Capsaicin, the main pungent capsaicinoid of Capsicum species, is often described as either an antioxidant or a pro-oxidant compound. This binary view is useful but does not fully explain its effects on cellular redox homeostasis. The response to capsaicin depends on dose, exposure time, cell type, metabolic state, mitochondrial function, antioxidant capacity, and TRPV1 expression. Capsaicin can modulate reactive oxygen species (ROS) production through TRPV1-dependent calcium signaling, but also through TRPV1-independent effects on plasma and mitochondrial membranes. These mechanisms influence mitochondrial bioenergetics, membrane potential, lipid peroxidation, and redox-sensitive signaling. Moderate ROS formation may support adaptive responses, including Nrf2 activation, mitochondrial quality control, and cellular stress tolerance. In contrast, persistent or excessive ROS accumulation may promote mitochondrial dysfunction, apoptosis, and oxidative cell death. Evidence for capsaicin-associated ferroptosis is emerging, particularly through changes in lipid peroxidation, glutathione availability, GPX4 activity, and SLC7A11 expression or activity, but remains incomplete in many models. This review summarizes current evidence on capsaicin-mediated ROS regulation, mitochondrial stress, TRPV1-dependent and TRPV1-independent mechanisms, ferroptosis-related pathways, and methodological challenges in oxidative stress assessment.
Kuželová et al. (Wed,) studied this question.