WASHINGTON, DC—Do antioxidants help or hinder conventional cancer therapy? The question is one of the most contentious in cancer care today, not to mention one of the hottest topics at conferences on natural medicine.
A few things seem clear: many people with cancer want to take antioxidant vitamins, believing they will reduce side-effects of conventional treatments or possibly inhibit tumor growth; science on the topic is incomplete, with data available to support either view; opinions are very strong on both sides.
A panel of physicians and patient advocates summarized the conflict at the Comprehensive Cancer Care 2000 conference, sponsored jointly by the Center for Mind-Body Medicine, the University of Texas–Houston, the National Cancer Institute, and the National Center for Complementary and Alternative Medicine.
David Rosenthal, MD, director of Harvard University Health Services and immediate past-president of the American Cancer Society, said there is a great deal of evidence, both good and bad, on both sides. But he cautioned participants to take into account the quality of the data. “There are many things we don’t know, especially in uncontrolled situations with lots of variables.”
At issue is whether the free-radical scavenging mechanisms by which antioxidants are thought to reduce adverse effects of chemo- or radiotherapy will also interfere with anti-tumor effects. This is the view of many conventional oncologists, who insist—despite the absence of solid data—that free-radical generation is essential for effective tumor-killing and that antioxidants interfere with the therapies they give.
Moderator Henry Dreher, a medical writer who also counsels cancer patients on complementary therapy options, said people with cancer often find themselves barraged with conflicting information at a time when they most in need clarity. “Half the world warns the patients against antioxidants, while the other half warns them they may be giving themselves short-shrift if they don’t take them. No one is neutral.” His point was well-illustrated during the panel discussion.
Ralph Moss, PhD, who writes The Moss Reports and Cancer Decisions, two newsletters on alternative therapies for cancer, strongly believes antioxidants “prevent or diminish side-effects of therapy and help in cancer healing.” He made brief reference to 150 studies on the interaction between antioxidants—including vitamins A, C, and E and glutamine—most of which support this belief.
“Anecdotally, almost without exception, people feel better if they are using antioxidants during chemotherapy,” said Dr. Moss. Oncologists recognize that antioxidants help with side-effects of chemotherapy, “but they think if they’re preventing side effects, they’re also preventing the desired effects,” Dr. Moss noted. “I think the data prove otherwise.”
Rudolph Salganik, MD, PhD, a research professor of nutrition at the University of North Carolina, disagreed. Although free radicals in the body damage cells and promote carcinogenesis, Dr. Salganik believes they also play a vital role in apoptosis (programmed cell death). “Most anti-cancer drugs kill cancer cells by apoptosis,” said Dr. Salganik. Megadoses of antioxidants that destroy free radicals, “reduce the effectiveness of chemotherapy drugs,” he said.
Dr. Salganik’s recently published murine study (Carcinogenesis, 2000; 21(5):909–14) supports this hypothesis. Making a trans-species leap, he theorized that his findings could explain the widely reported observation of increased cancer incidence in smokers on beta-carotene: the beta-carotene inhibited apoptosis which could have been mitigating the neoplastic process in these high-risk individuals.
According to Kenneth Conklin, MD, PhD, an anesthesiologist and medical acupuncturist at UCLA, both sides are right and both are wrong. He believes the current contention over antioxidants reflects a general lack of understanding of oxidative stress in health and disease, and an over-simplification of very complex biochemical questions.
Speaking at the American Academy of Medical Acupuncture’s annual symposium, Dr. Conklin said his interest in this question grew out of his wife’s experience with cancer. Armed with extensive training in biochemistry, he culled all literature on the issue, and synthesized a comprehensive but individualized holistic approach to adjunctive cancer care that includes dietary changes, acupuncture and selective use of supplements.
He explained that all cellular metabolic processes generate free radicals and reactive oxygen species, and all animals have enzyme systems for detoxifying them. Oxidative stress occurs when production of these molecules outstrips the enzymatic ability to neutralize them. This occurs in any state of excessive cellular respiration, whether caused by extreme exercise, exposure to environmental toxins, or disease states including cancer.
Oxidative stress is detrimental because reactive oxygen species damage micronuclear structures and cell organelles, and impair DNA replication and cell division.
“Cell growth rate is almost perfectly inversely related to oxidative stress,” Dr. Conklin said. All fast-dividing cell types such as bone marrow, hair follicles, and many forms of cancer, show direct slow-downs of cell division as oxidative stress increases.
He held that most conventional cancer chemotherapies work by inhibiting synthesis of DNA precursors or cross-linking tumor cell DNA. The paradox is, these same drugs also markedly increase oxidative stress, and this slows growth rate in the fast-turnover tumor tissue, rendering it progressively less susceptible to the primary drug effect as treatment continues.
In short, these drugs end up short-circuiting their own effects. This paradox is most pronounced with the anthracyclines (adriamycin and doxorubicin), the chemotherapy drugs that cause the greatest increase in oxidative stress.
So, what of antioxidant vitamins? Dr. Conklin, who receives referrals from a number of LA-area oncologists, believes they can enhance anti-cancer effects. “Antioxidants reduce oxidative stress, thus allowing the target cells to grow and divide rapidly, spending more time in the S, G2 and M phases of the cell cycle,” where they are more susceptible to the killing effects of chemotherapy. He strongly differs with prevailing oncologic opinion, contending that, “Free radical generation is not a mechanism of cancer cell-killing.”
In treating cancer patients, he often recommends that they take antioxidants during chemotherapy. Though the regimens can be tailored depending on the type of tumor and chemotherapy agents used, they generally include high-isoflavone soy protein powders, vitamin E (400 IU mixed tocopherols), vitamin C (500 mg, with bioflavinoids), and co-enzyme Q10 (50 mg/day).
But he cautioned against putting too much faith in antioxidants; they only have real benefits in conditions of intense oxidative stress. Cancer cells not under any oxidative stress show no response to vitamin E, and this probably holds for other anti-oxidants as well. He also challenged the notion that antioxidants can reduce chemotherapy side-effects like nausea, mucositis, and myelosuppression, since these are not really mediated by free-radicals.
Clearly far more research needs to be done before this complex clinical question can be definitively answered.
THE REDUX: Many cancer patients want to use antioxidant vitamins during chemotherapy, believing they reduce side-effects, enhance anti-tumor effects, and promote well-being. Experts are divided: some argue that free-radical generation is an essential chemotherapeutic mechanism and that antioxidants interfere with drug effects; others hold that the vitamins maintain tumor cells in the cell-cycle phases most susceptible to anti-tumor drugs. There is evidence—none of it definitive—supporting both views. Further research on the role of oxidative stress in health and disease is needed to resolve this clinical quandary. More on this topic in the February issue of Holistic Primary Care.
