pyrophosphate and ferric-pyrophosphate

Treatment of anemia remains an integral component in the care of patients with end stage kidney disease receiving dialysis. Currently, both erythropoiesis stimulating agents and iron replacement agents remain important anemia management strategies for patients undergoing hemodialysis (HD). Ferric pyrophosphate citrate (FPC) was approved by the U.S. Food and Drug Administration in January 2015 as an iron replacement product in adult patients receiving long-term maintenance HD. FPC is administered to patients on HD through the dialysate. Multicenter randomized, placebo-controlled phase three clinical studies (CRUISE 1 and 2) have found dialysate FPC to maintain hemoglobin level and iron balance in patients receiving chronic HD. Adverse events were similar in both the dialysate FPC-treated and placebo groups. Another study showed a significant reduction in the prescribed erythropoietin-stimulating agents dose at the end of treatment in the dialysate FPC-treated group compared with placebo. These studies have shown that dialysate FPC is efficacious and well tolerated. In this article, we review clinical studies evaluating the efficacy and safety of FPC and also propose a protocol for iron replacement in HD units where dialysate FPC is to be used.

Topics: Anemia; Clinical Trials as Topic; Diphosphates; Hematinics; Humans; Iron; Kidney Failure, Chronic; Renal Dialysis

Management of anemia remains an integral component in the care of patients with chronic kidney disease undergoing hemodialysis. In addition to erythropoiesis-stimulating agents, iron-replacement agents remain a key strategy for anemia treatment in this patient population. Ferric pyrophosphate citrate (FPC), a novel iron-replacement agent, was approved by the US Food and Drug Administration in January 2015 for use in adult patients receiving chronic hemodialysis (HD). This iron product is administered to patients on HD via the dialysate. The recently published, multicenter, randomized, placebo-controlled, phase 3 clinical trials found FPC to maintain hemoglobin level and iron balance in patients undergoing chronic HD. The mean hemoglobin level in these phase 3 clinical studies was maintained from baseline to the end of the treatment in the dialysate iron (FPC-treated) group, however, it decreased by 0.4 g/dL in the control group (P < 0.001). Adverse and serious adverse events were similar in both groups. Another recent study showed a significant reduction in the prescribed ESA dose at the end of treatment in the FPC-treated group compared with placebo. These studies have shown that FPC administered via the dialysate is efficacious and apparently well tolerated. In this article, in addition to reviewing the clinical studies evaluating the efficacy and safety of FPC, we propose a protocol for iron management in HD centers where FPC is to be used.

Topics: Anemia, Iron-Deficiency; Dialysis Solutions; Diphosphates; Ferric Compounds; Hematinics; Humans; Iron; Kidney Failure, Chronic; Renal Dialysis

The objective of this short review is to evaluate the efficacy of ferric pyrophosphate citrate and to determine its place in therapy based on the current published literature.. A literature search was conducted and pared down to yield 4 placebo controlled Phase II and III clinically relevant trials.. Ferric pyrophosphate citrate is a new intradialytic iron supplementation product that has been found to reduce the dose of erythropoiesis-stimulating agents and intravenous iron supplementation and to increase serum ferritin concentrations.. This agent may be administered to patients with stage 5 chronic kidney disease receiving hemodialysis as a new iron supplementation option to maintain hemoglobin, transferrin saturation, and ferritin concentrations.

Topics: Administration, Intravenous; Citrates; Dietary Supplements; Diphosphates; Ferritins; Hematinics; Hemoglobins; Humans; Iron; Renal Dialysis; Renal Insufficiency, Chronic

Ferric pyrophosphate citrate (FPC) is indicated to maintain hemoglobin in patients with stage 5 hemodialysis-dependent chronic kidney disease on chronic hemodialysis by addition to the dialysate. An intravenous (IV) FPC presentation containing 6.75 mg of iron in 4.5 mL was developed. The objective was to establish the equivalence of iron delivery via dialysate and IV infusion using a pharmacokinetic approach. An open-label, randomized, multiple-period, single-dose, crossover study was conducted in 27 patients with CKD-5HD. Each patient received (1) a basal iron profile over 12 hours, (2) FPC 6.75 mg Fe IV predialyzer, (3) FPC 6.75 mg Fe IV postdialyzer, and (4) FPC 2 μM (110 μg Fe/L of hemodialysate). Serum and plasma iron was analyzed for total Fe and transferrin bound iron (TBI). Equivalence was determined by comparing maximum observed concentration and area under the concentration-time curve from time 0 to the last observation of 110 μg Fe/L of hemodialysate (reference) and test treatments Fe predialyzer and postdialyzer iron profiles. The main outcome measure was the measurement of bioequivalence between the reference and test treatments. Bioequivalence parameters showed that infusion of FPC iron IV, predialyzer and postdialyzer delivered equivalent iron as via hemodialysate. The increment in serum total Fe from predialysis to postdialysis was the same as observed in the long-term clinical studies of FPC. FPC IV was well tolerated. IV infusion of 6.75 mg iron as FPC during 3 hours of HD delivers an equivalent amount of iron as when Triferic is delivered via hemodialysate. The IV presentation of FPC extends the ability to provide FPC iron to all patients receiving hemodialysis or hemodiafiltration.

Topics: Administration, Intravenous; Citric Acid; Cross-Over Studies; Dialysis Solutions; Diphosphates; Hematinics; Humans; Iron; Kidney Failure, Chronic; Renal Dialysis

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

Altered martial indices before orthopedic surgery are associated with higher rates of complications and greatly affect the patient's functional ability. Oral supplements can optimize the preoperative martial status, with clinical efficacy and the patient's tolerability being highly dependent on the pharmaceutical formula. Patients undergoing elective hip/knee arthroplasty were randomized to be supplemented with a 30-day oral therapy of sucrosomial ferric pyrophosphate plus L-ascorbic acid. The tolerability was 2.7% among treated patients. Adjustments for confounding factors, such as iron absorption influencers, showed a relevant response limited to older patients (≥ 65 years old), whose uncharacterized Hb loss was averted upon treatment with iron formula. Older patients with no support lost -2.8 ± 5.1%, while the intervention group gained +0.7 ± 4.6% of circulating hemoglobin from baseline (

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Ascorbic Acid; Dietary Supplements; Diphosphates; Female; Ferric Compounds; Hematinics; Hematology; Hemoglobins; Humans; Iron; Male; Middle Aged; Preoperative Care

Bouillon cubes are a potential vehicle for iron fortification. They are currently fortified with ferric pyrophosphate (FePP), which is known to be poorly absorbed. The objective of this study was to assess the iron absorption of Aspergillus oryzae grown in FePP (ASP-p) and compare it with FePP and ferrous sulfate (FeSO4)-fortified bouillon cubes.. In 2 single-blinded, crossover studies, healthy women with serum ferritin concentrations <40 μg/L were randomly assigned to consume a rice-vegetable meal with iron-fortified chicken bouillon. Subjects in study I (n = 17, 18-26 y) consumed iron from both iron sources as 57FePP and 58ASP-p (intrinsically labeled with 58FePP) with a meal containing 4.2 mg of total iron provided for 3 d. Study II (n = 18, 18-29 y) was similar except that subjects consumed 57FeSO4 and 58ASP-p. Whole-blood stable isotope enrichment after 14 d was used to measure fractional iron absorption. Hemoglobin, hematocrit, serum ferritin, hepcidin, and serum C-reactive protein were analyzed at baseline and at 14 d. A t test was used to compare the mean differences in fractional absorptions within each study and baseline characteristics between studies.. Geometric mean (95% CI) fractional iron absorption of FePP [0.94% (0.63%, 1.40%)] was lower than ASP-p [2.20% (1.47%, 3.30%)] (P < 0.0001) in study I. In study II, ASP-p fractional absorption [2.98% (2.03%, 4.38%)] was lower than that of FeSO4 [9.88% (6.70%, 14.59%)] (P < 0.0001). Both ferritin (r = -0.41, P = 0.014) and hepcidin (r = -0.42, P = 0.01) concentrations were inversely correlated with ASP-p iron absorption. Fractional absorption of ASP-p was also positively correlated with FePP (r = 0.92, P < 0.0001) and FeSO4 (r = 0.52, P < 0.02) absorption.. ASP-p-fortified bouillon provided 2.3-fold higher absorbable iron than the currently used FePP. Bouillon fortified with ASP-p may contribute sufficient bioavailable iron to meet the daily iron requirements in young women only if consumed with other iron-fortified staple foods. This trial was registered at clinicaltrials.gov as NCT03586245.

Topics: Adolescent; Adult; Aspergillus oryzae; Cross-Over Studies; Diphosphates; Female; Food, Fortified; Humans; Iron; Young Adult

Background Anemia is a clinical condition frequently seen in patients with inflammatory bowel disease, which is responsible for a significant loss of quality of life. Objective To assess the efficacy and safety of using oral liposomal iron to treat iron deficiency anemia in inflammatory bowel disease patients, as well as assess the impact of this treatment on psychometric scores. Methods Patients with inactive/mildly active inflammatory bowel disease were screened for anemia in this interventional pilot study conducted from November 2016 to March 2018. Patients with mild anemia were treated with oral liposomal iron for 8 weeks. Main outcome measure The primary endpoint of the study was the response to liposomal oral iron therapy. Treatment response was defined as patients who achieved a hemoglobin increase of ≥ 1 g/dL and/or hemoglobin normalization by the 8th week of treatment. Results Out of 200 screened patients, 40 (20%) had anemia. Of the 21 patients who completed treatment, 13 (62%) responded to oral liposomal iron replacement therapy (mean increases of hemoglobin from 11.4 to 12.6 g/dL). The transferrin saturation index increased by an average of 10.2 (p = 0.006) and the quality of life by 26.3 (p < 0.0001). There was also a mean reduction of 9.2 in the perception of fatigue (p < 0.0001). Conclusion Treatment with oral liposomal iron is effective in improving mild iron deficiency anemia and quality of life, as well as in decreasing fatigue in patients with inactive or mildly active inflammatory bowel disease.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Diphosphates; Drug Carriers; Fatigue; Female; Hemoglobins; Humans; Inflammatory Bowel Diseases; Iron; Liposomes; Male; Middle Aged; Prospective Studies; Quality of Life; Transferrin; Young Adult

Iron deficiency is the most common nutritional deficiency in advanced cancer patients and causes anaemia. Iron deficiency anaemia treatment (i.e. intravenous or oral iron administration) has been demonstrated to be effective but is often associated with adverse reactions. Micronised microencapsulated ferric pyrophosphate (MMFP) is a recently developed formulation characterised by a higher intestinal bioavailability due to the small particle size distribution at nanometer level. The aim of this study was to evaluate the efficacy of an oral administration of 30 mg of MMFP associated with 80 mg of ascorbic acid in advanced cancer patients with hyposideraemia.. This was an observational prospective cohort study (10 months) conducted on 42 adult patients with advanced cancer and serum iron levels lower than 60 μg/dL. All patients received one capsule/day for 30 days of a supplement containing 30 mg of MMFP and 80 mg of ascorbic acid. At enrolment (T0) and at 30 days (T1) patients were subjected to blood sampling for evaluation of serum iron, ferritinaemia and blood count. In addition, any undesirable effects reported by patients were evaluated.. MMFP treatment increased sideraemia from 36.1±8.37 μg/dL to 73.22±28.60 μg/dL, haemoglobin from 10.43±1.09 g/dL to 11.52±1.90 g/dL, and ferritinaemia from 42.10±16.90 ng/mL to 123.33±55.79 ng/mL. No adverse effects were noted from the use of MMFP supplementation.. The supplementation of 30 mg/d of MMFP in combination with 80 mg/d of ascorbic acid in advanced cancer patients with hyposideraemia led to a significant increase in sideraemia and ferritinaemia. Moreover, in some of the patients whose serum iron level did not increase, an increase in haemoglobin was observed.

Topics: Administration, Intravenous; Administration, Oral; Aged; Anemia, Iron-Deficiency; Diphosphates; Female; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Neoplasms; Pilot Projects; Prospective Studies

It is challenging to find an iron compound that combines good bioavailability with minimal sensory changes when added to seasonings or condiments. Ferric pyrophosphate (FePP) is currently used to fortify bouillon cubes, but its bioavailability is generally low. Previously, the addition of a stabilizer, sodium pyrophosphate (NaPP), improved iron bioavailability from a bouillon drink.. We assessed whether there is a dose-response effect of added NaPP on iron bioavailability from local meals prepared with intrinsically labeled FePP-fortified bouillon cubes in young Nigerian women using iron stable isotope techniques.. In a double-blind, randomized, cross-over trial, women (n = 24; aged 18-40 y; mean BMI 20.5 kg/m2) consumed a Nigerian breakfast and lunch for 5 d prepared with bouillon cubes containing 2.5 mg 57Fe (as FePP) and 3 different molar ratios of NaPP: 57Fe (0:1, 3:1, and 6:1). Iron bioavailability was assessed by measuring 57Fe incorporation into erythrocytes 16 d after each 5 d NaPP: 57Fe feeding period. Data were analyzed using a linear regression model of log iron absorption on NaPP ratio, with body weight and baseline body iron stores as covariates and subject as a random intercept.. Of the women included, 46% were anemic and 26% were iron deficient. Iron bioavailability was 10.8, 9.8, and 11.0% for the 0:1, 3:1, and 6:1 NaPP:57Fe treatments, respectively. There was no dose-response effect of an increasing NaPP:57Fe ratio (β ± SE: 0.003 ± 0.028, P = 0.45).. In this study, the addition of NaPP did not increase iron bioavailability from FePP-fortified bouillon cubes. However, iron bioavailability from the Nigerian meals prepared with FePP-fortified bouillon cubes was higher than expected. These results are encouraging for the potential of bouillon cubes as a fortification vehicle. Further studies are needed to assess the effect of FePP-fortified bouillon cubes on improving iron status in low-income populations. This trial was registered at clinicaltrials.gov as NCT02815449.

Topics: Adult; Anemia; Anemia, Iron-Deficiency; Biological Availability; Cross-Over Studies; Diphosphates; Double-Blind Method; Erythrocytes; Female; Food, Fortified; Humans; Intestinal Absorption; Iron; Iron Isotopes; Meals; Nigeria; Young Adult

This study aimed at evaluating the effects obtained by administering 30 mg of micronised dispersible ferric pyrophosphate plus 300 mg of alpha-lactalbumin (MDFP-AL) compared to 80 mg of ferrous gluconate (FG) in pregnant women affected by iron-deficiency anemia (IDA).. We considered eligible all second-trimester singleton pregnancies in women affected by IDA. We excluded any other disease, twin pregnancies, any other pharmacologic/nutraceutical treatments (besides folic acid) before/during pregnancy. We randomized patients in two groups: one underwent treatment with 1 tablet of MDFP-AL/day, the other one with 1 tablet of FG/day, for 30 days. We evaluated hemoglobin (Hb), ferritin, red blood cells (RBCs), serum iron, hematocrit (Hct), and side effects at baseline (T0), after 15 days (T1) and 30 days (T2).. 50 women met the inclusion/exclusion criteria. We did not observe significant differences between the two groups for mean age, gestational age at the enrollment and parity. In MDFP-AL group, after 15 days (T1) Hb, ferritin, serum iron and Hct and were significantly improved respect to baseline (T0); after 30 days (T2), all the parameters, including RBCs, were significantly improved respect to baseline (T0). Similarly, in FG group the investigated parameters were improved both after 15 (T1) and 30 days (T2) respect to baseline (T0), although less in percentage terms respect to MDFP-AL group. The side effects rate was 24% in FG group, whereas MDFP-AL group did not show any significant side effect.. Overall, MDFP-AL is more effective and safe than FG for the treatment of IDA in pregnant women.

Topics: Adult; Anemia, Iron-Deficiency; Diphosphates; Double-Blind Method; Drug Compounding; Female; Ferrous Compounds; Gestational Age; Humans; Iron; Lactalbumin; Pregnancy; Prospective Studies; Young Adult

Iron deficiency is a common cause of anemia in pediatric patients with hemodialysis-dependent chronic kidney disease (CKD-5HD). Ferric pyrophosphate citrate (FPC, Triferic®) donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Administration of FPC via dialysate or intravenously (IV) may provide a suitable therapeutic option to current IV iron preparations for these patients.. The pharmacokinetics and safety of FPC administered via dialysate and IV to patients aged < 6 years (n = 3), 6 to < 12 years (n = 4), and 12 to <18 years (n = 15) were investigated in a multicenter, open-label, two-period, single-dose study. FPC (0.07 mg iron/kg) was infused IV into the venous blood return line during hemodialysis session no. 1. FPC iron was added to bicarbonate concentrate to deliver 2 μM (110 μg/L) iron via dialysate during hemodialysis session no. 2.. Mean serum total iron concentrations peaked 3 to 4 h after administration via dialysate and 2 to 4 h after IV administration and returned to baseline by 10 h after the start of hemodialysis for both routes. Iron exposure was greater after administration via dialysate than after IV administration. The absolute amount of absorbed iron after administration via dialysate roughly doubled with increasing age, but the weight-normalized amount of absorbed iron was relatively constant across age groups (~ 0.06-0.10 mg/kg). FPC was well tolerated in the small number of patients studied.. FPC iron can be administered to pediatric patients with CKD-5HD via dialysate or by the IV route. Further study of FPC administered to maintain hemoglobin concentration is indicated.

Topics: Administration, Intravenous; Adolescent; Anemia, Iron-Deficiency; Child; Child, Preschool; Dialysis Solutions; Diphosphates; Feasibility Studies; Female; Hematinics; Hemoglobins; Humans; Infant; Iron; Male; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome

Ferric pyrophosphate citrate (Triferic) is a water-soluble iron salt that is administered via dialysate to maintain iron balance and hemoglobin in hemodialysis patients. This double-blind, randomized, placebo-controlled, single-, ascending-dose study was conducted to evaluate the pharmacokinetics and safety of intravenous ferric pyrophosphate citrate in 48 healthy iron-replete subjects (drug, n = 36; placebo, n = 12). Single doses of 2.5, 5.0, 7.5, or 10 mg of ferric pyrophosphate citrate or placebo were administered over 4 hours, and single doses of 15 or 20 mg of ferric pyrophosphate citrate or placebo were administered over 12 hours via intravenous infusion. Serum total iron (sFe

Topics: Administration, Intravenous; Adolescent; Adult; Biomarkers; Citrates; Diphosphates; Dose-Response Relationship, Drug; Double-Blind Method; Female; Half-Life; Healthy Volunteers; Hematinics; Humans; Inflammation Mediators; Iron; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Young Adult

Iron fortification of rice is a promising strategy for improving iron nutrition. However, it is technically challenging because rice is consumed as intact grains, and ferric pyrophosphate (FePP), which is usually used for rice fortification, has low bioavailability.. We investigated whether the addition of a citric acid/trisodium citrate (CA/TSC) mixture before extrusion increases iron absorption in humans from FePP-fortified extruded rice grains.. We conducted an iron absorption study in iron-sufficient young women (n = 20), in which each participant consumed 4 different meals (4 mg Fe/meal): 1) extruded FePP-fortified rice (No CA/TSC); 2) extruded FePP-fortified rice with CA/TSC added before extrusion (CA/TSC extruded); 3) extruded FePP-fortified rice with CA/TSC solution added after cooking and before consumption (CA/TSC solution); and 4) nonextruded rice fortified with a FeSO4 solution added after cooking and before consumption (reference). Iron absorption was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. In in vitro experiments, we assessed the soluble and dialyzable iron from rice meals in which CA/TSC was added at different preparation stages and from meals with different iron:CA:TSC ratios.. Fractional iron absorption was significantly higher from CA/TSC-extruded meals (3.2%) than from No CA/TSC (1.7%) and CA/TSC solution (1.7%; all P < 0.05) and was not different from the FeSO4 reference meal (3.4%). In vitro solubility and dialyzability were higher in CA/TSC-extruded rice than in rice with No CA/TSC and CA/TSC solution, and solubility increased with higher amounts of added CA and TSC in extruded rice.. Iron bioavailability nearly doubled when CA/TSC was extruded with FePP into fortified rice, resulting in iron bioavailability comparable to that of FeSO4 We attribute this effect to an in situ generation of soluble FePP citrate moieties during extrusion and/or cooking because of the close physical proximity of FePP and CA/TSC in the extruded rice matrix. This trial was registered at clinicaltrials.gov as NCT02176759.

Topics: Adolescent; Adult; Biological Availability; Body Mass Index; Body Weight; C-Reactive Protein; Citrates; Citric Acid; Cooking; Cross-Over Studies; Diphosphates; Erythrocytes; Female; Food, Fortified; Humans; Iron; Iron, Dietary; Nutritional Status; Oryza; Single-Blind Method; Young Adult

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

Administration of ferric pyrophosphate citrate (FPC, Triferic™) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration.. Two identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 µM FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from baseline to end of treatment (EoT). Secondary end points included reticulocyte hemoglobin content (CHr) and serum ferritin.. In both trials, Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group (P < 0.001, combined results; 95% confidence interval [CI] 0.2-0.6). Placebo treatment resulted in significantly larger mean decreases from baseline in CHr (-0.9 pg versus -0.4 pg, P < 0.001) and serum ferritin (-133.1 µg/L versus -69.7 µg/L, P < 0.001) than FPC treatment. The proportions of patients with adverse and serious adverse events were similar in both treatment groups.. FPC delivered via dialysate during hemodialysis replaces iron losses, maintains Hgb concentrations, does not increase iron stores and exhibits a safety profile similar to placebo. FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Dialysis Solutions; Dietary Supplements; Diphosphates; Female; Ferric Compounds; Hematinics; Hemoglobins; Humans; Iron; Male; Middle Aged; Prospective Studies; Renal Dialysis; Single-Blind Method; Treatment Outcome

Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children.. A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4).. After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 μg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001).. IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions.. http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012.

Topics: Amodiaquine; Anemia; Antimalarials; Child, Preschool; Cote d'Ivoire; Diphosphates; Drug Combinations; Edetic Acid; Ferric Compounds; Food, Fortified; Hemoglobins; Humans; Infant; Inflammation; Iron; Iron Deficiencies; Malaria; Male; Prevalence; Pyrimethamine; Sulfadoxine

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

To investigate the effect of iron supplementation on iron deficiency anemia of childbearing age women, and to find out the optimal amount of iron intake for maintaining their health.. 74 childbearing age women aged 21 to 45 years with anemia were randomly assigned to intervention or control group by hemoglobin content, and a iron nutrition packet (mainly composed of ferric pyrophosphate and ferrous fumarate, containing iron 8 mg) or a placebo packet was given daily for six months, respectively. Hemoglobin, serum ferritin, food frequency and 24h dietary recall survey were performed before intervention and three and six months after intervention.. Hemoglobin and serum ferritin of the intervention group were significantly higher (P < 0.01) than that in control group after six months. The number of women with hemoglobin > or = 120 g/L in intervention and control group was 15 (44.1%) and 5 (14.3%), respectively (P < 0.01). The number of women with serum ferritin > or = 15 micro g/L in intervention and control group was 11 (34.4%) and 4 (12.5%), respectively (P < 0.05). The average dietary iron intake was 14.0 mg/d, mainly from plant foods. There was a positive correlation of total iron intake (dietary iron plus iron supplements) with hemoglobin (r = 0.57, P < 0.01). More menstrual blood and dietary fiber were the risk factors for iron deficiency anemia (P < 0.05).. The anemic status in childbearing age women could be improved by providing iron 8 mg daily for six months consecutively. Daily dietary intake of iron 23.2 mg can meet the requirement of maintaining normal iron storage for childbearing age women.

Topics: Adult; Anemia, Iron-Deficiency; Diphosphates; Female; Ferrous Compounds; Humans; Iron; Middle Aged; 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

Fe-deficiency anaemia is a worldwide health problem. We studied the influence of consuming an Fe-fortified fruit juice on Fe status in menstruating women. A randomised, double-blind, placebo-controlled study of 16 weeks of duration was performed. Subjects were randomised into two groups: the P group (n 58) or the F group (n 64), and consumed, as a supplement to their usual diet, 500 ml/d of a placebo fruit juice or an Fe-fortified fruit juice, respectively. The Fe-fortified fruit juice, containing microencapsulated iron pyrophosphate, provided 18 mg Fe/d (100 % of the RDA). At baseline and monthly, dietary intake, body weight and Fe parameters were determined: total erythrocytes, haematocrit, mean corpuscular volume (MCV), red blood cell distribution width (RDW), Hb, serum Fe, serum ferritin, serum transferrin, transferrin saturation, soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZnPP). The fruit juice consumption involved increased intake of carbohydrates and vitamin C, and increased BMI within normal limits. Ferritin was higher in the F group after week 4 (P < 0·05) and became 80 % higher than in the P group after week 16 (P < 0·001), and transferrin decreased in the F group compared with the P group after week 4 (P < 0·001). RDW was higher at weeks 4 and 8 in the F group compared with the P group (P < 0·05). Transferrin saturation increased after week 8, and haematocrit, MCV and Hb increased after week 12, in the F group compared with the P group. Serum Fe did not change. sTfR and ZnPP decreased in the F group at week 16 (P < 0·05). Iron pyrophosphate-fortified fruit juice improves Fe status and may be used to prevent Fe-deficiency anaemia.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Beverages; Blood Pressure; Body Weight; Diet; Dietary Supplements; Diphosphates; Double-Blind Method; Drug Compounding; Feeding Behavior; Female; Fruit; Humans; Iron; Motor Activity; Spain; Young Adult

Micronized ferric pyrophosphate (MFPP) in extruded rice kernels mixed in a rice-based meal could be an effective strategy for improving iron status of children in India.. The objective was to determine the impact of MFPP supplied through extruded rice kernels in a rice-based meal on iron status of children participating in the midday meal (MDM) scheme in India.. The sensory characteristics of cooked rice containing MFPP in extruded rice kernels, in vitro availability, and loss of iron during cooking from a typical MDM consisting of 125 g rice (dry weight) containing 19 mg Fe [fortified rice (FR); normal rice mixed with Ultra Rice (extruded kernels containing MFPP of ∼3.14-μm mean particle size)] in comparison with unfortified rice (UFR) were tested. A double-blind, 8-mo, placebo-controlled trial was conducted in 5-11-y-old schoolchildren (n = 140) who were randomly assigned to receive either an FR-MDM or a UFR-MDM. Average consumption amounts of the MDM, height, weight, hemoglobin, ferritin, and C-reactive protein were measured at baseline and at 8 mo.. The sensory qualities of cooked FR and UFR were similar. The in vitro iron availability from FR-MDM (1.3%) was significantly (P < 0.05) lower than that from UFR-MDM (3.3%). Providing FR-MDM to the schoolchildren for 8 mo improved ferritin significantly (P < 0.001), by 8.2 ± 2.10 μg/L. However, the increase in hemoglobin was similar between groups (FR: 0.99 ± 0.10 g/dL; UFR: 1.15 ± 0.10 g/dL), which suggests that other factors beyond additional iron intake had a large influence on hemoglobin concentration. The prevalence of iron deficiency decreased significantly (P < 0.05) in the FR group (33-14%) and increased marginally in the UFR group (31-37%). The prevalence of anemia and iron deficiency anemia was similar between groups at baseline and at 8 mo.. Regular intake of 19 mg Fe/d in MFPP supplied through extruded rice kernels improves iron stores and reduces iron deficiency among schoolchildren in India.

Topics: Anemia, Iron-Deficiency; C-Reactive Protein; Child; Child, Preschool; Diphosphates; Double-Blind Method; Female; Ferritins; Food, Fortified; Hemoglobins; Humans; India; Iron; Male; Oryza; Placebos; Rural Population; Schools; Statistics, Nonparametric

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

Random serial sampling is widely used in population pharmacokinetic studies and may have advantages compared with conventional fixed time-point evaluation of iron fortification.. Our objective was to validate random serial sampling to judge the efficacy of iron fortification of a low-fat margarine.. We conducted a 32-wk placebo-controlled, double-blind, iron-intervention trial in 18-40-y-old Swiss women (n = 142) with serum ferritin (SF) concentrations <25 μg/L. Women were randomly assigned to 3 groups to receive 20 g margarine, with 14 mg added iron as either micronized ground ferric pyrophosphate (MGFePP) or sodium iron edetate (NaFeEDTA), or placebo daily. We measured hemoglobin and iron status of subjects at 2 fixed time points (at baseline and the endpoint) plus 3 randomly assigned time points between 4 and 28 wk. With the use of bootstrapping, the number of observations per individual was reduced to 3 and then compared with the 5-time-point data. Mixed-effects models were used to estimate iron repletion over time for random sampling, and analysis of covariance was used for fixed time-point sampling.. Body iron stores increased in women who received MGFePP or NaFeEDTA compared with women who received placebo (P < 0.05). The increase in body iron stores with NaFeEDTA fortification was 2-3 times the increase with MGFePP fortification (P < 0.05); the difference was more marked in women with baseline SF concentrations <15 μg/L (P < 0.05). Random serial sampling reduced the required sample size per group to one-tenth of that for 2 fixed time points. Compared with the 5-time-point analysis, the 3-time-point sparse sampling generated comparable estimates of efficacy.. When used to evaluate the efficacy of iron fortificants, random serial sampling can reduce the sample size, invasiveness, and costs while increasing sensitivity. Random serial sampling more clearly describes the pattern of iron repletion and may prove useful in evaluating other micronutrient interventions.

Topics: Adolescent; Adult; Analysis of Variance; Anemia, Iron-Deficiency; Diphosphates; Double-Blind Method; Edetic Acid; Female; Ferric Compounds; Ferritins; Food, Fortified; Humans; Iron; Iron, Dietary; Margarine; Models, Biological; Nutrition Assessment; Sample Size; Young Adult

Preventing iron deficiency has been a main target of the World Health Organization since 1992. Difficulties to reach dietary recommended iron intakes and to enhance iron absorption should be overcome. We compared in iron-deficient women the bioavailability of iron of three meat pate products enriched with ferrous sulfate, ferric pyrophosphate encapsulated in liposomes, or ferric pyrophosphate encapsulated in liposomes plus a hemoglobin-based meat pigment.. Seventeen women with low iron stores (ferritin <30 microg/L) took part in a three-way, randomized, crossover, double-blind postprandial intervention. Test meals consisted of 80 g of the three different enriched meat pate products, which were spread on two slices of white bread. The pate composition was 13.5 g of protein/100 g, 30 g of fat/100 g (49% monounsaturated fatty acids, 35% saturated fatty acids, 16% polyunsaturated fatty acids), 1 g of carbohydrates/100 g, and 19 mg of total iron (including 15 mg of iron from the test fortificants). Blood samples were taken at baseline and each hour for 6 h after eating the meal and serum iron was determined.. Serum iron concentration evolution during the postprandial study was similar with the three meals, and maximum concentrations were obtained between hours 2 and 4. The effect of type of fortificant was not significant.. Consumption of meat pate fortified with ferric pyrophosphate encapsulated in liposomes can be part of a dietary strategy for preventing iron deficiency in humans. The addition of larger amounts of a meat pigment rich in heme iron should be further studied.

Topics: Adult; Anemia, Iron-Deficiency; Area Under Curve; Biological Availability; Cross-Over Studies; Diphosphates; Double-Blind Method; Female; Food, Fortified; Humans; Intestinal Absorption; Iron; Iron, Dietary; Liposomes; Meat Products; Postprandial Period; 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

Universal fortification of staple foods with iron has been widely promoted as a cost-effective strategy to reduce iron deficiency in developing-country populations. Nonetheless, relatively few efficacy trials have been reported to date to demonstrate impact on iron status. The Ultra Rice technology provides a means of delivering fortificant iron via rice.. The objective of this study was to test the efficacy of rice fortified with microencapsulated, micronized iron pyrophosphate to improve the iron status of women in Mexico in a randomized, controlled intervention trial.. Nonpregnant, nonlactating women 18 to 49 years of age were recruited from six factories. The women received a daily portion of cooked rice 5 days per week for a period of 6 months, before and after which iron status indicators were determined in venous blood samples.. The average intake of iron from the fortificant was 13 mg/day. Mean plasma ferritin concentration and estimated body iron stores were significantly higher, and transferrin receptors were lower, in the iron-fortified rice group following the intervention. Mean hemoglobin concentration also increased in the treatment group, but the increase was significant only when the analysis was restricted to those with baseline hemoglobin < 12.8 g/dL. The absolute reduction in anemia and iron deficiency was 10.3 and 15.1 percentage points, respectively. Total iron intake from fortificant was a significant covariate of change in body iron stores. The overall prevalence of anemia was reduced by 80%.. Fortification of rice with iron using this technology is an efficacious strategy for preventing iron deficiency.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Diphosphates; Female; Ferritins; Food, Fortified; Hemoglobins; Humans; Iron; Iron, Dietary; Mexico; Middle Aged; Nutritional Status; Oryza; Prevalence; Receptors, Transferrin; Treatment Outcome

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

Dual fortification of salt with iodine and iron could be a sustainable approach to combating iodine and iron deficiencies.. We compared the efficacy of dual-fortified salt (DFS) made by using 2 proposed contrasting formulas-one fortifying with iron as micronized ground ferric pyrophosphate (MGFePP) and the other with iron as encapsulated ferrous fumarate (EFF)-with the efficacy of iodized salt (IS) in schoolchildren in rural southern India.. After stability and acceptability testing, a double-blind, household-based intervention was conducted in 5-15-y-old children (n = 458) randomly assigned into 3 groups to receive IS or DFS with iron as MGFePP or EFF, both at 2 mg/g salt. We measured hemoglobin, iron status, and urinary iodine at baseline, 5 mo, and 10 mo.. Median serum ferritin and calculated median body iron improved significantly in the 2 groups receiving iron. After 10 mo, the prevalence of anemia decreased from 16.8% to 7.7% in the MGFePP group (P < 0.05) and from 15.1% to 5.0% in the EFF group (P < 0.01). The median urinary iodine concentration increased significantly in the IS and EFF groups (P < 0.001) but not in the MGFePP group. Losses of iodine in salt with 1.8% moisture were high for MGFePP, whereas the EFF segregated in salt with 0.5% moisture and caused color changes in some local foods.. Both DFSs were efficacious in reducing the prevalence of anemia and iron deficiency in school-age children. Local salt characteristics should be taken into consideration when choosing an iron fortificant for DFS to achieve optimal iodine stability and color.

Topics: Adolescent; Anemia, Iron-Deficiency; Biological Availability; Child; Child Nutritional Physiological Phenomena; Child, Preschool; Diphosphates; Double-Blind Method; Female; Ferritins; Ferrous Compounds; Food, Fortified; Goiter; Hemoglobins; Humans; India; Iodine; Iron; Iron Deficiencies; Iron, Dietary; Male; Prevalence; Rural Health; Sodium Chloride, Dietary; Treatment Outcome

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

Chronic lead poisoning and iron deficiency are concentrated in urban children from lower socioeconomic strata, and both impair neurocognitive development. Our study objective was to determine if iron fortification reduces blood lead levels in urban, lead-exposed, iron-deficient children in Bangalore, India.. A randomized, double-blind, controlled school-based feeding trial was done in 5- to 13-year-old iron-deficient children (n = 186). At baseline, a high prevalence of lead poisoning was found in the younger children. Subsequently, all 5- to 9-year-old children participating in the trial (n = 134) were followed to determine if iron fortification would affect their blood lead levels.. Children were dewormed and fed 6 days/week for 16 weeks either an iron-fortified rice meal (approximately 15 mg of iron per day as ferric pyrophosphate) or an identical control meal without added iron. Feeding was directly supervised and compliance monitored.. Hemoglobin, serum ferritin, C-reactive protein, transferrin receptor, zinc protoporphyrin, and blood lead concentrations were measured.. The prevalence of iron deficiency was significantly reduced in the iron group (from 70% to 28%) compared with the control group (76% to 55%). There was a significant decrease in median blood lead concentration in the iron group compared with the control group. The prevalence of blood lead levels > or =10 microg/dL was significantly reduced in the iron group (from 65% to 29%) compared with the control group (68% to 55%).. Our findings suggest providing iron in a fortified food to lead-exposed children may reduce chronic lead intoxication. Iron fortification may be an effective and sustainable strategy to accompany environmental lead abatement.

Topics: Adolescent; Child; Child, Preschool; Diphosphates; Double-Blind Method; Food, Fortified; Humans; India; Iron; Iron Deficiencies; Lead; Lead Poisoning; Urban Population

Deficiencies of iron and iodine are common in West Africa, and salt is one of very few food vehicles available for fortification. Salt dual-fortified with iodine and micronized ground ferric pyrophosphate (FePP) was tested for its efficacy in rural, tropical Côte d'Ivoire. First, salt and iron intakes, and iron bioavailability were estimated using 3-d weighed food records in 24 households. Local iodized salt was then fortified with 3 mg Fe/g salt as ground FePP (mean particle size = 2.5 mum), and stability, sensory and acceptability trials were done. The dual fortified salt (DFS) was distributed to households and its efficacy compared with that of iodized salt (IS) in a 6-mo, double-blind trial in 5- to 15-y-old iron-deficient children (n = 123). All children were dewormed at baseline. After 6 mo, serum ferritin (SF) and transferrin receptor (TfR) concentrations as well as body iron stores improved significantly in the DFS group but not in the IS GROUP (P < 0.05). Body iron increased from 4.6 +/- 2.7 to 5.9 +/- 2.7 mg/kg (mean +/- SD) in the DFS group; concentrations before and after treatment in the IS group were 5.5 +/- 2.9 and 5.6 +/- 3.1 mg/kg, respectively. The hemoglobin concentration and the prevalence of anemia did not change in either group. The prevalences of malaria, soil-transmitted helminths, and riboflavin deficiency were 55, 14, and 66%, respectively. In tropical West Africa, low-grade salt fortified with micronized ground FePP increased body iron stores but not hemoglobin in children. Iron utilization may have been impaired by the high prevalence of malaria and concurrent nutrient deficiencies.

Topics: Adolescent; Anemia, Iron-Deficiency; Biological Availability; Child; Child, Preschool; Cote d'Ivoire; Diphosphates; Double-Blind Method; Female; Hemoglobins; Humans; Intestinal Absorption; Iodine; Iron; Iron, Dietary; Malaria; Male; Prevalence; Rural Health; Sodium Chloride, Dietary

Home-fortification of complementary foods with micronutrients (including iron) as Sprinkles is a new strategy to control iron deficiency and anaemia in developing countries. However, the most effective dose and form of iron is not known. The purpose of this study was to compare the efficacy of various doses (12.5, 20 or 30 mg) and treatment methods (multi-micronutrient Sprinkles vs. ferrous sulphate drops) on haemoglobin (Hb) concentration after 8 weeks of treatment in anaemic children. In total, 133 anaemic Ghanaian children (Hb 70-99 g L(-1)) aged 6-18 months were randomly assigned to one of five daily interventions for 8 weeks. Out of the five interventions, four used Sprinkles, and one used iron drops. Of the four Sprinkles groups, three included 12.5, 20 or 30 mg of iron as ferrous fumarate, and one included 20 mg of iron as ferric pyrophosphate. The iron drops group included 12.5 mg of iron as liquid ferrous sulphate. Hb concentrations were measured at baseline, week 3 and week 8. The primary outcome measure was Hb concentration at 8 weeks after treatment. We compared differences in Hb and ferritin concentrations and prevalence of iron deficiency anaemia (Hb < 100 g L(-1) and soluble transferrin receptor concentrations >8.5 mg L(-1)) from baseline to 8 weeks within and between groups. Adherence and reporting of side effects (staining of the teeth, ease of use, diarrhoea and darkening of stools) were compared between groups. Mean change in Hb was 1.4 g L(-1) (SD = 1.8) (P = 0.0001). Change in Hb concentrations from baseline to 8 weeks was significant in all groups (P = 0.0001-0.0007), with no differences across groups. Geometric means of serum ferritin varied from 18.6 to 44.0 microg L(-1) at baseline. At week 8, these means were in the interval of 48.0-78.3 microg L(-1), with no group differences. Prevalence of iron deficiency anaemia decreased significantly from baseline to 8 weeks in all groups with the exception of the iron drops group, with no group differences. Adherence was lower in the drops group (64%) as compared with Sprinkles groups (84%). Greater staining of the teeth and less ease of use were reported in the drops group as compared with Sprinkles groups. A dose as low as 12.5 mg of iron as ferrous fumarate when provided as Sprinkles may be effective in anaemic children.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Capsules; Dietary Supplements; Diphosphates; Dose-Response Relationship, Drug; Female; Ferrous Compounds; Food, Fortified; Ghana; Hemoglobins; Humans; Infant; Iron; Male; Micronutrients; Patient Compliance; Prospective Studies; Treatment Outcome

Iron fortification of rice could be an effective strategy for reducing iron deficiency anemia in South Asia.. We aimed to determine whether extruded rice grains fortified with micronized ground ferric pyrophosphate (MGFP) would increase body iron stores in children.. In a double-blind, 7-mo, school-based feeding trial in Bangalore, India, iron-depleted, 6-13-y-old children (n = 184) were randomly assigned to receive either a rice-based lunch meal fortified with 20 mg Fe as MGFP or an identical but unfortified control meal. The meals were consumed under direct supervision, and daily leftovers were weighed. All children were dewormed at baseline and at 3.5 mo. Iron status and hemoglobin were measured at baseline, 3.5 mo, and 7 mo.. At baseline, the prevalences of iron deficiency and iron deficiency anemia in the total sample were 78% and 29%, respectively. After 7 mo of feeding, there was a significant increase in body iron stores in both study groups (P < 0.001), with a greater increase in the iron group than in the control group (P < 0.05). There was a significant time x treatment interaction for iron deficiency, which fell from 78% to 25% in the dewormed iron group and from 79% to 49% in the dewormed control group. Iron deficiency anemia decreased from 30% to 15% (NS) in the iron group but remained virtually unchanged in the control group (28% and 27%). In sensory tests, the MGFP-fortified rice (fortified at 3 and 5 mg Fe/100 g) was indistinguishable from natural rice, in both cooked and uncooked form.. Extruded rice fortified with MGFP has excellent sensory characteristics. Fed in a school lunch meal, it increases iron stores and reduces the prevalence of iron deficiency in Indian children.

Topics: Adolescent; Anemia, Iron-Deficiency; Biological Availability; Child; Diphosphates; Double-Blind Method; Female; Food Services; Food, Fortified; Hemoglobins; Humans; India; Iron; Male; Oryza; School Health Services

In many developing countries, children are at high risk for both goiter and anemia. In areas of subsistence farming in rural Africa, salt is one of the few regularly purchased food items and could be a good fortification vehicle for iodine and iron, provided that a stable yet bioavailable iron fortificant is used.. We tested the efficacy of salt dual-fortified with iodine and micronized ferric pyrophosphate for reducing the prevalence of iodine and iron deficiencies in children.. In rural northern Morocco, we fortified local salt with 25 microg I (as potassium iodate)/g salt and 2 mg Fe (as micronized ferric pyrophosphate; mean particle size = 2.5 microm)/g salt. After storage and acceptability trials, we compared the efficacy of the dual-fortified salt (DFS) with that of iodized salt in a 10-mo, randomized, double-blind trial in iodine-deficient 6-15-y-old children (n = 158) with a high prevalence of anemia.. After storage for 6 mo, there were no significant differences in iodine content or color lightness between the DFS and iodized salt. During the efficacy trial, the DFS provided approximately 18 mg Fe/d; iron absorption was estimated to be approximately 2%. After 10 mo of treatment in the DFS group, mean hemoglobin increased by 16 g/L (P < 0.01), iron status and body iron stores increased significantly (P < 0.01), and the prevalence of iron deficiency anemia decreased from 30% at baseline to 5% (P < 0.001). In both groups, urinary iodine (P < 0.001) and thyroid volume (P < 0.01) improved significantly from baseline.. A DFS containing iodine and micronized ferric pyrophosphate can be an effective fortification strategy in rural Africa.

Topics: Adolescent; Adolescent Nutritional Physiological Phenomena; Anemia, Iron-Deficiency; Biological Availability; Child; Child Nutritional Physiological Phenomena; Diphosphates; Double-Blind Method; Female; Food Handling; Food, Fortified; Goiter; Humans; Intestinal Absorption; Iodine; Iron; Iron, Dietary; Male; Morocco; Prevalence; Rural Health; Sodium Chloride, Dietary; Thyroid Gland; Time Factors; Treatment Outcome

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

Infant cereals are commonly fortified with insoluble iron compounds with low relative bioavailability, such as ferric pyrophosphate, because of organoleptic changes that occur after addition of water-soluble iron sources.. Our objective was to compare iron bioavailability from ferric pyrophosphate with an alternative iron source that is soluble in dilute acid, ferrous fumarate, and to evaluate the influence of ascorbic acid on iron bioavailability from ferrous fumarate in infants.. Iron bioavailability was measured as the incorporation of stable iron isotopes into erythrocytes 14 d after administration of labeled test meals (25 g dry wheat and soy infant cereal, 100 g water, and 2.5 mg Fe as [57Fe]ferric pyrophosphate or [57Fe]ferrous fumarate). Ascorbic acid was added to all test meals (25 mg in study 1 or 25 or 50 mg in study 2). Infants were fed each test meal on 4 consecutive days under standardized conditions. The 2 different test meals within each study were administered 2 wk apart in a crossover design.. Geometric mean iron bioavailability was significantly higher from [57Fe]ferrous fumarate than from [57Fe]ferric pyrophosphate [4.1% (range: 1.7-14.7%) compared with 1.3% (range: 0. 7-2.7%); n = 8, P = 0.008]. In this study, doubling the ascorbic acid content did not further enhance iron bioavailability; the geometric means (range) were 3.4% (1.9-6.6%) and 4.2% (1.2-18.7%) for the test meals with 25 and 50 mg ascorbic acid added, respectively (n = 9).. Iron bioavailability from iron-fortified infant cereals can be improved by using an iron compound with high relative bioavailability and by ensuring adequate ascorbic acid content of the product.

Topics: Biological Availability; Diphosphates; Edible Grain; Erythrocytes; Female; Ferrous Compounds; Food, Fortified; Glycine max; Humans; Infant; Infant Food; Iron; Iron Isotopes; Male; Triticum

Soluble iron salts are toxic for parenteral administration because free iron catalyzes free radical generation. Pyrophosphate strongly complexes iron and enhances iron transport between transferrin, ferritin, and tissues. Hemodialysis patients need iron to replenish ongoing losses. We evaluated the short-term safety and efficacy of infusing soluble ferric pyrophosphate by dialysate.. Maintenance hemodialysis patients receiving erythropoietin were stabilized on regular doses of intravenous (i.v.) iron dextran after oral iron supplements were discontinued. During the treatment phase, 10 patients received ferric pyrophosphate via hemodialysis as monthly dialysate iron concentrations were progressively increased from 2, 4, 8, to 12 micrograms/dl and were then sustained for two additional months at 12 micrograms/dl (dialysate iron group); 11 control patients were continued on i.v. iron dextran (i.v. iron group).. Hemoglobin, serum iron parameters, and the erythropoietin dose did not change significantly from month 0 to month 6, both within and between the two groups. The weekly dose of i.v. iron (mean +/- SD) needed to maintain iron balance during month 6 was 56 +/- 37 mg in the i.v. iron group compared with 10 +/- 23 mg in the dialysate iron group (P = 0.001). Intravenous iron was required by all 11 patients in the i.v. iron group compared with only 2 of the 10 patients receiving 12 micrograms/dl dialysate iron. The incidence of adverse effects was similar in both groups.. Slow infusion of soluble iron pyrophosphate by hemodialysis may be a safe and effective alternative to the i.v. administration of colloidal iron dextran in maintenance hemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Dialysis Solutions; Diphosphates; Drug Administration Routes; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Solubility; Transferrin

To evaluate the role of recombinant human erythropoietin in reducing the need for homologous blood transfusion during operations by studying its effect on the recovery of postoperative anaemia.. Randomised controlled trial.. University hospital, Japan.. 10 patients with gastric cancer undergoing distal gastrectomy.. 5 Patients were given erythropoietin 200 IU/kg/day together with ferric pyrophosphate 40 mg/day intravenously for seven days before operation and 14 days afterwards, and 5 were given ferric pyrophosphate 40 mg/day alone (control group).. Packed cell volume, haemoglobin concentration, and white and red cell counts.. There was no significant change in packed cell volume after the operation in the erythropoietin group, but in the control group it dropped from a mean (SD) of 0.378 (0.074) before operation to 0.329 (0.068) on day 1 (p < 0.05). Haemoglobin concentrations were significantly higher in the erythropoietin group than the control group on day 7 (mean (SD) 137 (14) compared with 110 (19) p < 0.05), and on day 10 (140 (9) compared with 108 (15) p < 0.01) after operation.. Erythropoietin prevented postoperative anaemia after gastrectomy as judged by packed cell volume, haemoglobin concentration, and red cell count. Erythropoietin given before and after operation therefore has the potential to reduce the need for homologous blood transfusion during and after major operations.

Topics: Adult; Aged; Anemia; Blood Cell Count; Diphosphates; Erythropoietin; Female; Gastrectomy; Hematocrit; Hemoglobins; Humans; Iron; Male; Middle Aged; Pilot Projects; Postoperative Care; Postoperative Complications; Preoperative Care; Recombinant Proteins; Stomach Neoplasms; 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

Topics: Diphosphates; Ferric Compounds; Food, Fortified; Iron; Phenols; Salts

To evaluate the potential ethnic differences of ferric pyrophosphate citrate (FPC, Triferic) in healthy subjects and patients with hemodialysis-dependent stage 5 chronic kidney disease (CKD-5HD) and identify covariates that may influence pharmacokinetics (PK) of FPC.. Data were collected from 2 Asian and 4 non-Asian clinical studies involving healthy subjects and CKD-5HD patients. Three population PK models were developed: M1 for intravenous (IV) administration of FPC in healthy subjects; M2 for dialysate administration of FPC in CKD-5HD patients; M3 for pre-dialyzer administration of FPC in CKD-5HD patients. All the models were fitted to concentration versus time data of FPC using the nonlinear mixed effect approach with the NONMEM. In total, 26 Asians and 65 non-Asians were included in the final model analysis database. Forty healthy subjects were administered FPC via intravenous (IV) route and 51 patients with CKD-5HD via dialysate (N = 50) and pre-dialyzer blood circuit administration (N = 51). The PK parameters of FPC IV were similar. The population PK model showed good parameter precision and reliability as shown by model evaluation, and no relevant influence of ethnicity on PK parameters was observed. In healthy subjects, the maximum observed plasma concentration (C. The population pharmacokinetics model successfully described the PK parameters of FPC in healthy subjects and CKD-5HD patients and were comparable between Asian and non-Asian populations.

Topics: Citrates; Dialysis Solutions; Diphosphates; Ethnicity; Hematinics; Humans; Iron; Kidney Failure, Chronic; Reproducibility of Results

Anemia is a common complication in patients with hemodialysis-dependent chronic kidney disease (HDD-CKD). Anemia is principally the result of erythropoietin deficiency, inflammation, and iron deficiency. High molecular weight iron oxide nanoparticles (IONP) are routinely administered intravenously to replace iron losses and, although effective, there are lingering concerns about possible safety issues. Ferric pyrophosphate citrate (FPC, Triferic, Triferic AVNU [Triferic and Triferic AVNU are the proprietary name for ferric pyrophosphate citrate. Triferic and Triferic AVNU are registered trademarks of Rockwell medical Inc.]) is a complex iron salt that donates iron directly to plasma transferrin. FPC is devoid of any carbohydrate moiety and is administered

Topics: Anemia; Anemia, Iron-Deficiency; Citrates; Dialysis Solutions; Diphosphates; Ferric Compounds; Hemoglobins; Humans; Inflammation; Iron; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome

This study aimed to determine the effects of liposomal iron pyrophosphate/ascorbic acid on clinical and psychological outcomes in pregnant women. Women at the 11th-13th weeks of gestation with iron deficiency anaemia assuming Sideremil™ from April 2018 to May 2019 were recruited. Haematochemical, obstetric, neonatal and psychological outcomes were investigated at the enrolment, 21-23 weeks of gestation, 30-32 weeks of gestation and after 6 weeks from childbirth. Results showed significant positive effects on haemoglobin, ferritin, sideremia and transferrin levels, compared to baseline data. A significant improvement of anxiety and depression levels was also observed. Regarding the quality of life, all the domains significantly improved, especially the Physical Role domain. Our results indicate that Sideremil

Topics: Anemia, Iron-Deficiency; Ascorbic Acid; Dietary Supplements; Diphosphates; Female; Humans; Infant, Newborn; Iron; Iron Deficiencies; Pregnancy; Pregnant Women; Quality of Life

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

This paper presents a comparative evaluation of different oral ferric iron formulations for ability to retain Fe

Topics: Animals; Biological Transport; Body Fluids; Caco-2 Cells; Diphosphates; Dosage Forms; Drug Liberation; Humans; Intestinal Mucosa; Iron; Lecithins; Rats; Sucrose

The prevalence of iron deficiency anemia (IDA) is predominant in women and children especially in developing countries. The disorder affects cognitive functions and physical activity. Although oral iron supplementation and parenteral therapy remains the preferred choice of treatment, gastric side effects and risk of iron overload decreases adherence to therapy. Transdermal route is an established approach, which circumvents the side effects associated with conventional therapy. In this project, an attempt was made to investigate the use of rapidly dissolving microneedles loaded with ferric pyrophosphate (FPP) as a potential therapeutic approach for management of IDA. Microneedle array patches were made using the micromolding technique and tested in vitro using rat skin to check the duration required for dissolution/disappearance of needles. The ability of FPP-loaded microneedles to replenish iron was investigated in anemic rats. Rats were fed iron-deficient diet for 5 weeks to induce IDA following which microneedle treatment was initiated. Recovery of rats from anemic state was monitored by measuring hematological and biochemical parameters. Results from in vivo study displayed significant improvements in hemoglobin and serum iron levels after 2-week treatment with FPP-loaded microneedles. The study effectively demonstrated the potential of microneedle-mediated iron replenishment for treatment of IDA.

Topics: Administration, Cutaneous; Anemia, Iron-Deficiency; Animals; Diphosphates; Drug Delivery Systems; Humans; Iron; Male; Needles; Rats; Rats, Sprague-Dawley; Skin Absorption; Solubility; Transdermal Patch

The present study aimed to demonstrate that Sideral

Topics: Animals; Diphosphates; Intestinal Absorption; Iron; Lecithins; Macrophages; Male; Microscopy, Confocal; Rats; Rats, Wistar

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

There are several options available for intravenous application of iron supplements, but they all have a similar structure:-an iron core surrounded by a carbohydrate coating. These nanoparticles require processing by the reticuloendothelial system to release iron, which is subsequently picked up by the iron-binding protein transferrin and distributed throughout the body, with most of the iron supplied to the bone marrow. This process risks exposing cells and tissues to free iron, which is potentially toxic due to its high redox activity. A new parenteral iron formation, ferric pyrophosphate citrate (FPC), has a novel structure that differs from conventional intravenous iron formulations, consisting of an iron atom complexed to one pyrophosphate and two citrate anions. In this study, we show that FPC can directly transfer iron to apo-transferrin. Kinetic analyses reveal that FPC donates iron to apo-transferrin with fast binding kinetics. In addition, the crystal structure of transferrin bound to FPC shows that FPC can donate iron to both iron-binding sites found within the transferrin structure. Examination of the iron-binding sites demonstrates that the iron atoms in both sites are fully encapsulated, forming bonds with amino acid side chains in the protein as well as pyrophosphate and carbonate anions. Taken together, these data demonstrate that, unlike intravenous iron formulations, FPC can directly and rapidly donate iron to transferrin in a manner that does not expose cells and tissues to the damaging effects of free, redox-active iron.

Topics: Binding Sites; Citric Acid; Crystallography, X-Ray; Diphosphates; Humans; Iron; Kinetics; Models, Molecular; Transferrin

Iron deficiency is a significant health problem across the world. While many patients benefit from oral iron supplements, some, including those on hemodialysis require intravenous iron therapy to maintain adequate iron levels. Until recently, all iron compounds suitable for parenteral administration were colloidal iron-carbohydrate conjugates that require uptake and processing by macrophages. These compounds are associated with variable risk of anaphylaxis, oxidative stress, and inflammation, depending on their physicochemical characteristics. Ferric pyrophosphate citrate (FPC) is a novel iron compound that was approved for parenteral administration by US Food and Drug Administration in 2015. Here we report the physicochemical characteristics of FPC. FPC is a noncolloidal, highly water soluble, complex iron salt that does not contain a carbohydrate moiety. X-ray absorption spectroscopy data indicate that FPC consists of iron (III) complexed with one pyrophosphate and two citrate molecules in the solid state. This structure is preserved in solution and stable for several months, rendering it suitable for pharmaceutical applications in solid or solution state.

Topics: Chemistry, Physical; Citric Acid; Diphosphates; Iron; Molecular Structure

Topics: Adsorption; Diphosphates; Hemoglobins; Humans; Iron; Isotopes; Mass Spectrometry; Metal Nanoparticles

Topics: Anemia, Iron-Deficiency; Animals; Diphosphates; Disease Models, Animal; Injections, Intraperitoneal; Iron; Peritoneal Dialysis; Pilot Projects; Rabbits; Random Allocation; Reference Values; Risk Factors; Treatment Outcome

Currently, the iron compounds are administered via oral and parenteral routes in patients of all ages, to treat iron deficiency. Despite continued efforts to supplement iron via these conventional routes, iron deficiency still remains the most prevalent nutritional disorder all over the world. Transdermal replenishment of iron is a novel, potential approach of iron replenishment. Ferric pyrophosphate (FPP) was found to be a suitable source of iron for transdermal replenishment. The safety of FPP was assessed in this project by challenging the dermal fibroblast cells with high concentration of FPP. The cell viability assay and reactive oxygen species assay were performed. The soluble microneedle array was developed, incorporated with FPP and the kinetics of free iron in the skin; extracellular fluid following dermal administration of microneedle array was investigated in hairless rats. From the cell based assays, FPP was selected as one of the potential iron sources for transdermal delivery. The microneedles were found to dissolve in the skin fluid within 3 hours of administration. The FPP concentration in the dermal extracellular fluid declined after complete dissolution of the microneedle array. Overall, the studies demonstrated the safety of FPP for dermal delivery and the feasibility of soluble microneedle approach for transdermal iron replenishment therapy.

Topics: Administration, Cutaneous; Animals; Cell Survival; Diphosphates; Drug Delivery Systems; Fibroblasts; Humans; Iron; Kinetics; Microinjections; Needles; Rats; Rats, Hairless; Reactive Oxygen Species; Safety; Skin; Skin Absorption

Ferric pyrophosphate (FePP) is a widely used iron source in food fortification and in nutritional supplements, due to its white colour, that is very uncommon for insoluble Fe salts. Although its dissolution is an important determinant of Fe adsorption in human body, the solubility characteristics of FePP are complex and not well understood. This report is a study on the solubility of FePP as a function of pH and excess of pyrophosphate ions. FePP powder is sparingly soluble in the pH range of 3-6 but slightly soluble at pH<2 and pH>8. In the presence of pyrophosphate ions the solubility of FePP strongly increases at pH 5-8.5 due to formation a soluble complex between Fe(III) and pyrophosphate ions, which leads to an 8-10-fold increase in the total ionic iron concentration. This finding is beneficial for enhancing iron bioavailability, which important for the design of fortified food, beverages, and nutraceutical products.

Topics: Beverages; Biological Availability; Dietary Supplements; Diphosphates; Food, Fortified; Humans; Iron; Solubility

Iron deficiency anemia is one of the major nutritional deficiency disorders. Iron deficiency anemia occurs due to decreased absorption of iron from diet, chronic blood loss and other associated diseases. The importance of iron and deleterious effects of iron deficiency anemia are discussed briefly in this review followed by the transdermal approaches to deliver iron. Transdermal delivery of iron would be able to overcome the side effects associated with conventional oral and parenteral iron therapy and improves the patient compliance. During preliminary investigations, ferric pyrophosphate and iron dextran were selected as iron sources for transdermal delivery. Different biophysical techniques were explored to assess their efficiency in delivering iron across the skin, and in vivo studies were carried out using anemic rat model. Transdermal iron delivery is a promising approach that could make a huge positive impact on patients suffering with iron deficiency.

Topics: Administration, Cutaneous; Anemia, Iron-Deficiency; Animals; Diphosphates; Drug Delivery Systems; Humans; Iontophoresis; Iron; Iron-Dextran Complex; Rats; Skin Absorption; Technology, Pharmaceutical

Ferric pyrophosphate is a widely used material in the area of mineral fortification but its synthesis and properties in colloidal form are largely unknown. In this article, we report on the synthesis and characterisation of colloidal iron(III) pyrophosphate particles with potential for application as a food additive in iron-fortified products. We present a convenient and food grade synthetic method yielding stable colloids of nanometre size with a distinctive white colour, a unique characteristic for iron-containing colloids. Physical properties of the colloids were investigated using different techniques, to assess particle crystallinity, surface charge, mass density, refractive index, internal structure, elemental composition and magnetic properties. The findings of this research are especially relevant for food and beverage science and technology and will help develop a more effective use of these fortifiers in colloidal form.

Topics: Colloids; Diphosphates; Ferric Compounds; Iron

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 ability to acquire iron from various sources has been demonstrated to be a major determinant in the pathogenesis of Neisseria meningitidis. Outside the cells, iron is bound to transferrin in serum, or to lactoferrin in mucosal secretions. Meningococci can extract iron from iron-loaded human transferrin by the TbpA/TbpB outer membrane complex. Moreover, N. meningitidis expresses the LbpA/LbpB outer membrane complex, which can extract iron from iron-loaded human lactoferrin. Iron transport through the outer membrane requires energy provided by the ExbB-ExbD-TonB complex. After transportation through the outer membrane, iron is bound by periplasmic protein FbpA and is addressed to the FbpBC inner membrane transporter. Iron-complexing compounds like citrate and pyrophosphate have been shown to support meningococcal growth ex vivo. The use of iron pyrophosphate as an iron source by N. meningitidis was previously described, but has not been investigated. Pyrophosphate was shown to participate in iron transfer from transferrin to ferritin. In this report, we investigated the use of ferric pyrophosphate as an iron source by N. meningitidis both ex vivo and in a mouse model. We showed that pyrophosphate was able to sustain N. meningitidis growth when desferal was used as an iron chelator. Addition of a pyrophosphate analogue to bacterial suspension at millimolar concentrations supported N. meningitidis survival in the mouse model. Finally, we show that pyrophosphate enabled TonB-independent ex vivo use of iron-loaded human or bovine transferrin as an iron source by N. meningitidis. Our data suggest that, in addition to acquiring iron through sophisticated systems, N. meningitidis is able to use simple strategies to acquire iron from a wide range of sources so as to sustain bacterial survival.

Topics: Animals; Bacterial Proteins; Biological Transport; Deferoxamine; Diphosphates; Disease Models, Animal; Humans; Iron; Membrane Proteins; Meningitis, Meningococcal; Mice; Microbial Viability; Neisseria meningitidis; Transferrin

This study aimed to evaluate iron (Fe) bioavailability in Wistar rats fed with rice fortified with micronized ferric pyrophosphate (FP) by Ultra Rice (UR) technology with or without addition of yacon flour as a source of 7.5% of fructooligosaccharides (FOS). Diets were supplied with 12 mg iron/kg from the following sources: ferrous sulfate (FS - control diet), fortified rice with micronized ferric pyrophosphate (Ultra Rice) (UR diet), ferrous sulfate + yacon flour (FS + Y diet) or Ultra Rice + yacon flour (UR + Y diet). Blood samples were collected at the end of depletion and repletion stages for determination of hemoglobin concentration and calculation of the relative biological value (RBV). Also, the content of short chain fatty acids (SCFA) (acetic, propionic and butyric acids) from animals' stools and caecum weight were determined. The UR diet showed high iron bioavailability (RBV = 84.7%). However, the addition of yacon flour in the diet containing fortified rice (UR + Y diet) decreased RBV (63.1%) significantly below the other three groups (p < 0.05). Groups that received yacon flour showed higher acetic acid values compared to those who did not. In conclusion, fortified UR with micronized ferric pyrophosphate showed high iron bioavailability but the addition of yacon flour at 7.5% FOS reduced iron bioavailability despite increased caecum weight and SCFA concentration.

Topics: Animal Feed; Animals; Asteraceae; Biological Availability; Body Weight; Diphosphates; Fatty Acids, Volatile; Feces; Food, Fortified; Iron; Iron, Dietary; Male; Oryza; Rats; Rats, Wistar

Iontophoretic mediated transdermal delivery of ferric pyrophosphate (FPP) in combination with microneedle pretreatment was investigated as a potential treatment for iron deficiency anemia (IDA).. In vitro transdermal delivery studies were performed using hairless rat skin and pharmacodynamic studies were performed in hairless anemic rat model. The hematological and biochemical parameters like hemoglobin, hematocrit and % serum transferrin were monitored in rats at healthy, anemic condition and post treatment. Micropores created by the microneedles were visualized in histological skin sections after staining with hemotoxylin and eosin. The recovery of micropores was investigated in vivo by measuring Transepidermal water loss (TEWL) at different time points.. The passive, microneedle and iontophoresis mediated delivery did not lead to significant improvement in hematological and biochemical parameters in anemic rats, when used individually. When iontophoresis (0.15 mA/cm(2) for 4 hours) was combined with microneedle pretreatment (for 2 min), therapeutically adequate amount of FPP was delivered and there was significant recovery of rats from IDA.. Microneedle and iontophoresis mediated delivery of iron via transdermal route could be developed as a potential treatment for IDA. The transdermal controlled delivery of iron could become a potential, safe and effective alternative to parenteral iron therapy.

Topics: Administration, Cutaneous; Anemia, Iron-Deficiency; Animals; Diphosphates; Drug Delivery Systems; Erythrocytes; Iontophoresis; Iron; Male; Needles; Rats; Rats, Hairless

The objective of this study was to investigate the feasibility of rapid administration of iron via transdermal route as an alternative to parenteral route of administration. In vitro drug delivery studies were carried out using porcine epidermis mounted on Franz diffusion cells. The effect of chemical permeation enhancers and physical techniques (constant voltage iontophoresis, electroporation and combination of electroporation with iontophoresis) on the transport of ferric pyrophosphate (FPP) was studied. Transepidermal water loss (TEWL) and electrical resistance were measured in order to see the effect of these techniques on the skin barrier function. The amount of FPP permeated was not enhanced significantly with the use of any of the enhancers (P > 0.05). It was found that constant voltage iontophoresis (0.5, 2 or 4 V) for about 30 min across electroporated epidermis (120 V, 100 pulses, 10 ms at 5 Hz) enhanced the delivery of FPP over control in the range of 2- to 42-fold. Hence, a therapeutically required dose of iron could be delivered by transdermal route using electrically-mediated techniques.

Topics: Administration, Cutaneous; Anemia, Iron-Deficiency; Animals; Diphosphates; Drug Delivery Systems; Electroporation; Epidermis; Humans; Iontophoresis; Iron; Skin Absorption; Sus scrofa

Bovine serum albumin (BSA) microspheres of ferric pyrophosphate (FPP) intended for passive targeting to the Peyer's patches has been proposed for oral iron supplementation. Microspheres prepared by emulsification chemical cross linking method were characterized for surface topography, entrapment efficiency, particle size, particle charge and in vitro drug release. Microspheres of batch C with FPP to BSA ratio of 1:5 were found to be most suitable for targeting as they exhibited high entrapment (83.88 +/- 4.31), high monodispersity (span = 1.24 +/- 0.01), and least particle size (d(vm) = 4.40 +/- 0.01). In addition the amount of iron retained in these microspheres despite exposure to simulated gastrointestinal conditions for 5 h was found to be 83.72 +/- 4.22%, the highest in the three batches. The in vivo serum iron profiles in normal rats following oral administration displayed a reduced T(max) (2 h), elevated C(max) (106.06 +/- 12.18 mug/dL) and increased AUC (0-16 h) (647.44 +/- 52.33 mug.h/dL) for these microspheres which significantly differed (P <0.05) from FPP solution indicating a higher iron repletion potential of the BSA microspheres.

Topics: Administration, Oral; Animals; Area Under Curve; Cattle; Chemistry, Pharmaceutical; Diphosphates; Drug Carriers; Drug Delivery Systems; Iron; Male; Microspheres; Particle Size; Peyer's Patches; Rats; Rats, Sprague-Dawley; Serum Albumin, Bovine; Time Factors

Topics: Diphosphates; Female; Gynecology; Humans; Inservice Training; Iron; Iron Chelating Agents; Iron, Dietary; Obstetrics; Poland; Practice Guidelines as Topic; Quality Assurance, Health Care; Societies, Medical; Women's Health

A new pyrophosphate compound Li(2)FeP(2)O(7) was synthesized by a conventional solid-state reaction, and its crystal structure was determined. Its reversible electrode operation at ca. 3.5 V vs Li was identified with the capacity of a one-electron theoretical value of 110 mAh g(-1) even for ca. 1 μm particles without any special efforts such as nanosizing or carbon coating. Li(2)FeP(2)O(7) and its derivatives should provide a new platform for related lithium battery electrode research and could be potential competitors to commercial olivine LiFePO(4), which has been recognized as the most promising positive cathode for a lithium-ion battery system for large-scale applications, such as plug-in hybrid electric vehicles.

Topics: Diphosphates; Electric Power Supplies; Electrochemistry; Electrodes; Iron; Lithium; Models, Molecular

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

Transdermal delivery of iron can overcome the GI side effects and the discomfort associated with parenteral administration. Slow and prolonged transdermal delivery of iron would also avoid potential oversaturation of transferrin and overcome accumulation of free iron in the systemic circulation. Ferric pyrophosphate (FPP) has been demonstrated to be safe for systemic administration. Passive transdermal delivery of FPP is poor due to the impermeable skin barrier. Irontophoresis was developed for transdermal delivery of FPP. The predictability and programmability of the technique was assessed in vitro across the hairless rat skin. Following Irontophoresis for 6 h in hairless rats, the total serum iron concentration increased from 182.36 +/- 39.93 microg/dL to 317.56 +/- 28.33 microg/dL and the transferrin saturation increased from 44.6% +/- 2.2% to 60.8% +/- 6.7%. Irontophoresis based iron therapy could be relatively more patient compliant, safe and effective treatment for iron deficiency anemia condition.

Topics: Administration, Cutaneous; Animals; Diphosphates; Drug Delivery Systems; In Vitro Techniques; Iontophoresis; Iron; Rats; Rats, Hairless; Skin Absorption

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

Iron bioavailability from supplements and fortificants varies depending upon the form of the iron and the presence or absence of iron absorption enhancers and inhibitors. Our objectives were to compare the effects of pH and selected enhancers and inhibitors and food matrices on the bioavailability of iron in soluble ferric pyrophosphate (SFP) to other iron fortificants using a Caco-2 cell culture model with or without the combination of in vitro digestion. Ferritin formation was the highest in cells treated with SFP compared to those treated with other iron compounds or chelates. Exposure to pH 2 followed by adjustment to pH 7 markedly decreased FeSO(4) bioavailability but had a smaller effect on bioavailabilities from SFP and sodium iron(III) ethylenediaminetetraacetate (NaFeEDTA), suggesting that chelating agents minimize the effects of pH on iron bioavailability. Adding ascorbic acid (AA) and cysteine to SFP in a 20:1 molar ratio increased ferritin formation by 3- and 2-fold, respectively, whereas adding citrate had no significant effect on the bioavailability of SFP. Adding phytic acid (10:1) and tannic acid (1:1) to iron decreased iron bioavailability from SFP by 91 and 99%, respectively. The addition of zinc had a marked inhibitory effect on iron bioavailability. Calcium and magnesium also inhibited iron bioavailability but to a lesser extent. Incorporating SFP in rice greatly reduced iron bioavailability from SFP, but this effect can be partially reversed with the addition of AA. SFP and FeSO(4) were taken up similarly when added to nonfat dry milk. Our results suggest that dietary factors known to enhance and inhibit iron bioavailability from various iron sources affect iron bioavailability from SFP in similar directions. However, the magnitude of the effects of iron absorption inhibitors on SFP iron appears to be smaller than on iron salts, such as FeSO(4) and FeCl(3). This supports the hypothesis that SFP is a promising iron source for food fortification and dietary supplements.

Topics: Biological Availability; Caco-2 Cells; Diphosphates; Humans; Iron; Iron Chelating Agents; Iron, Dietary; Models, Biological; Phytic Acid; Solubility; Tannins

Food iron (Fe) fortification is an adequate approach for preventing Fe-deficiency anemia. Poorly water-soluble Fe compounds have good sensory attributes but low bioavailability. The reduction of the particle size of Fe fortificants and the addition of ascorbic acid might increase the bioavailability of low-soluble compounds. The present work aims to compare the Fe absorption and bioavailability of micronized dispersible ferric pyrophosphate (MDFP) (poorly soluble) to ferrous sufate (FS) (highly soluble) added to a fruit juice in presence or absence of ascorbic acid (AA) by using the hemoglobin repletion assay in rats.. After a hemoglobin depletion period, four fruit juices comprised of (1) FS, (2) MDFP, (3) FS + AA, (4) MDFP + AA were produced and administered to a different group of rats (n = 18) over 21 days. During the repletion period, Fe balance, hemoglobin regeneration efficiency (HRE), relative bioavailability (RBV) and Fe tissue content were determined in the short, medium and long term.. Fe absorption and bioavailability showed no significant differences between fortifying the fruit juice with FS or MDFP. The addition of AA to the juice enhanced Fe absorption during the long-term balance study within the same Fe source. HRE and Fe utilization increased after AA addition in both FS and MDFP groups in every period.. Fe absorption and bioavailability from MDFP were comparable to FS added to a fruit juice in rats. Further, the addition of AA enhanced Fe absorption in the long term, as well as Fe bioavailability throughout the repletion period regardless of the Fe source employed.

Topics: Anemia, Iron-Deficiency; Animals; Antioxidants; Ascorbic Acid; Beverages; Biological Availability; Dietary Supplements; Diphosphates; Food, Fortified; Hemoglobins; Intestinal Absorption; Iron; Iron, Dietary; Male; Particle Size; Random Allocation; Rats; Rats, Sprague-Dawley; Solubility

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

Food iron fortification can be a good strategy to prevent iron deficiency. Iron bioavailability from cocoa powder enriched with ferric pyrophosphate encapsulated in liposomes or ferrous fumarate was assessed in rats.. Three groups of rats consumed during 28 days either a control diet or two diets prepared with ferric pyrophosphate- or ferrous fumarate-enriched cocoa powder as the unique source of iron. Body weight and food intake were monitored and last-week feces were collected. On day 28, animals were sacrificed and livers and spleens were removed. Hemoglobin and total iron binding capacity (TIBC) were determined.. There were no significant differences in body weight and food intake. Apparent iron absorption and % absorption/intake were significantly lower in rats consuming enriched cocoa compared to the control group, without significant differences due to the iron form. Enriched cocoa groups showed significantly lower spleen iron content and concentration than the control. Liver iron was lower in the ferric pyrophosphate group compared to the other two groups. Hemoglobin and TIBC values showed a deficient iron status in ferric pyrophosphate rats.. Cocoa powder is a good vehicle for iron fortification when enriched with ferrous fumarate compared to ferric pyrophosphate encapsulated in liposomes.

Topics: Anemia, Iron-Deficiency; Animals; Biological Availability; Cacao; Diet; Diphosphates; Female; Ferrous Compounds; Food, Fortified; Hemoglobins; Iron; Iron, Dietary; Liposomes; Liver; Male; Random Allocation; Rats; Rats, Wistar; Spleen

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

The antioxidant effect of 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-alpha]pyraz in-3-one (MCLA), a Cypridina luciferin analog that acts as a chemiluminescence probe to detect O2.-, was investigated. MCLA produced a lag in oxygen consumption induced by cumene hydroperoxide in microsomes or by 2,2'-azobis (2-amidinopropane) dihydrochloride in liposomes and disappeared during the duration of the lag. MCLA profoundly inhibited the propagation reaction in Fe2+-dependent lipid peroxidation in liposomes, and MCLA disappearance accompanied by suppression of oxygen consumption markedly occurred in liposomes susceptible to peroxidation. Thiobarbituric acid-reactive substances in all systems used were also suppressed by MCLA dose dependently. These results indicate that MCLA has an antioxidant property through scavenging free radicals.

Topics: Amidines; Animals; Antioxidants; Benzene Derivatives; Diphosphates; Free Radical Scavengers; Imidazoles; Iron; Lipid Peroxidation; Liposomes; Luminescent Measurements; Male; Microsomes, Liver; Molecular Probes; Oxygen Consumption; Pyrazines; Rats; Rats, Sprague-Dawley; Superoxides; Thiobarbituric Acid Reactive Substances

Calcium stimulates hepatocyte iron uptake from transferrin, ferric-iron-pyrophosphate and ferrous-iron-ascorbate. Maximal stimulation of iron uptake is observed at 1-1.5 mM of extra-cellular calcium and the effect is reversible and immediate. Neither the receptor affinity for transferrin, nor the total amounts of transferrin associated with the cells or the rate of transferrin endocytosis are significantly affected by calcium. In the presence of calcium the rate of iron uptake of non-transferrin bound iron increases abruptly at approximate 17 degrees C and 27 degrees C and as assessed by Arrhenius plots, the activation energy is reduced in a calcium dependent manner at approx. 27 degrees C. At a similar temperature, i.e., between 25 degrees C and 28 degrees C, calcium increases the rates of cellular iron uptake from transferrin in a way that is not reflected in the rate of transferrin endocytosis. By the results of this study it is concluded that calcium increases iron transport across the plasma membrane by a mechanism dependent on membrane fluidity.

Topics: Animals; Ascorbic Acid; Calcium; Cell Separation; Diphosphates; Endocytosis; Ferrous Compounds; Iron; Kinetics; Liver; Male; Rats; Rats, Inbred Strains; Temperature; Transferrin

The growth in liquid media of Legionella pneumophila serogroups 1-6 was monitored turbidimetrically and factors affecting growth rate were studied. The presence of inhibitors, use of detoxifying agents and the method of broth preparation each had significant effects on cultivation. Cysteine was essential for growth; the optimal concentration was 100 micrograms/ml, but supplemental iron had no demonstrable effect.

Topics: Culture Media; Cysteine; Diphosphates; Erythrocytes; Iron; Legionella; Sodium Chloride