Vitamin C May Reduce Response to Chemotherapy

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Linus ing convincingly showed that cancer

patients are almost invariably low in vitamin C.

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Vitamin C May Reduce Response to Chemotherapy

Zosia Chustecka

Medscape Medical News 2008. © 2008 Medscape

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.