the data reveal that only supplement usage poses a risk (the UL applies only to the supplement); in this case only the supplement intake distribution requires analysis. For example, for nutrients such as magnesium, folate, niacin, and vitamin E no information exists on adverse effects occurring from the nutrient when consumption is from foods; adverse effects have been seen only when the nutrient was consumed as a supplement, as a fortificant added to food (e.g., folate), or in over-the-counter medications (e.g., magnesium in antacids). In each of these cases the significance of the risk requires consideration of more than the fraction of the population that exceeds the UL. Currently, population usual intake distributions can be estimated, but the shape of the UL risk curve is unknown. When this information is available, however, the probability approach, as described in Chapter 4, can be used to assess the proportion of the population potentially at risk of adverse effects. The underlying assumption is that there is a threshold below which there is negligible risk from overconsumption and above which dose-response curves for toxicological assessment can be linear, exponential, or some other shape.
Although members of the general population should be advised not to routinely exceed the UL, intake above the UL may be appropriate for investigation within well-controlled clinical trials. Clinical trials of doses above the UL should not be discouraged as long as subjects participating in these trials have signed informed consent documents regarding possible adverse effects, and as long as these trials employ appropriate safety monitoring of trial subjects. In addition, the UL is not meant to apply to individuals who are receiving a high dose of a nutrient under medical supervision.
The UL is typically derived to apply to the most sensitive members of the general population. For this reason, many members of the population may regularly consume nutrients at or even somewhat above the UL without experiencing adverse effects. However, because there is no way to establish which individuals are the most sensitive, it is necessary to interpret the UL as applying to all individuals.
The need for ULs derives largely from regular, self-prescribed use of large amounts of highly fortified foods, regular consumption of a large number of moderately fortified foods, or nonfood sources such as nutritional supplements, or any combination of the three, by significant proportions of the population. Few nutrients are consumed through the food supply in amounts that could cause toxicity.