Isoflavones Derived from Soy, Red Clover, and Kudzu in Safety Assessments: Identity, Form, Quantity, and Product Matrix Considerations

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.