Effect of Vitamin D Supplementation on Sputum Culture Conversion in Tuberculosis

In a subgroup of patients with multidrug-resistant tuberculosis, vitamin D supplementation accelerated sputum culture conversion.

As a whole, vitamin D supplementation did not affect sputum culture conversion in patients with pulmonary tuberculosis (TB), but in the subgroup of patients with multidrug-resistant TB, vitamin D supplementation did accelerate sputum culture conversion, according to a meta-analysis published in European Respiratory Journal.

Researchers gathered individual participant data from double-blind randomized placebo-controlled clinical trials to analyze overall efficacy and whether potential effect-modifiers affected the intervention outcome. Clinical trials were included if vitamin D was supplemented to standard antimicrobial treatments and sputum cultures and/or smear conversions were reported. Collected data included time from the start of treatment to stable sputum culture or smear conversions, the presence of potential effect-modifying variables, and occurrence of adverse events. The primary outcome was defined as the time from the start of treatment to stable sputum culture conversion and further analysis was completed on potential effect-modifying variables.

Of the 1850 patients from 8 clinical trials included in this meta-analysis, 35.1% were women, 15.8% were HIV positive, and 4.1% had multidrug-resistant TB. Overall, vitamin D supplementation did not affect the length of time between the start of treatment and sputum culture conversion (adjusted hazard ratio [aHR], 1.06; 95% CI, 0.91-1.23; P =.44). Analyzing potential effect-modifying variables revealed that patients with multidrug-resistant TB showed a significant association between vitamin D supplementation and an accelerated sputum culture conversion (aHR, 13.44; 95% CI, 2.96-60.90; P =.001), when excluding patients sensitive to rifampicin or isoniazid.

In addition, patients with multidrug-resistant TB were more often vitamin D deficient at baseline than patients without multidrug-resistant pulmonary TB (61.8% vs 41.4%, respectively, P =.003). Regarding adverse events, there were no significant differences between the patients receiving vitamin D supplementation and the patients receiving the placebo.

Limitations of this study included the potential publication bias due to the small number of clinical trials included and the relatively short-term follow-up provided by the clinical trials.

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“[A]djunctive vitamin D does not influence time to sputum culture conversion in drug-sensitive pulmonary tuberculosis, but it may accelerate sputum culture conversion in patients with multidrug-resistant disease,” The researchers concluded.


Jolliffe DA, Ganmaa D, Wejse C, et al. Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data [published online February 6, 2019]. Eur Respir J. doi:10.1183/13993003.02003-2018