The Potential of Iodine and Iron Double-Fortified Salt Compared with Iron-Fortified Staple Foods to Increase Population Iron Status.

The potential of double-fortified salt (DFS) to improve population iron status is compared with the potential of iron-fortified wheat flour, maize flour, rice grains, and milk products. The potential for a positive impact on iron status is based on reported efficacy studies, consumption patterns, the extent of industrialization, and whether there are remaining technical issues with the fortification technologies. Efficacy studies with DFS, and with iron-fortified wheat flour, maize flour, and rice, have all reported good potential to improve population iron status. Iron-fortified milk powder has shown good impact in young children. When these foods are industrially fortified in modern, automated facilities, with high-level quality control and assurance practices, high-quality raw materials, and a wide population coverage, all vehicles have good potential to improve iron status. Relative to other fortification vehicles, fortification practices with wheat flour are the most advanced and iron-fortified wheat flour has the highest potential for impact in the short- to medium-term in countries where wheat flour is consumed as a staple. Liquid milk has the least potential, mainly because an acceptable iron fortification technology has not yet been developed. Maize is still predominantly milled in small-scale local mills and, although the extruded rice premix technology holds great promise, it is still under development. Salt has a proven record as an excellent vehicle for iodine fortification and has demonstrated good potential for iron fortification. However, technical issues remain with DFS and further studies are needed to better understand and avoid color formation and iron-catalyzed iodine losses in both high- and low-quality salts under different storage conditions. There is currently a risk that the introduction of DFS may jeopardize the success of existing salt iodization programs because the addition of iron may increase iodine losses and cause unacceptable color formation.

Key Considerations for Policymakers-Iodized Salt as a Vehicle for Iron Fortification: Current Evidence, Challenges, and Knowledge Gaps.

Could DFS help prevent iron deficiency and anemia? Studies in controlled settings (efficacy) demonstrate that double-fortified salt (DFS; iron added to iodized salt) reduces the prevalence of anemia and iron deficiency anemia. Studies in program settings (effectiveness) are limited and reported differing levels of DFS coverage, resulting in mixed evidence of impact on anemia. What iron formulations are available and how do they affect iodized salt? Ferrous sulfate and encapsulated ferrous fumarate (both with various enhancers and/or coating materials) are the main iron formulations currently in use for DFS. Adding iron to iodized salt may lead to adverse changes in the product, specifically discoloration and losses in iodine content. These changes are greatest when the iodized salt used in DFS production is of low quality (e.g., contain impurities, has high moisture, and is of large crystal size). DFS requires iodized salt of the highest quality and a high-quality iron formulation in order to minimize adverse sensory changes and iodine losses. Appropriate packaging of iodized salt is also important to prevent losses. What is known about the minimum requirements to manufacture DFS? DFS producers must use high-quality refined iodized salt meeting the minimum standards for DFS production (which is higher than standards for salt intended for iodization alone), and an iron formulation for which there are rigid quality-assurance measures to ensure consistent quality and blending techniques. The actual proportion of iodized salt meeting the stringent requirements necessary for DFS production is unclear, but likely to be low in many countries, especially those with fragmented salt industries and a low proportion of industrially produced salt. What are the financial implications of adding iron to iodized salt? As a result of higher input costs both for input salt and the iron compound, DFS is more expensive to produce than iodized salt and thus has a higher production cost. Various grades of iodized salt are produced and consumed in different sectors of the market. Experience in India indicates that, on average, producing DFS costs 31-40 US dollars/metric ton or 0.03-0.04 US dollars/kg more than high-quality refined iodized salt. The exact impact of this production-level cost difference on profit margins and consumer price is specific to the conditions of different salt markets. Factors such as transport costs, customary wholesale and retail mark-ups, and taxes all vary greatly and need to be assessed on a case by case basis. Is DFS in alignment with salt-reduction efforts? The WHO has long recognized that salt iodization is an important public health intervention to achieve optimal iodine nutrition and is compatible with salt-reduction goals. Fortification of salt (with any nutrient) should not be used to justify or encourage an increase in salt intake to the public. Any effort to expand salt fortification to other nutrients should be done in close consultation with WHO and those working on salt reduction. What has been the experience with DFS delivery under different platforms? To date, DFS has been introduced into the retail market and in social safety net (primarily in India) programs, but sensory changes in DFS have been raised as concerns. The higher price for DFS has limited expansion in the retail market. In social safety net programs where the cost of DFS is subsidized for beneficiaries, programs must consider long-term resourcing for sustainability. Overall: The optimal production and delivery of DFS are still under development, as many challenges need to be overcome. There is a beneficial impact on hemoglobin in efficacy trials. Thus, if those conditions can be replicated in programs or the technology can be adapted to better fit current production and delivery realities, DFS may provide an effective contribution in countries that need additional food-fortification vehicles to improve iron intake.

Sequential electron-transfer and proton-transfer pathways in hydride-transfer reactions from dihydronicotinamide adenine dinucleotide analogues to non-heme oxoiron(IV) complexes and p-chloranil. Detection of radical cations of NADH analogues in acid-promoted hydride-transfer reactions.

Hydride transfer from dihydronicotinamide adenine dinucleotide (NADH) analogues, such as 10-methyl-9,10-dihydroacridine (AcrH 2) and its derivatives, 1-benzyl-1,4-dihydronicotinamide (BNAH), and their deuterated compounds, to non-heme oxoiron(IV) complexes such as [(L)Fe (IV)(O)] (2+) (L = N4Py, Bn-TPEN, and TMC) occurs to yield the corresponding NAD (+) analogues and non-heme iron(II) complexes in acetonitrile. Hydride transfer from the NADH analogues to p-chloranil (Cl 4Q) also occurs to produce the corresponding NAD (+) analogues and the hydroquinone anion (Cl 4QH (-)). The logarithms of the observed second-order rate constants (log k H) of hydride transfer from NADH analogues to non-heme oxoiron(IV) complexes are linearly correlated with those of hydride transfer from the same series of NADH analogues to Cl 4Q, including similar kinetic deuterium isotope effects. The log k H values of hydride transfer from NADH analogues to non-heme oxoiron(IV) complexes are also linearly correlated with those of deprotonation of the radical cations of NADH analogues. Such linear correlations indicate that overall hydride-transfer reactions of NADH analogues to both non-heme oxoiron(IV) complexes and Cl 4Q occur via electron transfer from NADH analogues to the oxoiron(IV) complexes, followed by rate-limiting deprotonation from the radical cations of NADH analogues and subsequent rapid electron transfer from the deprotonated radicals to the Fe(III) complexes to yield the corresponding NAD (+) analogues and the Fe(II) complexes. The electron-transfer pathway was accelerated by the presence of perchloric acid, and the resulting radical cations of NADH analogues were detected by electron spin resonance spectroscopy and UV-vis spectrophotometry in the acid-promoted hydride-transfer reactions from NADH analogues to non-heme oxoiron(IV) complexes. This result provides the first direct evidence that a hydride transfer from NADH analogues to non-heme oxoiron(IV) complexes proceeds via an electron-transfer pathway.