VITAMIN C: LABORATORY TESTS INDICATE ANTIVIRAL EFFECT

A series of laboratory tests at the Linus Pauling Institute
of Science and Medicine in Palo Alto, California found that
ascorbate (vitamin C) reduced the growth of HIV in cultured
human lymphocytes, in concentrations not harmful to the cells.
The experimental study, conducted by Steve Harakeh, Ph.D., and
Raxit J. Jariwalla, Ph.D., appears in the September issue of the
Proceedings of the National Academy of Sciences, USA; results
were also presented September 11 at "Ascorbic Acid: Biological
Functions and Relation to Cancer," an international symposium
sponsored by the U.S. National Cancer Institute, and National
Institute of Diabetes and Digestive and Kidney Diseases, in
Bethesda, Maryland. The study is extensive and hard to
summarize, but it showed a substantial reduction in measures
of viral activity (p24, reverse transcriptase, and syncytia
formation) without toxicity to cells at concentrations of 25 to
150 mcg/ml, with the higher concentrations working better.

How much vitamin C would be needed to reach these levels in
blood serum? This study did not measure blood levels, but the
published paper cited measurements by others. One researcher
found an average blood level of 28.91 mcg/ml after oral use of
10 grams of vitamin C. Another found that intravenous infusion
of 50 grams a day led to a peak plasma level of 796 mcg/ml.

Comment

This research appears to have been carefully done; many
measurements were made and the results all point in the same
direction. We raised several questions, however, and gave Dr.
Jariwalla a chance to respond.

One potential limitation is that this study used cultured
cells and viruses, which have been bred in laboratories; recently
scientists have learned that viruses and cells freshly obtained
from patients can give different, and presumably more reliable,
results in drug screening. In our interview, Dr. Jariwalla noted
that at this time there is no evidence that strains differ in
resistance to ascorbate -- but that different strains have not yet
been tested.

One question about the usefulness of vitamin C concerns
the relatively narrow range between effective and toxic doses
found in this study. Effectiveness began to be seen at 25
mcg/ml, but toxicity was found at 400 and above; half or more
of the cells were killed by exposure to 400 mcg/ml or greater
for four days. The therapeutic range is therefore fairly narrow;
for some drugs, the corresponding ratio between effective and
toxic doses is a thousand or more, compared to 16 (400 divided
by 25) in this laboratory test of vitamin C.

Dr. Jariwalla said that "although this may be so, there is
no evidence of ascorbate toxicity found in human beings when
large doses have been taken. The only side effect of high doses
of ascorbate is a mild laxative effect. There are no reliable
reports of severe ascorbate toxicity, such as acidosis or kidney
stones."

Several years ago there was much interest in high-dose
vitamin C as an AIDS treatment. By the end of 1987 this interest
had greatly diminished, although some people continue to use the
treatment today. One reason we have been skeptical of vitamin
C is that if the treatment had worked well, it seems unlikely
that the community would have stopped using it.

Dr. Jariwalla said that interest in vitamin C as a
potential AIDS treatment had diminished for several reasons.
fFirst, the emphasis shifted to AZT and other nucleoside analogs as
antivirals. Second, no clinical trials of vitamin C and AIDS got off
the ground. And third, no hard scientific evidence of the effect
of ascorbate on the AIDS virus was available until now.

At least two clinical trials were proposed years ago by
leading AIDS researchers, but no funding was available. The Linus
Pauling Institute, which has long been interested in vitamin C,
has heard "a number of reports...from AIDS patients who had
taken high doses of vitamin C and had experienced a marked
improvement in their condition" (quote from a press release
accompanying the recently published article). It is possible that
results today could be better than those of several years ago,
when treatment was only used late in the illness. Today,
treatments are started earlier; and AZT and others antivirals
make possible combination therapies, which were not available
during the time of great interest in vitamin C. The article
suggests a rationale for such combinations.

We asked Dr. Jariwalla what the study suggested about an
appropriate dose of vitamin C. He said other results indicate
that at least 10 grams orally would be needed to obtain the
minimum blood levels for antiviral effect. Higher doses can be
obtained through intravenous infusion, to reach plasma levels in
the range found most effective in the laboratory tests. He
cautioned, however, that further clinical studies are required to
establish the optimum method of administration for
maintaining high levels of ascorbate in the blood.

Note: large doses of vitamin C are usually taken as a powder,
not as pills. We asked about the different forms of the vitamin
which are available. The Linus Pauling Institute sent us an
information sheet which said that "Vitamin C, from Bronson
Pharmaceuticals, La Canada, California, is available in the form
of ascorbic acid, sodium ascorbate, calcium ascorbate, or sodium
ascorbate and ascorbic acid combination." The sodium or
calcium ascorbate salts are used to reduce slight acidity in the
urine due to ascorbic acid. Dr. Jariwalla said that for oral use of
high doses, the mixture of sodium ascorbate and ascorbic acid
should be used -- or calcium ascorbate for persons on a sodium-
restricted diet.

We suggest that patients discuss vitamin C, or any treatment
they are considering, with their physician. A nutritionist told us
that some patients have sought treatment for diarrhea, not
realizing that it was caused by taking too much vitamin C; until
they told their physician that they were using the vitamin, the
actual cause of the diarrhea was not suspected. Persons should
also realize that suddenly stopping high doses of vitamin C can
cause deficiency symptoms, as the body is used to the large
amounts and temporarily unable to use the small amounts in
the normal diet efficiently.

We also called Bonnie Broderick, R.D., M.P.H., who is HIV
nutritionist for the early intervention project of the Santa Clara
(California) Department of Public Health. She was concerned
that large doses of vitamin C could interact with other nutrients,
especially vitamin B12 and copper, possibly causing deficiency
symptoms of those nutrients. She also referred us to a chart in
Nutrition Action Healthletter, October 1987, which listed
possible adverse effects of high doses of vitamin C; the chart is
based on a book, The Right Dose: How to Take Vitamins and
Minerals Safely, by Patricia Hausman, M.S., published by Rodale
Press, Emmaus, Pennsylvania, 1987. Because of the possibility
of adverse effects, she is not recommending high-dose vitamin C
until clinical trials have shown an antiviral effect or other
benefit in people.

We asked Dr. Jariwalla what he thought would be the next step
in organizing studies. (Financing, of course, is a major
requirement; the Linus Pauling Institute study was funded by
private donations, and by the Japan Shipbuilding Industry
Foundation; research grants will be sought for further studies.)
Dr. Jariwalla replied that two main avenues are being explored.
First, the Linus Pauling Institute is inviting researchers at
hospitals, clinics, community-based organizations, etc., to start
clinical studies. The Institute itself does not do clinical trials, but
can collaborate with others who initiate them. And second, the
Linus Pauling Institute has urged the National Institute of
Allergy and Infectious Diseases to undertake clinical studies. Dr.
Jariwalla said that "the new evidence provides a strong
scientific basis to conduct clinical trials of vitamin C in AIDS."

References

(1) Harakeh S, Jariwalla RJ, and Pauling L. Suppression of
human immunodeficiency virus replication by ascorbate in
chronically and acutely infected cells. Proceedings of the
National Academy of Sciences, USA. September 1990; volume
87, pages 7245-7249.