Micronutrient Fortification  
Evaluating the Bioavailability of Elemental Iron Powders Used for Food Fortification

Elemental iron powders, the most commonly used iron food fortificants worldwide, differ significantly in characteristics related to bioavailability. Though elemental irons are often preferred because they are low cost and cause few problems with color, flavor and rancidity in food products, some of these products are not sufficiently well absorbed to improve iron status. This was among the key findings of SUSTAINís rigorous assessment of commercial iron products widely used to fortify foods for populations burdened by iron deficiency. Various in vitro and in vivo laboratory methods used to screen commercial iron powders for predicted bioavailability were also found to differ in practicality, reliability and sensitivity.

The assessment was designed to support informed choice/regulation of products in initiatives to address iron deficiency. It was undertaken after participants at an international workshop in Monterrey Mexico in 2000 identified serious shortcomings in previous bioavailability research on elemental irons. Reported bioavailabilities ranged from 5% to 145% relative to the standard, ferrous sulfate. Adding to the confusion, products tested were not always properly identified. Whether the data had any useful bearing on the efficacy of current commercial iron fortificants was doubtful, and a new, rigorous assessment of current products was called for.

Research design: To rigorously assess all commercially available iron powders, and to evaluate bioavailability screening methods, SUSTAIN recruited participants from research institutions worldwide and from each of the companies that supply elemental iron fortificants globally. The evaluation began with physiochemical measurements to characterize the physical properties of a standardized sample pool of powders as a basis for determining which were most closely correlated with biological absorption (Pennsylvania State University). In vitro and in vivo screens and studies with human volunteers were performed on the same set of samples. In vitro methodologies utilized included dissolution rate in dilute hydrochloric acid (evaluated through an inter-laboratory study), dialysis (Swiss Federal Institute of Technology), and Caco-2 cell iron uptake (Cornell University). In vivo screenings were based on AOAC rat hemoglobin repletion (USDA).

In a clinical study, plasma iron tolerance tests were performed in each of 32 healthy male blood donors aged between 35and 61 yrs (Sahlgrenska University Hospital, Sweden). Two widely used products that seemed most promising based on these preliminary screens were evaluated in a final clinical study with female volunteers selected for mild iron deficiency. In this double blind intervention trial impact on iron status was measured at mid and end points when fortified snacks were fed to the Thai women 6 times a week over 35 weeks (Mahidol University, Thailand).

Results: Significant differences were found among products even within the same category (e.g., among electrolytic or carbonyl elemental irons), but produced by different companies. The predicted bioavailability of some carbonyl and electrolytic iron powders was found to be adequate for effective food fortification if addition levels are adequate. Other elemental irons (such as Hydrogen Reduced/AC-325 and Other Reduced/Atomet 95SP) were found not likely to have an impact on iron nutrition at the fortification levels currently employed. In the final human clinical trial, the relative efficacy of the electrolytic and H-reduced Fe powders was 77% and 49%, compared to ferrous sulfate. Because of the variability documented among products, screening of all products for predicted bioavailability is essential. In addition to these valuable insights about the relative bioavailability of products used globally for food fortification this research initiative helped clarify which methodologies are most useful for narrowing the selection of candidates to evaluate in clinical trials.

Prototype screening tool: Dissolution rate of an iron powder in dilute hydrochloric acid was found to be a more sensitive, reliable and cost-effective predictor of biological absorption than other bioavailability screening methodologies evaluated. SUSTAIN thus developed a prototype for a new low cost rapid screening tool based on dissolution rate for evaluating the bioavailability of different iron fortificants.

Impact and dissemination: The new knowledge generated about product attributes that affect bioavailability was acknowledged by several industry partners, and fueled industry research and development efforts to improve products offered. SUSTAIN made the standardized sample pool assembled for this project available to other researchers, who subsequently provided data that was directly comparable to results from this initiative. Studies based on the sample pool have been conducted in the U.S. China and Kuwait.

The project task force report "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" appears in The International Journal for Vitamin & Nutrition Research.

Acknowledgements: We would like to thank the Bill & Melinda Gates Foundation and the Micronutrient Initiative for their support of this project. We are also grateful for volunteer, in kind and pro bono contributions to its success.

Project related publications include: