title: Review of high-dose intravenous vitamin C as an anticancer agent.
abstract: In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial.
authors.affiliation: Auckland City Hospital, Auckland, New Zealand.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Wilson
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Baguley
authors.forename: Clare
authors.initials: C
authors.lastname: Wall
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jameson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Findlay
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D009369:Neoplasms / Q000188:drug therapy*; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D014815:Vitamins; D001205:Ascorbic Acid
keywords: cancer; pro-oxidant; vitamin C