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.