Vitamin D May Accelerate Recovery From Tuberculosis in Certain Patients

Laurie Barclay, MD

January 06, 2011

January 6, 2011 — In patients given standard treatment for tuberculosis (TB), adjunctive vitamin D significantly hastened sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism, but not in the whole study population, according to the results of a multicenter, randomized, double-blind, controlled trial reported online January 6 in The Lancet.

"Vitamin D was used to treat [TB] in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro," write Adrian R. Martineau, MD, from Queen Mary University of London, United Kingdom, and colleagues. "Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent."

In London, 146 adults with sputum smear–positive pulmonary TB were randomly assigned to receive 2.5 mg vitamin D3 or placebo at baseline and at 14, 28, and 42 days after starting standard therapy for TB. The main study outcome was time from starting antimicrobial therapy to sputum culture conversion. To determine the effect of the vitamin D receptor genotype on response to vitamin D3, patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were performed.

"The findings of this great promise in speeding up the antibiotic treatment of TB for those patients which are receptive to vitamin D," Ian Jarrold, Research Manager for the British Lung Foundation, said in a news release. "The treatment process is currently very long and can be costly so any headway made in the medical research field for this disease is welcome to improve outcomes for patients."

Of 126 patients included in the primary efficacy analysis, 62 were randomly assigned to receive adjunctive vitamin D therapy, and 64 to receive placebo. At 56 days, mean serum 25-hydroxyvitamin D concentration was 101.4 nmol/L in the vitamin D group and 22.8 nmol/L in the placebo group (95% confidence interval [CI] for difference, 68.6 - 88.2 nmol/L; P < .0001).

In the intervention group, median time to sputum culture conversion was 36.0 days compared with 43.5 days in the placebo group (adjusted hazard ratio [HR], 1.39; 95% confidence interval [CI], 0.90 - 2.16; P = .14). TaqI genotype, but not FokI genotype, significantly modified the effect of adjunctive vitamin D on time to sputum culture conversion (P for interaction = .03 for TaqI, .85 for FokI). Only patients with the tt genotype of TaqI had enhanced response to vitamin D supplementation (HR, 8.09; 95% CI, 1.36 - 48.01; P =. 02). This genotype was only found in 8% of patients (5 people) in the vitamin D group and in 11% of patients (7 people) in the placebo group.

"Administration of four doses of 2.5 mg vitamin D3 increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary [TB]," the study authors write. "Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism."

Limitations of this study include that serum 25-hydroxyvitamin D concentration greater than 75 nmol/L was not achieved in all patients in the intervention group, and that follow-up was limited to 56 days.

In an accompanying comment, Reinhold Vieth, PhD, from the University of Toronto in Canada, calls for current evidence-based data, not solely randomized controlled trials evaluating treatment, to dictate nutritional guidelines and public health policy for vitamin D to prevent latent TB infection.

"The demand, as stated by the Institute of Medicine, for nothing but the highest, most compelling standard of evidence will force yet another decade of inaction to address vitamin D inadequacy in patients with [TB], for which a safe and simple preventive measure was evident 10 years ago," Dr. Vieth writes. "Evidence-based medicine and health policy need to go beyond a fixation on randomised trials of the sort that are unlikely to happen for prevention of most diseases. Evidence-based policy needs to be realistic and to pay more than lip service to the various types of evidence available."

The British Lung Foundation supported this study. Merck Serono donated €7000 to Queen Mary, University of London, to support an academic meeting entitled "Vitamin D: Mechanisms of Action in Health and Disease"; this meeting was convened by 2 of the study authors. All other study authors have disclosed no relevant financial relationships. Merck Serono donated Vigantol and Miglyol oils and assayed vitamin D3 concentrations in vials of placebo and active study preparations. Dr. Vieth has been a consultant for Ortho Clinical Diagnostics and Merck Serono; has a grant from Dairy Farmers of Canada; received payment for lectures including service on speaker bureaus from Merck and Company, Carlson Laboratories, and DiaSorin Inc; and is related to employees in the dietary supplement industry.

Lancet. Published online January 6, 2011.


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