Christine Hotz

Biofortification: a new tool to reduce micronutrient malnutrition.

Background The density of minerals and vitamins in food staples eaten widely by the poor may be increased either through conventional plant breeding or through the use of transgenic techniques, a process known as biofortification. Objective HarvestPlus seeks to develop and distribute varieties of food staples (rice, wheat, maize, cassava, pearl millet, beans, and sweet potato) that are high in iron, zinc, and provitamin A through an interdisciplinary, global alliance of scientific institutions and implementing agencies in developing and developed countries. Methods In broad terms, three things must happen for biofortification to be successful. First, the breeding must be successful—high nutrient density must be combined with high yields and high profitability. Second, efficacy must be demonstrated—the micronutrient status of human subjects must be shown to improve when they are consuming the biofortified varieties as normally eaten. Thus, sufficient nutrients must be retained in processing and cooking and these nutrients must be sufficiently bioavailable. Third, the biofortified crops must be adopted by farmers and consumed by those suffering from micronutrient malnutrition in significant numbers. Results Biofortified crops offer a rural-based intervention that, by design, initially reaches these more remote populations, which comprise a majority of the under-nourished in many countries, and then penetrates to urban populations as production surpluses are marketed. In this way, biofortification complements fortification and supplementation programs, which work best in centralized urban areas and then reach into rural areas with good infrastructure. Conclusions Initial investments in agricultural research at a central location can generate high recurrent benefits at low cost as adapted, biofortified varieties become available in country after country across time at low recurrent costs.

Indicators of zinc status at the population level: a review of the evidence

The role of zinc deficiency as an important cause of morbidity and impaired linear growth has prompted the need to identify indicators of population zinc status. Three indicators have been recommended - prevalence of zinc intakes below the estimated average requirement (EAR), percentage with low serum zinc concentrations, and percentage of children aged < 5 years who are stunted. This review outlines steps to estimate the prevalence of inadequate intakes, and confirm their validity based on the EARs set by International Zinc Nutrition Collaborative Group. Next, the appropriateness of serum zinc as a biochemical marker for population zinc status is confirmed by a summary of: (a) the response of serum zinc concentrations to zinc intakes; (b) usefulness of serum zinc concentrations to predict functional responses to zinc interventions; (c) relationship between initial serum zinc and change in serum zinc in response to interventions. Height- or length-for-age was chosen as the best functional outcome after considering the responses of growth, infectious diseases (diarrhoea, pneumonia), and developmental outcomes in zinc supplementation trials and correlation studies. The potential of other zinc biomarkers such as zinc concentrations in hair, cells, zinc-metalloenzymes, and zinc-binding proteins, such as metallothionein, is also discussed. Molecular techniques employing reverse transcriptase (RT)-polymerase chain reaction to measure mRNA in metallothionein and ZIP1 transporter hold promise, as do kinetic markers such as exchangeable zinc pools (EZP) and plasma zinc turnover rates. More research is needed to establish the validity, specificity, sensitivity, and feasibility of these new biomarkers, especially in community-settings.

Conclusions of the Joint WHO/UNICEF/IAEA/IZiNCG Interagency Meeting on Zinc Status Indicators

Zinc deficiency is an important cause of morbidity in developing countries, particularly among young children, yet little information is available on the global prevalence of zinc deficiency. A working group meeting was convened by the World Health Organization (WHO), the United Nations Childrens Fund (UNICEF), the International Atomic Energy Agency (IAEA), and the International Zinc Nutrition Consultative Group (IZiNCG) to review methods of assessing population zinc status and provide standard recommendations for the use of specific biochemical, dietary, and functional indicators of zinc status in populations. The recommended biochemical indicator is the prevalence of serum zinc concentration less than the age/sex/time of day-specific cutoffs; when the prevalence is greater than 20%, intervention to improve zinc status is recommended. For dietary indicators, the prevalence (or probability) of zinc intakes below the appropriate estimated average requirement (EAR) should be used, as determined from quantitative dietary intake assessments. Where the prevalence of inadequate intakes of zinc is greater than 25%, the risk of zinc deficiency is considered to be elevated. Previous studies indicate that stunted children respond to zinc supplementation with increased growth. When the prevalence of low height-for-age is 20% or more, the prevalence of zinc deficiency may also be elevated. Ideally, all three types of indicators would be used together to obtain the best estimate of the risk of zinc deficiency in a population and to identify specific subgroups with elevated risk. These recommended indicators should be applied for national assessment of zinc status and to indicate the need for zinc interventions. The prevalence of low serum zinc and inadequate zinc intakes may be used to evaluate their impact on the target populations zinc status.

A large-scale intervention to introduce orange sweet potato in rural Mozambique increases vitamin A intakes among children and women.

β-Carotene-rich orange sweet potato (OSP) has been shown to improve vitamin A status of infants and young children in controlled efficacy trials and in a small-scale effectiveness study with intensive exposure to project inputs. However, the potential of this important food crop to reduce the risk of vitamin A deficiency in deficient populations will depend on the ability to distribute OSP vines and promote its household production and consumption on a large scale. In rural Mozambique, we conducted a randomised, controlled effectiveness study of a large-scale intervention to promote household-level OSP production and consumption using integrated agricultural, demand creation/behaviour change and marketing components. The following two intervention models were compared: a low-intensity (1 year) and a high-intensity (nearly 3 years) training model. The primary nutrition outcomes were OSP and vitamin A intakes by children 6-35 months and 3-5·5 years of age, and women. The intervention resulted in significant net increases in OSP intakes (model 1: 46, 48 and 97 g/d) and vitamin A intakes (model 1: 263, 254 and 492 μg retinol activity equivalents/d) among the younger children, older children and women, respectively. OSP accounted for 47-60 % of all sweet potato consumed and, among reference children, provided 80 % of total vitamin A intakes. A similar magnitude of impact was observed for both models, suggesting that group-level trainings in nutrition and agriculture could be limited to the first project year without compromising impact. Introduction of OSP to rural, sweet potato-producing communities in Mozambique is an effective way to improve vitamin A intakes.

The usefulness of in vitro models to predict the bioavailability of iron and zinc: A consensus statement from the HarvestPlus expert consultation

A combination of dietary and host-related factors determines iron and zinc absorption, and several in vitro methods have been developed as preliminary screening tools for assessing bioavailability. An expert committee has reviewed evidence for their usefulness and reached a consensus. Dialyzability (with and without simulated digestion) gives some useful information but cannot predict the correct magnitude of response and may sometimes predict the wrong direction of response. Caco-2 cell systems (with and without simulated digestion) have been developed for iron availability, but the magnitude of different effects does not always agree with results obtained in human volunteers, and the data for zinc are too limited to draw conclusions about the validity of the method. Caco-2 methodologies vary significantly between laboratories and require experienced technicians and good quality cell culture facilities to obtain reproducible results. Algorithms can provide semi-quantitative information enabling diets to be classified as high, moderate, or low bioavailability. While in vitro methods can be used to generate ideas and develop hypotheses, they cannot be used alone for important decisions concerning food fortification policy, selection of varieties for plant breeding programs, or for new product development in the food industry. Ultimately human studies are required for such determinations.

Very Low Adequacy of Micronutrient Intakes by Young Children and Women in Rural Bangladesh Is Primarily Explained by Low Food Intake and Limited Diversity

Documentation of micronutrient intake inadequacies among developing country populations is important for planning interventions to control micronutrient deficiencies. The objective of this study was to quantify micronutrient intakes by young children and their primary female caregivers in rural Bangladesh. We measured 24-h dietary intakes on 2 nonconsecutive days in a representative sample of 480 children (ages 24-48 mo) and women in 2 subdistricts of northern Bangladesh by using 12-h weighed food records and subsequent 12-h recall in homes. We calculated the probability of adequacy (PA) of usual intakes of 11 micronutrients and an overall mean PA, and evaluated dietary diversity by counting the total number of 9 food groups consumed. The overall adequacy of micronutrient intakes was compared to dietary diversity scores using correlation and multivariate regression analyses. The overall mean prevalence of adequacy of micronutrient intakes for children was 43% and for women was 26%. For children, the prevalence of adequate intakes for each of the 11 micronutrients ranged from a mean of 0 for calcium to 95% for vitamin B-6 and was <50% for iron, calcium, riboflavin, folate, and vitamin B-12. For women, mean or median adequacy was <50% for all nutrients except vitamin B-6 and niacin and was <1% for calcium, vitamin A, riboflavin, folate, and vitamin B-12. The mean PA (MPA) was correlated with energy intake and dietary diversity, and multivariate models including these variables explained 71-76% of the variance in MPA. The degree of micronutrient inadequacy among young children and women in rural Bangladesh is alarming and is primarily explained by diets low in energy and little diversity of foods.

From harvest to health: Challenges for developing biofortified staple foods and determining their impact on micronutrient status

Background The use of conventional breeding techniques and biotechnology to improve the micronutrient quality of staple crops is a new strategy to address micronutrient deficiencies in developing countries. This strategy, referred to as “biofortification,” is being developed and implemented through the international alliance of HarvestPlus to improve iron, zinc, and vitamin A status in low-income populations. Objective The objective of this paper is to review the challenges faced by nutritionists to determine and demonstrate the ability of biofortified crops to have an impact on the nutritional and health status of target populations. Methods We reviewed available published and unpublished information that is needed to design and evaluate this strategy, including issues related to micronutrient retention in staple foods, micronutrient bioavailability from plant foods, and evidence for the efficacy of high-micronutrient-content staple foods to improve micronutrient status. Results Further information is needed on the retention of micronutrients in staple foods, in particular of provitamin A carotenoids, when stored and prepared under different conditions. The low bioavailability of iron from staple foods and the ability to demonstrate an impact on zinc status are specific challenges that need to be addressed. In target countries, infections and other micronutrient deficiencies may confound the ability to affect micronutrient status, and this must be taken into account in community-based studies. Conclusions Information to date suggests that biofortification has the potential to contribute to increased micronutrient intakes and improved micronutrient status. The success of this strategy will require the collaboration between health and agriculture sectors.

The Quantity of Zinc Absorbed from Wheat in Adult Women Is Enhanced by Biofortification

Biofortification of crops that provide major food staples to large, poor rural populations offers an appealing strategy for diminishing public health problems attributable to micronutrient deficiencies. The objective of this first-stage human study was to determine the increase in quantity of zinc (Zn) absorbed achieved by biofortifying wheat with Zn. Secondary objectives included evaluating the magnitude of the measured increases in Zn absorption as a function of dietary Zn and phytate. The biofortified and control wheats were extracted at high (95%) and moderate (80%) levels and Zn and phytate concentrations measured. Adult women with habitual diets high in phytate consumed 300 g of 95 or 80% extracted wheat as tortillas for 2 consecutive days using either biofortified (41 mg Zn/g) or control (24 mg Zn/g) wheat. All meals for the 2-d experiment were extrinsically labeled with Zn stable isotopes and fractional absorption of Zn determined by a dual isotope tracer ratio technique. Zn intake from the biofortified wheat diet was 5.7 mg/d (72%) higher at 95% extraction (P < 0.001) and 2.7 mg/d (68%) higher at 80% extraction compared with the corresponding control wheat (P = 0.007). Zn absorption from biofortified wheat meals was (mean +/- SD) 2.1 +/- 0.7 and 2.0 +/- 0.4 mg/d for 95 and 80% extraction, respectively, both of which were 0.5 mg/d higher than for the corresponding control wheat (P < 0.05). Results were consistent with those predicted by a trivariate model of Zn absorption as a function of dietary Zn and phytate. Potentially valuable increases in Zn absorption can be achieved from biofortification of wheat with Zn.

Recent Advances in Knowledge of Zinc Nutrition and Human Health

Zinc deficiency increases the risk and severity of a variety of infections, restricts physical growth, and affects specific outcomes of pregnancy. Global recognition of the importance of zinc nutrition in public health has expanded dramatically in recent years, and more experience has accumulated on the design and implementation of zinc intervention programs. Therefore, the Steering Committee of the International Zinc Nutrition Consultative Group (IZiNCG) completed a second IZiNCG technical document that reexamines the latest information on the intervention strategies that have been developed to enhance zinc nutrition and control zinc deficiency. In particular, the document reviews the current evidence regarding preventive zinc supplementation and the role of zinc as adjunctive therapy for selected infections, zinc fortification, and dietary diversification or modification strategies, including the promotion and protection of breastfeeding and biofortification. The purposes of this introductory paper are to summarize new guidelines on the assessment of population zinc status, as recommended by the World Health Organization (WHO), the United Nations Childrens Fund (UNICEF), the International Atomic Energy Agency (IAEA), and IZiNCG, and to provide an overview on several new advances in zinc metabolism. The following papers will then review the intervention strategies individually.

The Current High Prevalence of Dietary Zinc Inadequacy among Children and Women in Rural Bangladesh Could Be Substantially Ameliorated by Zinc Biofortification of Rice

Rural Bangladeshi populations have a high risk of zinc deficiency due to their consumption of a predominantly rice-based diet with few animal-source foods. Breeding rice for higher zinc content would offer a sustainable approach to increase the populations zinc intakes. The objectives of the study were to quantify usual rice and zinc intakes in young children and their adult female primary caregivers and to simulate the potential impact of zinc-biofortified rice on their zinc intakes. We measured dietary intake in a representative sample of 480 children (ages 24-48 mo) and their female caregivers residing in 2 rural districts of northern Bangladesh. Dietary intakes were estimated by 12-h weighed records and 12-h recall in homes on 2 nonconsecutive days. Serum zinc concentrations were determined in a subsample of children. The median (25th, 75th percentile) rice intakes of children and female caregivers were 134 (99, 172) and 420 (365, 476) g raw weight/d, respectively. The median zinc intakes were 2.5 (2.1, 2.9) and 5.4 (4.8, 6.1) mg/d in children and women, respectively. Twenty-four percent of children had low serum zinc concentrations ( < 9.9 micromol/L) after adjusting for elevated acute phase proteins. Rice was the main source of zinc intake, providing 49 and 69% of dietary zinc to children and women, respectively. The prevalence of inadequate zinc intakes was high in both the children (22%) and women (73-100%). Simulated increases in rice zinc content to levels currently achievable through selective breeding decreased the estimated prevalence of inadequacy to 9% in children and 20-85% in women, depending on the assumptions used to estimate absorption. Rural Bangladeshi children and women have inadequate intakes of zinc. Zinc biofortification of rice has the potential to markedly improve the zinc adequacy of their diets.