pyrophosphate and ferrous-sulfate

Ferrous ammonium phosphate (FAP) is an iron salt that has been developed for the fortification of food matrices sensitive to color and flavor changes. The objective of the study was to measure iron absorption from FAP in young children and compare it to a previous evaluation of FAP in young women. A double-blind randomized crossover study with two parallel arms was used to evaluate the iron absorption from FAP added to reconstituted milk powder in comparison to that from ferrous sulfate (FeSO4) and ferric pyrophosphate (FePP). Iron absorption was measured in 39 children aged 3- to 6-years-old using erythrocyte incorporation of stable Fe isotopes (57Fe, 58Fe). The geometric mean iron absorption in iron replete children from FAP, FeSO4 and FePP from milk was 8.3%, 7.6% and 2.1%, respectively. Iron absorption from FAP and FeSO4 fortified milk was not significantly different (p = 0.199); however, it was significantly higher than from FePP fortified milk (p < 0.001). Iron bioavailability from FAP and FePP relative to FeSO4 (relative bioavailability (RBV)) was 110% and 33%, respectively. The RBV of FAP (110%) in iron replete children was higher than previously reported RBV (71%) in mainly iron deficient women. The difference in iron status between the children and women in the respective studies may explain the different RBV values and is discussed.

Topics: Animals; Biological Availability; Child; Child, Preschool; Cross-Over Studies; Diphosphates; Female; Ferrous Compounds; Food, Fortified; Humans; Intestinal Absorption; Iron; Iron Isotopes; Iron, Dietary; Isotopes; Milk; Phosphates

Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.

Topics: Adolescent; Adult; Biological Availability; Caco-2 Cells; Digestion; Diphosphates; Erythrocytes; Female; Ferritins; Ferrous Compounds; Food, Fortified; Humans; Intestinal Absorption; Iron; Solubility; Young Adult

The main purpose of this study was to establish bioavailability data in humans for the new (Fe) fortification compound ferrous ammonium phosphate (FAP), which was specially developed for fortification of difficult-to-fortify foods where soluble Fe compounds cannot be used due to their negative impact on product stability.. A double-blind, randomized clinical trial with cross-over design was conducted to obtain bioavailability data for FAP in humans. In this trial, Fe absorption from FAP-fortified full-cream milk powder was compared to that from ferric pyrophosphate (FPP) and ferrous sulfate. Fe absorption was determined in 38 young women using the erythrocyte incorporation dual stable isotope technique (⁵⁷Fe, ⁵⁸Fe).. Geometric mean Fe absorption from ferrous sulfate, FAP and FPP was 10.4, 7.4 and 3.3 %, respectively. Fe from FAP was significantly better absorbed from milk than Fe from FPP (p < 0.0001). Fe absorption from FAP was significantly lower than Fe absorption from ferrous sulfate, which was used as water-soluble reference compound (p = 0.0002). Absorption ratios of FAP and FPP relative to ferrous sulfate as a measure of relative bioavailability were 0.71 and 0.32, respectively.. The results of the present studies show that replacing FPP with FAP in full-cream milk could significantly improve iron bioavailability.

Topics: Adult; Beverages; Cross-Over Studies; Dairy Products; Diphosphates; Double-Blind Method; Erythrocytes; Female; Ferrous Compounds; Food, Fortified; Food, Preserved; Humans; Intestinal Absorption; Iron; Iron Isotopes; Iron, Dietary; Nutritive Value; Phosphates; Solubility; Young Adult

Fe absorption from water-soluble forms of Fe is inversely proportional to Fe status in humans. Whether this is true for poorly soluble Fe compounds is uncertain. Our objectives were therefore (1) to compare the up-regulation of Fe absorption at low Fe status from ferrous sulphate (FS) and ferric pyrophosphate (FPP) and (2) to compare the efficacy of FS with FPP in a fortification trial to increase body Fe stores in Fe-deficient children v. Fe-sufficient children. Using stable isotopes in test meals in young women (n 49) selected for low and high Fe status, we compared the absorption of FPP with FS. We analysed data from previous efficacy trials in children (n 258) to determine whether Fe status at baseline predicted response to FS v. FPP as salt fortificants. Plasma ferritin was a strong negative predictor of Fe bioavailability from FS (P < 0·0001) but not from FPP. In the efficacy trials, body Fe at baseline was a negative predictor of the change in body Fe for both FPP and FS, but the effect was significantly greater with FS (P < 0·01). Because Fe deficiency up-regulates Fe absorption from FS but not from FPP, food fortification with FS may have relatively greater impact in Fe-deficient children. Thus, more soluble Fe compounds not only demonstrate better overall absorption and can be used at lower fortification levels, but they also have the added advantage that, because their absorption is up-regulated in Fe deficiency, they innately 'target' Fe-deficient individuals in a population.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Biological Availability; C-Reactive Protein; Child; Diphosphates; Female; Ferritins; Ferrous Compounds; Food, Fortified; Hemoglobins; Humans; Intestinal Absorption; Intestines; Iodine; Iron; Iron Isotopes; Iron, Dietary; Male; Nutritional Status; Sodium Chloride, Dietary; Solubility; Young Adult

Difructose anhydride III (DFAIII) is an indigestible disaccharide and has been shown to enhance iron absorption in animal studies; however, the effect has not been investigated in anemic subjects. We investigated the efficacy of co-administration of DFAIII with water-insoluble iron in the treatment of iron deficiency anemia in Vietnamese women. One hundred sixty-eight moderately anemic women (80 g/L

Topics: Adjuvants, Pharmaceutic; Adult; Algorithms; Anemia, Iron-Deficiency; Biological Availability; Diphosphates; Disaccharides; Double-Blind Method; Female; Ferrous Compounds; Hemoglobins; Humans; Iron; Middle Aged; Nutritional Status; Receptors, Transferrin; Severity of Illness Index; Solubility; Time Factors; Transferrin; Vietnam; Young Adult

Non-water-soluble iron compounds have been reported to be less well absorbed than ferrous sulfate in young children, and concern has been raised about their usefulness as food fortificants.. The objective was to evaluate the usefulness of ferrous fumarate and ferric pyrophosphate, compared with ferrous sulfate, in maintaining hemoglobin concentrations >105 g/L in Bangladeshi children.. Two hundred thirty-five children aged 7-24 mo (hemoglobin >105 g/L) were randomly assigned in a double-blind study to receive an infant cereal fortified with ferrous fumarate, ferric pyrophosphate, or ferrous sulfate. One serving of cereal (9.3 mg Fe; molar ratio of ascorbic acid to iron of 3:1) was consumed per day, 6 d/wk, for 9 mo. Blood samples were drawn at 4.5 and 9 mo.. Raw data were reformatted, and a "time to event" was calculated that corresponded to reaching the following thresholds: hemoglobin <105 g/L, plasma ferritin <12 microg/L, or plasma C-reactive protein >10 mg/L at baseline, 4.5 mo, or 9 mo. Data were censored when children did not reach the threshold or were lost to follow-up. A Kaplan-Meier approach was used to compare the 3 groups. No statistically significant differences were observed for hemoglobin <105 g/L (P = 0.943), plasma ferritin <12 microg/L (P = 0.601), or plasma C-reactive protein >10 mg/L (P = 0.508).. Contrary to earlier concerns, these results do not indicate differences in usefulness between water-soluble and non-water-soluble iron compounds in maintaining hemoglobin concentrations and preventing iron deficiency. These data will be important in the development of food-fortification strategies to combat anemia and iron deficiency in highly vulnerable population groups.

Topics: Anemia, Iron-Deficiency; Ascorbic Acid; Bangladesh; C-Reactive Protein; Child, Preschool; Diphosphates; Female; Ferritins; Ferrous Compounds; Food, Fortified; Hemoglobins; Humans; Infant; Iron; Iron, Dietary; Male; Trace Elements

Iron deficiency anemia (IDA) in the Philippines is a serious public health problem. Fortifying rice offers a great opportunity to control IDA. However, information on other types of fortificants that can be used is scarce.. To compare the effects of two types of iron fortificants in rice in improving the hematological status of schoolchildren.. 180 randomly selected 6-to 9-year-old anemic children were randomly allocated to three groups in a double-blinded manner: One group received iron-enriched rice (IER) with extruded iron premix rice (IPR) using ferrous sulfate as fortificant (ExFeSO4); the second group received IER with extruded IPR using micronized dispersible ferric pyrophosphate (ExFeP80); and the third group received non-fortified rice (Control). These were administered daily for 5 days a week for 6 months. Blood samples were collected at baseline after 3 and 6 months.. At baseline, one child in the ExFeP80 group was suffering from IDA; at 3 months, no IDA was found in any groups; while at 6 months, one child in the ExFeP80 developed IDA. The baseline prevalence of anemia in all groups, which was 100%, was significantly reduced to 51%, 54%, and 63% in the ExFeSO4, ExFeP80 and Control groups respectively. After 6 months, further significant reductions were observed in the ExFeSO4 (38%) and ExFeP80 (33%) but remained at 63% in the Control group. Greater, significant increases were also observed in plasma ferritin in the fortified groups than in the Control group from baseline to 6 months. The predictors of change in hemoglobin (Hb) and plasma ferritin were group allocation and basal values.. The consumption of rice fortified with FeP80 using extrusion technology has similar effects as that of FeSO4 in reducing the prevalence of IDA among schoolchildren.

Topics: Anemia, Iron-Deficiency; C-Reactive Protein; Child; Child Nutritional Physiological Phenomena; Diphosphates; Double-Blind Method; Eating; Ferritins; Ferrous Compounds; Food, Fortified; Hemoglobins; Humans; Iron; Oryza; Philippines; Statistics, Nonparametric; Vitamin A

Although ferric pyrophosphate is a promising compound for iron fortification of foods, few data are available on the effect of food matrices, processing, and ascorbic acid on its bioavailability.. We compared the relative bioavailability (RBV) of ferrous sulfate in an experimental form of micronized dispersible ferric pyrophosphate (MDFP) in a wheat-milk infant cereal given with and without ascorbic acid with the RBV of MDFP from a processed and unprocessed rice meal.. A crossover design was used to measure iron absorption in young women (n = 26) from test meals fortified with isotopically labeled [57Fe]-MDFP and [58Fe]-ferrous sulfate, based on erythrocyte incorporation of stable isotope labels 14 d later.. Geometric mean iron absorption from the wheat-based meal fortified with MDFP was 2.0% and that from the meal fortified with ferrous sulfate was 3.2% (RBV = 62). The addition of ascorbic acid at a molar ratio of 4:1 to iron increased iron absorption from MDFP to 5.8% and that from ferrous sulfate to 14.8% (RBV = 39). In the rice meals, mean iron absorption from MDFP added to the rice at the time of feeding was 1.7%, and that from ferrous sulfate was 11.6% (RBV = 15). The mean iron absorption from MDFP extruded into artificial rice grains was 3.0% and that from ferrous sulfate in unprocessed rice was 12.6% (RBV = 24). Sixteen of 26 subjects were iron deficient. Iron status was a highly significant predictor of the RBV of MDFP (P < 0.001).. RBV of the experimental MDFP varied markedly with food matrix and iron status. Assigning a single RBV value to poorly soluble compounds may be of limited value in evaluating their suitability for food fortification.

Topics: Absorption; Adult; Antioxidants; Ascorbic Acid; Biological Availability; Cross-Over Studies; Diphosphates; Female; Ferritins; Ferrous Compounds; Food; Food Handling; Food, Fortified; Humans; Intestinal Absorption; Iron; Iron Isotopes; Nutritional Status; Oryza; Triticum

The effects of added ascorbic acid and particle size on iron absorption from ferric pyrophosphate were evaluated in adult women (9-10 women/study) based on erythrocyte incorporation of iron stable isotopes (57Fe or 58Fe) 14 days after administration. Three separate studies were made with test meals of iron-fortified infant cereal (5 mg iron/meal) and the results are presented as geometric means and relative bioavailability values (RBV, FeSO4 = 100%). The results of study 1 showed that iron absorption was significantly lower from ferric pyrophosphate (mean particle size 8.5 microm) than from FeSO4 in meals without ascorbic acid (0.9 vs. 2.6%, p < 0.0001, RBV 36%) and in the same meals with ascorbic acid added at a 4:1 molar ratio relative to fortification iron (2.3 vs. 9.7%, p < 0.0001, RBV 23%). Ascorbic acid increased iron absorption from ferric pyrophosphate slightly less (2.6-fold) than from FeSO4 (3.7-fold) (p < 0.05). In studies 2 and 3, RBV of ferric pyrophosphate with an average particle size of 6.7 microm and 12.5 pm was not significantly different at 52 and 42% (p > 0.05), respectively. In conclusion, the addition of ascorbic acid increased fractional iron absorption from ferric pyrophosphate significantly, but to a lesser extent than from FeSO4. Decreasing the mean particle size to 6.7 microm did not significantly increase iron absorption from ferric pyrophosphate.

Topics: Adult; Ascorbic Acid; Biological Availability; Diphosphates; Erythrocytes; Female; Ferrous Compounds; Humans; Iron; Iron Isotopes; Iron, Dietary; Particle Size; Time Factors

An evaluation was made into the usefulness of ferrous fumarate as an iron fortificant for an experimental chocolate drink powder targetted to children and adolescents. Organoleptically ferrous furmarate was acceptable when the chocolate drink powder was reconstituted in milk or water that was heated to less than 80 degrees. Unacceptable colour changes occurred, however, when boiling milk or water were used. In human Fe absorption studies when the Fe compounds were added to the chocolate drink immediately before consumption, ferrous fumarate was 3.31% absorbed compared with 2.82% for ferrous sulphate and 2.11% for ferric pyrophosphate. When the Fe compounds were processed during the manufacture of the chocolate drink powder, the absorption of ferrous furmarate was 5.27%, ferrous sulphate 2.62% and ferric pyrophosphate 0.55%. Ascorbic acid had little or no effect on the absorption of ferrous furmarate. It is concluded that food processing can influence the relative absorption of fortification Fe and that, if not reconstituted with boiling milk or water, ferrous fumarate could be a useful compound for the fortification of chocolate drink powders.

Topics: Adolescent; Ascorbic Acid; Beverages; Biological Availability; Cacao; Child; Diphosphates; Ferrous Compounds; Food Handling; Food, Fortified; Humans; Intestinal Absorption; Iron; Iron Radioisotopes

Although acute consumption of high doses of prebiotic galacto-oligosaccharides (GOS) increases fractional iron absorption (FIA) from ferrous fumarate (FeFum), it is uncertain if low doses of GOS have this effect. Furthermore, whether GOS improve iron absorption from other commonly used iron compounds and whether ascorbic acid (AA) enhances the effect of GOS on iron absorption from FeFum is unclear.. In iron-depleted women [serum ferritin (SF) <30 μg/L], we assessed: 1) whether the acute enhancing effect of GOS on FeFum is dose dependent; 2) if GOS would affect FIA from ferrous sulfate (FeSO4) or ferric pyrophosphate (FePP); and 3) if AA and GOS given together enhance FIA from FeFum to a greater extent compared with GOS alone.. We recruited 46 women (mean age 22.0 y, mean BMI 21.3 kg/m2, median SF 17.1 μg/L), and measured FIA from 14 mg iron labeled with stable isotopes in the following conditions: 1) FIA from FeFum given with 3.5 g, 7 g GOS, and without GOS; 2) FIA from FeSO4 and FePP given with and without 15 g GOS; and 3) FIA from FeFum given with 7 g GOS with and without 93 mg AA. FIA was measured as erythrocyte incorporation of stable isotopes after 14 d. Comparisons were made using paired samples t-test or Wilcoxon rank sum test where appropriate.. Giving 7 g of GOS significantly increased FIA from FeFum (+26%; P = 0.039), whereas 3.5 g GOS did not (P = 0.130). GOS did not significantly increase FIA from FeSO4 (P = 0.998) or FePP (P = 0.059). FIA from FeFum given with GOS and AA was significantly higher compared with FeFum given with GOS alone (+30%; P <0.001).. In iron-depleted women, GOS does not increase FIA from FeSO4 or FePP, but it increases FIA from FeFum. Thus, a combination of FeFum and GOS may be a well-absorbed formula for iron supplements. The study was registered at clinicaltrials.gov as NCT03762148.

Topics: Anemia, Iron-Deficiency; Biological Transport; Cross-Over Studies; Diphosphates; Drug Administration Schedule; Female; Ferrous Compounds; Humans; Iron; Iron Isotopes; Prebiotics; Prospective Studies; Young Adult

A new iron-casein complex (ICC) has been developed for iron (Fe) fortification of dairy matrices. The objective was to assess the impact of ascorbic acid (AA) on its in vitro bioavailability in comparison with ferrous sulfate (FeSO

Topics: Ascorbic Acid; Biological Availability; Caco-2 Cells; Caseins; Cells, Cultured; Diphosphates; Ferrous Compounds; Food, Fortified; Humans; In Vitro Techniques; Iron

Sucrosomial

Topics: Anemia, Iron-Deficiency; Animals; Diphosphates; Disease Models, Animal; Female; Ferric Compounds; Ferrous Compounds; Hep G2 Cells; Hepcidins; Humans; Inflammation; Intestinal Absorption; Intestines; Iron; Iron Deficiencies; Mice, Inbred BALB C

The present study investigated the effects of fructo-oligosaccharides (FOS) on the bioavailability of Fe from ferric pyrophosphate (FP), a water-insoluble compound, in Fe-deficient anaemic rats that were subjected to a Hb repletion assay. Male Wistar rats (n 64) were fed adequate or low (8 mg/kg) Fe diets for 15 d followed by 1 or 2 weeks of Fe repletion with diets providing 35 mg Fe/kg as ferrous sulphate (FS), FP or FP that was mixed with 7·5% FOS in the form of yacon flour or Raftilose P95 (RAF), a purified source of FOS. The effects of FOS were observed within the 1st week of the repletion period. Fe bioavailability was improved by FOS supplementation, as measured by Hb regeneration efficiency and hepatic Fe stores, which were more pronounced in the RAF group. Moreover, RAF supplementation resulted in a higher biological value relative to that of the FP group. FOS supplementation resulted in caecal enlargement, in addition to acidification and Fe species redistribution in the caecal contents relative to the control rats. These effects occurred concomitantly with decreased ferroportin (FPN)-1 expression in the caecal mucosa, which was similar in magnitude to that observed in the FS group. Caecum mucosal morphometry was influenced by FOS supplementation, whereas crypt fission and cell proliferation were highest in the caecum of the RAF group. These results reinforce the effects of FOS as Fe bioavailability enhancers in anaemic rats that are sustained by early changes in their caecal environment (decreased mucosal FPN-1 expression and increased Fe absorbability, crypt fission and cellularity).

Topics: Anemia, Iron-Deficiency; Animals; Brazil; Cation Transport Proteins; Cecum; Cell Proliferation; Diphosphates; Ferrous Compounds; Food, Fortified; Fructose; Gastrointestinal Contents; Hemoglobins; Intestinal Mucosa; Iron; Iron, Dietary; Male; Nutritive Value; Oligosaccharides; Plant Roots; Prebiotics; Rats, Wistar; Tracheophyta

The purpose of the present work was to evaluate the iron bioavailability of a new ferric pyrophosphate salt stabilized and solubilized with glycine. The prophylactic-preventive test in rats, using ferrous sulfate as the reference standard, was applied as the evaluating methodology both using water and yogurt as vehicles. Fifty female Sprague-Dawley rats weaned were randomized into five different groups (group 1: FeSO(4); group 2: pyr; group 3: FeSO(4) + yogurt; group 4: pyr + yogurt and group 5: control). The iron bioavailability (BioFe) of each compound was calculated using the formula proposed by Dutra-de-Oliveira et al. where BioFe % = (HbFef - HbFei) x 100/ToFeIn. Finally, the iron bioavailability results of each iron source were also given as relative biological value (RBV) using ferrous sulfate as the reference standard. The results showed that both BioFe % and RBV % of the new iron source tested is similar to that of the reference standard independently of the vehicle employed for the fortification procedure (FeSO(4) 49.46 +/- 12.0% and 100%; Pyr 52.66 +/- 15.02% and 106%; FeSO(4) + yogurth 54.39 +/- 13.92% and 110%; Pyr + yogurt 61.97 +/- 13.54% and 125%; Control 25.30 +/- 6.60, p < 0.05). Therefore, the stabilized and soluble ferric pyrophosphate may be considered as an optimal iron source for food fortification.

Topics: Analysis of Variance; Animals; Biological Availability; Diet; Diphosphates; Female; Ferrous Compounds; Food, Fortified; Iron; Iron, Dietary; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Standards; Solubility; Water; Yogurt

Food iron fortification is a sustainable and relatively simple strategy to reduce/prevent iron deficiency but is a challenge for the food industry because of possible adverse organoleptic changes caused by the added iron. A micronized dispersible ferric pyrophosphate, trademarked as SunActive Fe, has recently been developed. SunActive Fe has a small particle size, is water soluble and may be suitable for fortifying liquid products.. To determine the relative bioavailability of SunActive Fe and its suitability for addition to pure apple juice.. Iron absorption from SunActive Fe added to pure apple juice (Minute Maid) was compared with absorption from ferrous sulphate, a highly bioavailable form of iron, in 15 women with relatively low iron stores. Both forms of iron were enriched with an iron stable isotope and iron absorption from the apple juice drinks was calculated from the isotopic enrichment of red blood cells 14 days after the last test meal.. Although mean absorption of iron from SunActive Fe was significantly lower than from ferrous sulphate (5.5% compared with 9.1%), the mean bioavailability of SunActive Fe iron relative to ferrous sulphate was 0.6, indicating that it is a good source of bioavailable iron. Iron Absorption from SunActive Fe was positively correlated (r = 0.97, P = 0.01) with absorption from ferrous sulphate, and negatively correlated with serum ferritin concentration (ferrous sulphate r = -0.81, P < 0.001; SunActive Fe r = -0.76, P = 0.01).. SunActive Fe was well absorbed from apple juice and is a potentially useful fortificant for liquid food products.

Topics: Absorption; Adolescent; Adult; Aged; Beverages; Biological Availability; C-Reactive Protein; Diphosphates; Female; Ferritins; Ferrous Compounds; Food, Fortified; Fruit; Hemoglobins; Humans; Iron; Iron Deficiencies; Iron Isotopes; Malus; Middle Aged; Particle Size

Multicopper oxidases have been described to have functions in copper tolerance, manganese oxidation, and iron oxidation in a range of bacteria. The putative cytoplasmic membrane multicopper oxidase from Legionella pneumophila was investigated. The mcoL gene was found to be critical for aerobic extracellular growth under either iron-limiting conditions or in the presence of ferrous Fe(II) iron, as a sole source of this essential metal. The mcoL mutants showed minor growth defects when grown in the presence of Fe(III) as the iron source. In contrast, intracellular growth and survival was not affected by the absence of the mcoL gene regardless of available iron concentration. The evidence presented here could indicate a possible role for mcoL in prevention of the toxic effects of ferrous iron during aerobic conditions. However, a function in high-affinity acquisition of iron could also be possible given the inability of the McoL mutants to grow aerobically under iron-limiting conditions.

Topics: Aerobiosis; Animals; Base Sequence; Cell Membrane; Copper Sulfate; Diphosphates; Disk Diffusion Antimicrobial Tests; DNA, Bacterial; Ferrous Compounds; Genes, Bacterial; Hartmannella; Humans; Iron; Laccase; Legionella pneumophila; Legionnaires' Disease; Molecular Sequence Data; Mutagenesis, Insertional; Oxidoreductases; Sequence Analysis, DNA; U937 Cells

The aim of this study was to investigate the in vitro antioxidant profile of different bisphosphonates. Bisphosphonates were tested for their xanthine oxidase and microsomal lipid peroxidation inhibiting capacity. Furthermore, the effect of these different compounds on DPPH, a stable radical, was investigated. Clodronate, risedronate, and pyrophosphate were further tested for their hydroxyl radical scavenging activity. None of the tested compounds showed xanthine oxidase inhibiting activity or DPPH scavenging activity. All the tested bisphosphonates exhibited inhibiting capacities on the microsomal lipid peroxidation. The hydroxyl radical scavenging activity was dependent on the order of adding the different reagents and was highest for risedronate. Bisphosphonates possess an inhibiting activity on the microsomal lipid peroxidation and the Fenton reaction. In these reactions iron plays an important role suggesting that the selective in vitro antioxidant properties of the bisphosphonates are due to their iron chelating characteristics.

Topics: Animals; Antioxidants; Biphenyl Compounds; Diphosphates; Diphosphonates; Fatty Acids; Ferrous Compounds; Free Radical Scavengers; Free Radicals; Hydroxyl Radical; Lipid Peroxidation; Microsomes, Liver; Picrates; Rats; Xanthine Oxidase

Ferric pyrophosphate is a water-insoluble Fe compound used to fortify infant cereals and chocolate-drink powders as it causes no organoleptic changes to the food vehicle. However, it is only of low absorption in man. Recently, an innovative ferric pyrophosphate has been developed (Sunactive Fe trade mark ) based on small-particle-size ferric pyrophosphate (average size 0.3 microm) mixed with emulsifiers, so that it remains in suspension in liquid products. The aim of the present studies was to compare Fe absorption of micronised, dispersible ferric pyrophosphate (Sunactive Fe trade mark ) with that of ferrous sulfate in an infant cereal and a yoghurt drink. Two separate Fe absorption studies were made in adult women (ten women/study). Fe absorption was based on the erythrocyte incorporation of stable isotopes ((57)Fe and (58)Fe) 14 d after the intake of labelled test meals of infant cereal (study 1) or yoghurt drink (study 2). Each test meal was fortified with 5 mg Fe as ferrous sulfate or micronised, dispersible ferric pyrophosphate. Results are presented as geometric means. There was no statistically significant difference between Fe absorption from micronised, dispersible ferric pyrophosphate- and ferrous sulfate-fortified infant cereal (3.4 and 4.1 % respectively; P=0.24) and yoghurt drink (3.9 and 4.2 % respectively; P=0.72). The results of the present studies show that micronised, dispersible ferric pyrophosphate is as well absorbed as ferrous sulfate in adults. The high relative Fe bioavailability of micronised, dispersible ferric pyrophosphate indicates the potential usefulness of this compound for food fortification.

Topics: Absorption; Adult; Beverages; Biological Availability; Diphosphates; Edible Grain; Erythrocytes; Female; Ferrous Compounds; Food, Fortified; Humans; Iron; Iron Isotopes; Iron, Dietary; Yogurt

Unlike commercial ferric pyrophosphate, micronized dispersible ferric pyrophosphate (MDFP: Sun-Active Fe) does not precipitate and is completely dispersible in liquid form. MDFP shows a sharp particle size distribution at a nanometer level, which is several times smaller than that of commercial ferric pyrophosphate. The bioavailability of MDFP was compared to ferric pyrophosphate, sodium ferrous citrate, and ferrous sulfate by three bioavailability tests in rats; namely the serum iron concentration curve, the hemoglobin regeneration efficiency, and Association of Official Analytical Chemists' hemoglobin repletion test. The high area under curve value, a lag in peak time, and continued high serum iron concentration by MDFP over the other iron compounds indicates a sustained release of iron in the serum iron concentration curve method. MDFP showed the highest hemoglobin regeneration efficiency among all the iron compounds tested. The relative biological value of MDFP per unit of ferrous sulfate in each bioavailability test showed a high value as compared to other iron compounds. The above results suggest that MDFP is an ideal compound with high bioavailability for iron fortification in various liquid applications.

Topics: Analysis of Variance; Animals; Area Under Curve; Biological Availability; Citric Acid; Diphosphates; Ferrous Compounds; Hemoglobins; Iron; Iron, Dietary; Male; Particle Size; Rats; Rats, Sprague-Dawley

Particle size is an important determinant of Fe absorption from poorly soluble Fe compounds in foods. Decreasing the particle size of elemental iron powders increases their absorption. The effect of a reduction in particle size on the bioavailability of ferric pyrophosphate (FePP) is unclear. Encapsulation of iron compounds for food fortification may protect against adverse sensory changes, but at the same time may reduce bioavailability. The hemoglobin (Hb) repletion method in weanling Sprague-Dawley rats (n = 100) was used to compare the relative bioavailability (RBV) of 4 forms of FePP: 1) regular FePP [mean particle size (MPS) approximately 21 microm]; 2) MPS approximately 2.5 microm; 3) MPS approximately 2.5 microm encapsulated in hydrogenated palm oil; and 4) MPS approximately 0.5 microm with emulsifiers. The RBV compared with ferrous sulfate was calculated by the slope-ratio technique. The RBV was 43% for encapsulated MPS approximately 2.5 microm, significantly lower than the other FePP compounds (P < 0.05), 59% for the regular FePP, and 69% for MPS approximately 2.5 microm, not different from each other but significantly lower than ferrous sulfate (P < 0.05), and 95% for emulsified MPS approximately 0.5 microm, comparable to ferrous sulfate. Encapsulation of FePP with hydrogenated palm oil at a capsule:substrate ratio of 60:40 decreased RBV. Particle size reduction increases the RBV of FePP and may make this compound more useful for food fortification.

Topics: Animals; Biological Availability; Capsules; Diphosphates; Ferrous Compounds; Intestinal Absorption; Iron; Male; Rats; Rats, Sprague-Dawley

Although potassium sorbate (PS), ascorbic acid and ferric or ferrous salts (Fe-salts) are used widely in combination as food additives, the strong reactivity of PS and oxidative potency of ascorbic acid in the presence of Fe-salts might form toxic compounds in food during its deposit and distribution. In the present paper, the reaction mixture of PS, ascorbic acid and Fe-salts was evaluated for mutagenicity and DNA-damaging activity by means of the Ames test and rec-assay. Effective lethality was observed in the rec-assay. No mutagenicity was induced in either Salmonella typhimurium strains TA98 (with or without S-9 mix) or TA100 (with S-9 mix). In contrast, a dose-dependent mutagenic effect was obtained when applied to strain TA100 without S-9 mix. The mutagenic activity became stronger increasing with the reaction period. Furthermore, the reaction products obtained in a nitrogen atmosphere did not show any mutagenic and DNA-damaging activity. PS, ascorbic acid and Fe-salts were inactive when they were used separately. Omission of one component from the mixture of PS, ascorbic acid and Fe-salt turned the reaction system inactive. These results demonstrate that ascorbic acid and Fe-salt oxidized PS and the oxidative products caused mutagenicity and DNA-damaging activity.

Topics: Ascorbic Acid; Diphosphates; DNA Damage; Edetic Acid; Ferric Compounds; Ferrous Compounds; Food Preservatives; Iron; Mutagenicity Tests; Ribosomal Proteins; Salmonella typhimurium; Sorbic Acid

The absorption of ciprofloxacin has been reported to be impaired by concomitant administration of ferrous sulphate. The effects of sodium ferrous citrate and ferric pyrophosphate, which have been used as extensively as ferrous sulphate, on the absorption of ciprofloxacin were compared with that of ferrous sulphate. The effects of ascorbic acid on the interactions between ciprofloxacin and each iron compound were studied in mice. Mice were treated orally with ciprofloxacin (50 mg kg(-1)) alone, the iron compound (ferrous sulphate, sodium ferrous citrate or ferric pyrophosphate; 50 mg elemental iron kg(-1)) alone, ciprofloxacin with each iron compound or ciprofloxacin in combination with each iron compound and ascorbic acid (250 mg kg(-1)). The maximum serum concentration of ciprofloxacin was significantly (P < 0.01) reduced from 1.15+/-0.11 microg mL(-1) (ciprofloxacin alone) to 0.17+/-0.01, 0.27+/-0.01 or 0.28+/-0.02 microg mL(-1), respectively, when ferrous sulphate, sodium ferrous citrate or ferric pyrophosphate was administered along with ciprofloxacin. The addition of ascorbic acid did not affect the inhibitory effects of each iron compound on the absorption of ciprofloxacin. Ciprofloxacin did not affect the variation of serum iron levels after administration of each iron compound. The addition of ascorbic acid significantly (P < 0.01) enhanced the increase in serum iron concentration after administration of sodium ferrous citrate, showing an increase from 270+/-6 microg dL(-1) to 463+/-11 microg dL(-1) compared with an increase from 248+/-8 microg dL(-1) to 394+/-18 microg dL(-1) after administration of sodium ferrous citrate alone. Ascorbic acid also caused a significant (P < 0.01) increase in serum iron concentration from 261+/-16 microg dL(-1) to 360+/-12 microg dL(-1) after administration of ferric pyrophosphate, although it did not affect the levels after ferrous sulphate administration. The results suggest that sodium ferrous citrate and ferric pyrophosphate should not be administered with ciprofloxacin (as for ferrous sulphate) and that sodium ferrous citrate is converted to the ferric form more easily than ferrous sulphate. This difference in convertibility might contribute to a clinical difference between sodium ferrous citrate and ferrous sulphate.

Topics: Absorption; Administration, Oral; Animals; Anti-Infective Agents; Ascorbic Acid; Ciprofloxacin; Citric Acid; Diphosphates; Drug Interactions; Ferrous Compounds; Iron; Iron Compounds; Male; Mice

Using paraquat, adriamycin, and anthraquinone 6-sulfonate, we have investigated the ability of radical-driven Fenton reactions to oxidize formate or deoxyribose when catalyzed by iron complexed with citrate, ADP, ATP, or pyrophosphate. Radicals were generated either radiolytically or enzymatically with xanthine oxidase or ferredoxin reductase. With each radical source, the citrate, ADP, and ATP complexes were at least 50% as active as Fe(EDTA) at catalyzing deoxyribose oxidation, and slightly less active as catalysts of CO2 formation from formate. Fe(pyrophosphate) was less efficient and in some cases inactive. Although it is not possible to definitively identify the oxidant involved, it behaved more like the hydroxyl radical than the proposed ferryl or peroxoferrous species formed in equivalent reactions catalyzed by nonchelated iron, which can oxidize deoxyribose but not formate. Chelator concentrations of 1-2 mM were required for maximum effect, which implies that the major effect of the chelators is on the reactivity of Fe2+ in the Fenton reaction with H2O2. This also suggests that any iron available physiologically could participate in the Fenton reaction in a nonchelated form, and produce a ferryl species rather than the hydroxyl radical. Reactions of the organic radicals contrast with the equivalent reactions of superoxide (Haber-Weiss reaction) for which the same iron chelates are all very inefficient catalysts. Fenton reactions driven by organic reducing radicals may therefore contribute more to the toxicity of redox cycling compounds than equivalent reactions of superoxide.

Topics: Adenine Nucleotides; Adenosine Diphosphate; Adenosine Triphosphate; Chelating Agents; Citrates; Citric Acid; Deoxyribose; Diphosphates; Doxorubicin; Ferrous Compounds; Free Radicals; Hydrogen Peroxide; Hydroxides; Hydroxyl Radical; Iron; Paraquat; Superoxides