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Is Vitamin C Harmful to Cancer Patients?

In a recent presentation at the American Cancer Society meeting, Dr. David Golde of Memorial Sloan-Kettering Cancer Center speculated that supplemental vitamin C may be harmful to cancer patients. Dr. Golde had previously shown how vitamin C gets into and accumulates in cancer cells. Golde and others are concerned that the extra vitamin C in cancer cells may enhance their growth or protect them from the cell-killing free radicals produced by radiation and some chemotherapeutic drugs.

While different cancer cells may respond differently to vitamin C, it is important to view these concerns in the context of the experimental cell culture, small animal, and human clinical studies. In some cell culture and small animal studies, vitamin C has enhanced cancer cell growth. Dr. Chan Park has found that the growth of leukemic cells from some leukemia patients put into culture was enhanced by vitamin C. The growth of cells taken from other leukemia patients was either inhibited or unaffected by vitamin C. It is unknown whether similar effects would have been observed in the same patients taking supplemental vitamin C. Dr. Joel Schwartz of the National Institutes of Health has published studies in which supplemental vitamin C enhanced the growth of tumors induced in hamsters by a chemical carcinogen. Interestingly, the growth of tumors was significantly inhibited by supplemental vitamin E and by a mixture of antioxidants, including beta-carotene, vitamin E, and vitamin C.

Studies published by LPI scientists since the 1970s have demonstrated that supplemental vitamin C delays the onset of tumors in mice that developed spontaneous mammary tumors, in mice exposed to ultraviolet radiation, and in guinea pigs implanted with liver cancer cells. In these experiments, vitamin C did not appreciably affect the growth rate of tumors once they formed. Other studies published by Dr. Constance Tsao and her colleagues at LPI showed that supplemental vitamin C (sometimes combined with oxidation products of vitamin C) inhibited the growth of human colon, lung, and mammary tumors implanted into mice. LPI investigations also demonstrated that vitamin C and its derivatives have anticancer effects against a number of cancer cell lines in culture.

What about clinical studies on vitamin C in cancer patients? Dr. Pauling and his medical collaborator, Dr. Ewan Cameron, former Chief of Surgery at Vale of Leven Hospital in Scotland, published numerous papers on the response of cancer patients given large doses of supplemental vitamin C as an adjunct to the appropriate conventional treatment for cancer. In their book Cancer and Vitamin C, they concluded that supplemental vitamin C is of benefit to most cancer patients. The benefits ranged from an increased sense of well-being to a prolongation of survival times in terminal patients to rare complete regressions. However, two clinical studies carried out by Drs. Edward Creagan and Charles Moertel of the Mayo Clinic and published in 1979 and 1985 showed no benefit from supplemental vitamin C on survival time. As Drs. Cameron and Pauling pointed out, however, the patients in the first Mayo Clinic study had undergone extensive chemotherapy that damaged their immune systems prior to the use of vitamin C. In the second study, supplemental vitamin C was abruptly stopped after only about two months. There was also evidence that some of the patients in the placebo group were taking extra vitamin C, thus muddying the differences between groups.

When Cancer and Vitamin C was first published in 1979, Drs. Cameron and Pauling noted that little information was available on the interaction between vitamin C and chemotherapeutic drugs. They cautioned that patients undergoing aggressive chemotherapy expected to be curative should refrain from taking large doses of vitamin C at the same time in case the vitamin interfered with the drug action. There is some evidence that vitamin C increases the activity of liver enzymes that detoxify xenobiotics, including drugs. When the chemotherapy was merely palliative, Drs. Cameron and Pauling did not believe that the use of concurrent vitamin C was contraindicated. They believed that vitamin C potentiates radiation, and even many clinicians who disagree on this point nevertheless agree that supplemental vitamin C given after radiation ameliorates radiation sickness.

In the early 1990s, Dr. Pauling published two papers with Dr. Abram Hoffer, who developed a regimen for use in cancer patients that includes B vitamins, vitamin E, large doses of vitamin C, beta-carotene, selenium, zinc, and other substances. The statistical analysis of their data revealed that about 40% of the cancer patients survived five years or more after the initiation of the regimen. (A new book by Dr. Hoffer, Vitamin C & Cancer, features major contributions by Linus Pauling and further discussion of these results.) Only about 10% of the patients treated by Dr. Cameron in Scotland with vitamin C alone survived as long, although all of the Scottish study patients had terminal cancer. These studies, as well as Dr. Cameronís studies in Scotland, were not designed as placebo-controlled, randomized, double-blind trials because of ethical concerns and practical problems concerning appropriate placebos.

Interestingly, Dr. Hofferís regimen is remarkably similar to that recommended by Dr. Kedar Prasad of the University of Colorado and his colleagues, who advocate the use of a combination of B vitamins, large doses of calcium ascorbate (vitamin C), vitamin E, and beta-carotene for cancer patients undergoing either chemotherapy or radiation. Dr. Prasad acknowledges the accumulation of antioxidant vitamins in cancer cells, but argues that this has favorable biochemical effects, including the inhibition of oncogenes and the induction of factors that inhibit cell growth, favor differentiation, or induce apoptosis (programmed cell death). In an extensive and well-referenced recent review published in the Journal of the American College of Nutrition, Dr. Prasad presented results from cell culture experiments demonstrating that the killing effect of many cancer drugs or radiation on mouse and human cancer cells is enhanced in the presence of vitamins C or E. Of course, cell culture studies (or animal studies) cannot always predict what will happen in humans. In another extensive review published in Alternative Medicine Review in 1999, Drs. Lamson and Brignall reached conclusions similar to those of Dr. Prasad. These authors noted that "considerable data exists showing increased effectiveness of many cancer therapeutic agents, as well as a decrease in adverse effects, when given concurrently with antioxidants."

A Finnish non-randomized clinical study published in Anticancer Research in 1992 by Dr. Kaakkola and colleagues showed that the provision of B vitamins, large doses of vitamins C and E, beta-carotene, fatty acids, and minerals in combination with chemotherapy and radiation to patients with small-cell lung cancer resulted in significantly prolonged survival, especially when started early. These patients were compared to patients in other studies who were treated only with chemotherapy and radiation. Another clinical study by Dr. Emmanuel Cheraskin published in 1968 showed that the response to radiation among women with cervical carcinoma was enhanced by daily supplements of 750 mg of vitamin C given during radiation.

What can we conclude about vitamin C and cancer? While the theoretical speculation by Dr. Golde seems plausible, there is no clinical evidence that supplemental antioxidant vitamins, including vitamin C, harm cancer patients. Indeed, much of the recent cell culture and clinical research suggests that a combination of antioxidant vitamins and minerals as an adjunct to conventional therapy may have benefit. This is a complex issue, however, and there is clearly more to learn from controlled clinical trials about the use of these modalities in treating cancer before definitive conclusions can be drawn.