High-Dose Intravenous Ascorbate as a Pro-Oxidant Inducing Cancer Cell Death
Vitamin C (ascorbate) is a well-known antioxidant, and it plays important roles in maintaining normal cellular redox status and functions. In contrast, when high-dose intravenous ascorbate (IVC) is administered to patients, it bypasses the normal physiologic concentrations and establishes higher pharmacologic concentrations. These high ascorbate concentrations exhibit pro-oxidant effects by mediating hydrogen peroxide (H2O2) formation in the extracellular spaces. The formation of peroxide is present at tissue sites but is not present in the bloodstream, and it is dependent on drastically changed extracellular ascorbate concentrations. This pro-oxidant function of ascorbate exerts a cytotoxic effect on cancer cells while sparing normal cells. Thus, IVC works as a prodrug to deliver H2O2 to tissue sites. These findings provide a biological plausibility to the anticancer therapeutic effects of vitamin C and a mechanistic reasoning in clarifying the controversies in the history of using vitamin C as a cancer treatment. The plausibility of ascorbate as an anticancer treatment is now being investigated in clinical research.