L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial

Randomized, double-blind, placebo-controlled factorial trial in adults with newly diagnosed smear-positive pulmonary tuberculosis in Timika, Indonesia. Participants received standard anti-TB therapy with adjunctive L-arginine and/or vitamin D, and outcomes were assessed through 8 weeks of treatment.

Adults with pulmonary tuberculosis received standard anti-TB therapy plus adjunctive oral L-arginine hydrochloride 6 g daily for 8 weeks and/or oral cholecalciferol 50,000 IU at baseline and day 28 in a randomized factorial design. Active regimens included L-arginine plus active vitamin D, L-arginine plus vitamin D placebo, or vitamin D plus L-arginine placebo; one additional arm received both placebos.

Neither L-arginine nor vitamin D improved microbiological or clinical outcomes when added to standard tuberculosis treatment. At week 4, culture negativity was 21/37 (57) in the L-arginine plus vitamin D arm, 27/39 (69) in the L-arginine plus placebo arm, and 23/38 (61) in the placebo L-arginine plus vitamin D arm. Pooled analyses also showed no meaningful advantage for L-arginine versus no L-arginine (48/76 [63.2%] versus 48/79 [60.8%]) or for vitamin D versus no vitamin D (44/75 [58.7%] versus 52/80 [65.0%]). There were no significant differences in week 8 culture conversion or clinical score, and the authors found no evidence of interaction between the two supplements.

The trial may have been underpowered to detect small benefits, so modest effects cannot be excluded. Baseline imbalances in sex, HIV status, and X-ray severity were noted, and active-arm demographic detail was limited. The 8-week intervention window may also have been too short to capture clinically meaningful differences in all outcomes.