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.