title: Vitamin C pharmacokinetics: implications for oral and intravenous use.
abstract: BACKGROUND
  Vitamin C at high concentrations is toxic to cancer cells in vitro. Early clinical studies of vitamin C in patients with terminal cancer suggested clinical benefit, but 2 double-blind, placebo-controlled trials showed none. However, these studies used different routes of administration.
  
  
  OBJECTIVE
  To determine whether plasma vitamin C concentrations vary substantially with the route of administration.
  
  
  METHODS
  Dose concentration studies and pharmacokinetic modeling.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  17 healthy hospitalized volunteers.
  
  
  METHODS
  Vitamin C plasma and urine concentrations were measured after administration of oral and intravenous doses at a dose range of 0.015 to 1.25 g, and plasma concentrations were calculated for a dose range of 1 to 100 g.
  
  
  RESULTS
  Peak plasma vitamin C concentrations were higher after administration of intravenous doses than after administration of oral doses (P < 0.001), and the difference increased according to dose. Vitamin C at a dose of 1.25 g administered orally produced mean (+/-sd) peak plasma concentrations of 134.8 +/- 20.6 micromol/L compared with 885 +/- 201.2 micromol/L for intravenous administration. For the maximum tolerated oral dose of 3 g every 4 hours, pharmacokinetic modeling predicted peak plasma vitamin C concentrations of 220 micromol/L and 13 400 micromol/L for a 50-g intravenous dose. Peak predicted urine concentrations of vitamin C from intravenous administration were 140-fold higher than those from maximum oral doses.
  
  
  CONCLUSIONS
  Patient data are not available to confirm pharmacokinetic modeling at high doses and in patients with cancer.
  
  
  CONCLUSIONS
  Oral vitamin C produces plasma concentrations that are tightly controlled. Only intravenous administration of vitamin C produces high plasma and urine concentrations that might have antitumor activity. Because efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institut, and the Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1372, USA.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Padayatty
authors.forename: He
authors.initials: H
authors.lastname: Sun
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Wang
authors.forename: Hugh D
authors.initials: HD
authors.lastname: Riordan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Arie
authors.initials: A
authors.lastname: Katz
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wesley
authors.forename: Mark
authors.initials: M
authors.lastname: Levine
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D012016:Reference Values
chemical_list: D000970:Antineoplastic Agents; D001205:Ascorbic Acid