The strong interest in how dietary choices and supplements affect disease has led to large scale human trials. In prostate cancer (PC), it was shown that surprisingly, disease risk is significantly increased when men take the anti-oxidant dietary supplement vitamin E. However, it has remained unclear if vice versa, pro-oxidant supplements are a viable strategy to stave off the disease. We show that the vitamin K precursor menadione sodium bisulfite (MSB) suppresses PC progression in mouse and kills cells through a novel oxidative cell death, distinct from ferroptosis. Using genome wide CRISPR screens and cell death analysis, we find that MSB antagonizes the primordial class III PI 3- Kinase VPS34, which is essential for endosomal identity and sorting. MSB phenocopies genetic or pharmacological loss of endosomal VPS34 kinase function, but under oxidative control, pointing to a redox checkpoint in endosomal sorting. Therefore, we tested MSB in a mouse model of the incurable X- linked myotubular myopathy, a fatal muscle weakness syndrome driven by congenital loss of MTM1, the phosphatase iii antagonist of PI 3-Kinase VPS34. We show that dietary MSB improves muscle fiber diameter, motor function, and that it significantly extends life span. Thus, we propose that dietary MSB is an effective and safe oxidative antagonist of class III PI 3-Kinase VPS34 in multiple disease settings. These findings contribute to the emerging understanding of pro- oxidant selectivity and show how definition of the pathways they impinge on can give rise to unexpected therapeutic opportunities.