and International Atomic Energy Agency 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 excessive intake of one nutrient may alter in detrimental ways the health benefits conferred by another. 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.
ULs are useful because of the increased interest in and availability of fortified foods, the increased use of dietary supplements, and the growing recognition of the health consequences of excesses, as well as inadequacies of nutrient intakes. ULs are based on total intake of a nutrient from food, water, and supplements if adverse effects have been associated with total intake. However, if adverse effects have been associated with intake from supplements or food fortificants only, the UL is based on nutrient intake from these sources only, not on total intake. The UL applies to chronic daily use.
For many nutrients, there are insufficient data on which to develop a UL. This does not mean that there is no potential for adverse effects resulting from high intake. When data about adverse effects are extremely limited, extra caution may be warranted.
Like all chemical agents, nutrients can produce adverse health effects if intakes from any combination of food, water, nutrient supplements, and pharmacological 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 for most members of the general population, including sensitive individuals. For some nutrients or food components, these intake levels may however pose a risk for subpopulations with extreme or distinct vulnerabilities.
Whether routine, long-term intake above the UL is safe is not well documented. Although members of the general population should not 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 toxicity and as long as these trials employ appropriate safety monitoring of trial subjects.