The high-stakes drama in the news this spring told the tale of a teen with cancer leaving town with his mother, who wanted him to have alternative treatment instead of court-ordered chemotherapy.1,2 The panoply of cures peddled for both human and veterinary cancer patients can end up consuming the most limited resources: time and money. People’s allegiance sometimes splits between the tried and true and the too good to –be true. Many pick the middle ground of choosing both, hoping to offset the envisioned misery of chemotherapy with feel-good supplements. All too often, however, fact-based information about supplements and cancer becomes buried in the chaos of the Internet. In truth, herbs and supplements can often improve well-being and even outcomes when given appropriately. When administered injudiciously, however, they risk lowering the therapeutic value of chemotherapy and radiation.3 The oft-touted garlic, for example, induces the P-glycoprotein drug efflux transport system to aid the body in ridding itself of perceived toxins such as chemotherapeutics.4 In addition, antioxidants can counter the pro-oxidant effects of chemotherapy and radiation, and plant-derived anticoagulants can predispose patients to unexpected bleeding. Antioxidants Megadose vitamin regimens occupy center stage in the alternative cancer therapy world. An antioxidant/pro-oxidant interaction may alter expected outcomes usually obtained with chemotherapy alone, such as disease progression, antitumor response and survival.5,6 Indeed, as shown in a large human trial, supplemental vitamin E given daily during radiation therapy significantly lessened the acute side effects of radiation.7 But the all-cause mortality rate in the supplement group outweighed that of the placebo group, bolstering previous reports that suggested high-dose vitamin E could be harmful. In contrast, boosting beta carotene in the diet brought down the incidence of severe side effects and local cancer recurrence.8 How badly antioxidants interfere with conventional therapy depends on how strongly the latter depends on oxidation for its tumor-killing value. Radiation therapy produces reactive oxygen species, while most chemotherapy drugs have additional antitumor mechanisms. Since the effects of radiation last for weeks, some suggest avoiding antioxidants for weeks after radiotherapy stops. If the patient is receiving palliative radiation instead of curative, antioxidants may counter treatment-related adverse effects needed for the short term. For chemotherapy, some discourage antioxidant supplements throughout the entire course, which may last months.9 Herbs With Anticoagulant Effects Botanicals such as angelica root, dong guai, German chamomile, red clover and ginseng increase the risk of bleeding; garlic, ginkgo and saw palmetto sometimes have significant anticoagulant actions.10 Cancer patients may already have thrombocytopenia from chemotherapy or myelosuppression from bone marrow invasion that compromises their capacity to clot. Clinicians unaware of herbal antiplatelet effects may find themselves surprised by bleeding during biopsies or surgeries. Because of this, the American Society of Anesthesiologists recommends that human patients discontinue dietary supplements at least two weeks before surgery.11 Can Drugs and Supplements Peacefully Coexist? As stated earlier, certain supplements can benefit cancer patients by elevating quality of life or addressing specific treatment-related issues.12 While more remains to be known, some steps can be taken to improve quality of life during cancer treatment. Medicinal Mushrooms Mushroom mixtures and mushroom-derived polysaccharide preparations modify tumor response and improve immune function in patients with solid tumors.13 A proprietary, protein-bound polysaccharide extract of Coriolus versicolor reduced serum levels of immunosuppressive acidic protein in Stage II and III colorectal cancer patients, increased five-year disease-free survival and decreased relative risk of regional metastases. A meta-analysis of three trials involving over 1,000 subjects with colorectal cancer confirmed these results. A variety of other medicinal mushrooms and extracts have proven beneficial, improving immune parameters such as natural killer cell activity and cytokines sans significant toxicity. The still unanswered question regarding medicinal mushrooms pertains to their risk or value in lymphoma, given their immunostimulatory effects. And while a study of a standardized extract of Maitake mushroom in dogs with lymphoma reported no objective value, two dogs did develop hyphema and one, petechiae.14 These agents can inhibit platelet function; whether the bleeding noted in this study related to the Maitake or the lymphoma remained unanswered. Glutamine Something as simple as glutamine, given as an oral rinse that is then swallowed, decreases stomatitis, a common sequela of radiation therapy to the head and neck. It also may prevent chemotherapy- or radiation-induced intestinal toxicity and decrease the incidence and severity of chemotherapy-related neuropathy.15 Fish Oils Omega-3 fatty acid-rich fish oil can stabilize or reduce cancer-related cachexia.16 More importantly, these long-chain n-3 polyunsaturated fatty acids (PUFAs) can alter the toxicities or activities of several cancer drugs as well as modulate tumor cell response to chemotherapy.17 Because PUFAs readily incorporate into cell membranes and membrane-associated lipid rafts, they affect signaling protein activities of cells. They appear to increase the tumor cell’s susceptibility to apoptosis by altering its expression or function of apoptotic proteins. Further, they modulate the activity of transcription factors such as nuclear factor-kappa-B. In some cases, n-3 PUFAs may increase the effectiveness of chemotherapy by elevating drug uptake or activation. Regarding supplement-chemotherapy interaction, no significant differences in doxorubicin pharmacokinetics appeared in dogs with lymphoma who received a diet with high, rather than low, amounts of n-3 fatty acid.18 This provided reassurance that fatty acid supplementation will not interfere with chemotherapy. Perhaps one day, oncologists will know enough about herb-drug interactions that they will prescribe natural products precisely in order to reduce drug dosages. The side effects will be more patient wellness. Narda Robinson, DVM, DO, Dipl. ABMA, FAAMA, offers an evidential and scientific perspective on the latest trends in complementary and alternative veterinary medicine. She oversees complementary veterinary education at Colorado State University. <HOME> FOOTNOTES 1. The Associated Press. “Judge rules family can’t refuse chemo for boy.” Updated May 19, 2009. Accessed at www.msnbc.msn.com/id/30763438/ on May 22, 2009. 2. The Associated Press. “Teen cancer patient, mom on the run.” Posted May 21, 2009. Accessed at news.aol.ca/article/teen-cancer-patient-mom-on-the-run/628206/ on May 23, 2009. 3. Hwang S-W, Han H-S, and Lim KY. “Drug interaction between complementary herbal medicines and gefitinib.” Journal of Thoracic Oncology. 2008;3(8):942. 4. Engdal S, Klepp O, and Nilsen OG. “Identification and exploration of herb-drug combinations used by cancer patients.” Integrative Cancer Therapies. 2009;8(1):29-36. 5-6. Michaud LB, Karpinski JP, Jones KL, et al. “Dietary supplements in patients with cancer: Risks and key concepts, Part 1.” Am J Health-Syst Pharm. 2007;64:369-381. 7. Bairati I, Meyer F, Jobin E, et al. “Antioxidant vitamins supplementation and mortality: A randomized trial in head and neck cancer patients.” Int J Cancer. 2006;119:2221-2224. 8. Meyer F, Bairati I, Jobin E, et al. “Acute adverse effects of radiation therapy and local recurrence in relation to dietary and plasma beta carotene and alpha tocopherol in head and neck cancer patients.” Nutrition and Cancer. 2007;59(1):29-35. 9-11. Michaud LB, Karpinski JP, Jones KL, et al. “Dietary supplements in patients with cancer: Risks and key concepts, Part 1.” Am J Health-Syst Pharm. 2007;64:369-381. 12-13. Hardy ML. “Dietary supplement use in cancer care: Help or harm.” Hematol Oncol Clin North Am. 2008;22(4):581-617, vii. Review. 14. Griessmayr PC, Gautheir M, Barber LG, et al. “Mushroom-derived maitake PETfraction as a single agent for the treatment of lymphoma in dogs.” Journal of Veterinary Internal Medicine. 2007;21(6):1409-1412. 15-16. Hardy ML. “Dietary supplement use in cancer care: Help or harm.” Hematol Oncol Clin North Am. 2008;22(4):581-617, vii. Review. 17. Biondo PD, Brindley DN, Sawyer MB, et al. “The potential for treatment with dietary long-chain polyunsaturated n-3 fatty acids during chemotherapy.” Journal of Nutritional Biochemistry. 2008;19:787-796. 18. Selting KA, Ogilvie GK, Gustafson DL, et al. “Evaluation of the effects of dietary n-3 fatty acid supplementation on the pharmacokinetics of doxorubicin in dogs with lymphoma.” American Journal of Veterinary Research. 2006;67(1):145-151.
