Assessing the safety of botanicals containing isoflavones hinges primarily upon their
potential to elicit effects on estrogen metabolism, but this assessment can only be
reliably conducted with adequate characterization of the isoflavones involved. Of
particular relevance to the regulatory context are soy (Glycine max), red clover (Trifolium pratense), and kudzu (Pueraria montana). Each of these species can contain variable quantities and congeners of isoflavones,
rendering the consistent preparation of these products critical to quality control
and, ultimately, safety and efficacy. Aglycone forms of the isoflavones have generally
been regarded as more readily absorbable than their glycosidic counterparts. However,
glycosidic forms of certain isoflavones, such as puerarin, can also be absorbed to
a significant extent, so when they are present, safety should be assessed using glycosidic
isoflavone amounts rather than the conventional aglycone equivalents. To complicate
matters, absorption rates for the isoflavones can also be affected by the product's
matrix, suggesting that the isoflavones may also be absorbed by other means than simply
passive diffusion. Thus, thoroughly assessing the safety profile of a given isoflavone
preparation requires detailed characterization of the product as a whole and the product's
recommended conditions of use. Nevertheless, in the absence of this product specific
characterization, limited inferences from the broader data can also be applied to
appropriately address uncertainties and mitigate the potential for risk.