is compacted in a capsule where taste and sheer volume of the material does not limit consumption, then there is a greater likelihood of an adverse reaction compared with the same botanical that was traditionally ingested in smaller amounts.

• Is the modern duration of use consistent with historical use patterns? The duration of use needs to be considered because acute, short-term, and long-term intakes all have different safety implications. A lack of adverse events reported for a botanical traditionally used only for a few days has little or no relevance to safety of the same botanical when it is chronically ingested. When considering how the current duration of use compares with traditional duration of use, it may be helpful to also consider whether the modern day indication is consistent with traditional indications. The modern uses of some botanicals, especially for nonmedical indications such as memory enhancement and ergogenics, may lead consumers to chronically use dietary supplements that were never used chronically in traditional medicine. In summary, concern is increased if the substance is now used for longer duration than it was traditionally.

• Is the modern reason for using the substance consistent with historical indication for its use? The reason for using the substance does not in itself provide information about its safety as a dietary supplement, but comparing the modern and traditional indications may provide clues for comparing historical and modern use. For example, some indications are more consistent with external use versus ingestion. Similarly, some indications are more consistent with long-term use (e.g., to lose weight) compared with short-term use (e.g., to treat an asthma attack).

• Is the target population similar to that which used the substance historically? Is the current user population similar to that which used the substance historically? People vary in their response to bioactive compounds. Due to physiological condition or other reasons, particular subpopulations may be more likely to suffer a serious adverse reaction than other groups. Thus, the modern use of a dietary supplement ingredient by populations that have not traditionally consumed the ingredients reduces the relevance of safe historical use information. A change in usage does not necessarily in and of itself raise the level of concern; however, if the supplement ingredient is now used by a subpopulation that may be more susceptible to adverse effects, concern may be warranted.

The fact that a botanical or other dietary supplement ingredient has been used for centuries is not prima facie evidence that it is safe. If the current preparation concentrates constituents, if the current use is more frequent or of longer duration, if the substance was not historically in-