Two popular complementary, alternative, and integrative medicine
therapies, high-dose intravenous
ascorbic acid (AA) and intravenous
glutathione (GSH), are often coadministered to
cancer patients with unclear efficacy and
drug-drug interaction. In this study we provide the first survey evidence for clinical use of iv GSH with iv AA. To address questions of efficacy and
drug-drug interaction, we tested 10
cancer cell lines with
AA, GSH, and their combination. The results showed that pharmacologic AA induced cytotoxicity in all tested
cancer cells, with IC(50) less than 4 mM, a concentration easily achievable in humans. GSH reduced cytotoxicity by 10-95% by attenuating AA-induced H(2)O(2) production. Treatment in mouse
pancreatic cancer xenografts showed that intraperitoneal AA at 4 g/kg daily reduced
tumor volume by 42%. Addition of intraperitoneal GSH inhibited the AA-induced
tumor volume reduction. Although all treatments (
AA, GSH, and AA+GSH) improved survival rate, AA+GSH inhibited the cytotoxic effect of AA alone and failed to provide further survival benefit. These data confirm the pro-oxidative anti-
cancer mechanism of pharmacologic AA and suggest that AA and GSH administered together provide no additional benefit compared with AA alone. There is an antagonism between ascorbate and
glutathione in treating
cancer, and therefore iv AA and iv GSH should not be coadministered to
cancer patients on the same day.