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Dietary Supplements: A Framework for Evaluating Safety
As described in Appendix J, the relationship of chaparral tea to adverse effects is less clear (hence there would be no solid line path between the tea and the adverse livers effect box). It is apparent from Figure 11-1 that if NDGA was found to be a component in chaparral tea, greater concern would be appropriate. Finally, this diagram illustrates how there may be some consistency between the proximal tubule damage observed in rodents following NDGA ingestion and the metabolism of NDGA to an orthoquinone derivative. In summary, it is the pattern of consistency and biological plausibility, illustrated by more than one path from chaparral to adverse liver effects, that raises even more concern about the safety of chaparral, especially when not prepared as a tea and when ingested by subpopulations particularly vulnerable because they have pre-existing liver conditions.
Use of External Advisory Committee
In the prototype development process, external experts were used to simulate the prescribed process of bringing in expertise particular to the ingredient’s safety concerns. Consultation with experts on the specific dietary supplement ingredient, the adverse effects of concern, the physiological system of concern, and the categories of data in need of review were all important to the development of relevant conclusions and recommendations, especially when data were sparse, inconsistent, or difficult to interpret. For example, it was helpful to have physicians and scientists very familiar with insulin and glucose regulation to consider glucosamine, experts in melatonin biology and endocrinology for melatonin consideration, experts familiar with metal toxicology and carcinogenicity to help with chromium picolinate, and experts in plant chemistry as chaparral and NDGA were considered. The Framework process outlined in Chapter 11 suggests that FDA may also want to involve external experts when data are not clear-cut, when expertise in particular aspects of human physiology is necessary and when the data to be considered require additional expertise to interpret.
Notably, in the process used to test and improve the Framework, working groups were organized to guide data collection into monographs, but it is not envisioned that FDA will use such working groups to prepare monographs. Instead, FDA will probably choose to collate data into a monograph form in-house or by using outside contractors. Where FDA may choose to involve external experts, if internal expertise needs to be supplemented is in conducting the integrative evaluation (i.e., the actual analysis of how to interpret the data and develop a conclusion).