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Compendium April 2009 (Vol 31, No 4)

Focus on Nutrition — Antioxidants in Cancer Treatment: Helpful or Harmful?

by Lisa M. Freeman, DVM, PhD, DACVN

    Abstract

    Nutrition is an important component of the care of dogs and cats with cancer, and dietary supplement use is common in this patient population. Antioxidants are thought to be among the most commonly used supplements. While antioxidants have potential benefi ts for cancer patients, they also may have detrimental effects. Therefore, information regarding the overall diet, including dietary supplements, should be collected for every cancer patient and carefully assessed, with specific attention to antioxidants, to identify areas in which the patient's medical care can be optimized.

    Veterinarians are commonly faced with questions from pet owners about nutrition, but when an animal has cancer, such questions are even more likely. Most owners of dogs and cats with cancer want to know everything from whether diet contributed to the development of the cancer to whether they should change their pet's diet to whether dietary supplements should be administered as part of their pet's treatment. Advertisements for dietary supplements abound in magazines for pet owners and veterinarians alike, and it can be tempting for owners of pets with cancer to believe the claims of disease treatments or cures that are supposed to come from a few pills. If owners do not ask their veterinarians questions about these claims, they often use the Internet to try to get the answers for themselves. Therefore, it is important to be aware of both the potential benefits and risks of dietary supplements.

    Nutrition in Pets with Cancer

    Nutrition should be an integral part of the management of every cancer patient. Cancer patients may be predisposed to weight loss, malnutrition, and specific nutrient deficiencies during treatment. Therefore, it is important to maintain optimal weight and prevent nutritional deficiencies in these patients to improve their outcome.1-3 It is also important to avoid excesses of overall calories and individual nutrients. Obesity resulting from excessive caloric intake is a common problem in animals with cancer.1,2 Body weight, body condition score, and muscle condition (i.e., whether muscle loss is occurring) should be assessed at each visit. Obtaining a thorough diet history allows the veterinarian to determine whether the animal is eating an appropriate diet, whether deficiencies or excesses are likely to occur, and whether components of the diet are working with or against the selected therapeutic plan for the patient. This information can then be used to make necessary modifications to ensure optimal care.

    The Importance of Diet History

    Dietary supplementation is extremely common in today's society. More than half of all Americans take dietary supplements on a regular basis.4-6 Fewer pets in the general population receive dietary supplements; in one study of pet owners, approximately only 10% of dogs and cats were receiving supplements, with multivitamins, chondroprotectives, and fatty acid supplements being the most common.7 However, in populations with disease conditions, dietary supplement use is higher. Dietary supplements are used in 31% of dogs and 13% of cats with cardiac disease, respectively,8,9 and in >50% of dogs and cats with cancer.10 People with chronic diseases use supplements even more commonly than the general population, and only a small proportion of these patients tell their health care providers about their supplement use.11 With the increase in supplement use in populations with diseases comes an increased risk for interaction between supplements or between supplements and medications. Because animals with cancer are one of the most likely populations to be receiving dietary supplements, an important part of a thorough diet history is to specifically ask owners if they are giving supplements to their pets.

    A thorough diet history is one of the keys to providing optimal care for animals with cancer. Questions should include the specific food (brand and specific type), amounts and frequency of feeding, types and amounts of treats and table foods, whether the animal is eating an unconventional diet (e.g., homemade, raw meat), and whether dietary supplements are being used. Dietary supplements can be a particular issue because owners often do not consider them to be either drugs or part of the diet. Therefore, if owners are not specifically questioned about the use of dietary supplements, they usually do not mention them. Veterinarians should ask about the types, brands, and doses of supplements being administered. This information can help to determine whether supplements are being used and dosed appropriately and whether they might interact with any drugs or nutrients being used as therapy.

    Antioxidants

    Antioxidants are thought to be among the most commonly used dietary supplements in animals with cancer. They are typically administered with the goal of aiding in the treatment of cancer, enhancing immune function, or reducing treatment toxicity. Endogenous antioxidants include enzymes (e.g., glutathione peroxidase, superoxide dismutase), free radical scavengers (e.g., vitamins A, C, and E), and metal chelators (e.g., transferrin). Normally, these antioxidants compensate for the production of oxidants known as reactive oxygen species (e.g., hydrogen peroxide, superoxide anions, hydroxyl radicals), which are normal by-products of aerobic metabolism. However, when oxidant production is excessive or antioxidant production is insufficient, an imbalance known as oxidative stress occurs. Excessive oxidants damage DNA, lipids, and proteins and increase the production of inflammatory mediators, among other deleterious effects. It has been hypothesized that oxidative stress increases the risk for certain types of cancer, and it is theorized to play an important role in the aging process. Therefore, antioxidants (both endogenous and supplemental) have been extensively studied in terms of their efficacy in reducing the development of cancer, with variable success. Another area of great interest and controversy is the use of antioxidants during the treatment of cancer, whether alone or in conjunction with chemotherapy or radiation therapy.

    Antioxidants have a number of potential benefits in cancer patients. Oxidative stress has been associated with increased morbidity and mortality for a number of human cancers, and recent studies have demonstrated oxidative stress in dogs with mammary tumors and lymphoma.12-14 Reactive oxygen species can contribute to malignant transformation and neoplastic cell proliferation and so could contribute to disease progression. Therefore, boosting antioxidant reserves and reducing oxidative stress might reduce tumor growth or metastasis. Another potential benefit of antioxidants is protection against radiation- and chemotherapy-induced adverse effects (e.g., gastrointestinal, renal, and cardiac toxicities); some, but not all, studies in rodent models and people have shown modest benefits. These potential benefits are the rationale behind the high use of various antioxidants during cancer treatment.

    However, there also are potential detrimental effects of antioxidants in patients undergoing treatment for cancer. The efficacy of radiation therapy and of many chemotherapeutic agents depends on the development of reactive oxygen species. Therefore, reduced treatment efficacy is possible if antioxidants are used concurrently with these therapies. Because of these competing effects, there is a great deal of controversy among human oncologists as to whether antioxidants are beneficial, innocuous, or detrimental.15-17 Antioxidants do not all behave similarly, and some have significantly different effects depending on their dose and form and what other medications and supplements are being concurrently administered. Therefore, evaluating whether one has benefits (or adverse effects) can be a complicated endeavor.

    In addition to the specific pros and cons of antioxidants are the general issues that are of concern with all human and veterinary dietary supplements: safety, efficacy, dose, bioavailability, dissolvability, and quality control. Until additional data are available, I recommend against the use of antioxidants during radiation therapy or chemotherapy in dogs and cats with cancer.

    Conclusion

    Once veterinarians determine what foods and supplements owners are giving their pets, they may need to gather additional information about their safety, efficacy, and potential for interaction with each other and other therapies. Some of the Web sites listed in  Box 1 can be useful for this purpose. Because there is little governmental regulation of dietary supplements, pet owners should consider selecting dietary supplements that bear the logo of the Dietary Supplement Verification Program, which tests human dietary supplements for ingredients, concentrations, dissolvability, and contaminants. Another good resource is Consumerlab.com, which performs independent testing of health and nutrition products (primarily human supplements, but also some pet products). As of 2008 (2009 or 2010 for smaller companies), the US Food and Drug Administration is instituting regulations that require supplements to be made using Good Manufacturing Practices and to meet quality standards.18

    Web Exclusive

    Download a diet history form .

    Downloadable PDF

    Dr. Freeman discloses that she has received research funding from Nestlé Purina PetCare, Boehringer Ingelheim, and the Waltham Centre for Pet Nutrition and that she has served on a Nestlé Purina Scientific Advisory Council.

    1. Michel KE, Sorenmo K, Shofer FS. Evaluation of body condition and weight loss in dogs presented to a veterinary oncology service. J Vet Intern Med 2004;18:692-695.

    2. Weeth LP, Fascetti AJ, Kass PH, et al. Prevalence of obese dogs in a population of dogs with cancer. Am J Vet Res 2007;68:389-398.

    3. Baez JL, Michel KE, Sorenmo K, Shofer FS. A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients. J Feline Med Surg 2007;9:411-417.

    4. Balluz LS, Kieszak MA, Philen RM, et al. Vitamin and mineral supplement use in the United States: results from the third national health and nutrition examination survey. Arch Fam Med 2000;9:258-262.

    5. Balluz LS, Okoro CA, Bowman BA, et al. Vitamin or supplement use among adults, behavioral risk factor surveillance system, 13 states, 2001. Public Health Rep 2005;120:117-123.

    6. Archer SL, Stamler J, Moag-Stahlberg A, et al. Association of dietary supplement use with specific micronutrient intakes among middle-aged American men and women: the INTERMAP study. J Am Diet Assoc 2005;105:1106-1114.

    7. Freeman LM, Abood SK, Fascetti AJ, et al. Disease prevalence among dogs and cats in the United States and Australia and proportions of dogs and cats that receive therapeutic diet or dietary supplements. JAVMA 2006;229:531-534.

    8. Freeman LM, Rush JE, Cahalane AK, et al. Dietary patterns in dogs with cardiac disease. JAVMA 2003; 223:1301-1305.

    9. Torin DS, Freeman LM, Rush JE. Dietary patterns of cats with cardiac disease. JAVMA 2007;230:862-867.

    10. Lana SE, Kogan LR, Crump KA, et al. The use of complementary and alternative therapies in dogs and cats with cancer. JAAHA 2006;42:361-365.

    11. Ball SD, Kertesz D, Moyer-Mileur LJ. Dietary supplement use is prevalent among children with a chronic disease. J Am Diet Assoc 2005;105:78-84.

    12. Szczubial M, Kankofer M, Lopuszynski W, et al. Oxidative stress parameters in bitches with mammary gland tumours. J Vet Med A Physiol Pathol Clin Med 2004;51:336-340.

    13. Vajdovich PT, Kriska T, Mezes M, et al. Redox status of dogs with non-Hodgkin lymphomas. An ESR study. Cancer Lett 2005;224:339-346.

    14. Winter JL, Barber L, Griessmayr PC, et al. Antioxidant status and biomarkers of oxidative stress in canine lymphoma. J Vet Intern Med 2009;23:311-316.

    15. D'Andrea GM. Use of antioxidants during chemotherapy and radiotherapy should be avoided. CA Cancer J Clin 2005;55:319-321.

    16. Block KI, Koch AC, Mead MN, et al. Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials. Cancer Treat Rev 2007;33:407-418.

    17. Moss RW. Do antioxidants interfere with radiation therapy for cancer? Integr Cancer Ther 2007;6:281-292.

    18. United States Food and Drug Administration. Fact sheet: dietary supplement current good manufacturing practices (CGMPs) and interim final rule (IFR) facts. Accessed March 2009 at www.cfsan.fda.gov/~dms/dscgmps6.html.

    References »

    NEXT: Hypernatremia

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