Oral Ferrous Iron Research Articles

Comparative study on efficacy, tolerability, and cost of different iron supplements among antenatal women with iron-deficiency anemia

Background: Anemia is one of the most common medical complications encountered during pregnancy. India is among the countries with maximum prevalence of anemia in the world. The commonly used treatment for iron-deficiency anemia is oral iron preparations such as ferrous sulfate, ferrous gluconate, ferrous ascorbate, ferrous fumarate, and parenteral iron sucrose. Aims and Objectives: The aims of this study were to assess the mean change in the hemoglobin levels from baseline up to 60th day of treatment with different iron supplements and to assess its cost effectiveness ratio. Materials and Methods: This was a prospective interventional clinical end point study conducted at Sri Venkateshwaraa Medical College Hospital and Research Center, Puducherry, India, from December 2019 to December 2020, among 84 antenatal women (>14 weeks) with iron-deficiency anemia. After getting ethics committee approval, the participants who fulfilled the inclusion and exclusion criteria were randomized to respective treatment groups. Group 1 (n = 21) received ferrous sulfate 200 mg, Group 2 (n = 21) received ferrous ascorbate 200 mg, Group 3 (n = 21) received ferrous fumarate 200 mg twice daily for a period of 60 days, and Group 4 (n = 21) received Iron sucrose 200 mg, based on iron requirement in divided doses and administered once in 2 weeks for a period of 60 days. Hemoglobin (Hb), RBC count, mean corpuscular volume, mea n corpuscular Hb (MCH), MCHC, WBC, platelet count, and cost of the treatment were assessed before and at the end of 60 days. Data were analyzed using GraphPad Prism software version 7.0 using Student “t”-test and one-way ANOVA. Results: We observed a significant (P < 0.001) rise in the mean Hb level from 10.4 ± 0.4, 10.4 ± 0.5, 10.4 ± 0.5 and 8.5 ± 0.3 to 11.2 ± 0.6 (P = 0.0001), 11.1 ± 0.6 (P = 0.0001), 11.3 ± 0.8(P = 0.0001), and 10.9 ± 0.6 (P = 0.0001) in Group 1, 2, 3, and 4, respectively. The average cost effectiveness ratio, with respect to Groups 1, 2, 3, and 4 was Rs. 675, Rs. 1782.9, Rs. 1110.7, and Rs. 786.7 per increase in Hb%, respectively. Conclusion: The outcome of this study proved the effective role of various oral ferrous iron preparations and all of them were found to be equally efficacious in improving the Hb concentration. However, the injectable iron sucrose showed a significant improvement in mean hemoglobin percentage compared to the various oral preparations. However, on analyzing the cost-effectiveness ratio, it was found out that the cost incurred per increase in Hb% was less in ferrous sulfate group, followed by iron sucrose, ferrous fumarate, and ferrous ascorbate. The results of this study can be helpful in pharmacoeconomical decision making while selecting a cost effective iron supplement for treating iron-deficiency anemia.

A Novel Ferritin-Core Analog Is a Safe and Effective Alternative to Oral Ferrous Iron for Treating Iron Deficiency during Pregnancy in Mice

BackgroundMany women enter pregnancy with iron stores that are insufficient to maintain maternal iron balance and support fetal development and consequently, often require iron supplements. However, the side effects associated with many currently available iron supplements can limit compliance. ObjectiveThis study aimed to test the safety and efficacy of a novel nanoparticulate iron supplement, a dietary ferritin analog termed iron hydroxide adipate tartrate (IHAT), in pregnant mice. MethodsFemale C57BL/6 mice were maintained on either an iron-deficient or a control diet for 2 wk prior to timed mating to develop iron-deficient or iron-sufficient pregnancy models, respectively. Mice from each model were then gavaged daily with 10 mg iron/kg body weight as either IHAT or ferrous sulfate, or with water only, beginning on embryonic day (E) 4.5. Mice were killed on E18.5 and maternal iron and hematological parameters were measured. The expression of genes encoding iron transporters and oxidative stress markers in the duodenum and placenta were determined, along with hepatic expression of the gene encoding the iron regulatory hormone hepcidin and fetal iron. ResultsOral IHAT and ferrous sulfate were equally effective at increasing maternal hemoglobin (20.2% and 16.9%, respectively) and hepatic iron (30.2% and 29.3%, respectively), as well as total fetal iron (99.7% and 83.8%, respectively), in iron-deficient pregnant mice compared with those gavaged with water only, with no change in oxidative stress markers seen with either treatment. However, there was a significant increase in the placental expression of the oxidative stress marker heme oxygenase 1 in iron-replete pregnant mice treated with ferrous sulfate when compared with iron-replete pregnant mice gavaged with IHAT (96.9%, P<0.05). ConclusionsIHAT has proved a safe and effective alternative to oral ferrous sulfate in mice, and it has potential for treating iron deficiency in human pregnancy.

Current views on the pharmacological correction of iron deficiency conditions in gynecological practice

The review considers features of iron and folic acid (FA) pharmacokinetics, which affect the effective micronutrient support: molecular mechanisms of absorption and distribution, homeostatic processes of maintaining plasma vitamin and mineral levels by the feedback mechanism, including by regulating the deposition. An important characteristic of ferrokinetics is the presence of unique iron exporter ferroportin which is controlled by a family of iron regulatory proteins. Systemic ferrotherapy and oral rout of iron delivery are distinguished. In general, parenteral iron preparation complexes consist of Fe(III) oxide/hydroxide core stabilized by a carbohydrate polymer shell. Once entering the bloodstream, iron complexes are absorbed by resident macrophages of the reticuloendothelial system of the liver, spleen and bone marrow. Systemic Fe(III) preparations are prodrugs, the active part of which, i.e. iron is released in the lysosomal matrix of phagocytes. Oral iron preparations are divided into those containing bivalent (ferrous) and trivalent (ferric) iron. The article discusses factors determining the differences in the absorption of oral ferrous and ferric iron preparation, the spectrum of side effects, as well as key pharmaceutical approaches to increase the tolerance and adherence of ferrotherapy. These include using preparations containing Fe(II) organic compounds that have a lower dissociation rate than inorganic iron salts as well as slowing down the release of the active Fe(II) pharmaceutical substance from the drug. The review pays special attention to folates as iron synergists and examines the features of FA pharmacokinetics, the molecular basis of synergism, and substantiates the use of combined iron and FA preparations.

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.

Effects of vitamin D prophylaxis on oral iron treatments of iron deficiency anemia.

Iron deficiency anemia causes a decrease in immune response to infections, physical working capacity and response to metabolic stress. It also causes behavioral, perceptual and cognitive disorders. Therefore, as soon as iron deficiency anemia is diagnosed, it should be treated immediately. In this study, it was investigated retrospectively whether there was a difference in treatment efficacy between the administration of oral ferrous or ferric iron and vitamin D at the same time and at different time. A total of sixty patients under 1 year who attended the pediatrics outpatient clinic for pale and diagnosed with iron deficiency anemia. Patients were randomly divided into 4 groups. Anemia was defined as hemoglobin below <2 SD according to age and gender. Iron deficiency was definied with serum iron, iron-binding capacity, ferritin and transferin saturation below the range for age and gender appropriates. All patients were seen at the outpatient clinic for 1st, 3rd month of the treatment. There were a statistically significant differences between the groups in terms of increase in Hb values according to time (1st month, 3rd month, 1st and 3rd month). There was no statistically significant difference between the groups in terms of the recovery of anemia after treatment. It was concluded that iron treatment in babies with iron deficiency anemia is not affected by the administration of vitamin D prophylaxis at the same time or at different times, and therefore both treatments can be administered at the same time to increase drug compliance.

Oral iron supplementation with sodium ferrous citrate reduces the serum intact and c-terminal fibroblast growth factor 23 levels of maintenance haemodialysis patients.

ABSTRACTAimIron deficiency stimulates fibroblast growth factor 23 (FGF23) transcription. This study aimed to determine whether oral ferrous iron (Fe2+) reduces the serum FGF23 levels of iron‐deficient maintenance haemodialysis (MHD) patients in the same way as oral ferric iron (Fe3+)MethodsThirty‐one MHD patients with iron deficiency were enrolled in this prospective study. Patients who had taken iron supplements during the 8 weeks before the study were excluded. The patients’ iron stores and their serum FGF23, phosphate, intact parathyroid hormone (iPTH), albumin, C‐reactive protein (CRP), and albumin‐adjusted calcium (Ca) levels were examined at the baseline and after 3 months’ treatment with sodium ferrous citrate (Fe2+).ResultsThe patients’ transferrin saturation values and serum iron and ferritin levels were significantly increased after 3 months’ treatment (P < 0.01), as were their serum albumin levels (P < 0.05). Conversely, their serum intact FGF23 (iFGF23) [1820 (342–4370) vs 1240 (214–2940) pg/mL, P < 0.05], C‐terminal FGF23 (cFGF23) [309 (120–1211) vs 259 (99–600) pg/mL, P < 0.05)], and CRP levels (P < 0.01) were significantly reduced after 3 months’ treatment. No changes were detected in the patients’ serum iFGF23:cFGF23 ratios or their serum phosphate, Ca, or iPTH levels. The changes in the patients’ serum iFGF23 and cFGF23 levels induced by sodium ferrous citrate supplementation were shown to be attributable to changes in their serum ferritin levels (P < 0.05).ConclusionShort‐term oral iron supplementation with sodium ferrous citrate replenished the iron stores and reduced the serum iFGF23 and cFGF23 levels of MHD patients with iron deficiency without affecting their serum phosphate, Ca, or iPTH levels.

Iron Deficiency Anemia in Pregnancy and Treatment Options: A Patient-Preference Study [1L

INTRODUCTION: As many as 17% of Canadian women suffer from iron deficiency anemia (IDA) in pregnancy. Treatment options include oral ferrous salts, haem iron, intravenous (IV) iron and blood transfusions. Trade-offs pregnant women are willing to make to alleviate symptoms of IDA have not been determined. This study elicits preferences of pregnant women for health-states arising from IDA and the use of various treatment options. METHODS: A cross-sectional study was conducted on pregnant women with and without IDA. Participants were presented with five vignettes representing maternal health-states arising from IDA in pregnancy. They were asked to rank these states and assign them values on a visual analogue scale, by the standard gamble, and by time trade-off methods. Utility values (preferences) of women with and without IDA, obtained from these methods were presented on a scale of 0-100 where 0 represented death and 100 represented perfect health. RESULTS: 60 pregnant women (30 with IDA and 30 without) completed the interviews. With all three methods, utility values were lowest for blood transfusion and highest for oral iron. Regardless of the evaluation method, there was no difference in utility values for treatment with oral ferrous salts vs. haem iron or between women with or without IDA. CONCLUSION: Women acknowledge that symptoms of IDA in pregnancy reduce quality of life. Despite side effects and frequency of administration, oral iron is preferred over IV iron and blood transfusion. Confirmation of these findings in larger studies would directly inform clinical practice and research.

Ferric maltol in iron deficiency anaemia in patients with inflammatory bowel disease: a guide to its use

Ferric maltol (Feraccru®) is an option for the oral treatment of iron deficiency anaemia (IDA) in patients with inflammatory bowel disease (IBD). In the ferric maltol complex, iron is stabilized in the ferric form (thereby minimizing the potential for mucosal toxicity), while also making the iron highly available for absorption (allowing relatively low dosages of elemental iron to be administered). In patients with IDA associated with IBD who were unable take oral ferrous iron, oral ferric maltol 30 mg twice daily rapidly improved haemoglobin levels and other anaemia-related parameters. It is generally well tolerated, with treatment-related adverse events being mild to moderate in severity and gastrointestinal in nature.

Iron Deficiency and Anaemia in Pregnant Women in Malaysia ? Still a Significant and Challenging Health Problem

Background: Iron deficiency (ID) is the most frequent cause of anaemia (IDA) in women of reproductive age and pregnant women. Recommended cut-off value for anaemia in women of reproductive age is haemoglobin (Hb) <12.0 g/dL and in pregnancy Hb <11.0 g/dL. Serum ferritin <15-20 μg/L is consistent with ID; Hb below cut-off values and ferritin <12-15 μg/L is consistent with IDA. Methods: Literature survey on publications and guidelines on the frequency of ID and IDA in Malaysia compared with Western countries. Results: Prevalence of anaemia in women of reproductive age is ~30% and in pregnant women ~40%. With advancing pregnancy the frequency of anaemia increases, due to deficiency of iron and hematinic vitamins (folate, vitamin B12). Iron demands in pregnancy cannot be fulfilled by dietary iron intake but require oral iron supplementation. If the mother has IDA, the newborn has a high risk of ID and IDA. ID and IDA have multiple negative effects in both infants and adults. Oral iron prophylaxis should start at 10-12 weeks gestation. Among pregnant women in Malaysia 80-90%, have low iron status and 38-42% develop anaemia. Consequently, the prophylactic oral iron dose should be 100 mg ferrous iron/day. IDA is treated with oral ferrous iron 180-200 mg/day and Hb should be checked after 2-3 weeks. If there is no increase in Hb, due to poor compliance and/or impaired iron absorption, or the anaemia is severe (Hb <8.0 g/dL) treatment with intravenous iron is indicated. Conclusions: In Malaysia, anaemia in pregnant women still constitute a major and challenging health problem. We are aware of the causes for anaemia and we know the solutions, so efforts should focus on better implementation of early oral iron and vitamin prophylaxis, early diagnosis of anaemia, and on increasing the low compliance of the women to the prophylaxis programs.

Evaluation of ferric and ferrous iron therapies in women with iron deficiency anaemia.

Introduction. Different ferric and ferrous iron preparations can be used as oral iron supplements. Our aim was to compare the effects of oral ferric and ferrous iron therapies in women with iron deficiency anaemia. Methods. The present study included 104 women diagnosed with iron deficiency anaemia after evaluation. In the evaluations performed to detect the aetiology underlying the iron deficiency anaemia, it was found and treated. After the detection of the iron deficiency anaemia aetiology and treatment of the underlying aetiology, the ferric group consisted of 30 patients treated with oral ferric protein succinylate tablets (2 × 40 mg elemental iron/day), and the second group consisted of 34 patients treated with oral ferrous glycine sulphate tablets (2 × 40 mg elemental iron/day) for three months. In all patients, the following laboratory evaluations were performed before beginning treatment and after treatment. Results. The mean haemoglobin and haematocrit increases were 0.95 g/dL and 2.62% in the ferric group, while they were 2.25 g/dL and 5.91% in the ferrous group, respectively. A significant difference was found between the groups regarding the increase in haemoglobin and haematocrit values (P < 0.05). Conclusion. Data are submitted on the good tolerability, higher efficacy, and lower cost of the ferrous preparation used in our study.

The effect of intravenous and oral iron administration on perioperative anaemia and transfusion requirements in patients undergoing elective cardiac surgery: a randomized clinical trial

Anaemia is a frequent complication after cardiopulmonary bypass surgery. Iron therapy has been variably employed by medical centres over the years. In our study we test the clinical effectiveness of intravenous and oral iron supplementation in correcting anaemia, and its impact on blood transfusion requirements, in patients undergoing cardiopulmonary bypass surgery. A double-blind, randomized, placebo-controlled clinical trial with three parallel groups of patients. Group I (n = 54): intravenous iron(III)-hydroxide sucrose complex, three doses of 100 mg/24 h during pre- and postoperative hospitalization and 1 pill/24 h of oral placebo in the same period and during 1 month after discharge. Group II (n = 53): oral ferrous fumarate iron 1 pill/24 h pre- and postoperatively and during 1 month after discharge, and intravenous placebo while hospitalized. Group III (n = 52): oral and intravenous placebo pre- and postoperatively, following the same protocol. Data were collected preoperatively, at theatre, at intensive care unit admission, before hospital discharge and 1 month later. (1) Baseline clinical and demographic characteristics and surgical procedures were similar in the three groups; (2) no inter-group differences were found in haemoglobin and haematocrit during the postoperative period; (3) the intravenous iron group showed higher serum ferritin levels at hospital discharge (1321 ± 495 ng/ml; P < 0.001) and 1 month later (610 ± 387; P < 0.001) compared with the other groups and (4) we did not observe statistical differences in blood transfusion requirements between the three groups. The use of intravenous or oral iron supplementation proved ineffective in correcting anaemia after cardiopulmonary bypass and did not reduce blood transfusion requirements. [Current Controlled Trials number: NCT01078818 (oral and intravenous iron in patients postoperative cardiovascular surgery under EC)].

Postpartum anemia II: prevention and treatment

This review focuses on the prevention and treatment of anemia in women who have just given childbirth (postpartum anemia). The problem of anemia both prepartum and postpartum is far more prevalent in developing countries than in the Western societies. The conditions for mother and child in the postpartum, nursing, and lactation period should be as favorable as possible. Many young mothers have a troublesome life due to iron deficiency and iron deficiency anemia (IDA) causing a plethora of symptoms including fatigue, physical disability, cognitive problems, and psychiatric disorders. Routine screening for postpartum anemia should be considered as part of the national maternal health programs. Major causes of postpartum anemia are prepartum iron deficiency and IDA in combination with excessive blood losses at delivery. Postpartum anemia should be defined as a hemoglobin level of <110g/l at 1week postpartum and <120g/l at 8weeks postpartum. Bleeding exceeding normal blood losses of approximately 300ml may lead to rapid depletion of body iron reserves and may, unless treated, elicit long-standing iron deficiency and IDA in the postpartum period. The prophylaxis of postpartum anemia should begin already in early pregnancy in order to ensure a good iron status prior to delivery. The most reliable way to obtain this goal is to give prophylactic oral ferrous iron supplements 30-50mg daily from early pregnancy and take obstetric precautions in pregnancies at risk for complications. In the treatment of slight-to-moderate postpartum IDA, the first choice should be oral ferrous iron 100 to 200mg daily; it is essential to analyze hemoglobin after approximately 2weeks in order to check whether treatment works. In severe IDA, intravenous ferric iron in doses ranging from 800 to 1,500mg should be considered as first choice. In a few women with severe anemia and blunted erythropoiesis due to infection and/or inflammation, additional recombinant human erythropoietin may be considered. Blood transfusion should be restricted to women who develop circulatory instability due to postpartum hemorrhage. National health authorities should establish guidelines to combat iron deficiency in pregnancy and postpartum in order to facilitate a prosperous future for both mothers and children in a continuing globalized world.

Prepartum anaemia: prevention and treatment

This review focuses on the occurrence, prevention and treatment of anaemia during pregnancy in Western societies. Iron deficiency anaemia (IDA) is the most prevalent deficiency disorder and the most frequent form of anaemia in pregnant women. Minor causes of anaemia are folate and vitamin B12 deficiency, haemoglobinopathy and haemolytic anaemia. Anaemia is defined as haemoglobin of <110 g/L in the first and third trimester and <105 g/L in the second trimester. The diagnosis relies on haemoglobin, a full blood count and plasma ferritin, which can be supported by plasma transferrin saturation and serum soluble transferrin receptor. Among fertile, non-pregnant women, approximately 40% have ferritin of <or=30 microg/L, i.e. small or absent iron reserves and therefore an unfavourable iron status with respect to upcoming pregnancy. The prevalence of prepartum anaemia in the third trimester ranges 14-52% in women taking placebo and 0-25% in women taking iron supplements, dependent on the doses of iron. In studies incorporating serum ferritin, the frequency of IDA in placebo-treated women ranges 12-17% and in iron-supplemented women 0-3%. Requirements for absorbed iron increase during pregnancy from 0.8 mg/day in the first trimester to 7.5 mg/day in the third trimester, on the average approximately 4.4 mg/day, and dietary measures are inadequate to reduce the frequency of prepartum IDA. However, IDA is efficiently prevented by oral iron supplements in doses of 30-40 mg ferrous iron taken between meals from early pregnancy to delivery. Treatment of IDA should aim at replenishing body iron deficits by oral and/or intravenous administration of iron. In women with slight to moderate IDA, i.e. haemoglobin of 90-105 g/L, treatment with oral ferrous iron of approximately 100 mg/day between meals is the therapeutic option in the first and second trimester; haemoglobin should be checked after 2 weeks and provided an increase of >or=10 g/L, oral iron therapy has proved effective and should continue. Treatment with intravenous iron is superior to oral iron with respect to the haematological response. Intravenous iron is considered safe in the second and third trimester, while there is little experience in the first trimester. Intravenous iron of 600-1,200 mg should be considered: (1) as second option if oral iron fails to increase haemoglobin within 2 weeks; (2) as first option at profound IDA, i.e. haemoglobin of <90 g/L in any trimester beyond 14 weeks gestation; and (3) as first option for IDA in third trimester. Profound IDA has serious consequences for both woman and foetus and requires prompt intervention with intravenous iron. This is especially important for the safety of women who for various reasons oppose blood transfusions.

Low-Dose Oral Ferrous Fumarate Aggravated Intestinal Inflammation in Rats With Dss-Induced Colitis

Oral ferrous iron therapy may reinforce intestinal inflammation. One possible mechanism is by catalyzing the production of reactive oxygen species. We studied the effects of low-dose oral ferrous fumarate on intestinal inflammation and plasma redox status in dextran sulfate sodium (DSS)-induced colitis in rats. Forty male Wistar rats were divided into 5 groups: no intervention, sham gavage (distilled water), ferrous fumarate, DSS, and ferrous fumarate + DSS. Ferrous fumarate was dissolved in distilled water (0.60 mg Fe/kg per day) and administered by gavage on days 1 to 14. All rats were fed a standard diet. Colitis was induced by 5% DSS in drinking water on days 8 to 14. Rats were killed on day 16. Histologic colitis scores, fecal granulocyte marker protein, plasma malondialdehyde, plasma antioxidant vitamins, and plasma aminothiols were measured. DSS significantly increased histologic colitis scores (P < 0.001) and fecal granulocyte marker protein (P < 0.01). Ferrous fumarate further increased histologic colitis scores (P < 0.01) in DSS-induced colitis. DSS + ferrous fumarate decreased plasma vitamin A compared with controls (P < 0.01). Otherwise, no changes were seen in plasma malondialdehyde, plasma antioxidant vitamins, or plasma aminothiols. Low-dose oral ferrous iron enhanced intestinal inflammation in DSS-induced colitis in rats.

Correction of Uremic Iron Deficiency Anemia in Hemodialyzed Patients: A Prospective Study

This prospective study was designed to evaluate the eventual correction of anemia and iron status in 39 iron-deficient uremics starting hemodialysis. Nine patients (control group) had no iron supplementation, 10 had oral ferrous iron, and 20 were treated with intravenous iron gluconate. Follow-up periods were 12 months for the control group and 26 months for patients treated with oral or intravenous iron. No patient was treated with erythropoietin. At zero time, all patients were anemic (Hb <78 g/l) and showed signs of severe iron deficiency, diagnosed on the basis of depleted bone marrow iron stores, reduced hemoglobin iron, and transferrin saturation <21%. The hemoglobin levels, observed in patients of the control and the oral iron groups at the end of the follow-up periods, were not significantly different from those detected at zero time. In contradistinction, patients treated with intravenous iron showed after 26 months of follow-up a significant increase of blood hemoglobin values, reaching a mean value of 126 g/l. So far, this evidence supports both the concept that iron absorption is compromised in chronic uremics and that the parenteral way is the more effective route for iron replacement in this specific group of patients.

Iron Deficiency in Adolescents and Young Adults.

In brief After childhood, iron deficiency is mainly a problem in females, but it also occurs in males aged 11 to 14 years. Inadequate dietary intake of iron is the major cause of iron deficiency, but factors such as gastrointestinal (GI) blood loss may contribute to this problem. Mild anemia may impair sports performance, and some research suggests that iron deficiency without anemia also has an adverse effect. The diagnosis of iron deficiency should be based on the patient's serum ferritin and hemoglobin concentrations. Treatment requires therapeutic doses of oral ferrous iron for several months.

Iron deficiency anaemia with hypoproteinaemia.

Forty two children were admitted to this hospital between 1975 and 1980 with severe iron deficiency anaemia and 8 of them also had oedema caused by a low concentration of serum proteins. These 8 patients, aged 8-24 months, and 13 age matched controls were investigated. The patients had excessive faecal loss of 59FeCl or 51Cr-albumin, or both; their jejunal biopsy specimens showed little decrease in the ratio of villous height to crypt depth; and they had fewer intraepithelial lymphocytes and cells containing IgA than controls. They were all treated with an oral ferrous iron preparation and the oedema, hypoproteinaemia, and low haemoglobin concentrations rapidly resolved. These results show that immunologically mediated hypersensitivity is not implicated in iron deficiency anaemia associated with hypoproteinaemia.

Nutritional iron deficiency anemia in lactoovo-vegetarians

Although it was postulated that pure nutritional iron deficiency anemia does not exist in advanced countries two children and one adult with iron deficiency anemia due to iron malnutrition were observed within a year. All three subjects were living on a lactoovo-vegetarian diet for several years. Food iron malabsorption was excluded by the demonstrated increased59Fe-absorption. Normal whole body59Fe-elimination rates were measured over 173 to 259 days and excluded latent minor gastrointestinal or urogenital blood losses as a cause of iron deficiency anemia. The discrimination between iron malnutrition, maldigestion or malabsorption, gastrointestinal or urogenital blood losses and a higher iron requirement in pregnancy or infancy is based on the quantitative estimation of59Fe-absorption from59Fe-labeled ferrous iron and meat iron as well as the precise measurement of the whole body59Fe-elimination rate. Daily iron deficits of 0.5 and 1.2 mg Fe were calculated for males and menstruating females respectively if the subjects are wanted to live with normal iron stores on a lactoovo-vegetarian diet. The deficit is reduced to 0.66 mg Fe/d if depleted iron stores are acceptable in females with average menstrual blood losses. The dietary iron deficits can be easily compensated by giving 50 mg Fe2+/day for 51, 126 and 28 days/year respectively, in the form of an oral ferrous iron preparation of well known bioavailability.

Whole body (59)Fe-elimination rates and corresponding blood losses in patients with factitious anemia induced by self-blood letting.

Factitious anemia induced by self-bloodletting is a rare cause of chronic haemorrhagic iron deficiency anemia. Within a year two cases from Southern Germany were identified and quantitated for blood losses by whole body counting of retained iron. Whereas the 2 patients did not lose much blood (6–10 ml blood/day equivalent to 0.12–0.34%59Fe-whole body elimination/day) during their observation within the hospital their blood losses increased to 41–187 ml/day (=whole body59Fe-elimination rates of 0.8 to 6.1%/day) upon release from the hospital. Although they lost about 5 liter blood in 50 days faecal occult blood tests were always negative and the daily faecal and urinary59Fe-excretion was with 0.018–0.031%/day within the normal range. Haemoglobin and erythrocyte levels were stable during the periods of clinical observation when the whole body59Fe-elimination rates were only just above the normal range (0.12–0.21%/d). These values dropped however to very low values during or following periods of extremely elevated whole body59Fe-elimination rates (1–6%/d=46–187 ml blood loss/d) immediately after release of the patients from the hospital. One patient received more than 400 blood and erythrocyte infusions (∼84 g iron) and absorbed about 8 g food iron within 10 years. Nevertheless she was always severely anemic (5 g% haemoglobin) and had no storage iron in the tissues. She must have lost about 92 g iron in 10 years (= 529 liter blood) or 25 mg Fe/d (= 145 ml blood/d) by self bloodletting avoiding the otherwise extreme generalized transfusion haemosiderosis. Blood losses of up to 145 ml/d (= 50 mg Fe/d) can be compensated by oral ferrous iron therapy with 4×50=200 mg Fe2+/d. The patients did however refuse to take oral or parenteral iron and insisted in one case on regular blood transfusions twice per week.