1. Free Radic Biol Med. 2009 Jul 1;47(1):32-40. Epub 2009 Feb 28.

Pharmacologic concentrations of ascorbate are achieved by parenteral
administration and exhibit antitumoral effects.

Verrax J, Calderon PB.

PMNT Unit, Louvain Drug Research Institute, Université Catholique de Louvain,
1200 Bruxelles, Belgium.

Comment in:
    Free Radic Biol Med. 2009 Jul 1;47(1):27-9.

Recently, it has been proposed that pharmacologic concentrations of ascorbate
(vitamin C) can be reached by intravenous injection. Because high doses of
ascorbate have been described to possess anticancer effects, the therapeutic
potential of these concentrations has been studied, both in vitro and in vivo. By
using 2-h exposures, a protocol that mimics a parenteral use, we observed that
pharmacologic concentrations of ascorbate killed various cancer cell lines very
efficiently (EC(50) ranging from 3 to 7 mM). The mechanism of cytotoxicity is
based on the production of extracellular hydrogen peroxide and involves
intracellular transition metals. In agreement with what has been previously
published, our in vivo results show that both intravenous and intraperitoneal
administration of ascorbate induced pharmacologic concentrations (up to 20 mM) in
blood. In contrast, the concentrations reached orally remained physiological.
According to pharmacokinetic data, parenteral administration of ascorbate
decreased the growth rate of a murine hepatoma, whereas oral administration of
the same dosage did not. We also report that pharmacologic concentrations of
ascorbate did not interfere with but rather reinforced the activity of five
important chemotherapeutic drugs. Taken together, these results confirm that oral
and parenteral administration of ascorbate are not comparable, the latter
resulting in pharmacologic concentrations of ascorbate that exhibit interesting
anticancer properties.

PMID: 19254759 [PubMed - in process]