferrozine method, and circulating NTBI concentration was determined with a fluorometric competitive binding assay. Kinetic responses and maximal cumulative changes in serum concentrations of iron and NTBI were compared between the four treatments. Comparison was made with data from the same protocol in iron-adequate men. Results The serum iron and NTBI responses to ferrous sulfate were significantly greater than those to water and the other two iron compounds. Serum iron responses to IPM did not differ from those to water alone. Conclusions The administration of the two “slow-release” iron compounds, NaFeEDTA and IPM, resulted in a highly significant suppression of the appearance of NTBI in the circulation in the postsupplement period. These two bioavailable forms of iron supplement could represent a safe option for supplementation in malarial areas. The slope of the iron—NTBI relationship is steeper in men than in women.

Food variety, dietary diversity, and food characteristics among convenience samples of Guatemalan women

OBJECTIVE To compare variety and diversity patterns and dietary characteristics in Guatemalan women. MATERIAL AND METHODS Two non-consecutive 24-h recalls were conducted in convenience samples of 20 rural Mayan women and 20 urban students. Diversity scores were computed using three food-group systems.Variety and diversity scores and dietary origin and characteristics were compared between settings using independent t-test or Mann-Whitney-U-test. RESULTS Dietary variety and diversity were generally greater in the urban sample when compared to the rural sample, depending on the number of days and food-group system used for evaluation.The diet was predominantly plant-based and composed of non-fortified food items in both areas.The rural diet was predominantly composed of traditional,non-processed foods. The urban diet was mostly based on non-traditional and processed items. CONCLUSION Considerations of intervention strategies for dietary improvement and health protection for the Guatemalan countryside should still rely on promotion and preservation of traditional food selection.

Equivalent Effects on Fecal Reactive Oxygen Species Generation with Oral Supplementation of Three Iron Compounds: Ferrous Sulfate, Sodium Iron EDTA and Iron Polymaltose

Background: In any context of iron supplementation in the prenatal prophylaxis or therapeutic dosage range, a large amount will remain unabsorbed and pass through the intestinal tract into the colonic digesta possibly causing increased oxidation. Aim: To compare the generation of fecal reactive oxygen species (ROS) in situ after daily consumption of 100 mg of elemental iron in three frequently used forms of iron supplements. Methods: Ten healthy, iron-repleted adult males were investigated before and during supplementation with three oral iron compounds: 100 mg of oral iron were given as ferrous sulfate, Na Fe-EDTA and iron polymaltose for 6 days to each subject in an individually stratified sequence. Stool samples were collected and analyzed for iron content and the in situ generation of fecal ROS. Results: Significant increases in fecal ROS generation were observed during oral iron supplementation. No statistical differences were seen in either residual concentrations of non-heme iron in stool or the level of fecal ROS generation between the three Fe compounds. There was, however, a significant association between the iron concentration in the stool and ROS generation. Conclusion: In spite of the differences in their chemical characteristics, none of the three distinct iron complexes reduced oxidative stress in the intestinal lumen.

FRESHWATER CRABS IN LAKE ATITLÁN, GUATEMALA: NOT A SINGLE-SPECIES FISHERY

Guatemala harbors a rich fauna of freshwater crabs of Pseudothelphusidae, consisting of 11 currently valid species in six genera. As far as we know, the only freshwater crab fishery in the Americas takes place in Lake Atitlan in Guatemala, and the species sustaining the artisanal crab fishery is supposedly Potamocarcinus guatemalensis (Rathbun, 1905). However, a close examination of the gonopods from specimens recently captured in Lake Atitlan revealed that they belonged to Raddaus bocourti (A. Milne-Edwards, 1866) and Potamocarcinus magnus (Rathbun, 1896). Another species, R. tuberculatus (Rathbun, 1897) has been reported from the surroundings of Lake Atitlan, but its occurrence in the lake itself remains to be confirmed. The presence of at least two freshwater crab species of two different genera has important implications for the management of this artisanal fishing activity, because local and regional authorities erroneously assumed to deal with a single-species fishery.

Response of urinary biomarkers of systemic oxidation to oral iron supplementation in healthy men.

Background Urinary biomarkers are used in assessment of severe, clinical oxidative stress. Little is known, however, about their diagnostic value within the normative range. Objective To evaluate the response of urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxy-2-deoxyguanosine (8-OHdG) as indicators of systemic oxidation in response to short-term oral iron and antioxidant supplementation. Methods Five healthy adult men participated in the pilot study phase and 12 in the definitive intervention trial. For 7 days each, separated by 12-day washouts, the subjects received different treatment regimens, consisting of 120 mg of iron, 120 mg of iron in refined palm oil, and 120 mg of iron in palm oil combined with one of the two doses of Carotino® Tocotrienol Carotene Mixed Concentrate (CTCMC). Creatinine-normalized urinary TBARS and 8-OHdG concentrations were quantified in samples taken from subjects with and without active supplementation. Temporal and correlative associations between TBARS and 8-OHdG were explored. Results Daily intake of supplemental iron failed to produce any increment in urinary excretion of TBARS or 8-OHdG. However, a significant within-individual correlation between the urinary biomarkers was observed (Spearman r = 0.697, p < .0001, n = 466). Both doses of CTCMC significantly lowered urinary excretion of both oxidation indicators. Conclusions Despite the lack of effect of oral iron on the biomarkers of systemic oxidation, they show a strong and significant mutual association within the nonpathological range of oxidative stress in healthy male adults.

Contribution of a novel high-density micronutrient condiment (HDMC) to nutrient adequacy of home-prepared Guatemalan dishes.

Background The diet of low-income Guatemalan populations is mostly plant-based, deficient in some vitamins and minerals, and rich in antinutritional compounds that reduce the bioavailability of several micronutrients. Objective To describe the manner in which low-income Guatemalan women in rural and urban settings would prepare dishes for main meals using a high-density multimicronutrient condiment (HDMC) and to compare the nutrient density and contribution to the recommended dietary allowance (RDA) of the dishes with and without added HDMC. Methods A sample of 30 women, 15 each from rural and urban households, were enrolled. The women were given 20 g of the HDMC and asked to prepare a dish at home, serve it to their families at a time of their own choosing, record the recipe and the amount of condiment added, and report these facts to an interviewer on the following day. The nutrient content of each dish was calculated from food-composition table values for raw, whole ingredients and the package label values for the HDMC. Results For all dishes combined, the HDMC provided on average 78% of the total vitamins. The proportion of the total vitamins provided by the HDMC varied greatly among different dishes. Typically a single serving of a dish without added HDMC provided less than half of the RDA (vitamin B12 and folate) for children and adult women. The midday meal is the most important meal of the day and should provide at least half of the RDA of all essential nutrients. With the HDMC added, the dishes on average provided 2 to 10 times the RDA for nutrients such as vitamins B6 and C and niacin in the reference children, and just satisfied the RDA intake for corresponding nutrients in adult women. Conclusions The proportion of the RDAs of micronutrients provided by this novel, micronutrient-rich condiment varies over a wide range, depending on idiosyncrasies of recipe ingredients, amounts of condiment added, individuals served, and age- and physiology-dependent requirements. HDMCs could provide an efficient way to deliver essential micronutrients to vulnerable populations.

Differences in circulating non-transferrin-bound iron after oral administration of ferrous sulfate, sodium iron EDTA, or iron polymaltose in women with marginal iron stores

Background. The adverse interactions between iron supplements and malaria have driven the assessment of new therapeutic options for anemia prophylaxis in areas holoendemic for falciparum malaria. Objective. To determine the responses of circulating non-transferrin-bound iron (NTBI) and plasma iron to three different oral iron compounds – ferrous sulfate, sodium iron ethylenediaminetetraacetate (NaFeEDTA), and iron polymaltose (IPM) – in women with marginal iron stores. Methods. Serum samples from 10 Guatemalan women with marginal iron stores were collected every 90 minutes over a period of 270 minutes, after the individually randomized administration of 100 mg of iron from each of the three studied iron compounds or water alone. Serum iron concentration was quantified by the ferrozine method, and circulating NTBI concentration was determined with a fluorometric competitive binding assay. Kinetic responses and maximal cumulative changes in serum concentrations of iron and NTBI were compared between the four treatments. Comparison was made with data from the same protocol in iron-adequate men. Conclusions. The administration of the two “slow-release” iron compounds, NaFeEDTA and IPM, resulted in a highly significant suppression of the appearance of NTBI in the circulation in the postsupplement period. These two bioavailable forms of iron supplement could represent a safe option for supplementation in malarial areas. The slope of the iron – NTBI relationship is steeper in men than in women.