Barber, Matthew David
Metabolic abnormalities in advanced pancreatic cancer and their modulation by an eicosapentaenoic acid-based preparation.
MD thesis, University of Glasgow.
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A combination of a nutritional supplement and eicosapentaenoic acid was given to patients with advanced pancreatic cancer to assess its effect on the ongoing cachectic process. The administration of a fish oil-enriched nutritional supplement providing 2g eicosapentaenoic acid and around 600kcal per day resulted in a significant change in the metabolic disposition of patients with advanced pancreatic cancer. Consumption of the supplement resulted in a reversal of weight loss and a gain in lean body mass in association with a reversal of negative nitrogen balance. Performance status and appetite improved. Production of interleukin-6 was reduced and the acute phase protein response stabilised, insulin concentration increased and proteolysis inducing factor excretion fell. These changes were associated with a rise in energy intake, a fall in relative resting energy expenditure and a normalisation of the metabolic response to feeding and substrate utilisation. The increase in acute phase protein synthesis with feeding was abolished after the administration of the fish oil-enriched nutritional supplement.
The progressive nutritional and functional deterioration of advanced pancreatic cancer patients thus seems to be associated with broadly pro-inflammatory metabolic mediators and a progressive acute phase protein response. This deterioration may in part be resistant to conventional nutritional supplementation because of further stimulation of acute phase protein production by feeding.
The provision of a fish oil-enriched nutritional supplement normalises the metabolic milieu, stabilises the acute phase protein response and abolishes the stimulation of acute phase protein production by feeding. One explanation to account for the effects observed after intervention would be that it to allows dietary amino acids to be used for lean tissue anabolism with the consequent potential for quality of life and survival benefit.
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