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Background: Anemia, iron deficiency, and iodine deficiency are problems of important public health concern in many parts of the world, with consequences for the health, development, and work capacity of populations. Several countries are beginning to implement double fortified salt (DFS) programs to simultaneously address iodine and iron deficiencies., Objective: Our objective was to summarize the evidence for efficacy and effectiveness of DFS on the full range of status and functional outcomes and across different implementation and evaluation designs essential to successful interventions., Methods: We conducted a systematic review and meta-analysis of published and gray literature examining the effects of DFS on nutritional status, cognition, work productivity, development, and morbidity of all population groups. We searched for articles in Medline, Embase, CINAHL, Cochrane Central Register, and ProQuest for randomized trials, quasi-randomized trials, and program effectiveness evaluations., Results: A total of 22 studies (N individuals = 52,758) were included. Efficacy studies indicated a significant overall positive effect on hemoglobin concentration [standardized mean difference (95% CI): 0.33 (0.18, 0.48)], ferritin [0.42 (0.08, 0.76)], anemia [risk ratio (95% CI): 0.80 (0.70, 0.92)], and iron deficiency anemia [0.36 (0.24, 0.55)]. Effects on urinary iodine concentration were not significantly different between DFS and iodized salt. The impact on functional outcomes was mixed. Only 2 effectiveness studies were identified. They reported programmatic challenges including low coverage, suboptimal DFS quality, and storage constraints., Conclusions: Given the biological benefits of DFS across several populations in efficacy research, additional evaluations of robust DFS programs delivered at scale, which consider effective implementation and measure appropriate biomarkers, are needed., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2021.)

Background: Anemia prevalence in India remains high despite preventive iron supplementation programs. Consequently, concurrent national policies of iron fortification of staple foods have been initiated., Objectives: This study evaluated the relation between dietary iron intake and anemia (hemoglobin <12 g/dL) in women of reproductive age (WRA; 15-49 y) with respect to iron fortification in India., Methods: Data from 2 national surveys were used. Data on hemoglobin in WRA were sourced from the National Family Health Survey-4, whereas dietary intakes were sourced from the National Sample Survey. Adjusted odds for anemia with increasing iron intake were estimated, along with the effect of modulating nutrients such as vitamins B-12 and C, from statistically matched household data from the 2 surveys. The risks of inadequate (less than the Estimated Average Requirement for WRA) and excess (more than the tolerable upper limit for WRA) intakes of iron were estimated by the probability approach., Results: The relation between iron intake and the odds of anemia was weak (OR: 0.992; 95% CI: 0.991, 0.994); increasing iron intake by 10 mg/d reduced the odds of anemia by 8%. Phytate and vitamin B-12 and C intakes modified this relation by reducing the odds by 1.5% when vitamin B-12 and C intakes were set at 2 μg/d and 40 mg/d, respectively. The additional intake of 10 mg/d of fortified iron reduced the risk of dietary iron inadequacy from 24-94% to 9-39% across states, with no risk of excess iron intake. Approximately doubling this additional iron intake reduced the risk of inadequacy to 2-12%, but the risk of excess intake reached 22%., Conclusions: Providing fortified iron alone may not result in substantial anemia reduction among WRA in India and could have variable benefits and risks across states. Geographically nuanced dietary strategies that include limited fortification and the intake of other beneficial nutrients should be carefully considered., (Copyright © American Society for Nutrition 2019.)

Background: Iron deficiency (ID) and vitamin D deficiency (VDD) are significant pediatric health issues in New Zealand and Australia and remain prevalent micronutrient deficiencies in young children globally., Objective: We aimed to investigate the effect of a micronutrient-fortified, reduced-energy growing-up milk (GUMLi) compared with cow milk (CM) consumed for 1 y on dietary iron and vitamin D intakes and the status of New Zealand and Australian children at 2 y of age., Methods: The GUMLi Trial was a multicenter, double-blind, randomized controlled trial in 160 healthy 1-y-old New Zealand and Australian children conducted in 2015-2017. Participants were randomly assigned 1:1 to receive GUMLi (1.7 mg Fe/100 mL; 1.3 µg cholecalciferol/100 mL) or CM (0.02 mg Fe/100 mL; 0.06 µg cholecalciferol/100 mL) for 12 mo. Secondary outcomes, reported here, included change in dietary iron and vitamin D intakes, iron status, and 25-hydroxyvitamin D [25(OH)D] concentrations from blood samples at age 2 y. All regression models were adjusted for baseline outcome and study center., Results: GUMLi was a large contributor to dietary intakes of iron and vitamin D after 12 mo when compared with intakes from food and CM. The adjusted mean difference between groups for serum ferritin concentrations was 17.8 µg/L (95% CI: 13.6, 22.0 µg/L; P < 0.0001), and for 25(OH)D it was 16.6 nmol/L (95% CI: 9.9, 23.3 nmol/L; P < 0.0001). After 12 mo, ID was present in 16 (24%) participants in the CM group and 5 (7%) participants in the GUMLi group (P = 0.009), and the prevalence of VDD in the CM group increased to 14% (n = 10) and decreased to 3% (n = 2) (P = 0.03) in the GUMLi group., Conclusion: In comparison with CM, GUMLi significantly improved dietary iron and vitamin D intakes and the iron and vitamin D status of healthy children at 2 y of age. This trial was registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12614000918628.

Background: Maternal health and nutrition play a crucial role in early child growth and development. However, little is known about the benefits of preconception micronutrient interventions beyond the role of folic acid (FA) and neural tube defects. Objective: We evaluated the impact of weekly preconception multiple micronutrient (MM) or iron and folic acid (IFA) supplementation on child growth and development through the age of 2 y compared with FA alone. Methods: We followed 1599 offspring born to women who participated in a randomized controlled trial of preconception supplementation in Vietnam. Women received weekly supplements that contained either 2800 μg FA, 60 mg Fe and 2800 μg FA, or 15 MMs including IFA, from baseline until conception followed by daily prenatal IFA supplements until delivery. Child anthropometry was measured at birth and at 3, 6, 12, 18, and 24 mo. Child development was measured with the use of the Bayley Scales for Infant Development III at 24 mo. Results: The groups were similar for baseline maternal and offspring birth characteristics. At 24 mo of age, the offspring in the IFA group had significantly higher length-for-age z scores (LAZs) (0.14; 95% CI: 0.03, 0.26), reduced risk of being stunted (0.87; 95% CI: 0.76, 0.99), and smaller yearly decline in LAZs (0.10; 95% CI: 0.04, 0.15) than the offspring in the FA group. Similar trends were found for the offspring in the MM group compared with the FA group for LAZs (0.10; 95% CI: -0.02, 0.22) and the risk of being stunted (0.88; 95% CI: 0.77, 1.01). Offspring in the IFA group had improved motor development ( P = 0.03), especially fine motor development (0.41; 95% CI: 0.05, 0.77), at the age of 24 mo, but there were no differences for measures of cognition or language. Conclusions: Preconception supplementation with IFA improved linear growth and fine motor development at 2 y of age compared with FA. Future studies should examine whether these effects persist and improve child health and schooling. The trial was registered at clinicaltrials.gov as NCT01665378., Competing Interests: Author disclosures: PHN, IG-C, MFY, TVT, HH, HN, SN, AMD, RM, and UR, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: Food-based strategies to reduce nutritional iron deficiency have not been universally successful. Biofortification has the potential to become a sustainable, inexpensive, and effective solution., Objective: This randomized controlled trial was conducted to determine the efficacy of iron-biofortified beans (Fe-Beans) to improve iron status in Rwandan women., Methods: A total of 195 women (aged 18-27 y) with serum ferritin <20 μg/L were randomly assigned to receive either Fe-Beans, with 86 mg Fe/kg, or standard unfortified beans (Control-Beans), with 50 mg Fe/kg, 2 times/d for 128 d in Huye, Rwanda. Iron status was assessed by hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), and body iron (BI); inflammation was assessed by serum C-reactive protein (CRP) and serum α1-acid glycoprotein (AGP). Anthropometric measurements were performed at baseline and at end line. Random weekly serial sampling was used to collect blood during the middle 8 wk of the feeding trial. Mixed-effects regression analysis with repeated measurements was used to evaluate the effect of Fe-Beans compared with Control-Beans on iron biomarkers throughout the course of the study., Results: At baseline, 86% of subjects were iron-deficient (serum ferritin <15 μg/L) and 37% were anemic (hemoglobin <120 g/L). Both groups consumed an average of 336 g wet beans/d. The Fe-Beans group consumed 14.5 ± 1.6 mg Fe/d from biofortified beans, whereas the Control-Beans group consumed 8.6 ± 0.8 mg Fe/d from standard beans (P < 0.05). Repeated-measures analyses showed significant time-by-treatment interactions for hemoglobin, log serum ferritin, and BI (P < 0.05). The Fe-Beans group had significantly greater increases in hemoglobin (3.8 g/L), log serum ferritin (0.1 log μg/L), and BI (0.5 mg/kg) than did controls after 128 d. For every 1 g Fe consumed from beans over the 128 study days, there was a significant 4.2-g/L increase in hemoglobin (P < 0.05)., Conclusion: The consumption of iron-biofortified beans significantly improved iron status in Rwandan women. This trial was registered at clinicaltrials.gov as NCT01594359., (© 2016 American Society for Nutrition.)

Background: Phytic acid (PA) is a major inhibitor of iron bioavailability from beans, and high PA concentrations might limit the positive effect of biofortified beans (BBs) on iron status. Low-phytic acid (lpa) bean varieties could increase iron bioavailability., Objective: We set out to test whether lpa beans provide more bioavailable iron than a BB variety when served as part of a composite meal in a bean-consuming population with low iron status., Methods: Dietary iron absorption from lpa, iron-biofortified, and control beans (CBs) (regular iron and PA concentrations) was compared in 25 nonpregnant young women with low iron status with the use of a multiple-meal crossover design. Iron absorption was measured with stable iron isotopes., Results: PA concentration in lpa beans was ∼10% of BBs and CBs, and iron concentration in BBs was ∼2- and 1.5-fold compared with CBs and lpa beans, respectively. Fractional iron absorption from lpa beans [8.6% (95% CI: 4.8%, 15.5%)], BBs [7.3% (95% CI: 4.0%, 13.4%)], and CBs [8.0% (95% CI: 4.4%, 14.6%)] did not significantly differ. The total amount of iron absorbed from lpa beans and BBs was 421 μg (95% CI: 234, 756 μg) and 431 μg (95% CI: 237, 786 μg), respectively, and did not significantly differ, but was >50% higher (P < 0.005) than from CBs (278 μg; 95% CI: 150, 499 μg). In our trial, the lpa beans were hard to cook, and their consumption caused transient adverse digestive side effects in ∼95% of participants. Gel electrophoresis analysis showed phytohemagglutinin L (PHA-L) residues in cooked lpa beans., Conclusion: BBs and lpa beans provided more bioavailable iron than control beans and could reduce dietary iron deficiency. Digestive side effects of lpa beans were likely caused by PHA-L, but it is unclear to what extent the associated digestive problems reduced iron bioavailability. This trial was registered at clinicaltrials.gov as NCT02215278., (© 2016 American Society for Nutrition.)

Background: Low iron absorption from important staple foods may contribute to iron deficiency in developing countries. To date, few studies have examined the iron bioavailability of pulse crops as commonly prepared and consumed by humans., Objective: The objectives were to characterize the iron absorption from a test meal of intrinsically labeled (57)Fe lentils prepared as dal, to compare the bioavailability of iron from (57)Fe in dal with that observed for a reference dose of (58)Fe as ferrous sulfate, and to assess associations between iron absorption and iron status indicators., Methods: This crossover study included 19 nonpregnant women (n = 6 anemic; hemoglobin: <12.0 g/dL) who consumed 2 test meals on consecutive days in a counter-balanced order, ferrous sulfate (7 mg FeSO4 plus 1 mg (58)Fe) and 330 g dal (lentils enriched to 85.1% with (57)Fe, 8 mg native (57)Fe). Iron absorption was determined by analyzing blood samples taken 14 d after dosing with the use of magnetic sector thermal ionization mass spectrometry., Results: We found that the mean iron absorption from the dal was 2.20% ± 3.40% and was significantly lower than the 23.6% ± 13.2% observed from the same iron load given as ferrous sulfate (P < 0.001). Absorption of non-heme iron from dal and from ferrous sulfate was inversely associated with serum ferritin (SF; r = -0.50, P = 0.05 and r = -0.81, P < 0.001, respectively) and serum hepcidin (r = -0.45, P = 0.05 and r = -0.60, P = 0.007, respectively). Anemic women absorbed more iron from either source (1.20% from dal, P = 0.10; 18.3% from ferrous sulfate, P = 0.001) compared with women who were iron replete., Conclusions: Iron absorption from the dal was low overall but upregulated in anemic women. Both SF and hepcidin were inversely associated with iron absorption from both a supplemental and a food-based non-heme iron source in nonanemic and anemic women., (© 2015 American Society for Nutrition.)

Despite growing wealth and a strengthening government commitment to improve livelihoods and welfare, many students across rural China have inadequate access to micronutrient-rich diets. Poor diets can lead to nutritional problems, such as iron-deficiency anemia, that can adversely affect health, attention, learning, and mental health. The overall goal of this paper is to assess the impact of multiple micronutrient supplementation (MMS) on anemia and anxiety among students in poor areas of rural China. To achieve this goal, we conducted a randomized controlled trial in 54 randomly chosen elementary schools in 8 of the poorest counties in Shaanxi Province in Northwest China. Study participants were 2730 fourth-grade students, mostly aged 10-12 y. Schools were randomly assigned to 1 of 2 groups: a control group that received no intervention and an intervention group that received a daily MMS with 5 mg of iron (ferrous sulfate) for 5 mo. Our primary outcome measures were hemoglobin (Hb) concentrations (assessed by HemoCue 201+ technology), anemia prevalence (defined as Hb) concentrations ≤120 g/L), and anxiety (using a written mental health test). The results showed that 42.4% of students were anemic at baseline. The Hb concentration was 121.7 ± 10.7 g/L in the treatment group and 123.4 ± 11.4 g/L in the control group. MMS increased Hb concentrations by 1.7 g/L ± 0.15 and reduced anemia rates by 7.0 percentage points (P < 0.05). Anxiety was reduced by 0.30 SDs (P < 0.01). MMS reduced both anemia and anxiety. Our results should encourage further research on the linkages between nutrition and mental health in a development context.

Excessive iron consumption during pregnancy can lead to increased oxidative stress in the maternal body, which may result in adverse pregnancy outcomes. Glutathione S-transferases (GSTs) originate from a superfamily of detoxifying enzymes that play a role in reducing xenobiotic compounds and oxidative stress. The aim of this study was to determine the relationship among GST gene expression, maternal iron intake during pregnancy, and neonatal birth weight. The study participants were 1087 Korean gravidas and their newborns recruited for the Mothers and Children's Environmental Health study between 2006 and 2010. A 24-h dietary recall interview was conducted to estimate iron intake; additional intake through nutritional supplements was thoroughly investigated. Deletion polymorphisms of GSTM1 and GSTT1 were genotyped using PCR. Dietary iron consumption during pregnancy was positively associated with birth weight in pregnant women who were GSTM1-present after adjustment for the following covariates: maternal age, prepregnancy BMI, mother's education level, log-transformed urinary cotinine level, infant gender, gestational age at term, log-transformed energy intake, parity, and the use of folic acid supplements (P < 0.05). There were interactions between the GSTM1 genotype and iron intakes from animal foods (P < 0.05), diet (P < 0.05), and diet with supplements (P < 0.05). No relationship was found between maternal iron intake and birth weight for the GSTT1 polymorphism. This study demonstrates that increased iron consumption during pregnancy may improve infant birth weight for mothers who are GSTM1-present, but it might not be beneficial for mothers with the GSTM1-null genotype.

Questions have been raised about potentially negative effects of antenatal folic acid use in populations with a high prevalence of vitamin B-12 deficiency. Our objective was to examine the association between maternal folate and vitamin B-12 status in pregnancy on offspring insulin resistance and examine whether the effects of maternal micronutrient supplementation varied by baseline maternal folate and/or vitamin B-12 status. Pregnant women were cluster randomized to receive daily supplements containing vitamin A alone or with folic acid, folic acid+iron, folic acid+iron+zinc, or a multiple micronutrient. In a subsample (n = 1132), micronutrient status biomarkers were analyzed at baseline and late pregnancy. Children born to the women who participated in the trial were visited at 6-8 y of age. Fasting plasma glucose and insulin were used to estimate insulin resistance using the homeostasis model assessment (HOMA-IR). Children whose mothers were deficient in vitamin B-12 (<148 pmol/L, 27%) during early pregnancy had a 26.7% increase in HOMA-IR (P = 0.02), but there was no association with maternal folate status. Among children born to women who were vitamin B-12 deficient at baseline, the percent difference in HOMA-IR compared to the control group was 15.1% (95% CI: -35.9, 106.4), 4.9% (-41.6, 88.5), 3.3% (-38.4, 73.5), and 18.1% (-29.0, 96.7) in the folic acid, folic acid-iron, folic acid-iron-zinc, and multiple micronutrient supplementation groups, respectively, none of which were significant. Maternal vitamin B-12 deficiency is associated with an elevated risk of insulin resistance, but supplementation with folic acid or other micronutrients led to no significant change in insulin resistance in school-aged offspring.

Iron deficiency is among the most prevalent of nutrient-related diseases worldwide, but the long-term consequences of maternal and neonatal iron deficiency on offspring are not well characterized. We investigated the effects of a postweaning iron-adequate diet following neonatal iron deficiency on the expression of genes involved in iron acquisition and homeostasis. Pregnant rats were fed an iron-adequate diet (0.08 g iron/kg diet) until gestational d 15, at which time they were divided into 2 groups: 1) a control group fed an iron-adequate diet, and 2) an iron-deficient group fed an iron-deficient diet (0.005 g iron/kg diet) through postnatal d (P) 23 (weaning). After weaning, pups from both dietary treatment groups were fed an iron-adequate diet until adulthood (P75). Rat pups that were iron deficient during the neonatal period (IDIA) had reduced weight gain and hemoglobin concentrations and decreased levels of serum, liver, and spleen iron on P75 compared with rats that were iron sufficient throughout early life (IA). IDIA rats developed erythrocytosis during postweaning development. Further, hepatic expression of hepcidin in IDIA rats was 1.4-fold greater than in IA rats, which paralleled an upregulation of IL-1 expression in the serum. Our data suggest that an iron-adequate diet following neonatal iron deficiency induced an inflammatory milieu that affected iron homeostasis and early growth and development.

Deficiencies of iron and iodine are common in West Africa, and salt is one of very few food vehicles available for fortification. Salt dual-fortified with iodine and micronized ground ferric pyrophosphate (FePP) was tested for its efficacy in rural, tropical Côte d'Ivoire. First, salt and iron intakes, and iron bioavailability were estimated using 3-d weighed food records in 24 households. Local iodized salt was then fortified with 3 mg Fe/g salt as ground FePP (mean particle size = 2.5 mum), and stability, sensory and acceptability trials were done. The dual fortified salt (DFS) was distributed to households and its efficacy compared with that of iodized salt (IS) in a 6-mo, double-blind trial in 5- to 15-y-old iron-deficient children (n = 123). All children were dewormed at baseline. After 6 mo, serum ferritin (SF) and transferrin receptor (TfR) concentrations as well as body iron stores improved significantly in the DFS group but not in the IS GROUP (P < 0.05). Body iron increased from 4.6 +/- 2.7 to 5.9 +/- 2.7 mg/kg (mean +/- SD) in the DFS group; concentrations before and after treatment in the IS group were 5.5 +/- 2.9 and 5.6 +/- 3.1 mg/kg, respectively. The hemoglobin concentration and the prevalence of anemia did not change in either group. The prevalences of malaria, soil-transmitted helminths, and riboflavin deficiency were 55, 14, and 66%, respectively. In tropical West Africa, low-grade salt fortified with micronized ground FePP increased body iron stores but not hemoglobin in children. Iron utilization may have been impaired by the high prevalence of malaria and concurrent nutrient deficiencies.

The need for combined and integrated strategies to address iron deficiency is widely recognized, utilizing targeted supplementation, as well as food based strategies including both fortified and nonfortified foods. The challenge is not so much knowing "what" to do as is understanding "how" to implement effective and sustainable interventions. Because the causes of iron and other micronutrient deficiencies are complex, including inadequate food intake, unsanitary conditions and inadequate health services, the solutions may also be complex, requiring multisectoral and interdisciplinary approaches. Top-down strategies are unlikely to be effective and sustainable. Rather, the beneficiaries of the program at the community level must be able to understand malnutrition in simple terms, to envisage potential solutions and to become "demanders" of services. The experience in Thailand provides an example of a country-wide, community-based and participatory approach utilizing facilitators and motivators at the local level to implement and sustain interventions. The experience in Thailand indicates the potential for developing effective and sustainable interventions to address iron deficiency and other micronutrient problems as part of a broad, community-based effort.

This paper provides a synopsis of the experience in combating iron deficiency in industrialized countries and identifies the reasons for the considerable success and future challenges. Significant progress has been made over the last century in reducing and even eliminating iron deficiency in many industrialized countries. Current estimates are that the prevalence of iron deficiency has declined to <20% in many of these countries, even among women and young children, compared with 30 to 70% in many developing countries. The reasons for this success cannot be attributed solely to a single approach but rather to a range of factors that have occurred over time as a result of both economic development and the implementation of specific policies. Several factors have contributed to improving both iron intakes and reducing iron losses; these include fortification, supplementation, dietary diversification and public health measures. For example, the decline in anemia in infants can be attributed to the introduction of iron-fortified formula and complementary foods in the 1960s to 1970s. Similarly, the enrichment and fortification of cereals with iron that began during World War II in North America and Europe is a result of effective public-private partnerships. Despite these successes, iron deficiency remains a public health concern in industrialized countries for selected subgroups such as women of reproductive age with excess menstrual losses and pregnant women who cannot meet increased requirements from the diet alone. Constant vigilance and innovative approaches for screening and combating this problem are thus still required even in developed countries.

Iron fortification has been used to enhance iron intake in many developed countries for more than 50 years, but only in the last decade has this strategy been applied on a large scale to other parts of the world. Iron fortification of rice is being instituted in the Philippines. Initially, the rice will be produced in government-controlled rice mills and sold at low cost mainly to low income families. Efforts to improve the technology (using coating or extrusion techniques) are currently underway to reduce cost and minimize losses during storage and washing. Effectiveness and feasibility studies are required to test the new technologies and processing/distribution systems. In Venezuela in 1993, the government instituted a mandatory program of iron fortification to enrich precooked corn flour followed by the voluntary fortification of wheat flour. Surveys in school children subsequently showed a sharp drop in iron deficiency. Fortification of fish sauce in Vietnam has shown promising initial results in reducing anemia among anemic, nonpregnant female factory workers. Iron-fortified soy sauce has been shown to reduce anemia in initial studies in children in China, and a large-scale efficacy trial is now underway. These examples indicate that iron fortification of staple foods and condiments holds great promise for the prevention of iron deficiency.

Iron supplementation is probably the best available option to effectively address iron deficiency in pregnant women and young children because it can be targeted specifically to these high-risk groups. However, technical and practical barriers exist: limited information on the effectiveness of supplementation interventions, side effects that affect compliance, and supply/distribution constraints. An innovative approach to addressing these constraints is the use of sprinkles of powdered, microencapsulated ferrous fumarate that can be added directly to any semi-liquid food without changing their taste or consistency. This technique has been tested in initial trials in Ghana and found to be as effective as iron drops. Another approach to improve the effectiveness of iron interventions is through information, education and communication (IEC) programs. These interventions can help modify consumer behavior in some cases, but in some countries, geographic location, variations in language and population size can make the cost of IEC programs very high. IEC strategies in Indonesia aimed at increasing demand for iron supplements by systematic dissemination of specific messages, improving the quality and variety of tablets, increasing the availability and access to supplements by engaging the commercial sector, enrolling traditional birth attendants and other community volunteers in selling supplements. Key issues to be addressed include clarifying optimal starting points and duration of supplementation interventions--based on individual status or population prevalence, defining hemoglobin and ferritin cutoffs at which treatment should be instigated and evaluating the effectiveness of intermittent supplementation with multiple micronutrients.

Industrialized nations have been successful in reducing incidences of iron deficiency through utilization of multifaceted strategies that build on the capabilities of successful alliances between the public and private sectors. In comparison to developing nations, which have an estimated prevalence of iron deficiency of approximately 40%, the prevalence in industrialized countries is approximately 5%. Such low rates were achieved by various initiatives including widespread availability of affordable iron-fortified foods and implementation of national, science-based programs. Despite these successes, however, iron deficiency remains a critical problem among certain subpopulations (e.g., people of low socioeconomic status or recent immigrants who do not consume iron-fortified foods). Strengthening alliances among the private and public sectors and academia in communications efforts about iron deficiency and promoting iron-rich foods as well as iron-fortified foods is necessary to reduce iron deficiency in these populations.

Kazakhstan and the central Asian republics of Uzbekistan, the Kyrgyz Republic, Tajikistan and Turkmenistan have developed anemia prevention and control (APC) policies based on multiple interventions, including education and promotion, oral supplementation of high risk groups and fortification of wheat flour with iron and other micronutrients. These national strategies are aimed at reducing the prevalence of anemia and iron deficiency among young children and women of child-bearing age. Strategy development has been assisted by funding and technical assistance from the United Nations Children's Fund (UNICEF) with additional technical support from the International Nutrition Foundation, the United Nations University and various national institutions. These countries have been among the most advanced in adopting national strategies that include multiple interventions in an overall package, and national interest in APC remains high. However, reviews of APC activities conducted in 2001 suggests the need for modification and enhancement of current efforts and for a shift to national-level actions if these countries are to progress toward current and future goals. Increased commitment and determination, by both national groups and international organizations, are required to achieve and sustain improvement in micronutrient nutrition.

The main barriers to successful iron fortification are the following: 1) finding an iron compound that is adequately absorbed but causes no sensory changes to the food vehicle; and 2) overcoming the inhibitory effect on iron absorption of dietary components such as phytic acid, phenolic compounds and calcium. These barriers have been successfully overcome with some food vehicles but not with others. Iron-fortified fish sauce, soy sauce, curry powder, sugar, dried milk, infant formula and cereal based complementary foods have been demonstrated to improve iron status in targeted populations. The reasons for this success include the use of soluble iron such as ferrous sulfate, the addition of ascorbic acid as an absorption enhancer or the use of NaFeEDTA to overcome the negative effect of phytic acid. In contrast, at the present time, it is not possible to guarantee a similar successful fortification of cereal flours or salt. There is considerable doubt that the elemental iron powders currently used to fortify cereal flours are adequately absorbed, and there is an urgent need to investigate their potential for improving iron status. Better absorbed alternative compounds for cereal fortification include encapsulated ferrous sulfate and NaFeEDTA, which, unlike ferrous sulfate, do not provoke fat oxidation of cereals during storage. Encapsulated compounds also offer a possibility to fortify low grade salt without causing off-colors or iodine loss. Finally, a new and useful additional approach to ensuring adequate iron absorption from cereal based complementary foods is the complete degradation of phytic acid with added phytases or by activating native cereal phytases.

Iron fortification of food is a methodology utilized worldwide to address iron deficiency. A critical problem in some food fortification programs is the lack of bioavailability of iron compounds. This article reviews presentations on iron fortification programs in the Americas and the technical and practical barriers faced by the programs. Effective programmatic strategies will incorporate systematic consideration of sound program management, ensure consumption of fortified foods, and promote advocacy and supportive legislation. However, these factors are often overlooked or are not addressed coherently. Key components to consider in implementation of iron fortification programs include: utilization of foods and condiments containing fortificants that are bioavailable; program development and its implementation coordinated with targeted communications; utilizing resources from public/private sector partnerships; and operational research on how to overcome practical barriers for successful implementation of fortification.

Delivering iron fortified foods that provide meaningful levels of bioavailable iron without altering the accepted appearance and taste of the product presents multiple challenges. Issues relating to food technology, product formulation, acceptance and efficacy evaluation, marketing and quality control must all be addressed. Procter & Gamble Company has developed a unique technology that stabilizes iron in an aqueous system. Utilizing this technology, a fortified powder drink has been developed that is easy to distribute, store and use and that delivers 20-30% of the U. S. RDA for iron, as well as significant amounts of vitamin A, iodine, zinc and vitamin C in a single serving. Acceptance, bioavailability and effectiveness trials have all produced positive results. This type of fortified product can contribute to alleviating iron deficiency but requires scaling up, packaging, quality control and distribution through normal trade channels and public institutions to have a sustainable impact. To be effective, a well-planned communications campaign should also accompany any major iron fortification program. Eradication of iron deficiency anemia can be done but requires a holistic approach that addresses multiple barriers and leverages the untapped expertise and strength of the alliance between public and private sectors.

Adolescence is characterized by a large growth spurt and the acquisition of adult phenotypes and biologic rhythms. During this period, iron requirements increase dramatically in both boys and girls as a result of the expansion of the total blood volume, the increase in lean body mass and the onset of menses in young females. The overall iron requirements increase from a preadolescent level of approximately 0.7-0.9 mg Fe/d to as much as 2.2 mg Fe/d or perhaps more in heavily menstruating young women. These increased requirements are associated with the timing and size of the growth spurt as well as sexual maturation and the onset of menses. The available data on iron intakes in adolescents suggest that adolescent girls are unlikely to acquire substantial iron stores during this time period because intakes may average as little as 10-11 mg Fe/d. The bioavailability from diets in developing and industrialized countries indicates a negative iron balance is likely in many female populations. The low iron stores in these young women of reproductive age will make them susceptible to iron deficiency anemia during pregnancy because dietary intakes alone are insufficient, in most cases, to meet the requirements of pregnancy.

Peru has high rates of iron deficiency anemia. The prevalence is 35% in nonpregnant women of fertile age and 24.7% in adolescent girls in slums of periurban Lima. The major cause of anemia is low intake of dietary iron. A community-based, randomized behavioral and dietary intervention trial was conducted to improve dietary iron intake and iron bioavailability of adolescent girls living in periurban areas of Lima, Peru. Results show that there was a change in knowledge about anemia and improved dietary iron intake in the 71 girls who completed the study compared with the 66 girls in the control group. Although the 9-mo. intervention was not sufficient to improve hemoglobin levels significantly, there appeared to be a protective effect in maintaining the iron status of girls in comparison with the control group.

Iron deficiency in young rats leads to a decrease in brain iron and ferritin concentrations, an increase in transferrin (Tf) concentration, and an increased rate of uptake of iron from the plasma pool. We conducted two experiments to determine whether brain iron, Tf and ferritin respond quickly to iron repletion and to determine whether brain regions respond heterogeneously. Weanling male Sprague-Dawley rats were fed an iron-deficient diet (<5 mg/kg Fe) for 2 wk followed by an iron-adequate diet (REPL group, 35 mg/kg Fe in Experiment 1 and 15 mg/kg Fe in Experiment 2) for 2 or 4 wks, respectively. Age-matched iron-deficient (ID) and control rats composed the other two groups. Fourteen days of repletion with 35 mg/kg Fe dietary treatment were adequate to normalize hematology, brain microsomal and cytosolic Fe and brain ferritin (Experiment 1). Brain transferrin concentrations in REPL rats, however, were significantly above the levels of controls. Regional brain iron decreased heterogeneously due to dietary iron deficiency (Experiment 2), with some regions having a propensity to keep iron (e.g., substantia nigra, pons, and thalamus) and others losing significant amounts of iron (cortex and hippocampus). Ferritin and Tf concentrations also varied significantly across brain regions in ID and control rats. The hippocampus had the most dramatic Tf response to iron deficiency with elevations of approximately 100%, whereas other regions, except striatum, were unaffected. The brain of developing rats thus distributes iron and iron regulatory proteins differently from the brain of adult rats and is quite avid in its reacquisition of iron during iron therapy.