Skip to main content Accessibility help
×
×
Home

Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis

  • Adrian R. Martineau (a1)
Abstract

Tuberculosis (TB) is a major cause of mortality, responsible for 1·68 million deaths worldwide in 2009. The global prevalence of latent Mycobacterium tuberculosis infection is estimated to be 32%, and this carries a 5–20% lifetime risk of reactivation disease. The emergence of drug-resistant organisms necessitates the development of new agents to enhance the response to antimicrobial therapy for active TB. Vitamin D was used to treat TB in the pre-antibiotic era, and its active metabolite, 1,25-dihydoxyvitamin D, has long been known to enhance the immune response to mycobacteria in vitro. Vitamin D deficiency is common in patients with active TB, and several clinical trials have evaluated the role of adjunctive vitamin D supplementation in its treatment. Results of these studies are conflicting, reflecting variation between studies in baseline vitamin D status of participants, dosing regimens and outcome measures. Vitamin D deficiency is also recognised to be highly prevalent among people with latent M. tuberculosis infection in both high- and low-burden settings, and there is a wealth of observational epidemiological evidence linking vitamin D deficiency with increased risk of reactivation disease. Randomised controlled trials of vitamin D supplementation for the prevention of active TB have yet to be performed, however. The conduct of such trials is a research priority, given the safety and low cost of vitamin D supplementation, and the potentially huge public health consequences of positive results.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis
      Available formats
      ×
Copyright
Corresponding author
Corresponding author: Dr Adrian Martineau, fax +44 207 882 2552, email a.martineau@qmul.ac.uk
References
Hide All
1. Dye, C, Scheele, S, Dolin, P et al. (1999) Consensus statement. Global burden of tuberculosis: Estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 282, 677686.
2. Horsburgh, CR Jr (2004) Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 350, 20602067.
3. Wood, R, Maartens, G & Lombard, CJ (2000) Risk factors for developing tuberculosis in HIV-1-infected adults from communities with a low or very high incidence of tuberculosis. J Acquir Immune Defic Syndr 23, 7580.
4. WHO (2010) Global Tuberculosis Control: WHO Report 2010. Geneva: WHO Press.
5. Raab, W (1946) Vitamin D – its bactericidal action. Chest 12, 409415.
6. Rook, GA, Steele, J, Fraher, L et al. (1986) Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 57, 159163.
7. Liu, PT, Stenger, S, Li, H et al. (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311, 17701773.
8. Krutzik, SR, Hewison, M, Liu, PT et al. (2008) IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway. J Immunol 181, 71157120.
9. Vieth, R, McCarten, K & Norwich, KH (1990) Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production. Am J Physiol 258, E780E789.
10. Vieth, R (2005) The pharmacology of vitamin D, including fortification strategies. In Vitamin D pp. 995–1015 [Glorieux, FH, Pike, JW and Feldman, D]. London: Academic Press.
11. Norman, AW, Mizwicki, MT & Norman, DP (2004) Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model. Nat Rev Drug Discov 3, 2741.
12. Martineau, AR, Wilkinson, KA, Newton, SM et al. (2007) IFN-γ- and TNF-independent vitamin D-inducible human suppression of mycobacteria: The role of cathelicidin LL-37. J Immunol 178, 71907198.
13. Rockett, KA, Brookes, R, Udalova, I et al. (1998) 1,25-dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line. Infect Immun 66, 53145321.
14. Sly, LM, Lopez, M, Nauseef, WM et al. (2001) 1alpha,25-dihydroxyvitamin D3-induced monocyte antimycobacterial activity is regulated by phosphatidylinositol 3-kinase and mediated by the NADPH-dependent phagocyte oxidase. J Biol Chem 276, 3548235493.
15. Anand, K & Kaul, D (2003) Vitamin D3-dependent pathway regulates TACO gene transcription. Biochem Biophys Res Commun 310, 876877.
16. Hmama, Z, Sendide, K, Talal, A et al. (2004) Quantitative analysis of phagolysosome fusion in intact cells: Inhibition by mycobacterial lipoarabinomannan and rescue by an 1alpha,25-dihydroxyvitamin D3-phosphoinositide 3-kinase pathway. J Cell Sci 117, 21312140.
17. Coussens, A, Timms, PM, Boucher, BJ et al. (2009) 1alpha,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection. Immunology 127, 539548.
18. Liu, PT, Schenk, M, Walker, VP et al. (2009) Convergence of IL-1beta and VDR activation pathways in human TLR2/1-induced antimicrobial responses. PLoS ONE 4, e5810.
19. Martineau, AR, Newton, SM, Wilkinson, KA et al. (2007) Neutrophil-mediated innate immune resistance to mycobacteria. J Clin Invest 117, 19881994.
20. Yuk, JM, Shin, DM, Lee, HM et al. (2009) Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe 6, 231243.
21. Shin, DM, Yuk, JM, Lee, HM et al. (2010) Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signalling. Cell Microbiol 12, 16481665.
22. Liu, PT, Stenger, S, Tang, DH et al. (2007) Cutting edge: Vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol 179, 20602063.
23. Glisson, F, Bate, G & Regemorter, A (1651) A Treatise of the Rickets: being A Disease Common to Children. London: P. Cole.
24. De Ugarte, DA, Shapiro, NL & Williams, HL (2003) Tuberculous mediastinal mass presenting with stridor in a 3-month-old child. J Pediatr Surg 38, 624625.
25. Chapman, HT (1849) On the use of cod-liver oil in diseases of the bones and joints, in consumption and in other maladies attended by great emaciation. Pharm Trans, 116.
26. Karyadi, E, West, CE, Schultink, W et al. (2002) A double-blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: Effects on clinical response and nutritional status. Am J Clin Nutr 75, 720727.
27. Mayer, E (1938) Heliotherapy of tuberculosis. Ann Int Med 11, 18561860.
28. Roelandts, R (2005) A new light on Niels Finsen, a century after his Nobel Prize. Photodermatol Photoimmunol Photomed 21, 115117.
29. Askew, FA, Bruce, HM, Callow, RK et al. (1931) Crystalline vitamin D. Nature 128, 758.
30. Charpy, J (1950) Quelques traitments vitaminés ou par substances fonctionelles en dermatologie. Bull Méd 24, 505.
31. Martineau, AR, Honecker, FU, Wilkinson, RJ et al. (2007) Vitamin D in the treatment of pulmonary tuberculosis. J Steroid Biochem Mol Biol 103, 793798.
32. Davies, PD (1985) A possible link between vitamin D deficiency and impaired host defence to Mycobacterium tuberculosis . Tubercle 66, 301306.
33. Davies, PD, Brown, RC & Woodhead, JS (1985) Serum concentrations of vitamin D metabolites in untreated tuberculosis. Thorax 40, 187190.
34. Davies, PD, Church, HA, Brown, RC et al. (1987) Raised serum calcium in tuberculosis patients in Africa. Eur J Respir Dis 71, 341344.
35. Davies, PD, Church, HA, Bovornkitti, S et al. (1988) Altered vitamin D homeostasis in tuberculosis. Int Med Thailand 4, 4547.
36. Wilkinson, RJ, Llewelyn, M, Toossi, Z et al. (2000) Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: A case-control study. Lancet 355, 618621.
37. Sasidharan, PK, Rajeev, E & Vijayakumari, V (2002) Tuberculosis and vitamin D deficiency. J Assoc Physicians India 50, 554558.
38. Sita-Lumsden, A, Lapthorn, G, Swaminathan, R et al. (2007) Reactivation of tuberculosis and vitamin D deficiency: The contribution of diet and exposure to sunlight. Thorax 62, 10031007.
39. Gibney, KB, MacGregor, L, Leder, K et al. (2008) Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. Clin Infect Dis 46, 443446.
40. Ho-Pham, LT, Nguyen, ND, Nguyen, TT et al. (2010) Association between vitamin D insufficiency and tuberculosis in a Vietnamese population. BMC Infect Dis 10, 306.
41. Grange, JM, Davies, PD, Brown, RC et al. (1985) A study of vitamin D levels in Indonesian patients with untreated pulmonary tuberculosis. Tubercle 66, 187191.
42. Chan, TY, Poon, P, Pang, J et al. (1994) A study of calcium and vitamin D metabolism in Chinese patients with pulmonary tuberculosis. J Trop Med Hyg 97, 2630.
43. Martineau, AR, Leandro, AC, Anderson, ST et al. (2010) Association between Gc genotype and susceptibility to TB is dependent on vitamin D status. Eur Respir J 35, 11061112.
44. Nielsen, NO, Skifte, T, Andersson, M et al. (2010) Both high and low serum vitamin D concentrations are associated with tuberculosis: A case-control study in Greenland. Br J Nutr 104, 14871489.
45. Bellamy, R, Ruwende, C, Corrah, T et al. (1999) Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene. J Infect Dis 179, 721724.
46. Gao, L, Tao, Y, Zhang, L et al. (2010) Vitamin D receptor genetic polymorphisms and tuberculosis: Updated systematic review and meta-analysis. Int J Tuberc Lung Dis 14, 1523.
47. Arnaud, J & Constans, J (1993) Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet 92, 183188.
48. Lauridsen, AL, Vestergaard, P, Hermann, AP et al. (2005) Plasma concentrations of 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D are related to the phenotype of Gc (vitamin D-binding protein): A cross-sectional study on 595 early postmenopausal women. Calcif Tissue Int 77, 1522.
49. Abbas, S, Linseisen, J, Slanger, T et al. (2008) The Gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status. Cancer Epidemiol Biomarkers Prev 17, 13391343.
50. Papiha, SS, Agarwal, SS & White, I (1983) Association between phosphoglucomutase (PGM1) and group-specific component (Gc) subtypes and tuberculosis. J Med Genet 20, 220222.
51. Spitsyn, VA & Titenko, NV (1990) Subtypes of serum group specific component (Gc) in normal conditions and in pathology. Genetika 26, 749759.
52. Bahr, GM, Eales, LJ, Nye, KE et al. (1989) An association between Gc (vitamin D-binding protein) alleles and susceptibility to rheumatic fever. Immunology 67, 126128.
53. Roth, DE, Soto, G, Arenas, F et al. (2004) Association between vitamin D receptor gene polymorphisms and response to treatment of pulmonary tuberculosis. J Infect Dis 190, 920927.
54. Babb, C, van der Merwe, L, Beyers, N et al. (2007) Vitamin D receptor gene polymorphisms and sputum conversion time in pulmonary tuberculosis patients. Tuberculosis (Edinb) 87, 295302.
55. Talat, N, Perry, S, Parsonnet, J et al. (2010) Vitamin D deficiency and tuberculosis progression. Emerg Infect Dis 16, 853855.
56. Kampmann, B, Gaora, PO, Snewin, VA et al. (2000) Evaluation of human antimycobacterial immunity using recombinant reporter mycobacteria. J Infect Dis 182, 895901.
57. Martineau, AR, Wilkinson, RJ, Wilkinson, KA et al. (2007) A single dose of vitamin D enhances immunity to mycobacteria. Am J Respir Crit Care Med 176, 208213.
58. Gwinup, G, Randazzo, G & Elias, A (1981) The influence of vitamin D intake on serum calcium in tuberculosis. Acta Endocrinol (Copenh) 97, 114117.
59. Martineau, AR, Nanzer, AM, Satkunam, KR et al. (2009) Influence of a single oral dose of vitamin D2 on serum 25-hydroxyvitamin D concentrations in tuberculosis patients. Int J Tuberc Lung Dis 13, 119125.
60. Narang, NK, Gupta, RC & Jain, MK (1984) Role of vitamin D in pulmonary tuberculosis. J Assoc Physicians India 32, 185188.
61. Tjellesen, L, Hummer, L, Christiansen, C et al. (1986) Serum concentration of vitamin D metabolites during treatment with vitamin D2 and D3 in normal premenopausal women. Bone Miner 1, 407413.
62. Stern, PH, Taylor, AB, Bell, NH et al. (1981) Demonstration that circulating 1 alpha, 25-dihydroxyvitamin D is loosely regulated in normal children. J Clin Invest 68, 13741377.
63. Morcos, MM, Gabr, AA, Samuel, S et al. (1998) Vitamin D administration to tuberculous children and its value. Boll Chim Farm 137, 157164.
64. Nursyam, EW, Amin, Z & Rumende, CM (2006) The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med Indones 38, 35.
65. Wejse, C, Gomes, VF, Rabna, P et al. (2009) Vitamin D as supplementary treatment for tuberculosis: A double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 179, 843850.
66. Martineau, AR, Timms, PM, Bothamley, GH et al. (2011) High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: A double-blind randomised controlled trial. Lancet 377, 242250.
67. Vieth, R (2011) Vitamin D nutrient to treat TB begs the prevention question. Lancet 377, 189190.
68. Ferebee, SH (1970) Controlled chemoprophylaxis trials in tuberculosis. A general review. Bibl Tuberc 26, 28–106.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed