scholarly journals Postnatal Iron Supplementation with Ferrous Sulfate vs. Ferrous Bis-Glycinate Chelate: Effects on Iron Metabolism, Growth, and Central Nervous System Development in Sprague Dawley Rat Pups

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1406
Author(s):  
Shasta McMillen ◽  
Bo Lönnerdal
Keyword(s):  
Ferrous Sulfate ◽  
Iron Supplementation ◽  
Brain Size ◽  
System Development ◽  
Iron Status ◽  
Nervous System Development ◽  
Iron Regulation ◽  
Sprague Dawley ◽  
Excess Iron ◽  
Rat Pups

Iron-fortified formulas and iron drops (both usually ferrous sulfate, FS) prevent early life iron deficiency, but may delay growth and adversely affect neurodevelopment by providing excess iron. We used a rat pup model to investigate iron status, growth, and development outcomes following daily iron supplementation (10 mg iron/kg body weight, representative of iron-fortified formula levels) with FS or an alternative, bioavailable form of iron, ferrous bis-glycinate chelate (FC). On postnatal day (PD) 2, sex-matched rat litters (n = 3 litters, 10 pups each) were randomly assigned to receive FS, FC, or vehicle control until PD 14. On PD 15, we evaluated systemic iron regulation and CNS mineral interactions and we interrogated iron loading outcomes in the hippocampus, in search of mechanisms by which iron may influence neurodevelopment. Body iron stores were elevated substantially in iron-supplemented pups. All pups gained weight normally, but brain size on PD 15 was dependent on iron source. This may have been associated with reduced hippocampal oxidative stress but was not associated with CNS mineral interactions, iron regulation, or myelination, as these were unchanged with iron supplementation. Additional studies are warranted to investigate iron form effects on neurodevelopment so that iron recommendations can be optimized for all infants.

scholarly journals Assessment of Gastrointestinal Symptoms and Non-transferrin Bound Iron After Oral Ferrous Sulfate and Iron-enriched Aspergillus Oryzae Supplementation in Women (P24-039-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Amanda Bries ◽  
Chong Wang ◽  
Brian Wels ◽  
Isaac Agbemafle ◽  
Olivia Meier ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Ferrous Sulfate ◽  
Serum Iron ◽  
Iron Supplementation ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Deficiency Anemia ◽  
Iron Supplements

Abstract Objectives Iron deficiency anemia (IDA) is a widespread nutritional deficiency. Iron supplementation with ferrous sulfate (FeSO4) is the most common strategy to treat IDA; however, the compliance with daily FeSO4 administration is poor, due to contraindicating side effects. Previously, we have reported that A. oryzae (Ultimine®; ULT) is a novel iron source. Therefore, the objective of this study was to determine the biochemical assessment, non-transferrin bound iron (NTBI) and commonly related gastrointestinal side effects to assess the safety of A. oryzae compared to FeSO4. Methods Female participants (n = 16) with serum ferritin concentrations 40 µg/L were randomized to a double-blind, 9-wk cross-over study with a 3-wk placebo washout period between treatments. Oral iron supplements (65 mg Fe), FeSO4 and ULT were administered for 21 consecutive days for each subject. Side effect questionnaires were collected 3d/wk over the 9-wk study period. Side effects and biochemical markers (nausea, heartburn, abdominal pain, fatigue, headache, diarrhea, constipation, oxidative stress and liver and kidney function) from iron supplementation were evaluated, along with serum iron, % transferrin saturation (TS) and NBTI 8 h curves. Results Serum iron, TS, and NTBI were all markedly higher with FeSO4 at each time-point from 2–8 hours (P < 0.001) compared to ULT, whereas NTBI was undetected. Among treatments, FeSO4 resulted in higher inflammation, though not statistically significant. Compliance based on returned pills was higher with ULT (97.3%) than placebo and FeSO4 (95.2% and 93.2%, respectively). Subjects taking FeSO4 reported abdominal discomfort 2% more than ULT, which was not significantly different. FeSO4 caused marginally higher incidence of combined nauseation, constipation and diarrhea when subjects were taking FeSO4 (P < 0.07). Iron status was maintained similarly by both oral iron supplements. Oxidative stress, inflammation, kidney and liver function markers were not elevated with ULT supplementation, suggesting safety of its consumption. Conclusions Better compliance and less gastrointestinal related side effects were reported with ULT compared to FeSO4, while maintaining normal iron status. Our data suggests ULT is a safe oral iron supplement for treatment of IDA. Funding Sources Cura Global Health, Inc.

scholarly journals Iron Supplementation Confers Protection on Disease Severity in Dextran Sodium Sulfate (DSS)-Induced Colitis in Rats (OR15-05-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Amanda Bries ◽  
Rachel Derscheid ◽  
Paige Curry ◽  
Joe Webb ◽  
Olivia Meier ◽  
...  
Keyword(s):  
Disease Activity ◽  
Iron Supplementation ◽  
Iron Homeostasis ◽  
Iron Status ◽  
Fold Increase ◽  
Deficiency Anemia ◽  
State University ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Funding Sources

Abstract Objectives Koji iron, enriched with FeSO4 (Ultimine®; ULT), is a novel source of supplemental iron. Previously, we reported ULT had similar absorption as ferrous sulfate (FeSO4), while resulting in less reported adverse effects in women. Iron deficiency anemia is a common manifestation of inflammatory bowel disease (IBD) due to malabsorption and gastrointestinal (GI) bleeding. Therefore, the objective of our study was to identify the efficacy of 2 forms of iron supplementation on impaired GI integrity and anemia caused by dextran sulfate sodium (DSS)-induced colitis. Methods Six wk old Sprague Dawley rats (n = 40) were randomly assigned to one of four treatment groups (n = 10/group): 1) Control with no DSS; 2) Control + DSS only (Nfe); 3) DSS + ULT; 4) DSS + FeSO4. Animals were maintained on the AIN-93 G diets for 7 d. Colitis was induced by administering fresh 3.5% (w/v) DSS ad lib throughout the study. Daily iron supplementation (6 mg Fe/kg BW) was provided in a pulverized treat, and disease activity indices were observed (gross bleeding, stool consistency and weight loss). Histological scoring of colonic ulcerations, inflammation and grade were assessed. Iron status indicators and liver hepcidin were detected using ELISA and qRT-PCR, respectively. Results The severity score of IBD was significantly higher in the animals without iron supplementation than those treated with iron (P < 0.0001). Moreover, iron supplementation protected against diminished hemoglobin and hematocrit levels as a result of DSS treatment (P = 0.001 and P = 0.03, respectively); whereas, these parameters were not significantly (NS) different between ULT and FeSO4. Improvement was found with post mortem disease score of DSS-induced rats with ULT compared to FeSO4 and Nfe by 14% and 39%, respectively (NS). Compared to healthy controls, FeSO4 resulted in a 3.5-fold increase in liver hepcidin gene expression, whereas ULT caused no change. Conclusions The results of this study highlight the beneficial effects iron supplementation has on the disease activity evoked by severe GI inflammation. Furthermore, this data suggests ULT attenuates the progression of IBD by supporting iron homeostasis. Additional analyses will explore the possible mechanisms of these results by identifying the systemic inflammation. Funding Sources College of Human Sciences, Iowa State University Collaborative Seed Grant Program.

scholarly journals The Effectiveness of Different Doses of Iron Supplementation and the Prenatal Determinants of Maternal Iron Status in Pregnant Spanish Women: ECLIPSES Study

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2418 ◽  
Author(s):  
Lucía Iglesias Vázquez ◽  
Victoria Arija ◽  
Núria Aranda ◽  
Estefanía Aparicio ◽  
Núria Serrat ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Early Pregnancy ◽  
Iron Supplementation ◽  
Iron Status ◽  
Deficiency Anemia ◽  
Hfe Gene ◽  
Excess Iron ◽  
Spanish Women ◽  
Maternal Iron ◽  
Different Doses

Iron deficiency (ID), anemia, iron deficiency anemia (IDA) and excess iron (hemoconcentration) harm maternal–fetal health. We evaluated the effectiveness of different doses of iron supplementation adjusted for the initial levels of hemoglobin (Hb) on maternal iron status and described some associated prenatal determinants. The ECLIPSES study included 791 women, randomized into two groups: Stratum 1 (Hb = 110–130g/L, received 40 or 80mg iron daily) and Stratum 2 (Hb > 130g/L, received 20 or 40mg iron daily). Clinical, biochemical, and genetic information was collected during pregnancy, as were lifestyle and sociodemographic characteristics. In Stratum 1, using 80 mg/d instead of 40 mg/d protected against ID on week 36. Only women with ID on week 12 benefited from the protection against anemia and IDA by increasing Hb levels. In Stratum 2, using 20 mg/d instead of 40 mg/d reduced the risk of hemoconcentration in women with initial serum ferritin (SF) ≥ 15 μg/L, while 40 mg/d improved SF levels on week 36 in women with ID in early pregnancy. Mutations in the HFE gene increased the risk of hemoconcentration. Iron supplementation should be adjusted to early pregnancy levels of Hb and iron stores. Mutations of the HFE gene should be evaluated in women with high Hb levels in early pregnancy.

Maternal Hyperglycemia Leads to Gender-Dependent Deficits in Learning and Memory in Offspring

2003 ◽  
Vol 228 (2) ◽  
pp. 152-159 ◽  
Author(s):  
B.A. Kinney ◽  
M.B. Rabe ◽  
R.A. Jensen ◽  
R.W. Steger
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
System Development ◽  
Inhibitory Avoidance ◽  
Female Offspring ◽  
Nervous System Development ◽  
Diabetic Woman ◽  
Sprague Dawley ◽  
Increased Risk ◽  
And Control

Pregnancy in the diabetic woman has long been associated with an increased risk of congenital malformation in the offspring. However, little is known about the effects of maternal diabetes on development of the central nervous system. To begin to gain an understanding of this problem, diabetes was induced in adult female Sprague-Dawley rats by injection with streptozotocin. Only animals with serum glucose levels greater than 200 mg/dl were used. Diabetic and control females were bred, and all newborn pups were cross-fostered to nondiabetic mothers. At 60 days of age, pups were tested in an elevated plus-maze to assess differences in emotionality and anxiety. There were no significant differences between offspring of diabetic dams and controls on this measure. All pups were then housed individually, put on food restriction, and maintained at 85% of their ad libitum weight. They were then trained in a Lashley III maze, which assesses learning and retention capability. The female offspring of diabetic dams performed poorer than controls, a finding that was supported by inhibitory avoidance data from a separate group of animals. All animals were then trained in a radial-arm maze. Results failed to find differences between experimental and control animals. It was concluded that the diabetic intrauterine environment has gender-specific effects on central nervous system development.

scholarly journals Is Iron Supplementation Harmful in Populations Where Iron Deficiency Is Not the Cause of Anemia? Protocol for a 12 Week RCT in Cambodia

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1737-1737
Author(s):  
Jordie Fischer ◽  
David Goldfarb ◽  
Rajavel Elango ◽  
Crystal Karakochuk
Keyword(s):  
Iron Deficiency ◽  
Ferrous Sulfate ◽  
Iron Supplementation ◽  
Intestinal Inflammation ◽  
Iron Status ◽  
World Health ◽  
Iron Supplement ◽  
Childbearing Age ◽  
Gut Inflammation ◽  
Increased Risk

Abstract Objectives In 2016, the World Health Organization set a global policy recommending daily iron supplementation (60 mg elemental iron) for women living in countries with anemia prevalence &gt;40%, such as in Cambodia (45%). However, recent studies have shown the prevalence of iron deficiency (ferritin &lt; 15 μg/L) to be low in Cambodian women (∼3%). Further, iron supplementation may be harmful in women with genetic hemoglobin disorders, which are common in Cambodia (60%), as they are already at an increased risk of iron overload. Iron salts (e.g., ferrous sulfate) are the most common form of iron supplement but have poor bioavailability. Less than 20% of the iron is absorbed in the gut, and the remaining 80% passes unabsorbed into the colon, potentially increasing the risk of pathogen growth and gut inflammation. Alternatively, ferrous bisglycinate is a newer form of iron supplement that has 2–4x higher bioavailability than ferrous sulfate.   Our objectives are to assess in women of childbearing age in Cambodia: i) the non-inferiority of 18 mg iron as ferrous bisglycinate as compared to 60 mg iron as ferrous sulfate on mean ferritin concentrations; and ii) if ferrous sulfate administration is associated with increased intestinal inflammation and enteropathogen abundance, as compared to placebo or ferrous bisglycinate. Methods We will undertake a double-blind three-arm RCT in Kampong Thom province, Cambodia. We will recruit and randomize 480 non-pregnant women (18–45 years) to receive 60 mg ferrous sulfate, 18 mg ferrous bisglycinate, or placebo, for 12 weeks. We will collect blood and stool samples at baseline and 12 weeks, which will be used to measure hemoglobin and ferritin concentrations for iron status, fecal calprotectin, a marker of gut inflammation, and perform multiplex molecular enteropathogen testing. Results N/A Conclusions The findings of this trial will contribute to the evidence for safe and effective iron supplementation for women worldwide. Funding Sources Canadian Institutes of Health Research.

scholarly journals The effect of iron supplementation on birth outcome in mothers with high hemoglobin: a randomized double-blind clinical trial study

2019 ◽  
Author(s):  
Leila Alizadeh ◽  
Leili Salehi ◽  
Mostafa Ashrafi Osalou
Keyword(s):  
Clinical Trial ◽  
Birth Weight ◽  
Pregnant Women ◽  
Head Circumference ◽  
Ferrous Sulfate ◽  
Neonatal Jaundice ◽  
Iron Supplementation ◽  
Iron Status ◽  
Intervention Group ◽  
Double Blind

Abstract Background: Although Iron supplementation is a chief component of prenatal care to prevent anemia in pregnant women, Extreme maternal iron status may adversely affect pregnancy outcome. The aim of this study was to examine the effect of iron supplementation on birth outcomes among pregnant women with high hemoglobin. Methods: In a randomized, double-blind, placebo-controlled trial,189 women who had a hemoglobin concentration more than 13.2 g/dl and a serum Ferritin level higher than 15 μg/l between the 16th and 20th weeks of pregnancy took either one 50 mg tablet of ferrous sulfate daily or placebo during their pregnancies. The data obtained from 13 pregnant women were not used in final analysis for different reasons. After birth, the birth weight, head circumference and birth height in each group were measured and compared, and also two groups compared due to risk of neonatal jaundice. Results: The mean of maternal age and pre- pregnancy BMI was 26.11±5.13, 23.9±2.32, respectively. There were no statistically significant differences between the two groups with respect to birth weight and height, but the difference in head circumference was significant (P=0.003). Also, the risk of neonatal jaundice in intervention group was more than that in control (P=0.005). Conclusion: Iron supplementation in mothers with high hemoglobin did not increase the risk of maternal anemia or low birth weight, but the supplementation increased the risk of jaundice in newborns. It was an interesting finding that the birth head circumference was larger in the non-supplement group than that in the intervention group. Key words: Pregnancy, ferrous sulfate, Birth Weight, Head Circumference, Neonatal jaundice. Clinical trial registration: IRCT2013020612383N1, Registered 27.06.2014

Assessing Former Preterm Neonates for Iron Deficiency at Four Months of Age: Is Breastfeeding a Risk Factor?

2021 ◽  
Vol 104 (6) ◽  
pp. 998-1004
Keyword(s):  
Cohort Study ◽  
Iron Deficiency ◽  
Preterm Infants ◽  
Ferrous Sulfate ◽  
Iron Supplementation ◽  
Iron Status ◽  
University Hospital ◽  
Deficiency Anemia ◽  
Increased Risk

Objective: To determine the incidence and risk factors of iron deficiency (ID) among preterm infants when they reached four months postnatal age. Materials and Methods: The present study was a prospective cohort study. Infants born at 34 weeks’ gestation or earlier, weighing 2,000 grams or less, and treated at a university hospital in Bangkok, Thailand between January 2010 and June 2014 were enrolled. Study data collected included demographic and clinical information during hospitalization, breast milk or formula, and iron supplementation reported during follow-up visits, and studies of iron status at 4-months postnatal age. Univariate and multivariate analyses were performed to identify factors associated with ID. Results: One hundred twenty-one infants completed the four months follow-up. At hospital discharge, all infants were exclusively or partially breastfed. Prophylactic ferrous sulfate was prescribed in 110 infants. At 4-month, 65% were exclusively or partially breastfed. Incidence of biochemical ID or ID anemia in exclusively breastfed, partially breastfed, and formula-fed infant were 19%, 6.9%, and 4.8%, respectively. After adjusting for birth weight and prophylactic ferrous sulfate supplementation, breastfeeding was not associated with increased risk of ID or ID anemia. Conclusion: Incidence of ID at 4-month postnatal age of exclusively breastfed, partially breastfed, and formula-fed preterm infant were not statistically different. Prophylactic iron supplementation at 2 to 4 mg/kg/day should be prescribed to all exclusively or partially breastfed preterm infants of 34 weeks’ gestation or less to prevent ID. The authors recommend checking iron status at the 4-month postnatal time point regardless of feeding type. Trial registration: Thai Clinical Trials Registry, TCTR20201028002 Keywords: Breastfeeding; Cohort study; Infant iron status; Iron deficiency anemia; Iron supplements; Preterm infants

scholarly journals Secondary Hemochromatosis due to Chronic Oral Iron Supplementation

2017 ◽  
Vol 2017 ◽  
pp. 1-3
Author(s):  
Ronald Lands ◽  
Emmanuel Isang
Keyword(s):  
Diabetes Mellitus ◽  
Iron Overload ◽  
Liver Damage ◽  
Ferrous Sulfate ◽  
Iron Supplementation ◽  
Geriatric Patients ◽  
Hepatic Cirrhosis ◽  
Hfe Gene ◽  
Excess Iron ◽  
Chronic Ingestion

Iron may accumulate in excess due to a mutation in the HFE gene that upregulates absorption or when it is ingested or infused at levels that exceed the body’s ability to clear it. Excess iron deposition in parenchymal tissue causes injury and ultimately organ dysfunction. Diabetes mellitus and hepatic cirrhosis due to pancreas and liver damage are just two examples of diseases that result from iron overload. Despite the rapid growth of information regarding iron metabolism and iron overload states, the most effective treatment is still serial phlebotomies. We present a patient who developed iron overload due to chronic ingestion of oral ferrous sulfate. This case illustrates the importance of querying geriatric patients regarding their use of nonprescription iron products without a medical indication.

scholarly journals The Clinical Iron Supplement Fer-In-Sol Improves Fetal Iron Status and Brain Weight in Rats Prenatally Exposed to Alcohol

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 687-687
Author(s):  
Kaylee Helfrich ◽  
Nipun Saini ◽  
Sze Ting (Cecilia) Kwan ◽  
Olivia Rivera ◽  
Susan Smith
Keyword(s):  
Iron Deficiency ◽  
Ferrous Sulfate ◽  
Iron Supplementation ◽  
Iron Status ◽  
Fetal Brain ◽  
Alcohol Exposure ◽  
Brain Weight ◽  
Heart Weight ◽  
Iron Supplement ◽  
Fetal Outcomes

Abstract Objectives Prenatal alcohol exposure (PAE) causes iron deficiency in fetal rats, even when their mothers consume enough iron. Increasing maternal dietary iron improves fetal outcomes, including blood status, brain iron, and proinflammatory cytokines. Clinically, gestational iron deficiency is widespread, with a great need for effective iron interventions in alcohol-exposed pregnancies. Here, we test the ability of a popular clinical iron supplement, Fer-In-Sol (ferrous sulfate), to mitigate PAE's effects when co-administered with alcohol during pregnancy. We hypothesized that the prenatal iron supplement would normalize fetal iron status and have minimal adverse effects on the PAE dams and fetuses. Methods Pregnant Long-Evans rats consumed an iron-adequate diet (AIN-76A, 100 ppm iron) and received 5 g/kg alcohol or isocaloric maltodextrin (MD) by gavage on gestational days (GD) 13.5–19.5. Some dams received 6 mg/kg oral iron as ferrous sulfate from GD12.5–19.5, generating a 2 × 2 design. At GD20.5, we used an ANOVA to analyze mothers and fetuses, with litter as the experimental unit. Results Iron had no effect on PAE-induced reductions in maternal gestational weight gain (P = 0.7818) or maternal food intake (P = 0.7299). Iron did not mitigate a PAE-induced 17% reduction in fetal weight (P = 0.4803). Although iron failed to improve a 10% reduction in placental efficiency (P = 0.0589) or 10% elevation in relative heart weight (P = 0.2958) due to PAE, iron did elevate PAE fetal brain weight by 5%, and it no longer differed from MD-controls (P = 0.5255). Furthermore, iron normalized fetal hematology values in PAE, and improved fetal red blood cell numbers (P = 0.0458) and hematocrit (P = 0.0439) and trended to normalize hemoglobin (P = 0.0585). Iron did not significantly alter maternal blood, suggesting that this iron dose was not excessive. As expected, PAE increased malondialdehyde (MDA) levels in maternal (+10%, P = 0.0224) and fetal livers (+44%, P &lt; 0.0001). Iron supplementation caused an additional, modest rise in maternal (+15%, P = 0.0042) and fetal (+22%, P = 0.0093) livers. Conclusions These data show that maternal iron supplementation improves select fetal outcomes in PAE, including brain weight and blood values, and suggests that this may be a clinically feasible approach to improve prenatal iron status and fetal outcomes in PAE pregnancies. Funding Sources NIAAA NIDDK.

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

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