Nutritional and Health-Related Environmental Studies (NAHRES)

Using nuclear techniques to develop and evaluate food-based strategies to prevent micronutrient deficiencies in young children.

Brief summary

Maternal and child nutrition during pregnancy and up to two years of age are critical for a child’s future. Appropriate feeding practices are essential for achieving optimal child growth, development and health. The World Health Organization and UNICEF recommend exclusive breastfeeding for the first six months of life and thereafter, infants should be given nutritionally adequate and safe complementary foods while breastfeeding continues up to the age of two years or beyond. In contrast to the high nutritional requirements in the first two years of life, traditional complementary foods in low-income countries are low in nutrient density. These foods are predominantly plant-based and generally monotonous with high contents of phytic acid and phenolic compounds, but negligible quantities of animal source foods or fruits and vegetables rich in ascorbic-acid, vitamin A and provitamin A carotenoids. They provide insufficient bioavailable amounts of key nutrients such as iron, zinc and vitamin A. Besides, the concentration of certain nutrients can be low in human milk due to mothers’ poor status and low intake. The proposed CRP will contribute new knowledge on dietary diversification and modification approaches that optimize trace element bioavailability and increase trace element and vitamin density to enhance the nutrient intake from plant-based local complementary foods and human milk. Stable isotope methods will be used to evaluate trace element bioavailability, zinc and vitamin A status and infants’ human milk intake. The overall goal is to contribute to the design of effective, feasible and sustainable interventions based on locally available foods that help prevent micronutrient deficiencies of infants and young children.


Adequate nutrition during infancy and early childhood is fundamental to the development of each child’s full human potential. The period from birth to two years of age is a “critical window” for the promotion of optimal growth, health and behavioural development. WHO and UNICEF jointly developed the global strategy for infant and young child feeding that emphasizes the need for comprehensive national policies on promoting appropriate feeding for infants and young children (1). It is a guide for action and recommends exclusive breastfeeding for the first six months of life. Thereafter infants should receive nutritionally adequate and safe complementary foods while breastfeeding continues for up to two years of age or beyond. The importance of the window of opportunity from pregnancy through age two has been recently reiterated by the launch of two initiatives: (I) “1,000 Days: Change a Life, Change the Future – Partnering to Reduce Child Malnutrition”, which supports early childhood malnutrition interventions (, and (II) “Scaling Up Nutrition (SUN): A Framework for Action”, which outlines key priorities for action to improve infant and child nutrition (

In resource-poor households in low-income countries traditional complementary foods are predominantly plant-based and generally provide insufficient amounts of certain key nutrients (particularly iron, zinc and vitamin A) to meet the recommended nutrient intakes during the age range of 6-24 months (2). The foods used are monotonous with emphasis on unrefined cereals or legumes that contain high amounts of phytic acid and phenolic compounds and with negligible quantities of animal source foods, and fruits and vegetables rich in ascorbic-acid, vitamin A and provitamin A carotenoids. As a result, these home prepared complementary foods often have low nutrient density and low bioavailability of trace elements, especially of iron and zinc (3). In addition, mothers’ poor status and low intake of some micronutrients can affect the concentration of these micronutrients in human milk. In the case of vitamin A, the content in human milk is dependent on mothers’ status and intake and is the main determinant of infant status because stores are low at birth (4). In contrast, in the case of iron and zinc, the concentrations of these trace elements in human milk are normally low, regardless of maternal intake and stores, and therefore the infant’s reserves at birth determine infant status (5, 6).

Options to improve trace element bioavailability

The inhibitory effect of phytic acid, the major phosphorus storage compound in the grain, on iron and zinc absorption has been demonstrated in adults and infants in studies with isotopic tracers (3, 7, 8, 9). Degradation of phytate can be accomplished domestically by activating the native phytase using traditional household methods such as fermentation, germination and soaking, or commercially by adding exogenous phytase. Commercial dephytinization can lead to complete degradation of phytate in cereal- and/or legume-based complementary foods, whereas household strategies can remove only about 20-50% of the phytate (10, 11). Almost complete degradation has resulted in increases in the absorption of iron from cereal porridges in adults (12) and in the iron bioavailability from soy infant formula to infants (9). Similarly, almost complete dephytinization of a cereal-based complementary food showed a beneficial effect on fractional absorption of zinc in adults (13). It has not been investigated whether the partial reduction of phytate by household strategies can enhance trace element absorption from plant-based complementary foods in infants (3). However, Hurrell et al concluded that phytic acid:iron molar ratios should be decreased to below 1:1 and preferably below 0.4:1 to achieve a 2-fold increase in iron absorption (14). For zinc, dietary phytate:zinc molar ratios below 18:1 are desired to markedly improve zinc absorption (3). Phenolic compounds are also strong inhibitors of trace element absorption (15, 16, 17). They are present in plant foods. For example, in common beans both polyphenols and phytic acid contribute to low iron bioavailability and iron absorption improved in young women only after dephytinization and dehulling of the beans (17).

An unidentified component of muscle tissue from meat, poultry or fish significantly enhances non-heme iron bioavailability, especially from phytate-containing cereal- and legume-based meals. This effect has been demonstrated in infants and adults (18, 19, 20). In addition, meat, in particular red meat, provides highly bioavailable heme iron and zinc. Ascorbic acid substantially enhances iron absorption, primarily by reducing ferric iron to the ferrous state and thus preventing its reaction with inhibitors (21). The ability of ascorbic acid to overcome the inhibiting effect of phytic acid depends on the levels of iron, phytic acid, and ascorbic acid in the food or meal. For meals containing low to medium levels of inhibitors, a molar ratio of ascorbic acid:iron of 2:1 enhances iron absorption, whereas for meals containing high levels of inhibitors, molar ratios of ascorbic acid:iron above 4:1 might be required (22). Human milk could be an alternative source of ascorbic acid for breastfed children in settings where fruits and fruit juices are rarely included in the young child’s diet due to limited availability, affordability, or tradition. However, no significant difference in iron bioavailability was found in Bangladeshi infants and children between a local complementary food based on rice and lentils consumed with water and that consumed with human milk, although human milk contributed significant quantities of ascorbic acid (23). A follow-up study in Pakistani infants confirmed that data on the enhancing effect of added ascorbic acid on iron bioavailability cannot be extrapolated to when human milk is the source of ascorbic acid (24).

Examples of interventions to improve iron and zinc bioavailability from plant-based complementary foods include the promotion of adding animal-source foods (muscle tissue) and ascorbic acid sources (fruits, fruit juices) to complementary foods. To date, there are significant gaps in our knowledge on dose-response effects of different types of muscle tissue (e.g., red meat, fish, or chicken) on trace element absorption when added to different inhibitory plant-based complementary foods. Therefore, assessing minimum amounts of animal-source foods required to achieve a significant enhancing effect would be critical in resource-poor settings, where increasing dietary diversity is often constrained by a lack of resources for producing and purchasing higher quality foods. Other approaches to improve iron and zinc bioavailability include the degradation of phytic acid by adding exogenous phytase or by fermentation, germination, and soaking to activate the native phytase, as outlined above. Assessing food safety (e.g., availability of adequate supplies of safe water), feasibility (in particular time requirements for process) and efficacy of different household modification approaches would provide important new evidence on how to enhance nutrient intake. A combination of approaches, e.g. enrichment with animal-source foods or ascorbic acid-rich foods and dephytinization of grains or legumes might be necessary to increase the likelihood of overcoming the low micronutrient content of plant-based complementary foods used in low-income countries.

Options to improve provitamin A carotenoid and vitamin A intake

Animal source foods such as liver and eggs have a high density of preformed vitamin A (retinol), but are often scarce and expensive in developing countries. Therefore, the consumption of dark-green leafy vegetables and yellow- and orange-colored fruits and vegetables is promoted because of their content of provitamin A carotenoids, mainly ß-carotene. In developing countries, provitamin A carotenoids in vegetables and fruits provide the majority of daily vitamin A intakes. The human body can convert these provitamin A carotenoids into the active form of vitamin A, retinol and its derivatives. However, this conversion is rather inefficient because ß-carotene is tightly bound by plant cellular matrices. Data from human studies show that the conversion efficiency of dietary ß-carotene is in the range of 3.6-28:1 by weight. There is evidence that provitamin A carotenoids in orange fruits and vegetables have a higher bioconversion efficiency than those in dark-green leafy vegetables (25). The bioavailability of food carotenoids and the efficiency of conversion of provitamin A carotenoids into vitamin A are affected by chemical structure of the provitamin A carotenoid, food matrix, food preparation, fat content of a meal, amount of provitamin A carotenoids in a meal, interactions with other carotenoids and/or micronutrients in the diet, and host factors including host vitamin A status and host genetic characteristics (26). Ingesting fat along with carotenoids is crucial for carotenoid absorption. Data from Filipino schoolchildren suggest that only small amounts of dietary fat, 2.4 g per meal, are needed for optimal absorption of provitamin A carotenoids from cooked yellow and green-leafy vegetable meals (27). Another potentially good source of pre-formed vitamin A, particularly for infants, is human milk. Colostrum is rich in pre-formed vitamin A and the mature milk of well-nourished women contains sufficient preformed vitamin A to meet the infant's metabolic requirements and to accumulate safe and adequate stores of the vitamin (28).

The proposed CRP will focus on sustainable approaches to eradicate vitamin A deficiency in young children as a public health problem through increased intake of provitamin A carotenoids and preformed vitamin A from local complementary foods and increased intake of retinol from human milk. Examples of such approaches are the promotion of adding foods rich in provitamin A carotenoids or animal-source foods such as liver and eggs that are rich in preformed vitamin A to local complementary foods. Evaluating the effect of these two approaches on vitamin A status would yield important information on minimum amounts of different foods required to improve vitamin A status. In addition, approaches to increase human milk retinol through increased lactating mothers’ consumption of provitamin A carotenoids or preformed vitamin A could be assessed and their effect on the infants’ vitamin A intake and status evaluated. This includes the consumption of fortified cooking oil with preformed vitamin A, an effective and low cost intervention at large-scale that is adopted in an increasing number of countries. The absorption and metabolism of vitamin A, iron and zinc are interconnected and therefore, the effect of poor status of one micronutrient on absorption and utilisation of other micronutrients should be considered (29, 30).

In conclusion, there is need for innovative strategies to improve the nutritional quality of local plant-based complementary foods and human milk consumed by infants and young children in resource-poor areas. Strategies include interventions that promote knowledge and skills to maximise the use of locally-available, high-quality micronutrient dense foods, as outlined above. However, there will be no single universal “best” package of interventions to improve the quality of complementary feeding because both the needs of and the options for accessing appropriate foods in the target population vary greatly. Aspects such as practicability, cultural acceptance and palatability will be crucial in ensuring adoption of proposed new practices and thus sustainable improvement of complementary feeding. In this CRP, stable isotope methods will be used to evaluate trace element bioavailability, zinc and vitamin A status and infants’ human milk intake. The experimental evidence gained on innovative strategies of dietary modifications to enhance the nutrient intake from plant-based local complementary foods and human milk could help prevent the development of micronutrient deficiencies and improve the quality of growth in early life.

Analytical techniques to be used

Stable isotopes of iron and zinc will be used to measure iron and zinc bioavailability from improved complementary foods. To evaluate the impact of improved zinc intake and bioavailability, stable isotopes of zinc will be used to measure the exchangeable zinc pool. The analysis of the stable iron and zinc isotopes in biological samples will be undertaken using thermal ionization mass spectrometry (TIMS) or inductively-coupled plasma mass spectrometry (ICPMS).

To evaluate the efficacy of improved complementary feeding on infants’ vitamin A status, the total body vitamin A pool size will be estimated using vitamin A labelled either with the stable isotope of hydrogen (deuterium, 2H) or with the stable isotope of carbon (13C). For the estimation of total body vitamin A pool size gas-chromatograph-mass spectrometry (GC-MS) or gas-chromatograph-combustion-isotope ratio mass spectrometry (GC-C-IRMS) will be used depending on whether deuterium labelled retinol or carbon-13 labelled retinol is measured.

To assess nutrient intake from human milk, the amount of human milk taken in by the infant will be measured using the well-established deuterium oxide ‘dose-to-mother’ technique. Deuterium enrichment of urine and/or saliva samples will be analysed by Fourier Transformed Infrared Spectrometer (FTIR) or by isotope ratio mass spectrometry (IRMS).


Overall objective

The overall objective is to contribute new information on infant feeding practices and body composition of infants and young children during the first 2 years of life.

Specific Research Objectives (Purpose)

The CRP intends to:

  • Evaluate the efficacy of single or combined strategies to degrade phytic acid and to enrich with animal-source foods or ascorbic acid-rich foods on bioavailability of iron and zinc from plant-based local complementary foods.
  • Evaluate the dose-response effects of dietary enhancers such as muscle tissue and ascorbic acid on bioavailability of iron and zinc from plant-based local complementary foods.
  • Evaluate the dose-response effects of animal-source and other nutrient-dense foods added to plant-based local complementary foods on exchangeable zinc and total body vitamin A pool size.
  • Evaluate the efficacy of approaches to increase lactating mothers’ provitamin A carotenoid or preformed vitamin A intake on human milk retinol and infants’ vitamin A intake and status.

Expected research outputs
  • New data on food-based strategies to improve iron and zinc intake from plant-based local complementary foods.
  • New data on amounts of different dietary enhancers required to improve bioavailability of trace elements from plant-based local complementary foods (dose-response effects).
  • New data on dose-response effects of animal-source and other nutrient-dense foods added to plant-based local complementary foods on exchangeable zinc and total body vitamin A pool size..
  • New data on food-based strategies to enhance human milk retinol concentration, infants’ vitamin A intake and total body vitamin A pool size.
  • Publications in the form of scientific reports and peer reviewed papers.

Expected Research Outcomes

To contribute to best practices using food-based strategies to inform the design of effective and practical interventions aimed at preventing micronutrient deficiencies in infants and young children in developing countries.

Proposal submission forms

Research institutions in Member States interested in participating in this CRP are invited to submit proposals directly to the Research Contracts Administration Section (NACA) of the International Atomic Energy Agency: or to Ms Cornelia Loechl: The forms can be downloaded from For more information about research contracts and research agreements, please visit our web-site:

Deadline for submission of proposals

Proposals must be received no later than than 31 August 2011.
Transmission via Email is acceptable if all required signatures are scanned.

For additional information, please contact:
Cornelia Loechl
Nutrition Scientist
Nutritional and Health-Related Environmental Studies Section
Division of Human Health
International Atomic Energy Agency (IAEA)
Wagramer Strasse 5
A-1400 Vienna, Austria
Phone: +43-1-2600-21635 or 21674
Fax: +43-1-2600-7

  1. WORLD HEALTH ORGANIZATION, UNICEF, Global Strategy for Infant and Young Child Feeding, WHO, Geneva (2003).
  2. DEWEY, K.G., BROWN, K.H., Update on technical issues concerning complementary feeding of young children in developing countries and implications for intervention programs, Food Nutr Bull. 24(1) (2003) 5-28.
  3. GIBSON, R.S., BAILEY, K.B., GIBBS, M. et al., A review of phytate, iron, zinc and calcium concentrations in plant-based complementary foods used in low-income countries and implications for bioavailability, Food Nutr Bull. 31(2) (2010) S134-S146.
  4. BLACK, R.E., ALLEN, L.H., BHUTTA, Z.A., et al., Maternal and child undernutrition: global and regional exposures and health consequences, The Lancet 371 (2008) 243-260.
  5. DALLMAN, P.R., Changing Iron Needs from Birth through Adolescence, Nutritional Anemias, edited by S.J. Fomon and S. Zlotkin, Nestle Nutrition Workshop Series 30 (1992) 29-38.
  6. KREBS, N.F., Dietary Zinc and Iron Sources, Physical Growth and Cognitive Development of Breastfed Infants, J. Nutr. 130 (2000) 358S-360S.
  7. GIBSON, R.S., ANDERSON, V.P., A review of interventions based on dietary diversification or modification strategies with the potential to enhance intakes of total and absorbable zinc, Food Nutr Bull. 30(1) (2009) S108-S143.
  8. HAMBIDGE, K.M., MILLER, L.V., WESTCOTT, J.E. et al., Zinc bioavailability and homeostasis, Am J Clin Nutr 91 (2010) 1478S-83S.
  9. DAVIDSSON, L., GALAN, P., KASTENMAYER, P., et al., Iron Bioavailability Studied in Infants : The Influence of Phytic Acid and Ascorbic Acid in Infant Formulas Based on Soy Isolate, Pediatr Res 36 (1994) 816-822.
  10. EGLI, I.M., Traditional Food Processing Methods to Increase Mineral Bioavailability from Cereal and Legume Based Weaning Foods, PhD thesis, Swiss Federal Institute of Technology, Zurich (2003).
  11. HOTZ, C., GIBSON, R.S., Assessment of Home-Based Processing Methods To Reduce the Phytate Content and Phytate/Zinc Molar Ratio of White Maize (Zea mays), J. Agric. Food Chem. 49 (2001) 692-698.
  12. HURRELL, R.F., REDDY, M.B., JUILLERAT, M.-A., et al., Degradation of phytic acid in cereal porridges improves iron absorption by human subjects, Am J Clin Nutr 77 (2003) 1213-9.
  13. EGLI, I., DAVIDSSON, L., ZEDER, C., et al., Dephytinization of a Complementary Food Based on Wheat and Soy Increases Zinc, but Not Copper, Apparent Absorption in Adults, J. Nutr. 134 (2004) 1077-1080.
  14. HURRELL, R.F., Phytic Acid Degradation as a Means of Improving Iron Absorption, Int. J. Vitam. Nutr. Res. 74(6) (2004) 445-452.
  15. HURRELL, R.F., REDDY, M., COOK, J.D., Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages, Br J Nutr. 81 (1999) 289-295.
  16. TUNTAWIROON, M., SRITONGKUL, N., BRUNE, M., et al., Dose-dependent inhibitory effect of phenolic compounds in foods on nonheme-iron absorption in men, Am J Clin Nutr 53 (1991) 554-7.
  17. PETRY, N., EGLI, I., ZEDER, C., et al., Polyphenols and Phytic Acid Contribute to the Low Iron Bioavailability from Common Beans in Young Women, J. Nutr. 140 (2010) 1977-1982.
  18. HURRELL, R.F., REDDY, M.B., JUILLERAT, M., et al., Meat Protein Fractions Enhance Nonheme Iron Absorption in Humans, J. Nutr. 136 (2006) 2808-2812.
  19. ENGELMANN, M.D.M., DAVIDSSON, L., SANDSTROM, B., et al., The Influence of Meat on Nonheme Iron Absorption in Infants, Pediatr Res 43 (1998) 768-773.
  20. BACH KRISTENSEN, M., HELS, O., MORBERG, C., et al., Pork meat increases iron absorption from a 5-day fully controlled diet when compared to a vegetarian diet with similar vitamin C and phytic acid content, Br J Nutr. 94 (2005) 78-83.
  21. HALLBERG, L., HULTHEN, L., Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron, Am J Clin Nutr 71 (2000) 1147-60.
  22. HURRELL, R.F., Fortification: Overcoming Technical and Practical Barriers, J. Nutr. 132 (2002) 806S-812S.
  23. DAVIDSSON, L., JAMIL, K.A., SARKER, S.A., et al., Human milk as a source of ascorbic acid: no enhancing effect on iron bioavailability from a traditional complementary food consumed by Bangladeshi infants and young children, Am J Clin Nutr 79 (2004) 1073-7.
  24. JIWANI, A., DAVIDSSON, L., ZEDER, C., et al., Iron bioavailability from a traditional complementary food « khichuri » consumed by Pakistani infants; the effect of added ascorbic acid and human milk intake, Abstract, World Congress of Paediatric Gastroenterology, Hepatology and Nutrition, Iguazu Falls, Brazil, 16-20 August (2008).
  25. TANG, G., Bioconversion of dietary provitamin A carotenoids to vitamin A in humans, Am J Clin Nutr 91 (2010) 1468S-73S.
  26. TANUMIHARDJO S.A., PALACIOS N., PIXLEY K.P., Provitamin A Carotenoid Bioavailability: What Really Matters?, Int. J. Vitam. Nutr. Res. 80(4-5) (2010) 336-350.
  27. RIBAYA-MERCADO, J.D., MARAMAG, C.C., TENGCO, L.W., et al., Carotene-rich plant foods ingested with minimal dietary fat enhance the total-body vitamin A pool size in Filipino schoolchildren as assessed by stable-isotope-dilution methodology, Am J Clin Nutr 85 (2007) 1041-9.
  28. STOLTZFUS, R.J., UNDERWOOD, B.A., Breast-milk vitamin A as an indicator of the vitamin A status of women and infants, Bulletin of the World Health Organization 73(5) (1995) 703-711.
  29. SANDSTRÖM, B., Micronutrient interactions: effects on absorption and bioavailability, Br J Nutr. 85 (2001) S181-5.
  30. LÖNNERDAL, B., Dietary Factors Influencing Zinc Absorption, J. Nutr. 130 (2000) 1378S-1383S.