Source: UNIVERSITY OF CALIFORNIA, DAVIS submitted to
BIOAVAILABILITY OF VITAMIN A & ZINC FROM SELECTED FOODS OF POTENTIAL USE FOR INTERVENTION PROGRAMS IN POPLUATIONS AT HIGH RISK OF DEFICIENCY
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0154928
Grant No.
(N/A)
Project No.
CA-D*-NTR-5388-H
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Oct 1, 2000
Project End Date
Sep 30, 2005
Grant Year
(N/A)
Project Director
Brown, K. H.
Recipient Organization
UNIVERSITY OF CALIFORNIA, DAVIS
410 MRAK HALL
DAVIS,CA 95616-8671
Performing Department
NUTRITION
Non Technical Summary
(N/A)
Animal Health Component
30%
Research Effort Categories
Basic
70%
Applied
30%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
70160991010100%
Goals / Objectives
1. To assess the bioavailability of vitamin A from selected plant sources in Bangladeshi volunteers, using the paired deuterated retinol dilution technique; and to assess the validity of a simplified technique to estimate vitamin A bioavailability, using plasma isotopic ratios of retinol within 1-3 weeks of initiating consumption of a single major source of the vitamin. 2. To assess the efficacy of local plant or animal sources of vitamin A or vitamin A-fortified rice in the treatment of maternal night blindness during pregnancy in Nepalese women. 3. To assess in adult volunteers the absorption of zinc from wheat products fortified with either zinc sulfate or zinc oxide. 4. To assess in Peruvian children at risk of zinc deficiency the net absorption of zinc and iron from wheat products fortified with iron and different levels of zinc.
Project Methods
Study 1. Bioavailability of carotenoids from plant sources, as assessed by paired deuterated retinol dilution studies. The newly developed deuterated-retinol dilution technique will be used to measure the change in vitamin A reserves before and after a 60-d period of daily supplementation of a very low vitamin A-containing basal diet with theoretically equivalent amounts (1.5 ug RE; using the beta-carotene:retinol equivalency ratio of 6:1) of either retinol, beta-carotene, spinach, mango, or (corn oil) placebo. Study 2. Use of local Nepalese foods and vitamin A fortified rice in the treatment of maternal nightblindness during pregnancy. Pregnant women with abnormal dark adaptation, who are free from infectious or chronic disease will be invited to participate in the study. Study 3. B Absorption of zinc from wheat products fortified with zinc oxide or zinc sulfate. Twenty-six adult male volunteers not habitually consuming iron- or zinc-containing supplements and who are free from gastrointestinal disorders will be included in the study. Study 4. Absorption of zinc and iron from (doubly-) fortified wheat. The study is designed as a double-blind, randomized, community-based clinical trial.

Progress 10/01/00 to 09/30/05

Outputs
During the project period, we learned that: 1) micronutrient-fortified complementary foods are a suitable means to enhance iron and vitamin A status of infants at risk of deficiency; 2) zinc supplementation reduces the risk of diarrhea and pneumonia among children in low-income populations; 3) zinc supplementation increases to growth of stunted (but not non-stunted) children; 4) multiple micronutrient supplementation increased the growth of Mexican infants; 5) NaFeEDTA enhances iron absorption from a fortified, cereal-based complementary food; 6) reduction of the phytate content of common cereals by genetic modification increases iron absorption; 7) zinc fortification does not adversely affect sensory properties of wheat products; 8) zinc is absorbed equally well from foods fortified with either zinc sulfate or zinc oxide; 9) spinach and orange sweet potatoes contribute to the vitamin A reserves of adult men, and vitamin A bioavailability from these sources is consistent with recently updated dietary reference intakes; 10) maternal nightblindness during pregnancy responds to food sources of vitamin A (liver, spinach or carrots) as well as vitamin A capsules; and 11) zinc intakes of a high percentage of US pre-school children exceeds recommended upper limits.

Impacts
These results have important implications for developing strategies to enhance micronutrient intake and status of populations at risk of deficiency. Moreover, the findings emphasize the importance of selected micronutrients for maintaining childrens growth and preventing common childhood infections. The results of the vitamin A absorption studies indicate that plant-derived sources of vitamin A can satisfy physiological requirements of this nutrient.

Publications

  • Brown KH, Peerson JM, Kimmons JE, Hotz C. Options for achieving adequate intake from home-prepared complementary food in low income countries. In: Black RE, Michaelsen KF, eds., Public Health Issues in Infant and Child Nutrition. Philadelphia, PA: Lippincott Williams & Wilkins, pp. 239-256, 2002.
  • Lopez de Romana D, Brown KH, Guinard J-X. Sensory trial to assess the acceptability of zinc fortificants added to iron-fortified wheat products. J Food Sci 67:461-465, 2002.
  • Brown KH, Peerson JM, Rivera J, Allen LH. Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials. Am J Clin Nutr 75:1062-1071, 2002.
  • Haskell MJ, Lembcke JL, Salazar M, Green MH, Peerson JM, Brown KH. Population-based plasma kinetics of an oral dose of [2H4] retinyl acetate among preschool-aged, Peruvian children. Am J Clin Nutr 77:681-686, 2003.
  • Dewey KG, Brown KH. Update on technical issues concerning complementary feeding of young children in developing countries and implications for intervention programs. Food Nutr Bull 24:5-28, 2003.
  • Brown KH. Diarrhea and malnutrition. J Nutr 133:328S-332S, 2003.
  • Ruel MT, Brown KH, Caulfield LE. Moving forward with complementary feeding: Indicators and research priorities. FCND Discussion Paper No. 146. Washington, DC: International Food Policy Research Institute, 2003.
  • Hotz C, Lowe NM, Araya M, Brown KH. Assessment of the trace element status of individuals and populations: The example of zinc and copper. J Nutr 133:1563S-1568S, 2003.
  • Lopez de Romana, D, Lonnerdal B, Brown, KH. Absorption of zinc from wheat products fortified with iron and either zinc sulfate or zinc oxide. Am J Clin Nutr 78:279-283, 2003.
  • Brown KH. Commentary: Zinc and child growth. Intl J Epidemiol 32:1103-1104, 2003.
  • Hotz C, Peerson JM, Brown KH. Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: reanalysis of the second National Health and Nutrition Examination Survey data (1976-1980). Am J Clin Nutr 78:756-764, 2003.
  • Arsenault JE, Brown KH. Zinc intake of US preschool children exceeds new dietary reference intakes. Am J Clin Nutr 78:1011-1017, 2003.
  • Mendoza C, Peerson JM, Brown KH, Lonnerdal B. Effect of a micronutrient fortificant mixture and 2 amounts of calcium of iron and zinc absorption from a processed food supplement. Am J Clin Nutr 79:244-250, 2004.
  • Lartey A, Manu A, Brown KH, Dewey KG. Predictors of micronutrient status among six to twelve-month-old breast-fed Ghanaian infants. J Nutr 130:199-207, 2000.
  • Lartey A, Manu A, Brown KH, Peerson JM, Dewey KG. Predictors of growth from 1 to 18 months among breast-fed Ghanaian infants. Europ J Clin Nutr 54:41-49, 2000.
  • Brown KH, Lutter, CK. Potential role of processed complementary foods in the improvement of early childhood nutrition in Latin America. Food Nutr Bull 21:5-11, 2000.
  • Zinc Investigators Collaborative Group (Bhutta ZA, Bird SM, Black RE, Brown KH, Gardner JM, Hidayat A, Khatun F, Martorell R, Ninh NX, Penny ME, Rosado JL, Roy SK, Ruel M, Sazawal S, Shankar A). Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 72:1516-1522, 2000.
  • Brown KH, Wuehler SE (eds,). Zinc and human health: results of recent trials and implications for program interventions and research. The Micronutrient Initiative, Ottawa, Canada, 2000.
  • Mendoza C, Viteri FE, Lonnerdal B, Raboy V, Young KA, Brown KH. Absorption of iron from unmodified maize and genetically altered, low-phytate maize fortified with ferrous sulfate or sodium iron EDTA. Am J Clin Nutr 73:80-85, 2001.
  • Dewey KG, Cohen RJ, Brown KH, Rivera LL. Effects of exclusive breastfeeding for four versus six months on maternal nutritional status and infant motor development: Results of two randomized trials in Honduras. J Nutr 131:262-267, 2001.
  • Hotz C, Brown KH. Identifying populations at risk of zinc deficiency: the use of supplementation trials. Nutr Rev 59:80-84, 2001.
  • Brown KH, Wuehler SE, Peerson JM. The importance of zinc in human nutrition and estimation of the global prevalence of zinc deficiency. Food Nutr Bull 22: 113-125, 2001.
  • Rivera JA, Gonzalez-Cossio T, Flores M, Romero M, Rivera M, Tellez-Rojo MM, Rosado JL, Brown KH. Multiple micronutrient supplementation increases the growth of Mexican infants. Am J Clin Nutr 74:657-663, 2001.
  • Brown KH. A rational approach to feeding infants and young children with acute diarrhea. In: Lifschitz CH, ed, Pediatric gastroenterology and nutrition in clinical practice. New York: Marcel Dekker, Inc, 2001.
  • Penny ME, Marin RM, Duran A, Peerson JM, Lanata CF, Lonnerdal B, Black RE, Brown, KH. Randomized, controlled trial of the effect of daily supplementation with zinc or multiple micronutrients on morbidity, growth, and micronutrient status of young, Peruvian children. Am J Clin Nutr 79:457-465, 2004.
  • Hotz C, Brown KH (eds,). Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 25:S94-S203, 2004.
  • Dewey KG, Cohen RJ, Brown KH. Exclusive breast-feeding for 6 months, with iron supplementation, maintains adequate micronutrient status among term, low birthweight, breast-fed infants in Honduras. J Nutr 134:1091-1098, 2004.
  • Haskell MJ, Jamil KM, Hassan F, Peerson JM, Hossain, MI, Fuchs GJ, Brown KH. Daily consumption of Indian Spinach (Basella alba) or sweet potatoes has a positive impact on total body vitamin A stores of Bangladeshi men. Am J Clin Nutr 80:705-714, 2004.
  • Kimmons JE, Dewey KG, Haque E, Chakraborty MS, Osendarp SJM, Brown KH. Behavior-change trials to assess the feasibility of improving complementary feeding practices and micronutrient intake of infants in rural Bangladesh. Food Nutr Bull 25:228-238, 2004.


Progress 01/01/04 to 12/31/04

Outputs
During the past year, several studies were completed on: 1) the effects of different fortification mixtures on the absorption of iron and zinc from processed food supplements designed for young children, 2) the effects of zinc supplementation alone or with other micronutrients on illness risk, growth and micronutrient status of young children, 3) the effects of infant feeding interventions (varied duration of exclusive breast feeding and different systems of delivering micronutrients) on infant risk of micronutrient deficiency, and 4) bioavailability of vitamin A from different food sources. The study of fortificant mixtures indicated that iron was absorbed 70% more efficiently from a mixture containing NaFeEDTA than from one containing ferrous sulfate, but the amount of calcium in the mixture did not affect iron absorption; zinc absorption did not differ when zinc was provided as zinc sulfate or zinc methionine, although higher calcium intake had a marginally negative effect on zinc absorption. The study of zinc supplementation found that zinc alone reduced symptoms of infectious morbidity, whereas simultaneous provision of zinc with other micronutrients increased the risk of these illnesses. A study of infant feeding practices indicated that low birth weight (LBW), exclusively breast fed infants who received iron supplements from 4-6 mo and LBW infants who received complementary foods beginning at 4 mo had higher iron status at 6 mo than unsupplemented EBF infants. In another study of complementary feeding practices, mothers were able to implement short-term recommended changes in feeding behaviors, including increasing meal frequency, increasing the amount of food provided, decreasing viscosity and thereby enhancing the energy density of semi-solid preparations and successfully administering different types of micronutrient supplements. The study of food sources of vitamin A showed that both green leafy vegetables and yellow-orange sweet potatoes had a positive impact on vitamin A reserves, with estimated equivalency factors of 10:1 and 13:1, respectively, in relation to retinyl palmitate.

Impacts
The results of these studies can be used to formulate appropriate fortified foods for young children, to plan micronutrient supplementation programs, and to develop appropriate recommendations for young child feeding and practical guidelines for satisfying vitamin A requirements.

Publications

  • Penny ME, Marin RM, Duran A, Peerson JM, Lanata CF, Lonnerdal B, Black RE, Brown, KH Randomized, controlled trial of the effect of daily supplementation with zinc or multiple micronutrients on morbidity, growth, and micronutrient status of young, Peruvian children. Am J Clin Nutr 79:457-465, 2004.
  • Hotz C, Brown KH (eds.). Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 25:S94-S203, 2004.
  • Haskell MJ, Jamil KM, Hassan F, Peerson JM, Hossain, MI, Fuchs GJ, Brown KH. Daily consumption of Indian Spinach (Basella alba) or sweet potatoes has a positive impact on total body vitamin A stores of Bangladeshi men. Am J Clin Nutr 80:705-714, 2004.
  • Dewey KG, Cohen RJ, Brown KH. Exclusive breast-feeding for 6 months, with iron supplementation, maintains adequate micronutrient status among term, low birthweight, breast-fed infants in Honduras. J Nutr 134:1091-1098, 2004.
  • Kimmons JE, Dewey KG, Haque E, Chakraborty MS, Osendarp SJM, Brown KH. Behavior-change trials to assess the feasibility of improving complementary feeding practices and micronutrient intake of infants in rural Bangladesh. Food Nutr Bull 25:228-238, 2004.


Progress 01/01/03 to 12/31/03

Outputs
1. Progress report B During the past year, several studies were completed on: 1) the kinetics of equilibration of an oral dose of a vitamin A tracer (tetra-deuterated retinol) administered to young children, 2) assessment of zinc status, using dietary and biochemical techniques, and 3) absorption of zinc fortificants added to food. The vitamin A studies extend our earlier work in adults, in which we validated the use of the deuterated retinol dilution (DRD) test to assess total body vitamin A reserves quantitatively. The DRD test requires an assumption of equilibration of the labeled oral dose with pre-existing body reserves, so preliminary studies were completed to determine the kinetics of this equilibration process by collecting multiple blood samples from adult volunteers. Because we are not able to collect frequent blood samples from young children, we examined Apopulation equilibration@ by measuring plasma isotopic ratios in groups of children who were examined on one or two occasions at different intervals following consumption of the oral dose of labeled retinol. One of the studies of assessment of zinc status examined current zinc intakes (1994-98) by a representative sample of US children in relation to the recently revised Dietary Reference Intakes. Almost all children were consuming usual zinc intakes greater than the current RDA and high percentages (51-92% of children <4 yrs of age) were consuming levels greater than the safe upper limit. A significant increase in zinc intakes during the period of study was attributable to increased consumption of zinc-fortified foods. Another study relevant to assessment of zinc status reexamined NHANES serum zinc data to establish appropriate statistical cutoffs (based on the 2.5th percentile) for defining adequate serum zinc concentration. The results indicated that appropriate cutoffs should be specific for males and females, age group, time of day of blood sampling, and fasting status. Radio-labeled tracer studies (using whole-body counting) were completed in adult volunteers to assess zinc absorption from higher and lower phytate-containing wheat products fortified with either zinc sulfate or zinc oxide. As expected, fractional absorption was less with higher phytate diets. However, there were no significant differences in absorption in relation to the chemical form of the fortificant.

Impacts
Results of the vitamin A studies can be used to develop guidelines for implementing a novel test (the deuterated retinol dilution test) to assess the amount of vitamin A stored in the body. The analyses of dietary intake indicate that US children consume adequate amounts of zinc; but considerable numbers of younger children consume more than the safe upper limit, and consumption of zinc from fortified foods is increasing. The cutoffs established by re-analysis of data on serum zinc concentrations can be applied to assess zinc status. The zinc absorption studies indicate that either of the zinc salts assessed can be used to fortify wheat products.

Publications

  • Arsenault JE, Brown KH. Zinc intake of US preschool children exceeds new dietary reference intakes. Am J Clin Nutr 78:1011-1017, 2003.
  • Brown KH. Diarrhea and malnutrition. J Nutr 133:328S-332S, 2003.
  • Haskell MJ, Lembcke JL, Salazar M, Green MH, Peerson JM, Brown KH. Population-based plasma kinetics of an oral dose of [2H4] retinyl acetate among preschool-aged, Peruvian children. Am J Clin Nutr 77:681-686, 2003.
  • Dewey KG, Brown KH. Update on technical issues concerning complementary feeding of young children in developing countries and implications for intervention programs. Food Nutr Bull 24:5-28, 2003.
  • Ruel MT, Brown KH, Caulfied LE. Moving forward with complementary feeding: Indicators and research priorities. FCND Discussion Paper No. 146. Washington, DC: International Food Policy Research Institute, 2003.
  • Hotz C, Lowe NM, Araya M, Brown KH. Assessment of the trace element status of individuals and populations: The example of zinc and copper. J Nutr 133:1563S-1568S, 2003.
  • Lopez de Romana, D, Lonnerdal B, Brown, KH. Absorption of zinc from wheat products fortified with iron and either zinc sulfate or zinc oxide. Am J Clin Nutr 78:279-283, 2003.
  • Brown KH. Commentary: Zinc and child growth. Intl J Epidemiol 32:1103-1104, 2003.
  • Hotz C, Peerson JM, Brown KH. Suggested lower cutoffs of serum zinc concentrations for assessing zinc status: reanalysis of the second National Health and Nutrition Examination Survey data (1976-1980). Am J Clin Nutr 78:756-764, 2003.


Progress 01/01/02 to 12/31/02

Outputs
During the past year several studies were completed on: a) the effect of zinc supplementation on young children's growth, b) the effects of varied levels of zinc fortification on the acceptability of wheat products, and c) absorption of zinc from wheat products fortified with either zinc oxide or zinc sulfate. In a meta-analysis of 33 trials conducted in pre-pubertal children, we found that zinc supplementation produced highly significant, positive responses in height and weight increments, with effect sizes of 0.350 and 0.309 SD, respectively, and a large increase in serum zinc concentration, with an effect size of 0.820 SD. Growth responses were greater in children with low initial weight-for-age Z-scores, and in those aged >6 mo with low initial height-for-age. In a study of the sensory acceptability of products made from fortified wheat flour, volunteer subjects rated their degree of liking (DOL) for flavor and texture of bread and noodles fortified with 30 mg of iron as FeSO4/kg flour and either 60 or 100 mg of zinc/kg flour, as either ZnSO4 or ZnO. All products were generally well liked and there were no differences among breads and only minor among noodles by type of fortification. In a study of zinc absorption from wheat products fortified with either ZnSO4 or ZnO, healthy adult male volunteers received either low-phytate bread meals or higher-phytate porridge meals once weekly on two occasions. The meals were fortified with one of the two zinc salts (60 mg elemental zinc/kg wheat flour) during week 1 and the other during week 2, in random order. Zinc absorption was assessed using an isotopic tracer and whole-body counting. Zinc absorption from bread was significantly greater than from porridge (13.8% versus 6.4%, respectively), presumably due to the effect of phytate. Controlling for the type of diet, there were no statistically significant differences in the mean zinc absorption from meals fortified with ZnSO4 compared with those that were fortified with ZnO. In addition to the foregoing, zinc-related studies, the data collection phases were completed for one study in Bangladesh adult volunteers of vitamin A bioavailability from carotenoid-containing foods and for another study of the treatment of maternal nightblindness during pregnancy, using locally available, vitamin A-containing foods in rural Nepal. The final results of the latter two studies are still pending.

Impacts
Results of the zinc-related studies indicate that zinc supplementation increases the linear growth and weight gain of children with stunting and/or underweight. Interventions to improve children's zinc nutriture should be considered in populations at risk of zinc deficiency. The population mean serum zinc concentration is a useful indicator of successful delivery and absorption of zinc supplements in children. Zinc fortification is an alternative method for improving population zinc status. Our studies indicate that zinc-fortified wheat products will be well accepted. Either ZnSO4 or ZnO can be used to fortify wheat products consumed by presumably healthy persons.

Publications

  • Brown KH, Peerson JM, Rivera J, Allen LH. 2002. Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials. Am J Clin Nutr 75:1062-71.
  • Lopez de Romana D, Brown KH, Guinard J-X. 2002. Sensory trial to assess the acceptability of zinc fortificants added to iron-fortified wheat products. J Food Sci 67: 461-465.
  • Lopez de Romana D, Brown, KH. 2001. Absorption of zinc from wheat products that have been fortified with iron and ether zinc sulfate or zinc oxide. Annals of Nutrition & Metabolism. 45:361.
  • Haskell MJ, Jamil KMA, Hossain MI, Fuch G, Peerson JM, Wahed MA, Brown KH. 2001. Response of estimated total body vitamin A stores to daily supplementation with green leafy vegetables or sweet potatoes in Bangladeshi men. Annals of Nutrition & Metabolism. 45:37.
  • Haskell MJ, Pandey P, Graham JM, Peerson JM, Shrestha RK, Brown KH. 2002. Response of plasma retinol and carotenoid concentrations of nightblind, pregnant Nepalese women to daily supplementation with locally available vitamin A-rich foods or vitamin A-fortified Ultra-RiceTM. Federation of American Societies for Experimental Biology 16:A276
  • Brown KH, Peerson JM, Kimmons JE, Hotz C. 2002. Options for achieving adequate intake from home-prepared complementary food in low-income countries. In: Black RE, Michaelsen KF, eds., Public Health Issues in Infant and Child Nutrition. Philadelphia, PA: Lippincott Williams & Wilkins, pp. 239-256.


Progress 01/01/01 to 12/31/01

Outputs
&#65279;During the past year several studies were completed on: a) mineral (iron) absorption from iron-fortified, genetically-modified, low-phytate maize, b) the effect of multiple micronutrient supplementation on young children's growth, and c) the effects of varied duration of exclusive breast feeding on maternal nutritional status and infant motor development. Additionally, analyses were completed to development estimates of the global prevalence of inadequate zinc intake, using data from national food balance sheets. In previous studies we had found that iron absorption from low-phytate maize was approximately 50% greater than from wild-type maize. In the recently completed studies we learned that there was no difference in iron absorption from porridges that were prepared from the two types of maize when they were fortified with additional iron. Iron absorption was greater when maize was fortified with EDTA-iron than with iron sulfate. In studies of multiple micronutrient supplementation of Mexican pre-school children, we found that supplemented infants, but not older children, had increased rates of growth compared with unsupplemented counterparts. In randomized trials of four versus six months of exclusive breast feeding (EBF), we found that mothers of infants with longer duration of EBF were more likely to be amenorrheic at six months post-partum, and their infants crawled sooner and were more likely to be walking at 12 months. The analyses of national food balance sheets suggest that nearly half the world's population is at risk of inadequate zinc intake.

Impacts
&#65279;The advantage of low-phytate maize for enhanced iron absorption may be eliminated when the cereal is fortified with additional iron. Infants at risk of growth stunting and micronutrient deficiency may benefit from multiple micronutrient supplementation. Exclusive breast feeding until six months is advantageous for both mothers and infants. Zinc deficiency may be common in many parts of the world, and interventions should be considered to improve zinc status.

Publications

  • Rivera JA, Gonzalez-Cossio T, Flores M, Romero M, Rivera M, Tellez-Rojo MM, Rosado JL, Brown KH. 2001. Multiple micronutrient supplementation increases the growth of Mexican infants. Am J Clin Nutr 74: 657-663.
  • Hotz C, Brown KH. 2001. Identifying populations at risk of zinc deficiency: the use of supplementation trials. Nutr Rev 59: 80-84.
  • Brown KH. 2001 Relations between gastrointestinal infections and childhood malnutrition. In: Suskind RM, Tontisirin K, eds., Nutrition, Immunity and Infection in Infants and Children. Philadelphia, PA: Lippincott Williams & Wilkins, pp. 319-335.
  • Brown KH. 2001. A rational approach to feeding infants and young children with acute diarrhea. In: Lifschitz CH, ed, Pediatric gastroenterology and nutrition in clinical practice. New York: Marcel Dekker, Inc.
  • Mendoza C, Viteri FE, Lonnerdal B, Raboy V, Young KA, Brown KH. 2001. Absorption of iron from unmodified maize and genetically altered, low-phytate maize fortified with ferrous sulfate or sodium iron EDTA. Am J Clin Nutr 73: 80-85.
  • Dewey KG, Cohen RJ, Brown KH, Rivera LL. 2001 Effects of exclusive breastfeeding for four versus six months on maternal nutritional status and infant motor development: Results of two randomized trials in Honduras. J. Nutr 131: 262-267.
  • Brown KH, Wuehler SE, Peerson JM.2001 The importance of zinc in human nutrition and estimation of the global prevalence of zinc deficiency. Food Nutr Bull 22: 113-125.


Progress 01/01/00 to 12/31/00

Outputs
&#65279;During the past year several studies were completed on selected issues concerning infant feeding in low-income countries, with particular focus on the effects of different feeding regimens on infant growth, micronutrient status, and hydration status. Other analyses were carried out to determine the effect of zinc supplementation on the severity of childhood diarrhea. A community-based intervention trial completed in rural Ghana found that infants who received a micronutrient-fortified, centrally processed complementary food from 6-12 months of age had higher levels of serum ferritin and serum retinol at 12 months than those who received locally available, non-fortified processed foods or home-available food mixtures. Prevalence of fever and diarrhea was negatively associated with the growth of these children and maternal educational level was positively associated their growth. In other studies of exclusively breast fed, low birth weight Honduran infants, measurements of daytime urine output and urinary specific gravity indicated that the infants' hydration status was adequate, even in hot environmental conditions, so no additional water is required by these infants. Analysis of pooled data from three randomized trials of children with acute diarrhea indicated that zinc-supplemented children had a 15% lower probability of diarrhea continuing on a particular day, and analysis of pooled results from four randomized trials of children with persistent diarrhea indicated that those who were supplemented with zinc had a 24% lower probability of continuing diarrhea and a 42% reduced chance of treatment failure or death.

Impacts
&#65279;The foregoing study results have several policy implications. Micronutrient fortification of processed infant foods is an efficacious method to enhance the micronutrient status of infants at risk of deficiency. Greater education of girls in low-income settings may result in improved nutritional status of their children. Zinc supplementation of children with acute and persistent diarrhea in high-risk populations can reduce diarrheal severity and/or duration.

Publications

  • Lartey A, Manu A, Brown KH, Dewey KG. 2000. Predictors of micronutrient status among six- to twelve-month-old breast-fed Ghanaian infants. J Nutr 130: 199-207.
  • Lartey A, Manu A, Brown KH, Peerson JM, Dewey KG. 2000. Predictors of growth from 1 to 18 months among breast-fed Ghanaian infants. Europ J Clin Nutr 54: 41-49.
  • Brown KH, Lutter, CK. 2000. Potential role of processed complementary foods in the improvement of early childhood nutrition in Latin America. Food Nutr Bull 21:5-11.
  • Cohen RJ, Brown KH, Rivera LL, Dewey KG. 2000. Exclusively breastfed, low birthweight term infants do not need supplemental water. Acta Paediatr 89:550-552.


Progress 01/01/99 to 12/31/99

Outputs
During the past year, our research group continued studies of several aspects of complementary feeding of young children in low-income countires, with particular attention to the nutritional content, physical characteristics, and age of introduction of these foods and relationships between different feeding practices and abnormalities of intestinal function. We found that amylase treatment of a high-energy-density, cereal-based porridge increased the amounts consumed by young Peruvian children. Addition of a mutliple micronutrient fortificant to a centrally processed complementary food improved the vitamin A and iron status of Ghanaian infants, but did not affect their growth compared with several non-fortified products. There was no advantage with respect to growth or energy intake when nutrionally complete, hygienic complementary foods were introduced to low-birth-weight Honduran infants at four versus six months of age. Non-breastfeeding, low weight-for-age, and recent diarrhea were all independently associated with abornal intestinal permeability in Guatemalan infants. Other studies of the effect of zinc supplementation and the severity of infections found that the duration of diarrhea was reduced in zinc-supplemented children. Finally, studies completed in Bangladesh showed that the deuterated retinol dilution test - a recently developed technique to assess total body vitamin A pool size - could detect expected changes in vitamin A status following different levels of supplementation of adult volunteers who were consuming a low-vitamin A diet.

Impacts
(N/A)

Publications

  • BENNETT VA, MORALES E., GONZALEZ J, PEERSON JM, LOPEZ DE ROMANA G, BROWN KH, 1999. Effects of dietary viscosity and energy density on total daily energy consumption by young Peruvian children. Am J Clin Nutr 70:285-291.
  • PENNY ME, PEERSON JM, MARIN RM, DURAN A, LANATA CF, LONNERDAL B, BLACK RE, BROWN KH, 1999. Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhea in Lima, Peru. J Pediatr 135:208-217.
  • LARTEY A, MANU A, BROWN KH, PEERSON JM, DEWEY KG, 1999. A randomized, community-based trial of the effects of improved, centrally processed complementary foods on growth and mircronutrient status of Ghanaian infants from 6 to 12 mo of age. Am J Clin Nutr 70:391-404.
  • HASKELL MJ, MAZUMDER RN, PEERSON JM, JONES AD, WAHED MA, MAHALANABIS D, BROWN KH, 1999. Use of the deuterated-retinol technique to assess total-body vitamin A stores of adult volunteers consuming different amounts of vitamin A. Am J Clin Nur 70:874-880.
  • DEWEY KG, COHEN RJ, BROWN KH, RIVERA LL, 1999. Age of introduction of complementary foods and growth of term, low-birth-weight, breast-fed infants: a randomized intervention study in Honduras. Am J Clin Nutr 69:679-86.
  • ZINC INVESTIGATORS' COLLABORATIVE GROUP (BHUTTA ZA, BLACK RE, BROWN KH, MEEKS-GARDNER J, GORE S, HIDAYAT A, KHATUN F, MARTORELL R, NINH NX, PENNY ME, ROSADO JL, ROY SK, RUEL M, SAZAWAL S, SHANKAR A) 1999. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomized controlled trials. J Pediatr 135:689-97.
  • GOTO K, CHEW F, TORUN B, PEERSON JM, BROWN KH, 1999. Epidemiology of altered intestinal permeability to lactulose and mannitol in Guatemalan infants. J Pediatr Gastroenterol Nutr 28:282-290.


Progress 01/01/98 to 12/01/98

Outputs
Research completed during the past year examined several aspects of the diagnosis, treatment, and prevention of micronutrient (iron, zinc, vitamin A) deficiencies in low-income populations. We published results from a prospective intervention trial in Honduras that confirmed earlier reports of increased rates of anemia in low-birth weight infants, regardless of the timing of introduction of complementary foods, and we found that infants whose birth weights were at the lower range of normal were less likely to be anemic at six months of age if they began receiving iron-containing complementary foods at four months of age rather than at six months. We also published the first of a series of studies examining the effect of genetically modified, low-phytate maize on iron absorption. We found that substituting low-phytate maize for wild type maize increased the absorption of iron from tortillas by approximately 50%. We analyzed the effect of zinc supplementation on children's growth, both in the context of a randomized intervention trial in Guatemala and in a meta-analysis of more than 20 previously completed human trials. In both cases, zinc supplementation increased the growth of stunted, but not non-stunted, children. We also continued our research to examine the validity and proper application of the newly developed deuterated retinol dilution technique, and we found that the time for equilibration of an oral dose of labeled retinol did not differ in groups of individuals with either adequate or low vitamin A reserves.

Impacts
(N/A)

Publications

  • DEWEY, K. G., COHEN, R. J., RIVERA, L. L., and BROWN, K. H. 1998. Effects of age of introduction of complementary foods on iron status of breastfed infants in Honduras. Am. J. Clin. Nutr. 76:878-84.
  • MENDOZA, C., VITERI, F. E., LONNERDAL, B., YOUNG, K. A., RABOY, V., and BROWN, K. H. 1998. Effect of genetically modified low-phytate maize on absorption of iron from tortilla. Am. J. Clin. Nutr.
  • BROWN, K. H., PEERSON, J. M., and ALLEN, L. H. 1998. Effect of zinc supplementation on children's growth: A meta-analysis of intervention trials. Bibliotheca. Nutritio. et Dieta. 54:76-83.
  • RIVERA, J. A., RUEL, M. T., SANTIZO, M-C., BROWN, K. H., and LONNERDAL, B. 1998. Zinc supplementation improves the growth of stunted rural Guatemalan infants. J. Nutr. 128:556-62.
  • HASKELL, M. J., ISLAM, M. A., HANDELMAN, G. J., PEERSON, J. M., JONES, A. D., WAHED, M. A., MAHALANABIS, D., and BROWN, K. H. 1998. Plasma kinetics of an oral dose of [(superscript 2)H]retinyl acetate in human subjects with estimated low.
  • BROWN, K. H. 1998. Effect of infections on plasma zinc concentration and implications for zinc status assessment in low-income countries. Am. J. Clin. Nutr. 68:425S-429S.
  • BROWN, K.H., DEWEY, K. G., and ALLEN. L. H. 1998. Complementary Feeding of Young Children in Developing Countries: A Review of Current Scientific Knowledge. World Health Organization


Progress 01/01/97 to 12/01/97

Outputs
During the past year several studies were completed concerning different aspects of feeding of young children in low-income settings, with particular focus on selected micronutrients and on the development of new techniques to assess children's dietary intake and micronutrient status. A double-masked, community-based zinc supplementation trial was completed in rural Guatemala infants. Zinc-supplemented infants (particularly boys) had fewer episodes of diarrhea, and infants who were initially stunted (low height-for-age) had greater linear growth following daily zinc administration. A meta-analysis was also completed to assess the impact of zinc supplementation on children's growth, using results from a sizeable number of previously published and unpublished trials. Overall, there was a small, but highly significant, positive impact of zinc on children's linear growth and weight gain. Increased length gain was restricted to those studies that enrolled children who were initially stunted, and greater weight gain was restricted to those studies that enrolled children who were initially stunted, and greater weight gain occurred primarily in those studies that included children with lower initial mean serum zinc concentrations. We also published the first of several studies of a novel stable-isotope dilution technique to assess total body vitamin A reserves. We found a significant correlation between the results of the deuterated-retinol technique and hepatic concentration of vitamin A measured in Bangladesh surgical patients.

Impacts
(N/A)

Publications

  • BENTLEY, M. E., CAULFIELD, L. E., RAM, M., SANTIZO, M. C., HURTADO, E., RIVERA, J. A., RUEL, M. T. and BROWN, K. H. 1997. Zinc supplementation affects the activity patterns of rural Guatemalan
  • LEMBCKE, J. L., PEERSON, J. M. and BROWN, K. H. 1997. Acceptability, safety, and digestibility of spray-dried bovine serum added to diets of recovering malnourished children. J. of Pediatric Gastroenterology and Nutrition 25:381-384.
  • RUEL, M. T., DEWEY, K. G., MARTINEZ, C., FLORES, R. and BROWN, K. H. 1997. Validation of single daytime samples of human milk to estimate the 24-h concentration of lipids in urban Guatemalan mothers. Am. J. Clin. Nutr. 65:439-44.
  • DEWEY, K. G., COHEN, R. J., LANDA RIVER, L., CANAHUATI, J. and BROWN, K. H. 1997. Effects of age at introduction of complementary foods to breast-fed infants on duration of lactational amenorrhea in Honduran women. Am. J. Clin. Nutr. 65:.
  • RUEL, M. T., RIVERA, J. A., SANTIZO, M-C., LONNERDAL, B. and BROWN, K. H. 1997. Impact of zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan children.
  • BROWN, K. H. 1997. Complementary feeding in developing countries: factors affecting energy intake. Proc. Nutr. Soc. 56:139-148.
  • HASKELL, M. J., HANDLEMAN, G. J., PEERSON, J. M., JONES, A. D., ATAIRABBI, M., AWAL, M.. A., WAHED, M. A., MAHALANABIS, D. and BROWN, K. H. 1997. Assessment of vitamin A status by the deuterated-retinol-dilution technique and comparison.


Progress 01/01/96 to 12/30/96

Outputs
During the past year several studies were completed of relevance to various aspects of children's nutrition, including assessment of current recommendations for protein intake, novel methods to enhance iron absorption from common foods, and development of guidelines for the dietary management of infections. In studies of children recovering from severe protein-energy malnutrition we found that intakes of protein at current FAO/WHO levels (4.8-5.5% of energy, depending on age) resulted in similar physical growth and changes in body composition as more generous protein intakes. In another set of studies in adult human volunteers, we compared iron bioavailability from genetically modified low-phytate maize and from the parent wild strain, using the extrinsic tag method. Iron uptake increased significantly by approximately 50% with the low-phytate maize. We also participated in a multi-center, descriptive epidemiological study of a treatment algorithm for the management of children with persistent diarrhea. Short term treatment was accomplished safely and effectively in the majority of patients, by using treatment relying primarily on mixed diets prepared from common foods and simple clinical treatment guidelines.

Impacts
(N/A)

Publications

  • L., BLACK, R.E. and BROWN, K.H. 1996. Feeding practices and growth among low-income Peruvian infants: a comparison of internationally recommended definitions. International Journal.
  • ASHRAFH, B.M.K.; BHATNAGAR, S.; BHUTTA, Z.; BROWN, K.H.; DUNG, P.T.; FONTAINE, O., GARCIA, J.A.; ISSANIZ, L.Y.; MAHALANABIS, D; MITRA, A.K.; MOLLA, A.M.; NIZAMI, S.Q.; NURKO, S.; PENNY, M.; SINGH, K.D.; SNYDER, J.D.; THANH, P.N.; THOBANI,. BROWN, K.H. 1996. Special issue on cereal based oral rehydration therapy for diarrhea. Food and Nutrition Bulletin. 17:93-97.
  • COMMITTEE ON INTERNATIONAL NUTRITION, FOOD AND NUTRITION BOARD, BOARD ON INTERNATIONAL HEALTH, INSTITUTE OF MEDICINE. 1996. Vitamin C in Food Aid Commodities. Initial Review of a Pilot Program. Washington DC: National Academy Press, 1-62.
  • DEWEY, K.G., COHEN, R.J., RIVERA, L. L., CANAHUATI, J. and BROWN, K.H. 1996. Do exclusively breast-fed infants require extra protein. Pediatric Research. 39(2):303-307.
  • LONNERDAL, B., ZAVALETA, N., KUSUNOKI, L., LANATA, C. F., PEERSON, J.M. and BROWN, K.H. 1996. Effect of postpartum maternal infection on proteins and trace elements in colostrum and early milk. Acta Paediatrica. 85(5):537-542.
  • PIWOZ, E. G., CREED de KANASHIRO, H., LOPEZ de ROMANA, G.


Progress 01/01/95 to 12/30/95

Outputs
During the past year several studies were carried out on the relationships between micronutrient status and risk of diarrheal diseases. A randomized, double-blind community intervention trial was completed in Guatemala to assess the effect of zinc supplementation on incidence rates of diarrhea in young children. Boys, but not girls, who received zinc had significantly lower rates of diarrhea during a six-month period of prospective observation. A similar study has been initiated in Peru to examine the impact of zinc alone or zinc and other minerals and vitamins on the duration of episodes of persistent childhood diarrhea and the subsequent growth and morbidity of affected children. The field work has been completed for this latter study, and the results are currently under analysis. Other studies have been completed to assess the effects of different macronutrient profiles and diversity of the diet on children's total daily energy intakes. There were no differences in total energy intakes in relation to the proportion of total energy provided as starch or sugar, but intakes increased significantly when saccharine was added to the high starch diet. In other studies total daily energy intakes from isoenergetic diets increased when more of the energy was provided as fat. Children also consumed significantly more of a varied diet than one in which variety was restricted. Studies of the deuterated retinol dilution technique to assess vitamin A status were also continued.

Impacts
(N/A)

Publications

  • MOLINA, S., VETTORAZZI, C., PEERSON, J.M., SOLOMONS, N.W. and BROWN, K.H. 1995. Clinical trial of glucose-oral rehydration solution (ORS), Rice Dextrin-ORS, and rice flour-ORS for the management of children with acute diarrhea and mild. DEWEY, K.G., PEERSON, J.M., BROWN, K.H., KREBS, N.F., MICHAELSEN, K.F., PERSSON, L.A., SALMENPERA, L., WHITEHEAD, R.G., YEUNG, D.L. and WHO Working Group on Infant Growth. 1995. Growth of breast-fed infants deviates from current reference.
  • BROWN, K.H., SANCHEZ-GRINAN, M., PEREZ, F., PEERSON, J.M., GANOZA, L. and STERN, J. S. 1995. Effects of dietary energy density and feeding frequency on total daily energy intakes by recovering malnourished children. Am. J. Clin. Nutr. 62:.
  • COHEN, R.J., BROWN, K.H., CANAHUATI, J., RIVERA, L.L. and DEWEY, K.G. 1995. Determinants of growth from birth to 12 months among breast-fed Honduran infants in relation to age of introduction to complementary foods. Pediatrics 96(3):504-.
  • PEREZ-ESCAMILLA, R., COHEN, R.J., BROWN, K.H., RIVERA, L.L., CANAHUATI, J. and DEWEY, K.G. 1995. Maternal anthropometric status and lactation performance in a low income Honduran population: evidence for the role of infants. Am. J. Clin.
  • BENTLEY, M.E., ELDER, J., FUKUMOTO, M., STALLINGS, R.H., JACOBY, E. and BROWN, K.H. 1995. Acute childhood diarrhoea and maternal time allocation in the Northe.


Progress 01/01/94 to 12/30/94

Outputs
During the past year several studies of the relationships between infection and children's nutrition were completed and one new study was initiated. Research in Nigeria and Mexico found that local diets composed of maize, cowpea, and palm oil (Nigeria) or rice, chicken, beans, carrots, and oil (Mexico) did not increase the amount of fecal excretion by children with acute diarrhea when compared with commercially available lactose-free, soy-protein-isolate infant formula. The duration of liquid stool excretion was substantially reduced with the local diets. In Mexico, there was a significant reduction in treatment failure rates with the local diet. A community-based intervention trial was initiated in Peru to examine the effect of supplemental zinc or zinc and other minerals and vitamins on the severity of illness and subsequent growth and morbidity of children with persistent diarrhea. Other studies of recovering malnourished children found that both frequency of feeding and energy density of diets were independently and positively associated with total daily energy intake. Additional studies to examine the relationships between specific macronutrient components of the diet and total daily energy intake were begun. Studies of the application of the deuterated retinol dilution test to assess vitamin A status were continued.

Impacts
(N/A)

Publications

  • BROWN, K.H., PEERSON, J.M. and FONTAINE, O. 1994. Use of nonhuman milks in the dietary management of young children with acute diarrhea: a meta-analysis of clinical trials. Pediatrics 93:17-27.
  • PIWOZ, E.G., CREED DE KANASHIRO, H., LOPEZ DE ROMANA, G., BLACK, R.E. and BROWN, K.H. 1994. Within- and between-individual variation in energy intakes by low-income Peruvian infants. Eur. J. Clin. Nutr. 48:333-340.
  • BROWN, K.H. 1994. Reestablishment of a section on international nutrition in the AJCN. Am. J. Clin. Nutr. 59:1263-1264.
  • GRANGE, A.O., SANTOSHAM, M., AYODELE, A.K., IESI, A., STALLINGS, R.Y. and BROWN, K.H. 1994. Evaluation of a maize-cowpea-palm oil diet for the dietary management of Nigerian children with acute, watery diarrhea. Acta Paediatr. 83:825-832.
  • SCHROEDER, D.G. and BROWN, K.H. 1994. Nutritional status as a predictor of child survival: summarizing the association and quantifying its global impact. Bull. WHO 72(4):569-579.


Progress 01/01/93 to 12/30/93

Outputs
During the past year additional studies of the relationships between nutrition and infection were carried out. A meta-analysis of clinical trials regarding the appropriate use of milk-containing diets for children with acute diarrhea indicated that continued milk feeding is appropriate for children with mild diarrhea and dehydration. A clinical trial of three oral rehydration solutions (ORS) found that stool output was reduced with rice flour ORS compared with glucose-ORS and rice-dextrin ORS. A community trial found no advantage of reduce viscosity diets for children with diarrhea. A field study of the effect of infection on assessment of trace element status of high risk populations with frequent infections found that rates of zinc deficiency may be slightly underestimated and rates of iron deficiency may be considerably overestimated when selected biochemical indicators are used. New lines of research were initiated on: 1) dietary factors that influence young children's energy intake, 2) novel interventions to improve iron status in low-income communities, and 3) use of the deuterated retinol dilution technique to assess vitamin A status.

Impacts
(N/A)

Publications


    Progress 01/01/92 to 12/30/92

    Outputs
    During the past year one clinical trial concerning the dietary management of children with acute diarrhea has been completed, two trials of improved oral rehydration therapy have been initiated, and funding has been approved for a new study of the effect of supplements of either zinc only or zinc and multiple vitamins and minerals on the severity and duration of persistent diarrhea. The just completed study compared the clinical and nutritional outcomes of acute diarrhea among children who received either a lactose-free, low-fiber soy protein formula or the same formula supplemented with 0.6 g/100 ml soy polysaccharide. There were no differences between treatment groups in formula intake, stool excretion, apparent macronutrient absorption, or change in body weight during the six-day observation periods. Nearly three fourths of the supplemental fiber was fermented in the GI tract, and children who received fiber had dramatic reductions in the median duration of liquid stool excretion from 163 to 43 hours.

    Impacts
    (N/A)

    Publications

    • SANCHEZ-GRINAN, M.I., PEERSON, J.M. and BROWN, K.H. 1992 Effect of dietary energy density on total ad-libitum energy consumption by recovering malnourished children. European Journal of Clinical Nutrition 46:197-204.
    • PIWOZ, E.G., PEERSON, J.M. and BROWN, K.H. 1992 Potential for misclassification of infants' growth increments by using existing reference data. American Journal of Clinical Nutrition 56:58-64.
    • GARZA, C., BLACK, R.E., BROWN, K.H., CASH, R.A., HARPER, J.M., KEUSCH, G. and PELTO, G.H.. 1992. Nutrition Issues in Developing Countries, Part I: Diarrheal Diseases. Subcommittee on Nutrition and Diarrheal Diseases Control, Committee.
    • ALARCON, P., MONTOYA, R., RIVERA, J., PEREZ, F., PEERSON, J.M. and BROWN, K.H. 1992. Effect of inclusion of beans in a mixed diet for the treatment of Peruvian children with acute watery diarrhea. Pediatrics 90:58-65.
    • HENNING, B., STEWART, K., ZAMAN, K., ALAM, A.N., BROWN, K.H. and BLACK, R.E. 1992. Lack of therapeutic efficacy of vitamin A for non-cholera, watery diarrhea in Bangladeshi children. European Journal of Clinical Nutrition 46:437-443.
    • LEMBCKE, J.L. and BROWN, K.H. 1992 Effect of milk-containing diets on the severity and duration of childhood diarrhea. Acta Paediatrica Supplement 381:87-92.
    • BROWN, K.H. and PEREZ, F. 1992 Determinants of dietary intake during childhood diarrhea & implications for appropriate nutritional therapy. Acta Paediatrica S.


    Progress 07/01/91 to 12/30/91

    Outputs
    During the past year several clinical trials were completed to assess the optimal dietary management of children with acute diarrhea. We found that mixed diets available in poor households in developing countries could be safely and efficiently used in place of more costly infant formulas. We also learned that cereal-milk mixtures are better tolerated by young children during diarrhea than is milk alone, regardless of whether the lactose component was prehydrolyzed by exogenous beta-galactosidase. Finally, we found that inclusion of beans in a mixed diet had only minor effects on the amount of fecal excretion during diarrhea and did not adversely affect the outcome of therapy. We also initiated our first set of studies to assess the effects of specific dietary components on the total energy intake by older infants and young children. Children who received somewhat diluted weaning foods (50 kcal/100 g) consumed consistently greater amounts of the diet than those who received a similar diet at twice the energy concentration (100 kcal/100 g), but the former children still consumed significantly less total energy. The results of this pilot study have enabled us to plan more extensive evaluations of the independent effects of energy density and feeding frequency on total energy intake.

    Impacts
    (N/A)

    Publications