Oral Iron Absorption Test: A Simple Test with Relevance in the Clinical Setting.

BACKGROUND: Iron deficiency anemia is a widespread problem. Although oral and intravenous therapy are available, iron malabsorption is a distinct possibility. OBJECTIVES: To evaluate the applicability of the oral iron absorption test (OIAT) as a simple and effective means of determining the degree of oral iron absorption. METHODS: The study comprised 81 patients diagnosed with iron deficiency anemia who were referred to a hematology outpatient clinic. Participants were given two ferrous sulphate tablets. Iron levels in the blood were evaluated at intervals from 30 to 180 minutes after iron administration. RESULTS: We divided patients into three distinct groups. The first group consisted of patients with little iron absorption with a maximum iron increment (Cmax) in the blood of 0-49 ug/dl. The second group had a moderate maximum absorption of 50-100 ug/dl, while a third group had considerable absorption of with maximum iron increase of over 100 ug/dl. CONCLUSIONS: The oral iron absorption test, although not clearly standardized, is easy to conduct in any outpatient clinic. This test can readily and clearly determine absorption or nonabsorption of iron. This test can have major implications on the need of oral or intravenous iron therapy and can also determine the need for further gastrointestinal evaluation of the small intestine, where iron absorption takes place and the success of therapy on subsequent iron absorption.

Iron-Containing Oral Contraceptives and Their Effect on Hemoglobin and Biomarkers of Iron Status: A Narrative Review.

Oral contraceptive use has been associated with decreased menstrual blood losses; thus, can independently reduce the risk of anemia and iron deficiency in women. Manufacturers have recently started to include supplemental iron in the non-hormonal placebo tablets of some contraceptives. The aims of this narrative review are: (i) to describe the relationship between oral contraceptive use and both anemia and iron status in women; (ii) to describe the current formulations of iron-containing oral contraceptives (ICOC) available on the market; and (iii) to systematically review the existing literature on the effect of ICOC on biomarkers of anemia and iron status in women. We discovered 21 brands of ICOC, most commonly including 25 mg elemental iron as ferrous fumarate, for seven days, per monthly tablet package. Our search identified one randomized trial evaluating the effectiveness of ICOC use compared to two non-ICOC on increasing hemoglobin (Hb) and iron status biomarker concentrations in women; whereafter 12 months of contraception use, there were no significant differences in Hb concentration nor markers of iron status between the groups. ICOC has the potential to be a cost-effective solution to address both family planning needs and iron deficiency anemia. Yet, more rigorous trials evaluating the effectiveness of ICOC on improving markers of anemia and iron deficiency, as well as investigating the safety of its consumption among iron-replete populations, are warranted.

Electrochemical detection of alkaline phosphatase activity through enzyme-catalyzed reaction using aminoferrocene as an electroactive probe.

As a nonspecific phosphomonoesterase, alkaline phosphatase (ALP) plays a pivotal role in tissue mineralization and osteogenesis which is an important biomarker for the clinical diagnosis of bone and hepatobiliary diseases. Herein, we described a novel electrochemical method that used aminoferrocene (AFC) as an electroactive probe for the ALP activity detection. In the condition with imidazole and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), the AFC probe could be directly labeled on single-stranded DNA (ssDNA) by one-step conjugation. Specifically, thiolated ssDNA at 3'-terminals was modified to the electrode surface through Au-S bond. In the condition without ALP, AFC could be labeled on ssDNA by conjugating with phosphate groups. In the presence of ALP, phosphate groups were catalyzed to be removed from the 5'-terminal of ssDNA. The AFC probe cannot be labeled on ssDNA. Thus, the electrochemical detection of ALP activity was achieved. Under optimal conditions, the strategy presented a good linear relationship between current intensity and ALP concentration in the range of 20 to 100 mU/mL with the limit of detection (LOD) of 1.48 mU/mL. More importantly, the approach rendered high selectivity and satisfactory applicability for ALP activity detection. In addition, this method has merits of ease of operation, low cost, and environmental friendliness. Thus, this strategy presents great potential for ALP activity detection in practical applications. An easy, sensitive and reliable strategy was developed for the detection of alkaline phosphatase activity via electrochemical "Signal off".

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.

Consumption of Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate: A Stable Iron Isotope Study in Iron-Depleted Young Women.

BACKGROUND: Animal studies suggest prebiotics can increase iron absorption, but results from human studies are equivocal. OBJECTIVES: In iron-depleted women, before (baseline) and after daily consumption of galacto-oligosaccharides (GOS) for 4 wk, we sought to assess fractional iron absorption (FIA) from an iron supplement given with and without single doses of GOS in test meals or water. METHODS: In all women (n = 34; median serum ferritin concentration = 16.4 µg/L), FIA from doses of 14 mg iron labeled with stable isotopes was measured in the following conditions at baseline: 1) FIA from ferrous fumarate (FeFum) in water given with and without 15 g GOS; 2) FIA from FeFum in a test meal given with and without 15 g GOS; 3) FIA from ferrous sulfate (FeSO4) in a test meal given without 15 g GOS. All subjects then consumed âˆ¼15 g GOS daily for 4 wk. Then the following conditions were tested: 4) FIA from FeFum in a test meal with and without 15 g GOS; and 5) FIA from FeSO4 in a test meal with 15 g GOS. FIA was measured as erythrocyte incorporation of stable isotopes. RESULTS: At baseline, GOS significantly increased FIA from FeFum when given with water (+61%; P < 0.001) and the meal (+28%; P = 0.002). After 4 wk of GOS consumption, GOS again significantly increased FIA from FeFum in the meal (+29%; P = 0.044). However, compared with baseline, consumption of GOS for 4 wk did not significantly enhance absorption from FeFum in the meal given without GOS. FIA from FeSO4 given with GOS in a meal after 4 wk of GOS consumption was not significantly greater than FIA from FeSO4 in a meal without GOS at baseline. CONCLUSIONS: In iron-depleted women, GOS given with FeFum increases FIA, but 4 wk of GOS consumption did not enhance this effect. The study was registered at clinicaltrials.gov as NCT03325270.

Predicting iron absorption from an effervescent iron supplement in obese patients before and after Roux-en-Y gastric bypass: a preliminary study.

BACKGROUND & AIMS: Oral iron absorption is hampered in obese and bariatric patients, especially after Roux-en-Y gastric bypass (RYGB). As a result, iron deficiency, which is common in both patient groups, can be difficult to treat by oral supplements, often necessitating a switch to parenteral administration. The aim of this study was to find possible predictors of the extent of absorption of an effervescent iron gluconate oral supplement, which enables to pre-emptively identify those patients in which oral supplementation is likely to fail. METHODS: The pharmacokinetic properties of 695 mg effervescent iron gluconate (80 mg Fe2+) were assessed in 13 obese patients (female = 10; mean age ± SD: 45.2 ± 12.5years) pre- and six months post-RYGB by measuring serum iron concentrations during 24 hours and by calculating the adjusted for baseline AUC0-24h, Cmax and Tmax. A multivariate regression analysis was performed to investigate the effect of hepcidin concentration, iron and hematologic indices, personal and anthropometric characteristics on iron absorption. Subsequently, Receiver Operating Characteristic (ROC) curves were used to propose the cut-off value for hepcidin concentrations above which obese patients are unlikely to benefit from oral iron supplementation. Data are expressed as mean ± SD. RESULTS: Low iron status persisted after surgery as there was no significant difference observed in TSAT (17.3 ± 5.2 vs. 20.2 ± 6.6%), ferritin (91.8 ± 68.6 vs. 136.2 ± 176.9 µg/L) and hepcidin concentration (32.0 ± 30.1 vs. 28.3 ± 21.3 ng/mL) after RYGB. The absorption of effervescent iron gluconate was similar pre- and post-RYGB [AUC0-24h,pre-RYGB: 28.6 ± 10.8 µg/dL*h; AUC0-24h,post-RYGB: 27.5 ± 9.11 µg/dL*h (P = 0.84)]. Post-RYGB, iron AUC0-24h showed a strong negative correlation with both hepcidin concentrations and TSAT (R=-0.51; P = 0.08 and R=-0.81; P = 0.001), respectively. Pre-RYGB, there was a clear trend for the same negative correlations for hepcidin concentrations and TSAT (R=-0.47; P = 0.11 ;R=-0.41; P = 0.16), respectively. Taking pre-and post-RYGB data together, the negative correlations were confirmed for hepcidin concentrations and TSAT (R=-0.54; P = 0.004; R=-0.60; P = 0.001), respectively. The AUCROC = 0.87 (95%CI 0.71; 1.00) showed an optimal sensitivity/specificity cut-off at hepcidin concentrations of 26.8 ng/mL. CONCLUSIONS: The iron AUC0-24h showed a negative correlation with the hepcidin concentration and TSAT of obese patients, in particular post-RYGB. Therefore, our data support the use of hepcidin concentration and TSAT to distinguish potential responders from non-responders for iron supplementation particularly post-RYGB. Additionally, this study showed that the pharmacokinetic properties of iron gluconate from an effervescent tablet were unaffected by RYGB-surgery.

Effect of sub-chronic ferrous sulfate treatment on motor skills, hematological and biochemical parameters in rats.

This study investigated the effects of ferrous sulfate (FeSO4) on motor skills, hematological and biochemical parameters in rats. Adult rats were treated with dose of iron (280 mg/L, per os) for 15 consecutive days in drinking water. No significant difference was noticed for the motor skills in the stationary beam (p = 0.23) and suspended string tests (p = 0.48) between control and iron-treated rats. However, iron-treated rats showed a significant increase in white blood cells count (p = 0.01), mean corpuscular volume values (p = 0.02) and decrease in frequency of peristaltic contractions of the fragment of the intestine (in vitro) compared to control rats (p = 0.01). No significant difference in plasma iron level (p = 0.89) and transferrin amount were observed after iron treatment (p = 0.65). The findings indicate that iron treatment at 280 mg/L, per os for 15 consecutive days in adult rats induced increase of hematological parameters (sign of a potential inflammation), but not motor skills deficit.

Effectiveness of a Program Intervention with Reduced-Iron Multiple Micronutrient Powders on Iron Status, Morbidity and Growth in Young Children in Ethiopia.

Despite the potential for improving iron status and child growth in low- and middle-income settings, concerns on the safety of high iron dosages of Micronutrient Powders (MNP currently limit their applicability in programs. We examined the effectiveness and risks of an integrated complementary feeding program with low iron dose (6 mg/serving) MNP among 6⁻23-month-old Ethiopian children using a quasi-experimental study design comparing children from five intervention districts (n = 1172) to those from four matched non-intervention districts (n = 1137). Haemoglobin concentrations increased in intervention and decreased in non-intervention children (group-difference +3.17 g/L), but without improvement in iron stores. Intervention children were 2.31 times more likely to have diarrhoea and 2.08 times more likely to have common cold and flu, but these differences decreased towards the end of the intervention. At end line, intervention children had higher mean Height-for-Age Zscore (HAZ) and a 51% reduced odds of being stunted compared to non-intervention children. MNP with low iron dose, when provided combined with other Infant and Young Child Feeding (IYCF) interventions, marginally improved haemoglobin status and resulted in a remarkable improvement in linear growth in 6⁻23-month-old children. These benefits likely outweigh the relatively small increase in the risk of diarrhoea.

Eleven Weeks of Iron Supplementation Does Not Maintain Iron Status for an Entire Competitive Season in Elite Female Volleyball Players: A Follow-Up Study.

BACKGROUND: Even though iron supplementation can be effective, it is necessary to be cautious of toxicity and aim to do no harm, therefore, it is important to examine the length of time the benefits of iron supplementation can be maintained following its cessation. The main purpose of this study was to analyze if iron stores and strength performance were maintained in elite female volleyball players for the final 18 weeks of a competitive season following the cessation of 11 weeks of iron supplementation. METHODS: Twenty-two volleyballers (age: 27.0 ± 5.6 years.) were assigned to two groups (iron treatment group-ITG, n = 11 or control gropu-CG, n = 11) at the beginning of a previous trial (T0) and ITG consumed 325mg/d of ferrous sulphate for 11 weeks (T11). Then, in the present study iron status and strength were measured again 10 (T21) and 18 weeks later (T29) after the cessation of supplementation. RESULTS: At the end of the previous trial (T11), ITG maintained iron status as measured by hematological parameters (serum iron-sFE, serum ferritin-FER, transferrin saturation index-TSI, and hemogloblin-Hb), however, CG showed a decrease in these markers at T11. Further, from T0 to T11 ITG experienced greater (p < 0.05) changes in clean and jerk, power clean, and total mean strength (TMS-sum of all strength tests) than CG. In the present, follow-up investigation, there was a group-by-time interaction in favor of CG vs. ITG from T11 to T21 for FER (p = 0.028) and Hb (p = 0.042). Further, there was an increase for CG (p < 0.001) in power clean for CG from T11 (38.4 ± 1.7 kg) to T21 (41.3 ± 1.9 kg) and T29 (41.8 ± 1.7 kg), but no change for power clean in ITG (p > 0.05). A group-by-time interaction from T11 to T29 occurred in favor of CG for half-squat (p = 0.049) and TMS (p = 0.049). CONCLUSION: Our findings suggest that the benefits of iron supplementation are not sustained in elite female volleyballers if supplementation is ceased for 18 weeks.

Oral Versus Intravenous Iron Supplementation for the Treatment of Iron Deficiency Anemia in Patients on Maintenance Hemodialysis-Effect on Fibroblast Growth Factor-23 Metabolism.

OBJECTIVE: Iron administration affects serum levels of intact (I-) fibroblast growth factor-23 (FGF23) and its cleavage product C-terminal (C-) FGF23 in iron-deficient patients on maintenance hemodialysis (MHD). The objective of this study was to compare the effect of oral or intravenous iron administration on serum levels of I-FGF23 and C-FGF23 in iron-deficient patients on MHD. DESIGN AND METHODS: A prospective randomized study. SUBJECTS: Participants on MHD with severe iron deficiency (n = 61). INTERVENTION: Participants were randomized to receive oral iron (50 mg of sodium ferrous citrate daily; oral group, n = 29) or intravenous iron (40 mg of saccharated ferric oxide weekly; IV group, n = 32). MAIN OUTCOME MEASURE: Changes in I-FGF23 and C-FGF23 after 10 weeks of treatment. RESULTS: Iron supplementation significantly increased hemoglobin, mean corpuscular volume, ferritin, and transferrin saturation rate, and decreased erythropoiesis-stimulating agent dose and erythropoiesis-stimulating agent resistance index value. Serum phosphate, calcium, and intact parathyroid hormone levels did not change significantly during the study. I-FGF23 levels increased significantly in the IV group and did not change in the oral group, whereas C-FGF23 levels were significantly reduced in both groups. Serum interleukin-6 and tumor necrosis factor-α levels were increased in both groups. Multiple regression analysis indicated the relationship between iron or erythropoiesis and FGF23 metabolism. CONCLUSION: Iron administration to patients on MHD with severe iron deficiency decreased C-FGF23 levels, whereas intravenous iron increased I-FGF23 levels though oral iron did not. If the target of chronic kidney disease-mineral and bone disorder therapy is reducing I-FGF23 levels, we suggest the use of oral iron.

Preclinical pharmacokinetic profiling of IQG-607, a potential oral metallodrug to treat tuberculosis.

IQG-607 is an analog of isoniazid with anti-tuberculosis activity. This work describes the development and validation of an HPLC method to quantify pentacyano(isoniazid)ferrate(II) compound (IQG-607) and the pharmacokinetic studies of this compound in mice. The method showed linearity in the 0.5-50µg/mL concentration range (r=0.9992). Intra- and inter-day precision was <5%, and the recovery ranged from 92.07 to 107.68%. IQG-607 was stable in plasma for at least 30days at -80°C and, after plasma processing, for 4h in the auto-sampler maintained on ice (recovery >85%). The applicability of the method for pharmacokinetic studies was determined after intravenous (i.v.) and oral (fasted and fed conditions) administration to mice. IQG-607 levels in plasma were quantified at time points for up to 2.5h. A short half-life (t1/2) (1.14h), a high clearance (CL) (3.89L/h/kg), a moderate volume of distribution at steady state (Vdss) of 1.22L/kg, were observed after i.v. (50mg/kg) administration. Similar results were obtained for oral administration (250mg/kg) under fasted and fed conditions. The oral bioavailability (F), approximately 4%, was not altered by feeding. Plasma protein binding was 88.87±0.9%. The results described here provide novel insights into a pivotal criterion to warrant further efforts to be pursued towards attempts to translate this chemical compound into a chemotherapeutic agent to treat TB.

In Haitian women and preschool children, iron absorption from wheat flour-based meals fortified with sodium iron EDTA is higher than that from meals fortified with ferrous fumarate, and is not affected by Helicobacter pylori infection in children.

Fe fortification of wheat flour was proposed in Haiti to combat Fe deficiency, but Fe bioavailability from fortificants has never been investigated in Haitian women or preschool children, two key target groups. We aimed to investigate the bioavailability of ferrous fumarate (FeFum), NaFeEDTA and their combination from fortified wheat flour. We recruited twenty-two healthy mother-child pairs in Port au Prince, Haiti, for an Fe-absorption study. We administered stable Fe isotopes as FeFum or NaFeEDTA individually in low-extraction wheat flour bread rolls consumed by all participants in a randomised, cross-over design. In a final, identical meal, consumed only by the women, FeFum+NaFeEDTA was administered. We measured Fe absorption by using erythrocyte incorporation of stable isotopes 14 d after consumption of each meal, and determined Fe status, inflammatory markers and Helicobacter pylori infection. Fe absorption (geometric mean was 9·24 (95 % CI 6·35, 13·44) and 9·26 (95 % CI 7·00, 12·31) from FeFum and 13·06 (95 % CI 9·23, 19·10) and 12·99 (95 % CI 9·18, 18·39) from NaFeEDTA in mothers and children, respectively (P<0·05 between compounds). Fe absorption from FeFum+NaFeEDTA was 11·09 (95 % CI 7·45, 17·34) and did not differ from the other two meals. H. pylori infection did not influence Fe absorption in children. In conclusion, in Haitian women and children, Fe absorption from NaFeEDTA was 40 % higher than from FeFum, and the combination FeFum+NaFeEDTA did not significantly increase Fe absorption compared with FeFum alone. In the context of Haiti, where the high costs of NaFeEDTA may not be affordable, the use of FeFum at 60 mg Fe/kg flour may be a preferable, cost-effective fortification strategy.

Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants.

Background: Whether consumption of prebiotics increases iron absorption in infants is unclear.Objective: We set out to determine whether prebiotic consumption affects iron absorption from a micronutrient powder (MNP) containing a mixture of ferrous fumarate and sodium iron EDTA (FeFum+NaFeEDTA) in Kenyan infants.Design: Infants (n = 50; aged 6-14 mo) consumed maize porridge that was fortified with an MNP containing FeFum+NaFeEDTA and 7.5 g galacto-oligosaccharides (GOSs) (Fe+GOS group, n = 22) or the same MNP without GOSs (Fe group, n = 28) each day for 3 wk. Then, on 2 consecutive days, we fed all infants isotopically labeled maize porridge and MNP test meals containing 5 mg Fe as 57FeFum+Na58FeEDTA or ferrous sulfate (54FeSO4). Iron absorption was measured as the erythrocyte incorporation of stable isotopes. Iron markers, fecal pH, and bacterial groups were assessed at baseline and 3 wk. Comparisons within and between groups were done with the use of mixed-effects models.Results: There was a significant group-by-compound interaction on iron absorption (P = 0.011). The median percentages of fractional iron absorption from FeFum+NaFeEDTA and from FeSO4 in the Fe group were 11.6% (IQR: 6.9-19.9%) and 20.3% (IQR: 14.2-25.7%), respectively, (P < 0.001) and, in the Fe+GOS group, were 18.8% (IQR: 8.3-37.5%) and 25.5% (IQR: 15.1-37.8%), respectively (P = 0.124). Between groups, iron absorption was greater from the FeFum+NaFeEDTA (P = 0.047) in the Fe+GOS group but not from the FeSO4 (P = 0.653). The relative iron bioavailability from FeFum+NaFeEDTA compared with FeSO4 was higher in the Fe+GOS group than in the Fe group (88% compared with 63%; P = 0.006). There was a significant time-by-group interaction on Bifidobacterium spp. (P = 0.008) and Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.018); Lactobacillus/Pediococcus/Leuconostoc spp. decreased in the Fe group (P = 0.013), and there was a nonsignificant trend toward higher Bifidobacterium spp. in the Fe+GOS group (P = 0.099). At 3 wk, iron absorption was negatively correlated with fecal pH (P < 0.001) and positively correlated with Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.001).Conclusion: GOS consumption by infants increased iron absorption by 62% from an MNP containing FeFum+NaFeEDTA, thereby possibly reflecting greater colonic iron absorption. This trial was registered at clinicaltrials.gov as NCT02666417.

Iron bioavailability from fresh cheese fortified with iron-enriched yeast.

PURPOSE: An iron-enriched yeast able to lyse at body temperature was developed for iron fortification of chilled dairy products. The aim was to evaluate iron (Fe) absorption from iron-enriched yeast or ferrous sulfate added to fresh cheese. METHODS: Two stable isotope studies with a crossover design were conducted in 32 young women. Fe absorption from fresh cheese fortified with iron-enriched yeast (2.5 mg 58Fe) was compared to that from ferrous sulfate (2.5 mg 57Fe) when ingested with fresh cheese alone or with fresh cheese consumed with bread and butter. Iron absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal. RESULTS: Geometric mean fractional iron absorption from fresh cheese fortified with iron-enriched yeast consumed alone was significantly lower than from the cheese fortified with FeSO4 (20.5 vs. 28.7 %; p = 0.0007). When the fresh cheese was consumed with bread and butter, iron absorption from both fortificants decreased to 6.9 % from the iron-enriched yeast compared to 8.4 % from ferrous sulfate. The relative bioavailability of the iron-enriched yeast compared to ferrous sulfate was 0.72 for the cheese consumed alone and 0.82 for cheese consumed with bread and butter (p = 0.157). CONCLUSIONS: Iron from iron-enriched yeast was 72-82 % as well absorbed as ferrous sulfate indicating that the yeast lysed during digestion and released its iron.

Acute Copper and Ascorbic Acid Supplementation Inhibits Non-heme Iron Absorption in Humans.

The objective of the study is to determine the effect of copper (Cu) plus the reducing agent ascorbic acid (AA) on the absorption of non-heme iron (Fe). Experimental study with block design in which each subject was his own control. After signing an informed consent, 14 adult women using an effective method of contraception and negative pregnancy test received 0.5 mg Fe, as ferrous sulfate, alone or with Cu, as copper sulfate, plus ascorbic acid (AA/Cu 2/1 molar ratio) at 4/1; 6/1 and 8/1 Cu/Fe molar ratios as an aqueous solution on days 1, 2, 14, and 15 of the study. Fe absorption was assessed by erythrocyte incorporation of iron radioisotopes (55)Fe and (59)Fe. Geometric mean (range ± SD) absorption of Fe at 4/1 and 6/1 Cu/Fe molar ratios (and AA/Cu 2/1 molar ratio) and Fe alone was 57.4 % (35.7-92.1 %), 64.2 % (45.8-89.9 %), and 38.8 % (20.4-73.8 %), respectively (ANOVA for repeated measures p < 0.001; post hoc test Scheffé, p < 0.05). This is attributable to the enhancing effect of AA on non-heme Fe absorption; however, Fe absorption at Cu/Fe 8/1 molar ratio was 47.3 % (27.7-80.8) (p = NS compared with Fe alone). It was expected that Fe absorption would have been equal or greater than at 4/1 and 6/1 molar ratios. Copper in the presence of ascorbic acid inhibits non-heme Fe absorption at Cu/Fe 8/1 molar ratio.

Iron Absorption from Two Milk Formulas Fortified with Iron Sulfate Stabilized with Maltodextrin and Citric Acid.

BACKGROUND: Fortification of milk formulas with iron is a strategy widely used, but the absorption of non-heme iron is low. The purpose of this study was to measure the bioavailability of two iron fortified milk formulas designed to cover toddlers´ nutritional needs. These milks were fortified with iron sulfate stabilized with maltodextrin and citric acid. METHODS: 15 women (33-47 years old) participated in study. They received on different days, after an overnight fast, 200 mL of Formula A; 200 mL of Formula B; 30 mL of a solution of iron and ascorbic acid as reference dose and 200 mL of full fat cow's milk fortified with iron as ferrous sulfate. Milk formulas and reference dose were labeled with radioisotopes (59)Fe or (55)Fe, and the absorption of iron measured by erythrocyte incorporation of radioactive Fe. RESULTS: The geometric mean iron absorption corrected to 40% of the reference dose was 20.6% for Formula A and 20.7% for Formula B, versus 7.5% of iron fortified cow's milk (p < 0.001). The post hoc Sheffé indeed differences between the milk formulas and the cow's milk (p < 0.001). CONCLUSION: Formulas A and B contain highly bioavailable iron, which contributes to covering toddlers´ requirements of this micronutrient.

Oral iron absorption test should not be performed with iron drops containing ferric iron.

INTRODUCTION: In an oral iron absorption test (OIAT), the rise in plasma iron concentration after oral ingestion of iron is a measure of intestinal iron absorption. We describe results of the OIAT using two different formulations of oral iron drops. METHODS: The study included all patients who had an OIAT performed at the Department of Internal Medicine, Farsø, Aalborg University Hospital, Denmark, from 1 January 2013 to 17 June 2014 (n = 24) using ferrous iron drops "Glycifer" and from 18 June to 3 November 2014 (n = 17) using ferric iron drops "Medic". A venous blood sample was drawn before and then 90, 180 and 240 min. after the intake of 9 ml iron drops of the "Glycifer" brand (270 mg ferrous iron) or the intake of 11 ml iron drops of the "Medic" brand (264 mg ferric iron). RESULTS: The patient characteristics (ferrous versus ferric iron drops) were similar in terms of gender, age, haemoglobin, ferritin and previous gastric bypass surgery. The fasting baseline plasma iron concentration was median 5 µmol/l in both groups (p = 0.4). The maximum plasma iron concen-tration increase from baseline after oral intake of the iron drops was median 2 µmol/l (range: 0-8 µmol/l) in the group given ferric iron drops and 48 µmol/l (range: 14-78 µmol/l) when ferrous iron drops were used (p < 0.001). CONCLUSION: OIAT performed with ferrous or ferric iron drops showed very different results with a lack of plasma iron concentration increase after ingestion of ferric iron drops. FUNDING: none. TRIAL REGISTRATION: not relevant.

Reference values for oral iron absorption of bivalent iron in healthy volunteers.

BACKROUND: It is a challenge to establish the cause of iron deficiency in the absence of obvious reasons. There has been no prospectively validated oral iron absorption test (OIAT) that could confidently confirm or exclude iron malabsorption. The aim, therefore, was the establishment of an OIAT with defining reference values of plasma iron in healthy volunteers. METHODS: We included 49 healthy volunteers who received 200 mg of bivalent ferrous fumarate in fasting condition and measured plasma iron after 2 and 4 hours as well as after 3 and 5 days. After a wash-out phase, 23 healthy volunteers proceeded to receive trivalent iron hydroxide polymaltose in fasting condition, and 11 participants were tested without iron. RESULTS: Reference values of absolute and relative plasma iron after oral iron ingestion could be established. There was a significant increase of plasma iron after bivalent iron intake within 4 hours after ingestion (absolute increase after 4h: from initially 17 ± 4 µmol/l to 35 ± 12 µmol/l in females and from 21 ± 7 µmol/l to 33 ± 11 µmol/l in males, relative plasma iron concentration (defined reference: 1.0) after 4 h: 2.1 ± 0.7 in females and 1.7 ± 0.6 in males). There was no relevant increase with trivalent iron nor without iron. Relative iron increase correlates to iron storage. In general, females had lower ferritin levels and thus higher increases of plasma iron. CONCLUSION: An OIAT in healthy volunteers could be established. Its prospective validation using bivalent iron in iron deficiency is desirable.

Iron deficiency during pregnancy: the consequences for placental function and fetal outcome.

This review examines the importance of the placenta in iron metabolism during development and the effect of iron deficiency on maternal and fetal physiology. Iron is an essential micronutrient, required for a wide variety of biological processes. During pregnancy, the mother has to deplete her iron stores in order to provide the baby with adequate amounts. Trans-placental iron transfer involves binding transferrin (Tf)-bound iron to the Tf receptor, uptake into an endosome, acidification, release of iron through divalent metal transporter 1, efflux across the basolateral membrane through ferroportin and oxidation of Fe(II) by zyklopen. An additional haem transport system has been hypothesised, which may explain why certain gene knockouts are not lethal for the developing fetus. Iron deficiency is a common phenomenon during pregnancy, and the placenta adapts by up-regulating its transfer systems, maintaining iron at the expense of the mother. Despite these adaptations, deficiency cannot be completely prevented, and the offspring suffers both short- and long-term consequences. Some of these, at least, may arise from decreased expression of genes involved in the cell cycle and altered expression of transcription factors, such as c-myc, which in turn can produce, for example, kidneys with reduced numbers of nephrons. The mechanism whereby these changes are induced is not certain, but may simply be as a result of the reduced availability of iron resulting in decreased enzyme activity. Since these changes are so significant, and because some of the changes are irreversible, we believe that iron prophylaxis should be considered in all pregnancies.

[Dietary supplement of iron for iron deficiency]. / Kosttilskudd med jern ved jernmangel.

BACKGROUND: A low supply of iron in the diet may result in iron deficiency and mild iron-deficiency anaemia in healthy individuals. Women are more susceptible than men because of menstrual iron loss. We compared the effect of a low dose of iron, administered as a dietary supplement, with a high pharmacological dose of iron to otherwise healthy individuals with iron deficiency and mild iron deficiency anaemia. MATERIAL AND METHOD: In a randomised, double-blind trial conducted in 2000-2001, 73 women and three men with iron deficiency received either 27.6 mg of iron consisting of ferrous fumarate enriched with 13% haem iron, or 100 mg ferrosulphate daily for 12 weeks. Blood samples were analysed four times in the course of the treatment. RESULTS: The median ferritin value rose by 13 and 7 µg/l in the high-dose and low-dose group, respectively. The increase in ferritin was significantly higher in the high-dose than in the low dose group ( < 0.001). There was no statistically significant difference between the groups in the change in Hb, serum-iron or serum-iron binding capacity. The median haemoglobin value increased by 0.4 g/100 ml in both groups. Gastrointestinal side effects were experienced by 58% in the high-dose group and 35% in the low-dose group. Four subjects in the high-dose group and one in the low-dose group broke off the treatment because of side effects. INTERPRETATION: A supplement of low-dose iron is enough to increase iron stores in cases of nutritional iron deficiency in healthy individuals and to optimise haemoglobin. High-dose iron caused the largest increase in iron stores. Low-dose iron resulted in the least side effects.