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Objectives Since the 1990s, programs for the control of micronutrient deficiencies became a public health priority for many governments, including the countries partnering the project "Sustainable Micronutrient Interventions to Control Deficiencies and Improve Nutritional Status and General Health in Asia" (SMILING): Cambodia, Indonesia, Laos-PDR, Thailand and Vietnam. The aim of this study was to map which micronutrient deficiencies have been addressed and which interventions were in place in the SMILING countries. Methods The mapping covered the period up to 2012. Updated information from relevant surveys after 2012 is included in this paper after the completion of the SMILING project. The mapping of micronutrient status was limited to either national or at least large-scale surveys. Information on nutrition interventions obtained through a systematic mapping of national programs combined with a snowball collection from various sources. Results Among the five SMILING countries, Thailand differed historically by an early implementation of a nationwide community-based nutrition program, contributing to reductions in undernutrition and micronutrient deficiencies. For Cambodia, Indonesia, Laos PDR, and Vietnam, some national programs addressing micronutrients have been implemented following adjusted international recommendations. National surveys on micronutrient status were scattered and inconsistent across the countries in design and frequency. Conclusion for practice In conclusion, some micronutrient deficiencies were addressed in national interventions but the evidence of effects was generally lacking because of limited nationally representative data collected. Improvement of intervention programs to efficiently reduce or eliminate micronutrient deficiencies requires more systematic monitoring and evaluation of effects of interventions in order to identify best practices.

Objectives Micronutrient deficiencies, in southeast Asia (SE Asia), remain a public health challenge. We evaluated whether promoting the consumption of locally available nutritious foods, which is a low-risk micronutrient intervention, alone can ensure dietary adequacy, for women of reproductive age and 6-23 m old children. Methods Representative dietary data from Cambodia, Indonesia, Lao PDR, Thailand and Vietnam were analysed using linear programming analysis to identify nutrients that are likely low in personal food environments (problem nutrients), and to formulate food-based recommendations (FBRs) for three to six target populations per country. Results The number of problem nutrients ranged from zero for 12-23 m olds in Indonesia, Thailand and Vietnam to six for pregnant women in Cambodia. The FBRs selected for each target population, if adopted, would ensure a low percentage of the population was at risk of inadequate intakes for five to ten micronutrients, depending on the country and target population. Of the 11 micronutrients modelled, requirements for iron, calcium and folate were most difficult to meet (>= 10 of the 24 target populations), using FBRs alone. The number of individual FBRs selected per set, for each target population, ranged from three to eight; and often included meat, fish or eggs, liver/organ meats, vegetables and fruits. Conclusions for practice Intervention strategies need to increase access to nutritious foods, including products fortified with micronutrients, in SE Asia, when aiming to ensure dietary adequacy for most individuals in the population.

Background The “Sustainable Micronutrient Interventions to Control Deficiencies and Improve Nutritional Status and General Health in Asia” project (SMILING), funded by the European Commission, is a transnational collaboration of research institutions and implementation agencies in five Southeast Asian countries—Cambodia, Indonesia, Laos PDR, Thailand, and Vietnam—with European partners, to support the application of state-of-the art knowledge to alleviate micronutrient malnutrition in Southeast Asia. Objective The major expected outcomes are to improve micronutrient status on a large scale, to identify priority interventions in each Southeast Asian country, and to develop a road map for decision makers and donors for inclusion of these priority interventions into the national policy. Methods SMILING has been built around a strong project consortium that works on a constant and proactive exchange of data and analyses between partners and allows for the differences in contexts and development stages of the countries, as well as a strong North—South—South collaboration and colearning. Results The selection of Southeast Asian countries considered the range of social and economic development, the extent of micronutrient malnutrition, and capacity and past success in nutrition improvement efforts. SMILING is applying innovative tools that support nutrition policy-making and programming. The mathematical modeling technique combined with linear programming will provide insight into which food-based strategies have the potential to provide essential (micro) nutrients for women and young children. Multicriteria mapping will offer a flexible decision-aiding tool taking into account the variability and uncertainty of opinions from key stakeholders. The lessons learned throughout the project will be widely disseminated.

The ability to develop evidence-based clinical guidance and effective programs and policies to achieve global health promotion and disease prevention goals depends on the availability of valid and reliable data. With specific regard to the role of food and nutrition in achieving those goals, relevant data are developed with the use of biomarkers that reflect nutrient exposure, status, and functional effect. A need exists to promote the discovery, development, and use of biomarkers across a range of applications. In addition, a process is needed to harmonize the global health community's decision making about what biomarkers are best suited for a given use under specific conditions and settings. To address these needs, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, organized a conference entitled "Biomarkers of Nutrition for Development: Building a Consensus," which was hosted by the International Atomic Energy Agency. Partners included key multilateral, US agencies and public and private organizations. The assembly endorsed the utility of this initiative and the need for the BOND (Biomarkers of Nutrition for Development) project to continue. A consensus was reached on the requirement to develop a process to inform the community about the relative strengths or weaknesses and specific applications of various biomarkers under defined conditions. The articles in this supplement summarize the deliberations of the 4 working groups: research, clinical, policy, and programmatic. Also described are content presentations on the harmonization processes, the evidence base for biomarkers for 5 case-study micronutrients, and new frontiers in science and technology.

Adequate dietary zinc is essential for appropriate growth, neurological development, and immune function in all age groups, especially in children. Eggs are a potentially attractive means of delivering dietary zinc. This study used an in vitro continuous-flow dialysis (CFD) method to determine the effect of cooking (boiling or frying) on bioaccessibility of zinc from eggs which had been biofortified in vivo. The intrinsically zinc-enriched eggs with the highest level of zinc (18 μg/g) provided the highest available zinc at 75%. There was no statistically significant difference in the bioaccessibility of zinc from eggs enriched with inorganic zinc versus enrichment with organic zinc. The intrinsically zinc-enriched eggs from hens fed both organic and inorganic forms with the maximum available zinc (about 13.5 μg zinc/g) were selected to study the effect of cooking. Boiling and frying did not have any adverse effect on zinc bioaccessibility in the eggs intrinsically enriched with inorganic zinc. However, boiling reduced by about 6% and frying reduced by about 10% the bioaccessible zinc in the control and eggs intrinsically enriched with organic zinc. One intrinsically enriched egg could provide 142% of the daily zinc requirement for a child aged one year.

To evaluate effects of Fe supplementation and sex on the prevalence of anaemia and Fe status in infants in South-East Asia, biochemical data from four parallel, randomized, double-blind trials with Fe and/or Zn supplementation in infants (n 2452) in Indonesia, Thailand and Vietnam was pooled. At recruitment (5 months of age), Hb concentrations were slightly but significantly lower in boy infants compared with girl infants (108·7 g/l v. 111.4 g/l, P = 0·04). At 11 months of age, boy infants not receiving Fe had significantly lower Hb (106·2 g/l v. 111.0 g/l, P v. 21.1 g/l, P

Deficiencies of iron and zinc are prevalent worldwide. Interactions between these micronutrients therefore have important consequences, also for supplementation. To investigate effects on hemoglobin and zinc concentrations and interactions of iron and zinc supplementation in infants, data from 4 parallel, randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam were pooled. Infants (n=2468), aged 4-6 mo, were supplemented daily with iron (10 mg) and/or zinc (10 mg) for 6 mo. At 3 sites, infants were given vitamin A capsules (VAC) at recruitment. Combined supplementation reduced prevalences of anemia by 21% (P

Chili and turmeric are common spices in indigenous diets in tropical regions. Being rich in phenolic compounds, they would be expected to bind iron (Fe)(3) in the intestine and inhibit Fe absorption in humans. Three experiments were conducted in healthy young women (n = 10/study) to assess the effect of chili and turmeric on Fe absorption from a rice-based meal containing vegetables and iron fortified fish sauce in vivo. Iron absorption was determined by erythrocyte incorporation of stable isotope labels ((57)Fe/(58)Fe) using a randomized crossover design. Addition of freeze-dried chili (4.2 g dry powder, 25 mg polyphenols as gallic acid equivalents) reduced Fe absorption from the meal by 38% (6.0% with chili vs. 9.7% without chili, P = 0.0017). Turmeric (0.5 g dry powder, 50 mg polyphenols as gallic acid equivalents) did not inhibit iron absorption (P = 0.91). A possible effect of chili on gastric acid secretion was indirectly assessed by comparing Fe absorption from acid soluble [(57)Fe]-ferric pyrophosphate relative to water soluble [(58)Fe]-ferrous sulfate from the same meal in the presence and absence of chili. Chili did not enhance gastric acid secretion. Relative Fe bioavailability of ferric pyrophosphate was 5.4% in presence of chili and 6.4% in absence of chili (P = 0.47). Despite the much higher amount of phenolics in the turmeric meal, it did not affect iron absorption. We conclude that both phenol quality and quantity determine the inhibitory effect of phenolic compounds on iron absorption.

Vitamin A deficiency is a major global public health problem. Among the variety of techniques that are available for assessing human vitamin A status, evaluating the provitamin A nutritional values of foodstuffs and estimating human vitamin A requirements, isotope dilution provides the most accurate estimates. Although the relative expense of isotope dilution restricts its applications, it has an important function as the standard of reference for other techniques. Mathematical modelling plays an indispensable role in the interpretation of isotope dilution data. This review summarises recent applications of stable isotope methodology to determine human vitamin A status, estimate human vitamin A requirements, and calculate the bioconversion and bioefficacy of food carotenoids.

Background: Iron deficiency is assumed to be the major cause of anemia in northeast Thailand but other factors may be involved. Objective: We determined the prevalence of anemia among schoolchildren in northeast Thailand and the role of hemoglobinopathies selected micronutrient deficiencies and other factors in hemoglobin status. Design: Blood samples were collected from 567 children aged 6-12.9 y attending 10 primary schools for the determination of a complete blood count and hemoglobin type [Hb AA (normal hemoglobin) Hb AE (heterozygous for Hb type E) and Hb EE(homozygous for Hb type E)] and the measurement of serum ferritin transferring receptor retinal vitamin B-12 and plasma and erythrocyte folate concentrations. Children with a C-reactive protein concentration = 10 mg/L (n=12) which indicated infection were excluded. Results: The prevalence of anemia was 31%. Age hemoglobin type and serum retinol were the major predictors of hemoglobin concentration. Hb AA and Hb AE children with anemia had lower (P

(a) To measure iron absorption by human subjects from citric acid stabilized fish sauce fortified with ferrous sulfate, ferric ammonium citrate or ferrous lactate and (b) to identify the effect of added citric acid (3 g/l) on iron absorption from ferrous sulfate fortified fish sauce.Iron absorption from the intrinsically labeled compounds was determined via erythrocyte incorporation of isotopic labels ((57)Fe and (58)Fe) using a randomized crossover design. In three separate absorption studies, 10 adult women each consumed a basic test meal of rice and vegetable soup seasoned with isotopically labeled, iron fortified fish sauce.Iron absorption was significantly lower from ferrous lactate and from ferric ammonium citrate fortified fish sauce than from ferrous sulfate fortified fish sauce. Fractional iron absorption (geometric mean; -1s.d., +1s.d.) was 8.7(3.6; 21.4)% for ferrous lactate compared to 13.0(5.4; 31.4)% from ferrous sulfate, P = 0.003 (study 1) and 6.0(2.5; 14.3)% from ferric ammonium citrate relative to 11.7(4.4; 30.7)% from ferrous sulfate, P0.001, in study 2. Citric acid added at a molar ratio of approximately 2.5 to iron had no effect on iron absorption from ferrous sulfate (study 3). Iron absorption in the presence of citric acid was 14.1(6.4; 30.8)% compared to 12.0(5.8; 24.7)% in its absence (P = 0.26).Iron absorption was 50-100% higher from ferrous sulphate fortified fish sauce than from fish sauce fortified with ferric ammonium citrate or ferrous lactate. In the presence of citric acid as a chelator, ferrous sulfate would appear to be a useful fortificant for fish sauce.International Atomic Energy Agency (IAEA), Vienna, Austria.

To prolong consumption of β-carotene and vitamin A-rich foods in Thailand during off-season, plant foods such as ripe mango, ripe papaya, pumpkin, Pak Sien (a local Thai vegetable), and Chinese green cabbage were preserved by candying and pickling. Chicken liver was incorporated into local rice-flour chips. Pumpkin was also stored as fresh whole fruit at room temperature. β-Carotene loss in candied mango and papaya during processing was 17 to 18%, and loss continued from 30 to 40% during storage over 3 months. In contrast, β-carotene contents increased during fermentation of pickled Pak Sien and Chinese green cabbage, ranging from 30 to 40%. A 3-month storage of fresh whole pumpkin in the shade led to as much as a 1263% increase of β-carotene concentrations. On the other hand, vitamin A content was reduced about 50% during the processing of fried chicken liver chips and continued to lose 16% more during storage. Afin de prolonger la consommation d'aliments riches en vitamine A une fois la saison ecoulee, les produits (mangue, papaye, Pak sien, chou chinois) sont confits et mis au vinaigre. Le potiron est entrepose a temperature ambiante, et du foie de poulet est incorpore dans des chips de farine de riz. Les mangues et papayes confites et entreposees subissent une perte importante dans le teneur en vitamine A. Par contre, la teneur en vitamine A augmente dans les aliments fermentes et mis au vinaigre. Le potiron stocke a l'obscurite s'enrichit de 1263% en β-carotene. Mais, la teneur en vitamine A du foie de poulet diminue lors de sa transformation et de son entreposage

This article provides a summary of the symposium "Multiple Micronutrient Interventions during Early Childhood: Moving toward Evidence-Based Policy and Program Planning." The symposium reviewed the strength of evidence of multiple micronutrient interventions on child health, growth, and development, case examples demonstrating how information from program evaluations and the local context can be used to improve program design and performance, and the process by which evidence evolves, resulting in guidelines for policy-makers and program managers. The presentations highlighted the importance of an interactive platform at the country level where the scientific community and country stakeholders exchange ideas, develop a priority implementation research agenda, and clarify key issues to generate and modify policy and programs based on the best evidence available and the ability to deliver results in real time.

Objective To determine the performance of a portable fluorometer for measuring serum retinol (SR) concentration. Design and methods Serum samples were obtained from 75 factory worker women and 143 school children. SR concentration was quantified using a portable fluorometer (‘CRAFTi’) and HPLC analysis. Results SR by HPLC (1.23 ± 0.43 μmol/L) and CRAFTi (1.16 ± 0.46 μmol/L) was significantly correlated. Sensitivity and specificity were 85.3% and 78.0% (cutoff of 1.05 μmol/L). Kappa statistics showed moderate agreement. Conclusions CRAFTi portable fluorometer is a promising field-friendly tool for screening vitamin A deficiency.

Inadequate vitamin A (VA) nutrition continues to be a major problem worldwide, and many interventions being implemented to improve VA status in various populations need to be evaluated. The interpretation of results after an intervention depends greatly on the method selected to assess VA status. To evaluate the effect of an intervention on VA status, researchers in Cameroon, India, Indonesia, Mexico, Senegal and Zambia have used serum retinol as an indicator, and have not always found improvement in response to supplementation. One problem is that homeostatic control of serum retinol may mask positive effects of treatment in that changes in concentration are observed only when status is either moderately to severely depleted or excessive. Because VA is stored mainly in the liver, measurements of hepatic VA stores are the “gold standard” for assessing VA status. Dose response tests such as the relative dose response (RDR) and the modified relative dose response (MRDR), allow a qualitative assessment of VA liver stores. On the other hand, the use of the vitamin A-labeled isotope dilution (VALID) technique, (using 13C or 2H-labeled retinyl acetate) serves as an indirect method to quantitatively estimate total body and liver VA stores. Countries including Cameroon, China, Ghana, Mexico, Thailand and Zambia are now applying the VALID method to sensitively assess changes in VA status during interventions, or to estimate a population’s dietary requirement for VA. Transition to the use of more sensitive biochemical indicators of VA status such as the VALID technique is needed to effectively assess interventions in populations where mild to moderate VA deficiency is more prevalent than severe deficiency.

Vitamin A (VA)-fortified rice is a potential intervention strategy to prevent VA deficiency in at-risk populations. Hot-extruded, triple-fortified rice grains with added VA, zinc, and iron were produced by hot extrusion technology and their ability to improve VA status was tested in Thai schoolchildren. The fortification levels were 10 mg of iron, 9 mg of zinc, and 1.05 mg of VA/g extruded rice. A paired stable isotope dilution technique with labeled ¹³C₂-retinyl acetate (¹³C-RID) was used to quantify VA pool size at the beginning and end of the feeding period. Fifty healthy schoolchildren with a serum retinol (SR) concentration of >0.7 μmol/L were randomly assigned to 2 groups to receive either triple-fortified rice (n = 25) or natural rice (n = 25) for 2 mo as part of the daily school meal. The fortified grains, mixed 1:50 with regular rice, were estimated to provide an extra 890 μg of VA/d, 5 d/wk. ¹³C₂-retinyl acetate (1.0 μmol) was administered orally to each child before and at the end of the feeding period to estimate total body reserves (TBRs) of VA, which increased significantly (P < 0.05) in the intervention group from 153 ± 66 μmol retinol at baseline to 269 ± 148 μmol retinol after 2 mo of feeding. There was no change in the TBRs of VA in the control group (108 ± 67 vs. 124 ± 89 μmol retinol) (P = 0.22). Serum retinol remained unchanged in both groups. We conclude that VA-fortified, hot-extruded rice is an efficacious vehicle to provide additional VA to at-risk populations, and that the efficacy of VA-fortified foods can be usefully monitored by the ¹³C-RID measurement of TBRs of VA but not by changes in SR concentration.

Amidst the picture of subclinical vitamin A deficiency in north and north-east Thailand, hospital records revealed 31 cases of infant xerophthalmia in the lower southern region in 1991. Major risk factors included inadequate breastfeeding, consumption of non-fortified sweetened condensed milk, and the presence of pneumonia, diarrhoea, or both. A survey conducted jointly by the Ministry of Public Health (MOPH) and the Institute of Nutrition, Mahidol University (INMU), indicated a public health problem of vitamin A deficiency in pre-school children. A partnership relationship was established between MOPH as an implementation agency and INMU in the technical support role towards alleviating vitamin A deficiency in the lower southern provinces. Intervention began with distribution of high-dose vitamin A capsules in the high-risk areas, followed by fortification of sweetened condensed milk with vitamin A (330 retinol equivalents/100 g). At the same time, a dietary diversification strategy was planned to promote consumption of vitamin A–rich foods in the local menus or fish chips enriched with chicken or beef liver. No new cases of xerophthalmia have been reported since 1995. Periodic subsample surveys indicated that the severity of the problem has declined to a subclinical stage. Key elements of progress include partnership between MOPH and INMU from planning to implementation, transition of MOPH to a more preventive and promotive approach, continuous communication from top to grass-roots-level officers, and coupling of research with programmes.

Retinol and β-carotene contents of raw and home-prepared indigenous foods in Northeast Thailand were studied. The criteria used to select the vitamin A-rich foods were high retinol or β-carotene contents of the individual food items, the amount and frequency of consumption, preference of consumption and food availability. Items selected were chicken liver, chicken egg, ivy gourd, amaranth, swamp cabbage (Chinese), Chinese cabbage, pumpkin, yellow sweet potato and two traditional menu items, kang-nho-mai and om-kruang-nai-kai. Raw food items were purchased from the local market; the traditional cooking procedures of the community were duplicated in the laboratory. Retinol and β-carotene contents were determined prior to and following cooking using HPLC methodology. The results indicated that boiling intact chicken liver resulted in 5% loss of retinol; boiling with cutting into small pieces and grilling resulted in losses of 8 and 16%, respectively. Greater losses (43%) were observed for egg omelet compared to hard-boiled egg (11%). For vegetables, blanching resulted in 7–11% loss of β-carotene, while steaming, frying and boiling showed losses of 15, 18 and 43%, respectively. Traditional foods such as bambooshoot soup (Kang-nho-mai) and chicken organ soup (Om-kruang-nai-kai) exhibited β-carotene losses ranging from 6–21%.

Thailand is classified by the World Health Organization as a country with a moderate level of subclinical vitamin A deficiency. in 1992 the eruption of infant xerophthalmia in the country's lower region led to the universal distribution of vitamin A capsules among infants (50,000 IU for those < 6 months old, 100,000 IU for those 6–12 months old) and pre-school children (200,000 IU) in high-risk areas every 6 months. Since then, no new cases of xerophthalmia have arisen. the universal distribution programme covered the period 1992 to 1998. However, to control the problem and prevent it from reoccurring once capsule distribution is discontinued, a food-based strategy for the prevention of vitamin A deficiency is being undertaken in southern Thailand. This strategy has two components: recommendation of vitamin A–rich food recipes for consumption by pregnant women, and development of vitamin A–rich snacks targeted at children. Both of these components have been adopted and successfully promoted by the Health Promotion Center (Region 12) in southern Thailand as part of public special events, regular counselling, and education programmes, and as micro-level income-generation projects by community women's groups.

Monitoring and evaluation are essential components of vitamin A intervention programs. They enable program managers to track progress in achieving their goals. Recommendations for outcome indicators are based on suggestions from the International Vitamin A Consultative Group Meeting (IVACG) workshop in late October 2000 in Annecy, France, followed by a pre-XX IVACG meeting in Hanoi, Vietnam. In areas with detectable xerophthalmia or eye signs, a fall in the prevalence of Bitot's spots to0.5% and a decrease in night blindness during pregnancy to5% indicates that vitamin A deficiency (VAD) is no longer a public health problem, although it still may be responsible for excess morbidity and mortality. Pupillary dark adaptation has been proposed as an objective indicator of vitamin A status. A program is considered to have made progress when the mean pupillary threshold improves to better than -1.24 log cd/m(2). For biochemical indices, the shift of mean or median values or the frequency distribution of preschool children with serum retinol concentration below 0.70 micromol (20 microg/dL), lactating mothers with breast milk retinol values below 0.70 micromol (6 microg per g of milk fat) or below 1.05 micromol (8 microg per g of milk fat) are useful to monitor program progress.

Linear growth faltering during the first 2 years of life is a common feature in most developing countries, eventually leading to stunting, meaning that height falls below two standard deviations of the reference. Stunting is associated with increased morbidity and mortality. Growth faltering is a multi-factorial process, with inadequate intakes of protein, energy, and/or micronutrients all contributing to suboptimal growth. To investigate whether inadequate intakes of iron and/or zinc contribute to growth faltering in infancy in South-East Asia, a multi-country trial was conducted between 1997 and 2000: the SEAMTIZI trial with study sites in Vietnam, Thailand, and Indonesia (two sites). In the SEAMTIZI trial, infants (mean age 5 months) received 10 mg of iron, 10 mg of zinc, 10 mg of both iron and zinc, or placebo daily for 6 months. The SEAMTIZI trial showed that blanket supplementation with iron or zinc could not prevent the progressive decrease in anthropometric Z-scores during the first year of life in SE Asia. At the end of the study, overall stunting prevalence was above 20%, although there were marked differences between the sites. Boy infants had a much higher risk of becoming stunted than girl infants. Baseline factors such as anemia and birth weight influenced the effect of supplementation, with a beneficial effect of zinc supplementation in anemic infants but no effect in non-anemic infants. As blanket supplementation with iron or zinc will not be beneficial to all recipients, and may have adverse effects in some, underlying mechanisms and baseline factors need to be identified to allow targeting only those who may benefit. Development of a multi-factorial approach to prevent growth faltering rather than a search for a single micronutrient that does it all, a ‘Golden bullet,’ is urgently needed.

Micronutrient deficiencies are associated with impaired growth and cognitive function. A school-based fortification program might benefit schoolchildren but a high prevalence of parasite infestation might affect effectiveness. A randomized, double-blind, placebo-controlled 2 × 2 factorial trial was conducted to assess the efficacy of multi-micronutrient fortified biscuits with or without de-worming on growth, cognitive function, and parasite load in Vietnamese schoolchildren. Schoolchildren (n = 510), 6-8 years of age were randomly allocated to receive albendazole or placebo at baseline and four months of multi-micronutrient fortified biscuits (FB) or non-fortified biscuits. Children receiving FB for four months scored higher on two cognitive tests: Raven's Colored Progressive Matrices and the Digit Span Forward test. Children receiving albendazole plus FB had the lowest parasite load after four months. In children receiving FB, mid-upper arm circumference was slightly improved (+0.082 cm) but there were no differences in other indexes of anthropometry. Combining multi-micronutrient fortified biscuits with de-worming is an effective strategy.

Concurrent micronutrient deficiencies are prevalent among Vietnamese school children. A school-based program providing food fortified with multiple micronutrients could be a cost-effective and sustainable strategy to improve health and cognitive function of school children. However, the efficacy of such an intervention may be compromised by the high prevalence of parasitic infestation. To evaluate the efficacy of school-based intervention using multi-micronutrient-fortified biscuits with or without deworming on anemia and micronutrient status in Vietnamese schoolchildren, a randomized, double-blind, placebo-controlled trial was conducted among 510 primary schoolchildren, aged 6-8 y, in rural Vietnam. Albendazole (Alb) (400 mg) or placebo was given at baseline. Nonfortified or multi-micronutrient-fortified biscuits including iron (6 mg), zinc (5.6 mg), iodine (35 microg), and vitamin A (300 microg retinol equivalents) were given 5 d/wk for 4 mo. Multi-micronutrient fortification significantly improved the concentrations of hemoglobin (+1.87 g/L; 95% CI: 0.78, 2.96), plasma ferritin (+7.5 microg/L; 95% CI: 2.8, 12.6), body iron (+0.56 mg/kg body weight; 95% CI: 0.29, 0.84), plasma zinc (+0.61 micromol/L; 95% CI: 0.26, 0.95), plasma retinol (+0.041 micromol/L; 95% CI: 0.001, 0.08), and urinary iodine (+22.49 micromol/L; 95% CI: 7.68, 37.31). Fortification reduced the risk of anemia and deficiencies of zinc and iodine by >40%. Parasitic infestation did not affect fortification efficacy, whereas fortification significantly enhanced deworming efficacy, with the lowest reinfection rates in children receiving both micronutrients and Alb. Multi-micronutrient fortification of biscuits is an effective strategy to improve the micronutrient status of Vietnamese schoolchildren and enhances effectiveness of deworming.

Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall, neither iron nor zinc supplementation prevented the progressive growth faltering during infancy, which is common in many developing countries. However, infants who received zinc were less likely to be stunted at the end of the supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher risk of being stunted at the end of the study than girls (P0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P0.01), but with no effect of zinc supplementation on growth in infants not anemic at baseline. Iron supplementation negatively affected linear growth in infants with a birth weight of3500 g (estimated effect size, -0. 14 HAZ score; P0.01), but with no significant effect in infants with a lower birth weight. This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some. Hence, interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies.

Deficiencies of iron and zinc are prevalent worldwide. Interactions between these micronutrients therefore have important consequences, also for supplementation. To investigate effects on hemoglobin and zinc concentrations and interactions of iron and zinc supplementation in infants, data from 4 parallel, randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam were pooled. Infants (n=2468), aged 4-6 mo, were supplemented daily with iron (10 mg) and/or zinc (10 mg) for 6 mo. At 3 sites, infants were given vitamin A capsules (VAC) at recruitment. Combined supplementation reduced prevalences of anemia by 21% (P0.01) and zinc deficiency by 10% (P0.05) but was less effective (P0.05) than supplementation with either iron (28% reduction in anemia) or zinc alone (18% reduction in zinc deficiency). Iron reduced the effect of zinc supplementation (interaction P0.01), but had no separate effect on zinc status, whereas zinc supplementation had a negative effect on hemoglobin concentrations (-2.5 g/L, P0.001), independent of iron supplementation (Pinteraction=0.25). The effect of iron supplementation on hemoglobin concentrations was almost twice as large in boys than in girls (effect size 12.0 vs. 6.8 g/L, respectively). In infants not receiving iron, VAC administration tended to be associated with lower (3.2%, P=0.07) hemoglobin concentrations. Combined supplementation of iron and zinc was safe and effective in reducing the high prevalences of anemia and iron and zinc deficiencies. Zinc supplementation may negatively affect iron status but iron supplementation does not seem to affect zinc status. Furthermore, VAC administration in the absence of iron supplementation may increase the incidence of anemia.

Iron deficiency is prevalent in children and infants worldwide. Zinc deficiency may be prevalent, but data are lacking. Both iron and zinc deficiency negatively affect growth and psychomotor development. Combined iron and zinc supplementation might be beneficial, but the potential interactions need to be verified. In a randomized, placebo-controlled trial using 2 x 2 factorial design, 609 Thai infants aged 4-6 mo were supplemented daily with 10 mg of iron and/or 10 mg of zinc for 6 mo to investigate effects and interactions on micronutrient status and growth. Iron supplementation alone increased hemoglobin and ferritin concentrations more than iron and zinc combined. Anemia prevalence was significantly lower in infants receiving only iron than in infants receiving iron and zinc combined. Baseline iron deficiency was very low, and iron deficiency anemia was almost nil. After supplementation, prevalence of iron deficiency and iron deficiency anemia were significantly higher in infants receiving placebo and zinc than in those receiving iron or iron and zinc. Serum zinc was higher in infants receiving zinc (16.7 +/- 5.2 micromol/L), iron and zinc (12.1 +/- 3.8 micromol/L) or iron alone (11.5 +/- 2.5 micromol/L) than in the placebo group (9.8 +/- 1.9 micromol/L). Iron and zinc interacted to affect iron and zinc status, but not hemoglobin. Iron supplementation had a small but significant effect on ponderal growth, whereas zinc supplementation did not. To conclude, in Thai infants, iron supplementation improved hemoglobin, iron status, and ponderal growth, whereas zinc supplementation improved zinc status. Overall, for infants, combined iron and zinc supplementation is preferable to iron or zinc supplementation alone.

Micronutrient deficiencies during childhood can contribute to impairments in growth, immune competence, and mental and physical development, and the coexistence of several such deficiencies can adversely affect the efficacy of single micronutrient interventions.To assess the prevalence of zinc and iodine deficiency and their interrelationships with vitamin A deficiency and anemia and associations with socio-economic status, hemoglobin type, and anthropometry in a cross-sectional study.A total of 10 primary schools in North East Thailand.Non-fasting venipuncture blood samples and casual urine samples were collected from 567 children aged 6-13 years. Anthropometric measures and serum zinc, albumin, C-reactive protein and urinary iodine, are reported here and integrated with published data on vitamin A, anemia, and socio-economic status.Of the children, 57% had low serum zinc and 83% had urinary iodine levels below the 100 microg/l cutoff. Suboptimal serum zinc and urinary iodine concentrations may result from low intakes of zinc and iodized salt. Significant risk factors for low serum zinc were serum retinol1.05 micromol/l and being male. Those for urinary iodine100 microg/l were height-for-age scoremedian and being female. For serum retinol1.05 micromol/l, risk factors were low hemoglobin, low serum zinc, and9 years, and for low hemoglobin indicative of anemia risk factors were9 years, AE hemoglobinopathy, and serum retinol1.05 micromol/l. Of the children, 60% were at risk of two or more coexisting micronutrient deficiencies, most commonly suboptimal urinary iodine and low serum zinc.The findings emphasize the need for multimicronutrient interventions in North East Thailand.

The isotope dilution technique involving deuterated retinol has been developed to quantitatively estimate total body reserves of vitamin A in humans. The technique provided good estimates in comparison to hepatic vitamin A concentrations in Bangladeshi surgical patients. Kinetic studies in the United States, Bangladesh, and Guatemala indicated the mean equilibration time of 17 to 20 days irrespective of the size of hepatic reserves. Due to the controversy surrounding the efficacy of a carotene-rich diet on improvement of vitamin A status, the isotope dilution technique was proposed to pursue this research question further (IAEA's coordinated research program). In the Philippines, schoolchildren with low serum retinol concentrations showed significant improvement in total body vitamin A stores following intake of carotene-rich foods (orange fruits and vegetables), using a three-day deuterated-retinol-dilution procedure. When Chinese kindergarten children were fed green and yellow vegetables during the winter, their total body vitamin A stores were sustained as compared to a steady decline of vitamin A stores in the control children. Likewise, daily consumption of purified beta-carotene or a diet rich in provitamin A carotenoids were shown to prevent a loss in total body vitamin A stores among Thai lactating women during the rice-planting season. These studies demonstrate potentials of the isotope dilution technique to evaluate the impact of provitamin A carotenoid intervention programs.

Anemia and co-existing deficiencies of zinc, iron, iodine, and vitamin A occur among children in many developing countries including NE Thailand, probably contributing to impairments in growth, immune competence, and cognition. Sustainable strategies are urgently required to combat these deficiencies. We assessed the efficacy of a micronutrient-fortified seasoning powder served with a school lunch on reducing anemia and improving the micronutrient status of rural NE Thai children. Children (n = 569) aged 5.5-13.4y from 10 schools were randomly assigned to receive a seasoning powder either unfortified or fortified with zinc (5 mg), iron (5 mg), vitamin A (270 microg), and iodine (50 microg) (per serving) and incorporated into a school lunch prepared centrally and delivered 5 d/wk for 31 wk. Teachers monitored school lunch consumption. Baseline and final micronutrient status, hemoglobinopathies, and infection or inflammation were assessed from blood and urine samples. For the primary outcome, anemia (based on hemoglobin), no intervention effect was apparent (odds ratio: 1.02 95% CI: 0.69, 1.51) after adjustment for design strata. The odds of zinc (based on serum zinc) and urinary iodine deficiency in the fortified group were 0.63 (0.42, 0.94) and 0.52 (0.38, 0.71) times those in the unfortified group, respectively. Fortification had no effect on serum retinol (0.61: 0.25,1.51), ferritin (1.12: 0.43, 2.96), or mean red cell volume (1.16: 0.82, 1.64). Therefore, a micronutrient-fortified seasoning powder is a promising vehicle for improving zinc, iodine, and hemoglobin status, and its potential for incorporation into lunch programs in day care centers and schools in NE Thailand warrants investigation.

Background Reductions in iodine and zinc deficiencies and improvements in hemoglobin were achieved from a micronutrient-fortified seasoning powder consumed in school lunches by children in northeast Thailand. Objective The objective was to determine whether fortification with 4 micronutrients in a school lunch results in changes in children's growth, morbidity, and cognitive function compared with no fortification. Design In a randomized controlled trial of 569 children aged 5.5-13.4 y from 10 schools, we compared the efficacy of a seasoning powder fortified with or without 5 mg Fe, 5 mg Zn, 50 mug I, and 270 mug vitamin A per serving consumed with a school lunch 5 d/wk. Here we report on results of the secondary functional outcomes. Results The groups were comparable concerning compliance and loss to follow-up. The intervention had no statistically significant effect on anthropometric measures over 31 wk, but reduced the incidence of respiratory-related illnesses [rate ratio (RR): 0.83; 95% CI: 0.73, 0.94], symptoms of runny nose (RR: 0.80; 95% CI: 0.70, 0.92), cough (RR: 0.80; 95% CI: 0.66, 0.96), and diarrhea (RR: 0.38; 95% CI: 0.16, 0.90). For the visual recall test, those in the fortified group recalled 0.5 more items (95% CI: 0.1, 0.9) than did the controls. There were no statistically significant differences between groups in the results of the digits forward and backward tests or in school grades at the conclusion of the 2 semesters. Conclusion The beneficial effects on morbidity and visual recall over a short period, in addition to some biochemical improvements, highlight the potential of this micronutrient-fortified seasoning powder supplied in a school lunch. This trial was registered at clinical trials.gov as ACTRN12605000341628.