High-dose Oral Iron Research Articles

Impact on oxidative stress of oral, high-dose, iron supplementation for management of iron deficiency after bariatric surgery, a preliminary study

ObjectivesHigh-dose oral iron supplementation for patients who develop iron deficiency after bariatric surgery may induce oxidative stress in the gastrointestine. The study’s objective was to test this hypothesis by determining the impact of high-dose oral iron on systemic oxidative stress. MethodsWe used archived plasma samples from a randomized controlled clinical trial (NCT 02404012) comparing FeSO4 (195 mg/day, NatureMade®, West Hills, CA) with a heme iron polypeptide (HIP, 60.4 mg/day, Proferrin®, Colorado Biolabs, Lafayette, CO) for 8 weeks. Systemic oxidative stress was measured using malondialdehyde and total antioxidant capacity (MDA, Abcam, ab238537 and TAC, Abcam, ab65329 Cambridge, UK) assays. Data was log-transformed and presented as means and standard deviations; a mixed model was used to determine the effects of time (0, 2, 4, and 8 weeks) and treatment (FeSO4 versus HIP) on oxidative stress. ResultsThe FeSO4 (N = 8) and HIP (N = 5) participants were balanced in body mass index (35.0 ± 5.5 kg/m2), race (93 % White), time post-surgery (7.3 ± 3.3 years), as well as serum concentrations of iron (P > 0.05). The FeSO4 group tended to be older (44.3 ± 4.5 years) and they had lower concentrations of serum ferritin (6.5 ± 2.7 µg/mL) than the HIP (38.2 ± 9.3 years, and 12.9 ± 16.8 µg/mL) group (P = 0.080, and P = 0.017 respectively). We observed a larger increase in serum iron in the FeSO4 group during the 8 weeks of Fe supplementation, compared to that in the HIP group (p = 0.004). We observed a decreasing trend in MDA over the 8 weeks (p = 0.080) in the FeSO4 treatment group. There were no significant differences in TAC between and within FeSO4 and HIP groups over the 8 week supplementation period. ConclusionsThis preliminary study suggests that high-dose oral iron supplementation for iron deficiency does not adversely impact systemic oxidative stress in patients undergoing bariatric surgery.

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

BackgroundAnaemia 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.MethodsThis 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.DiscussionThe 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 2020Clinicaltrials.govNCT04976179. Registered on 26 July 2021The current protocol version is version 2.1 (080/080/2021).

Spray-Dried Whey Protein Concentrate-Iron Complex: Preparation and Physicochemical Characterization.

SUMMARYPoor absorption of iron from food and oral iron formulations results in extensive use of high-dose oral iron, which is not tolerated. Disposal of whey, a byproduct of the cheese industry, causes environmental pollution. Whey proteins have the ability to bind significant amount of iron, thereby reducing its chemical reactivity and incompatibility with other components in foods. To make iron compatible with food, it was complexed with whey protein concentrate (WPC). After complexation, centrifugation and ultrafiltration techniques were utilised to eliminate the insoluble and free iron from the solution. To enable the availability of whey protein concentrate–iron (WPC–Fe) complex in the powder form, spray drying technique was used. Optimized spray drying conditions used for the preparation were: inlet temperature 180 °C, flow rate 2.66 mL/min and solution of total solids 15%. The complex was observed to be stable under different processing conditions. The in vitro bioaccessibility (iron uptake) of the bound iron from the WPC–Fe complex was significantly higher (p<0.05) than that from iron(II) sulphate under simulated gastrointestinal conditions. WPC–Fe complex with improved iron bioaccessibility could safely substitute iron fortificants in different functional food preparations.

Novel Iron-Whey Protein Microspheres Protect Gut Epithelial Cells from Iron-Related Oxidative Stress and Damage and Improve Iron Absorption in Fasting Adults

Background: Iron food fortification and oral iron formulations are frequently limited by poor absorption, resulting in the widespread use of high-dose oral iron, which is poorly tolerated. Methods: We evaluated novel iron-denatured whey protein (Iron-WP) microspheres on reactive oxygen species (ROS) and viability in gut epithelial (HT29) cells. We compared iron absorption from Iron-WP versus equimolar-dose (25 mg elemental iron) ferrous sulphate (FeSO₄) in a prospective, randomised, cross-over study in fasting volunteers (n = 21 per group) dependent on relative iron depletion (a ferritin level ≤/>30 ng/mL). Results: Iron-WP caused less ROS generation and better HT29 cell viability than equimolar FeSO₄. Iron-WP also showed better absorption with a maximal 149 ± 39% increase in serum iron compared to 65 ± 14% for FeSO₄ (p = 0.01). The response to both treatments was dependent on relative iron depletion, and multi-variable analysis showed that better absorption with Iron-WP was independent of baseline serum iron, ferritin, transferrin saturation, and haemoglobin in the overall group and in the sub-cohort with relative iron depletion at baseline (p < 0.01). Conclusions: Novel Iron-WP microspheres may protect gut epithelial cells and improve the absorption of iron versus FeSO₄. Further evaluation of this approach to food fortification and supplementation with iron is warranted.

Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency

Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF (<40%) and iron deficiency, defined as a serum ferritin level of 15 to 100 ng/mL or a serum ferritin level of 101 to 299 ng/mL with transferrin saturation of less than 20%. Participants were enrolled between September 2014 and November 2015 at 23 US sites. Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P > .05. Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. clinicaltrials.gov Identifier: NCT02188784.

Common Misconceptions in the Diagnosis and Management of Anemia in Inflammatory Bowel Disease

Anemia is the most common systemic complication of inflammatory bowel disease (IBD); so common that it is almost invariably not investigated and rarely treated. Several misconceptions are the reason for these clinical errors, and our goal will be to review them. The most common misconceptions are: anemia is uncommon in IBD; iron deficiency is also uncommon; just by treating the intestinal disease, anemia will be corrected; iron deficiency is the only cause for anemia in IBD; ferritin is an accurate parameter for the diagnosis of iron deficiency in IBD; the impact of anemia on the quality of life of IBD patients is limited; iron supplementation is rarely needed in IBD; high-dose oral iron solves the problem of iron malabsorption in IBD; intravenous (IV) iron is dangerous and of no proven benefit in IBD; IV iron is useful only for severe anemia; and erythropoietin has no role in the treatment of IBD anemia. These misconceptions are not evidence-based. On the contrary, there is enough evidence to support the following statements: (a) anemia is very common in IBD, (b) anemia should be investigated with care because many factors can be responsible, (c) treatment of anemia results in clear improvement in the objective parameters of well-being, especially in the quality of life, (d) IV iron is safe and effective in the treatment of iron deficiency anemia in IBD patients, and (e) erythropoietin is useful in a subset of patients with refractory anemia. Anemia diagnosis and treatment must not be neglected in IBD patients, and several misconceptions should be promptly abandoned.

Oxidative Stress Markers and Antioxidant Status after Oral Iron Supplementation to Very Low Birth Weight Infants

To evaluate whether our current practice of giving iron 18 mg daily to 6-week-old infants with very low birth weight (VLBW) was associated with increased oxidative stress markers or decreased antioxidant status. The study was a prospective observational study of 21 healthy VLBW infants (born at gestational age <32 weeks, birth weight <1500 g). Blood and urine were sampled twice before starting iron supplementation at 6 weeks postnatal age and after 1 week of iron supplementation at age 7 weeks. Urine 8-isoprostane was analyzed by gas chromatography-mass spectrometry and plasma total hydroperoxides were measured. Antioxidant status was assessed by ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), ferric-reducing ability of plasma, and plasma glutathione. After 1 week of iron supplementation, no significant changes in urine 8-isoprostane or plasma total hydroperoxides were seen, and plasma antioxidants were largely unchanged. Markers of oxidative stress in urine and plasma antioxidant status in healthy VLBW infants fed human milk remained unchanged after high-dose oral iron supplementation.

Is Absorption of High-Dose Oral Iron Sufficient in Peritoneal Dialysis Patients?

Iron supplementation plays a major role in erythropoietin-treated end-stage renal disease patients. For peritoneal dialysis (PD) patients, oral iron substitution is more convenient than intravenous therapy. However, disturbed iron absorption and adverse effects may be limiting factors for oral treatment. Nevertheless, we compared the response to a high-dose and low-dose oral iron absorption test between PD patients and healthy control subjects. In 34 PD patients and 15 healthy control subjects, blood samples were taken at baseline as well as 2, 4, and 8 hours after oral intake of 4 tablets iron sulfate (105 mg elemental iron per tablet). In a subgroup of 6 PD patients and 6 control subjects, the oral iron absorption test was repeated using 1 tablet iron sulfate. There was no significant difference in the increase in serum iron during the test between the two groups. As known for healthy subjects, iron absorption was significantly better in PD patients with absolute iron deficiency compared to those with functional iron deficiency. Iron-repleted PD patients showed the lowest iron absorption, indicating that a high dose of oral iron did not overwhelm the ability of the bowel tract to reject unneeded iron. Increasing the oral iron dose from 1 to 4 tablets was followed by a better response in a small subgroup of PD patients compared to control subjects. Side effects such as nausea and vomiting occurred more frequently during high-dose oral iron in control subjects than in PD patients (20% vs 8.8%). High-dose oral iron is well absorbed in iron-depleted PD patients. This kind of oral iron therapy should be considered in some subgroups of PD patients with iron deficiency, particularly in those patients with poor vascularization of arm veins or intolerance to intravenous iron preparations.

Assessing iron status in children with chronic renal failure on erythropoietin: which measurements should we use?

Iron deficiency severely limits the efficacy of recombinant human erythropoietin (EPO). In order to determine how best to identify and monitor children at risk of developing iron deficiency, we serially measured several parameters of iron status in nine children before and during a 24-week period of EPO therapy. Serum ferritin was the best predictor of development of iron deficiency, five of the nine children developed iron deficiency, characterised by a poor haemoglobin response or evidence of microcytosis and hypochromia; all had a serum ferritin of 60 micrograms/l or less at the start of EPO. Haemoglobin response was also related to change in mean red cell volume (MCV); a falling MCV, irrespective of absolute value, accompanying a poor response to EPO. Iron treatment in five children resulted in significant improvements in haemoglobin and iron status parameters. Although MCV remained low, there was a marked increase in red cell volume distribution width after iron, which may be of value in monitoring the response to iron therapy. We suggest that children with a serum ferritin of 60 micrograms/l or less and those who develop a falling MCV during EPO treatment should receive high-dose oral iron supplementation before and during treatment with EPO.