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Dietary Supplements: A Framework for Evaluating Safety
level of antiviral activity, cancer patients must maintain an effective concentration of chemotherapeutic agents, those with organ transplants must maintain a therapeutic level of immunosuppressant, and those with hypertension must maintain effective levels of antihypertensive drugs. Conversely, interactions can raise a drug’s level (or that of the dietary supplement ingredient itself) above the therapeutic range, which may lead to toxic effects.
Interactions can be detected with human, animal, or in vitro studies or predicted on the basis of how related substances behave. Therefore, types of interactions are discussed in this chapter, experimental methods for identifying ingredients that may cause these types of interactions are described, and guidance on how to interpret the results from studies using these methods is provided. In addition, types of individuals most vulnerable to the various types of interactions are discussed.
TYPES OF INTERACTIONS
There are numerous mechanisms for interactions among xenobiotics, but most can be categorized as direct chemical-chemical, pharmacodynamic, or pharmacokinetic interactions.
Direct Chemical-Chemical Interactions
The formation of chemical-chemical complexes can modify the action of one or both chemicals. In general, these types of interactions require ingestion of both chemicals within a relatively short time of each other. An example of a direct chemical-chemical interaction occurs in the small intestine, where calcium carbonate taken as a supplement may bind to an acid substance, such as the antibiotic tetracycline, to form an insoluble product (Gugler and Allgayer, 1990). In this case, since the acid was a drug, the action of the drug would be reduced or lost. Other examples include cholestyramine, which adsorbs other drugs, thereby decreasing their availability for absorption, and antacids, which can block iron or zinc uptake. In addition to forming complexes, antacids may significantly change the rate of absorption of other chemicals by altering gastric pH or gastric emptying time, depending on the extent to which pH affects the amount of chemical in the un-ionized state (Azarnoff and Hurwitz, 1970; Hurwitz, 1971, 1977; Hurwitz and Scholzman, 1974; Hurwitz and Sheehan, 1971; Hurwitz et al., 1976).
Pharmacodynamic interactions are interactions that result in a change in the response to either the dietary supplement ingredient or the xenobiotic,