Application of a Key Events Dose-Response Analysis to Nutrients: A Case Study with Vitamin A (Retinol)

The methodology used to establish tolerable upper intake levels (UL) for nutrients borrows heavily from risk assessment methods used by toxicologists. Empirical data are used to identify intake levels associated with adverse effects, and Uncertainty Factors (UF) are applied to establish ULs, which in turn inform public health decisions and standards. Use of UFs reflects lack of knowledge regarding the biological events that underlie response to the intake of a given nutrient, and also regarding the sources of variability in that response. In this paper, the Key Events Dose-Response Framework (KEDRF) is used to systematically consider the major biological steps that lead from the intake of the preformed vitamin A to excess systemic levels, and subsequently to increased risk of adverse effects. Each step is examined with regard to factors that influence whether there is progression toward the adverse effect of concern. The role of homeostatic mechanisms is discussed, along with the types of research needed to improve understanding of dose-response for vitamin A. This initial analysis illustrates the potential of the KEDRF as a useful analytical tool for integrating current knowledge regarding dose-response, generating questions that will focus future research efforts, and clarifying how improved knowledge and data could be used to reduce reliance on UFs

Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: an insulin signaling pathway approach

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ESPEN guidelines on artificial enteral nutrition--percutaneous endoscopic gastrostomy (PEG)

Based on many recently published clinical studies our earlier view of PEG being primarily linked to advanced stages of mainly malignant diseases has switched to support for earlier decision making in a large variety of potential patients with different underlying diseases. Patients with advanced cancer, end-stage diseases or advanced dementia are not usually considered appropriate candidates for artificial feeding via PEG tubes. Overall published data support an individualized but critical and restrictive approach to PEG feeding in such patients. In experienced hands PEG placement and feeding is a safe and highly effective procedure if modern devices are used and established standards are adhered to. Nevertheless, decision making is still difficult in many cases having always an individual character. Prospective clinical studies have shown, that guidelines help to improve the appropriateness of patients selection and play a proactive role in the decision making for medically adequate PEG insertion with a consecutively improved outcome. Enteral nutrition via a tube system inserted with endoscopic guidance is an efficient, highly effective and easy to use technique, associated with a low rate of complications, which allows the maintenance of adequate enteral nutrition of patients who are unable to ingest sufficient nutrients orally. Clinical studies have demonstrated the high level of acceptance by patients and the marked improvement in nutritional status and general well being of such patients. In order to prevent deterioration of nutritional status and to improve their overall quality of life, the decision whether or not to use an enteral tube system for feeding should be taken at a much earlier stage and should be more frequently positive in appropriate patients who fulfil the above mentioned and discussed criteria