Oral administration of lactoferrin increases hemoglobin and total serum iron in pregnant women.

Iron deficiency anemia (IDA) during pregnancy continues to be of world-wide concern. IDA is a risk factor for preterm delivery and subsequent low birth weight, and possibly for poor neonatal health. Iron supplementation in pregnancy is a widely recommended practice, yet intervention programs have met with many controversies. In our study, 300 women at different trimesters of pregnancy were enrolled in a trial of oral administration of ferrous sulfate (520 mg once a day) or 30% iron-saturated bovine lactoferrin (bLf) (100 mg twice a day). Pregnant women refusing treatment represented the control group. In this group hemoglobin and total serum iron values measured after 30 d without treatment decreased significantly, especially in women at 18-31 weeks of pregnancy. In contrast, after 30 d of oral administration of bLf, hemoglobin and total serum iron values increased and to a greater extent than those observed in women treated orally for 30 d with ferrous sulfate, independently of the trimester of pregnancy. Unlike ferrous sulfate, bLf did not result in any side effects. These findings lead us to hypothesize that lactoferrin could influence iron homeostasis directly or through other proteins involved in iron transport out of the intestinal cells into the blood.     

Lactoferrin efficacy versus ferrous sulfate in curing iron deficiency and iron deficiency anemia in pregnant women

Iron deficiency (ID) and iron deficiency anemia (IDA) are the most common iron disorders throughout the world. ID and IDA, particularly caused by increased iron requirements during pregnancy, represent a high risk for preterm delivery, fetal growth retardation, low birth weight, and inferior neonatal health. Oral administration of ferrous sulfate to cure ID and IDA in pregnancy often fails to increase hematological parameters, causes adverse effects and increases inflammation. Recently, we have demonstrated safety and efficacy of oral administration of 30% iron saturated bovine lactoferrin (bLf) in pregnant women suffering from ID and IDA. Oral administration of bLf significantly increases the number of red blood cells, hemoglobin, total serum iron and serum ferritin already after 30 days of the treatment. The increasing of hematological values by bLf is related to the decrease of serum IL-6 and the increase of serum hepcidin, detected as prohepcidin, whereas ferrous sulfate increases IL-6 and fails to increase hematological parameters and prohepcidin. bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA in pregnant women.     

Once Weekly Low-dose Iron Supplementation Effectively Improved Iron Status in Adolescent Girls

Iron supplementation has been suggested as a strategy for prevention and treatment of iron deficiency (ID) and iron deficiency anemia (IDA) in many countries, but non-compliance of daily regimens and common dosage remain as major challenges. The aim of this study was to investigate the effects of low dose once weekly iron supplementation in adolescent girls. The study was designed as a community-based, randomized, supplementation trial. The initial sample consisted of 200 female high school students, aged 14–16 years old, of whom 193 students concluded the study. They were randomly selected and assigned into either iron-supplemented group (ISG) or iron-unsupplemented group (IUG). The ISG received 150 mg ferrous sulfate once weekly for 16 weeks, whereas the IUG received nothing. Weight, height, and hematological parameters were measured and compared between the two groups before and after the intervention. There was no significant difference between the initial measures of the two groups before the intervention. After 16 weeks of intervention, mean of hemoglobin and serum ferritin improved significantly in ISG compared to IUG. At the beginning of the study, percent of anemia, IDA, and ID in ISG were 12.5%, 8.3%, and 30.2%, whereas these figures for IUG in this period of study were 14.4, 10.3, and 38.2, respectively, which were not significantly different between the two groups. However, percentages of the above items at the end of study in ISG were 2.1%, 0%, and 21.9%, respectively. In contrast to IUG, all cases of IDA were abolished in the ISG. Our study showed that once weekly supplementation of 150 mg ferrous sulfate for 16 weeks significantly improved iron status in female adolescents and effectively treated IDA. There is no need for higher dosage of iron for supplementation that may cause adverse effects and bear higher costs.     

Non-transferrin-bound iron in plasma following administration of oral iron drugs

Non-transferrin-bound iron (NTBI) was detected in serum samples from volunteers with normal iron stores or from patients with iron deficiency anaemia after oral application of pharmaceutical iron preparations. Following a 100 mg ferrous iron dosage, NTBI values up to 9 μM were found within the time period of 1–4 h after administration whereas transferrin saturation was clearly below 100%. Smaller iron dosages (10 and 30 mg) gave lower but still measurable NTBI values. The physiological relevance of this finding for patients under iron medication has to be elucidated.     

生血宁片联合琥珀酸亚铁片治疗妊娠期缺铁性贫血患者的疗效及对铁代谢的影响

目的:探讨生血宁片联合琥珀酸亚铁片治疗妊娠期缺铁性贫血患者的疗效及对铁代谢的影响。方法:选取2015年2月-2017年2月我院收治的妊娠期缺铁性贫血患者200例为研究对象。将其以随机数字表法分成对照组(n=100)和研究组(n=100)。对照组予以口服琥珀酸亚铁片治疗,研究组则予以生血宁片联合琥珀酸亚铁片治疗,两组均连续治疗4周。分别比较两组临床疗效、治疗前后血液学指标、治疗前后铁代谢指标以及不良妊娠结局情况。结果:研究组治疗总有效率明显较对照组升高(P0.05)。治疗后两组患者血红蛋白(Hb)、红细胞(RBC)、平均红细胞体积(MCV)以及平均红细胞血红蛋白浓度(MCHC)水平均明显高于治疗前,且研究组高于对照组(P0.05)。治疗后两组患者血清铁、转铁蛋白饱和度(TSAT)水平均明显高于治疗前,且研究组又明显高于对照组(P0.05)。与对照组比较,研究组不良妊娠结局发生率降低(P0.05)。结论:生血宁片联合琥珀酸亚铁片治疗妊娠期缺铁性贫血患者的临床疗效显著,改善患者血液学指标以及铁代谢水平,降低不良妊娠结局发生风险,值得临床推广应用。     

Effects of iron(II) salts and iron(III) complexes on trace element status in children with iron-deficiency anemia

Iron-deficiency anemia (IDA) is the most common nutritional deficiency in childhood throughout the world. Although it has been shown that IRA is associated with elevated plasma copper and depleted zinc levels in children, there are conflicting results on the effect of iron supplementation on the absorption of these elements. The aim of this study was to investigate the effects of ferrous and ferric iron supplementation on the trace element status in children (n=25, aged 8-168 mo) with IDA. Fourteen of them were treated with ferric hydroxide-polymaltose complex (Ferrum, Vifor, Switzerland) (6 mg/d in the first 3 mo for initial therapy and 3 mg/kg for 3 mo as maintenance); the others were treated with a ferrous sulfate complex (FerroSanol, Schwarz, Germany) (6 mg/d in the first 3 mo for initial therapy and 3 mg/kg for 3 mo as maintenance). Plasma copper, zinc, and ceruloplasmin levels as well as hematological parameters were determined at baseline and the first, third, and sixth month of the treatment period. The hemoglobin and iron levels of patients in both groups were higher in the first and sixth months compared to baseline. Although the ceruloplasmin levels were depleted (48.9 mg/dL vs 41.4 mg/dL, p=0.035) during ferrous iron treatment, the copper and zinc levels remained unchanged. On the other hand, ferric iron supplementation led to an increase in zinc levels in the sixth month of treatment (0.77 mg/L vs 1.0 mg/L, p=0.021). The plasma copper levels were lower in the ferrous iron-treated group at the end of the first month of treatment than in the ferric irontreated group (1.06 mg/L vs 1.29 mg/L, p=0.008). In conclusion, our data showed that copper and ceruloplasmin metabolisms were affected by ferrous iron supplementation, whereas ferric iron kept them to normal levels of zinc, possibly by affecting their absorption. We conclude that the copper and zinc status of patients with IDA should be taken into consideration before and after iron therapy.     

THE NEWER HEMATINICS,THEIR USE AND ABUSE

The newer hematinics are merely refinements of preexisting forms of treatment, but they have aided particularly in a better understanding of the deficiency states. The intrinsic factor of Castle has not been isolated from the gastric juice, and the interrelationships of this substance with the extrinsic factor (vitamin B₁₂) and folic acid have not been defined at this time. Vitamin B₁₂ appears to be the active principle of refined liver extract and alone is probably adequate treatment for pernicious anemia. The other varieties of megaloblastic anemia may result from deficiency of vitamin B₁₂ or folic acid, although generally treatment with the latter brings about complete and lasting remission.The use of multihematinics and multivitamin preparations containing folic acid is to be condemned, particularly because of the possibility of their obscuring anemia and thwarting diagnosis of pernicious anemia until neurologic complications have taken place.Saccharated oxide of iron is a relatively safe preparation for intravenous administration, but the indications for its use are few. Because the body has no mechanism for iron excretion, only the amount of iron necessary to make up a deficiency should be given, although there is no definite evidence that hemochromatosis results from overdosage.     

The newer hematinics,their use and abuse

The newer hematinics are merely refinements of preexisting forms of treatment, but they have aided particularly in a better understanding of the deficiency states. The intrinsic factor of Castle has not been isolated from the gastric juice, and the interrelationships of this substance with the extrinsic factor (vitamin B(12)) and folic acid have not been defined at this time. Vitamin B(12) appears to be the active principle of refined liver extract and alone is probably adequate treatment for pernicious anemia. The other varieties of megaloblastic anemia may result from deficiency of vitamin B(12) or folic acid, although generally treatment with the latter brings about complete and lasting remission. The use of multihematinics and multivitamin preparations containing folic acid is to be condemned, particularly because of the possibility of their obscuring anemia and thwarting diagnosis of pernicious anemia until neurologic complications have taken place. Saccharated oxide of iron is a relatively safe preparation for intravenous administration, but the indications for its use are few. Because the body has no mechanism for iron excretion, only the amount of iron necessary to make up a deficiency should be given, although there is no definite evidence that hemochromatosis results from overdosage.     

The Effect of Iron Treatment on Adhesion Molecules in Patients with Iron Deficiency Anemia

The present study was aimed to determine the effect of iron supplementation on levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with iron deficiency anemia (IDA). In this study, 26 female patients diagnosed with iron deficiency were treated approximately 3 months of oral iron supplementation (99 ± 10 days; ferrous glycine sulfate; 100 mg/day of elemental iron). Levels of sICAM-1 and sVCAM-1 were assessed prior to treatment and after approximately 3 months of treatment and compared with 26 healthy female subjects. A significant increase in sVCAM levels was found in the patients with iron deficiency at the end of the treatment relative to pretreatment levels compared to controls, whereas no significant differences were determined in sICAM levels. In the posttreatment period, no significant change was observed in sICAM levels compared to the pretreatment levels, whereas sVCAM levels decreased. However, after the treatment period, the sVCAM, hemoglobin, mean corpuscular volume (MCV), and serum ferritin levels did not return to the normal range compared to the controls. Pretreatment sVCAM-1 levels were inversely correlated with levels of hemoglobin, hemotocrit, MCV, serum iron, and ferritin. After treatment, the sVCAM-1 levels were negatively correlated with ferritin levels. Levels of sVCAM were significantly higher in patients with IDA than controls. After the treatment period, the sVCAM levels were not completely normalized in patients with IDA compared to controls, regardless of the presence of inadequate levels of hemoglobin, MCV, and serum ferritin. Thus, iron supplementation not only ameliorates anemia, but may also reduce the inflammation markers in cases with IDA.     

Effects of iron sources on the growth and lipid/carbohydrate production of marine microalga <Emphasis Type="Italic">Dunaliella tertiolecta</Emphasis>

The effects of iron sources with different speciation and anionic moieties (ferric chloride, ferrous chloride, ferric EDTA, ferrous EDTA, ferric ammonium sulfate, and ferrous ammonium sulfate) on the cell growth and the production of energy storage (lipid and carbohydrate) from Dunaliella tertiolecta were investigated. The influence of iron dosage was also compared in the range from 0.65 mg/L (1X) to 6.5 mg/L (10X) as Fe concentration. Best cell growth rate was achieved when ferrous ammonium sulfate was used. Ferric EDTA resulted in higher lipid content than other iron sources, while ferrous ammonium sulfate favored the accumulation of carbohydrate among six iron sources. The accumulations of lipid and carbohydrate as energy storage competed each other and thus both contents did not increase together. In the presence of ferric EDTA, lipid content is increasing, while carbohydrate content is decreasing. On the contrary, lipid content is decreasing while carbohydrate is increasing in the presence of ferric ammonium sulfate. Because the overall carbohydrate content was larger than that of lipid, bioethanol production would be more advantageous than biodiesel production with the present D. tertiolecta strain if the carbohydrate in D. tertiolecta contains a high fraction of glucose with a good saccharification yield.     

Selective Alteration in Blood-Brain Barrier and Insulin Transport in Iron-Deficient Rats

Nutritional iron deficiency induced in rats causes a significant reduction in level of brain nonheme iron and is accompanied by selective reduction of dopamine D2 receptor Bmax. Our previous studies have clearly demonstrated that these alterations can be restored to normal by supplementation with ferrous sulfate; however, neither brain nonheme iron level nor dopamine D2 receptor Bmax can be increased beyond control values even after long-term iron therapy. The possibility that iron deficiency can induce the breakdown of the blood-brain barrier (BBB) was examined. A 70 and 100% increase in brain uptake index (BUI) for L-glucose and insulin, respectively, were noted in iron-deficient rats. However, the BUI for valine was decreased by 40%, and those for L-norepinephrine and glycine were unchanged. In addition, it was demonstrated that in normal rats insulin is transported into the brain. The data show that iron deficiency selectively affects the integrity of the BBB for insulin, glucose, and valine transport. Whether the effect of iron deficiency on the BBB is at the level of the capillary endothelial cell tight junction is not yet known. However, this study has shown that an important nutritional disorder (iron-deficiency anemia) has a profound effect on the BBB and brain function.     

SULFATE REQUIREMENT FOR IRON OXIDATION BY THIOBACILLUS FERROOXIDANS

Lazaroff, Norman (British Columbia Research Council, Vancouver, B.C., Canada). Sulfate requirement for iron oxidation by Thiobacillus ferrooxidans. J. Bacteriol. 85:78-83. 1963.-The growth of Thiobacillus ferrooxidans is initially inhibited in media containing ferrous chloride in place of ferrous sulfate. This inhibition of growth is due to the requirement of a high relative proportion of sulfate ions to chloride (or other anions) for iron oxidation. Adaptation takes place, producing strains which are able to oxidize iron in media containing an initially unfavorable anionic composition. Adaptation is possibly due to the selection of spontaneous mutants capable of oxidizing iron in high chloride, low sulfate media. Such cells are found at a frequency of 10(-5) of the population of unadapted cultures.     

Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis

BackgroundThe tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.ObjectiveOur aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate.MethodsSystematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GI side-effects that included ferrous sulfate and a comparator that was either placebo or intravenous (IV) iron. Random effects meta-analysis modelling was undertaken and study heterogeneity was summarised using I² statistics.ResultsForty three trials comprising 6831 adult participants were included. Twenty trials (n = 3168) had a placebo arm and twenty three trials (n = 3663) had an active comparator arm of IV iron. Ferrous sulfate supplementation significantly increased risk of GI side-effects versus placebo with an odds ratio (OR) of 2.32 [95% CI 1.74–3.08, p<0.0001, I² = 53.6%] and versus IV iron with an OR of 3.05 [95% CI 2.07-4.48, p<0.0001, I² = 41.6%]. Subgroup analysis in IBD patients showed a similar effect versus IV iron (OR = 3.14, 95% CI 1.34-7.36, p = 0.008, I² = 0%). Likewise, subgroup analysis of pooled data from 7 RCTs in pregnant women (n = 1028) showed a statistically significant increased risk of GI side-effects for ferrous sulfate although there was marked heterogeneity in the data (OR = 3.33, 95% CI 1.19-9.28, p = 0.02, I² = 66.1%). Meta-regression did not provide significant evidence of an association between the study OR and the iron dose.ConclusionsOur meta-analysis confirms that ferrous sulfate is associated with a significant increase in gastrointestinal-specific side-effects but does not find a relationship with dose.     

Studies on the Low Toxicity of Reduced Iron,B.P. 1932

Reduced iron, B.P. 1932, an old form of medicinal metallic iron powder, was given by mouth to albino rats. Measurable toxic effects were not produced until the dose reached 10 g./kg. body weight, which is 10 times the LD₅₀ of iron similarly given as ferrous sulfate. Death occurred at three days and after from doses of 60 to 100 g./kg. and was due to hemoconcentration and vascular congestion of the liver and kidneys resulting from absorption of iron through an inflamed gastrointestinal mucosa. Larger doses produced death in one to three days from bowel obstruction due to impaction of iron in the stomach and intestines. The results suggest that reduced iron is the least toxic of all iron medicinal preparations and that re-investigation of its therapeutic value is warranted.     

Bioavailability Studies of Stabilized Iron (II) Sulfate by Means of the Prophylactic-preventive Method

The bioavailability of stabilized ferrous sulfate was studied by means of the prophylactic-preventive test in rats. For comparative purposes, ferrous sulfate was used as reference standard. The test was performed in male weaned rats during 3 weeks, which were randomized into three groups of ten animals each. A control group received a basal diet of low iron content while the other groups received the same diet added with iron at a dose of 15 mg/kg as FeSO₄ 7H₂O and stabilized ferrous sulfate, respectively. Individual hemoglobin concentrations and weights were determined at the beginning and at the end of the study, and food intake was daily registered. Iron bioavailability (BioFe) of each source was calculated as the ratio between the amount of iron incorporated into hemoglobin during the treatment and the total iron intake per animal. A relative biological value was obtained as the ratio between the BioFe of stabilized ferrous sulfate and the reference standard given a value of 96%. Stabilized ferrous sulfate showed a high bioavailability, and when it is used to fortify dairy products as cheese and fluid milk in a dose of 15–20 mg of iron per kilogram, it behaved inertly in relation to the sensorial properties of the fortified food. These results suggest that this iron compound is a promising source to be use in food fortification.     

Medical Research Council announces $3 million supplement to 1978-79 budget

A retrospective review was done of the charts of 50 persons admitted to hospital for investigation of primary anemia. The duration of hospital stay was considered excessive for 80% of the patients and investigation was considered excessive for 34%. Nevertheless, underdiagnosis or misdiagnosis by the time of discharge was evident in 48% and was the result of inadequate investigation or faulty analysis of the results or both. Even when the type of anemia was established, investigations to determine the cause of specific deficiencies were frequently inadequate. Understandably treatment was inadequate for undiagnosed or misdiagnosed conditions but it was also inadequate for many correctly diagnosed conditions. Parenteral administration of iron was prescribed more often than oral administration, and 30% of patients with iron deficiency anemia failed to receive iron by either route. Most patients with vitamin B12 deficiency anemia received treatment late. Blood transfusion was given to 40% of patients but could be justified in only 16%.     

Hemoglobin deficit: an inherited hypochromic anemia in the mouse

The character and pathogenesis of hemoglobin deficit (gene symbol, hbd), an autosomal recessive trait in the mouse, were studied. The main hematological features of hemoglobin deficit are anemia, red cell hypochromia and microcytosis, and reticulocytosis. The absence of raised fecal urobilinogen excretion and frank hyperbilirubinemia and bilirubinuria suggests that excess hemolysis is not the primary cause of the anemia. The raised plasma iron concentration and the failure of the anemia to respond to parenteral iron treatment indicate that the anemia is not due to iron deficiency. The absence of siderocytes and sideroblasts suggests that anemia is probably not due to ferrochelatase deficiency. Thalassemia is excluded by the finding of balanced reticulocyte globin chain synthesis. The markedly elevated levels of free red cell protoporphyrin taken together with the other findings already noted suggest that the anemia of hemoglobin deficit is due to a defect in the erythroid cell iron procurement mechanisms leading in turn to diminished heme and hemoglobin synthesis.     

Bioavailability study of dried microencapsulated ferrous sulfate — SFE 171 — by means of the prophylactic-preventive method

Microencapsulated ferrous sulfate with soy lecithin (SFE-171) has been used as an iron source for the fortification of milk and dairy products. With the purpose to extend the use of this agent to other kind of foods or even to pharmaceutical preparations for oral administration, the SFE-171 was turned into a fluid powder (SFE-171-P) by means of vacuum drying. The iron bioavailability (BioFe) of SFE-171-P was evaluated in this work by means of the prophylactic-preventive method in rats, using ferrous sulfate as reference standard. Both iron sources were separately added to a basal diet of low iron content in a concentration of 10 mg iron/kg diet. Two groups of 10 weaned rats 25 days old received the fortified diets during 28 days, while a third group of the same size received the basal diet without iron additions. The weights and haemoglobin concentrations (HbC) of every animal were determined before and after the treatment, thus allowing the calculation of the mass of iron incorporated into haemoglobin (HbFe) during this period. The BioFe of the iron sources were obtained as the percentage ratio between the HbFe and the mass of iron consumed by each animal. The results were also given as Relative Biological Value (RBV), which relates the BioFe of the studied source with that of the reference standard. The liver iron concentration (LIC) of each animal was determined at the end of the experiment in order to evaluate the influence of the studied iron sources on the liver iron stores. SFE-171-P presented BioFe, RBV and LIC values of (47 ± 7) %, 109% and (46.6 ± 3.4) mg/kg respectively, while the corresponding values for the reference standard were of (43 ± 7)%, 100% and (45.0 ± 4.7) mg/kg. These results show that the drying process used to produce the SFE-171-P does not affect its bioavailability, which is also adequate for the potential use of this product in food fortification or with pharmaceutical purposes.     

Randomized Placebo-Controlled Trial of Helicobacter pylori Eradication for Iron-Deficiency Anemia in Preadolescent Children and Adolescents

Background. A few cases relating H. pylori infection to iron-deficiency anemia have been described recently. We investigated the role of H. pylori infection in iron-deficiency anemia in preadolescent children and adolescents.
Patients and Methods. We conducted a double-blind, placebo-controlled therapeutic trial in 43 subjects (mean age, 15.4 years) with iron-deficiency anemia. Endoscopy was performed, and biopsy specimens were examined by urease test and histological analysis. Twenty-two of 25 H. pylori –positive patients were assigned randomly to three groups. Group A patients were given oral ferrous sulfate and a 2-week course of bismuth subcitrate, amoxicillin, and metronidazole. Group B patients were given placebo for iron and a 2-week course of triple therapy. Group C patients were given oral ferrous sulfate and a 2-week course of placebo. Iron status was reassessed 4 weeks and 8 weeks after the 2-week regimen ended.
Results. Of the 43 subjects with iron-deficiency anemia, 25 (58.1%) had H. pylori in the antrum. Group A and B subjects, who received eradication therapy, showed a significant increase in hemoglobin level as compared with group C subjects at 8 weeks after therapy ( p = .0086).
Conclusions. Treatment of H. pylori infection was associated with more rapid response to oral iron therapy as compared with the use of iron therapy alone. Such treatment also led to enhanced iron absorption even in those subjects who did not receive oral iron therapy.     

Iron uncouples oxidative phosphorylation in brain mitochondria isolated from vitamin E-deficient rats

Few, if any, studies have examined the effect of vitamin E deficiency on brain mitochondrial oxidative phosphorylation. The latter was studied using brain mitochondria isolated from control and vitamin E-deficient rats (13 months of deficiency) after exposure to iron, an inducer of oxidative stress. Mitochondria were treated with iron (2 to 50 microM) added as ferrous ammonium sulfate. Rates of state 3 and state 4 respiration, respiratory control ratios, and ADP/O ratios were not affected by vitamin E deficiency alone. However, iron uncoupled oxidative phosphorylation in vitamin E-deficient mitochondria, but not in controls. In vitamin E-deficient mitochondria, iron decreased ADP/O ratios and markedly stimulated state 4 respiration; iron had only a modest effect on these parameters in control mitochondria. Thus, vitamin E may have an important role in sustaining oxidative phosphorylation. Low concentrations of iron (2 to 5 microM) oxidized mitochondrial tocopherol that exists in two pools. The release of iron in brain may impair oxidative phosphorylation, which would be exacerbated by vitamin E deficiency. The results are important for understanding the pathogenesis of human brain disorders known to be associated with abnormalities in mitochondrial function as well as iron homeostasis (e.g., Parkinson's disease).