Dietary protein and amino acid requirements of cancer patients have never been formally determined, and we have argued elsewhere that this is an important deficit in the literature that would hopefully draw the attention of nutritional scientists with appropriate expertise . Methods for the determination of human protein requirements continue to advance conceptually and technically, and the subset of these that are minimally invasive merit particular scrutiny for use, since patients with advanced malignancy may not tolerate extensive or invasive investigations. The indicator amino acid oxidation approach has been extensively developed for clinical use by Ball and co-workers [19,20]. This method is based on the principle that the oxidation of an indicator amino acid is high when a test amino acid is limiting for protein synthesis, and that indicator oxidation decreases to reach a low and constant value once amino acid requirements are met [19, 21]. Using this technique, breath and urine are the only samples required following the consumption of diet with a varying amount of the study amino acid and administration of the indicator amino acid tracer [19, 21]. The indicator amino acid oxidation technique has been used to determine amino acid requirements in healthy adults and in individuals with metabolic disorders and has found particular application in highly vulnerable populations such as premature neonates and children [19,21].
The plasma amino acid response to an infusion of an amino acid mixture is an indirect approach that has also been used to identify the amino acids that limit protein synthesis [22, 23]. This method is based on the differential behaviour of infused amino acids depending on whether the infusion oversupplies or undersupplies amino acids relative to requirements. If an amino acid is undersupplied, its plasma concentration will not rise during an amino acid infusion, because of its use for protein synthesis. By contrast, infusion of an amino acid that is already present at or above required amounts, will result in a steep rise in its plasma concentration. This approach has been used in HIV/AIDS patients  and was also used to manipulate parenteral amino acid formulation to meet the specific needs of hospitalised patients in an intensive care unit . The linear regression of plasma plateau concentrations of amino acids in response to an amino acid infusion was used to determine which amino acids were oversupplied or undersupplied in each individual patient. A par-enteral amino acid formulation that corrected these imbalances was then given for 5 days and resulted in improved nitrogen balance . The identification of limiting amino acids in cancer is an important step in determining appropriate dietary supplements that will promote lean tissue gain: however, to date this has not been accomplished in cancer patients.
Until such time as the amino acid requirements of cancer patients are empirically determined, a suitable starting point might be the recommended protein requirements of healthy persons in the range of ages of the average age of cancer diagnosis (65 years in Canada) and average age of cancer death (69 years), and thereafter to consider any factors that would tend to alter protein requirements relative to that value. Conventional dietary recommendations include protein intake for weight maintenance plus a factor for disease. For example, the Clinical Guide to Oncology Nutrition of the American Dietetic Association suggests a protein intake of 1.0-1.5 g protein/kg body weight per day , depending on patient, disease and treatment factors. It has been a long-standing convention to express protein intake as a constant function of body weight (i.e. per kg of body weight): however, Millward [25, 26] suggests that a nutrient density (i.e. P:E ratio) may be more useful to provide a basis for suggesting protein intakes. Based on the as sumption that the energy requirement is the major determinant of total intake, then if the protein requirement is expressed as a P:E ratio, the recommended intakes can be adjusted taking into account the factors that impact on energy requirements such as age, gender, body weight and activity level. The reader is referred to the work of Millward and Jackson  for the full details underlying this concept.
If one were to accept the arguments presented by Millward and Jackson, then a healthy 60- to 70-year-old man or woman weighing 70 kg with a low physical activity level of 1.5 times the basal metabolism value would require a dietary P:E ratio of at least 0.12 to maintain N balance. This might be considered to be a minimum amount, for the following reasons. The calculations by Millward are based on the assumption of energy balance, and do not take into account that at low energy intakes amino acids are diverted to energy-yielding reactions. The average energy intakes of advanced pancreatic cancer patients are in the vicinity of determined basal metabolic rate (22-25 kcal/kg body weight per day) and thus a significant fraction of individuals are not taking in enough energy even to match basal metabolism requirements [16, 27]. Also, the definition used by Millward and Jackson for calculation of the P:E ratio of sedentary persons is a physical activity level of 1.5 times basal metabolism value and there is evidence that the physical activity level of advanced cancer patients is of the order of 1.25 . Finally, no factor is added to these suggested protein intakes for the presence of disease.
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