Vitamin C May Reduce Response to Chemotherapy

Zosia Chustecka

October 02, 2008

October 2, 2008 — Large supplemental doses of vitamin C could interfere with the therapeutic cytotoxic effects of a wide range of chemotherapy agents, suggests a new preclinical study. Although the finding comes from research conducted in cancer cell lines and mice, the authors say the conditions they created are similar to those found in the body, and speculate that the same mechanism might affect patient outcomes.

"It is possible that vitamin C supplementation may alter the effectiveness of commonly used chemotherapeutic agents and adversely influence treatment outcome," the researchers write in the October 1 issue of Cancer Research.

Lead author Mark Heaney, MD, PhD, from Memorial Sloan-Kettering Cancer Center, in New York, New York, told Medscape Oncology that he advises his cancer patients to avoid supplemental vitamin C during chemotherapy. "I recommend that my patients continue to eat a well-balanced diet that includes fruits and vegetables that contain vitamin C."

"Such a diet could be expected to have moderate amounts of vitamin C as well as other important nutrients. There are no data to suggest that vitamin C obtained from fruits and vegetables is intrinsically different from vitamin C supplements. Given that our research was done in experimental model systems and was not a clinical trial, I am reluctant to predict a dose of supplemental vitamin C that could be extrapolated to our work. That said, oral vitamin C supplementation with doses as low as 250 mg over a 1-month period resulted in intracellular vitamin C concentrations in normal white blood cells that were close to those that we studied in white blood cell cancers," Dr. Heaney said.

Reduction in Cytotoxic Effect

Dr. Heaney and colleagues found that pretreatment with dehydroascorbic acid, which is the form that vitamin C takes within the body, produced a dose-dependent attenuation of cytotoxicity for 5 unrelated chemotherapy agents: doxorubicin, cisplatin, vincristine, methotrexate, and imatinib.

The cell culture studies showed that the cytotoxicity was reduced by 30% to 70%, depending on the drug. A similar effect was seen in the animal studies; cancer cells transplanted into mice were held in check by doxorubicin, but grew more rapidly when they had been pretreated with vitamin C.

"It was notable that the concentration of vitamin C measured in the tumors of the mice in this study was similar to what can be achieved in human leucocytes with oral vitamin C supplementation, suggesting that our study conditions were relevant to clinical conditions," the researchers write.

Wide Variety of Chemotherapeutics Affected

"The finding that vitamin C antagonized the cytotoxic effects of such a wide range of antineoplastic agents was unexpected," the researchers comment.

Dr. Heaney and colleagues explain that they had originally hypothesized that vitamin C, being a potent antioxidant, would antagonize the cytotoxic effects of antineoplastic agents that use reactive oxygen species, such as cisplatin and doxorubicin.

However, the finding that the cytotoxicity of other chemotherapeutic agents was also affected suggests that other mechanisms are involved. The researchers speculate that the effects might be mediated by mitochondrial membrane depolarization. All of the chemotherapeutic agents, even the highly targeted product imatinib, appear to act through this pathway. Previous studies, and some of the current results, show that vitamin C stabilizes the mitochondria. In this way, vitamin C antagonizes 1 of the cytotoxic actions of the chemotherapeutic drugs.

Many Cancer Patients Take Vitamin C

"Our study is a preclinical model that addresses only the situation when vitamin C is given in the setting of chemotherapy treatment," Dr. Heaney emphasized. There have been no clinical studies of this topic so far, he said.

However, the finding could be of potential concern because "many people, cancer patients included, take supplemental vitamin C," Dr. Heaney pointed out. Clinical studies of vitamin C supplementation in patients with advanced cancers have had mixed results. There are conflicting hypotheses, he explained. One theory is that vitamin C supplementation protects the cancer and is therefore detrimental to the patient. But there is also the opposite view, that vitamin C supplementation enhances the immune system or prevents indolent cancers from mutating more and becoming aggressive, which would be beneficial for the patient.

Asked to comment on this study, Len Lichtenfeld, MACP, deputy chief medical officer at the American Cancer Society said: "Vitamin C has a long history in cancer prevention and treatment. Although there is no evidence to demonstrate that vitamin C improves the outlook for patients with cancer, there are still reported observations that cancer patients continue to believe in the potential benefits of vitamin C. Although oncologists do not routinely recommend that patients with cancer take excessive doses of vitamin C, there are reports that cancer patients are being treated with vitamin C by alternative practitioners."

"Recently, there have been research papers [indicating] that intravenous vitamin C may be beneficial in reducing the growth rates of cancers in laboratory animals. There are human clinical trials underway to determine whether or not this approach will be helpful in patients being treated for cancer," Dr. Lichtenfeld added.

However, he points out that the current report suggests that in laboratory experiments, adding vitamin C to cancer cells may reduce the effectiveness of cancer chemotherapy drugs.

"Clearly, there remains an open question as to whether or not vitamin C supplementation is helpful or harmful in the treatment of patients with cancer. Until those questions are resolved with further clinical studies, it would be inappropriate to recommend that patients take large quantities of vitamin C if they have cancer," Dr. Lichtenfeld told Medscape Oncology.

The researchers have disclosed no relevant financial relationships.

Cancer Res. 2008;68:8031-8038.

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