Plasma and Nail Zinc Concentrations, But Not Hair Zinc, Respond Positively to Two Different Forms of Preventive Zinc Supplementation in Young Laotian Children: a Randomized Controlled Trial

K Ryan Wessells, Kenneth H Brown, Charles D Arnold, Maxwell A Barffour, Guy-Marino Hinnouho, David W Killilea, Sengchanh Kounnavong, Sonja Y Hess, K Ryan Wessells, Kenneth H Brown, Charles D Arnold, Maxwell A Barffour, Guy-Marino Hinnouho, David W Killilea, Sengchanh Kounnavong, Sonja Y Hess

Abstract

Plasma zinc concentrations (PZC) have been shown to significantly increase during zinc supplementation. This study investigated the effects of daily preventive zinc supplementation on hair and nail zinc concentrations compared with a control group. In a randomized controlled trial, 6- to 23-month-old children (n = 3407) in Lao PDR were randomly assigned to one of four groups and followed for ~ 36 weeks: daily preventive zinc dispersible tablet (7 mg/d; PZ), daily micronutrient powder (10 mg zinc/d; MNP), therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days; TZ), or daily placebo powder (Control). Plasma, hair, and nail zinc concentrations were assessed in a sub-sample of participants (n = 457) at baseline and endline. At baseline, 75% of children had low PZC (< 65 μg/dL). At endline, geometric mean (95% CI) PZC were greater in the PZ and MNP groups compared with the TZ and control groups (P < 0.01), but hair zinc concentrations did not differ among groups (P = 0.99). Nail zinc concentrations were marginally higher in the PZ (115.8 (111.6, 119.9) μg/g) and the MNP (117.8 (113.3, 122.3) μg/g) groups than in the TZ group (110.4 (106.0, 114.8) μg/g; P = 0.055) at endline. This study does not support the use of hair zinc as a biomarker of zinc exposure in young children. However, it provides some evidence that zinc concentrations in nails may respond to supplemental zinc interventions and supports the need for collecting additional data on this emerging biomarker.

Keywords: Biomarker; Hair; Nail; Plasma; Supplement; Zinc.

Conflict of interest statement

KHB and the spouse of SYH worked for the Bill & Melinda Gates Foundation, which provided part of the financial support. None of the other authors have a conflict of interest to declare. The sponsors had no involvement in the study design, analysis, and interpretation of data, report writing, or the decision to submit the article for publication.

Figures

Fig. 1
Fig. 1
Flowchart of participant progression through the randomized controlled trial In total, 492 children were included in analyses. All children for whom baseline and endline hair Zn concentrations were available (n = 368), or for whom endline nail zinc concentrations were available (n = 256), were included in the analyses of the impact of the intervention (primary objective). Among these children, 11 did not have analyzed plasma zinc concentrations and were thus not included in analyses investigating correlations between biomarkers (secondary objective). However, an additional 34 children who had measurements of baseline or endline hair zinc concentration, in addition to plasma zinc concentrations, were included in at least one of the correlational analyses (secondary objective).

References

    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. doi: 10.1371/journal.pone.0050568.
    1. Hess SY. National risk of zinc deficiency as estimated by national surveys. Food Nutr Bull. 2017;38(1):3–17. doi: 10.1177/0379572116689000.
    1. Brown KH, Peerson JM, Baker SK, Hess SY. Preventive zinc supplementation among infants, preschoolers, and older prepubertal children. Food Nutr Bull. 2009;30(Suppl 1):S12–S40. doi: 10.1177/15648265090301S103.
    1. Lazzerini M, Wanzira H. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2016;12:CD005436. doi: 10.1002/14651858.CD005436.pub5.
    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. 2016;146(Suppl 1):858S–885S. doi: 10.3945/jn.115.220079.
    1. Hess SY, Peerson JM, King JC, Brown KH. Use of serum zinc concentration as an indicator of population zinc status. Food Nutr Bull. 2007;28(3 Suppl):S403–S429. doi: 10.1177/15648265070283S303.
    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–2051S. doi: 10.3945/ajcn.2009.27230G.
    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):756–764. doi: 10.1093/ajcn/78.4.756.
    1. International Zinc Nutrition Consultative Group (2012) Assessing population zinc status with serum zinc concentration. IZiNCG technical brief no. 2. Available online: (accessed 26 March 2014)
    1. International Zinc Nutrition Consultative Group (2018) Assessing population zinc exposure with hair or nail zinc. IZiNCG Technical Brief No. 8. Available online: (accessed 9 July 2019)
    1. Wessells KR, Brown KH, Kounnavong S, Barffour MA, Hinnouho GM, Sayasone S, Stephensen CB, Ratsavong K, Larson CP, Arnold CD, Harding KB, Reinhart GA, Lertmemongkolchai G, Fucharoen S, Bernstein RM, Hess SY. Comparison of two forms of daily preventive zinc supplementation versus therapeutic zinc supplementation for diarrhea on young children’s physical growth and risk of infection: study design and rationale for a randomized controlled trial. BMC Nutr. 2018;4(39):39. doi: 10.1186/s40795-018-0247-6.
    1. Barffour MA, Hinnouho GM, Kounnavong S, Wessells KR, Ratsavong K, Bounheuang B, Chanhthavong B, Sitthideth D, Sengnam K, Arnold CD, Brown KH, Hess SY. Effects of daily zinc, daily multiple micronutrient powder, or therapeutic zinc supplementation for diarrhea prevention on physical growth, anemia, and micronutrient status in rural Laotian children: a randomized controlled trial. J Pediatr. 2019;207:80–89. doi: 10.1016/j.jpeds.2018.11.022.
    1. Kewcharoenwong C, Schuster GU, Wessells KR, Hinnouho GM, Barffour MA, Kounnavong S, Brown KH, Hess SY, Samer W, Tussakhon I, Lertmemongkolchai G, Peerson JM, Stephensen CB (2020) Daily preventive zinc supplementation decreases lymphocyte and eosinophil concentrations in rural Laotian children from communities with a high prevalence of zinc deficiency: results of a randomized controlled trial. J Nutr. 10.1093/jn/nxaa037
    1. Barffour MA, Hinnouho GM, Kounnavong S, Wessells KR, Ratsavong K, Bounheuang B, Chanhthavong B, Sitthideth D, Sengnam K, Arnold CD, Brown KH, Larson CP, Hess SY (2018) Effects of two forms of daily preventive zinc and therapeutic zinc supplementation for diarrhea on diarrhea and acute respiratory tract infections in Laotian children (OR32-05). Curr Develop Nutr 2(11). 10.1093/cdn/nzy039
    1. World Health Organization . Indicators for assessing infant and young child feeding practices: part 1 definitions. Geneva: World Health Organization; 2008.
    1. Coates J, Swindale A, Bilinksky P. Household food insecurity access scale (HFIAS) for measurement of household food access: Indicator guide (v. 3). Washington, D.C.: FHI 360/FANTA. Available online: (accessed on 7 November 2013)
    1. Cogill B. Anthropometric indicators measurement guide. Food and nutrition technical assistance project. Washington, DC: Academy for Educational Development; 2003.
    1. World Health Organization Multicentre Growth Reference Study Group WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006;450:76–85.
    1. Killilea DW, Ames BN. Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts. Proc Natl Acad Sci U S A. 2008;105(15):5768–5773. doi: 10.1073/pnas.0712401105.
    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):3127–3132. doi: 10.1093/jn/134.11.3127.
    1. Hess SY, Barffour MA, Hinnouho GM. Lao zinc study. Open Science Framework
    1. Johnston BC, Guyatt GH. Best (but oft-forgotten) practices: intention-to-treat, treatment adherence, and missing participant outcome data in the nutrition literature. Am J Clin Nutr. 2016;104(5):1197–1201. doi: 10.3945/ajcn.115.123315.
    1. Namaste SM, Aaron GJ, Varadhan R, Peerson JM, Suchdev PS, Group BW Methodologic approach for the biomarkers reflecting inflammation and nutritional determinants of anemia (BRINDA) project. Am J Clin Nutr. 2017;106(Suppl 1):333S–347S. doi: 10.3945/ajcn.116.142273.
    1. Brown K, Rivera J, Bhutta Z, Gibson R, King J, Lönnerdal B, Ruel M, Sandström 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:S99–S203. doi: 10.1177/15648265040251S204.
    1. Coates J, Swindale A, Bilinsky P. Household Food Insecurity Access Scale (HFIAS) for Measurement of Household Food Access: Indicator Guide (v. 3) Washington, DC: FHI 360/FANTA; 2007.
    1. Safely managed drinking water - thematic report on drinking water (2017) Geneva, Switzerland: World Health Organization. Available online: (accessed 27 February 2019)
    1. Zlotkin S, Arthur P, Schauer C, Antwi KY, Yeung G, Piekarz A. Home-fortification with iron and zinc sprinkles or iron sprinkles alone successfully treats anemia in infants and young children. J Nutr. 2003;133(4):1075–1080. doi: 10.1093/jn/133.4.1075.
    1. Jack SJ, Ou K, Chea M, Chhin L, Devenish R, Dunbar M, Eang C, Hou K, Ly S, Khin M, Prak S, Reach R, Talukder A, Tokmoh LO, Leon de la Barra S, Hill PC, Herbison P, Gibson RS. Effect of micronutrient sprinkles on reducing anemia: a cluster-randomized effectiveness trial. Arch Pediatr Adolesc Med. 2012;166(9):842–850. doi: 10.1001/archpediatrics.2012.1003.
    1. Umeta M, West CE, Haidar J, Deurenberg P, Hautvast JG. Zinc supplementation and stunted infants in Ethiopia: a randomised controlled trial. Lancet. 2000;355(9220):2021–2026. doi: 10.1016/S0140-6736(00)02348-5.
    1. Hambidge KM, Chavez MN, Brown RM, Walravens PA. Zinc nutritional status of young middle-income children and effects of consuming zinc-fortified breakfast cereals. Am J Clin Nutr. 1979;32(12):2532–2539. doi: 10.1093/ajcn/32.12.2532.
    1. Cavan KR, Gibson RS, Grazioso CF, Isalgue AM, Ruz M, Solomons NW. Growth and body composition of periurban Guatemalan children in relation to zinc status: a cross-sectional study. Am J Clin Nutr. 1993;57(3):334–343. doi: 10.1093/ajcn/57.3.334.
    1. Walravens PA, Hambidge KM. Growth of infants fed a zinc supplemented formula. Am J Clin Nutr. 1976;29(10):1114–1121. doi: 10.1093/ajcn/29.10.1114.
    1. Lachat CK, Van Camp JH, Mamiro PS, Wayua FO, Opsomer AS, Roberfroid DA, Kolsteren PW. Processing of complementary food does not increase hair zinc levels and growth of infants in Kilosa district, rural Tanzania. Br J Nutr. 2006;95(1):174–180. doi: 10.1079/BJN20051610.
    1. Ruz M, Castillo-Duran C, Lara X, Codoceo J, Rebolledo A, Atalah E. A 14-mo zinc-supplementation trial in apparently healthy Chilean preschool children. Am J Clin Nutr. 1997;66(6):1406–1413. doi: 10.1093/ajcn/66.6.1406.
    1. Walravens PA, Krebs NF, Hambidge KM. Linear growth of low income preschool children receiving a zinc supplement. Am J Clin Nutr. 1983;38(2):195–201. doi: 10.1093/ajcn/38.2.195.
    1. Morgan EJ, Heath AL, Szymlek-Gay EA, Gibson RS, Gray AR, Bailey KB, Ferguson EL. Red meat and a fortified manufactured toddler milk drink increase dietary zinc intakes without affecting zinc status of New Zealand toddlers. J Nutr. 2010;140(12):2221–2226. doi: 10.3945/jn.109.120717.
    1. Shaaban S, El-Hodhoh M, Nassar M, AE H, El-Arab S, Shaheen F. Zinc status of lactating Egyptian mothers and their infants: effect of maternal zinc supplementation. Nutr Res. 2005;25:45–53. doi: 10.1016/j.nutres.2004.10.006.
    1. Grazioso CF, Isalgue M, de Ramirez I, Ruz M, Solomons NW. The effect of zinc supplementation on parasitic reinfestation of Guatemalan schoolchildren. Am J Clin Nutr. 1993;57(5):673–678. doi: 10.1093/ajcn/57.5.673.
    1. Park JS, Chang JY, Hong J, Ko JS, Seo JK, Shin S, Lee EH. Nutritional zinc status in weaning infants: association with iron deficiency, age, and growth profile. Biol Trace Elem Res. 2012;150(1–3):91–102. doi: 10.1007/s12011-012-9509-3.
    1. McBean LD, Mahloudji M, Reinhold JG, Halsted JA. Correlation of zinc concentrations in human plasma and hair. Am J Clin Nutr. 1971;24(5):506–509. doi: 10.1093/ajcn/24.5.506.
    1. Sandstead HH, Prasad AS, Penland JG, Beck FW, Kaplan J, Egger NG, Alcock NW, Carroll RM, Ramanujam VM, Dayal HH, Rocco CD, Plotkin RA, Zavaleta AN. Zinc deficiency in Mexican American children: influence of zinc and other micronutrients on T cells, cytokines, and antiinflammatory plasma proteins. Am J Clin Nutr. 2008;88(4):1067–1073. doi: 10.1093/ajcn/88.4.1067.
    1. Yokoi K, Egger NG, Ramanujam VM, Alcock NW, Dayal HH, Penland JG, Sandstead HH. Association between plasma zinc concentration and zinc kinetic parameters in premenopausal women. Am J Physiol Endocrinol Metab. 2003;285(5):E1010–E1020. doi: 10.1152/ajpendo.00533.2002.
    1. Wessells KR, Jorgensen JM, Hess SY, Woodhouse LR, Peerson JM, Brown KH. Plasma zinc concentration responds rapidly to the initiation and discontinuation of short-term zinc supplementation in healthy men. J Nutr. 2010;140(12):2128–2133. doi: 10.3945/jn.110.122812.
    1. Hambidge KM, Hambidge C, Jacobs M, Baum JD. Low levels of zinc in hair, anorexia, poor growth, and hypogeusia in children. Pediatr Res. 1972;6(12):868–874. doi: 10.1203/00006450-197212000-00003.
    1. Klevay LM. Hair as a biopsy material. I Assessment of zinc nutriture. Am J Clin Nutr. 1970;23(3):284–289. doi: 10.1093/ajcn/23.3.284.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe