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Institute of Medicine (US) Food and Nutrition Board. Dietary Reference Intakes: A Risk Assessment Model for Establishing Upper Intake Levels for Nutrients. Washington (DC): National Academies Press (US); 1998.

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Dietary Reference Intakes: A Risk Assessment Model for Establishing Upper Intake Levels for Nutrients.

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Approach for Setting Dietary Reference Intakes, Including Tolerable Upper Intake Levels

The scientific data used to develop recommended intakes and ULs have come from observational and experimental studies. Studies published in peer-reviewed journals were the principal source of data. Life stage and gender were considered to the extent possible, but for some nutrients, the data did not provide a basis for proposing different requirements or upper levels for men and women or for adults in different age groups.

Three of the categories of reference values (EAR, RDA, and AI) are defined by specific criteria of nutrient adequacy; the fourth (UL) is defined by a specific endpoint of adverse effect if one is available. In all cases, data were examined closely to determine whether reduction of risk of a chronic degenerative disease or developmental abnormality could be used as a criterion of adequacy. The quality of studies was examined, considering study design, methods used for measuring intake and indicators of adequacy, and biases, interactions, and confounding factors. After careful review and analysis of the evidence, including examination of the extent of congruence of findings, scientific judgment was used to determine the basis for establishing the values.


The term "tolerable" was chosen because it connotes a level of intake that can, with high probability, be tolerated biologically by individuals; it does not imply acceptability of that level in any other sense. The setting of a UL does not indicate that nutrient intakes greater than the RDA or AI are recommended as being beneficial to an individual. Many individuals are self-medicating with nutrients for curative or treatment purposes. It is beyond the scope of the model at this time to address the possible therapeutic benefits of higher nutrient intakes that may offset the risk of adverse effects. The UL is not meant to apply to individuals who are being treated with the nutrient or food component under medical supervision.

The term "adverse effect" is defined as any significant alteration in the structure or function of the human organism (Klaassen et al., 1986), or any impairment of a physiologically important function, in accordance with the definition set by the joint World Health Organization, Food and Agriculture Organization of the United Nations, and International Atomic Energy Agency (WHO/FAO/IAEA) Expert Consultation in Trace Elements in Human Nutrition and Health (WHO, 1996). In the case of nutrients, it is exceedingly important to consider the possibility that the intake of one nutrient may alter in detrimental ways the health benefits conferred by another nutrient. Any such alteration (referred to as an adverse nutrient-nutrient interaction) is considered an adverse health effect. When evidence for such adverse interactions is available, it is considered in establishing a nutrient's UL.


Like all chemical agents, nutrients can produce adverse health effects if intakes from any combination of food, water, nutrient supplements, and pharmacologic agents are excessive. Some lower level of nutrient intake will ordinarily pose no likelihood (or risk) of adverse health effects in normal individuals even if the level is above that associated with any benefit. It is not possible to identify a single "risk-free" intake level for a nutrient that can be applied with certainty to all members of a population. However, it is possible to develop intake levels that are unlikely to pose risk of adverse health effects to most members of the general population, including sensitive individuals. For some nutrients or food components these intake levels may, however, pose a risk to subpopulations with extreme or distinct vulnerabilities.

Copyright © 1998, National Academy of Sciences.
Bookshelf ID: NBK45185
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