This revised competing renewal application outlines research aimed at both strengthening our previous conclusion that the current international estimates of the minimum physiological requirements for specific nutritional indispensable amino acids (IAA) are far too low and the tentative recommendations that we have proposed concerning the maintenance of protein nutritional status in healthy adults. Based on our recent findings and from research issues that we and others have raised the three specific aims are as follows: (1) to further explore and validate the concept of whole body tracer amino acid balance as a basis for establishing the requirements for specific indispensable amino acids.
This aim will involve a modification of the current """"""""gold standard"""""""" 24 hour tracer protocol, which we have been and continue to use as the central procedure for quantitation of dietary needs, by use of a numerical model to predict system behavior, derived from an analysis of isotopic data following a bolus administration of labeled tracer and which has been validated, in part. Additionally, aspects of nitrogen metabolism will be compared with the carbon balance/kinetic data; (2) to compare and contrast the direct amino acid oxidation and the indicator amino acid oxidation (IAA) approaches to estimate indispensable amino acid requirements. This will be performed using C-leucine and 13C-phenylalanine as test labeled indicators and also include an assessment of whether significant further changes in amino acid status occur between one and three weeks following a change in dietary IAA intake; (3) to begin to explore the question of the significance and nature of nutritional adaptation as a possible determinant of the requirements for specific indispensable amino acids and the applicability of estimates made in our previous studies to other healthy populations worldwide. This will be accomplished through comparative studies in healthy US subjects, studied at MIT, and healthy and chronically marginally malnourished Indian adults studies in Bangalore. The critical dietary test amino acid in this case will be lysine. The long-term objective of these studies is, through an improved understanding of the characteristics and regulation of the integrative aspects of body nitrogen and amino acid metabolism, to develop more appropriate tools for the diagnosis of protein (and amino acid) nutritional status and determination of nutritional requirements. Our short- term purpose is to (a) further understand why the earlier and internationally accepted estimates of amino acid requirements differ so markedly from those based on the concept and application of the tracer balance method and (b) strengthen and improve our proposed, tentative new requirement values, through refined methodology and expansion to another population of healthy adults.
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