Vitamin C pharmacokinetics: implications for oral and intravenous use.

Annals of internal medicine, 2004; 140 (7) doi:

Authors: Padayatty Sebastian J, Sun He, Wang Yaohui, Riordan Hugh D, Hewitt Stephen M et al.(3)

Affiliation: National Institutes of Health, United States

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.
DESIGN: Dose concentration studies and pharmacokinetic modeling.
SETTING: Academic medical center.
PARTICIPANTS: 17 healthy hospitalized volunteers.
MEASUREMENTS: 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.
LIMITATIONS: 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.

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