Effects of Vitamin C Supplementation on Tetrabenazine Treatment in a Caenorhabditis elegans Huntington's Disease Model.

Tetrabenazine, a VMAT2 inhibitor, is widely used to treat chorea in Huntington's disease by depleting monoamine neurotransmitters, particularly dopamine. However, this mechanism may indirectly increase oxidative stress due to enhanced metabolism and auto‑oxidation of cytosolic monoamines, generating reactive oxygen species. Using Caenorhabditis elegans polyglutamine models, this study investigated the effects of tetrabenazine and vitamin C supplementation on survival. These results indicate that tetrabenazine reduces survival, while vitamin C, a known antioxidant, mitigates these effects and improves outcomes, particularly in pathogenic poly‑Q strains. Our findings suggest that antioxidant supplementation may counteract tetrabenazine‑associated oxidative stress and enhance therapeutic efficacy in neurodegenerative disease.