Why do you think your paper is highly cited?

I believe this is perhaps a reflection of the increased interest in recent years in natural alternative therapies for the treatment and prevention of chronic diseases, and no doubt reflects the huge increase in the commercialization of dietary supplements.

  Does it describe a new discovery or new methodology that’s useful to others?

This work focuses more on the application of methodologies that have evolved over many years for the determination of the pharmacokinetics of an important class of phytoestrogens present in soy, rather than the specific discovery of new methodology. Nevertheless it describes for the first time the pharmacokinetics of isoflavones given orally as pure compounds to healthy adults and in addition it is the first report of the isoflavone composition of a range of phytoestrogen supplements sold over the counter and largely targeted to women’s health.

  What are the circumstances that lead you to do this research?

In the early 1980’s, following our original discovery of isoflavones in human urine and plasma and our proposal that these non-steroidal estrogens of dietary origin play a role in hormone-dependent diseases, there has been a wealth of scientific data showing biological effects of ingesting isoflavones from soy. While many clinical and dietary intervention studies have been carried out, for many years there was a paucity of data on their biological and metabolic fate of these phytoestrogens. Our studies were funded by the National Institutes of Health as part of our program to better understand the pharmacokinetics of isoflavones in soy, as this type of fundamental knowledge is crucial to the design of any clinical study aimed at investigating the clinical effects of these bioactive constituents. At the time when most of us were working with soy foods, industry began extracting isoflavones and packaging these in pills to be marketed as supplements. Given the rate at which phytoestrogens supplements were being marketed with their many unsubstantiated health claims we decided to take a careful look at the composition of isoflavone supplements. Do they really contain what they claim and can they really do what they claim became of interest to us.

  Can you summarize the significance of you paper in layman’s terms?

Our findings established for the first time how isoflavones behave after being ingested by healthy adults. Based on the pharmacokinetics, our studies suggest that for biological effects to be maximized it would be advantageous to consume isoflavones at regular intervals throughout the day to prevent the large fluctuation in plasma levels that otherwise are seen with just a single ingestion. These findings are of particular relevance to the food industry because our data suggests that foods that contain modest, rather than high levels of isoflavones, and that can be eaten throughout the day are likely to have the best effects. With regard to our findings on supplements these confirm the increasing concern of health professionals and consumers that a high proportion of supplements do not contain what is claimed and we found no two supplements to have the same isoflavone composition. This leaves the consumer in a quandary as to which supplement to purchase because in many cases it is not possible to know what the product really contains. Furthermore, one supplement we tested that claimed to increase a woman’s breast size by an estrogen effect on the breast was found to have no estrogen activity when chemically analyzed for phytoestrogens or when tested in an animal model for its estrogenicity. Until supplements are more rigorously regulated it will continue to be the case of ‘let the buyer beware’.

Kenneth D. R. Setchell, PhD.
Professor of Pediatrics
Director, Clinical Mass Spectrometry
Cincinnati Children's Hospital Medical center
3333 Burnet Avenue
Cincinnati, Ohio 45227