Antioxidants in Cancer: Helpful or Harmful?
ACVIM 2008
Lisa M. Freeman, DVM, PhD, DACVN
North Grafton, MA, USA

Nutrition and Cancer--An Overview

Most owners of animals with cancer have questions about nutrition--whether diet contributed to the development of the cancer, whether they should change to a different diet, and, probably one of the most common questions, whether any dietary supplements should be administered as part of their pet's treatment. Cancer patients have a variety of factors that may predispose them to malnutrition and specific nutrient deficiencies during treatment; the maintenance of optimal weight and preventing nutritional deficiencies can improve the patient's outcome. However, it is also important to avoid excesses--both of overall calories and of individual nutrients. Excessive calories leading to obesity is a common problem in animals with cancer. Animals with cancer also are one of the most likely populations to be receiving dietary supplements. Therefore, it is important to be aware of both the potential benefits and the potential risks of dietary supplements.

The Importance of Diet History

One of the keys to providing optimal care for animals with cancer is to obtain a thorough diet history--this includes the specific type of pet food, along with amounts and frequency of feeding, whether the animal is eating an unconventional diet (e.g., homemade, raw meat), types and amounts of treats and table foods, and dietary supplements. Dietary supplements can be a particular issue because they're often not considered by the owner to be either a drug or part of the diet. Therefore, if owners are not specifically questioned about the use of dietary supplements, they usually do not volunteer this information. One should ask the owner about the types, brand, and dose of supplements being given. This information can help to determine whether the supplement use and the dose are appropriate, and whether any drug-nutrient interactions might occur with other forms of therapy being used.

Dietary Supplements

Dietary supplementation is extremely common in today's society, with over half of all Americans taking dietary supplements on a regular basis. Dietary supplementation is much less common in the general pet population. In one study of pet owners, approximately 10% of all dogs and cats were receiving dietary supplements, with the most common ones being multivitamins, chondroprotectives, and fatty acid supplements (Freeman et al, 2006). However, in some populations, such as people or pets with disease conditions, dietary supplement use is higher. For example, in people with chronic diseases, supplement use is even more common than in the general population and only a small proportion of these patients have told their health care providers about the supplement use. In pets, dietary supplements are used in 31% of dogs and 13% of cats with cardiac disease, respectively (Freeman et al, 2003; Torin et al, 2007) and in >50% of dogs and cats with cancer (Lana et al, 2006). In magazines for pet owners and veterinarians alike, advertisements for dietary supplements abound. It can be tempting for owners of pets with cancer to believe the claims of disease treatment or cure that are supposed to come from giving a few pills. Not only is supplement use higher in populations with diseases, but there also is increased risk for interaction between multiple supplements or between dietary supplements and medications. Because the use of dietary supplements is becoming more common, it is important to specifically ask owners if they are giving them to their pets, as part of a thorough diet history. Once you find out what owners are giving their pets, you may then need to gather additional information. Since there is little governmental regulation over dietary supplements, pet owners should consider selecting dietary supplements for their pets that have the logo of the Dietary Supplement Verification Program (DSVP), 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 for small companies), the USDA is instituting regulations that require good manufacturing practices and meet quality standards.

Antioxidants

Antioxidants are one of the most commonly used dietary supplements in animals with cancer and are typically administered with the goal of aiding in the treatment of cancer, enhancing immune function, or reducing treatment toxicity. Reactive oxygen species [e.g., hydrogen peroxide (H2O2), superoxide (O2-), hydroxyl (OH)] are a normal by-product of aerobic metabolism. These reactive oxygen species are typically compensated for through the endogenous production of antioxidants. Endogenous antioxidants include enzymatic antioxidants (e.g., glutathione peroxidase and superoxide dismutase), free radical scavengers (e.g., vitamins A, C, and E), and metal chelators (e.g., metal chelators). However, when there is excessive production of antioxidants or insufficient antioxidant production, an imbalance occurs (i.e., oxidative stress). It has been hypothesized that oxidative stress increase the risk for certain types of cancer and even is one of the theories of aging.Excessive oxidants damage DNA, lipids, and proteins, as well as increase the production of inflammatory mediators, among other deleterious effects. Therefore, antioxidants (both endogenous and supplemental) have been extensively studied in terms of their efficacy in reducing the development of cancer (albeit with variable success). However, another area of great interest and controversy is the use of antioxidants during the treatment for cancer--whether in isolation or as part of chemotherapy or radiation therapy.

There are a number of potential beneficial effects of antioxidants in animals with cancer. Reactive oxygen species can contribute to malignant transformation and neoplastic cell proliferation. Oxidative stress has been associated with increased morbidity and mortality in a number of human cancers. Therefore, boosting antioxidant reserves and reducing oxidative stress could reduce tumor growth or metastasis. Another potential benefit of antioxidants is protection against radiation- and chemotherapy-induced side effects (e.g., gastrointestinal, renal, and cardiac toxicities). These potential benefits are the rationale behind the high usage of various antioxidants during cancer treatment. However, there also are potential detrimental effects of antioxidants in a patient undergoing treatment for cancer. The efficacy of many chemotherapeutic agents and radiation therapy depend on the development of reactive oxygen species. Therefore, reduced treatment efficacy is possible if antioxidants are being concurrently used. Antioxidants do not all behave similarly and some have significantly different effects depending on dose, form, and other medications and supplements being concurrently administered. In addition to the specific pros and cons of antioxidants are the general issues concerning all dietary supplements--safety, efficacy, dose, bioavailability, dissolution, and quality control.

Recently, our group completed a study evaluating whether dogs with lymphoma have an imbalance between oxidants and antioxidants (e.g., oxidative stress). In addition, the effects of chemotherapy and remission on oxidative stress were examined. The results of this study will be reported.

Nutrition should be an integral part of the management for every cancer patient. Obtaining a thorough diet history allows the veterinarian to determine whether the animal is eating an appropriate diet, if deficiencies or excesses are likely to occur, and if components of the diet are working with or against the selected therapeutic plan for the patient.

References

1.  AAFCO Official Publication (http://www.aafco.org/)

2.  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 Fel Med Surg 2007; 9: 411-417.

3.  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.

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

5.  Freeman LM, Rush JE, Cahalane AK, et al. Dietary patterns in dogs with cardiac disease. J Am Vet Med Assoc 2003; 223: 1301-1305.

6.  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. J Am Vet Med Assoc 2006;229: 531-534.

7.  Lana SE, Kogan LR, Crump KA, et al. The use of complementary and alternative therapies in dogs and cats with cancer. J Am Anim Hosp Assoc 2006; 42: 361-365.

8.  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.

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

10. National Research Council. Nutrient requirements of dogs and cats, 2006. National Academies Press.

11. PDR for Nonprescription Drugs, Dietary Supplements, and Herbs, 2008. Thomson Healthcare Publishers.

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

13. Torin DS, Freeman LM, Rush JE. Dietary patterns of cats with cardiac disease. J Am Vet Med Assoc2007; 230: 862-867

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

15. 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.

Websites

1.  American College of Veterinary Nutrition (ACVN): www.acvn.org

2.  ACVN Nutrition Resources (nutritional consultations with Diplomates of the ACVN, including homemade diets): http://www.aavn.org/site/view/58440_Nutrition%20Resources.pml;jsessionid=h8qpdmib0tfp9

3.  Consumerlab.com (independent testing of dietary supplements for purity, potency, bioavailability, etc): www.consumerlab.com

4.  FDA Center for Food Safety and Applied Nutrition (regulatory and safety issues, adverse event reporting, meetings, industry information): http://vm.cfsan.fda.gov/~dms/supplmnt.html

5.  NIH National Center for Complementary and Alternative Medicine: http://nccam.nih.gov

6.  NIH Office of Dietary Supplements (fact sheets, safety notices, database): http://dietary-supplements.info.nih.gov or www.nas.edu/nrc/

7.  Quackwatch ("Guide to health fraud, quackery, and intelligent decisions"): http://www.quackwatch.org

8.  USDA Food and Nutrition Information Center (general supplement and nutrition information, links to a variety of dietary supplement websites): http://www.nal.usda.gov/fnic/etext/000015.html

9.  United States Pharmacopeia Dietary Supplement Verification Program (voluntary verification program): http://www.usp.org/USPVerified

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Lisa Freeman, DVM, PhD, DACVN
Tufts Cummings School of Veterinary Medicine
N. Grafton, MA


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