Efficacy of ferric carboxymaltose for treatment of iron deficiency anemia diagnosed in the third trimester of pregnancy: A case-control study.

AIM: To assess the efficacy of intravenous ferric carboxymaltose (IV FCM) for the treatment of iron deficiency anemia (IDA) diagnosed de novo in the third trimester of pregnancy. METHODS: Case-control study conducted in pregnant women with IDA newly diagnosed in the third trimester of pregnancy. Women treated with a single IV FCM injection were included as cases and those who received daily 210 g of oral ferrous sulphate (FS) as controls. Controls were matched to cases in a 2:1 ratio by basal hemoglobin (Hb) concentration (±0.5 g/dl). RESULTS: A total of 35 cases and 70 controls were included in the study. The mean Hb concentration level significantly increased after iron treatment in both cases (from 9.3 ± 0.8 to 11.1 ± 0.8 g/dl, p < 0.0001) and controls (from 9.6 ± 0.9 to 10.9 ± 1 g/dl, p < 0.0001). The rate of women who exceeded the recommended threshold of 11 g/dl after treatment did not significantly differ between cases (63% (95%CI, 45%-79%)) and controls (56% (95%CI, 44%-68%)) (p = 0.48). Comparison of maternal and neonatal outcomes and adverse effects did not show any significant difference between groups. CONCLUSIONS: Our results suggest that IV FCM and oral FS can be considered equally effective in the treatment of IDA newly detected in the third trimester of pregnancy.

Tolerability of Oral Supplementation with Microencapsulated Ferric Saccharate Compared to Ferrous Sulphate in Healthy Premenopausal Woman: A Crossover, Randomized, Double-Blind Clinical Trial.

A single-center, crossover, randomized, double-blind, and controlled clinical study was conducted to assess the tolerability profile, especially with regard to gastrointestinal complaints, of oral supplementation with AB-Fortis®, a microencapsulated ferric saccharate (MFS), as compared with conventional ferrous sulphate (FS) in healthy premenopausal women. A dose of 60 mg/day of elemental iron was used. The test products were administered for 14 consecutive days with a washout period of two menstrual episodes and a minimum of one month between the two intervention periods. The subjects completed simple-to-answer questionnaires daily for 14 days during both the intervention and the washout periods, capturing the symptoms associated with oral iron supplementation and overall health aspects. Following product consumption, the incidences of symptoms, numbers of complaints/symptoms, overall intensity, and total days with symptoms were found to be significantly higher for FS consumption as compared to MFS. The better tolerability profile of MFS over FS was further substantiated when both products were compared to a real-life setting (i.e., the washout period). Overall, the administration of both study products was safe with no serious or significant adverse events reported. In summary, the current study shows the better tolerability of the MFS preparation when compared to that of the FS, presenting MFS as a well-tolerated and safe option for improving iron nutrition.

Comparison of efficacy & safety of iron polymaltose complex & ferrous ascorbate with ferrous sulphate in pregnant women with iron-deficiency anaemia.

Background & objectives: Iron-deficiency anaemia (IDA) is a common nutritional deficiency among pregnant women in India. It has a significant impact on the health of the mother as well as that of the foetus. IDA generally responds well to treatment with oral iron supplementation. However, oral iron supplements are toxic to the gastrointestinal mucosa and intolerance is common, resulting in poor compliance and failure of treatment. The iron salts such as iron hydroxide polymaltose complex (IPC) and ferrous ascorbate (FeA) are claimed to have low gastrointestinal intolerance, therefore better patient compliance than the conventionally used ferrous sulphate (FS). These preparations also claim to increase haemoglobin level faster as well as improve the iron storage better than FS. This study was done to compare the efficacy and safety of FS with IPC and FeA. Methods: It was a randomized, parallel, open label, study among pregnant women of gestational age between 12 to 26 wk with moderate anaemia. Patients were randomly allocated to receive either FS, IPC or FeA. They were then followed up for 90 days to observe for improvement in the haemoglobin levels and other haematological parameters or any adverse drug reaction. Results: The haemoglobin levels were comparable in the three groups except at day 90 when FeA group had significantly higher haemoglobin level as compared to FS group (P<0.05). The overall adverse effect profiles were also comparable among the study groups except epigastric pain which was more commonly reported in the FS group. Interpretation & conclusions: The results of the study showed that FS, IPC and FeA have comparable efficacy and safety profile in the treatment of IDA of pregnancy.

Fractional iron absorption from enteric-coated ferrous sulphate tablet.

Background & objectives: Iron supplementation is widely used public health measure to manage iron deficiency anaemia. In India, enteric-coated iron tablets are administered to adolescent boys and girls to avoid adverse effects such as gastritis, which reduces compliance, but this may result in poor iron absorption. Data on the absorption of iron from enteric-coated ferrous sulphate tablets are lacking. The present study using stable isotopic approach was aimed to measure iron absorption in iron deficient women. Methods: Iron absorption was measured from stable isotope-labelled enteric-coated ferrous sulphate ([57]Fe, ECFS) and uncoated ferrous sulphate ([58]Fe, UCFS) tablets in iron-deficient (n=9) women, aged 18-40 yr with no infection or inflammation. The two types of tablets (ECFS and UCFS) were administered on consecutive days, 60 min after breakfast, and the sequence being random. Blood samples were collected before dosing, and on day 15, to measure iron absorption from the shift in iron isotopic ratios in haemoglobin. Results: Eight women completed the iron absorption study. Iron absorption was found to be significantly lower in ECFS compared to UCFS (3.5 vs. 12%, P <0.05) consumption. Interpretation & conclusions: Our study showed poor iron bioavailability from ECFS, and supplementation programmes may consider UCFS tablets for better haematological outcomes.

Double emulsions for iron encapsulation: is a high concentration of lipophilic emulsifier ideal for physical and chemical stability?

BACKGROUND: Worldwide iron deficiency in diets has led to a growing interest in the development of food-compatible encapsulation systems for soluble iron, which are able to prevent iron's undesirable off-taste and pro-oxidant activity. Here, we explore the use of double emulsions for this purpose, and in particular, how the lipophilic emulsifier (polyglycerol polyricinoleate, PGPR) concentration influences the physicochemical stability of water-in-oil-in-water (W1 /O/W2 ) double emulsions containing ferrous sulphate in the inner water droplets. Double emulsions were prepared with sunflower oil containing 10 to 70 g kg-1 PGPR in the oil phase, and were monitored for droplet size distribution, morphology, encapsulation efficiency (EE) and oxidative stability over time. RESULTS: Fresh double emulsions showed an initial EE higher than 88%, but EE decreased upon storage, which occurred particularly fast and to a high extent in the emulsions prepared with low PGPR concentrations. All double emulsions underwent lipid oxidation, in particular those with the highest PGPR concentration, which could be due to the small inner droplet size and thus promoted contact between oil and the internal water phase. CONCLUSION: These results show that a too high PGPR concentration is not needed, and sometimes even adverse, when developing double emulsions as iron encapsulation systems. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Daily versus twice daily dose of ferrous sulphate supplementation in pregnant women: A randomized clinical trial.

BACKGROUND: The International Nutritional Anaemia Consultative Group has recommended a twice daily dose of 65 mg elemental iron supplementation in pregnant women living in areas where anaemia is prevalent contrary to the World Health Organization (WHO) universal recommendation of a daily dose of 60 mg. Whether twice or daily dose schedules proffer a better outcome is a subject of on-going research. OBJECTIVE: To compare the effectiveness of the once versus twice daily doses of ferrous sulphate in the prevention of iron deficiency anaemia in pregnancy. METHODS: There are about one hundred and eighty two (182) pregnant women at gestational ages of 14-24 weeks with haemoglobin (Hb) levels ≥10 g/dl but ≤14.5 g/dl were recruited during the antenatal booking clinic. They were randomized into receiving either once daily dose (65 mg of elemental iron) or twice daily dose (130 mg of elemental iron) of ferrous sulphate. Pre and post- supplementation haemoglobin, serum iron and ferritin levels were assessed at recruitment and at 37 weeks gestation respectively. RESULTS: Eighty-four (84) and 80 women respectively in the once and twice daily dose groups were analysed. The serum haemoglobin was significantly lower (P = 0.002) among those on once daily than those on twice daily supplementation. The side effects were however, significantly higher in the twice daily group (P = 0.005, P = 0.043 and P = 0.004 respectively). There were no differences between the serum ferritin levels pre and post supplementation in both groups just as they were no reported significant differences in both birth weight of neonates (P = 0.936) and average gestational age at delivery (P = 0.469) between the two groups. CONCLUSION: Once daily (65 mg elemental iron) ferrous sulphate is as effective as twice daily (130 mg elemental iron) dose regimen in prevention of Anaemia in pregnancy in a developing economy like Nigeria. Once daily dose possesses fewer side effects and guarantees better compliance in this study.

Iron bioavailability in 8-24-month-old Thai children from a micronutrient-fortified quick-cooking rice containing ferric ammonium citrate or a mixture of ferrous sulphate and ferric sodium ethylenediaminetetraacetic acid.

A quick-cooking rice, produced from broken rice, is a convenient ingredient for complementary foods in Thailand. The rice is fortified with micronutrients including iron during the processing procedure, which can cause unacceptable sensory changes. A quick-cooking rice fortified with ferric ammonium citrate (FAC) or a mixture of ferrous sulphate (FeSO4 ) and ferric sodium ethylenediaminetetraacetic acid (NaFeEDTA), with a 2:1 molar ratio of iron from FeSO4 : iron from NaFeEDTA (FeSO4 + NaFeEDTA), gave a product that was organoleptically acceptable. The study compared iron absorption by infants and young children fed with micronutrient-fortified quick-cooking rice containing the test iron compounds or FeSO4 . Micronutrient-fortified quick-cooking rice prepared as a traditional Thai dessert was fed to two groups of 15 8-24-month healthy Thai children. The iron fortificants were isotopically labelled with (57) Fe for the reference FeSO4 or (58) Fe for the tested fortificants, and iron absorption was quantified based on erythrocyte incorporation of the iron isotopes 14 days after feeding. The relative bioavailability of FAC and of the FeSO4 + NaFeEDTA was obtained by comparing their iron absorption with that of FeSO4 . Mean fractional iron absorption was 5.8% [±standard error (SE) 1.9] from FAC and 10.3% (±SE 1.9) from FeSO4 + NaFeEDTA. The relative bioavailability of FAC was 83% (P = 0.02). The relative bioavailability of FeSO4 + NaFeEDTA was 145% (P = 0.001). Iron absorption from the rice containing FAC or FeSO4 + NaFeEDTA was sufficiently high to be used in its formulation, although iron absorption from FeSO4 + NaFeEDTA was significantly higher (P < 0.00001).

Intravenous ferrous sucrose versus placebo in addition to oral iron therapy for the treatment of severe postpartum anaemia: a randomised controlled trial.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of intravenous iron versus placebo added to standard oral iron therapy in the treatment of severe postpartum anaemia. DESIGN: A randomised, double-blind, parallel-group, placebo-controlled clinical trial was performed in a single centre. SETTING: Hospital Clinic of Barcelona, Barcelona, Spain. POPULATION: A cohort of 72 women with severe postpartum anaemia (6.0-8.0 g/dl) treated with oral ferrous sulphate (two tablets of 525 mg). METHODS: Women were randomised to receive either intravenous ferrous sucrose (200 mg/24 hours for two consecutive days) or intravenous placebo, in addition to standard iron therapy. Clinical and laboratory data were obtained at 1, 2, and 6 weeks. MAIN OUTCOME MEASURES: Haemoglobin and haematocrit at 1, 2, and 6 weeks. Other haematological and clinical parameters, psychological status, and adverse side effects were also evaluated. RESULTS: Haemoglobin and haematocrit values were comparable in women receiving intravenous iron or placebo in addition to oral iron therapy at any of the time points. At 6 weeks, haemoglobin level (mean ± SD) was 12.2 ± 1.0 versus 12.2 ± 0.9 g/dl, with a mean difference of -0.03 (95% CI -0.6 to 0.6), in the placebo and in the intravenous iron groups, respectively. No differences were found between clinical symptoms of anaemia, psychological status, and adverse side effects between groups. CONCLUSIONS: Intravenous iron added to oral iron therapy did not show significant benefits over placebo, neither in haemoglobin rise nor in symptoms or adverse side effects.

[Prevalence of exogenous pigmentations and caries by intake of ferric supplements in primary dentition]. / Prevalencia de pigmentaciones exógenas y caries por ingesta de suplementos férricos en dentición primaria.

Objective: The aim of this study was to determine the prevalence of extrinsic black pigmentation in primary dentition and its relationship with dental caries in children aged 3 to 5 years. Materials and methods: The study design was descriptive, prospective, cross-sectional and observational; The sample of the present study consisted of 79 children who were receiving treatment with ferrous sulfate, who underwent a clinical examination and odontogram. To determine the presence of extrinsic black pigmentation, the Shourie classification was used. Results: A low prevalence of extrinsic pigmentation of 7.6% was found, and children with extrinsic pigmentation had a Ceod of 9.83+-3.601, while those children without the presence of pigmentations had a Ceod of 4.60+-3.248. Conclusions: A significant relationship was found between the Ceod index and extrinsic black pigmentation (p<0.001).

Management of Acute Ferrous Sulfate Poisoning Using Activated Charcoal Monotherapy: A Case Report.

A 13-year-old schoolgirl presented to a public hospital having ingested over 70 tablets of 65 mg of prescription ferrous sulphate within the last hour. She complained of a 7/10 sharp abdominal pain. Signs included lethargy, agony, diaphoresis, and frequent eructation. Gastrointestinal movements were audible and frequent. Heart rate was at 50 beats per minute with intact but weak pulsations. Blood pressure was at 95/65 mmHg. During the clerking, she started vomiting in pouts separated by few-minute intervals. The vomitus was watery, yellowish, and had a rusty-ironic smell. Serum iron was at 200 mcg/dL and 230 mcg/dL at the time of admission to the hospital and the time of discharge, respectively. The patient received intravenous Ringer's lactate solution. She was detoxified by the chewing of a single dose of 100 g activated charcoal. She stayed in remission throughout the follow-up. It was concluded that monotherapy with oral activated charcoal arrests the progress of the toxicodrome.

Impacts of iron on ultrastructural features of NCI-H295R cell line related to steroidogenesis.

The current study was intended to evaluate impacts of both iron (Fe) enrichment and overload (in the form of ferrous sulphate heptahydrate, FeSO4.7H2O) on ultrastructural characteristics of human adrenocarcinoma NCI-H295R cell line. Here, the NCI-H295R cells were treated with 0, 3.90, and 1000 µM FeSO4.7H2O, and consequently proceeded for purposes of ultrastructural studies. Micrographs taken under transmission electron microscope (TEM) were investigated from the qualitative and quantitative (unbiased stereological approaches) aspects, and obtained findings were compared among the three groups of the cells. The ultrastructural features related to the steroidogenic process were found to be similar between the untreated and both Fe-exposed cell populations, with conspicuous mitochondria with well-defined lamellar cristae (creating clusters of varying sizes in the regions of increased energy demands) and concentric whorls of smooth endoplasmic reticulum (SER) being the most noticeable characteristics. The precise estimates of the component (volume, surface) fractions of the nucleus, mitochondria, and lipid droplets (LDs), as well as of the nucleus/cytoplasm (N/C) ratio have revealed close similarities (P > 0.05) in all cell groups investigated. Nonetheless, the low concentration of FeSO4.7H2O exhibited beneficial action on ultrastructural organization of the NCI-H295R cells. In effect, these cells were distinguished by mitochondria with smoother surfaces and clearer outlines, higher density of thin, parallel lamellar cristae (deeply extending into the mitochondrial matrix), and more widespread distribution of fine SER tubules as compared to the control ones, all of them suggesting higher level of energy requirements and metabolic activity, and more intensive rate of steroidogenesis. Interestingly, no obvious ultrastructural modifications were observed in the NCI-H295R cells treated with high FeSO4.7H2O concentration. This finding can be linked to either an adaptive ultrastructural machinery of these cells to cope with the adverse effect of the element or to insufficient dose of FeSO4.7H2O (1000 µM) to induce ultrastructural signs of cytotoxicity. Purposefully, the results of the current study complement our previous paper dealing with impacts of FeSO4.7H2O on the NCI-H295R cell viability and steroidogenesis at the molecular level. Hence, they fill a knowledge gap considering structure-function coupling in this cellular model system upon the metal exposure. This integrated approach can enhance our understanding of the cellular responses to Fe enrichment and overload which can be helpful for individuals with reproductive health concerns.

Co-Administration of Iron and Bioavailable Curcumin Reduces Levels of Systemic Markers of Inflammation and Oxidative Stress in a Placebo-Controlled Randomised Study.

Ferrous sulphate (FS) is widely used as an iron supplement to treat iron deficiency (ID), but is known to induce inflammation causing gastric side-effects resulting in poor adherence to supplement regimens. Curcumin, a potent antioxidant, has been reported to suppress inflammation via down regulation of NF-κB. The aim of the present double blind, placebo-controlled randomised trial was to assess whether co-administration of FS with a formulated, bioavailable form of curcumin (HydroCurc™) could reduce systemic inflammation and/or gastrointestinal side-effects. This study recruited 155 healthy participants (79 males; 26.42 years ± 0.55 and 76 females; 25.82 years ± 0.54), randomly allocated to one of five different treatment groups: iron and curcumin placebo (FS0_Plac), low dose (18 mg) iron and curcumin placebo (FS18_Plac), low dose iron and curcumin (FS18_Curc), high dose (65 mg) iron and curcumin placebo (FS65_Plac), and high dose iron and curcumin (FS65_Curc). Completed questionnaires and blood samples were collected from all participants at baseline (day 1), mid-point (day 21), and at end-point (day 42). Results showed a significant reduction in IL-6 in the FS65_Curc group (0.06 pg/mL ± 0.02, p = 0.0073) between the mid-point and end-point. There was also a significant reduction in mean plasma TNF levels in the FS65_Curc (0.65 pg/mL ± 0.17, p = 0.0018), FS65_Plac (0.39 pg/mL ± 0.15, p = 0.0363), and FS18_Curc (0.35 pg/mL ± 0.13, p = 0.0288) groups from mid-point to end-point. A significant increase was observed in mean plasma TBARS levels (0.10 µM ± 0.04, p = 0.0283) in the F18_Plac group from baseline to end-point. There was a significant association with darker stools between FS0_Plac vs. FS65_Plac (p = 0.002, Fisher's exact test) suggesting that high iron dose in the absence of curcumin leads to darker stools. A reduction in inflammation-related markers in response to co-administering supplemental iron alongside formulated curcumin suggests a reduction in systemic inflammation. This supplementation approach may therefore be a more cost effective and convenient alternative to current oral iron-related treatments, with further research to be conducted.

Nanodiamond enhanced mechanical and biological properties of extrudable gelatin hydrogel cross-linked with tannic acid and ferrous sulphate.

BACKGROUND: The requirements for cell-encapsulated injectable and bioprintable hydrogels are extrusion ability, cell supportive micro-environment and reasonable post-printing stability for the acclimatization of the cells in the target site. Detonation nanodiamond (ND) has shown its potential to improve the mechanical and biological properties of such hydrogels. Enhancing the performance properties of natural biopolymer gelatin-based hydrogels can widen their biomedical application possibilities to various areas including drug delivery, tissue engineering and 3D bioprinting. METHOD: In this study, natural cross-linker tannic acid (TA) is used along with ferrous sulphate (FS) to optimize the swelling and disintegration of extrudable and 3D printable gelatin hydrogels. The amounts of TA and FS are restricted to improve the extrusion ability of the gels in 3D printing. Further, ND particles (detonation type) are dispersed using twin screw extrusion technology to study their effect on mechanical and biological properties of the 3D printing hydrogel. RESULTS: The improved dispersion of ND particles helps to improve compressive strength almost ten times and dynamic modulus three times using 40 mg ND (2% w/w of gelatin). The surface-functional groups of detonation ND also contributed for such improvement in mechanical properties due to higher interaction with the hydrogel matrix. The stability of the hydrogels in water was also improved to 7 days. Four times improvement of the cell growth and proliferation was observed in ND based hydrogel. CONCLUSION: The cell-supportive nature of these moderately stable and extrudable ND dispersed gelatin hydrogels makes them a good candidate for short term regenerative applications of cell-encapsulated injectable hydrogels with better mechanical properties.

Oral Ferrous Sulphate Improves Functional Capacity on Heart Failure Patients with Iron Deficiency Anemia.

Background: Iron deficiency anemia (IDA) in heart failure (HF) is associated with poor functional capacity. Several studies reported the benefit of iron therapy in HF with IDA on improving functional capacity. Therefore, we attempt to investigate the effect of oral iron supplementation on functional capacity in HF patients with IDA. Results: A double blind randomized controlled trial was conducted in National Cardiovascular Center Harapan Kita Hospital Universitas Indonesia. A total of 54 HFREF patients with IDA were enrolled and randomized to either oral Ferrous Sulphate (FS) 200 mg three times a day or placebo with 1:1 ratio for 12 weeks. Primary outcome was functional capacity measured by a six-minute walk test. There were 41 participants completed the study (FS n = 22, placebo n = 19). Ferrous sulphate significantly improved functional capacity changes (46.23 ± 35 m vs -13.7 ± 46 m, p < 0.001, CI -86.8 to -33.2) compared with placebo groups respectively after 12 weeks intervention. Conclusions: Oral FS supplementation for 12 weeks significantly improved functional capacity in HF patients with IDA. Trial registration: clinicaltrials.gov, NCT02998697. Registered 14 December 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02998697.

A Randomised Controlled Trial to Compare Injection Ferric Carboxymaltose and Oral Iron in Treating Iron Deficiency Anemia During Pregnancy.

Introduction: Iron deficiency anemia (IDA) in pregnancy has a prevalence as high as 40-60% in different countries of the world. Oral iron is used to treat his commonest medical disorder in pregnancy. Ferrous sulphate is associated with considerable side effects. Ferric carboxymaltose (FCM) is a newer iron preparation which allows for single and higher dose (up to 1000 mg) of IV iron infusion. This study was conducted to compare the efficacy of FCM and FS in treating IDA during pregnancy. Methods: A randomised control trial was done at a tertiary care centres involving 362 women (181 women each in FS and FCM group). The pregnant anemic women with IDA were enrolled between 18 and 34 weeks of pregnancy. They were given 1000 mg of FCM iv as single dose or were given FS tablets twice daily (120 mg iron daily). The data were collected for rise in the Hb and serum ferritin over a period of 6 weeks. Results: Nine and 18 patients were lost to follow-up in the FCM and FS group, respectively. The data were analysed as per protocol analysis. FCM group women showed 2.6 gm% rise in Hb compared to 1.7 gm% of FS group. One hundred and sixty-six out of 172 women in FS group achieved anemia correction at 6 weeks. No difference was observed in the neonatal outcome. No major side effects were observed in the either group. Conclusion: In our study, FCM was more effective than oral FS in increasing Hb in women with IDA during pregnancy. This clinical benefit with FCM was achieved without the concerns for safety and tolerability of the drug.

Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial.

BACKGROUND: Anaemia in pregnancy is highly prevalent in African countries. High-dose oral iron is the current recommended treatment for pregnancy-related iron deficiency anaemia (IDA) in Nigeria and other African countries. This oral regimen is often poorly tolerated and has several side effects. Parenteral iron preparations are now available for the treatment of IDA in pregnancy but not widely used in Africa. The IVON trial is investigating the comparative effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate standard-of-care for pregnancy-related IDA in Nigeria. We will also measure the implementation outcomes of acceptability, feasibility, fidelity, and cost-effectiveness for intravenous ferric carboxymaltose. METHODS: This is an open-label randomised controlled trial with a hybrid type 1 effectiveness-implementation design, conducted at 10 health facilities in Kano (Northern) and Lagos (Southern) states in Nigeria. A total of 1056 pregnant women at 20-32 weeks' gestational age with moderate or severe anaemia (Hb < 10g/dl) will be randomised 1:1 into two groups. The interventional treatment is one 1000-mg dose of intravenous ferric carboxymaltose at enrolment; the control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum. Primary outcome measures are (1) the prevalence of maternal anaemia at 36 weeks and (2) infant preterm birth (<37 weeks' gestation) and will be analysed by intention-to-treat. Maternal full blood count and iron panel will be assayed at 4 weeks post-enrolment, 36 weeks' gestation, delivery, and 6 weeks postpartum. Implementation outcomes of acceptability, feasibility, fidelity, and cost will be assessed with structured questionnaires, key informant interviews, and focus group discussions. DISCUSSION: The IVON trial could provide both effectiveness and implementation evidence to guide policy for integration and uptake of intravenous iron for treating anaemia in pregnancy in Nigeria and similar resource-limited, high-burden settings. If found effective, further studies exploring different intravenous iron doses are planned. TRIAL REGISTRATION: ISRCTN registry ISRCTN63484804 . Registered on 10 December 2020 Clinicaltrials.gov NCT04976179 . Registered on 26 July 2021 The current protocol version is version 2.1 (080/080/2021).

Acute Administration of Bioavailable Curcumin Alongside Ferrous Sulphate Supplements Does Not Impair Iron Absorption in Healthy Adults in a Randomised Trial.

Ferrous sulphate (FS) is a cost effective, readily available iron supplement for iron deficiency (ID). The pro-oxidant effect of oral ferrous iron is known to induce inflammation, causing gastric side-effects and resulting in poor compliance. Curcumin is a potent antioxidant and has also been shown to exhibit iron chelation in-vitro, although it is not established whether these effects are retained in-vivo. The aim of this study was therefore to assess the influence of a formulated bioavailable form of curcumin (HydroCurcTM; 500 mg) on acute iron absorption and status in a double blind, placebo-controlled randomized trial recruiting 155 healthy participants (79 males; 26.42 years ± 0.55 and 76 females; 25.82 years ± 0.54). Participants were randomly allocated to five different treatment groups: iron and curcumin placebo (FS0_Plac), low dose (18 mg) iron and curcumin placebo (FS18_Plac), low dose iron and curcumin (FS18_Curc), high dose (65 mg) iron and curcumin placebo (FS65_Plac), and high dose iron and curcumin (FS65_Curc). Participants were provided with the supplements according to their relevant treatment groups at baseline (0 min), and blood collection was carried out at 0 min and at 180 min following supplementation. In the treatment groups, significant difference was observed in mean serum iron between baseline (0 min) and at end-point (180 min) (F (1, 144) = 331.9, p < 0.0001) with statistically significant intra-group increases after 180 min (p < 0.0001) in the FS18_Plac (8.79 µmol/L), FS18_Curc (11.41 µmol/L), FS65_Plac (19.09 µmol/L), and FS65_Curc (16.39 µmol/L) groups. A significant difference was also observed between the two time points in serum TIBC levels and in whole blood haemoglobin (HGB) in the treatment groups, with a significant increase (1.55%/2.04 g/L) in HGB levels from baseline to end-point observed in the FS65_Curc group (p < 0.05). All groups receiving iron demonstrated an increase in transferrin saturation (TS%) in a dose-related manner, demonstrating that increases in serum iron are translated into increases in physiological iron transportation. This study demonstrates, for the first time, that regardless of ferrous dose, formulated curcumin in the form of HydroCurc™ does not negatively influence acute iron absorption in healthy humans.

Iron Protein Succinylate in the Management of Iron Deficiency Anemia: A Comparative Study with Ferrous Sulphate at Low and High Therapeutic Doses.

Oral iron supplementation constitutes the first line treatment for iron deficiency anemia (IDA), with daily doses between 80 mg and 200 mg of elemental iron. Ferrous salts, such as ferrous sulphate (FeSO4), while efficacious, frequently give rise to gastrointestinal side effects. In the present paper we attempted to directly compare the efficacy of an alternative to the FeSO4 formulation, which presents a better tolerability profile, iron protein succinylate (Ferplex®). In a diet-induced anemia model, rats were treated by oral gavage with vehicle, FeSO4, or Ferplex® at a human-dose equivalent of 80 mg and 200 mg of elemental iron. We evaluated the change in anemia-related hematological and biochemical parameters, conducting a histological examination of the intestine at sacrifice. Results indicate that both types of iron supplementation are equally effective in the treatment of IDA, restoring hemoglobin, hematocrit, erythrocytes, free iron and transferrin levels in 15 days, with no statistical differences between treated groups and control. The impact of anemia on body weight was also attenuated following treatment with both iron supplements. Thrombocyte and reticulocyte levels, altered by the anemic condition, returned to homeostasis after 15 days of either FeSO4 or Ferplex® treatment. Importantly, the lower and higher doses of iron were equally effective, thus supporting the current school of thought which states that lower therapeutic doses are sufficient for management of IDA. In addition, the study shows for the first time that oral treatment with Ferplex® does not increase serum hepcidin. Finally, Ferplex® induced minimal iron depositions in the intestinal tissue compared to FeSO4.

Mucoadhesive microspheres of ferrous sulphate - A novel approach for oral iron delivery in treating anemia.

Ferrous sulphate is a widely used oral iron supplement with low bioavailability and substantial side effects. In this study ferrous sulphate has been coated with highly mucoadhesive polymers such as hydroxypropylmethyl cellulose (HP), chitosan (CS) and carbopol (CP) by spray drying technique to produce mucoadhesive polymer coated microspheres with good yield and high encapsulation efficiency. Mucoadhesive coating may allow these microspheres to get attached to the intestine and hence better absorption of ferrous sulphate may be achieved. in vitro release studies from the microspheres show that the release follows non-Fickian zero order drug release. CP and CSHP coated microspheres showed good swelling(∼1200 to 2400 %) and mucoadhesion properties (58-95 %) indicating that they can swell and get attached to the intestine for longer time period as compared to free ferrous sulphate. All the microspheres were found to be non-cytotoxic in Caco2 cell lines and fibroblast cell lines. Cell uptake studies conducted on Caco2 cell lines showed that uptake of microspheres containing ferrous sulphate has an increased and sustained release to the cell as compared to free ferrous sulphate. Though cell uptake studies showed an increase in uptake for ferrous sulphate microspheres, comparable efficacy was observed upon administering ferrous sulphate microspheres and ferrous sulphate to phenyl hydrazine induced anemic rats.

Comparison between Iberet Folic® and Zincofer® in treatment of iron deficiency anaemia in pregnancy.

OBJECTIVES: To compare the effect of Iberet Folic® and Zincofer® on haemoglobin (Hb) and serum ferritin level; and its adverse effect. METHODS: This randomised controlled trial conducted from January 2018 until December 2018. Pregnant women below 34 weeks of gestation, with Hb concentration less than 11 g/dL and serum ferritin level less than 12 ug/L were randomised to receive either one tablet Zincofer® or one tablet Iberet Folate® daily for four weeks. Both groups were compared in terms of effect on Hb level, serum ferritin level, and other haematological indices adverse effect related to treatment, and treatment cost. RESULTS: Hundred and thirty patients were recruited in this study with 68 patients in Iberet Folic group and 62 patients in Zincofer group. The change in the Hb and serum ferritin level from baseline to day 30 did not differ significantly between treatment groups. The mean (±SD) change from baseline to day 30 was 2.15 (±0.59) g/dL in the Iberet Folic group, and 1.98 (±0.49) in the Zincofer (p value = 0.08). Mean serum ferritin at day 30 was 17.2 (±3.68) ug/L and 16.7 (±4.28) ug/L with 8.44 (±3.41) and 8.55 (±3.50) difference, respectively (p = 0.86). Adverse events were comparable in between groups, with p value >0.05. GI intolerance and constipation were among the common side effects, occurred in 34.6 and 29.2% cases, respectively. CONCLUSIONS: Zincofer® offers equivalent efficacy and side effect profile in comparison with Iberet Folic® for the treatment of iron deficiency anaemia (IDA) during pregnancy, but with lower cost.