Risk-benefit analysis of micronutrients.

Traditionally, different approaches have been used to determine the recommended dietary allowances for micronutrients, above which there is a low risk of deficiency, and safe upper levels, below which there is a negligible risk of toxicity. The advice given to risk managers has been in the form of point estimates, such as the recommended dietary allowance (RDA) and the tolerable upper level (UL). In future, the gap between the two intake-response curves may become narrower, as more sensitive indicators of deficiency and toxicity are used, and as health benefits above the recommended daily allowance are taken into account. This paper reviews the traditional approaches and proposes a novel approach to compare beneficial and adverse effects across intake levels. This model can provide advice for risk managers in a form that will allow the risk of deficiency or the risk of not experiencing the benefit to be weighed against the risk of toxicity. The model extends the approach used to estimate recommended dietary allowances to make it applicable to both beneficial and adverse effects and to extend the intake-incidence data to provide a range of estimates that can be considered by the risk manager. The data-requirements of the model are the incidence of a response at one or more levels of intake, and a suitable coefficient of variation to represent the person-to-person variations within the human population. A coefficient of variation of 10% or 15% has been used for established recommended dietary allowances and a value of 15% is proposed as default for considerations of benefit. A coefficient of variation of 45% is proposed as default for considerations of toxicity, based on analyses of human variability in the fate and effects of therapeutic drugs. Using this approach risk managers, working closely with risk assessors, will be able to define ranges of intake based on a balance between the risks of deficiency (or lack of benefit) and toxicity.