TY - JOUR
T1 - Application of a key events dose-response analysis to nutrients
T2 - A case study with vitamin a (Retinol)
AU - Ross, A. Catharine
AU - Russell, Robert M.
AU - Miller, Sanford A.
AU - Munro, Ian C.
AU - Rodricks, Joseph V.
AU - Yetley, Elizabeth A.
AU - Julien, Elizabethjulien
N1 - Funding Information:
Financial support for this project from the following sources is gratefully acknowledged: ILSI Research Foundation, Health Canada, Ajinomoto, Coca-Cola Company, Groupe Danone, Kellogg Company, Kraft Foods, Inc., Mars, Inc., Mead Johnson Nutritionals, Monsanto Company, Nestlé, PepsiCo, Inc., The Procter & Gamble Company, Syngenta Ltd., Flavor Extract Manufacturers Association, and Grocery Manufacturers Association. Assistance from Ms. Julie Fitzpatrick with coordination of the final preparation of these papers is also gratefully acknowledged.
PY - 2009/9
Y1 - 2009/9
N2 - 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.
AB - 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.
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U2 - 10.1080/10408390903098749
DO - 10.1080/10408390903098749
M3 - Article
C2 - 19690996
AN - SCOPUS:69849112943
SN - 1040-8398
VL - 49
SP - 708
EP - 717
JO - Critical reviews in food science and nutrition
JF - Critical reviews in food science and nutrition
IS - 8
ER -
