Immuno-nutrition: designer diets in cancer

Weight loss, associated with advanced stage of neoplastic disease, is negatively correlated with survival in cancer patients. Alterations in substrate metabolism contribute to the impaired nutritional status. Energy expenditure, assessed by indirect calorimetry, seems to be very variable. Hypermetabolism may occur frequently, but the increase in energy expenditure rarely exceeds 10-15%. Another hallmark of cancer is depression of both cellular and humoral immune functions. Glutamine, the most abundant amino acid in the body, is an important substrate for rapidly proliferating cells and tissues. Arginine has been shown to stimulate the immune system, to enhance wound healing and to decrease the rate of tumour growth. Dietary supplementation with omega-3 fatty acids shifts the production of prostaglandins from the dienoic to the trienoic variety, which is much less immunosuppressive. Finally, administration of oligonucleotides improved survival to a challenge with Candida albicans. The needs for nutritional support in cancer patients should be considered from at least two perspectives: curative versus palliative treatment. Several prospective, randomized, double-blind studies in cancer patients undergoing major upper gastrointestinal surgery demonstrated significant improvements in postoperative immunological responses, a reduction in the frequency of infections and wound complications and in the length of hospital stay in the group receiving a diet enriched with arginine, RNA and omega-3 fatty acids. However, the impact on mortality remains to be established. In palliative situations, no clinical data documenting beneficial effects of long-term nutritional support with designer diets have been published, probably as a consequence of persisting concern about promoting tumour growth. Moreover, because of the heterogeneity of this patient population such studies are difficult to perform. Finally, nutritional intervention for patients with terminal cancer remains highly controversial. The basis for improvements in nutritional support is a better understanding of the metabolism of cancer patients, especially in patients with advanced disease.