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Vitamin D as Supplementary Treatment for Tuberculosis

A Double-blind, Randomized, Placebo-controlled Trial

¹ Bandim Health Project, INDEPTH Network, Statens Serum Institute, Bissau, Guinea-Bissau; ² Infectious Disease Research Unit, Aarhus University Hospital, Skejby, Denmark; ³ Infectious Diseases Research Group, Department of Clinical Sciences, Lund University, Malmö, Sweden; ⁴ Department of Pathology, Herlev University Hospital, Copenhagen, Denmark; ⁵ Department of Internal Medicine, Aarhus University Hospital, Silkeborg, Denmark; and ⁶ Department of Infectious Diseases, Odense University Hospital, Odense, Denmark

Correspondence and requests for reprints should be addressed to Christian Wejse, M.D., Ph.D., Infectious Disease Research Unit, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, 8200 Aarhus N, Denmark. E-mail: wejse{at}dadlnet.dk

Rationale: Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis.

Objectives: To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality.

Methods: 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.

Measurements and Main Results: 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.

Conclusions: 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 www.controlled-trials.com/isrctn (ISRCTN35212132).

Key Words: vitamin D • tuberculosis • randomized clinical trial • clinical score • HIV

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Vitamin D insufficiency is associated with impaired immune function and increased risk of active tuberculosis (TB). Vitamin D has been used in the preantibiotic era in the treatment of TB. It has also been suggested as a supplementary/prophylactic treatment for TB, but only two small trials have assessed this. What This Study Adds to the Field Vitamin D can be given safely to patients with TB. Our study suggests no overall effect on clinical outcome or mortality with the doses used. The study raises the question of whether vitamin D has a differential effect depending on immune status.

 

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