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Occurrence of infections in schoolchildren subsequent to supplementation with vitamin D-calcium or zinc: a randomized, double-blind, placebo-controlled trial

  • Mandlik, Rubina (Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital) ;
  • Mughal, Zulf (Department of Pediatric Endocrinology & Metabolic Bone Diseases, Royal Manchester Children's Hospital) ;
  • Khadilkar, Anuradha (Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital) ;
  • Chiplonkar, Shashi (Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital) ;
  • Ekbote, Veena (Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital) ;
  • Kajale, Neha (Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital) ;
  • Patwardhan, Vivek (Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital) ;
  • Padidela, Raja (Department of Pediatric Endocrinology & Metabolic Bone Diseases, Royal Manchester Children's Hospital) ;
  • Khadilkar, Vaman (Hirabai Cowasji Jehangir Medical Research Institute, Jehangir Hospital)
  • Received : 2019.05.20
  • Accepted : 2019.08.13
  • Published : 2020.04.01

Abstract

BACKGROUND/OBJECTIVES: Vitamin D and zinc are recognized for their roles in immune-modulation, and their deficiencies are suggested to be important risk factors for childhood infections. This study, therefore, undertook to assess the occurrence of infections in rural Indian schoolchildren, subsequent to daily supplementation with vitamin D-calcium or zinc for 6 months. SUBJECTS/METHODS: This was a randomized, double-blind, placebo-controlled trial in apparently healthy 6-12 year-old rural Indian children, recruited to 3 study arms: vitamin D arm (1,000 IU D3 - 500 mg calcium, n = 135), zinc arm (10 mg, n = 150) and placebo arm (n = 150). The infection status was assessed using a validated questionnaire, and the biochemical parameters of serum 25(OH)D and serum zinc were measured by ELISA and colorimetry, respectively. The primary outcome variable was occurrence of infections (upper respiratory and total infections). RESULTS: Serum 25(OH)D concentration in the vitamin D arm improved significantly by 34%, from 59.7 ± 10.9 nmol/L to 80 ± 23.3 nmol/L (P < 0.0001), but no improvement was observed for serum zinc concentration. While there was significant increase in the percentage of children reporting no or mild upper respiratory tract infections (URTI) and total infections (TI) in all three groups, improvements in the supplemented groups were similar to the placebo group. However, the vitamin D arm reported lower URTI and TI status in the vitamin D sufficient versus insufficient children. Also, URTI and TI status were found to be significantly (P < 0.0001) lower in children with improved 25(OH)D versus unchanged 25(OH)D. CONCLUSIONS: Vitamin D-calcium supplementation helped to improve the vitamin D status but exerts no effect on the occurrence of infections when compared to the placebo group. Improvement in the serum 25(OH)D concentrations and attainment of vitamin D sufficiency may exert a beneficial effect on the infection status and needs to be investigated further. To evaluate the efficacy of zinc supplementation, higher dosages need to be administered in future studies.

References

  1. International Institute for Population Sciences. National Family Health Survey (NFHS-4): 2015-16. Mumbai: International Institute for Population Sciences; 2017.
  2. Scrimshaw NS. Effect of infection on nutritional status. Proc Natl Sci Counc Repub China B 1992;16:46-64.
  3. Maggini S, Wintergerst ES, Beveridge S, Hornig DH. Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. Br J Nutr 2007;98 Suppl 1:S29-35. https://doi.org/10.1017/S0007114507832971
  4. Suaini NH, Zhang Y, Vuillermin PJ, Allen KJ, Harrison LC. Immune modulation by vitamin D and its relevance to food allergy. Nutrients 2015;7:6088-108. https://doi.org/10.3390/nu7085271
  5. Wacker M, Holick MF. Vitamin D - effects on skeletal and extraskeletal health and the need for supplementation. Nutrients 2013;5:111-48. https://doi.org/10.3390/nu5010111
  6. Londhey V. Vitamin D deficiency: Indian scenario. J Assoc Physicians India 2011;59:695-6.
  7. Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D. Vitamin D status in Andhra Pradesh: a population-based study. Indian J Med Res 2008;127:211-8.
  8. Harinarayan C, Holick M, Prasad U V, Vani PS, Himabindu G. Vitamin D status and sun exposure in India. Dermatoendocrinol. 2013;5(1):130-41. https://doi.org/10.4161/derm.23873
  9. Clements MR, Johnson L, Fraser DR. A new mechanism for induced vitamin D deficiency in calcium deprivation. Nature 1987;325:62-5. https://doi.org/10.1038/325062a0
  10. Pettifor JM. Nutritional rickets: deficiency of vitamin D, calcium, or both? Am J Clin Nutr 2004;80:1725S-1729S. https://doi.org/10.1093/ajcn/80.6.1725S
  11. Khadilkar A, Kadam N, Chiplonkar S, Fischer PR, Khadilkar V. Schoolbased calcium-vitamin D with micronutrient supplementation enhances bone mass in underprivileged Indian premenarchal girls. Bone 2012;51:1-7. https://doi.org/10.1016/j.bone.2012.03.029
  12. Lappe JM, Heaney RP. Why randomized controlled trials of calcium and vitamin D sometimes fail. Dermatoendocrinol 2012;4:95-100. https://doi.org/10.4161/derm.19833
  13. Kapil U, Jain K. Magnitude of zinc deficiency amongst under five children in India. Indian J Pediatr 2011;78:1069-72. https://doi.org/10.1007/s12098-011-0379-z
  14. Tupe RP, Chiplonkar SA. Zinc supplementation improved cognitive performance and taste acuity in Indian adolescent girls. J Am Coll Nutr 2009;28:388-96. https://doi.org/10.1080/07315724.2009.10718101
  15. Sivakumar B, Vijayaraghavan K, Vazir S, Balakrishna N, Shatrugna V, Sarma KV, Nair KM, Raghuramulu N, Krishnaswamy K. Effect of micronutrient supplement on health and nutritional status of schoolchildren: study design. Nutrition 2006;22 Suppl:S1-7. https://doi.org/10.1016/j.nut.2005.07.009
  16. Thomas T, Eilander A, Muthayya S, McKay S, Thankachan P, Theis W, Gandhe A, Osendarp SJ, Kurpad AV. The effect of a 1-year multiple micronutrient or n-3 fatty acid fortified food intervention on morbidity in Indian school children. Eur J Clin Nutr 2012;66:452-8. https://doi.org/10.1038/ejcn.2011.178
  17. Ananthakrishnan S, Pani SP, Nalini P. A comprehensive study of morbidity in school age children. Indian Pediatr 2001;38:1009-17.
  18. Chowdhury SD, Ghosh T. Nutritional and socioeconomic status in cognitive development of Santal children of Purulia district, India. Ann Hum Biol 2011;38:188-93. https://doi.org/10.3109/03014460.2010.506887
  19. Manaseki-Holland S, Maroof Z, Bruce J, Mughal MZ, Masher MI, Bhutta ZA, Walraven G, Chandramohan D. Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial. Lancet 2012;379:1419-27. https://doi.org/10.1016/S0140-6736(11)61650-4
  20. Aluisio AR, Maroof Z, Chandramohan D, Bruce J, Mughal MZ, Bhutta Z, Walraven G, Masher MI, Ensink JH, Manaseki-Holland S. Vitamin D3 supplementation and childhood diarrhea: a randomized controlled trial. Pediatrics 2013;132:e832-40. https://doi.org/10.1542/peds.2012-3986
  21. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr 2010;91:1255-60. https://doi.org/10.3945/ajcn.2009.29094
  22. Lang PO, Aspinall R. Can we translate vitamin D immunomodulating effect on innate and adaptive immunity to vaccine response? Nutrients 2015;7:2044-60. https://doi.org/10.3390/nu7032044
  23. Kurugol Z, Bayram N, Atik T. Effect of zinc sulfate on common cold in children: randomized, double blind study. Pediatr Int 2007;49:842-7. https://doi.org/10.1111/j.1442-200X.2007.02448.x
  24. Muller O, Becher H, van Zweeden AB, Ye Y, Diallo DA, Konate AT, Gbangou A, Kouyate B, Garenne M. Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial. BMJ 2001;322:1567. https://doi.org/10.1136/bmj.322.7302.1567
  25. Some JW, Abbeddou S, Yakes Jimenez E, Hess SY, Ouedraogo ZP, Guissou RM, Vosti SA, Ouedraogo JB, Brown KH. Effect of zinc added to a daily small-quantity lipid-based nutrient supplement on diarrhoea, malaria, fever and respiratory infections in young children in rural Burkina Faso: a cluster-randomised trial. BMJ Open 2015;5:e007828. https://doi.org/10.1136/bmjopen-2015-007828
  26. Solar Energy Centre, MNRE; Indian Metrological Department. Typical Climatic Data for Selected Radiation Stations (The Data Period Covered: 1986-2000). Solar Radiation Hand Book (2008) [Internet]. New Delhi: Indian Metrological Department; 2008 [cited 2017 Oct 28]. Available from: http://www.indiaenvironmentportal.org.in/files/srd-sec.pdf.
  27. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-30. https://doi.org/10.1210/jc.2011-0385
  28. Indian Council of Medical Research. Nutrient Requirements & Recommended Dietary Allowances for Indians. Hyderabad: Expert Group of the Indian Council of Medical Research; 2009.
  29. Kumar N, Shekhar C, Kumar P, Kundu AS. Kuppuswamy's socioeconomic status scale-updating for 2007. Indian J Pediatr 2007.74:1131-2.
  30. Patwardhan VG, Khadilkar AV, Chiplonkar SA, Mughal ZM, Khadilkar VV. Varying relationship between 25-hydroxy-vitamin D, high density lipoprotein cholesterol, and serum 7-dehydrocholesterol reductase with sunlight exposure. J Clin Lipidol 2015;9:652-7. https://doi.org/10.1016/j.jacl.2015.05.007
  31. Deb S, Dutta S, Dasgupta A, Misra R. Relationship of personal hygiene with nutrition and morbidity profile: a study among primary school children in South Kolkata. Indian J Community Med 2010;35:280-4. https://doi.org/10.4103/0970-0218.66894
  32. Chiplonkar SA, Agte VV, Mengale SS, Tarwadi KV. Are lifestyle factors good predictors of retinol and vitamin C deficiency in apparently healthy adults? Eur J Clin Nutr 2002;56:96-104. https://doi.org/10.1038/sj.ejcn.1601291
  33. Khadilkar V, Yadav S, Agrawal KK, Tamboli S, Banerjee M, Cherian A, Goyal JP, Khadilkar A, Kumaravel V, Mohan V, Narayanappa D, Ray I, Yewale V; Indian Academy of Pediatrics Growth Charts Committee. Revised IAP growth charts for height, weight and body mass index for 5- to 18-year-old Indian children. Indian Pediatr 2015;52:47-55. https://doi.org/10.1007/s13312-015-0566-5
  34. Chiplonkar S. CDiet - BELLYCHEATERS [Internet]. Pune: BELLYCHEATERS; [cited 2018 Oct 5]. Available from: https://bellycheaters.com/cdiet/.
  35. Longvah T, Ananthan R, Bhaskarachary K, Venkaiah K; National Institute of Nutrition. Indian Food Composition Tables. 1st ed. Longvah T, editor. Hyderabad: National Institute of Nutrition; 2017.
  36. Chiplonkar SA, Agte VV. Extent of error in estimating nutrient intakes from food tables versus laboratory estimates of cooked foods. Asia Pac J Clin Nutr 2007;16:227-39.
  37. Brown KH. IZiNCG Technical Brief: Assessing Population Zinc Status with Serum Zinc Concentration. Davis (CA): International Zinc Nutrition Consultative Group; 2012.
  38. Bruijnzeels MA, Foets M, van der Wouden JC, Prins A, van den Heuvel WJ. Measuring morbidity of children in the community: a comparison of interview and diary data. Int J Epidemiol 1998;27:96-100. https://doi.org/10.1093/ije/27.1.96
  39. Mandlik R, Chiplonkar S, Kajale N, Khadilkar V, Khadilkar A. Infection status of rural schoolchildren and its relationship with Vitamin D concentrations. Indian J Pediatr 2019;86:675-80. https://doi.org/10.1007/s12098-019-02933-4
  40. Camargo CA Jr, Ganmaa D, Frazier AL, Kirchberg FF, Stuart JJ, Kleinman K, Sumberzul N, Rich-Edwards JW. Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia. Pediatrics 2012;130:e561-7. https://doi.org/10.1542/peds.2011-3029
  41. Shalini CN, Murthy NS, Shalini S, Dinesh R, Shivaraj NS, Suryanarayana SP. Comparison of nutritional status of rural and urban school students receiving midday meals in schools of Bengaluru, India: a cross sectional study. J Postgrad Med 2014;60:118-22. https://doi.org/10.4103/0022-3859.132309
  42. Mandlik R, Khadilkar A, Kajale N, Ekbote V, Patwardhan V, Mistry S, Khadilkar V, Chiplonkar S. Response of serum 25(OH)D to Vitamin D and calcium supplementation in school-children from a semi-rural setting in India. J Steroid Biochem Mol Biol 2018;180:35-40. https://doi.org/10.1016/j.jsbmb.2017.12.003
  43. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583.
  44. Mayo-Wilson E, Junior JA, Imdad A, Dean S, Chan XH, Chan ES, Jaswal A, Bhutta ZA. Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years of age. Cochrane Database Syst Rev 2014:CD009384.
  45. Moran VH, Stammers AL, Medina MW, Patel S, Dykes F, Souverein OW, Dullemeijer C, Perez-Rodrigo C, Serra-Majem L, Nissensohn M, Lowe NM. 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