Review
Vitamin D in the treatment of pulmonary tuberculosis

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Abstract

Vitamin D was used to treat tuberculosis in the pre-antibiotic era. New insights into the immunomodulatory properties of 1α,25-dihydroxy-vitamin D have rekindled interest in vitamin D as an adjunct to antituberculous therapy. We describe the historical use of vitamin D in tuberculosis treatment; discuss the mechanisms by which it may modulate host response to infection with Mycobacterium tuberculosis; and review three clinical trials and ten case series in which vitamin D has been used in the treatment of pulmonary tuberculosis.

Introduction

The resurgence of tuberculosis (TB) is a global emergency: in 2003 the disease caused an estimated 8.8 million new cases and 1.7 million deaths [1]. The development of new drugs to shorten treatment time and treat multi-drug resistant disease is a priority in controlling this epidemic [2]. Pharmacologic doses of vitamin D were used to treat TB in the pre-antibiotic era, but this practice fell out of widespread use with the introduction of effective anti-tuberculous chemotherapy. Interest in this area has recently been rekindled due to emerging evidence regarding the immunomodulatory properties of 1α,25-dihydroxyvitamin D (1α,25(OH)2D) in vitro.

Section snippets

Historical aspects

The use of vitamin D in TB treatment has a long history: in 1849 Williams reported results of administering fish liver oil to 234 TB cases, noting that ‘even in a few days…the appetite, flesh and strength were gradually improved’ and concluding that ‘the pure fresh oil from the liver of the cod is more beneficial in the treatment of pulmonary consumption than any agent, medicinal, dietetic, or regiminal, that has yet been employed’ [3]. Vitamin D3 was subsequently isolated from cod liver oil

Mechanism of action

Vitamin D has no direct antimycobacterial action, but its active metabolite 1α,25(OH)2D modulates host response to M. tuberculosis infection. In active disease the organism is contained within a central core of macrophages surrounded by T cells: the granuloma (Fig. 1). Expression of macrophage 25-hydroxy-vitamin D 1α-hydroxylase (1α-hydroxylase) is upregulated by ligation of macrophage toll-like receptors by M. tuberculosis antigens [7]. This enzyme metabolises 25-hydroxy-vitamin D (25(OH)D) to

Literature search

We identified 14 prospective clinical studies in which vitamin D had been administered to patients with PTB by searches of Medline, Oldmedline and reference lists from relevant articles. Search terms were “tuberculosis”, “vitamin D”, “calciferol”, “ergocalciferol” and “cholecalciferol”. Papers in all languages were considered. We obtained all papers but one [21]. Three studies were randomized controlled trials (RCT), and 10 were case series (four including patients administered concurrent

Discussion

We reviewed 3 RCT and 10 prospective cases series in which vitamin D was administered to patients with PTB. The only RCT to investigate effects of vitamin D on course of TB was of poor quality. In the absence of a control group of patients not receiving vitamin D, clinical observations reported in case series cannot reliably be attributed to vitamin D treatment. Four case series describe features consistent with paradoxical upgrading reaction. These reactions are defined as the worsening of

Acknowledgements

We thank John Nyman of St. Mary's Medical School library for obtaining copies of the papers for review. Adrian Martineau is supported by the British Lung Foundation.

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