pyrophosphate and Anemia--Iron-Deficiency

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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