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Cancer-induced Weight Loss
Wide alterations in carbohydrate, lipid and protein metabolism in the tumour-bearing host have been previously documented. Cancer anorexia/cachexia is characterised by a shift in nutrient use from the growth and maintenance of muscle mass to processes that support the immune response and affect disease resistance.1 These changes can result in an increased rate of muscle protein degradation and increase in acute-phase protein synthesis, with progressive depletion of lean body mass, with clinical evidence of cachexia. The majority of cancer patients experience weight loss as their disease progresses and, in general, weight loss is a major prognostic indicator of poor survival and impaired response to anti-neoplastic therapy.
Cancer cachexia is a multifactorial event and inflammation plays a relevant pathogenetic role. Studies have demonstrated that a variety of proinflammatory cytokines can lead directly to development of anorexia and metabolic changes and can be associated with the development of cachexia. In addition, the presence of a pro-inflammatory response (documented by an acute phase protein response) has been associated in a variety of human malignancies with accelerated weight loss, anorexia, hypermetabolism and a shortened duration of survival.
Not surprisingly, conventional nutritional support, whether in the form of oral feeding, enteral feeding or parenteral nutrition, has generally failed to either prolong survival or improve the outcome of conventional anti-neoplastic therapy.
Fish Oil and Eicosapentaenoic Acid
In healthy individuals and in patients with cancer, the production of pro-inflammatory cytokines such as interleukin (IL) 6, IL-1 and tumour necrosis factor (TFN) can be downregulated by omega-3 polyunsaturated fatty acid (FA) and eicosapentaenoic acid (EPA). Furthermore, the effects of proteolysisinducing factor (PIF), a cachectic factor produced by cancer tissue, are also inhibited by EPA.
In 1996, Wigmore et al. evaluated the effects of EPA in 18 patients with cachexia due to unresectable pancreatic cancer.2 The patients received approximately 12g of fish oil per day (2g of EPA per day) over a period of three months. This was associated with the arrest of cachexia in the majority of patients, with a small proportion of patients actually gaining weight. These findings contrast markedly with the natural history of pancreatic cancer in which patients progressively lose weight.