The Indian Journal of Pediatrics

, Volume 80, Issue 3, pp 215–218

Use of Vitamin D in Various Disorders

Special Article

Abstract

Approximately 1 billion people worldwide have been identified as vitamin D deficient in the 21st century, and the number is on the rise; non-classical actions of vitamin D were initially recognized around 30 y ago when receptors for vitamin D were detected in neoplastic cells lines. The aim of this review is to provide a brief overview of the non-classical actions of vitamin D. Reports describing the associations of non skeletal actions of vitamin D, especially pertaining to the immune system, inflammatory disorders, cancers and cardiovascular disease have been summarized in this paper. Reports support a role for the active form of vitamin D in mediating normal function of both the innate and adaptive immune systems. Studies also suggest a link between vitamin D deficiency and autoimmune diseases, such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus and type 1diabetes. There is believed to be an inverse association between serum 25-hydroxyvitamin D concentrations and the incidence of colorectal cancer, sporadic colorectal adenoma and breast cancer. Vitamin D deficiency has been linked with various cardiovascular diseases such as hypertension, myocardial infarction, and stroke. Several epidemiological and genetic studies suggest a strong association between vitamin D and non skeletal acute and chronic disorders. However, currently, robust clinical data are still lacking to support raising intake requirements and target vitamin D plasma levels. Nonetheless, the high prevalence of vitamin D deficiency is alarming and requires implementation of clear supplementation guidelines.

Keywords

Vitamin D Non skeletal Diabetes Cancer 

References

  1. 1.
    Shinchuk LM, Holick MF. Vitamin D and rehabilitation: improving functional outcomes. Nutr Clin Pract. 2007;22:297–304.PubMedCrossRefGoogle Scholar
  2. 2.
    Ekbote VH, Khadilkar AV, Mughal MZ, et al. Sunlight exposure and development of rickets in Indian toddlers. Indian J Pediatr. 2010;77:61–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Eisman JA, Martin TJ, MacIntyre I, Moseley JM. 1,25-dihydroxyvitamin-D-receptor in breast cancer cells. Lancet. 1979;2:1335.PubMedCrossRefGoogle Scholar
  4. 4.
    Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.PubMedCrossRefGoogle Scholar
  5. 5.
    Muszkat P, Camargo MB, Griz LH, Lazaretti-Castro M. Evidence-based non-skeletal actions of vitamin D. Arq Bras Endocrinol Metabol. 2010;54:110–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Martineau AR, Honecker FU, Wilkinson RJ, Griffiths CJ. Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol. 2007;103:793.PubMedCrossRefGoogle Scholar
  7. 7.
    Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Rheum Dis Clin North Am. 2012;38:125–39.PubMedCrossRefGoogle Scholar
  8. 8.
    Toubi E, Shoenfeld Y. The role of vitamin D in regulating immune responses. Isr Med Assoc J. 2010;12:174–5.PubMedGoogle Scholar
  9. 9.
    Segaert S. Vitamin D regulation of cathelicidin in the skin: toward a renaissance of vitamin D in dermatology? J Invest Dermatol. 2008;128:773–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Nizet V, Ohtake T, Lauth X, et al. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature. 2001;414:454–7. doi:10.1038/35106587.PubMedCrossRefGoogle Scholar
  11. 11.
    Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–3.PubMedCrossRefGoogle Scholar
  12. 12.
    Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25- dihydroxyvitamin D3. FASEB J. 2005;19:1067.PubMedCrossRefGoogle Scholar
  13. 13.
    Schauber J, Dorschner RA, Coda AB, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest. 2007;117:803.PubMedCrossRefGoogle Scholar
  14. 14.
    Yim S, Dhawan P, Ragunath C, Christakos S, Diamond G. Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25-dihydroxyvitamin D(3). J Cyst Fibros. 2007;6:403.PubMedCrossRefGoogle Scholar
  15. 15.
    Liu N, Kaplan AT, Low J, et al. Vitamin D induces innate antibacterial responses in human trophoblasts via an intracrine pathway. Biol Reprod. 2009;80:398.PubMedCrossRefGoogle Scholar
  16. 16.
    Hertting O, Holm Å, Lüthje P, et al. Vitamin D induction of the human antimicrobial Peptide cathelicidin in the urinary bladder. PLoS One. 2010;5:e15580.PubMedCrossRefGoogle Scholar
  17. 17.
    Finklea JD, Grossmann RE, Tangpricha V. Vitamin D and chronic lung disease: a review of molecular mechanisms and clinical studies. Adv Nutr. 2011;2:244–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008;37:113–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Li F, Peng M, Jiang L, et al. Vitamin D deficiency is associated with decreased lung function in Chinese  adults with asthma. Respiration. 2011;81:469–75.PubMedCrossRefGoogle Scholar
  20. 20.
    Morales E, Romieu I, Guerra S, et al. Maternal vitamin D status in pregnancy and risk of lower respiratory tract infections, wheezing, and asthma in offspring. Epidemiology. 2012;23:64–71.PubMedCrossRefGoogle Scholar
  21. 21.
    Cutolo M, Otsa K, Uprus M, Paolino S, Seriolo B. Vitamin D in rheumatoid arthritis. Autoimmun Rev. 2007;7:59–64.PubMedCrossRefGoogle Scholar
  22. 22.
    Doria A, Arienti S, Rampudda M, Canova M, Tonon M, Sarzi-Puttini P. Preventive strategies in systemic lupus erythematosus. Autoimmun Rev. 2008;7:192–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Carvalho JF, Blank M, Kiss E, Tarr T, Amital H, Shoenfeld Y. Anti-vitamin D, vitamin D, in SLE: preliminary results. Ann N Y Acad Sci. 2007;1109:550–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Borba VZ, Vieira JG, Kasamatsu T, Radominski SC, Sato EI, Lazaretti-Castro M. Vitamin D deficiency in patients with active systemic lupus erythematosus. Osteoporos Int. 2009;20:427–33.PubMedCrossRefGoogle Scholar
  25. 25.
    Kamen D, Aranow C. Vitamin D in systemic lupus erythematosus. Curr Opin Rheumatol. 2008;20:532–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Moghimi J, Sadeghi A, Malek M, Ghorbani R. Relationship between disease activity and serum levels of vitamin D and parathyroid hormone in rheumatoid arthritis. Endocr Regul. 2012;46:61–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Kaur H, Donaghue KC, Chan AK, et al. Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1diabetes. Diabetes Care. 2011;34:1400–2.PubMedCrossRefGoogle Scholar
  28. 28.
    Cooper JD, Smyth DJ, Walker NM, et al. Inherited variation in vitamin D genes is associated with predisposition to autoimmune disease type 1 diabetes. Diabetes. 2011;60:1624–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Sørensen IM, Joner G, Jenum PA, Eskild A, Torjesen PA, Stene LC. Maternal serum levels of 25-hydroxy-vitamin D during pregnancy and risk of type 1 diabetes in the offspring. Diabetes. 2012;61:175–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Boscoe FP, Schymura MJ. Solar ultraviolet- B exposure and cancer incidence and mortality in the United States, 1993–2002. BMC Cancer. 2006;6:264.PubMedCrossRefGoogle Scholar
  31. 31.
    Welsh J. Targets of vitamin D receptor signaling in the mammary gland. J Bone Miner Res. 2007;22:V86–90.PubMedCrossRefGoogle Scholar
  32. 32.
    Krishnan AV, Trump DL, Johnson CS, Feldman D. The role of vitamin D in cancer prevention and treatment. Endocrinol Metab Clin North Am. 2010;39:401–18.PubMedCrossRefGoogle Scholar
  33. 33.
    Martínez ME, Jacobs ET, Baron JA, Marshall JR, Byers T. Dietary supplements and cancer prevention: balancing potential benefitsagainst proven harms. J Natl Cancer Inst. 2012;104:732–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586–91.PubMedGoogle Scholar
  35. 35.
    IARC Working Group Report. Vitamin D and cancer. Lyon France: International Agency for Research on Cancer; 2008.Google Scholar
  36. 36.
    McGreevy C, Williams D. New insights about vitamin D and cardiovascular disease: a narrative review. Ann Intern Med. 2011;155:820–6.PubMedGoogle Scholar
  37. 37.
    Aggarwal N, Reis JP, Michos ED. Vitamin D deficiency and its implications on cardiovascular disease. Curr Cardio Risk Rep. 2010;4:68–75.CrossRefGoogle Scholar
  38. 38.
    Tishkoff DX, Nibbelink KA, Holmberg KH, Dandu L, Simpson RU. Functional vitamin D receptor (VDR) in the t-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility. Endocrinology. 2008;149:558–64.PubMedCrossRefGoogle Scholar
  39. 39.
    Müller K, Haahr PM, Diamant M, Rieneck K, Kharazmi A, Bendtzen K. 1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level. Cytokine. 1992;4:506–12.PubMedCrossRefGoogle Scholar
  40. 40.
    Schurgers LJ, Dissel PE, Spronk HM, et al. Role of vitamin K and vitamin K-dependent proteins in vascular calcification. Z Kardiol. 2001;90:57–63.PubMedCrossRefGoogle Scholar
  41. 41.
    Hagström E, Hellman P, Larsson TE, et al. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009;119:2765–71.PubMedCrossRefGoogle Scholar
  42. 42.
    Soni M, Kos K, Lang IA, Jones K, Melzer D, Llewellyn DJ. Vitamin D and cognitive function. Scand J Clin Lab Invest. 2012;243:79–82.PubMedGoogle Scholar
  43. 43.
    Soares MJ, Murhadi LL, Kurpad AV, Chan She Ping-Delfos WL, Piers LS. Mechanistic roles for calcium and vitamin D in the regulation of body weight. Obes Rev. 2012;13:592–605. doi:10.1111/j.1467-789X.2012.00986.x [Epub ahead of print].

Copyright information

© Dr. K C Chaudhuri Foundation 2012

Authors and Affiliations

  1. 1.Growth and Pediatric Endocrine Unit, Hirabai Cowasji Jehangir Medical Research InstituteJehangir HospitalPuneIndia
  2. 2.Growth and Endocrine Unit, Hirabai Cowasji Jehangir Medical Research InstituteOld Building Basement, Jehangir HospitalPuneIndia

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