Mechanisms of Vitamins Inhibiting Ferroptosis

Ferroptosis is an iron-dependent form of cell death, which is characterized by the uncontrolled and overwhelming peroxidation of cell membrane lipids. Ferroptosis has been implicated in the progression of various pathologies, including steatotic liver, heart failure, neurodegenerative diseases, and diabetes. Targeted inhibition of ferroptosis provides a promising strategy to treat ferroptosis-related diseases. Multivitamins, including vitamins A, B, C, D, E, and K, have shown a good ability to inhibit ferroptosis. For example, vitamin A significantly upregulated the expression of several key ferroptotic gatekeepers genes through nuclear retinoic acid receptors and retinoic X receptors (RAR/RXR). Vitamin B6 could compensate for the impaired glutathione (GSH) levels and restore Glutathione peroxidase 4 (GPX4) expression in cells, ultimately inhibiting ferroptosis. Vitamin D could up-regulate the expression of several anti-ferroptosis proteins by activating vitamin D receptors. Vitamin E and hydroquinone vitamin K (VKH₂) can directly inhibit the propagation of lipid peroxidation, thereby inhibiting ferroptosis. In this review, we summarize the currently understood mechanisms by which vitamins inhibit ferroptosis to provide reference information for future research on the development of ferroptosis inhibitors.