iological processes. Bioavailability influences a nutrient’s beneficial effects at physiological levels of intake and also may affect the nature and severity of toxicity due to excessive intakes. The concentration and chemical form of the nutrient, the nutrition and health of the individual, and excretory losses all affect bioavailability. Bioavailability data for specific nutrients must be considered and incorporated by the risk assessment process.

Some nutrients may be less readily absorbed when part of a meal than when consumed separately. Supplemental forms of some nutrients may require special consideration if they have higher bioavailability and therefore may present a greater risk of producing adverse effects than equivalent amounts from the natural form found in food.

A diverse array of adverse health effects can occur as a result of the interaction of nutrients. The potential risks of adverse nutrient-nutrient interactions increase when there is an imbalance in the intake of two or more nutrients. Excessive intake of one nutrient may interfere with absorption, excretion, transport, storage, function, or metabolism of a second nutrient. Possible adverse nutrient-nutrient interactions are considered as a part of setting a UL. Nutrient-nutrient interactions may be considered either as a critical endpoint on which to base a UL or as supportive evidence for a UL based on another endpoint.

In addition to nutrient interactions, other considerations have the potential to influence nutrient bioavailability, such as the nutritional status of an individual and the form of intake. These issues are considered in the risk assessment. With regard to the form of intake, fat soluble vitamins, such as vitamin A, are more readily absorbed when they are part of a meal that is high in fat. ULs must therefore be based on nutrients as part of the total diet, including the contribution from water. Nutrient supplements that are taken separately from food require special consideration, because they are likely to have different bioavailabilities and therefore may represent a greater risk of producing adverse effects in some cases.