Nutrition and Cancer: New Keys for Cure and Control 2003!
Gregory K. Ogilvie, DVM, DACVIM (Internal Medicine & Oncology)
Colorado State University
Ft. Collins, CO, USA

Nutritional therapy is a key component for the treatment of cancer cachexia and for actually helping control malignant disease in some situations. Specific nutrients can be used as powerful tools to reduce toxicity associated with chemotherapy, radiation therapy, and is important to enhance healing subsequent to surgery. There is little question that nutritional intervention must begin early and must be followed through aggressively to gain maximum benefit.....long before the patient exhibits evidence of weight loss, debilitation, or anorexia begin which can in turn enhance response to therapy and improve quality of life.

Metabolic Changes Associated with Cancer Cachexia

Clinically, in many patients there are three phases associated with cancer cachexia. The first phase is the preclinical "silent" phase is where the patient is not exhibiting any clinical signs of disease, yet there is evidence of biochemical changes such as hyperlactatemia, hyperinsulinemia and alterations in amino acid and lipid profiles. All of these alterations are of impending clinical importance, but the alterations in carbohydrate metabolism appear to be quite profound resulting in the production of tremendous amounts of lactate through energy inefficient anaerobic metabolism. The second phase is the clinical phase where the patient begins to exhibit weight loss, anorexia, lethargy and early evidence of weight loss. These patients are more likely to exhibit side effects associated with chemotherapy, radiation therapy, immune modulation, and surgery. The third and final phase of cancer cachexia is an accentuated form of the second phase; it is associated with marked debilitation, weakness and biochemical evidence of negative nitrogen balance that is also associated with clinical pathologic changes such as hypoalbuminemia. Cancer patients begin to loose carbohydrate and protein stores within the body. Loss of fat depots is the noted in this third and final stage of the disease. These patients literally waste away due to the physical effects of the malignancy and the resulting cancer induced alterations in metabolism.

Lipids and Cancer

The clinical impact of the abnormalities in lipid metabolism may be lessened with dietary therapy. In contrast to carbohydrates and proteins, some tumor cells have difficulty utilizing lipid as a fuel source while host tissues continue to oxidize lipids for energy. This has led to the hypothesis that diets relatively high in fat may be of benefit to the animal with cancer when compared to a diet high in simple carbohydrates. Further research may reveal that the type of fat, rather than the amount, may be of greater importance. In one study, mean nitrogen intake, nitrogen balance, in vitro lymphocyte mitogenesis, time for wound healing, the prevalence of wound complications, and the duration of hospitalization was significantly better in 85 surgical patients fed an omega-3 fatty acid supplement when compared to controls.37,38 Studies of polyunsaturated fatty acids (PUFA's) of the n-3 series, especially eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), indicate that these fatty acids may prevent the development of carcinogen-induced tumors, the growth of solid tumors, as well as the occurrence of cachexia and metastatic disease in experimental tumor models. Fatty acids of the n-3 series have been shown to normalize elevated blood lactic acid and insulin levels in nonmalignant conditions. In contrast, PUFA's of the n-6 series appear to enhance tumor development and metastases. These data, along with the epidemiological findings of an inverse relationship between dietary n-3 fatty acid intake and incidence of some cancer, is the basis of research to evaluate the potential benefit of n-3 fatty acids in the prevention of cancer cachexia and therapy of malignancy in cancer patients.

One such study was recently completed in dogs with lymphoma. A double blind, randomized study was recently reported to evaluate the hypothesis that polyunsaturated n-3 fatty acids and arginine can improve metabolic parameters, decrease chemical indices of inflammation, enhance quality of life, and extend disease-free interval and survival time in dogs treated for lymphoma. In that study, dogs fed the experimental diet had significantly higher serum levels of polyunsaturated n-3 fatty acids docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) as well as arginine when compared to controls. Both diets were formulated to be relatively low in simple carbohydrates, with moderate amounts of highly bioavailable proteins. This formulation is designed to enhance the effect of n-3 fatty acids. Higher serum levels of these n-3 fatty acids were associated with lesser plasma lactic acid responses to intravenous glucose and diet tolerance testing. Increasing C22:6 levels was significantly associated with longer disease free interval and survival time for dogs with stage III lymphoma fed the experimental diet.

Another study was recently completed that was designed to determine the effect of a diet supplemented with n-3 fatty acids and arginine on irradiated skin and oral mucosa, carbohydrate metabolism and quality of life in a group of dogs with nasal tumors.40 This study showed that fatty acids of the n-3 series normalize elevated blood lactic acid. In a dose dependent manner, n-3 fatty acids result in decreased histologic evidence of radiation damage to skin and mucosa and improve performance scores in dogs with malignant nasal tumors. This would obviously be of great benefit to the cancer patient receiving radiation therapy. These two studies confirm that diets supplemented with polyunsaturated n-3 fatty acids are of benefit for the cancer patient.

The bottom line is that n-3 fatty acids in moderate amounts appear to benefit the cancer patient. More specifically, a diet relatively high in n-3 fatty acids and relatively now in simple carbohydrates has been shown not only to improve alterations in metabolism associated with cancer, but also improve response to chemotherapy and decrease the adverse effects associated with radiation therapy.

Carbohydrate, Protein, Fat and Fiber, What Do I Feed My Dog with Cancer?

The data noted above suggest that a diet relatively low in simple carbohydrates, with moderate amounts of highly bioavailable proteins as well as soluble and insoluble fiber, and moderate amounts of polyunsaturated fatty acids of the n-3 series may be of value to the cancer patient. Research is needed to address the issue of optimum quantities of carbohydrates, proteins and fats, especially n-3 fatty acids. In addition, the ideal ratio of n-3 fatty acids to n-6 fatty acids also remains an unknown. The ideal diet is made of much more than carbohydrates, proteins and fats. A brief discussion about some of what is known about vitamins, minerals and other ingredients is listed below.

Nutritional Support for the Veterinary Cancer Patient

The first step is to enhance appetite. The owner should be given a short term and long range plan for the nutritional support of their pet. This plan allows the veterinary health care team and the owner to have a sequential plan for maintaining nutritional support by first enhancing appetite, second, using tube support in appropriate cases, and third, considering more advanced measures such as total parenteral nutrition for serious problems. The first step, enhancing appetite, begins with the basics: warming the food to just below body temperature; providing a selection of palatable, aromatic foods; and providing comfortable, stress-free surroundings. When these simple procedures fail, such chemical stimulants as benzodiazepine derivatives (e.g., diazepam and oxazepam) and antiserotonin agents (cyproheptadine and pizotifen) can be used. Cyproheptadine (2-4 mg daily or twice daily PO) generally is effective in stimulating appetite in cats, as are megestrol acetate (2.5 mg daily for 4 days, then every 2-3 days thereafter). These drugs can be used concurrently for maximal stimulation of the appetite. Diazepam (0.05-0.5 mg/kg IV) is great for short term therapy in the hospital, but is often not adequate for home therapy. Dogs and cats may have improved appetite when metoclopramide is given orally to decrease nausea associated with chemotherapy or surgery. When all the aforementioned fails, enteral nutritional support via nasogastric, esophagostomy, gastrostomy or jejunostomy tube feeding, designed to deliver nutrients to the GI tract should be considered.

Conclusions

1.  Dogs and cats with cancer have significant alterations in carbohydrate, lipid and protein metabolism that can result in cancer cachexia. These alterations in metabolism have the potential to decrease quality of life, reduce response to therapy and shorten survival times.

2.  While the ideal anticancer diet is not known, research to date would suggest that any nutritional support is better than none. Normal feeding practices should begin early before evidence of cachexia are noted, and plans should be designed to support the patient when voluntary feeding is not optimum. In addition, the following guidelines may be considered early for each patient:

a.  Arm clients with appropriate information, dietary plans and appetite stimulants such as cyproheptadine and megestrol acetate from the very beginning. The goal is to prevent anorexia and weight loss from ever happening.

b.  Consider foods that are highly bioavailable, easily digested, and highly palatable with a good smell and taste

c.  Consider foods that are relatively low in simple carbohydrates, moderate amounts of good quality sources of proteins and soluble and insoluble fiber, and moderate amounts of fats; fats of the n-3 fatty acid series may be effective in reducing or eliminating some of the metabolic alterations associated with cancer cachexia. Antioxidants are essential whenever n-3 fatty acids are used.

d.  Enhanced quantities of arginine, cystine and glutamine may be of value in maintaining a more normal immune, hematologic and gastrointestinal tract.

e.  Fiber, both soluble and insoluble, is essential to maintain normal bowel health. A diet with adequate amounts of fiber is essential to prevent or to treat various problems of the gastrointestinal tract.

3.  Each patient should be assessed as an individual and the nutritional profile, including the amount to be fed should be prescribed for each animal on a daily basis based on reassessments. As a general rule, with the exception of septic animals, dogs and cats with cancer, critical care illnesses, or that are recovering from surgery do not have energy needs that exceed those of normal animals. A formula that approximates the need for many animals with cancer in a resting state is as follows: 1.1[30(wt in kg) + 70]= kcals required per day.

4.  For maximum benefit, intervention should begin early in the course of the disease. The owner must have a clear plan for dietary intervention beginning first with the choice of nutrients, followed by appetite stimulants, and then on to feeding tubes for those patients that cannot or will not support themselves.

5.  Think ahead! Place feeding tubes early at the time of initial therapy in high risk cancer patients. It is better to place feeding tubes early and to remove them without use than to not provide nutritional therapy because of the lack of a feeding tube. See details above concerning placement of various tubes. As a general rule, esophagostomy tubes are the "work horse" of all tube feeding methods. Jejunostomy tubes can be used whenever vomiting or complications occur in the upper gastrointestinal tract that would preclude the use of these nasogastric, esophagostomy or gastrostomy tubes.

References

Adapted with permission from:

1.  Ogilvie GK, Moore AS. Managing the Veterinary Cancer Patient. Trenton NJ, Veterinary Learning Systems. 1995

2.  Ogilvie GK, Moore AS. Feline Oncology: A Comprehensive Guide for Compassionate Care. Trenton NJ, Veterinary Learning Systems. 2002

3.  Ogilvie GK, Moore AS. Canine Oncology: A Comprehensive Guide for Compassionate Care. Trenton NJ, Veterinary Learning Systems, In Press. http://www.vetlearn.com

Speaker Information
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Gregory K. Ogilvie, DVM, DACVIM (Internal Medicine, Oncology)
Colorado State University
Ft. Collins, CO, USA


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