Optimizing iron adequacy and absorption to prevent iron deficiency anemia: The role of combination of fortified iron and vitamin C

Iron is a vital nutrient to promote the availability of tissue oxygen, cell growth and control of differentiation, and energy metabolism. Preventing Iron Deficiency Anemia (IDA) is necessary because iron is vital to central nervous system growth and development especially in the first years of life. Iron-rich complementary foods are recommended in infants around 6 months of age because iron store is depleted. Better understanding of iron absorption process and factors affecting its absorption and bioavailability is necessary to prevent iron deficiency and can be a dietary strategy to mitigate iron deficiency. Meat and iron-fortified food are the main sources of iron in the diet, and it is essential to introduce supplementary food to improve iron absorption. Additional foods such as cereals, cow milk and soybeans such as phytate, polyphenol and calcium are inhibitors which require care to prevent IDA. Ascorbic acid is an effective iron-absorbing enhancer, which is useful to reduce the effects of any known nonheme iron inhibitor. In iron-fortified foods, Combination use of vitamin C (ascorbic acid) is recommended in molar ratio of 2:1 (with cow's milk and low-phytate cereal foods) and higher molar ratio of 4:1 (with higher phytate such as soybeans).

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Maturation, iron deficiency, and ligands in enteric radioiron transport in vitro

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1963.204.1.171 ◽

1963 ◽

Vol 204 (1) ◽

pp. 171-175 ◽

Cited By ~ 14

Author(s):

W. S. Ruliffson ◽

J. M. Hopping

Keyword(s):

Ascorbic Acid ◽

Iron Deficiency ◽

Iron Absorption ◽

Deficiency Anemia ◽

Anaerobic Incubation ◽

Reverse Effect ◽

Factors Affecting ◽

Everted Gut Sac

The effects in rats, of age, iron-deficiency anemia, and ascorbic acid, citrate, fluoride, and ethylenediaminetetraacetate (EDTA) on enteric radioiron transport were studied in vitro by an everted gut-sac technique. Sacs from young animals transported more than those from older ones. Proximal jejunal sacs from anemic animals transported more than similar sacs from nonanemic rats, but the reverse effect appeared in sacs formed from proximal duodenum. When added to media containing ascorbic acid or citrate, fluoride depressed transport as did anaerobic incubation in the presence of ascorbic acid. Anaerobic incubation in the presence of EDTA appeared to permit elevated transport. Ascorbic acid, citrate, and EDTA all enhanced the level of Fe59 appearing in serosal media. These results appear to agree with previously established in vivo phenomena and tend to validate the in vitro method as one of promise for further studies of factors affecting iron absorption and of the mechanism of iron absorption.

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Ferrous Sulfate Versus Ferrous Fumarate Plus Zinc Sulfate and Vitamin C for Treatment of Iron Deficiency Anemia in Children

Global Journal of Hematology and Blood Transfusion ◽

10.15379/2408-9877.2015.02.01.04 ◽

2015 ◽

Vol 2 (1) ◽

pp. 15-19

Author(s):

Ali Aycicek ◽

Keyword(s):

Iron Deficiency ◽

Vitamin C ◽

Iron Deficiency Anemia ◽

Ferrous Sulfate ◽

Zinc Sulfate ◽

Deficiency Anemia ◽

Ferrous Fumarate

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IRON ABSORPTION AND RESPONSE TO ORAL IRON THERAPY IN IRON DEFICIENCY ANEMIA ASSOCIATED TO ASYMPTOMATIC GIARDIASIS.

Pediatric Research ◽

10.1203/00006450-199306000-00039 ◽

1993 ◽

Vol 33 (6) ◽

pp. 661-661

Author(s):

Helena U Suzuki ◽

Mauro B Morais ◽

Jose N Corral ◽

Ulisses Fagundes-Neto ◽

Nelson L Machado

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Oral Iron ◽

Iron Therapy ◽

Deficiency Anemia ◽

Oral Iron Therapy

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Reply: Intravenous Ferumoxytol in Pediatric Patients With Iron-Deficiency Anemia

Annals of Pharmacotherapy ◽

10.1177/1060028017726796 ◽

2017 ◽

Vol 51 (12) ◽

pp. 1146-1146

Author(s):

Nabil E. Hassan

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Pediatric Patients ◽

Iron Absorption ◽

Deficiency Anemia

Iron Deficiency in children is common problem. Its mechanism could be nutritional or due to lack of iron absorption. Several conditions are associated with IDA. Presence of inflammation further complicate attempts to make a definitive diagnoses or accurately quantify reponse to therapy.

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Iron Amino Acid Chelates

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.74.6.435 ◽

2004 ◽

Vol 74 (6) ◽

pp. 435-443 ◽

Cited By ~ 29

Author(s):

Hertrampf ◽

Olivares

Keyword(s):

Amino Acid ◽

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Ferrous Sulfate ◽

Iron Absorption ◽

Iron Status ◽

Deficiency Anemia ◽

Efficacy Trials ◽

Food Matrices ◽

The Cost

Iron amino acid chelates, such as iron glycinate chelates, have been developed to be used as food fortificants and therapeutic agents in the prevention and treatment of iron deficiency anemia. Ferrous bis-glycine chelate (FeBC), ferric tris-glycine chelate, ferric glycinate, and ferrous bis-glycinate hydrochloride are available commercially. FeBC is the most studied and used form. Iron absorption from FeBC is affected by enhancers and inhibitors of iron absorption, but to a lesser extent than ferrous sulfate. Its absorption is regulated by iron stores. FeBC is better absorbed from milk, wheat, whole maize flour, and precooked corn flour than is ferrous sulfate. Supplementation trials have demonstrated that FeBC is efficacious in treating iron deficiency anemia. Consumption of FeBC-fortified liquid milk, dairy products, wheat rolls, and multi-nutrient beverages is associated with an improvement of iron status. The main limitations to the widespread use of FeBC in national fortification programs are the cost and the potential for promoting organoleptic changes in some food matrices. Additional research is required to establish the bioavailability of FeBC in different food matrices. Other amino acid chelates should also be evaluated. Finally there is an urgent need for more rigorous efficacy trials designed to define the relative merits of amino acid chelates when compared with bioavailable iron salts such as ferrous sulfate and ferrous fumarate and to determine appropriate fortification levels

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Intestinal expression of genes involved in iron absorption in humans

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00371.2001 ◽

2002 ◽

Vol 282 (4) ◽

pp. G598-G607 ◽

Cited By ~ 58

Author(s):

Andreas Rolfs ◽

Herbert L. Bonkovsky ◽

James G. Kohlroser ◽

Kristina McNeal ◽

Ashish Sharma ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Genetic Disorders ◽

Hereditary Hemochromatosis ◽

Transferrin Saturation ◽

High Serum ◽

Deficiency Anemia ◽

Dependent Manner ◽

Expression Levels

Hereditary hemochromatosis (HHC) is one of the most frequent genetic disorders in humans. In healthy individuals, absorption of iron in the intestine is tightly regulated by cells with the highest iron demand, in particular erythroid precursors. Cloning of intestinal iron transporter proteins provided new insight into mechanisms and regulation of intestinal iron absorption. The aim of this study was to assess whether, in humans, the two transporters are regulated in an iron-dependent manner and whether this regulation is disturbed in HHC. Using quantitative PCR, we measured mRNA expression of divalent cation transporter 1 (DCT1), iron-regulated gene 1 (IREG1), and hephaestin in duodenal biopsy samples of individuals with normal iron levels, iron-deficiency anemia, or iron overload. In controls, we found inverse relationships between the DCT1 splice form containing an iron-responsive element (IRE) and blood hemoglobin, serum transferrin saturation, or ferritin. Subjects with iron-deficiency anemia showed a significant increase in expression of the spliced form, DCT1(IRE) mRNA. Similarly, in subjects homozygous for the C282Y HFE mutation, DCT1(IRE) expression levels remained high despite high serum iron saturation. Furthermore, a significantly increased IREG1 expression was observed. Hephaestin did not exhibit a similar iron-dependent regulation. Our data show that expression levels of human DCT1 mRNA, and to a lesser extent IREG1 mRNA, are regulated in an iron-dependent manner, whereas mRNA of hephaestin is not affected. The lack of appropriate downregulation of apical and basolateral iron transporters in duodenum likely leads to excessive iron absorption in persons with HHC.

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Mutation of the gastric hydrogen-potassium ATPase alpha subunit causes iron-deficiency anemia in mice

Blood ◽

10.1182/blood-2011-04-350082 ◽

2011 ◽

Vol 118 (24) ◽

pp. 6418-6425 ◽

Cited By ~ 17

Author(s):

Lara Krieg ◽

Oren Milstein ◽

Philippe Krebs ◽

Yu Xia ◽

Bruce Beutler ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Osmotic Fragility ◽

Microcytic Anemia ◽

Deficiency Anemia ◽

Α Subunit ◽

Hypochromic Microcytic Anemia ◽

Gastric Proton Pump ◽

Potassium Atpase

Abstract Iron is an essential component of heme and hemoglobin, and therefore restriction of iron availability directly limits erythropoiesis. In the present study, we report a defect in iron absorption that results in iron-deficiency anemia, as revealed by an N-ethyl-N-nitrosourea–induced mouse phenotype called sublytic. Homozygous sublytic mice develop hypochromic microcytic anemia with reduced osmotic fragility of RBCs. The sublytic phenotype stems from impaired gastrointestinal iron absorption caused by a point mutation of the gastric hydrogen-potassium ATPase α subunit encoded by Atp4a, which results in achlorhydria. The anemia of sublytic homozygotes can be corrected by feeding with a high-iron diet or by parenteral injection of iron dextran; rescue can also be achieved by providing acidified drinking water to sublytic homozygotes. These findings establish the necessity of the gastric proton pump for iron absorption and effective erythropoiesis.

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Effects of Oral Vitamin C on Hepcidin Levels and Erythropoietin Requirements in Functional Iron Deficiency Anemia among Hemodialysis Patients

QJM ◽

10.1093/qjmed/hcab100.015 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Mahmoud Mohamed Zaki Ali ◽

Maha Abd ElMoniem Behairy ◽

Reem Mohsen El Sharabasy ◽

Ahmed Hamed Ahmed Gharib

Keyword(s):

Iron Deficiency ◽

Vitamin C ◽

Iron Deficiency Anemia ◽

Hemodialysis Patients ◽

Deficiency Anemia ◽

Study Group ◽

Oral Vitamin ◽

Functional Iron Deficiency ◽

Serum Hepcidin ◽

Hs Crp

Abstract Background Hepcidin has long been postulated as a key regulatory peptide in iron homeostasis. Its reduced clearance and elevated levels in hemodialysis (HD) patients lead to functional iron deficiency (FID) and ESA resistance. Vitamin C may be used as adjuvant therapy in FID anemia, but there are limited studies investigating the direct relation between vitamin C and hepcidin levels in HD patients. We aimed to test the reducing effect of Oral vitamin C therapy on hepcidin levels among hemodialysis patients with functional iron deficiency anemia. Patients and Methods This study is an open label randomized controlled clinical trial. It was conducted in the hemodialysis units of Ain Shams University hospitals. 48 adult prevalent HD patients were included and were divided into two groups. Group 1 (study group) included 31 patients who received the conventional treatment of erythropoietin stimulating agents (ESAs) together with oral supplementation of vitamin C 500 mg every other day for 3 months in addition to IV iron therapy. Group 2 (control group) included 17 patients who received only the conventional therapy of ESAs according to their hemoglobin (Hb) levels in addition to IV iron therapy. Laboratory parameters including serum hepcidin levels, highly sensitive CRP (hs-CRP) titer, CBC, kidney function tests and iron indices were measured at the baseline of the study and after 3 months. Results Oral vitamin C therapy resulted in a statistically significant reduction in both hepcidin and hs-CRP levels in the study group after 3 months. The study group showed a significant reduction in serum iron and ferritin levels (P < 0.05). A Decrease in EPO requirements and elevation of hemoglobin level were observed in the study group but were not statistically significant as a short term effect of oral vitamin C, in comparison to the control group. A highly significant correlation was observed between serum hepcidin and hs-CRP (R=0.46, P<0.01). Conclusion Oral vitamin C may be a promising therapy in decreasing serum hepcidin and hs-CRP levels in prevalent hemodialysis patients with functional iron deficiency anemia.

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