pared with modern formulations. In most cases, however, dosing comparisons are so imprecise that they should probably only be attempted when the modern formulation clearly provides doses that may be orders of magnitude higher than traditional doses. For example, consumption of a culinary botanical in small amounts is very different, and thus may have different effects, than consumption of large amounts of the same encapsulated botanical, rendering a safety extrapolation from culinary to supplemental use inappropriate. In summary, if the current level of intake is significantly above what has been traditionally recommended, then the level of concern should be increased.

• How similar is the current preparation to that used traditionally? Is the preparation a crude preparation, extract, or concentrate; a selected fraction; an isolated compound; or a mixture of these? As discussed above, the toxicity of a substance depends on the amount ingested. The method of preparation will impact the amount and types of chemical compounds ingested, thus potentially impacting an ingredient’s safety. The different methods of preparation are most clearly illustrated with botanicals. Traditionally, many orally ingested medicinal botanicals were administered as crude aqueous extractions of plant parts that were soaked, steeped, or boiled in water. Today’s supplement ingredients are often sold in a different form—as encapsulated dried botanicals, fluid extracts, solid extracts (e.g., capsules or tablets), or foodstuffs containing botanical extracts. The same plant can be used as an extract prepared from dried plant materials (an infusion) or as lyophilized plant made from whole fresh materials.

Whether a botanical with a history of benign use in infusions (teas) manifests new toxic effects when concentrated, lyophilized, or encapsulated will depend on where any toxic components are localized in the plant, their water solubility, their potency, and the likelihood that a person could consume enough of the active ingredients to cause an ill effect. Differences in safety profiles could also be expected for alcoholic versus aqueous extracts of plants with known toxic components. Alcohol and water extract different compounds, so alcohol extracts may contain a higher concentration of toxic compounds than aqueous extracts. Wormwood (Artemisia absinthium), for example, in an aqueous extract contains little thujone (a neurotoxin) (Tegtmeier and Harnischfeger, 1994), but may contain substantial amounts of thujone in alcohol extracts. In summary, if the method of preparation concentrates the bioactive compounds to a degree not known to be consistent with safe historical use, the level of concern should be raised.

In addition to preparations that might result in increased concentration of bioactives in the products ingested, it is also important to note that modern formulations may simply make the same substances more likely to be ingested in excessive amounts, which should raise concern. If a substance