lactoferrin and ferrous-sulfate

Ferrous sulfate is a commonly used iron supplement for the correction of iron-deficiency anemia but with frequent gastrointestinal side effects. Milk-derived iron-binding glycoprotein lactoferrin possesses well gastrointestinal tolerance and fewer side effects caused by the intake of high-dose iron. However, the underlying mechanism of the iron-enhancing effect of lactoferrin remains unclear. In addition, the comparative efficacies between lactoferrin and ferrous sulfate are also remained to be determined. We conducted a systematic review and meta-analysis on published intervention studies to investigate how lactoferrin modulate iron metabolism and evaluate the comparative effects between lactoferrin and ferrous sulfate supplementation on iron absorption, iron storage, erythropoiesis and inflammation. Lactoferrin supplementation had better effects on serum iron (WMD: 41.44 ug/dL; p < 0.00001), ferritin (WMD: 13.60 ng/mL; p = 0.003) and hemoglobin concentration (11.80 g/dL; p < 0.00001), but a reducing effect on fractional iron absorption (WMD: −2.08%; p = 0.02) and IL-6 levels (WMD: −45.59 pg/mL; p < 0.00001) compared with ferrous sulfate. In conclusion, this study supports lactoferrin as a superior supplement to ferrous sulfate regarding the improvement in serum iron parameters and hemoglobin levels. Considering the weak influence of lactoferrin on iron absorption, the anti-inflammation effect of lactoferrin may be the potential mechanism to explain its efficacy on iron status and erythropoiesis.

Topics: Anemia, Iron-Deficiency; Clinical Trials as Topic; Dietary Supplements; Ferrous Compounds; Humans; Lactoferrin

This systematic review and meta-analysis aimed to evaluate the efficacy of daily oral bovine lactoferrin versus daily oral ferrous iron preparations for treatment of iron deficiency anemia (IDA) during pregnancy. Searches were conducted on PubMed, ScienceDirect, ClinicalTrials.gov and CENTRAL databases from inception to February 2017 and the bibliographies of retrieved articles were screened. The PRISMA Statement was followed. Published English language randomized trials comparing lactoferrin with oral ferrous iron preparations in pregnant women with iron deficiency anemia were included. Quasi-randomized, non- randomized or studies including other known cause of anemia, gestational or pre-existent maternal diseases were excluded. Accordingly, 4 eligible trials (600 women) were analyzed. Primary outcome was change in hemoglobin level at 4 weeks of treatment. Secondary outcomes were; change in serum ferritin and iron, rates of gastrointestinal side effects, preterm birth, low birthweight, neonatal death and mean birthweight. Quality assessment was performed by the Cochrane risk of bias tool. Odds ratio and mean difference were used to integrate dichotomous and continuous outcomes respectively. Pooled estimates for change in hemoglobin levels at four weeks favored daily oral lactoferrin over daily oral ferrous sulphate (mean difference 0.77; 95% confidence interval [CI] 0.04-1.55; P=0.04, 4 trials, 600 women). However, after subgroup analysis (degree of anemia), no significant difference in hemoglobin levels were found between both groups in mild anemia (mean difference 0.80; 95% CI -0.21 to 1.82, 3 trials, 372 women), but a significant increase favoring lactoferrin was reported in moderate anemia (mean difference 0.68; 95% CI 0.53-0.83; P<0.00001, one trial, 228 women). Significantly less gastrointestinal side effects were reported with lactoferrin treatment. No significant differences existed with regard to other outcomes. In conclusion, for pregnant women with IDA, daily oral bovine lactoferrin is just as good as ferrous sulfate in improving hematological parameters with fewer gastrointestinal side effects. Thereby, lactoferrin should be the iron replacement agent of choice for treatment of IDA in pregnancy.

Topics: Anemia, Iron-Deficiency; Female; Ferrous Compounds; Humans; Lactoferrin; Pregnancy; Pregnancy Complications, Hematologic; Randomized Controlled Trials as Topic

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.

Topics: Anemia, Iron-Deficiency; Animals; Female; Ferrous Compounds; Humans; Iron Deficiencies; Lactoferrin; Pregnancy; Pregnancy Complications, Hematologic

Iron-deficiency anemia (IDA) is common in children with inflammatory bowel disease (IBD); however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. We compared the effect of lactoferrin versus oral ferrous sulfate for the treatment of IDA in children with IBD.. Ninety-two IBD children with IDA were included but only 80 children completed the study and they were randomized into two groups: ferrous sulfate group (n = 40) who received ferrous sulfate 6 mg/kg/day for 3 months and lactoferrin group (n = 40) who received lactoferrin 100 mg/day for 3 months. Complete blood count, serum iron, total iron-binding capacity (TIBC), transferrin saturation (TS), serum ferritin, interleukin-6 (IL-6), and hepcidin 25 were measured before and after the treatment.. Hemoglobin (Hb), mean corpuscular volume, serum iron, TS, and serum ferritin significantly increased, while TIBC decreased significantly after the administration of either ferrous sulfate or lactoferrin compared to their baseline data. In addition, lactoferrin significantly increased Hb, serum iron, TS, and serum ferritin compared to ferrous sulfate. Moreover, lactoferrin significantly decreased IL-6 and hepcidin levels.. Lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA.. The study was registered at www.pactr.org (PACTR202002763901803).. Iron-deficiency anemia (IDA) in children with inflammatory bowel disease (IBD) is treated with oral iron therapy; however, oral iron supplements are commonly associated with poor compliance due to gastrointestinal side effects. To the best of our knowledge, our study was the first in pediatrics that compared the effect of lactoferrin versus oral ferrous sulfate as an iron supplement for the treatment of IDA in children with IBD. We found that lactoferrin is a promising effective treatment with fewer side effects than oral elemental iron in children with IBD and IDA.

Topics: Anemia, Iron-Deficiency; Child; Chronic Disease; Female; Ferritins; Ferrous Compounds; Hemoglobins; Hepcidins; Humans; Inflammatory Bowel Diseases; Interleukin-6; Iron; Lactoferrin; Pregnancy; Pregnancy Complications, Hematologic

Whether lactoferrin (Lf) binds iron to facilitate its absorption or to sequester iron from potential enteropathogens remains uncertain. Bovine Lf is added to many infant formulas, but previous studies in infants reported that Lf had no effect on or inhibited iron absorption. The effects of the apo (iron-free) or the holo (iron-loaded) forms of Lf on iron absorption are unclear.. Our objective was to compare iron absorption from a maize-based porridge containing: 1) labeled ferrous sulfate (FeSO4) alone; 2) labeled FeSO4 given with bovine apo-Lf; and 3) intrinsically labeled bovine holo-Lf.. In a crossover study, we measured iron absorption in Kenyan infants (n = 25; mean ± SD age 4.2 ± 0.9 months; mean ± SD hemoglobin 109 ± 11 g/L) from maize-based test meals containing: 1) 1.5 mg of iron as 54Fe-labeled FeSO4; 2) 1.42 mg of iron as 58Fe-labeled FeSO4, given with 1.41 g apo-Lf (containing 0.08 mg iron); and 3) 1.41 g holo-Lf carrying 1.5 mg iron as 57Fe. The iron saturation levels of apo- and holo-Lf were 0.56% and 47.26%, respectively primary outcome was fractional iron absorption (FIA), assessed by erythrocyte incorporation of isotopic labels.. The FIA from the meal containing apo-Lf + FeSO4 (geometric mean, 9.8%; -SD and +SD, 5.4% and 17.5%) was higher than from the meals containing FeSO4 (geometric mean, 6.3%; -SD and +SD, 3.2% and 12.6%; P = 0.002) or holo-Lf (geometric mean, 5.0%; -SD and +SD, 2.8% and 8.9%; P <0.0001). There was no significant difference in FIA when comparing the meals containing holo-Lf versus FeSO4 alone (P = 0.24).. The amount of iron absorbed from holo-Lf was comparable to that of FeSO4, and the addition of apo-Lf to a test meal containing FeSO4 significantly increased (+56%) iron absorption. These findings suggest that Lf facilitates iron absorption in young infants. Because Lf binds iron with high affinity, it could be a safe way to provide iron to infants in low-income countries, where iron fortificants can adversely affect the gut microbiome and cause diarrhea. This study was registered at clinicaltrials.gov as NCT03617575.

Topics: Biological Transport; Cross-Over Studies; Female; Ferrous Compounds; Humans; Infant; Infant Formula; Iron; Iron Isotopes; Kenya; Lactoferrin; Male; Milk, Human

This study was conducted to evaluate the efficacy and safety of lactoferrin in comparison to ferrous sulphate for the treatment of iron deficiency anemia (IDA) during pregnancy.. This prospective, randomized, parallel-group, single-center study was conducted in the Department of Obstetrics and Gynecology at Menoufia University Hospital, Egypt and included a total of 200 pregnant women in the second trimester with IDA who were enrolled and randomly assigned either to receive 150 mg of dried ferrous sulphate capsules or lactoferrin 250 mg capsules once daily for eight consecutive weeks. The primary efficacy parameter was the amount of increase in hemoglobin concentration by 4 and 8 weeks, the adverse effects related to iron therapy and the patient compliance to the treatment.. Total increase in Hb after 2 months with lactoferrin was higher (2.26 ± 0.51 g/dL) compared to ferrous sulfate (1.11 ± 0.22 g/dL) (p < 0.001). Gastrointestinal adverse events occurred more frequently with ferrous sulphate than the lactoferrin group (p < 0.001). The number of women requesting change the drug was higher in the ferrous sulphate group (p < 0.001).. Lactoferrin was more effective than ferrous sulfate over a two-month period in pregnant women with IDA, with fewer gastrointestinal adverse events and better treatment acceptability.

Topics: Adult; Anemia, Iron-Deficiency; Female; Ferrous Compounds; Hematinics; Humans; Lactoferrin; Pregnancy; Pregnancy Complications, Hematologic; Young Adult

Objective Evaluate the safety and efficacy of bovine lactoferrin (bLf) versus the ferrous sulphate standard intervention in curing iron deficiency (ID) and ID anaemia (IDA) in pregnant women affected by hereditary thrombophilia (HT). Design Interventional study. Setting Secondary-level hospital for complicated pregnancies in Rome, Italy. Population 295 HT pregnant women (≥18 years) suffering from ID/IDA. Methods Women were enrolled in Arm A or B in accordance with their personal choice. In Arm A, 156 women received oral administration of 100 mg of bLf twice a day; in Arm B, 139 women received 520 mg of ferrous sulphate once a day. Therapies lasted until delivery. Main outcome measures Red blood cells, haemoglobin, total serum iron, serum ferritin (haematological parameters) were assayed before and every 30 days during therapy until delivery. Serum IL-6, key factor in inflammatory and iron homeostasis disorders, was detected at enrolment and after therapy at delivery. Possible maternal, foetal, and neonatal adverse effects were assessed. Results Haematological parameters were significantly higher in Arm A than in Arm B pregnant women (P ≤ 0.0001). Serum IL-6 significantly decreased in bLf-treated women and increased in ferrous sulphate-treated women. BLf did not exert any adverse effect. Adverse effects in 16.5 % of ferrous sulphate-treated women were recorded. Arm A women experienced no miscarriage compared to five miscarriages in Arm B women. Conclusions Differently from ferrous sulphate, bLf is safe and effective in curing ID/IDA associated with a consistent decrease of serum IL-6. The absence of miscarriage among bLf-treated women provided an unexpected benefit.. ClinicalTrials.gov Identifier NCT01221844.

Topics: Abortion, Spontaneous; Adolescent; Adult; Anemia, Iron-Deficiency; Animals; Cattle; Female; Ferrous Compounds; Humans; Infant, Newborn; Interleukin-6; Iron; Iron Deficiencies; Lactoferrin; Pregnancy; Pregnancy Complications, Hematologic; Thrombophilia; Young Adult

Lactoferrin (Lf) is an approximately 80-kDa iron-binding glycoprotein, belonging to the transferrin family, with well-known bacteriostatic and bactericidal properties. It is produced and stored in specific (secondary) neutrophil granules and released during neutrophil activation and degranulation. Nowadays, Lf has a well-known therapeutic indication for combating iron deficiency anemia (IDA) in pregnant women. Studies suggest that Lf plays an important role against cervicovaginal infections by decreasing cytokines levels, such as interleukin (IL)-6, in cervicovaginal fluid. The aim of this preliminary trial was to evaluate the effectiveness of Lf in preventing preterm delivery caused by cervical infections and ripening. From November 2009 to August 2010, 21 pregnant women (26-32 weeks pregnant), aged between 22 and 36 years, suffering from IDA, at risk of preterm delivery, were prospectively enrolled in the study. One group (N=14) received 100 mg of recombinant human lactoferrin (bLf) [corrected] (lattoferrina; AG-pharma) twice a day before meals, for one month. The other group (N=7) received 520 mg of ferrous sulfate (Ferro-Grad; Abbott Laboratories, USA) once a day. The patients underwent transvaginal ultrasound to evaluate cervical length and funneling, and vaginal swabs were used to detect infections and cervicovaginal fluid sample collection to determine IL-6 levels. The results showed a correlation between the oral administration of 200 mg of bLf [corrected] with both the normalization of vaginal flora (vaginal infection disappearance) and the decrease in IL-6 cervicovaginal fluid levels in women at risk of preterm delivery.

Topics: Administration, Oral; Adult; Anemia, Iron-Deficiency; Anti-Infective Agents; Cervix Mucus; Female; Ferrous Compounds; Gestational Age; Humans; Infant, Newborn; Interleukin-6; Lactoferrin; Pilot Projects; Pregnancy; Premature Birth; Prospective Studies; Recombinant Proteins; Ultrasonography; Vagina; Vaginal Smears; Vaginosis, Bacterial; Young Adult

To compare the effects of bovine lactoferrin with ferrous sulfate on iron nutritional status and to evaluate their tolerability in 100 pregnant women with iron deficiency anemia.. Prospective, randomized, controlled, double blind trial.. Obstetrics clinic of a University Department of Obstetrics and Gynecology.. One-hundred pregnant, healthy women to be treated either with one capsule of 100 mg bovine lactoferrin twice a day (Group A; n=49) and 520 mg ferrous sulfate once a day (Group B; n=48).. After 30 days, we evaluated hemoglobin (Hb), serum ferritin, serum iron and total iron- binding capacity (TIBC) values. All women were asked to keep a diary of five potential gastrointestinal side effects (abdominal pain, nausea, vomiting, diarrhea and constipation). For each symptom, patients had to rate its severity according to a scale ranging from 0 (absent) to 3 (severe).. Hb level before and after treatment. Secondary outcomes were serum ferritin, serum iron and TIBC levels and the difference in symptom scores between groups.. In Groups A and B, Hb, serum ferritin and iron were significantly increased while TIBC was significantly reduced in comparison with basal values. No significant differences were observed between Groups A and B. The median scores of abdominal pain and constipation were significantly higher in patients treated with ferrous sulfate in comparison with those treated with bovine lactoferrin.. The results show that bovine lactoferrin has the same efficacy as ferrous sulfate in restoring iron deposits with significantly fewer gastrointestinal side effects.

Topics: Administration, Oral; Adult; Anemia, Iron-Deficiency; Dietary Supplements; Double-Blind Method; Female; Ferrous Compounds; Hematinics; Humans; Lactoferrin; Pregnancy; Pregnancy Complications, Hematologic; Prospective Studies; Treatment Outcome; Young Adult

Lactoferrin is a major protein component of human milk, and it binds iron with high affinity. Because the human small intestine has receptors for lactoferrin, a role for it in iron absorption has been suggested.. The objective was to study the absorption of iron from extrinsically labeled purified recombinant human lactoferrin produced in rice and to compare it with the absorption of iron from ferrous sulfate.. On 2 occasions 4 wk apart, healthy young women (n = 20) were fed a standardized meal supplemented in randomized order with 59Fe as lactoferrin or as ferrous sulfate. Ten subjects received lactoferrin that had been heat-treated, and 10 subjects received untreated lactoferrin. Iron absorption was measured in a whole-body counter after 14 and 28 d and also was measured by red blood cell incorporation after 28 d.. The difference in whole-body iron absorption between heat-treated (24.6 +/- 20.8%; n = 10) and untreated (16.2 +/- 4.4%; n = 10) lactoferrin was not significant. The difference in whole-body iron absorption between the groups given lactoferrin (20.4 +/- 15.3%; n = 20) or ferrous sulfate (18.8 +/- 13.2%; n = 20) also was not significant. Serum ferritin and iron absorption were inversely correlated in subjects when they received either lactoferrin or ferrous sulfate, which suggested that iron is absorbed from the 2 sources by a similar mechanism.. Iron is equally well absorbed from lactoferrin (whether heat-treated or untreated) and ferrous sulfate. Thus, iron provided by dietary lactoferrin is likely to be well utilized in human adults.

Topics: Adult; Biological Availability; Cross-Over Studies; Erythrocytes; Female; Ferritins; Ferrous Compounds; Hemoglobins; Hot Temperature; Humans; Intestinal Absorption; Iron Radioisotopes; Iron, Dietary; Lactoferrin; Milk, Human; Oryza; Recombinant Proteins

The ability of a microbial invader to acquire iron from its vertebrate host has been recognized as an important virulence mechanism in some pathogenic bacteria. We examined the involvement of similar mechanisms in an experimental infection of mice by a protozoan pathogen of cattle, Tritrichomonas foetus. In a series of experiments, outbred ICR mice were inoculated intraperitoneally with two strains of T. foetus, the moderately virulent KV-1 (approximately 5% mortality rate) and the highly virulent LUB-1MIP (approximately 80% mortality rate). Treatment of mice with ferric ammonium citrate (FeAC) (100 mg/kg per day intraperitoneally) increased the mortality rate caused by the KV-1 infection up to the level determined for the highly virulent strain. The treatment effect was dose dependent and required early administration of FeAC after inoculation of parasites and its continued supply for at least 3 subsequent days. Daily sampling of peritoneal exudate showed that the infection-enhancing effect of iron overload was associated with a stimulation of parasite multiplication, which in the case of KV-1 infection was strongly suppressed in untreated mice. Consistent with these findings, the strain of lower virulence (KV-1) showed considerably lower efficiency accumulating radiolabeled iron from transferrin and a low-molecular source [Fe(III)nitrilotriacetic acid] in vitro. The results indicate an involvement of iron uptake mechanisms by the parasite as a virulence factor in T. foetus infection.

Topics: Animals; Disease Models, Animal; Ferric Compounds; Ferrous Compounds; Injections, Intraperitoneal; Iron; Lactoferrin; Male; Mice; Mice, Inbred ICR; Nitrilotriacetic Acid; Protozoan Infections; Quaternary Ammonium Compounds; Transferrin; Tritrichomonas foetus; Virulence

Data for 18 male and 18 female calves, born from primiparous and multiparous cows, were collected to determine the effect of supplemental lactoferrin and FeSO4 for 5 d after parturition on the Fe status of calves. Dietary treatments were 1) untreated, 2) 40 mg of Fe/d as FeSO4, and 3) 40 mg of Fe as FeSO4 plus 5 g of lactoferrin/d. Blood hematocrit and hemoglobin of calves born from primiparous cows at d 1 of age were lower than those of calves born from multiparous cows, but not different from those of their dams. Blood hematocrit and hemoglobin of male calves at d 1 of age were lower than those of female calves. Plasma Fe of primiparous cows at parturition was lower than that of multiparous cows, but plasma Fe of calves was not affected by parity of dam and sex of calf. Blood hematocrit and hemoglobin of untreated calves decreased from 1 to 10 d of age. Blood hematocrit and hemoglobin of calves treated with Fe of Fe plus lactoferrin increased from 2 to 10 d of age. Blood hematocrit and hemoglobin of calves treated with Fe plus lactoferrin were higher than those of calves treated with Fe at d 6 of age. Plasma Fe of calves treated with Fe or Fe plus lactoferrin increased temporarily at d 2 of age. Plasma Fe of calves treated with Fe plus lactoferrin at d 2 of age was lower than that of calves treated with Fe, but, at d 6 and 10 of age, plasma Fe of calves treated with Fe plus lactoferrin were higher.

Topics: Animals; Animals, Newborn; Cattle; Colostrum; Female; Ferrous Compounds; Hematocrit; Hemoglobins; Iron; Lactoferrin; Male; Nutritional Status; Parity

Iron is a growth requirement for virtually all microbes. In the human body, extracellular iron is sequestered from microbes by binding to proteins such as lactoferrin. In this study the effect of lactoferrin and human milk on Yersinia pseudotuberculosis was investigated. Its growth in vitro was inhibited by iron-free, but not iron saturated, pure lactoferrin or human milk. Iron-free human milk and to a less extent normal human milk were bactericidal for Y. pseudotuberculosis cells that were suspended in deionized water. The in vivo studies also show that iron-saturated lactoferrin enhanced growth, whereas, the viable count was reduced by iron-free pure lactoferrin and EDDA. Nine envelope proteins were decreased or disappeared upon growth in iron-deficient medium, whereas one new high molecular weight protein appeared under the same conditions.

Topics: Animals; Bacterial Outer Membrane Proteins; Chelating Agents; Edetic Acid; Electrophoresis, Polyacrylamide Gel; Ferrous Compounds; Humans; In Vitro Techniques; Iron; Lactoferrin; Mice; Milk, Human; Protein Binding; Time Factors; Yersinia pseudotuberculosis

Bordetella pertussis was grown in iron (Fe)-free defined medium to limit the growth of the organism. Doubling times of the Fe-starved organism increased by approximately 1 h, and a 40% reduction in the final extent of growth in Fe-depleted medium was observed. Under these conditions, a hydroxamate siderophore named bordetellin was secreted by B. pertussis. Lactoferrin and transferrin supported growth of B. pertussis even when the protein was sequestered inside dialysis tubing. This suggested that binding of lactoferrin and transferrin to B. pertussis was not essential and that bordetellin production plays a major role in Fe uptake. Solid-phase dot blot assays indicated weak binding of lactoferrin to the cell surface, consistent with previous reports of a lactoferrin receptor. Three new proteins of 97, 77, and 63 kDa were synthesized in response to Fe starvation. Fe-inducible proteins of 103, 72, 24, 21, and 18 kDa were also observed. The synthesis of lipopolysaccharide was also altered by Fe availability.

Topics: Blotting, Western; Bordetella pertussis; Cell Division; Cell Membrane; Electrophoresis, Polyacrylamide Gel; Ferrous Compounds; Hemin; Hydrogen-Ion Concentration; Iron; Iron Chelating Agents; Iron Deficiencies; Lactoferrin; Lipopolysaccharides; Membrane Proteins; Models, Biological; Receptors, Cell Surface; Receptors, Transferrin; Siderophores; Transferrin

Lactoferrin was examined for its effect on the growth of a human colon adenocarcinoma cell line (HT 29) in culture and its action was compared to that produced by transferrin and two different iron solutions (ferrous sulfate and ferric chloride). When transferrin was replaced by either iron solutions the cell grew in proportion to the quantity added and the maximal effect obtained was identical to that produced by transferrin alone. When transferrin was replaced by lactoferrin the cells were unable to proliferate for a long time. However, in the presence of low-concentration iron solutions, lactoferrin stimulated the cell growth, and the effect was more pronounced with the ferric chloride solution.

Topics: Adenocarcinoma; Cell Division; Cell Line; Chlorides; Colonic Neoplasms; Ferric Compounds; Ferrous Compounds; Humans; Kinetics; Lactoferrin; Lactoglobulins; Transferrin