supplement ingredient, or individuals in whom the specific adverse effects identified are more likely to be serious in comparison with the general population. Characteristics that contribute to such vulnerability may be physiological (including genetic predisposition), disease-related, or due to other aspects, such as lifestyle or therapeutic interventions that are commonly utilized by a subgroup.

Physiological characteristics frequently result in an individual’s increased susceptibility compared with the general population; an example of this is the change in the capacity to metabolize various dietary supplement ingredients across the lifespan. Changes in metabolism may lead to variable concentrations of active compounds at sites of action, resulting in different responses. For example, elderly individuals are a potential vulnerable subpopulation for some ingredients in that aging is associated with changes in the ability to digest, metabolize, or excrete some ingested substances (Munro, 1989; Rosenberg et al., 1989). Other age-related changes may involve receptors or kinetic parameters, such as the volume of distribution (Mangoni and Jackson, 2004).

Supplement ingredients that are normally excreted or altered by the kidney or liver may potentially pose a greater risk to the elderly subgroup than to a younger population. This fact should be considered for supplements specifically directed toward an older population, such as those consumed to prevent osteoporosis or Alzheimer’s disease.

Children also metabolize some chemical substances differently than do adults, which for certain supplement ingredients may make children more susceptible to adverse effects (Guzelian et al., 1992). This should be taken into consideration for supplements marketed toward children or likely to be given to children. Infants have limited liver function that may make them particularly susceptible to certain hepatotoxic substances (Brown, 1968).

Pregnancy-related physiological changes may make pregnant women more susceptible to adverse effects associated with particular dietary supplement ingredients. In addition, the fetus may also be particularly vulnerable; special concerns are warranted for supplement ingredients that may have teratogenic effects. Fetuses may be harmed if they are exposed to dangerous substances in utero, as may infants if they are exposed to substances released into human milk. A well-known example is the teratogenicity of high doses of vitamin A in the periconceptual period (Eckhoff and Nau, 1990; Lammer et al., 1985; Rothman et al., 1995). Animal studies or chemical