Vitamins A and D fail to protect against tuberculosis-drug-induced liver injury: A post hoc analysis of a previous randomized controlled trial.

ABSTRACT

OBJECTIVES: Vitamins A and D provided protection from xenobiotic-induced liver injury in previous animal studies. We conducted a post hoc analysis of our previous randomized controlled trial to investigate the effects of vitamin A and D supplementation on tuberculosis-drug-induced liver injury. METHODS: The trial was conducted in a hospital in Qingdao, China, from October 2012 to March, 2015. The control group received only tuberculosis treatment. The vitamin A, vitamin D, and vitamins A & D groups received, respectively, additional supplementation of 2000 IU/d vitamin A, 400 IU/d vitamin D, and a combination of 2000 IU/d vitamin A and 400 IU/d vitamin D. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, γ-glutamyltransferase, and cholinesterase were monitored throughout the treatment. Liver injury was defined as ALT or AST three times higher than the upper limit of normal, which was defined for AST, ALT, alkaline phosphatase, γ-glutamyltransferase, and cholinesterase, respectively, as 40 U/L, 40 U/L, 150 U/L, 40 U/L, and 10 500 U/L. RESULTS: Among the 753 participants, 11% exhibited liver injury. No significant effect of vitamin A or D supplementation was observed on the incidence of liver injury or on elevated liver indices including ALT, AST, alkaline phosphatase, γ-glutamyltransferase, and cholinesterase. The interaction between vitamin A and D supplementation was not significant. CONCLUSIONS: Vitamin A and D supplementation did not protect against tuberculosis-drug-induced liver injury. Future work should evaluate the effects of higher dosages of vitamins A and D and the effects of different genotypes for vitamin A and D metabolic enzymes or receptors.