A COMPARISON OF PHYSICAL PROPERTIES, SCREENING PROCEDURES AND A HUMAN EFFICACY TRIAL FOR PREDICTING THE BIOAVAILABILITY OF COMMERCIAL ELEMENTAL IRON POWDERS USED FOR FOOD FORTIFICATION

Authors: LYNCH, SEAN - E. VIRGINIA MED SCH; BOTHWELL, THOMAS - UNIV OF WITWATERSRAND; CAMPBELL, LOU - PENNSYLVANIA ST UNIV; COWAN, KRISTINA - PENNSYLVANIA ST UNIV; Glahn, Raymond; HALLBERG, LEIF - GOTEBORG UNIVERSITY; HOPPE, MICHAEL - GOTEBORG UNIVERSITY; HULTHEN, LENA - GOTEBORG UNIVERSITY; Hunt, Janet; HURRELL, RICHARD - SWISS RED INST OF TECH; MILLER, DENNIS - CORNELL UNIVERSITY; SWAIN, JAMES - CASE WEST RES UNIV; TURNER, LIZ - SUSTAIN, WASHINGTON DC; WINICHAGOON, PATTENEE - MAHIDOL UNIVERSITY; YEUNG, C - SD ST UNIV; ZEDER, CHRISTOPHE - SWISS FED INST OF TECH; ZIMMERMANN, MICHAEL - SWISS FED INST OF TECH

Submitted to: International Journal for Vitamin and Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/5/2007
Publication Date: 7/1/2007
Citation: Lynch, S.R., Bothwell, T., Campbell, L., Cowan, K., Glahn, R.P., Hallberg, L., Hoppe, M., Hulthen, L., Hunt, J.R., Hurrell, R.F., Miller, D., Swain, J., Turner, L., Winichagoon, P., Yeung, C.K., Zeder, C., Zimmermann, M.B. 2007. A comparison of physical properties, screening procedures and a human efficacy trial for predicting the bioavailability of commercial elemental iron powders used for food fortification. International Journal for Vitamin and Nutrition Research. 77:107-124.

Interpretive Summary: Elemental iron powders are widely used to fortify staple foods. This paper summarizes physical and chemical measurements that were conducted to assess the bioavailability of these iron powders relative to ferrous sulfate, along with validation of these assessments from a study with human subjects. Commercial elemental iron powders varied in bioavailability depending on the manufacturing process. Measurements of particle surface area and of solubility compared well with measurements conducted with animal absorption and with improvement of iron status in Thai women. The dissolution rate of the elemental iron powders in dilute acid, according to a standardized procedure, may be useful as an estimate of bioavailability. Carbonyl and electrolytic iron were found to have the best bioavailability of the iron powders, and reduced forms of iron were generally less bioavailable. This research will be useful in selecting iron products to fortify foods in areas of the world that need dietary iron fortification to fight a high incidence of iron deficiency and iron deficiency anemia.

Technical Abstract: Elemental iron powders are widely used to fortify staple foods. Experimental evidence indicates that there is considerable variation in the bioavailability of different products. For some powders, it may be too low to permit a significant impact on iron status. This study was designed to evaluate possible approaches to screening commercial iron powders for predicted bioavailability, to ascertain whether bioavailability is related to the method of manufacture and to identify products that have the potential to improve iron status. Nine commercial iron powders were allocated to one of five types based on the production process; carbonyl, electrolytic, hydrogen reduced (H-reduced), carbon monoxide reduced (CO-reduced) and other reduced. Structure by scanning electron microscopy and physical properties (particle size distribution, surface area, Fisher subsieve size, apparent and pycnometric density) were determined on all samples. Selected samples (one or more of each type depending on the cost of the assay) were then subjected to five screening procedures that have previously been advocated for predicting bioavailability in humans – dissolution rate in 0.1 mol/L HCl, relative bioavailability (RBV) with respect to ferrous sulfate by the AOAC rat hemoglobin repletion method, dialyzability and Caco-2 cell iron uptake, both after simulated in vitro gastrointestinal digestion, and plasma iron tolerance tests in human volunteers. The results for particle size distribution, surface area, Fisher subsieve size, dissolution rate in 0.1 mol/L HCl and RBV were significantly correlated and consistent for powders of the same type. However, values for different powder types were significantly different. There was no correlation between either dialyzability or Caco-2 cell uptake and the predicted bioavailability estimates based on the physical properties, dissolution rates, RBV in rats or human efficacy data. Although human plasma iron tolerance tests were in general agreement with the other measures of predicted bioavailability, they did not provide information that would have improved the precision of bioavailability estimates based on physical properties, dissolution in HCl and / or RBV in rats. Our observations indicate that the dissolution rate in 0.1 mol/L HCl under standardized conditions is highly predictive of potential bioavailability and that it would be the best approach to developing a reliable and sensitive screening procedure for predicting and monitoring the bioavailability of commercial elemental iron powder products. Some, but not all, of the carbonyl and electrolytic iron powders had the highest predicted bioavailability values. The predicted bioavailability for the reduced iron products was lower and variable, with the lowest values being recorded for the carbon monoxide and other reduced iron products. Two powder types were selected for a human efficacy trial, electrolytic (because it is the iron powder type recommended by WHO) and hydrogen reduced (because of its widespread use). Electrolytic/A131 and H-reduced/AC-325 had relative efficacies compared with ferrous sulfate monohydrate of 77% and 49%, based on the change in body iron stores in Thai women with low iron stores, who received an additional 12 mg iron per day, six days per week for 35 weeks in wheat-based snacks. Comparable values for dissolution rate in 0.1 mol/L HCl and RBV by the AOAC method were 72.5% and 54% for the electrolytic iron, and 37.6% and 42% for the H-reduced iron. We conclude that there is significant variability in the bioavailability of the commercial iron powders that we evaluated (those used for food fortification at the time that our studies were initiated) and that bioavailability is related in part to production method. The bioavailability of some carbonyl and electrolytic iron powders may be adequate for effective food fortification. Howeve