Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Nutrition and Health (including climate and ecological aspects)

Reference cut-offs to define low serum zinc concentrations in healthy 1–19 year old Indian children and adolescents

European Journal of Clinical Nutrition volume 76, pages 1150–1157 (2022)Cite this article

Subjects

A Correction to this article was published on 06 April 2022

This article has been updated

Abstract

Background/Objectives

Population zinc (Zn) status assessment is based on serum zinc concentration (SZC) cut-offs defined by the International Zinc Nutrition Consultative Group (IZiNCG). The objective of this study is to derive reference SZC cut-offs in apparently healthy 1-19 year Indian children and adolescents using comprehensive national nutrition survey (CNNS) data, and to measure the prevalence of Zn deficiency.

Subjects/Methods

Apparently healthy children (n = 12,473) were selected from the CNNS, by including the highest 2 wealth quintiles, and excluding stunted, thin and obese children, and those with CRP > 5 mg/L, anaemia, hypo-albuminemia, diabetes, recent diarrhoea and history of smoking. The 2.5th centile of age-based distributions defined the SZC cut-offs, used to measure the prevalence of Zn deficiency in India, as against the IZiNCG cut-offs.

Results

The present study SZC cut-offs were significantly lower, by 10–18 µg/dL, than the IZiNCG cut-offs; more in adolescents. Prevalence of Zn deficiency in the entire CNNS, with these cut-offs, was 2.7 (<10 years) to 5.5 (10-19 years) times lower than with the IZiNCG cut-offs. No geographical state, nor any age group, had Zn deficiency as a serious public health problem (≥20%). In contrast, with IZiNCG cut-offs, 9-27 states (depending on age group) had a public health problem.

Conclusions

The present study reference SZC cut-offs for Zn deficiency are lower than the IZiNCG cut-offs, and their rigorous selection from a national sample makes them more appropriate for use in India. A re-examination of the global applicability of IZiNCG recommended cut-offs in other LMICs appears appropriate.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Flowchart of participant exclusion.
Fig. 2: The distribution of serum zinc concentrations (µg/dL) stratified by age, gender and fasting status.
Fig. 3: Comparison of 2.5th centile serum zinc concentrations from the primary analytic sample with existing IZiNCG cut-offs.
Fig. 4: Weighted mean (95% CI) prevalence of low SZC in Indian children and adolescent with study cut-offs (2.5th centile) and IZiNCG cut-off.

Similar content being viewed by others

Data availability

The Ministry of Health and Family Welfare (MoHFW), Government of India, owns the CNNS data.

Change history

References

  1. Golden MH. Specific deficiencies versus growth failure: type I and type II nutrients. SCN N. 1995;12:10–14.

    Google Scholar 

  2. King JC, Shames DM, Woodhouse LR. Zinc homeostasis in humans. J Nutr. 2000;130:1360S–1366S. https://doi.org/10.1093/jn/130.5.1360S

    Article  CAS  PubMed  Google Scholar 

  3. Yakoob MY, Theodoratou E, Jabeen A, Imdad A, Eisele TP, Ferguson J, et al. Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria. BMC Public Health. 2011;11:S23 https://doi.org/10.1186/1471-2458-11-s3-s23

    Article  PubMed  PubMed Central  Google Scholar 

  4. Imdad A, Bhutta ZA. Effect of preventive zinc supplementation on linear growth in children under 5 years of age in developing countries: a meta-analysis of studies for input to the lives saved tool. BMC Public Health. 2011;11:S22 https://doi.org/10.1186/1471-2458-11-S3-S22

    Article  PubMed  PubMed Central  Google Scholar 

  5. Brown KH, Rivera JA, Bhutta Z, Gibson RS, King JC, et al. 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:S99–203.

    Article  Google Scholar 

  6. Srikumar TS, Johansson GK, Ockerman PA, Gustafsson JA, Akesson B. Trace element status in healthy subjects switching from a mixed to a lactovegetarian diet for 12 mo. Am J Clin Nutr. 1992;55:885–90. https://doi.org/10.1093/ajcn/55.4.885

    Article  CAS  PubMed  Google Scholar 

  7. Saunders AV, Craig WJ, Baines SK. Zinc and vegetarian diets. Med J Aust. 2013;199:S17–21.

    Article  Google Scholar 

  8. King JC, Brown KH, Gibson RS, Krebs NF, Lowe NM, Siekmann JH, et al. Biomarkers of Nutrition for Development (BOND)-Zinc Review. J Nutr. 2015;146:858s–885s. https://doi.org/10.3945/jn.115.220079

    Article  PubMed  Google Scholar 

  9. Moran VH, Stammers AL, Medina MW, Patel S, Dykes F, Souverein OW, et al. The relationship between zinc intake and serum/plasma zinc concentration in children: a systematic review and dose-response meta-analysis. Nutrients. 2012;4:841–58. https://doi.org/10.3390/nu4080841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. King JC. Yet again, serum zinc concentrations are unrelated to zinc intakes. J Nutr. 2018;148:1399–401. https://doi.org/10.1093/jn/nxy190

    Article  PubMed  Google Scholar 

  11. Shah D, Sachdev HS, Gera T, De-Regil LM, Peña-Rosas JP. Fortification of staple foods with zinc for improving zinc status and other health outcomes in the general population. Cochrane Database Syst Rev. 2016;6:Cd010697. https://doi.org/10.1002/14651858.CD010697.pub2

  12. Lowe NM, Fekete K, Decsi T. Methods of assessment of zinc status in humans: a systematic review. Am J Clin Nutr. 2009;89:2040s–2051s. https://doi.org/10.3945/ajcn.2009.27230G

    Article  CAS  PubMed  Google Scholar 

  13. 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:S403–429. https://doi.org/10.1177/15648265070283S303

    Article  PubMed  Google Scholar 

  14. 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;144:1204–10.

    Article  CAS  Google Scholar 

  15. Pullakhandam R, Agrawal PK, Peter R, Ghosh S, Reddy GB, Kulkarni B, et al. Prevalence of low serum zinc concentrations in Indian children and adolescents: findings from the Comprehensive National Nutrition Survey 2016–18. Am J Clin Nutr. 2021;114:638–48. https://doi.org/10.1093/ajcn/nqab066

    Article  PubMed  Google Scholar 

  16. Sachdev HS, Porwal A, Acharya R, Ashraf S, Ramesh S, Khan N, et al. Haemoglobin thresholds to define anaemia in a national sample of healthy children and adolescents aged 1-19 years in India: a population-based study. Lancet Glob Health. 2021;9:e822–e831. https://doi.org/10.1016/S2214-109X(21)00077-2

    Article  PubMed  PubMed Central  Google Scholar 

  17. CNNS. Ministry of Health and Family Welfare (MoHFW), Government of India, Comprehensive National Nutrition Survey (CNNS) National Report. New Delhi. In, 2019.

  18. NFHS. International Institute for Population Sciences (IIPS) and ICF. In: National Family Health Survey (NFHS-4), 2015–16: India. Mumbai: IIPS, 2015–16.

  19. WHO/UNICEF (2008) Joint Monitoring Programme (JMP) for Water Supply, Sanitation and Hygiene. JMP methodology 2017 update & SDG baselines [Internet]. Geneva (Switzerland) and New York (USA): JMP; 2018. Available from: https://washdata.org/sites/default/files/documents/reports/2018-04/. Accessed on 3rd March 2020.

  20. WHO. Growth reference data for 5–19 years: BMI-for-age (5–19 years) [Internet]. Geneva (Switzerland): WHO. Available from: https://www.who.int/toolkits/growth-reference-datafor-5to19-years/indicators/bmi-for-age. Accessed on 3rd March 2020.

  21. WHO. World Health Organization child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. 2006.

  22. Abraham RA, Agrawal PK, Acharya R, Sarna A, Ramesh S, Johnston R, et al. Effect of temperature and time delay in centrifugation on stability of select biomarkers of nutrition and non-communicable diseases in blood samples. Biochem Med. 2019;29:020708. https://doi.org/10.11613/bm.2019.020708

    Article  Google Scholar 

  23. McDonald CM, Suchdev PS, Krebs NF, Hess SY, Wessells KR, Ismaily S, et al. Adjusting plasma or serum zinc concentrations for inflammation: biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr. 2020;111:927–37. https://doi.org/10.1093/ajcn/nqz304

    Article  PubMed  PubMed Central  Google Scholar 

  24. Garcia-Casal MN, Pasricha S-R, Sharma AJ, Peña-Rosas JP. Use and interpretation of hemoglobin concentrations for assessing anemia status in individuals and populations: results from a WHO technical meeting. Ann NY Acad Sci. 2019;1450:5.

    Article  Google Scholar 

  25. Kim S, McClave SA, Martindale RG, Miller KR, Hurt RT. Hypoalbuminemia and clinical outcomes: what is the mechanism behind the relationship? Am Surg. 2017;83:1220–7. https://doi.org/10.1177/000313481708301123

    Article  PubMed  Google Scholar 

  26. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128:S213–56. https://doi.org/10.1542/peds.2009-2107C

  27. Cole TJ, Green PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med. 1992;11:1305–19. https://doi.org/10.1002/sim.4780111005

    Article  CAS  PubMed  Google Scholar 

  28. Chakraborti S, Li J. Confidence interval estimation of a normal percentile. Am Statistician. 2007;61:331–6. https://doi.org/10.1198/000313007×244457

    Article  Google Scholar 

  29. Ghosh S, Kurpad AV, Sachdev HS, Thomas T. Inflammation correction in micronutrient deficiency with censored inflammatory biomarkers. Am J Clin Nutr. 2020;113:47–54. https://doi.org/10.1093/ajcn/nqaa285

    Article  Google Scholar 

  30. Karr M, Mira M, Causer J, Earl J, Alperstein G, Wood F, et al. Age-specific reference intervals for plasma vitamins A, E and beta-carotene and for serum zinc, retinol-binding protein and prealbumin for Sydney children aged 9-62 months. Int J Vitam Nutr Res. 1997;67:432–6.

    CAS  PubMed  Google Scholar 

  31. Radhakrishna KV, Hemalatha R, Geddam JJ, Kumar PA, Balakrishna N, Shatrugna V. Effectiveness of zinc supplementation to full term normal infants: a community based double blind, randomized, controlled, clinical trial. PloS one. 2013;8:e61486. https://doi.org/10.1371/journal.pone.0061486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. IZiNCG. International Zinc Nutrition Consultative Group. Technical Brief No. 2. Assessing population zinc status with serum zinc concentration, 2nd Edn. 2012.

  33. Di Martino G, Matera MG, De Martino B, Vacca C, Di Martino S, Rossi F. Relationship between zinc and obesity. J Med. 1993;24:177–83.

    PubMed  Google Scholar 

  34. Houghton LA, Parnell WR, Thomson CD, Green TJ, Gibson RS. Serum zinc is a major predictor of anemia and mediates the effect of selenium on hemoglobin in school-aged children in a nationally representative survey in New Zealand. J Nutr. 2016;146:1670–6. https://doi.org/10.3945/jn.116.235127

    Article  CAS  PubMed  Google Scholar 

  35. Hennigar SR, Lieberman HR, Fulgoni VL 3rd, McClung JP. Serum zinc concentrations in the US population are related to sex, age, and time of blood draw but not dietary or supplemental zinc. J Nutr. 2018;148:1341–51. https://doi.org/10.1093/jn/nxy105

    Article  PubMed  Google Scholar 

  36. Lin CN, Wilson A, Church BB, Ehman S, Roberts WL, McMillin GA. Pediatric reference intervals for serum copper and zinc. Clin Chim Acta. 2012;413:612–5. https://doi.org/10.1016/j.cca.2011.12.005

    Article  CAS  PubMed  Google Scholar 

  37. Azemati B, Khoramdad M, Qorbani M, Rastad H, Shafiee G, Heshmat R, et al. Percentile values of serum zinc concentration and prevalence of its deficiency in Iranian children and adolescents: the CASPIAN-V study. J Pediatr Endocrinol Metab. 2020;33:525–31. https://doi.org/10.1515/jpem-2019-0520

    Article  CAS  PubMed  Google Scholar 

  38. Barman N, Salwa M, Ghosh D, Rahman MW, Uddin MN, Haque MA. Reference value for serum zinc level of adult population in Bangladesh. Ejifcc. 2020;31:117–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. National Nutrition Monitoring Bureau. Technical Report No. 27, Diet & nutritional status of urban population in India and prevalence of obesity, hypertension, diabetes and hyperlipidemia in urban men and women. A brief NNMB report on urban nutrition. Hyderabad: National Institution of Nutrition; 2017.

  40. Hunt JR, Beiseigel JM, Johnson LK. Adaptation in human zinc absorption as influenced by dietary zinc and bioavailability. Am J Clin Nutr. 2008;87:1336–45. https://doi.org/10.1093/ajcn/87.5.1336

    Article  CAS  PubMed  Google Scholar 

  41. Griffin IJ, Hicks PD, Liang LK, Abrams SA. Metabolic adaptations to low zinc intakes in premenarcheal girls. Am J Clin Nutr. 2004;80:385–90. https://doi.org/10.1093/ajcn/80.2.385

    Article  CAS  PubMed  Google Scholar 

  42. Roohani N, Hurrell R, Kelishadi R, Schulin R. Zinc and its importance for human health: An integrative review. J Res Med Sci. 2013;18:144–57.

    PubMed  PubMed Central  Google Scholar 

  43. Institute of Medicine (IOM): Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academies Press (US), Washington (DC), 2001.

  44. 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:e50568. https://doi.org/10.1371/journal.pone.0050568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Pinna K, Woodhouse LR, Sutherland B, Shames DM, King JC. Exchangeable zinc pool masses and turnover are maintained in healthy men with low zinc intakes. J Nutr. 2001;131:2288–94. https://doi.org/10.1093/jn/131.9.2288

    Article  CAS  PubMed  Google Scholar 

  46. Miller LV, Hambidge KM, Naake VL, Hong Z, Westcott JL, Fennessey PV. Size of the zinc pools that exchange rapidly with plasma zinc in humans: alternative techniques for measuring and relation to dietary zinc intake. J Nutr. 1994;124:268–76. https://doi.org/10.1093/jn/124.2.268

    Article  CAS  PubMed  Google Scholar 

  47. Pomeroy E, Mushrif-Tripathy V, Cole TJ, Wells JCK, Stock JT. Ancient origins of low lean mass among South Asians and implications for modern type 2 diabetes susceptibility. Sci Rep. 2019;9:10515. https://doi.org/10.1038/s41598-019-46960-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. D’Angelo S, Yajnik CS, Kumaran K, Joglekar C, Lubree H, Crozier SR, et al. Body size and body composition: a comparison of children in India and the UK through infancy and early childhood. J Epidemiol Community Health. 2015;69:1147–53. https://doi.org/10.1136/jech-2014-204998

    Article  PubMed  Google Scholar 

  49. Miller LV, Hambidge KM, King JC, Westcott JE, Krebs NF. Predictors of the size of the exchangeable zinc pool differ between children and adults. J Nutr. 2017;147:187–94. https://doi.org/10.3945/jn.116.239541

    Article  CAS  PubMed  Google Scholar 

  50. Kim J, Paik HY, Joung H, Woodhouse LR, King JC. Plasma zinc but not the exchangeable zinc pool size differs between young and older Korean women. Biol Trace Elem Res.2011;142:130–6. https://doi.org/10.1007/s12011-010-8758-2

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

HSS and AVK are recipients of the Wellcome Trust/Department of Biotechnology India Alliance Clinical/Public Health Research Centre Grant # IA/CRC/19/1/610006. RP, BK, GBR, and HR are supported by the Indian Council of Medical Research, Govt of India.

Author information

Authors and Affiliations

  1. National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India

    Raghu Pullakhandam, Bharati Kulkarni, G. Bhanuprakash Reddy & Hemalatha Rajkumar

  2. St John’s Medical College, Bangalore, India

    Santu Ghosh & Anura V. Kurpad

  3. Institute of Liver and Biliary Sciences, New Delhi, India

    Umesh Kapil

  4. Ministry of Health and Family Welfare, New Delhi, India

    Sila Deb

  5. Sitaram Bhartia Institute of Science and Research, New Delhi, India

    Harshpal S. Sachdev

Authors
  1. Raghu Pullakhandam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Santu Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bharati Kulkarni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Bhanuprakash Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hemalatha Rajkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Umesh Kapil
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sila Deb
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anura V. Kurpad
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Harshpal S. Sachdev
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HSS, AVK, SG, and RP conceptualized the manuscript, and RP wrote the first draft and revised under the supervision of HSS and AVK. SG led the statistical analysis with guidance from HSS and AVK. HSS, AVK, RP, SG, BK, GBR and HR contributed to the data interpretation and had access to all the data. All authors reviewed and approved the submitted manuscript. HSS and AVK had final responsibility for the decision to submit for publication.

Corresponding authors

Correspondence to Anura V. Kurpad or Harshpal S. Sachdev.

Ethics declarations

Competing interests

HSS designed the draft protocol of the CNNS with consultancy support from UNICEF, India. HSS, UK, and AVK were members of the Technical Advisory Committee of the CNNS, constituted by the Ministry of Health and Family Welfare of the Government of India, to oversee its conduct and analysis. HSS is a member of the WHO Nutrition Guidance Expert Advisory Subgroup on Diet and Health and Guideline Development Group on the use and interpretation of haemoglobin concentrations for assessing anaemia status in individuals and populations, member of the World Health Organization Nutrition Guidance Expert Advisory Subgroup on Diet and Health and Expert group on nutrient requirements: setting calcium, vitamin D and Zn nutrient intake values for children aged 0-4 years. He is also member of Expert Groups of the Ministry of Health and Family Welfare on Nutrition and Child Health. SD was involved in the CNNS study implementation. There were no other conflicts to declare. The views expressed here by the authors are in their individual capacity and should not be construed as views or recommendations of the institutions the authors belong to.

Ethical approval

The CNNS was conducted after obtaining due International Ethical approval from the Population Council’s International Review Board, New York, USA and National Ethical approval from Post Graduate Institute of Medical Education and Research, Chandigarh, India (Ref. 14).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pullakhandam, R., Ghosh, S., Kulkarni, B. et al. Reference cut-offs to define low serum zinc concentrations in healthy 1–19 year old Indian children and adolescents. Eur J Clin Nutr 76, 1150–1157 (2022). https://doi.org/10.1038/s41430-022-01088-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-022-01088-4

This article is cited by

Search

Advanced search

Quick links