02 August, 2004
VITAMIN C AND CANCER: NEW DEVELOPMENTS
Vitamin C is in the news again. A study carried out by a research
team from the Harvard School of Public Health and published July
1 in the New England Journal of Medicine (Fawzi, WW, 2004) showed
that a multivitamin supplement that included vitamin C significantly
slowed the onset of AIDS and provided an "effective, low-cost
means of delaying the initiation of antiretroviral therapy in HIV-infected
women." The total cost of the treatment was estimated by the
researchers to be about $15 per year. Here is yet another demonstration
of the astonishing power of food supplements, particularly antioxidants
such as vitamin C, to promote human health.
I am often asked whether or not vitamin C (ascorbic acid) is also
an effective way of fighting cancer. I answer that while there is
a growing body of scientific evidence to suggest that vitamin C
is useful in the prevention of cancer, the jury is still out on
its effectiveness as a cancer treatment. However, its low cost and
astonishing lack of toxicity make it an extremely attractive candidate
for further testing.
Representative of the investigations that are currently under way
concerning vitamin C's role in the treatment of cancer is the work
of Kedar N. Prasad, PhD, a professor of radiology at the University
of Colorado Health Sciences Center, Denver. Prasad has demonstrated
that vitamin C is capable of inhibiting the growth of cancer cells
in vitro. He advocates giving vitamin C and other antioxidants to
patients while they are undergoing conventional chemotherapy and
radiation. (I draw on his work in my book Antioxidants
for more information on my book,
Antioxidants Against Cancer.
Prasad's theory is that normal cells require only a minute, precisely
controlled amount of antioxidants in order to function. They reject
any excess. But among other defects, malignant cells have lost the
capacity to regulate their uptake of antioxidants such as vitamin
C and E. Antioxidants can therefore accumulate in cancer tissue
in levels that can lead to the breakdown and death of malignant
cells (Prasad 2003).
The history of research into vitamin C as a cancer treatment is
clouded with controversy. In the 1970s, a Scottish physician Ewan
Cameron, MD, teamed up with Linus Pauling, PhD, to write a book,
Cancer and Vitamin C, in which
they extolled the usefulness of vitamin C as a treatment for cancer.
(Pauling had previously published a book on vitamin C and the common
and Vitamin C became a bestseller and this fueled
public demand for investigation of the role of vitamin C in cancer
Pauling was a world-famous chemist, a two-time Nobel laureate,
with great medical achievements to his record. But he was not a
medical doctor, and this raised the ire of some medical critics
such as the self-proclaimed "quackbuster" Victor Herbert,
MD. However, the demand for a fair test of Pauling's thesis could
not be ignored indefinitely, and in time doctors at the Mayo Clinic,
Rochester, MN, undertook a clinical trial that was supposed to replicate
Drs. Cameron and Pauling's protocol.
In two often-cited papers, Charles Moertel, MD and his Mayo colleagues
claimed that vitamin C had absolutely no beneficial effect when
used in the treatment of patients with advanced cancer, regardless
of whether or not they had received prior chemotherapy (Creagan
1979 and Moertel 1985). Dr. Moertel was called the "foremost
professional demolition expert...of alternative cancer treatments"
(Richards 1991). Moertel's negative comments on the topic
included his assertion that evaluating alternative treatments was
a "waste of time and money...a waste of patient hope"
(Moertel 1989). His high-handed manner of testing vitamin
C convinced proponents that they had been set up for inevitable
defeat. But the damage had been done, and vitamin C was marginalized
as a cancer treatment.
Tale of Two Trials
Is there a good scientific reason why vitamin C might have failed
to show a beneficial effect in the Mayo Clinic trials while succeeding
in the hands of its proponents? It now appears that there was. In
the Mayo Clinic studies all patients received either vitamin C tablets
or an inert sugar pill. What was widely overlooked at the time was
that patients on the Cameron-Pauling protocol were given vitamin
C not only orally but also via intravenous injection.
A few practitioners—most notably Abram Hoffer, MD of Victoria,
British Columbia and Hugh Riordan, MD of the Center For the Improvement
Of Human Functioning International in Wichita, Kansas— continue
to use vitamin C intravenously at doses of up to 100 grams –
almost 4 ounces - per day. In fact, using high-dose intravenous
vitamin C has become a common procedure among CAM-oriented doctors,
although it is ignored by orthodox medicine – witness the
fact that in the decade since 1994 the number of presentations on
intravenous vitamin C at the American Society of Clinical Oncology
(ASCO) convention has been exactly zero.
New NIH Data
Could the route of administering vitamin C make a significant difference?
Yes it could. New data shows that how one gives ascorbic acid has
a big impact on the amount that actually becomes physiologically
available. An April, 2004 study by scientists at the US National
Institutes of Health (NIH) showed that much more vitamin C gets
taken up when it is given via the intravenous route than when the
vitamin is taken orally. The authors of the study include Sebastian
J. Padayatty, MD of the Molecular and Clinical Nutrition Section
at one of the NIH institutes, and his chief, Mark A. Levine, MD.
Both are highly regarded figures in academic circles. Dr. Levine
is a Harvard Medical School graduate who carried out the laboratory
work that convinced the National Academy of Science to increase
of the recommended daily allowance (RDA) of vitamin C. (In 2000,
the RDA for men was increased from 60 to 90 mg daily, and for women
the RDA was increased from 60 to 75 mg daily.)
In the Padayatty study, 17 healthy hospitalized volunteers were
given either oral or intravenous doses of vitamin C, and blood plasma
levels were calculated for a dose range of 1 to 100 grams. The authors
reported that "peak plasma vitamin C concentrations were higher
after administration of intravenous doses than after administration
of oral doses…and the difference increased according to dose."
In fact, the blood concentration of Vitamin C when given intravenously
was 6.6 times greater than when the same amount was given orally.
However, this hardly tells the full story. The maximum tolerated
doses also differed significantly according to whether the vitamin
C was administered orally or intravenously. The maximum tolerated
oral dose was calculated to be three grams every four hours, but
when the vitamin C was given intravenously the researchers found
they could give a 50 gram dose in the same period. Furthermore,
plasma concentrations up to sixty times greater could be achieved
using the intravenous route.
These NIH scientists observed that 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." They conclude that "the
efficacy of vitamin C treatment cannot be judged from clinical trials
that use only oral dosing," as the Mayo Clinic studies most
conspicuously did, and that "the role of vitamin C in cancer
treatment should be reevaluated" (Padayatti 2004). Coming
from such prestigious government scientists, publishing in the Annals
of Internal Medicine, I believe this is a convincing (albeit belated)
refutation of the poorly designed Mayo Clinic studies.
It is never easy to arrange clinical trials, especially of an agent
that has long been in the public domain and from whose sale no super-profits
can be expected. The way the drug approval system works in the United
States virtually requires the enthusiastic support of sponsors with
deep pockets (which almost invariably means a pharmaceutical company)
in order to see a new drug through the long, involved and expensive
process of drug approval. No non-toxic, readily available agent
has ever been approved by the Food and Drug Administration for the
treatment of cancer. Vitamin C at retail sells for around five cents
per gram. The cost of even 100 grams prepared for intravenous use
is still very inexpensive compared to patented chemotherapy. I therefore
don't think you will find many drug companies lining up to test
and market such a readily available agent. And so the question of
what vitamin C can do for patients—so fascinating and promising—has
remained in limbo.
However, things may be about to change. At a meeting of the American
College for the Advancement of Medicine (ACAM) in April, 2003, Jeanne
A. Drisko, MD, announced just such a clinical trial at her institution,
the University of Kansas Medical Center. Luckily, the Cancer Treatment
Research Foundation (CTRF) stepped forward to fund the Kansas City
clinical trial. A randomized controlled trial, with Dr. Drisko as
principal investigator, is now underway at the University of Kansas
Medical Center, evaluating the safety and efficacy of antioxidants
when added to chemotherapy in newly diagnosed ovarian cancer (Drisko
In a recent letter, Dr. Drisko wrote: "This is a randomized
study in newly diagnosed ovarian cancer (Stage III or IV). The study
subjects are randomized to receive either first-line chemotherapy
or first-line chemotherapy along with high-dose antioxidants. The
antioxidants are given both orally and intravenously. If randomized
to the antioxidant arm, patients receive daily oral vitamins A,
C, E and carotenoids, and intravenous (IV) vitamin C 2 times per
week for 12 months. We tailor the dose of the IV vitamin C to their
plasma vitamin C level - we try to get…the neoplastic cell
kill dose, using Dr. Hugh Riordan's protocol.
"At this plasma level, vitamin C is chemotoxic to the cancer
cells and appears to be non-toxic to healthy cells. But we are following
white cell and platelet counts and other markers for possible toxicity
from the vitamin C. Most patients need between 75 and 100 grams
infused to get to that plasma level. We can assure concerned oncologists
that it preliminarily does not appear that the high-dose antioxidants
are interfering with the chemotherapy at this time.
"In ovarian cancer," she continued, "the patients
are usually treated with chemotherapy during the first 5 to 6 months
(6 cycles of carboplatin and paclitaxel) so they are getting an
additional 6 to 7 months of antioxidants past the chemo. This study
is conducted under the oversight of the FDA with an Investigative
Drug (IND) number and has approval from the Human Subjects Committee
(i.e., the institutional review board) of the University of Kansas
Medical Center. So far, we have 14 patients enrolled and are hoping
to recruit 40. We have had 2 dropouts: 1 because she refused to
adhere to the treatment requirements and started smoking, and 1
because she was chemotherapy resistant to all chemotherapy by drug
assays" (Drisko 2004).
This trial is a very encouraging development. Dr. Drisko is a person
with credibility in both orthodox and CAM circles. She is thus in
an ideal position to do a study that will be not only rigorous but
entirely believable in its conclusions.
As some of you know, I wrote the authorized biography of Albert
Szent-Gyorgyi, MD, PhD, who won the 1937 Nobel Prize for his discovery
of vitamin C. In fact, it was he who named the vitamin ascorbic
acid and first predicted its use in cancer. When Szent-Gyorgyi was
on his deathbed, at the age of 93, Linus Pauling flew from California
to Szent-Gyorgi's home at Woods Hole, Mass., to say goodbye. Holding
his hand, Linus said wistfully, "You know, Albert, I always
thought that someday we two would work together." Szent-Gyorgyi
looked up and said, humorously, "Well, if not in this life,
then maybe in the next." Pauling himself died a few years later,
also at age 93. They were two of the greatest thinkers of the 20th
century and it was one of the great privileges of my life to know
them both. I like to think of the two of them smiling down at this
latest development in the fascinating saga of this amazing chemical.
To find out more about the Kansas clinical trial of vitamin C,
Jeanne Drisko, MD
Program in Integrative Medicine
Functional Medicine and Complementary and Alternative Therapies
University of Kansas Medical Center
Kansas City, KS 66160
Ralph W. Moss, Ph.D.
American College of Physicians (ACP). How vitamin C is
administered affects how much reaches the bloodstream and may affect
the results of studies of its potential effect on cancer. Annals
of Internal Medicine, Summaries for Patients, April 6, 2004.
Retrieved July 1, 2004 from:
Drisko JA, Chapman J, Hunter VJ. The use of antioxidants
with first-line chemotherapy in two cases of ovarian cancer. J
Am Coll Nutr. 2003 Apr;22(2):118-23.
Drisko JA. Personal communication, July 1, 2004.
Fawzi WW, et al. A randomized trial of multivitamin supplements
and HIV disease progression and mortality
N Engl J Med 2004;351:23-32.
Moertel, C.G. Interview on 'Health Report', ABC National
Radio, August 7, 1989 [cited in Richards].
Padayatty SJ, et al. Vitamin C pharmacokinetics: implications
for oral and intravenous use. Ann Intern Med. 2004 Apr 6;140(7):533-7.
Prasad KN. Antioxidants in cancer care: when and how to
use them as an adjunct to standard and experimental therapies. Expert
Rev Anticancer Ther. 2003 Dec;3(6):903-15.
Richards, Evelleen. Vitamin C and Cancer: Medicine or
Politics? New York: St. Martin's Press, 1991.
The news and other items in this newsletter are intended for informational
purposes only. Nothing in this newsletter is intended to be a substitute
for professional medical advice.