Pilot Randomized Trial of Vitamin D and Zinc Supplementation on Total Adenosine Deaminase in Pediatric Tuberculosis

Pediatric tuberculosis remains difficult to monitor using objective biomarkers. Total serum adenosine deaminase (ADA) reflects cellular immune activation, whereas vitamin D and zinc may modify antimycobacterial immunity. This pilot randomized trial evaluated whether adjunctive vitamin D or zinc altered serum ADA during the intensive phase of pediatric tuberculosis treatment. Thirty-three treatment-naive children with tuberculosis were randomized equally to standard anti-tuberculosis treatment (ATT) alone, ATT plus zinc, or ATT plus vitamin D. Total serum ADA was measured at baseline and after two months. The prespecified completer analysis compared change scores, while the primary adjusted analysis used analysis of covariance (ANCOVA) with post-treatment ADA as the outcome and baseline ADA as a covariate. A multiple-imputation intention-to-treat sensitivity analysis included all randomized participants. Twenty-two participants completed follow-up (ATT, n = 8; zinc, n = 8; vitamin D, n = 6). Unadjusted ADA decreased in all groups and most markedly in the vitamin D arm, but the between-group difference in change was not significant (p = 0.364). Baseline-adjusted ANCOVA also showed no treatment-group difference (F2,18 = 0.79; p = 0.470). Compared with ATT alone, the adjusted effects were −4.35 U/L for vitamin D (95% CI −15.70 to 7.00) and +2.26 U/L for zinc (95% CI −8.07 to 12.59). The intention-to-treat sensitivity analysis produced the same overall interpretation. In this underpowered pilot trial, adjunctive vitamin D or zinc did not significantly reduce total serum ADA beyond standard therapy. The large crude decline in the vitamin D arm was attenuated after adjustment for baseline imbalance and regression to the mean. Larger multicentre trials should confirm micronutrient repletion, measure ADA2, and prespecify methods for missing data.