Vitamin C Seen as Cancer-Fighter
- From: "TC" <tunderbar@xxxxxxxxxxx>
- Date: 14 Sep 2005 12:33:01 -0700
http://www.medpagetoday.com/HematologyOncology/LeukemiaLymphoma/tb/1733
IV Vitamin C Seen as Cancer-Fighter
By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of
Pennsylvania School of Medicine.
September 14, 2005
BETHESDA, Md., Sept. 14-Vitamin C (ascorbate) delivered to the
bloodstream in high concentrations could be a potent killer of cancer
cells, especially some lymphomas, suggested researchers at the National
Institutes of Health here.
In an in vitro study designed to mimic clinical intravenous delivery of
ascorbate, 20 mM of the substance killed five of 10 cancer cell lines,
while leaving four normal cell lines intact, reported Mark Levine,
M.D., of the National Institute for Diabetes and Digestive and Kidney
Diseases and colleagues.
Vitamin C in the extracellular but not intracellular environment
appears to mediate cancer cell death by stimulating production of
hydrogen peroxide (H2O2), the investigators found.
"Ascorbic acid (vitamin C, ascorbate) has a controversial history in
cancer treatment," Dr. Levine and colleagues wrote. "Observational
reports described ascorbate, given in pharmacologic doses of 10 g
daily, as effective in treating some cancers and in improving patient
well-being. Subsequently, the same dose had no effect on patient
well-being and survival in two double-blind placebo-controlled trials,
and ascorbate was discarded as a treatment modality."
The differences in outcomes of the observational studies and
placebo-controlled trials may have been due to differences in the
efficacy of vitamin C based on the route of administration, they
suggested. Ascorbate delivered intravenously can produce plasma
concentrations of the vitamin that are more than 25 times higher than
that produced by the same dose given orally, they added.
"Our goals were to address the following," Dr. Levine and colleagues
wrote. "Does ascorbate in pharmacologic concentrations kill cancer
cells, but not normal cells, using conditions that mimic IV use and a
clinically relevant time course? Is action dependent on extracellular
ascorbate, intracellular ascorbate, or both? If effective, what are the
mechanisms? Can ascorbate be delivered to tissues without harm? Are
there implications for other diseases?"
To answer at least some of these questions, they exposed 10 cancer cell
lines (five human and five mouse lines) and four normal human cell
lines to ascorbic acid for one hour, an exposure time similar to that
used in the clinic.
They first looked at the effects of pharmacologic concentrations of
ascorbate compared with normal (physiologic) concentrations, and found
that for five of nine cancer cell lines they looked at, an ascorbate
concentration of less than 5 mM caused a 50% drop in cell survival.
This concentration can be easily achieved with IV infusion, the
investigators said.
In contrast, the normal cells were all insensitive to ascorbate at the
same concentration.
They also conducted a separate study of Burkitt's lymphoma cells, a
particularly aggressive form of the cancer that is known to be
sensitive to ascorbate. They found that "ascorbate induced
concentration-dependent cell death, which was nearly 100% at 2 mM. As
ascorbate concentration increased, the pattern of death changed from
apoptosis to pyknosis/necrosis, a pattern suggestive of H2O2-mediated
cell death."
They found that apoptosis, or programmed cell death, occurred by about
six hours after the cells were exposed to ascorbate, and cell death by
pyknosis (i.e., degradation of the nucleus) was about 90% at 14 hours
after exposures. The ascorbate killed lymphoma cells, but largely
spared normal lymphocytes and monocytes, they noted.
Because the patterns of cell killing they saw implicated H2O2, they
added hydrogen peroxide to the cell lines, and found that it produced a
virtually identical lethal effect to that seen with ascorbate, as
confirmed by several different measures.
"Taken together, these data are consistent with the conclusion that
extracellular ascorbate induced cell death by formation of H2O2," they
wrote.
The mechanism by which ascorbate leads to increased formation of H2O2
is unknown as is the reason that cancer cells but not normal cells are
sensitive to H2O2.
The authors noted that clinical trials documenting the safety of high
pharmacologic concentrations of vitamin C are necessary.
"Complementary and alternative medicine practitioners worldwide
currently use ascorbate IV in doses as high as 70 g over several
hours," Dr. Levine and colleagues pointed out. "Because IV ascorbate is
easily available to people who seek it, a phase I safety trial in
patients with advanced cancer is justified and underway."
-----
Can we conclude that enough vitamin C daily can also prevent the
occurence of cancer?
TC
.
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