On infusion of high-dose ascorbate in treating cancer: Is it time for N-acetylcysteine pretreatment to enhance susceptibility and to lower side effects?

Ascorbate administered intravenously gives a high plasma concentration of this drug. Clinical trials with pancreatic carcinoma patients revealed their prolonged survival if treated with intravenous ascorbate. On the other hand, high plasma ascorbate concentration leads to severe side effects, such as nephrotoxicity. In the present paper, we advocate to lower intravenous ascorbate dosage along with monothiol N-acetylcysteine pretreatment due to anticipation of the same therapeutic effect but less or none of side effects. We describe in detail molecular mechanism of ascorbate action to be potentiated by N-acetylcysteine, as observed under in vitro conditions. Providing further arguments, we believe that the same mechanism may be employed in vivo.