Integrative Oncology: Complementary Therapies in Cancer Care

Barrie Cassileth; Marjet Heitzer; Jyothirmai Gubili

Disclosures

Cancer Chemother Rev. 2008;3(4):204-211. 

In This Article

Herbs and Other Dietary Supplements

Medicinal plants, used alone or in combination with other plants, have long been used in traditional medical systems, including traditional Chinese medicine and Ayurveda. Over the last two decades, the use of herbs and other botanicals in Europe and the USA has increased; nearly 20% of individuals in the USA reported using herbs to treat a specific health condition.[72] Herbs are the most commonly used complementary medicine in European cancer patients,[2,3] and among Japanese cancer patients using complementary medicine, most used herbs, mushrooms, and shark cartilage.[73]

Because botanicals are considered dietary supplements, they are sold over the counter without regulation by the Food and Drug Administration (FDA). However, lack of regulatory oversight poses many safety concerns. For example, poor quality control may result in contamination with other plant materials, pesticides, heavy metals, etc. Due to a lack of standardization, variability in product quality or levels of botanical agents may occur.

In addition to safety issues surrounding the lack of regulation, botanicals contain pharmacologically active compounds that may induce serious side effects, such as renal and hepatic failure, or may interact with prescription drugs.[74] Some herbs contain components that interfere with drugs metabolized via the cytochrome P-450 pathway.[75] These interactions can influence oncologic drug concentrations, thereby reducing their efficacy or increasing their toxicity. In fact, analysis of cancer patients using dietary supplements while receiving chemotherapy estimated that 27% were at risk for harmful drug-herb interactions.[76] In addition, certain botanicals may be harmful to some patients. For example, garlic, ginger, ginkgo, and ginseng possess anticoagulant effects or anti-platelet activities.[77] Therefore, patients using heparin, warfarin, aspirin, and other anticoagulants should avoid these botanicals. In addition, botanicals with estrogenic properties such as red clover, Dong quai, and soy should be avoided in patients with hormone- sensitive cancers.[78]

The use of other kinds of dietary supplements, such as vitamins, minerals, amino acids and enzymes, also has increased in recent years; 56-73% of cancer patients reported regular use of multivitamins,[79,80,81] although it is not necessarily clear whether these were USDA-level supplements or extremely high doses. Because many patients believe that anticancer therapies deplete them of important dietary vitamins and minerals, and because high doses of vitamins are promoted by many purveyors of related products, cancer patients often utilize megadoses of these agents, some of which are potent antioxidants (i.e. vitamin C, vitamin E, selenium, etc.). In addition, patients believe antioxidant supplementation will relieve radiotherapy and chemotherapy associated side effects.[82] However, clinical evidence regarding the safety and efficacy of antioxidant therapy is conflicting.[83] A recent review of randomized, controlled clinical studies in cancer patients found that antioxidant supplementation decreased chemotherapy associated side effects.[84] Conversely, antioxidant supplementation has been associated with increased mortality in cancer patients,[85] perhaps by reducing the efficacy of antineoplastic drugs.

The mechanism by which antioxidant supplements interact with chemotherapeutic drugs is not fully known. Many chemotherapy agents such as cisplatin and doxorubicin generate reactive oxygen species (ROS), so addition of potent antioxidants may reduce the efficacy of these drugs. For example, vitamin C reduces the efficacy of antineoplastic drugs whose cytotoxic effects are mediated by ROS; however, it also affects the efficacy of those that do not involve ROS production.[86] Therefore, vitamin C interacts with a wide range of chemotherapeutic agents, inhibiting mitochondrial membrane depolarization and perhaps cell death.[86] Thus, until studies determine the safety of antioxidant supplementation as well as appropriate dosage, cancer patients receiving chemotherapy and radiotherapy and those undergoing surgery should approach antioxidant supplements with caution.

Healthy individuals also use antioxidant supplementation as a means to prevent diseases such as cancer and cardiovascular disease, despite the absence of scientific proof. In fact, harmful rather than beneficial effects have been found in some studies that assessed the use of antioxidant supplementation for cancer prevention; there is increasing evidence that antioxidant supplementation may be linked to increased risk of developing certain cancers. For example, in male smokers, higher lung cancer incidence and mortality due to lung cancer was reported with beta carotene supplementation,[87] and long-term vitamin E supplementation may also increase lung cancer incidence.[88] Furthermore, antioxidant supplementation, which included a combination of vitamin C, vitamin E, beta carotene, selenium, and zinc, increased skin cancer in women.[89] In addition, a recent meta-analysis found that antioxidant supplementation, particularly beta carotene, may increase not only gastrointestinal cancer incidence but also all-cause mortality.[90,91] Subsequent in vitro and in vivo animal studies have reported tumor cell growth in response to various antioxidants. Specifically, beta carotene stimulated cellular proliferation in a pancreatic ductal adenocarcinoma cell line[92] and in lung cancer cell lines.[93] In an in vivo tumor model, vitamin C enhanced tumor growth.[94] Thus, the use of antioxidant supplementation for cancer prevention may be unwarranted, and antioxidant supplementation should be approached with caution in both healthy individuals as well as cancer patients.

Despite the lack of scientific data, most individuals consider botanicals as "natural" and "safe" as compared to conventional treatments. Of the individuals who reported using herbs (excluding Echinacea and ginseng), only one-third used them in accordance with evidencebased studies;[72] most received information pertaining to a specific herb from a friend and initiated herbal use without consulting their doctor.[73] Therefore, increased patient education on the appropriate use of dietary supplements by healthcare professionals is necessary. The Memorial Sloan-Kettering Cancer Center "AboutHerbs" Web site, http://www.mskcc.org/aboutherbs, is free to access, provides evidence-based and clinically useful information about more than 235 herbs and other botanicals as well as vitamins, other dietary supplements, and unproved cancer therapies, and is continually updated.

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