In the context of toxicity, the bioavailability of an ingested nutrient can be defined as its accessibility to normal metabolic and physiological 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. Factors that affect bioavailability include the concentration and chemical form of the nutrient, the nutrition and health of the individual, and excretory losses. Bioavailability data for specific nutrients must be considered and incorporated by the risk assessment process.

Some nutrients, for example, folate, may be less readily absorbed when they are part of a meal than when taken separately. Supplemental forms of some nutrients, such as some of the B vitamins, phosphorus, or magnesium, may require special consideration if they have higher bioavailability and therefore may present a higher risk of producing adverse effects than equivalent amounts from the natural form found in food.

Nutrient-Nutrient Interactions

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. For example, dietary interactions can affect the chemical forms of elements at the site of absorption through ligand binding or changes in the valence state of an element (Mertz et al., 1994). Phytates, phosphates, and tannins are among the most powerful depressants of bioavailability, and organic acids, such as citric and ascorbic acid, are strong enhancers for some minerals and trace elements. Thus dietary interactions strongly influence the bioavailability of elements by affecting their partition between the absorbed and the nonabsorbed portion of the diet. The large differences of bioavailability ensuing from these interactions support the need to specify the chemical form of the nutrient when setting ULs. Dietary interactions can also alter nutrient bioavailability through their effect on excretion. For example, dietary intake of protein, phosphorus, sodium, and chloride all affect urinary calcium excretion and hence calcium bioavailability. Interactions that significantly elevate or reduce bioavailability may represent adverse health effects.

Although it is critical to include knowledge of any such interactions in the risk assessment, it is difficult to evaluate the possibility of interactions without reference to a particular level of intake. This difficulty can be overcome if a UL for a nutrient or food component is first derived based on other measures of

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