ascorbic-acid and ferric-ammonium-citrate

Iron (Fe) encapsulation has the potential to help overcome several major challenges in Fe fortification of foods. It may decrease unwanted sensory changes in fortified products and reduce interactions of Fe with food components that lower Fe bioavailability. However, the effect of encapsulation per se on Fe bioavailability is a concern. Rat studies comparing encapsulated ferrous sulfate, ferric ammonium citrate, and ferrous fumarate to non-encapsulated compounds indicate that a ratio of capsule:substrate of > or = 60:40 may decrease the relative bioavailability (RBV) of the Fe by approximately 20%. At a ratio of capsule:substrate of < or = 50:50, the RBV of encapsulated ferrous sulfate appears to be similar to ferrous sulfate. Even minor changes in capsule composition may influence Fe bioavailability. Encapsulated ferrous fumarate given with ascorbic acid as a complementary food supplement and encapsulated ferrous sulfate fortified into salt have been shown to be efficacious in anemic children. For salt fortification, further refinements in Fe capsule design are needed to increase resistance to moisture and abrasion, while maintaining bioavailability. Studies evaluating the potential efficacy of encapsulated Fe in staple cereals (wheat and maize flours) are needed. A potential barrier to use of encapsulated forms of Fe in staple food fortification is the relatively low melting point of the capsules, which may cause unwanted sensory changes during food preparation. Research and development efforts to improve the quality of coatings and their resistance to high temperatures are ongoing. Process costs for encapsulation can be high, and unless they can be reduced, may limit applications. Further research is needed to determine which encapsulation technologies are most effective in ensuring iron bioavailability from encapsulated compounds.

Topics: Animals; Ascorbic Acid; Biological Availability; Capsules; Cote d'Ivoire; Edible Grain; Ferric Compounds; Ferrous Compounds; Food, Fortified; Ghana; Humans; Iodine; Iron Compounds; Liposomes; Morocco; Quaternary Ammonium Compounds; Rats; Sodium Chloride, Dietary; Taste

In 781 female college students, there were 41 cases of iron deficiency anemia, 209 of latent iron deficiency, 3 of other anemias, and 528 normal cases. Fifty-four volunteers recruited from the iron deficiency anemia and severe latent iron deficiency groups were randomly divided into 4 study groups. Groups I and III received 500 mg of vitamin C daily, and groups II and IV received ferric ammonium citrate (FeAC; equivalent to 6 mg iron) in addition to vitamin C for 9 weeks. Groups I and II were loaded by aerobic exercise at 50% VO2 max. Significant differences between groups were noted in serum ferritin (SF) in III/IV, hematocrit (Ht) in II/III and III/IV, and reticulocytes (RET) in I/II, I/IV, and III/IV. Hemoglobin (Hb) and other iron-related blood indices tended to normalize in groups II and IV when compared with the pre-values. VO2 max was elevated in groups I and II regardless of iron treatment, but was augmented more in group II than group I.

Topics: Adolescent; Adult; Anemia, Hypochromic; Ascorbic Acid; Drug Therapy, Combination; Exercise; Female; Ferric Compounds; Hemoglobins; Humans; Iron; Nutritional Status; Oxygen; Quaternary Ammonium Compounds

The increased accumulation of iron in the brain in Alzheimer's disease (AD) is well documented, and excess iron is strongly implicated in the pathogenesis of the disease. The adverse effects of accumulated iron in AD brain may include the oxidative stress, altered amyloid beta-metabolism and the augmented toxicity of metal-bound amyloid beta 42. In this study, we have shown that exogenously added iron in the form of ferric ammonium citrate (FAC) leads to considerable accumulation of amyloid precursor protein (APP) without a corresponding change in the concerned gene expression in cultured SHSY5Y cells during exposure up to 48 h. This phenomenon is also associated with increased β-secretase activity and augmented release of amyloid beta 42 in the medium. Further, the increase in β-secretase activity, in SHSY5Y cells, upon exposure to iron apparently involves reactive oxygen species (ROS) and NF-κB activation. The synthetic flavone negletein (5,6-dihydroxy-7-methoxyflavone), which is a known chelator for iron, can significantly prevent the effects of FAC on APP metabolism in SHSY5Y cells. Further, this compound inhibits the iron-dependent formation of ROS and also blocks the iron-induced oligomerization of amyloid beta 42 in vitro. In concentrations used in this study, negletein alone appears to have only marginal toxic effects on cell viability, but, on the other hand, the drug is capable of ameliorating the iron-induced loss of cell viability considerably. Our results provide the initial evidence of potential therapeutic effects of negletein, which should be explored in suitable animal models of AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Ascorbic Acid; Cell Line, Tumor; Ferric Compounds; Flavones; Humans; Hydroxyl Radical; Iron; Iron Chelating Agents; Models, Biological; Neuroblastoma; Neurons; NF-kappa B; Peptide Fragments; Polymerization; Quaternary Ammonium Compounds; Reactive Oxygen Species

The mitochondrial aconitase (mACON) containing a [4Fe-4S] cluster is regarded as the key enzyme for citrate oxidation in the epithelial cells of human prostate. In vitro studies using the human prostatic carcinoma cells, PC-3 cells, found that both hemin and ferric ammonium citrate (FAC) significantly increased mACON enzymatic activity and gene expression. The effect of FAC on mACON was enhanced 2-fold by co-treating with ascorbic acid but blocked by co-treating with iron chelator, deferoxamine mesylate. Hemin treatments blocked 30% of citrate secretion from PC-3 cells but upregualted 2-fold of intracellular ATP biosynthesis. Results from reporter assay by using a cytomegalovirus enhance/promoter driven luciferase mRNA ligated to the iron response element (IRE) of mACON as a reporter construct demonstrated that modulation of FAC on gene translation of mACON gene is dependent on the IRE. Transient gene expression assays indicated that upregulation of mACON gene transcription by FAC may through the putative antioxidant response element (ARE) signal pathway. This study provides the first evidence of the biologic mechanism of human mACON gene translation/transcription and suggests a regulatory link between the energy utilization and the iron metabolism in human prostatic carcinoma cells.

Topics: Aconitate Hydratase; Adenosine Triphosphate; Ascorbic Acid; Base Sequence; Cell Line, Tumor; Cell Proliferation; Chelating Agents; Citrates; Deferoxamine; Dose-Response Relationship, Drug; Ferric Compounds; Gene Expression Regulation, Neoplastic; Genes, Reporter; Genetic Vectors; Hemin; Humans; Immunoblotting; Iron; Male; Mitochondria; Molecular Sequence Data; Mutagenesis, Site-Directed; Prostatic Neoplasms; Protein Biosynthesis; Quaternary Ammonium Compounds; Signal Transduction; Transcription, Genetic; Up-Regulation

Ferritin is the major intracellular iron storage protein which has been shown to protect cells against oxidative damage. Recent reports that an inherited abnormality in human ferritin synthesis is associated with early bilateral cataracts underscore the importance of understanding ferritin synthesis and iron storage in lens epithelial cells. We previously demonstrated that ascorbic acid greatly increases de novo synthesis of ferritin in lens epithelial cells. The objectives of the present study were to determine: (1) the effects of ascorbic acid and ferric ammonium citrate on iron uptake by canine lens epithelial cells from iron bound to transferrin and from ferric chloride and (2) the incorporation of this element into ferritin. Iron uptake by lens epithelial cells from 59ferric chloride was 20 times higher than from 59iron-transferrin and iron deposition into ferritin was 8-fold higher when 59ferric chloride was the source. Ascorbic acid had a stimulatory effect on iron uptake from transferrin and on incorporation of this element into ferritin. The ascorbic acid-induced increase of iron uptake required de novo protein synthesis but not specifically de novo ferritin biosynthesis. Although ferritin is not directly involved in iron uptake, the level of ferritin protein could control the pool of intracellular iron. The present results indicate that iron homeostasis in lens epithelial cells is affected mainly by changes in apoferritin synthesis, which is greatly stimulated by ascorbic acid, rather than by altering the rate of protein degradation, which is very slow in these cells under all circumstances. Ferric ammonium citrate activates iron uptake from transferrin in a wide range of cell lines by generation of free radicals. Ferric ammonium citrate also increased iron uptake from Tf in lens epithelial cells. Ferric ammonium citrate treated cells incorporated 5 times more iron and deposited 2 times more iron into ferritin than control cells. Increased incorporation of iron into ferritin was due to ferric ammonium citrate-induced stimulation of de novo ferritin synthesis rather than an increased rate of iron deposition into pre-existing ferritin. Ferric ammonium citrate had a different effect on iron uptake from ferric chloride; total iron uptake was not significantly increased while deposition into ferritin was significantly decreased. These results demonstrate that iron homeostasis in lens epithelial cells is regulated by ascorbic acid and by changes in th

Topics: Animals; Apoferritins; Ascorbic Acid; Cells, Cultured; Chlorides; Dogs; Epithelial Cells; Ferric Compounds; Homeostasis; Humans; Infant, Newborn; Iron Radioisotopes; Lens, Crystalline; Quaternary Ammonium Compounds; Transferrin

The absorption and endogenous excretion of iron in man was studied by monitoring the fecal excretion of a stable iron isotope (58Fe). The study was carried out for 12 healthy volunteers who were divided into two groups. Group I received 58Fe-labeled ferric ammonium citrate (III) (58FeAC) equivalent to 6 mg of iron as a control, and group II received a combination of 500 mg of vitamin C and 58FeAC. A new formula was used to calculate the 58Fe absorption ratio reflecting the pool of iron in the intestinal cells, and the ratio was compared with that obtained from Janghorbani's formula, which has been used as one of the common methods. As a result, the 58Fe absorption ratio in group II was statistically significantly higher than that of group I (34.4 +/- 6.1% vs. 15.0 +/- 5.5%, M +/- SD) using Janghorbani's formula. The similar absorption ratio (34.1 +/- 6.0% vs. 14.8 +/- 5.5%) was also obtained by our new formula. Our results confirmed the previous findings that the availability of iron is stimulated by the supplementation of vitamin C. Both formulae agreed in the absorption of iron, indicating that the endogenous excretion of iron (caused by the desquamated cells) in the intestine does not disguise the iron absorption.

Topics: Absorption; Administration, Oral; Adult; Algorithms; Ascorbic Acid; Feces; Female; Ferric Compounds; Humans; Iron; Iron Isotopes; Male; Middle Aged; Neutron Activation Analysis; Quaternary Ammonium Compounds