Zinc Absorption and Endogenous Fecal Zinc Losses in Bangladeshi Toddlers at Risk for Environmental Enteric Dysfunction

Prasenjit Mondal, Julie M Long, Jamie E Westcott, M Munirul Islam, Mondar Ahmed, Mustafa Mahfuz, Tahmeed Ahmed, Leland V Miller, Nancy F Krebs, Prasenjit Mondal, Julie M Long, Jamie E Westcott, M Munirul Islam, Mondar Ahmed, Mustafa Mahfuz, Tahmeed Ahmed, Leland V Miller, Nancy F Krebs

Abstract

Objectives: Environmental enteric dysfunction (EED) impairs zinc absorption from food, and zinc deficiency may contribute to the poor growth associated with EED. We examined zinc absorption from a standardized aqueous zinc dose, and habitual daily endogenous fecal zinc excretion (EFZ) and compared these outcomes between children grouped by the lactulose to mannitol ratio (L:M).

Methods: Bangladeshi toddlers (18-24 months) with low (<0.09) and high (≥0.09) L:M were administered isotope-labeled 3 mg aqueous zinc in the fasted state. Fractional absorption of zinc (FAZ) and EFZ were measured by dual stable isotope tracer method and an isotope dilution method, respectively. Secondary aims included examining relationships of biomarkers of systemic and intestinal inflammation and gut function with FAZ and EFZ.

Results: Forty children completed the study; nearly all had evidence of EED. No differences in zinc homeostasis measurements (mean ± SD) were observed between high and low L:M groups: FAZ was 0.38 ± 0.19 and 0.31 ± 0.19, respectively; both figures were within estimated reference range. Means of EFZ were 0.73 ± 0.27 and 0.76 ± 0.20 mg/day for high and low L:M, respectively, and were 10% to 15% above estimated reference range. Regression analyses indicated that biomarkers of systemic inflammation were directly associated with increasing FAZ, consistent with increased gut permeability. Biomarkers of intestinal inflammation were negatively associated with EFZ, consistent with low-zinc intake and chronic deficiency.

Conclusions: In these children at risk of EED, endogenous zinc losses were not markedly increased. Results suggest that efforts to improve zinc status in EED should focus on substantially improving zinc intakes.

Trial registration: ClinicalTrials.gov NCT02760095.

Conflict of interest statement

The authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Fractional absorption of zinc versus quantity of ingested zinc shown for the aqueous fasting dose in the present study (circle symbols) and for a zinc-supplemented meal (x symbols) administered to a separate group of toddlers from the same Bangladeshi population (9). The greater variability in the fasting FAZ data is apparent, having a standard deviation of 0.19 compared with 0.06 for the FAZ from meals (taking into account the variation in FAZ with quantity of zinc in meal—dotted curve). ●—FAZ from aqueous zinc dose (high L:M, present study); —FAZ from aqueous zinc dose (low L:M, present study); x—FAZ from single meal supplemented with zinc. Data from (9). FAZ = fractional absorption of ingested zinc.

References

    1. Krebs NF, Miller LV, Hambidge KM. Zinc deficiency in infants and children: a review of its complex and synergistic interactions. Paediatr Intl Child Health 2014; 34:279–288.
    1. Young GP, Mortimer EK, Gopalsamy GL, et al. Zinc deficiency in children with environmental enteropathy-development of new strategies: report from an expert workshop. Am J Clin Nutr 2014; 100:1198–1207.
    1. Lindenmayer GW, Stoltzfus RJ, Prendergast AJ. Interactions between zinc deficiency and environmental enteropathy in developing countries. Adv Nutr 2014; 5:1–6.
    1. Owino V, Ahmed T, Freemark M, et al. Environmental enteric dysfunction and growth failure/stunting in global child health. Pediatr 2016; 138: pii: e20160641.
    1. Crane RJ, Jones KD, Berkley JA. Environmental enteric dysfunction: an overview. Food Nutr Bull 2015; 36 (1 Suppl):S76–S87.
    1. Guerrant RL, DeBoer MD, Moore SR, et al. The impoverished gut--a triple burden of diarrhoea, stunting and chronic disease. Nature Rev Gastroenterol Hepatol 2013; 10:220–229.
    1. Manary MJ, Abrams SA, Griffin IJ, et al. Perturbed zinc homeostasis in rural 3-5-y-old Malawian children is associated with abnormalities in intestinal permeability attributed to tropical enteropathy. Pediatr Res 2010; 67:671–675.
    1. May T, Westcott C, Thakwalakwa C, et al. Resistant starch does not affect zinc homeostasis in rural Malawian children. J Trace Elem Med Biol 2015; 30:43–48.
    1. Long JM, Mondal P, Westcott JE, et al. Zinc absorption from micronutrient powders is low in Bangladeshi toddlers at risk for environmental enteric dysfunction (EED) and may increase dietary zinc requirements. J Nutr 2019; 149:98–105.
    1. ICDDR B, UNICEF Bangladesh, GAIN, Institute of Public Health and Nutrition. National Micronutrients Status Survey 2011-12: final report. 2013.
    1. Hossain MI, Haque R, Mondal D, et al. Undernutrition, vitamin A and iron deficiency are associated with impaired intestinal mucosal permeability in young Bangladeshi children assessed by lactulose/mannitol test. PLoS One 2016; 11:e0164447.
    1. van Elburg RM, Uil JJ, Kokke FT, et al. Repeatability of the sugar-absorption test, using lactulose and mannitol, for measuring intestinal permeability for sugars. J Pediatr Gastroenterol Nutr 1995; 20:184–188.
    1. Boaz RT, Joseph AJ, Kang G, et al. Intestinal permeability in normally nourished and malnourished children with and without diarrhea. Indian Pediatr 2013; 50:152–153.
    1. Friel JK, Naake VL, Jr, Miller LV, et al. The analysis of stable isotopes in urine to determine the fractional absorption of zinc. Am J Clin Nutr 1992; 55:473–477.
    1. Krebs NF, Westcott JE, Culbertson DL, et al. Comparison of complementary feeding strategies to meet zinc requirements of older breastfed infants. Am J Clin Nutr 2012; 96:30–35.
    1. Krebs N, Miller LV, Naake VL, et al. The use of stable isotope techniques to assess zinc metabolism. J Nutr Biochem 1995; 6:292–307.
    1. World Health Organization. The WHO Child Growth Standards. Geneva: WHO; 2006.
    1. Campbell RK, Schulze KJ, Shaikh S, et al. Biomarkers of environmental enteric dysfunction among children in rural Bangladesh. J Pediatr Gastroenterol Nutr 2017; 65:40–46.
    1. Islam MM, Woodhouse LR, Hossain MB, et al. Total zinc absorption from a diet containing either conventional rice or higher-zinc rice does not differ among Bangladeshi preschool children. J Nutr 2013; 143:519–525.
    1. Chomba E, Westcott CM, Westcott JE, et al. Zinc absorption from biofortified maize meets the requirements of young rural Zambian children. J Nutr 2015; 145:514–519.
    1. Faubion WA, Camilleri M, Murray JA, et al. Improving the detection of environmental enteric dysfunction: a lactulose, rhamnose assay of intestinal permeability in children aged under 5 years exposed to poor sanitation and hygiene. BMJ Glob Health 2016; 1: e000066.
    1. Sheng XY, Hambidge KM, Zhu XX, et al. Major variables of zinc homeostasis in Chinese toddlers. Am J Clin Nutr 2006; 84:389–394.
    1. Tran CD, Miller LV, Krebs NF, et al. Zinc absorption as a function of the dose of zinc sulfate in aqueous solution. Am J Clin Nutr 2004; 80:1570–1573.
    1. Struijs MC, Diamond IR, de Silva N, et al. Establishing norms for intestinal length in children. J Pediatr Surg 2009; 44:933–938.
    1. Hambidge KM, Krebs NF, Westcott JE, et al. Changes in zinc absorption during development. J Pediatr 2006; 149 (5 Suppl):S64–S68.
    1. Weaver LT, Landymore-Lim L, Lucas A. Neonatal gastrointestinal growth and function: are they regulated by composition of feeds? Biol Neonate 1991; 59:336–345.
    1. Hounnou G, Destrieux C, Desme J, et al. Anatomical study of the length of the human intestine. Surg Radiol Anat 2002; 24:290–294.
    1. Miller LV, Hambidge KM, Krebs NF. Zinc absorption is not related to dietary phytate intake in infants and young children based on modeling combined data from multiple studies. J Nutr 2015; 145:1763–1769.
    1. Miller LV, Krebs NF, Hambidge KM. A mathematical model of zinc absorption in humans as a function of dietary zinc and phytate. J Nutr 2007; 137:135–141.
    1. EFSA Panel on Dietetic Products N, and Allergies. Scientific Opinion on Dietary Reference Values for Zinc. EFSA J 2014; 12:3844.
    1. Kosek M, Haque R, Lima A, et al. Fecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants. Am J Trop Med Hyg 2013; 88:390–396.
    1. R Core Team, R Foundation for Statistical Computing. R: a language and environment for statistical computing. Vienna, Austria: R Core Team; 2018. Available at: Accessed April 16, 2019.
    1. Food and Nutrition Board, Institute of Medicine Dietary Reference Intakes for Vitamin A, Vitamin K, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc. Washington, DC: National Academy Press; 2001.
    1. Krebs NF, Westcott J. Zinc and breastfed infants: if and when is there a risk of deficiency? Adv Exp Med Biol 2002; 503:69–75.
    1. Prendergast A, Kelly P. Enteropathies in the developing world: neglected effects on global health. Am J Trop Med Hyg 2012; 86:756–763.
    1. Kelly P, Banda T, Soko R, et al. Environmental enteropathy: imaging the cellular basis of disrupted barrier function. Gut 2014; 63 suppl 1:A54.
    1. Kelly P, Besa E, Zyambo K, et al. Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy. PLoS Negl Trop Dis 2016; 10:e0004600.
    1. Krebs NE, Hambidge KM. Zinc metabolism and homeostasis: the application of tracer techniques to human zinc physiology. Biometals 2001; 14:397–412.
    1. Gibson RS, King JC, Lowe N. A review of dietary zinc recommendations. Food Nutr Bull 2016; 37:443–460.
    1. Hambidge KM, Krebs NF. Interrelationships of key variables of human zinc homeostasis: relevance to dietary zinc requirements. Ann Rev Nutr 2001; 21:429–452.
    1. Crofton RW, Aggett PJ, Gvozdanovic S, et al. Zinc metabolism in celiac disease. Am J Clin Nutr 1990; 52:379–382.

Source: PubMed

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