SIGNIFICANCE: Ewan Cameron reported that ascorbate, given orally and 
intravenously at doses of up to 10 g/day, was effective in the treatment of 
cancer. Double-blind placebo-controlled clinical trials showed no survival 
advantage when the same doses of ascorbate were given orally, leading the 
medical and scientific communities to dismiss the use of ascorbate as a 
potential cancer treatment. However, the route of administration results in 
major differences in ascorbate bioavailability. Tissue and plasma concentrations 
are tightly controlled in response to oral administration, but this can be 
bypassed by intravenous administration. These data provide a plausible 
scientific rationale for the absence of a response to orally administered 
ascorbate in the Mayo clinic trials and indicate the need to reassess ascorbate 
as a cancer therapeutic.
RECENT ADVANCES: High dose ascorbate is selectively cytotoxic to cancer cell 
lines through the generation of extracellular hydrogen peroxide (H2O2). Murine 
xenograft models confirm a growth inhibitory effect of pharmacological 
concentrations. The safety of intravenous ascorbate has been verified in 
encouraging pilot clinical studies.
CRITICAL ISSUES: Neither the selective toxicity of pharmacologic ascorbate 
against cancer cells nor the mechanism of H2O2-mediated cytotoxicity is fully 
understood. Despite promising preclinical data, the question of clinical 
efficacy remains.
FUTURE DIRECTIONS: A full delineation of mechanism is of interest because it may 
indicate susceptible cancer types. Effects of pharmacologic ascorbate used in 
combination with standard treatments need to be defined. Most importantly, the 
clinical efficacy of ascorbate needs to be reassessed using proper dosing, route 
of administration, and controls.