Enhancement Of Nonheme Iron Absorption Research Articles

Non-Heme Iron Loading Capacities of Anchovy (Engraulis japonicus) Meat Fractions under Simulated Gastrointestinal Digestion.

A ferric oxyhydroxide nanoparticle (FeONP)-mediated mechanism has been suggested recently for anchovy (Engraulis japonicus) meat (AM) enhancement of non-heme iron absorption. The current paper fractionates AM biomass into protein (70.67%), lipid (20.98%), and carbohydrate (i.e., glycogen and mucopolysaccharide, 1.07%) and evaluates their capacities in templating the formation of FeONPs under simulated gastrointestinal digestion. Results show that their iron-loading capacities (mg/g) follow the ascending order glycogen (2.43 ± 0.65), protein (20.16 ± 0.56), AM (28.19 ± 0.86), lipid (33.60 ± 1.12), and mucopolysaccharide (541.33 ± 32.33). Protein and lipid act in synergy to contribute the overwhelming majority (about 90%) of AM's iron-loading capacity. l-α-Phosphatidylcholine and l-α-lysophosphatidylcholine are the predominant iron-loading fractions in the lipid digest. Dynamic light scattering and transmission electron microscopy exhibit coating of inorganic cores of the formed FeONPs with peptides or phospholipid-based mixed micelles. Overall, protein and phospholipid are key players in the nanoparticle-mediated "meat factor" mechanism.

Enhancement of non-heme iron absorption by anchovy (Engraulis japonicus) muscle protein hydrolysate involves a nanoparticle-mediated mechanism.

The mechanisms by which meat enhances human absorption of non-heme iron remain unknown. Recently, anchovy (Engraulis japonicus) muscle protein hydrolysate (AMPH) was found to mediate the formation of nanosized ferric hydrolysis products in vitro. The current paper evaluates the effects of AMPH on the bioavailability and the intestinal speciation of non-heme iron in rats, followed by an investigation of cellular uptake pathways of in vitro-formed AMPH-stabilized nanosized ferric hydrolysis products (ANPs) by polarized human intestinal epithelial (Caco-2) cells. The hemoglobin regeneration efficiencies in anemic rats followed the order ferric citrate (9.79 ± 2.02%) < commercial bare α-Fe2O3 nanoparticles (16.37 ± 6.65%) < mixture of ferric citrate and AMPH (40.33 ± 6.36%) ≈ ferrous sulfate (40.88 ± 7.67%) < ANPs (56.25 ± 11.35%). Percentage contents of intestinal low-molecular-weight iron in the groups of FC+AMPH, FeSO4, and ANPs were significantly lower than the corresponding hemoglobin regeneration efficiencies (P < 0.05), providing strong evidence for the involvement of nanosized iron in intestinal iron absorption from FC+AMPH, FeSO4, and ANPs. Calcein-fluorescence measurements of the labile iron pool of polarized Caco-2 cells revealed the involvement of both divalent transporter 1 and endocytosis in apical uptake of ANPs, with endocytosis dominating at acidic extracellular pH. Overall, AMPH enhancement of non-heme iron absorption involves a nanoparticle-mediated mechanism.

L-α-Glycerophosphocholine Contributes to Meat’s Enhancement of Nonheme Iron Absorption ,

In this research, our aim was to isolate and characterize the substance known as “meat factor,” which is reported to enhance nonheme iron absorption. We used various analytical techniques, and the final step was a human study to measure the effect of a candidate compound on iron absorption. Lean beef was selected for study, as it is known to increase nonheme iron absorption. Cooked ground beef was homogenized and aliquots were taken through a simulated gastric and intestinal digestion. This was followed by purification using fast protein liquid chromatography. The fractions were collected and applied to a Caco-2 cell system designed to measure iron absorption using radioiron. Fractions with an enhancing effect were analyzed by mass spectrometry, nuclear magnetic resonance, and HPLC, and a proposed empirical formula was obtained for the substance in the most active fraction (C8H20 NO6P). Tandem mass spectrometry was used to identify the compound as L-α-glycerophosphocholine (L-α) by comparing the spectra against authentic material. We added a commercially available food grade source of L-α to vegetarian lasagna, with and without 100 mg ascorbic acid (a known enhancer of nonheme iron absorption), at the same enhancer:iron molar ratio (2:1), and fed meals to 13 women of child-bearing age with low iron stores. The nonheme iron was labeled with stable isotopes of iron to provide a total dose per meal of 10 mg iron, and absorption was measured from erythrocyte incorporation. Nonheme iron absorption from lasagna was increased by the addition of either ascorbic acid (P = 0.010) or L-α (P = 0.023). We have identified L-α as a component of muscle tissue that enhances nonheme iron absorption, and this finding provides new opportunities for iron fortification of foods.

Enhancers of Iron Absorption: Ascorbic Acid and other Organic Acids

Ascorbic acid (AA), with its reducing and chelating properties, is the most efficient enhancer of non-heme iron absorption when its stability in the food vehicle is ensured. The number of studies investigating the effect of AA on ferrous sulfate absorption far outweighs that of other iron fortificants. The promotion of iron absorption in the presence of AA is more pronounced in meals containing inhibitors of iron absorption. Meals containing low to medium levels of inhibitors require the addition of AA at a molar ratio of 2:1 (e.g., 20 mg AA: 3 mg iron). To promote absorption in the presence of high levels of inhibitors, AA needs to be added at a molar ratio in excess of 4:1, which may be impractical. The effectiveness of AA in promoting absorption from less soluble compounds, such as ferrous fumarate and elemental iron, requires further investigation. The instability of AA during food processing, storage, and cooking, and the possibility of unwanted sensory changes limits the number of suitable food vehicles for AA, whether used as vitamin fortificant or as an iron enhancer. Suitable vehicles include dry-blended foods, such as complementary, precooked cereal-based infant foods, powdered milk, and other dry beverage products made for reconstitution that are packaged, stored, and prepared in a way that maximizes retention of this vitamin. The consumption of natural sources of Vitamin C (fruits and vegetables) with iron-fortified dry blended foods is also recommended. Encapsulation can mitigate some of the AA losses during processing and storage, but these interventions will also add cost. In addition, the bioavailability of encapsulated iron in the presence/absence of AA will need careful assessment in human clinical trials. The long-term effect of high AA intake on iron status may be less than predicted from single meal studies. The hypothesis that an overall increase of dietary AA intake, or fortification of some foods commonly consumed with the main meal with AA alone, may be as effective as the fortification of the same food vehicle with AA and iron, merits further investigation. This must involve the consideration of practicalities of implementation. To date, programs based on iron and AA fortification of infant formulas and cow's milk provide the strongest evidence for the efficacy of AA fortification. Present results suggest that the effect of organic acids, as measured by in vitro and in vivo methods, is dependent on the source of iron, the type and concentration of organic acid, pH, processing methods, and the food matrix. The iron absorption-enhancing effect of AA is more potent than that of other organic acids due to its ability to reduce ferric to ferrous iron. Based on the limited data available, other organic acids may only be effective at ratios of acid to iron in excess of 100 molar. This would translate into the minimum presence/addition of 1 g citric acid to a meal containing 3 mg iron. Further characterization of the effectiveness of various organic acids in promoting iron absorption is required, in particular with respect to the optimal molar ratio of organic acid to iron, and associated feasibility for food application purposes. The suggested amount of any organic acid required to produce a nutritional benefit will result in unwanted organoleptic changes in most foods, thus limiting its application to a small number of food vehicles (e.g., condiments, beverages). However, fermented foods that already contain high levels of organic acid may be suitable iron fortification vehicles.

Approaches to Improve Iron Bioavailability from Complementary Foods

The importance of trace element bioavailability in the etiology of nutritional deficiencies, for example in the etiology of iron deficiency and iron deficiency anemia, can be expected to be most pronounced in individuals with high requirements. Of special concern is the situation in poor communities where infants and young children are consuming monotonous, cereal-based diets. Traditionally, cereal-based gruels are often one of the first semisolid foods to be introduced into the infant's diet. These foods can be expected to have low energy and nutrient density as well as low bioavailability of iron due to the presence of phytic acid. Ascorbic acid is a potent enhancer of non-heme iron absorption that can overcome the inhibiting effect of phytic acid when present in high enough quantities. However, home prepared complementary foods based on cereals and legumes contain negligible amounts of ascorbic acid unless ascorbic acid-rich foods are mixed with the cereal or consumed at the same time. Different approaches to improve iron bioavailability from plant-based complementary foods, e.g., by enzymatic degradation of phytic acid and/or by increased consumption of ascorbic acid-rich foods, should be explored and adapted to local conditions. In addition, there is a need to evaluate efficacy and effectiveness of strategies to increase the dietary intake of bioavailable iron by dietary diversification and food fortification under realistic conditions.

Iron metabolism and requirements in early childhood: do we know enough?: a commentary by the ESPGHAN Committee on Nutrition.

*University of Lancashire, Lancashire, United Kingdom; †University of Milano, Milano, Italy; ‡University of Lund, Malmo, Sweden; §Hopital des Enfants Malades, Paris, France; Hopital Necker Enfants-Malades, Paris, France, ¶Umea University, Umea, Sweden; #University of Munich, Munich, Germany; **Free University of Amsterdam, Amsterdam, The Netherlands; ††Royal Veterinary and Agricultural University, Frederiksberg, Denmark; ‡‡CHUV University Hospital, Lausanne, Switzerland; §§University of Liege, Liege, Belgium; Medical University of Warsaw, Warsaw, Poland; and ¶¶University of Glasgow, Glasgow, United Kingdom

Histidine Content of Low-Molecular-Weight Beef Proteins Influences Nonheme Iron Bioavailability in Caco-2 Cells

The objective of this study was to isolate and characterize beef muscle proteins that enhance nonheme iron bioavailability. Beef sirloin was cooked, lyophilized and reconstituted with water before in vitro digestion. After centrifugation, the digest supernatant was sequentially ultrafiltered using 10- and 1-kDa molecular weight cut-off membranes. Nonheme iron bioavailability was assessed by Caco-2 cell monolayer (59)Fe uptake using an extrinsic labeling method. All ultrafiltration fractions significantly (P < 0.001) increased iron solubility at pH 6.0, compared with the blank. However, iron uptake was significantly (P < 0.001) greater than the blank only in the presence of the 1-kDa retentate (1KR). Therefore, the 1KR was chosen for further analysis. Immobilized metal affinity chromatography (IMAC) of the 1KR yielded four fractions, i.e., three distinct fractions (F1, F3, F4) and one fraction (F2) comprised of a few closely associated peaks. All four IMAC fractions resulted in significantly (P < 0.001) greater (two- to fivefold) iron solubility at pH 6.0, compared with the blank. Iron uptake with F2 and F4 was significantly greater than the blank (P < 0.001 and P < 0.05, respectively). Gel electrophoresis and matrix-assisted laser desorption/ionization analysis illustrated that F1-F4 contained many peptides ranging from 1- to 7-kDa. Amino acid composition analysis revealed that histidine concentration increased progressively from F1 to F4, corresponding to a general, but not parallel increase in iron solubility and uptake. Our results suggest that the enhancement of nonheme iron absorption by beef may be due to peptides produced during gastrointestinal digestion and that histidine content may be important.

The Influence of Meat on Nonheme Iron Absorption in Infants

During weaning the infant has a high iron requirement, and highly available dietary iron is needed to ensure optimal iron status. Muscle tissue has been identified as an enhancer of nonheme iron absorption in adults, although the influence of meat on nonheme iron absorption in infants has not been previously reported. The effect of the addition of 25 g of meat (lean beef) on nonheme iron absorption from a home-prepared vegetable purée meal (80 g of vegetables) was investigated in infants in the present study. The meals did not differ in their contents of other known enhancers or inhibitors of nonheme iron absorption. Incorporation of stable isotopes of iron (57Fe and 58Fe) into red blood cells 14 d after intake was used to measure iron absorption, using a cross-over design in eight healthy infants 43-49 wk of age. Nonheme iron absorption was significantly increased (p = 0.002) from the vegetable purée with added meat (geometric mean 15.0%) compared with the puréed vegetables (geometric mean 9.9%). These results thus suggest that meat is also an enhancer of nonheme iron absorption in infants and that nonheme iron absorption from weaning foods can be increased by the addition of meat.

The health effects of vitamin C supplementation: a review.

A comprehensive review of the literature indicates that populations with long-term consumption of higher than RDA levels of vitamin C (> or = 60 mg/day) from foods and/or supplements have reduced risks of cancer at several sites, cardiovascular disease, and cataracts. The safety of higher than RDA intakes of vitamin C is confirmed in eight placebo-controlled, double-blind studies and six non-placebo clinical trials in which up to 10,000 mg of vitamin C was consumed daily for up to 3 years. There are no clinical data which suggest that vitamin C's enhancement of non-heme iron absorption in individuals with low iron status could be a critical factor in the possible increased risk of heterozygous hemochromatosis-related cardiovascular disease. In fact, the cumulative data do not confirm that iron status is related to risk of cardiovascular disease. Moreover, higher than RDA intakes of vitamin C have been associated with several indices of lowered cardiovascular disease risk including increases in HDL, and decreases in LDL oxidation, blood pressure and cardiovascular mortality.

Inhibition of iron absorption by calcium in rats and dogs: Effects of mineral separation by time and enteric coating

It is known that in rats and humans, calcium markedly inhibits the absorption of iron when both minerals are present in the small intestine. The interaction between iron and calcium was studied in two species, rats and dogs. Female rats were orally dosed with 6 mg calcium as calcium citrate-malate followed by 70 ug iron as ferrous sulfate labeled with [59]Fe. Doses were separated by 0 to 180 min. Iron absorption was measured by using the whole-body isotope retention technique. We determined that iron and calcium must be separated by at least one hour to prevent a negative effect of calcium on iron absorption. This information was used to design tablets containing iron (radiolabeled with [59]Fe) and calcium. Iron tablets were made by enteric coating iron with or without ascorbic acid (an enhancer of non-heme iron absorption). The enteric coat delayed the release of iron into the small intestine by preventing iron dissolution in the stomach for at least one hour. Iron absorption from these tablets and uncoated tablets was measured in dogs using an assay of [59]Fe incorporation into hemoglobin. Calcium inhibited the absorption of uncoated iron-ascorbic acid by about 50%. However, when the enteric-coated iron-ascorbic acid tablets were dosed with calcium tablets, iron absorption was not inhibited. We conclude that calcium inhibits iron absorption in rats and dogs and that this inhibition can be overcome when the two minerals are separated by at least one hour, which may be achieved by enteric-coating the iron source.

Interaction of vitamin C and iron.

Food iron is absorbed by the intestinal mucosa from two separate pools of heme and nonheme iron. Heme iron, derived from hemoglobin and myoglobin, is well absorbed and relatively little affected by other foods eaten in the same meal. On the other hand, the absorption of nonheme iron, the major dietary pool, is greatly influenced by meal composition. Ascorbic acid is a powerful enhancer of nonheme iron absorption and can reverse the inhibiting effect of such substances as tea and calcium/phosphate. Its influence may be less pronounced in meals of high iron availability--those containing meat, fish, or poultry. The enhancement of iron absorption from vegetable meals is directly proportional to the quantity of ascorbic acid present. The absorption of soluble inorganic iron added to a meal increases in parallel with the absorption of nonheme iron, but ascorbic acid has a much smaller effect on insoluble iron compounds, such as ferric oxide or ferric hydroxide, which are common food contaminants. Ascorbic acid facilitates iron absorption by forming a chelate with ferric iron at acid pH that remains soluble at the alkaline pH of the duodenum. High cost and instability during food storage are the major obstacles to using ascorbic acid in programs designed to combat nutritional iron deficiency anemia.

Interrelation of amino acids and pH on intestinal iron absorption.

ARTICLESInterrelation of amino acids and pH on intestinal iron absorptionDJ Kroe, N Kaufman, JV Klavins, and TD KinneyDJ Kroe, N Kaufman, JV Klavins, and TD KinneyPublished Online:01 Aug 1966https://doi.org/10.1152/ajplegacy.1966.211.2.414MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByFormation mechanism and biological activity of novel thiolated human-like collagen iron complex3 February 2016 | Journal of Biomaterials Applications, Vol. 30, No. 8Bioavailability of iron from amino acid complex in weanling pigsAnimal Feed Science and Technology, Vol. 86, No. 1-2Effects of Amino Acids and Dipeptides on the Uptake and Transport of Iron by Caco-2 Cells Cultured in Serum-Free Medium.Food Science and Technology International, Tokyo, Vol. 3, No. 3Chicken extract stimulates haemoglobin restoration in iron deficient rats6 July 2009 | International Journal of Food Sciences and Nutrition, Vol. 47, No. 4Effects of amino acids on the absorption of trivalent chromium and its retention by regions of the rat small intestineNutrition Research, Vol. 10, No. 11A mechanistic hypothesis for meat enhancement of nonheme iron absorption: Stimulation of gastric secretions and iron chelationNutrition Research, Vol. 10, No. 8The effect of food stuffs commonly consumed in egypt on iron absorption and utilisationJournal of the Science of Food and Agriculture, Vol. 37, No. 1Effects of dietary proteins on iron bioavailability—A reviewFood Chemistry, Vol. 18, No. 1Neutron Activation of Iron Tablets to Evaluate the Effects of Glycine on Iron AbsorptionJournal of Pharmaceutical Sciences, Vol. 73, No. 11Effects of Divalent Amino Acids on Iron AbsorptionJournal of Pharmaceutical Sciences, Vol. 73, No. 9Intestinale Resorption von Eisen und chemisch verwandten MetallenRole of Animal Products in Trace Element NutritureIronZur Verwertung verschiedener Eisenverbindungen bei der Ratte13 May 2010 | Zentralblatt für Veterinärmedizin Reihe A, Vol. 23, No. 4Zum Einfluß organischer Liganden auf die Zn-Absorption in vitro9 October 2009 | Zeitschrift für Tierphysiologie Tierernährung und Futtermittelkunde, Vol. 35, No. 1-6Liver Iron: Changes Induced by Cooking and Acid-Peptic DigestionBritish Journal of Haematology, Vol. 26, No. 3Effect of Bound Gossypol on the Absorption of Iron by RatsThe Journal of Nutrition, Vol. 103, No. 6Absorption of iron protein-calorie deficient rats and immediate effects of re-feeding an adequate protein dietThe American Journal of Digestive Diseases, Vol. 17, No. 11Effect of Histidine and Ascorbic Acid on the Absorption and Retention of 59Fe by Iron-depleted RatsThe Journal of Nutrition, Vol. 102, No. 2Effect of Intestinal Microflora on Iron and Zinc Metabolism, and on Activities of Metalloenzymes in RatsThe Journal of Nutrition, Vol. 102, No. 1Effect of Phosphates Upon Iron Absorption Studied in Normal Human Subjects and in an Experimental Model Using DialysisGastroenterology, Vol. 61, No. 3Iron Absorption25 September 2008 | Clinical Toxicology, Vol. 4, No. 4Zinc, copper and manganese in the alimentary tract of sheep9 March 2007 | British Journal of Nutrition, Vol. 24, No. 3Metabolism of Iron and ManganeseJournal of Dairy Science, Vol. 53, No. 8The complexes of zinc, copper and manganese present in ryegrass9 March 2007 | British Journal of Nutrition, Vol. 24, No. 1Absorption of oral chelated ironBiochemical Medicine, Vol. 3, No. 4Effect of Histidine and Certain Other Amino Acids on the Absorption of Iron-59 by RatsThe Journal of Nutrition, Vol. 99, No. 1 More from this issue > Volume 211Issue 2August 1966Pages 414-418 Copyright & PermissionsCopyright © 1966 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1966.211.2.414PubMed5921103History Published online 1 August 1966 Published in print 1 August 1966 Metrics