April 2010 Issue Therapeutic Controversy — Is Supplementing Cancer Treatment With Antioxidants Helpful or Harmful? By Sharon Palmer, RD Today’s Dietitian Vol. 12 No. 4 P. 26 Today’s Dietitian taps into the hot debate among leading experts and highlights the importance of whole foods nutrition during therapy.
“Lay off your vitamins and dietary supplements” is common advice patients with cancer receive when they start treatment. Some health providers have even been known to take it a step further by suggesting that their patients avoid fruits and vegetables. Why would those words pass any health expert’s lips? It all boils down to what Keith Block, MD, medical director of the Block Center for Integrative Cancer Treatment in Evanston, Ill., calls the debate over antioxidants in cancer treatment. Do antioxidants help normal cells or tumor cells thrive? Do they interfere with the therapeutic effects of chemotherapy? These are big questions being raised in the oncology world—and there are no easy answers. Cancer experts seem to be split into two camps on the antioxidant issue. One side believes taking antioxidants during cancer treatment may interfere with chemotherapy and radiation by reducing their efficacy. Radiation and some chemotherapy agents work by generating free radicals that kill rapidly dividing cancer cells. Since antioxidants scavenge free radicals, the thinking is that they may interfere with these cancer treatments. The other side of the argument is that oxidation supports the growth of malignant cells, which may conflict with treatment. Thus, antioxidants may counter the harmful effects of oxidation in the malignancy process, boost the effects of the cancer therapy, and protect patients from the therapy’s toxic side effects. Supportive Evidence In some circles, there is mounting support for using antioxidants during cancer therapy. Block, who spoke at the Sixth Annual Nutrition and Health Conference in Chicago in May 2009, concedes that there is controversy about whether antioxidants protect normal cells or cancer cells. But he believes antioxidants should be administered with chemotherapy because oxidative stress initiates and promotes cancer cells; cancer patients often have low levels of antioxidants, which increases their susceptibility to side effects; and oxidative stress promotes cytotoxicity and serious side effects. To provide evidence-based science on this issue, Block conducted two systematic reviews. As discussed in a May 2007 issue of Cancer Treatment Reviews, his research team conducted a systematic review of published studies examining the effects of antioxidant supplements in chemotherapy, with 19 out of 845 studies meeting all evaluation criteria for the review. The researchers concluded there is no evidence supporting the theory that antioxidant supplements interfere with the therapeutic effects of chemotherapy agents. The review found that antioxidants may help increase survival rates, tumor response, and patients’ ability to tolerate treatment. Some of the antioxidants used in the trials included glutathione, vitamin A, vitamin C, vitamin E, ellagic acid, selenium, and beta-carotene. In the second systematic review examining the impact of antioxidant supplementation on chemotherapeutic toxicity, 33 out of 965 studies met the inclusion criteria. Antioxidants evaluated were glutathione, melatonin, vitamin A, an antioxidant mixture, N-acetylcysteine, vitamin E, selenium, L-carnitine, Coenzyme Q10, and ellagic acid. The majority of the
studies (23 out of 33) found evidence of decreased toxicities from the concurrent use of antioxidants with chemotherapy. Nine studies reported no difference in toxicities between the two groups. Only one study on vitamin A reported a significant increase in toxicity in the antioxidant group. Five studies reported that the antioxidant group completed more full doses of chemotherapy or had less dose reduction than control groups. The review findings were published in the International Journal of Cancer in 2008. According to Block, these reviews largely support the notion that antioxidants enhance treatment outcomes, increase survival times, and increase tumor responses. The majority of the studies show that the antioxidant group had decreased toxicities; antioxidants and chemotherapy are safely recommended for metastatic and palliative care patients; and there was no significant decrease in treatment efficacy. Kedar N. Prasad, PhD, founder of and chief scientific officer for Premier Micronutrient Corporation, is another leader in the realm of antioxidant therapy during cancer treatment. In 1979, he was the first to show that vitamin C can enhance the effect of radiation and chemotherapeutic agents on tumor cells. In 1982, he discovered that vitamin E succinate was the most effective form of vitamin E for killing cancer cells but not normal cells. “The controversy over antioxidants in cancer therapy is not justified. It’s a theoretical controversy because there is no data that will show that therapeutic doses of antioxidants do not protect normal cells and enhance effects of therapy on tumor cells,” reports Prasad. “Clinical studies show that people using chemotherapy experience severe peripheral neuropathy, and high doses of vitamin E markedly [decrease] neuropathy. In cancer of the head and neck, radiation-induced damage was improved by therapeutic doses of betacarotene, and it didn’t interfere with the therapy.” Prasad explains that the mechanisms by which antioxidants may help in cancer treatment go beyond the prevention of free radical damage. “Antioxidants function to prevent free radical damage, and that’s important. But at therapeutic doses, there are other mechanisms, such as induced apoptosis, decreased inflammation, and enormous change in gene expression,” says Prasad, who stresses that this is important because during chemotherapy, the body’s tissues are damaged by the production of free radicals and by severe inflammation. Prasad limits his recommendations for antioxidants during cancer treatment to therapeutic doses of dietary antioxidants such as vitamins A, C, and E and beta-carotene because other antioxidants made in the body, such as sulfhydral compounds like alpha-lipoic acid, may present toxicity concerns. Words of Caution Many cancer experts believe the science doesn’t yet fully support antioxidant use during cancer treatment. According to the American Institute for Cancer Research (AICR), the current evidence supports both views on antioxidants—that they could interfere with treatment and protect healthy cells and reduce side effects. A commentary on antioxidant use in cancer therapy was published in the Journal of the National Cancer Institute in 2008 by lead author Brian Lawenda, MD, MC, USN, clinical director of radiation oncology at the Naval Medical Center in San Diego. The article reports that despite nearly two decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy and radiation therapy, controversy remains. Lawenda notes that several randomized clinical trials found that the concurrent administration of antioxidants with chemotherapy or radiation therapy reduces treatmentrelated side effects; some data indicate antioxidants may protect healthy cells (as well as tumor cells) from oxidative damage generated by cancer therapy; and other data suggest that antioxidants can protect normal tissues from chemotherapy or radiation-induced damage without decreasing tumor control. But on the basis of reviewing published
randomized clinical trials, Lawenda’s team concluded that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival. Strength of the Science While the debate over this issue continues, the bottom line is that the scientific evidence is not for or against antioxidants in cancer treatment. “This is an area of controversy. As a conventional oncologist, it’s more of an issue of potentially interfering with conventional therapy and making it more toxic or less effective. But we don’t have a lot of evidence to support it one way or another. Adding to the confusion, some isolated antioxidant compounds have been shown to have prooxidant effects depending on the dose and route of administration, etc. Due to the complexity of all the variables involved in studying this question and how they impact a specific individual at a specific time, we are limited by what we can say regarding the effects of increasing or decreasing the amount of a specific antioxidant,” explains Lawenda. “In radiation therapy, there is at least one well-conducted phase 3 study that suggests that a specific high-dose antioxidant supplement potentially interferes with treatment. But with chemotherapy, it is much less clear. Radiation therapy and many chemotherapeutic agents cause oxidative damage in tumors during therapy and if you give antioxidants, it theoretically could inhibit the therapy.” Lawenda stresses that large-scale phase 3 trials are needed to help answer these questions, but this kind of research comes with a high price tag. Prasad believes antioxidants are controversial in cancer therapy because of two very important distinctions in antioxidant research. “First, there are two different kinds of doses of antioxidants used. You can divide the data on the role of antioxidants in cancer therapy in two categories: a preventive dose, which is a low dose, and a therapeutic dose, which is a high dose. For the preventive dose, the data has shown protection of normal cells and tumor cells. For the therapeutic dose, the data shows that it inhibits the growth of cancer cells but not the normal cells. People are looking at data for preventive doses, which is confusing. Another important thing that has caused controversy is that people are looking at data for cancer prevention, such as the beta-carotene trial that showed a link with lung cancer occurrence. This doesn’t make sense. The data is not the same for prevention of cancer and for people with cancer undergoing therapy.” Dietary Supplement Reality Put aside the antioxidant-cancer treatment debate for one minute to consider this: Dietary supplement use is common among the 10 million adults in the United States who have been diagnosed with cancer. According to a study conducted by the Fred Hutchinson Cancer Research Center and published in the Journal of Clinical Oncology in 2008, 64% to 81% of cancer survivors reported using a vitamin or mineral supplement. In comparison, about 50% of U.S. adults reported using dietary supplements. Between 14% and 32% of survivors initiated supplement use after their diagnosis. The most surprising finding from the study? Up to 68% of physicians might be unaware of their cancer patients’ supplement use. In a 2008 article published in Hematology/Oncology Clinics of North America, Mary Hardy, MD, medical director at the UCLA Center for Integrative Oncology, reported that despite high rates of dietary supplement use by patients throughout all phases of cancer care, conventional wisdom generally recommends complete avoidance of all dietary supplements, especially during chemotherapy and radiation. Thus, many patients don’t disclose their use of supplements to their physicians. Hardy found that a review of the clinical literature shows that some evidence for harm does exist; however, data also exist showing benefits from using certain well-qualified supplements. The moral of the story? Hardy suggests that physicians increase their
knowledge base about dietary supplement use in cancer and consider all of the data when advising patients. Healthcare providers may want to employ patient-centered strategies and reflect the complete array of available evidence that can lead to more nuanced messages about dietary supplement use in cancer. This sort of strategy may encourage patients to disclose their supplement use and increase safety and efficacy for patients choosing to use dietary supplements during cancer care. Jacki Glew, MS, RD, LDN, clinical nutrition specialist at the Block Center, says, “Most of the patients that come to us are very open to taking supplements during treatment. They have heard that Dr. Block has been using supplements concomitantly with chemotherapy with much success over the years, and that is often one of the reasons they visit the Block Center.” An Important Place for Nutrition There’s a saying that cancer treatment—however essential it is for survival—can get you before the cancer does. And there may be some truth to that. In a recent press release from the Block Center, David L. Katz, MD, MPH, FACPM, FACP, cofounder and director of the Yale-Griffin Prevention Research Center, teamed up with Block to report that up to 40% of patients with cancer die from complications from malnutrition, not the disease itself. In fact, 80% of patients with cancer develop some form of clinical malnutrition. Conventional medical advice for cancer may be to “eat whatever you want,” but this can feed into patients’ cancer, promote malnutrition, and contribute to an inability to tolerate treatment, according to the authors. Block reported in the release, “The heavy consumption of fats, refined flours, and sugars found in the traditional American diet can increase inflammation, contributing to a lack of appetite, more debilitating weight loss, and actually promote the very disease the patient is trying to fight.” Katz added, “Cancer may kill, in part, by causing starvation, and conventional therapies may actually exacerbate this aspect of the disease. While these treatments can effectively attack the cancer, they also take a toll on the patient. There is thus a need to combine effective assaults on cancer, with effective nurturing and nourishing of the body. Optimizing nutrition during and following cancer therapy is unquestionably a vital element in overcoming the disease and reclaiming good health.” Whole Food Sources Are Best While there may be controversy about whether people should opt for supplemental antioxidants during cancer treatment, there shouldn’t be any when it comes to antioxidants found in whole food sources. Lawenda says, “The best bet for now is the whole foods approach. Consuming antioxidants in whole foods vs. high-dose isolates is very unlikely to reach levels sufficiently high enough to interfere with treatment. The reasons why I recommend whole food vs. isolated antioxidants is because, generally, the studies to date that have been reported do not adequately answer this controversial question. As an integrative oncologist, I recommend a diet full of dietary antioxidants that are naturally produced, not isolated high-dose antioxidant supplements. Beyond simply acting as an antioxidant, there are interesting data on the anticancer effects of many phytonutrients. At this point, a whole food diet, where you eat at least three to four a day of fresh fruits and vegetables, is the safest.” “My motto is food first,” says Glew. “Supplements are just that—they supplement a healthy diet. Supplements cannot counteract a poor diet. That is why we spend plenty of time discussing nutrition with our patients to make sure that they understand that whole foods provide so much more than a supplement ever could. However, we do include supplements where needed. Many times, our patients come to us in such poor health after years of eating a diet lacking in nutrition that they are depleted of the necessary vitamins, minerals,
and phytochemicals that can help to control tumor growth by reducing inflammation and controlling the rate of cell division. We emphasize a diet rich in plant foods to help achieve this that includes plenty of vegetables, whole grains, fruits, and legumes with soy, fish, and occasional omega-3 eggs.” Enter Integrative Cancer Care Whether or not you support supplemental antioxidant therapy during cancer treatment, it’s hard to find fault with a cancer plan that includes the power of nutrition. Just take a look at how the Block Center handles cancer care. The center, founded by Keith and Penny Block— Penny serves as executive director—about 30 years ago, integrates conventional medicine protocols with advanced complementary therapies that address the physical, nutritional, psychosocial, and spiritual aspects of healing and recovery. “The role of integrative therapy is to reduce toxicity so that more people can tolerate full therapy and increase survival rates,” says Block. One of the leaders in nutritional therapy for cancer care, Block Nutrition Program’s aim is personalized nutrition for every person and lifestyle. An individual’s biochemical environment is assessed by evaluating markers of stress chemistry, inflammatory response, excessive growth signals, and immune disregulation. The emphasis is on a sound, specifically designed diet, enhanced by a carefully charted regimen of supplements and treatments meant to aid the body in ridding itself of disease, prevent further illness or recurrences, and sustain overall good health. RDs help incorporate the nutritional agenda into patients’ daily lives through recipes, cooking classes, seminars, and counseling. The diet that the Block Center recommends to reduce cancer recurrences is one rich in fiber, complex carbohydrates, fruits, vegetables, and plant sources of protein. Other healthy dietary staples may include foods rich in monounsaturated fats and energy- and nutrientdense foods such as avocados, olive oil, soy, and seed and nut butters. The Block Nutrition Program uses a basic exchange system that includes five basic exchanges for grains, vegetables, fruits, fats, and proteins to translate dietary recommendations into usable guidelines for meal planning. What about the dietary supplement regimen at the Block Center? Its policy is to suggest supplements for micronutrients, phytonutrients, and botanicals as an individualized regimen based on tumor type, biochemistry, and treatment stage. The goal is to enhance conventional treatment by minimizing side effects and bolstering the body’s anticancer defenses. This comes out of the Block Center’s position that even a well-balanced diet is often not enough to cope with appetite-destroying anxiety and traumatic treatments. Standard supplements may contain elements that might actually promote cancer growth, such as copper, folate, and high-dose B vitamins. Supplement quality can vary significantly; some may contain mercury, lead, and other contaminants, and some do not contain the quantity of active ingredients listed on the label. Thus, all of the supplements at the Block Center are scientifically formulated and tested under the center’s supervision. RDs Can Provide Knowledge and Support While it seems the controversy over antioxidant supplementation will likely continue in the coming years, it does appear that more cancer experts are acknowledging that nutrition can play an important role in treatment. Diana Dyer, MS, RD, a cancer nutrition expert, a cancer survivor, and the author of A Dietitian’s Cancer Story, sums it up well: “Every cancer treatment center could provide true comprehensive cancer care by having an RD as an integral member of the multidisciplinary team of oncology experts. The RD can help patients with questions regarding the use of all dietary supplements during cancer therapy and sort through the most up-to-date research specific to an individual’s type of cancer, chosen therapy, and goals to optimize the odds for both safety and potential benefit.”
— Sharon Palmer, RD, is a contributing editor at Today’s Dietitian and a freelance food and nutrition writer in southern California.
Nutrition Matters During Cancer Therapy Jacki Glew, MS, RD, LDN, clinical nutrition specialist at the Block Center for Integrative Cancer Treatment, shares her nutrition approach for patients facing cancer therapy: • Get lots of cancer-fighting phytochemicals in your diet by eating a rainbow of fruits and vegetables daily. The brighter the color, the more phytochemicals it contains. Choose organic when possible. • Sustain your energy by eating plenty of whole grains. Complex carbohydrates with fiber provide a slow, sustained supply of fuel. Avoid refined and processed grains/flours. • For protein, include legumes, unprocessed soy (tofu, tempeh, edamame), fish, and omega-3 eggs. Reduce or avoid red meat, pork, and dark meat poultry, which contain high amounts of inflammatory saturated fat and omega-6 fats and natural or added growth hormones that may spur growth rates of cancer cells. • Replace milk and other foods made from milk with rice, soy, oat, or nut alternatives. Milk has also been found to contain natural or added growth hormones that may spur growth rates of cancer cells but also contains casein, which can contribute to inflammation and decrease immunity. • Instead of refined sugars, choose fruits and lower glycemic sweeteners such as stevia and agave to satisfy cravings for sweets. • Limit total fat intake and shift to foods high in omega-3s and omega-9s such as fish, nuts, avocados, flax, and olives. Avoid trans fats. • Stay hydrated by drinking plenty of water but also include two to three cups of green or white tea to provide additional antioxidants.
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