Randomized controlled trial of zinc and vitamin A as co-adjuvants for the treatment of pulmonary tuberculosis.

OBJECTIVE

To assess the efficacy of weekly zinc or zinc plus retinol as adjuncts for the treatment of pulmonary tuberculosis.

METHODS

Double-blind, randomized, placebo-controlled trial in 350 patients >15 years old with smear-positive tuberculosis in Nigeria (ISRCTN36636609). In addition to antituberculous treatment, patients were randomly allocated to weekly supplements of zinc (90 mg), zinc plus retinol (5000 IU) or placebos for 6 months. Primary outcomes were time to sputum smear conversion and resolution of radiographic abnormalities.

RESULTS

After 8 weeks of treatment, 68% had achieved sputum smear conversion, and the median conversion time was 6.5 weeks. Hazard ratios (HR, 95%CI) for sputum conversion relative to the placebo group were not significant for zinc (1.07, 0.92-1.29) or zinc plus retinol (0.89, 0.76-1.07). Significant predictors of time to sputum conversion were lung abnormality score, sputum smear grade, age and serum C-reactive protein. HIV co-infection and gender were not independent predictors of time to sputum conversion. There were no significant differences between supplement groups in clinical, radiological or laboratory outcomes at 2 months or 6 months. There were 9, 9 and 2 deaths in patients receiving zinc, zinc plus retinol or placebos, respectively. Mortality in those who received zinc (HR 1.71, 0.88-3.58) or zinc plus retinol (HR 1.54, 0.78-3.26) did not differ significantly from those who received placebos. Most deaths occurred in patients co-infected with HIV.

CONCLUSIONS

Supplementation with zinc or zinc plus retinol did not lead to better outcomes than placebos, and caution is warranted regarding routine micronutrient supplementation, particularly in patients co-infected with HIV.