DO HERBS, VITAMINS, AND ANTIOXIDANTS ADVERSELY AFFECT CANCER THERAPIES?

​(preliminary report by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon)

For more than 30 years now, Chinese herbs and materials derived from the herbs, such as long chain polysaccharides, have been used as adjunct therapies for cancer patients.

This modern application was first developed clinically in China and Japan during the 1970s and was relayed to the rest of the world in 1983 through an international conference in Beijing which was followed up by press reports in English and other languages (see: Physiological responses to immunologically active polysaccharides).

The Institute for Traditional Medicine (ITM) made an effort to alert practitioners of Chinese medicine in the U.S. to this promising role for Chinese herbs immediately after that conference, with updated information provided as available over the years. The utilization of Chinese roots, leaves, and fruits (e.g., astragalus, gynostemia, Ligustrum, and lyceum), and several mushrooms (e.g., Coriolis, Ganoderma, cordyceps, and Lentinus) for cancer patients is now a routine procedure when these patients visit acupuncturists, naturopathic physicians, and others offering adjunctive cancer health care.

Within the past couple of years, however, an increasing number of patients have been told by their oncologists to avoid herbs, and to more generally avoid supplements (such as vitamins), or, even more broadly, simply avoid anything with antioxidant potential while they are undergoing cancer therapies.

The admonition itself is difficult to interpret, since all foods contain antioxidants and vitamins, and they also contain most of the other substances offered in dietary supplements. Most fruits, vegetables, beans, and nuts differ only slightly from herbs. A more specific recommendation is needed.

But first, the question arises: why are doctors giving these instructions? What kind of information is being released to the public?

I have attempted to trace back the origins of the restrictions imposed by some oncologists, and it seems that the primary instigator of the concern was Dr. David Golde at the Memorial Sloan-Kettering Cancer Center, even though he was not the first to raise the matter (but within a few months of being first).

The main issue he raised was the use of high doses of vitamin C, a therapy that has nothing directly to do with herbs. Herbs usually have little or no vitamin C; still, vitamin C is commonly prescribed or recommended as a supplement by practitioners involved in natural healing.

In a June 19, 2000 report of WebMD Medical News, the use of high doses of vitamin C to prevent heart disease, cancer, and other disorders, was called into question, and Dr. Golde’s research and comments were relayed (1, 2):

The first of two recent studies that called this notion [of taking high doses of vitamin C as a disease preventive] into question was carried out by David Golde, MD, physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York City, and described at an American Cancer Society meeting in March 2000.

Golde and his colleagues transplanted human cancer cells into mice, injected the mice with vitamin C, and then measured the amount of the vitamin in the cells. They found that cancer cells seem to soak up large amounts of vitamin C by converting it into a form that’s easier to absorb. The results, Golde says, raise the possibility that cancer cells may use vitamin C to shield themselves against radiation and chemotherapy.

The second study, performed by James Dwyer, Ph.D., an epidemiologist at the University of Southern California, caused an even bigger stir. Dwyer told an American Heart Association meeting in March 2000 that middle-aged men who took 500 milligrams of vitamin C supplements daily showed a rapid narrowing of their carotid arteries, which supply blood to the brain.

The studies sound alarming, but experts warn against making too much of them. While Golde says that cancer patients shouldn’t take large doses of the vitamin, other researchers say it’s far too early to make that recommendation.

There’s no evidence yet that C actually shields cancer cells from treatment, says Mark Levine, MD, an endocrinologist and Vitamin C expert at the National Institutes of Health. The cancers tested in Golde’s research, he says, may simply have grown from tissues that normally take in large amounts of the vitamin.

As for the heart disease finding, Dwyer himself cautioned that it is preliminary. The study lasted only 18 months and included just 573 men. And Robert Jacob, Ph.D., a research chemist with the U.S. Department of Agriculture, points out that previous studies suggested just the opposite-that vitamin C reduces the narrowing of carotid arteries.

From these very modest beginnings in Spring of 2000, the worry about antioxidants and cancer therapies grew, despite several warnings about the interpretation of data, such as those mentioned in the above analysis, and almost everyone who wished to provide a basis for the antioxidant and vitamin worry seemed to harken back to Dr. Golde’s very preliminary research.

A pharmacist, John Russo, Jr., wrote the following to caution his readers about the possible interaction of antioxidants with brachytherapy (radiation therapy where the radiation source is placed inside the body) for prostate cancer (3):

How might an antioxidant adversely affect brachytherapy?
The precise role that the antioxidant, vitamin C, plays in tumors is not known, but recent studies have shown possible interactions between dietary antioxidants and cancer treatment.

We know that vitamin C is a powerful antioxidant. It consumes free radicals, the toxic substances in the body that can be generated by chemotherapy agents to destroy cancer cells. “It is possible,” according to Dr. David Golde, Physician-in-Chief at Memorial Sloan-Kettering Cancer Center, “that taking large amounts of vitamin C could interfere with the effects of chemotherapy or even radiation therapy.” These therapies often kill cells, in part, by using oxidative mechanisms.

It’s conceivable then, that vitamin C might make cancer treatment less effective, and it is reasonable that cancer patients undergoing chemotherapy avoid taking large amounts of this vitamin.”

Building on past research

Earlier research by Dr. Golde and his colleagues established that specific glucose transporter molecules carry vitamin C into cells. This occurs once vitamin C, which is used by cells in the form of ascorbic acid, is converted into dehydroascorbic acid and transported into the cell. Once inside, the vitamin is converted back to ascorbic acid.

Applying this information to patient care

According to David Agus, an oncologist at Memorial Sloan-Kettering Cancer Center, we now know that tumors acquire and retain large amounts of vitamin C. And their nutritional needs appear to be similar to healthy cells that take in large amounts of the vitamin.”

However, what cancer cells do with the vitamin C after it is absorbed is not known. This will have to be determined before guidelines for the complementary use of antioxidants during chemotherapy and radiation become established.

Furthermore, research from University of Tubingen, School of Medicine in Germany suggests caution in applying this knowledge to all antioxidants in all types of malignancies. Examination of the modulation of drug-induced cytotoxicity and clonogenic cell death of glioma cells by three structurally unrelated antioxidants revealed that these antioxidants inhibit acute cytotoxicity and clonogenic cell death induced by cisplatin.

However, they had little effect on the toxicity of other cancer drugs including BCNU, doxorubicin, vincristine, cytarabine, or camptothecin.

In the discussion of brachytherapy, the pharmacist carries the implications over to chemotherapy agents, but mistakenly states that these function by producing free radicals. In general, this is not the case, and only applies to radiation (see explanation of mechanism, Appendix).

The research cited here about an inhibition of cisplatin therapy by antioxidants (but, notably, no effect of the tested antioxidants on several other chemotherapy drugs) was published in 1998 (4), and did not produce much interest at the time, nor has a follow-up report been published to date (end of 2002).

Glioma cells (a type of brain cancer) are normally resistant to the effects of chemotherapy, and the authors were examining factors influencing this already poor response. They determined, in their study, that cisplatin did not rely on free-radical formation to damage glioma cells, so antioxidant activity working directly against cisplatin effects was not an issue.

Rather, the substances tested in this in vitro study appeared to function by some other unknown mechanism.

By contrast, another platin drug, oxaliplatin, was used in a double-blind, placebo controlled clinical trial along with administration of the antioxidant glutathione (GSH; see Figure 1).

The authors concluded (5): “This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.”

This is an important finding, because it had been proposed that cancer cells could become resistant to platin drugs (e.g., cisplatin and carboplatin;) due to changes in the cancer cell membrane, where the resistance may be caused by the binding of platinum to intracellular thiols, such as glutathione.

This possibility, based on in vitro studies, implies that the interaction between platinum and GSH could prevent the active compounds from reaching the DNA nucleus. It is unclear at this point, whether administering glutathione can be recommended (as is often done by proponents of its protective effects), but this substance does not appear to have any direct interference with oxaliplatin when used clinically based on the recent clinical trial.

In vitro studies indicate that high intracellular glutathione levels protect cancer cells from the effects of chemotherapy, but this may not carry over to the clinical situation. A related concern about chemotherapy drug resistance has been raised about using antioxidants with cyclophosphamide, a particularly toxic anticancer drug. When the literature was reviewed, it was found that, if anything, the substances were beneficial for patients on cyclophosphamide therapy.
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ANTIOXIDANTS CANCER

CHINESE HERBS

VITAMINS