The effect of zinc-biofortified rice on zinc status of Bangladeshi preschool children: a randomized, double-masked, household-based, controlled trial

Roelinda Jongstra, Md Mokbul Hossain, Valeria Galetti, Andrew G Hall, Roberta R Holt, Colin I Cercamondi, Sabina F Rashid, Michael B Zimmermann, Malay K Mridha, Rita Wegmueller, Roelinda Jongstra, Md Mokbul Hossain, Valeria Galetti, Andrew G Hall, Roberta R Holt, Colin I Cercamondi, Sabina F Rashid, Michael B Zimmermann, Malay K Mridha, Rita Wegmueller

Abstract

Background: Zinc biofortification of rice could sustainably improve zinc status in countries where zinc deficiency is common and rice is a staple, but its efficacy has not been tested. Fatty acid desaturases (FADS) are putative new zinc status biomarkers.

Objectives: Our objective was to test the efficacy of zinc-biofortified rice (BFR) in preschool-aged children with zinc deficiency. Our hypothesis was that consumption of BFR would increase plasma zinc concentration (PZC).

Methods: We conducted a 9-mo, double-masked intervention trial in 12-36-mo-old rural Bangladeshi children, most of whom were zinc-deficient (PZC <70 µg/dL) and stunted (n = 520). The children were randomly assigned to receive either control rice (CR) or BFR provided in cooked portions to their households daily, with compliance monitoring. The primary outcome was PZC. Secondary outcomes were zinc deficiency, linear growth, infection-related morbidity, FADS activity indices, intestinal fatty acid binding protein (I-FABP) and fecal calprotectin. We applied sparse serial sampling for midpoint measures and analyzed data by intention-to-treat using mixed-effects models.

Results: At baseline, median (IQR) PZC was 60.4 (56.3-64.3) µg/dL, 78.1% of children were zinc deficient, and 59.7% were stunted. Mean ± SD daily zinc intakes from the CR and BFR during the trial were 1.20 ± 0.34 and 2.22 ± 0.47 mg/d, respectively (P < 0.001). There were no significant time-by-treatment effects on PZC, zinc deficiency prevalence, FADS activity, I-FABP, or fecal calprotectin (all P > 0.05). There was a time-treatment interaction for height-for-age z-scores (P < 0.001) favoring the BFR group. The morbidity longitudinal prevalence ratio was 1.08 (95% CI: 1.05, 1.12) comparing the BFR and CR groups, due to more upper respiratory tract illness in the BFR group.

Conclusions: Consumption of BFR for 9 mo providing ∼1 mg of additional zinc daily to Bangladeshi children did not significantly affect PZC, prevalence of zinc deficiency, or FADS activity.The trial was registered at clinicaltrials.gov as NCT03079583.

Keywords: Bangladesh; biofortification; calprotectin; fatty acid desaturases; intestinal fatty acid binding protein; plasma zinc concentration; preschool-age children; rice; zinc; zinc deficiency.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Study diagram. BRRI, Bangladesh Rice Research Institute; HAZ, height-for-age z-score.
FIGURE 2
FIGURE 2
Kinetic curves of plasma zinc concentration during the 36-wk intervention in Bangladeshi children, by group (control rice group n = 240, biofortified rice group n = 231). Lines show the fitted values using a local polynomial regression fit (function LOESS). Six data points were excluded that were outside the plasma zinc concentration range of 20–100 µg/dL.

References

    1. Gupta S, Brazier AKM, Lowe NM. Zinc deficiency in low- and middle-income countries: prevalence and approaches for mitigation. J Hum Nutr Diet. 2020;33(5):624–43.
    1. Walker CF, Ezzati M, Black R. Global and regional child mortality and burden of disease attributable to zinc deficiency. Eur J Clin Nutr. 2009;63(5):591–7.
    1. Wessells KR, Brown KH. Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting. PLoS One. 2012;7(11):e50568.
    1. Gibson RS, Manger MS, Krittaphol W, Pongcharoen T, Gowachirapant S, Bailey KB, Winichagoon P. Does zinc deficiency play a role in stunting among primary school children in NE Thailand?. Br J Nutr. 2007;97(1):167–75.
    1. Bangladesh Bureau of Statistics . Household income expenditure survey 2010. Dhaka (Bangladesh): Ministry of Planning, Government of the People's Republic of Bangladesh; 2011.
    1. Rahman S, Ahmed T, Rahman AS, Alam N, Ahmed AM, Ireen S, Chowdhury IA, Chowdhury FP, Rahman SM. Status of zinc nutrition in Bangladesh: the underlying associations. J Nutr Sci. 2016;5:e25.
    1. Bangladesh Bureau of Statistics . Bangladesh multiple indicator cluster survey 2019. Dhaka (Bangladesh): Bangladesh Bureau of Statistics; 2019.
    1. Bailey RL, West KP Jr, Black RE. The epidemiology of global micronutrient deficiencies. Ann Nutr Metab. 2015;66(Suppl. 2):22–33.
    1. Bouis HE, Saltzman A, Birol E. Improving nutrition through biofortification. Agriculture for improved nutrition: seizing the momentum. Wallingford(UK): International Food Policy Research Institute; 2019. Chapter 5.
    1. Brnic M, Wegmuller R, Melse-Boonstra A, Stomph T, Zeder C, Tay FM, Hurrell RF. Zinc absorption by adults is similar from intrinsically labeled zinc-biofortified rice and from rice fortified with labeled zinc sulfate. J Nutr. 2016;146(1):76–80.
    1. Jiang W, Struik P, Van Keulen H, Zhao M, Jin L, Stomph T. Does increased zinc uptake enhance grain zinc mass concentration in rice?. Ann Appl Biol. 2008;153(1):135–47.
    1. Graham RD, Welch RM, Bouis HE. Addressing micronutrient malnutrition through enhancing the nutritional quality of staple foods: principles, perspectives and knowledge gaps. Adv Agron. 2001:70:77–142.
    1. Trijatmiko KR, Duenas C, Tsakirpaloglou N, Torrizo L, Arines FM, Adeva C, Balindong J, Oliva N, Sapasap MV, Borrero Jet al. . Biofortified indica rice attains iron and zinc nutrition dietary targets in the field. Sci Rep. 2016;6(1):19792.
    1. King JC, Brown KH, Gibson RS, Krebs NF, Lowe NM, Siekmann JH, Raiten DJ. Biomarkers of Nutrition for Development (BOND)-Zinc review. J Nutr. 2015;146:858S–85S.
    1. Gibson RS, Hess SY, Hotz C, Brown KH.. Indicators of zinc status at the population level: a review of the evidence. Br J Nutr. 2008;99(S3):S14–23.
    1. Lowe NM, Fekete K, Decsi T. Methods of assessment of zinc status in humans: a systematic review. Am J Clin Nutr. 2009;89(6):2040S–51S.
    1. King JC. Yet again, serum zinc concentrations are unrelated to zinc intakes. J Nutr. 2018;148(9):1399–401.
    1. Moran VH, Stammers A-L, Medina MW, Patel S, Dykes F, Souverein OW, Dullemeijer C, Pérez-Rodrigo C, Serra-Majem L, Nissensohn M. The relationship between zinc intake and serum/plasma zinc concentration in children: a systematic review and dose-response meta-analysis. Nutrients. 2012;4(8):841–58.
    1. Knez M, Stangoulis JCR, Zec M, Debeljak-Martacic J, Pavlovic Z, Gurinovic M, Glibetic M. An initial evaluation of newly proposed biomarker of zinc status in humans – linoleic acid: dihomo-gamma-linolenic acid (LA:DGLA) ratio. Clin Nutr ESPEN. 2016;15:85–92.
    1. Chimhashu T, Malan L, Baumgartner J, van Jaarsveld PJ, Galetti V, Moretti D, Smuts CM, Zimmermann MB. Sensitivity of fatty acid desaturation and elongation to plasma zinc concentration: a randomised controlled trial in Beninese children. Br J Nutr. 2018;119(6):610–9.
    1. Horrobin DF, Cunnane SC. Interactions between zinc, essential fatty acids and prostaglandins: relevance to acrodermatitis enteropathica, total parenteral nutrition, the glucagonoma syndrome, diabetes, anorexia nervosa and sickle cell anaemia. Med Hypotheses. 1980;6(3):277–96.
    1. Ayala S, Brenner RR. Essential fatty acid status in zinc deficiency. Effect on lipid and fatty acid composition, desaturation activity and structure of microsomal membranes of rat liver and testes. Acta Physiol Lat Am. 1983;33(3):193–204.
    1. Knez M, Stangoulis J, Glibetic M, Tako E. The linoleic acid: dihomo-γ-linolenic acid ratio (LA:dGLA)—an emerging biomarker of Zn status. Nutrients. 2017;9(8):825.
    1. Massih YN, Hall AG, Suh J, King JC. Zinc supplements taken with food increase essential fatty acid desaturation indices in adult men compared with zinc taken in the fasted state. J Nutr. 2021;151(9):2583–9.
    1. Konikoff MR, Denson LA. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. Inflamm Bowel Dis. 2006;12(6):524–34.
    1. Ho SS, Keenan JI, Day AS. The role of gastrointestinal-related fatty acid-binding proteins as biomarkers in gastrointestinal diseases. Dig Dis Sci. 2020;65(2):376–90.
    1. Ohashi W, Fukada T. Contribution of zinc and zinc transporters in the pathogenesis of inflammatory bowel diseases. J Immunol Res. 2019;2019:8396878.
    1. International Zinc Nutrition Consultative Group (IZiNCG) . Assessing population zinc status with serum zinc concentration. IZiNCG/University of California;2012.
    1. de Onis M. Update on the implementation of the WHO child growth standards. World Rev Nutr Diet. 2013;106:75–82.
    1. World Health Organization (WHO) . Preventive chemotherapy in human helminthiasis. Coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers. WHO; 2006.
    1. Makower RU. Extraction and determination of phytic acid in beans (Phaseolus vulgaris). Cereal Chem. 1970;47:288–95.
    1. Galetti V, Mitchikpè CES, Kujinga P, Tossou F, Hounhouigan DJ, Zimmermann MB, Moretti D. Rural Beninese children are at risk of zinc deficiency according to stunting prevalence and plasma zinc concentration but not dietary zinc intakes. J Nutr. 2016;146(1):114–23.
    1. Erhardt JG, Estes JE, Pfeiffer CM, Biesalski HK, Craft NE. Combined measurement of ferritin, soluble transferrin receptor, retinol binding protein, and C-reactive protein by an inexpensive, sensitive, and simple sandwich enzyme-linked immunosorbent assay technique. J Nutr. 2004;134(11):3127–32.
    1. 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. 2003;78(4):756–64.
    1. icddr, b, UNICEF Bangladesh , GAIN, Institute of Public Health and Nutrition. National micronutrients status survey 2011–12. Final report. Dhaka (Bangladesh): icddr, b;2013.
    1. Namaste SM, Rohner F, Huang J, Bhushan NL, Flores-Ayala R, Kupka R, Mei Z, Rawat R, Williams AM, Raiten DJet al. . Adjusting ferritin concentrations for inflammation: biomarkers reflecting inflammation and nutritional determinants of anemia (BRINDA) project. Am J Clin Nutr. 2017;106(Suppl 1):359S–71S.
    1. World Health Organization (WHO) . Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations. WHO; 2011.
    1. World Health Organization (WHO) . Iron deficiency anaemia: assesment, prevention and control: a guide for programme managers. WHO;. 2001.
    1. Serafim V, Tiugan D-A, Andreescu N, Mihailescu A, Paul C, Velea I, Puiu M, Niculescu MD. Development and validation of a LC-MS/MS-based assay for quantification of free and total omega 3 and 6 fatty acids from human plasma. Molecules. 2019;24(2):360.
    1. Paganini D, Uyoga MA, Kortman GAM, Cercamondi CI, Moretti D, Barth-Jaeggi T, Schwab C, Boekhorst J, Timmerman HM, Lacroix Cet al. . Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: a randomised controlled study in Kenyan infants. Gut. 2017;66(11):1956–67.
    1. Pinkaew S, Winichagoon P, Hurrell RF, Wegmuller R. Extruded rice grains fortified with zinc, iron, and vitamin A increase zinc status of Thai school children when incorporated into a school lunch program. J Nutr. 2013;143(3):362–8.
    1. De Onis M, Onyango AW, Borghi E, Garza C, Yang H, Group W. Comparison of the World Health Organization (WHO) child growth standards and the National Center for Health Statistics/WHO international growth reference: implications for child health programmes. Public Health Nutr. 2006;9(7):942–7.
    1. McDonald CM, Suchdev PS, Krebs NF, Hess SY, Wessells KR, Ismaily S, Rahman S, Wieringa FT, Williams AM, Brown KHet al. . Adjusting plasma or serum zinc concentrations for inflammation: biomarkers reflecting inflammation and nutritional determinants of anemia (BRINDA) project. Am J Clin Nutr. 2020;111(4):927–37.
    1. Arsenault JE, Yakes EA, Islam MM, Hossain MB, Ahmed T, Hotz C, Lewis B, Rahman AS, Jamil KM, Brown KH. Very low adequacy of micronutrient intakes by young children and women in rural Bangladesh is primarily explained by low food intake and limited diversity. J Nutr. 2013;143(2):197–203.
    1. Brown KH, Rivera JA, Bhutta Z, Gibson RS, King JC, Lonnerdal B, Ruel MT, Sandtröm B, Wasantwisut E, Hotz C. International zinc nutrition consultative group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull. 2004;25(1 Suppl 2):S99–S203.
    1. Gibson R. Determining the risk of zinc deficiency: assessment of dietary zinc intake. 2nd ed. Davis (CA): International Zinc Nutrition Consultative Group (IZiNCG);2019. p.1–8.
    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(8):1763–9.
    1. Lindenmayer GW, Stoltzfus RJ, Prendergast AJ. Interactions between zinc deficiency and environmental enteropathy in developing countries. Adv Nutr. 2014;5(1):1–6.
    1. Brown KH, Lopez de Romana D, Arsenault JE, Peerson JM, Penny ME. Comparison of the effects of zinc delivered in a fortified food or a liquid supplement on the growth, morbidity, and plasma zinc concentrations of young Peruvian children. Am J Clin Nutr. 2007;85(2):538–47.
    1. Sazawal S, Dhingra U, Dhingra P, Dutta A, Deb S, Kumar J, Devi P, Prakash A. Efficacy of high zinc biofortified wheat in improvement of micronutrient status, and prevention of morbidity among preschool children and women – a double masked, randomized, controlled trial. Nutr J. 2018;17(1):86.
    1. Petry N, Olofin I, Boy E, Donahue Angel M, Rohner F. The effect of low dose iron and zinc intake on child micronutrient status and development during the first 1000 days of life: a systematic review and meta-analysis. Nutrients. 2016;8(12):773.
    1. Tsang BL, Holsted E, McDonald CM, Brown KH, Black R, Mbuya MNN, Grant F, Rowe LA, Manger MS. Effects of foods fortified with zinc, alone or cofortified with multiple micronutrients, on health and functional outcomes: a systematic review and meta-analysis. Adv Nutr. 2021;12(5):1821–37.
    1. Peña-Rosas JP, Mithra P, Unnikrishnan B, Kumar N, De-Regil LM, Nair NS, Garcia-Casal MN, Solon JA. Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition. Cochrane Database Syst Rev. 2019;(10):CD009902.
    1. Wessells KR, King JC, Brown KH. Development of a plasma zinc concentration cutoff to identify individuals with severe zinc deficiency based on results from adults undergoing experimental severe dietary zinc restriction and individuals with acrodermatitis enteropathica. J Nutr. 2014;144(8):1204–10.
    1. Liong EM, McDonald CM, Suh J, Westcott JL, Wong CP, Signorell C, King JC. Zinc-biofortified wheat intake and zinc status biomarkers in men: randomized controlled trial. J Nutr. 2021;151(7):1817–23.
    1. Hillbruner C, Egan R. Seasonality, household food security, and nutritional status in Dinajpur, Food Nutr Bull. 2008;29(3):221–31.
    1. Rashid DA, Smith LC, Rahman T. Determinants of dietary quality: evidence from Bangladesh. World Dev. 2011;39(12):2221–31.
    1. Fahim SM, Das S, Gazi MA, Mahfuz M, Ahmed T. Association of intestinal pathogens with faecal markers of environmental enteric dysfunction among slum-dwelling children in the first 2 years of life in Bangladesh. Trop Med Int Health. 2018;23(11):1242–50.
    1. Long JM, Mondal P, Westcott JE, Miller LV, Islam MM, Ahmed M, Mahfuz M, Ahmed T, Krebs NF. Zinc absorption from micronutrient powders is low in Bangladeshi toddlers at risk of environmental enteric dysfunction and may increase dietary zinc requirements. J Nutr. 2019;149(1):98–105.
    1. Canani RB, Rapacciuolo L, Romano M, De Horatio LT, Terrin G, Manguso F, Cirillo P, Paparo F, Troncone R. Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice. Dig Liver Dis. 2004;36(7):467–70.
    1. D'Haens G, Ferrante M, Vermeire S, Baert F, Noman M, Moortgat L, Geens P, Iwens D, Aerden I, Van Assche Get al. . Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(12):2218–24.
    1. Adriaanse MP, Mubarak A, Riedl R, Ten Kate F, Damoiseaux J, Buurman WA, Houwen R, Vreugdenhil A. Progress towards non-invasive diagnosis and follow-up of celiac disease in children; a prospective multicentre study to the usefulness of plasma I-FABP. Sci Rep. 2017;7(1):1–10.
    1. Uddin MI, Islam S, Nishat NS, Hossain M, Rafique TA, Rashu R, Hoq MR, Zhang Y, Saha A, Harris JBet al. . Biomarkers of environmental enteropathy are positively associated with immune responses to an oral cholera vaccine in Bangladeshi children. PLoS Negl Trop Dis. 2016;10(11):e0005039.
    1. Cascais-Figueiredo T, Austriaco-Teixeira P, Fantinatti M, Silva-Freitas ML, Santos-Oliveira JR, Coelho CH, Singer SM, Da-Cruz AM. Giardiasis alters intestinal fatty acid binding protein (I-FABP) and plasma cytokines levels in children in Brazil. Pathogens. 2020;9(1):7.
    1. Tam E, Keats EC, Rind F, Das JK, Bhutta AZA. Micronutrient supplementation and fortification interventions on health and development outcomes among children under-five in low- and middle-income countries: a systematic review and meta-analysis. Nutrients. 2020;12(2):289.
    1. Myers SS, Wessells KR, Kloog I, Zanobetti A, Schwartz J. Effect of increased concentrations of atmospheric carbon dioxide on the global threat of zinc deficiency: a modelling study. Lancet Glob Health. 2015;3(10):e639–45.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться