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Minerals, trace elements, Vit. D and bone health

Effect of vitamin D supplementation of low birth weight term Indian infants from birth on cytokine production at 6 months

Abstract

BACKGROUND/OBJECTIVES:

Vitamin D deficiency has been associated with impaired resistance to infection, which may be mediated by alterations in cytokine responses. We investigated the effect of vitamin D supplementation to infants on whole blood in-vitro cytokine production and on the inflammatory marker, plasma C-reactive protein (CRP).

SUBJECTS/METHODS:

Blood samples were taken at 6 months of age from infants participating in the DIVIDS (Delhi Infant Vitamin D Supplementation) randomized controlled trial of weekly vitamin D supplements (1400 IU=recommended intake) from birth to 6 months with the aim of decreasing mortality and severe morbidity. We measured plasma CRP and whole blood in-vitro production of tumour necrosis factor-α (TNFα), interferon-γ (INFγ), interleukin (IL)-10 and IL-13 following no stimulation or stimulation with lipopolysaccharide or phytohemagglutinin.

RESULTS:

Although the intervention improved vitamin D status in a severely deficient population, there were no differences between treatment groups in plasma CRP or in the production of any of the cytokines in either unstimulated or stimulated cultures. Recent illness had limited association with immunological markers. Plasma 25-hydroxyvitamin D levels were not associated with CRP or production of any cytokines.

CONCLUSIONS:

Vitamin D supplementation did not affect plasma CRP or whole blood cytokine production of vitamin D-deficient low birth weight infants. This is consistent with the lack of effect of vitamin D on mortality and severe morbidity among infants in the DIVIDS trial.

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References

  1. Wayse V, Yousafzai A, Mogale K, Filteau S : Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr 2004; 58, 563–567.

    Article  CAS  Google Scholar 

  2. Laaksi I, Ruohola JP, Tuohimaa P, Auvinen A, Haataja R, Pihlajamaki H et al. An association of serum vitamin D concentrations <40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr 2007; 86, 714–717.

    Article  CAS  Google Scholar 

  3. Roth DE, Shah R, Black RE, Baqui AH : Vitamin D status and acute lower respiratory infection in early childhood in Sylhet, Bangladesh. Acta Paediatr 2010; 99, 389–393.

    Article  CAS  Google Scholar 

  4. Gibney KB, MacGregor L, Leder K, Torresi J, Marshall C, Ebeling PR et al. Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. Clin Infect Dis 2008; 46, 443–446.

    Article  CAS  Google Scholar 

  5. Reid D, Toole BJ, Knox S, Talwar D, Harten J, O’Reilly DS et al. The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr 2011; 93, 1006–1011.

    Article  CAS  Google Scholar 

  6. Friis H, Range N, Pedersen ML, Molgaard C, Changalucha J, Krarup H et al. Hypovitaminosis D is common among pulmonary tuberculosis patients in Tanzania but is not explained by the acute phase response. J Nutr 2008; 138, 2474–2480.

    Article  CAS  Google Scholar 

  7. Newens K, Filteau S, Tomkins A : Plasma 25-hydroxyvitamin D does not vary over the course of a malarial infection. Trans R Soc Trop Med Hyg 2006; 100, 41–44.

    Article  CAS  Google Scholar 

  8. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S : Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr 2012; 95, 91–100.

    Article  CAS  Google Scholar 

  9. Penna G, Adorini L : 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000; 164, 2405–2411.

    Article  CAS  Google Scholar 

  10. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O’Garra A : 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 2001; 167, 4974–4980.

    Article  CAS  Google Scholar 

  11. Zhu Y, Mahon BD, Froicu M, Cantorna MT : Calcium and 1 alpha,25-dihydroxyvitamin D3 target the TNF-alpha pathway to suppress experimental inflammatory bowel disease. Eur J Immunol 2005; 35, 217–224.

    Article  CAS  Google Scholar 

  12. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R : Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006; 83, 754–759.

    Article  CAS  Google Scholar 

  13. Zittermann A, Frisch S, Berthold HK, Gotting C, Kuhn J, Kleesiek K et al. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr 2009; 89, 1321–1327.

    Article  CAS  Google Scholar 

  14. Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT : Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol 2003; 134, 128–132.

    Article  CAS  Google Scholar 

  15. Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D et al. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM 2002; 95, 787–796.

    Article  CAS  Google Scholar 

  16. Jorde R, Sneve M, Torjesen PA, Figenschau Y, Goransson LG, Omdal R : No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. Cytokine 2010; 50, 175–180.

    Article  CAS  Google Scholar 

  17. Kumar GT, Sachdev H, Chellani H, Rehman A, Singh V, Arora H et al. Effect of weekly vitamin D supplements to Indian low birth weight term infants on mortality, morbidity, and growth in the first 6 months of life: a randomised controlled trial. BMJ 2011; 342, d2975.

    Article  Google Scholar 

  18. Filmer D, Pritchett L : Estimating wealth effects without expenditure data – or tears: an application to educational enrolments in states of India. Demography 2001; 38, 115–132.

    CAS  Google Scholar 

  19. Wagner CL, Howard C, Hulsey TC, Lawrence RA, Taylor SN, Will H et al. Circulating 25-hydroxyvitamin D levels in fully breastfed infants on oral vitamin d supplementation. Int J Endocrinol 2010; 2010, 235035.

    Article  Google Scholar 

  20. Manaseki-Holland S, Qader G, Isaq Masher M, Bruce J, Zulf Mughal M, Chandramohan D et al. Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial. Trop Med Int Health 2010; 15, 1148–1155.

    Article  CAS  Google Scholar 

  21. Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 2011; 377, 242–250.

    Article  CAS  Google Scholar 

  22. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2009; 179, 843–850.

    Article  CAS  Google Scholar 

  23. Autier P, Gandini S : Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007; 167, 1730–1737.

    Article  CAS  Google Scholar 

  24. Nguyen-Vermillion A, Juul SE, McPherson RJ, Ledbetter DJ : Time course of C-reactive protein and inflammatory mediators after neonatal surgery. J Pediatr 2011; 159, 121–126.

    Article  CAS  Google Scholar 

  25. Thurnham DI : Plasma 25-hydroxy-cholecalciferol (vitamin D) is depressed by inflammation: implications and parallels with other micronutrients. Sight and Life Magazine [serial on the Internet] 2011 25: Available from: http://www.sightandlife.org/images/stories/pageimages/content/magazine/2011/25_2_11/sight_and_life_25_2_2011.pdf.

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Acknowledgements

We thank the infants and their families for their participation in the DIVIDS study and the field staff—Praveen, Aparna, Bunty, Sanjeev and Dinesh—for their work. We are grateful to Dr RN Salhan of Safdarjung Hospital and to the Data Safety and Monitoring Board—Dr Siddharth Ramji, Dr Shinjini Bhatnagar and Professor RM Pandey—for their help with the trial. We also extend our gratitude to Dr Ann Prentice and her team for helping set up the vitamin D assay in our laboratory, and to Dr Andrea Rehman and Dr Daniela Manno, London School of Hygiene and Tropical Medicine, for input into statistical analyses. We thank Dr Rajni Rani at National Institute of Immunology for advise on cytokine assays. We thank the Department of Biotechnology, Ministry of Science and Technology, Government of India; Nutrition Third World; and Sight and Life for funding the study.

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Correspondence to G Trilok-Kumar.

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Trilok-Kumar, G., Arora, H., Rajput, M. et al. Effect of vitamin D supplementation of low birth weight term Indian infants from birth on cytokine production at 6 months. Eur J Clin Nutr 66, 746–750 (2012). https://doi.org/10.1038/ejcn.2012.33

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  • DOI: https://doi.org/10.1038/ejcn.2012.33

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