Vitamin D as Supplementary Treatment for Tuberculosis - A Double-blind Randomized Placebo-controlled Trial

Infectious Disease Research Unit, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, 8200 Aarhus N, Denmark.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 02/2009; 179(9):843-50. DOI: 10.1164/rccm.200804-567OC
Source: PubMed


Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis.
To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality.
We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment.
The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2.
Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with (ISRCTN35212132).

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Available from: Christian Wejse, Mar 06, 2014
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    • "It was therefore tempting to test whether vitamin D could be used as a dietary supplement in TB treatment, since historically vitamin D sources like sunbathing and cod liver oil were used to treat TB. Many clinical trials have been performed to test this hypothesis; the results have however been inconclusive, with several studies showing positive results, especially in patients with vitamin D deficiency (Salahuddin et al. 2013; Kearns et al. 2014), but many other major clinical trials showing no benefits overall (Wejse et al. 2009; Martineau et al. 2011; Ralph et al. 2013; Kearns et al. 2014). It is still uncertain whether vitamin D will have any use in TB therapy, with some researchers advocating that better knowledge is needed about vitamin D concentrations for optimal immune response in order to perform adequate clinical trials (Ralph et al. 2013). "
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    • "The implications of this observation were seen in Salahuddin et al. [22], where only the vitamin D deficient subset of study participants experienced significant increases in IFN-g production following vitamin D administration . This may also explain the negative results in Wejse et al. [29], the only study with a mean baseline 25(OH)D concentration >30 ng/mL. Alternatively, as suggested by Heaney [45] "

    Full-text · Article · Aug 2014 · Journal of Clinical and Translational Endocrinology
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    • "Therefore, what are the barriers to translate scientific experience to clinical practice? Primarily, it is a number of null trials of vitamin D which have been recently conducted [87, 126–128]. However, the findings from these unsuccessful trials remain ambiguous as in many cases an argument could be given that the dose, regime, or metabolite used was incorrect, that the baseline context of vitamin D deficiency was not investigated or reported (we know that vitamin D has the greatest effect in those most deficient [23]), that the populations were not geographically at risk of deficiency, or that due to the interaction of vitamin D with genetic polymorphisms which are population specific, supplementation may have differential benefits for various populations, which again are affected by location and diet. "
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    ABSTRACT: Tuberculosis (TB) disease activation is now believed to arise due to a lack of inflammatory homeostatic control at either end of the spectrum of inflammation: either due to immunosuppression (decreased antimicrobial activity) or due to immune activation (excess/aberrant inflammation). Vitamin D metabolites can increase antimicrobial activity in innate immune cells, which, in the context of HIV-1 coinfection, have insufficient T cell-mediated help to combat Mycobacterium tuberculosis (MTB) infection. Moreover, maintaining vitamin D sufficiency prior to MTB infection enhances the innate antimicrobial response to T cell-mediated interferon- γ . Conversely, vitamin D can act to inhibit expression and secretion of a broad range of inflammatory mediators and matrix degrading enzymes driving immunopathology during active TB and antiretroviral- (ARV-) mediated immune reconstitution inflammatory syndrome (IRIS). Adjunct vitamin D therapy during treatment of active TB may therefore reduce lung pathology and TB morbidity, accelerate resolution of cavitation and thereby decrease the chance of transmission, improve lung function following therapy, prevent relapse, and prevent IRIS in those initiating ARVs. Future clinical trials of vitamin D for TB prevention and treatment must be designed to detect the most appropriate primary endpoint, which in some cases should be anti-inflammatory and not antimicrobial.
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