Fat loss accounts for the majority of weight loss occurring in cancer cachexia. Therefore, it is not surprising that human beings and animals with cancer have dramatic abnormalities in lipid metabolism.33-37 The decreased lipogenesis and increased lipolysis observed in humans and rodents with cancer cachexia result in increased levels of free fatty acids, very low density lipoproteins, triglycerides, plasma lipoproteins, and hormone dependent lipoprotein lipase activity, while levels of endothelial derived lipoprotein lipase decrease.34 Recently lipid profiles in dogs with a lymphoma were studied.35 It was determined that many of the alterations seen in other species with cancer were also present in dogs. These abnormalities did not normalize when clinical remission is obtained. The clinical significance of these abnormal lipid profiles in dogs with lymphoma is not known, however, abnormalities in lipid metabolism have been linked to a number of clinical problems including immunosuppression which correlates with decreased survival in affected humans.16,32,34
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.36 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 non-malignant 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.37 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.