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Focuses on the topics discussed during the session 3 of the general discussion at the Fourth Workshop on the Assessment of Adequate Intake of Dietary Amino Acids in Kobe-shi, Japan on October 28-29, 2004. Risk assessment on the dosage of branched-chain amino acids; Adverse effects of amino acids; Pharmacokinetics of branched-chain metabolites.

The safety assessment of high intake levels of individual amino acids cannot be based on data from nutritional studies with proteins. Routine toxicity tests designed to investigate a wide range of possible effects should be undertaken for hazard identification and characterization using studies selected to mirror the predicted pattern and duration of human exposure. The approach used to establish an acceptable daily intake level for additives and pesticides, based on defining a "no observed adverse effect" level in the experimental study and dividing by uncertainty factors that allow for species differences and human variability, has a long history of use for foreign compounds and would provide a suitable basis for determining health-based guidance values for single amino acids. The usual default uncertainty factors for toxicokinetics and toxicodynamics should be replaced by compound-specific values if suitable data are available. In addition, the usual uncertainty factors should be modified to more relevant default values based on species differences and human variability in the biodisposition of amino acids in general or of groups of metabolically interrelated amino acids. There would be no significant health concerns if the human intake levels were below a health-based guidance value developed using this approach. A population-distribution approach could be used to define the magnitude of any risk at intake levels above the guidance value. [ABSTRACT FROM AUTHOR]

Extensive discussion sessions were held at the end of each of the 2 d of the workshop. Through the course of the workshop, it became clear that there were different opinions on how to use uncertainty factors to obtain upper levels of intake from no observed adverse effect levels of a particular nutrient and that the selection of an appropriate uncertainty factor would be rather arbitrary. Much of the discussion centered around the potential for using metabolic limits, expressed as the level of intake at which the major pathway of metabolism may approach saturation and at which the amino acid is metabolized by alternative pathways, as a measurable early or surrogate marker for amino acid excess and possible toxicity. After extensive discussion on various conditions that would need to be satisfied for metabolic limits to be used as markers of excessive intake of amino acids, there was a general consensus that methods such as measuring oxidation limits are an attractive approach that merit future investigation, It was noted that there are many data on the clinical use of glutamine, whereas data for proline are very scarce. There was recognition that regardless of the available data, there is regulatory pressure for setting upper levels of intake for amino acids and that much more data are required. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at a workshop on the assessment of adequate intake of dietary amino acids is presented. The discussion centered on the problems raised in relation to setting a safe upper levels for sulfur-containing amino acids. Speakers have argued that in order to set a safe upper levels, it is essential to integrate data from a different sources including metabolic data, data from analysis in humans and data on inborn errors of metabolism.

Explores the risk assessment methods for amino acids. Development of biomarkers; Application of the high-resolution nuclear magnetic resonance spectroscopy.

Based on recent research, an upper limit of safe intake (ULSI) for leucine is proposed for healthy adults: 0.53 g/(kg-d). Because leucine has been used as a dietary supplement for many years in people practicing exercise and sport, further study with long-term exposure to leucine in this specific subpopulation should be performed to eventually adjust the ULSI. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at a symposium on the assessment of adequate intake of dietary amino acids is presented. Participants with toxicological and regulatory backgrounds commented on the paucity of the adverse effects of many micronutrients. The identification of metabolic limits for arginine or lysine excess was also recognized.

Information about several papers discussed at a symposium on the assessment of adequate intake of dietary amino acids is presented. Participants with toxicological and regulatory backgrounds commented on the paucity of the adverse effects of many micronutrients. The identification of metabolic limits for arginine or lysine excess was also recognized.