Standardized Extracts Needed for Evaluation of Supplements

WASHINGTON—With one third to one half of all Americans now using some kind of dietary supplement, the need is greater than ever for scientifically valid ways of testing and comparing the enormous range of substances now sold with minimal FDA oversight, Vay Liang W. Go, MD, said at the American Institute for Cancer Research conference on nutrition. Dr. Go is associate director, Center for Human Nutrition, UCLA.

A range of compounds has been identified in recent years that appear to have anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative properties, Dr. Go said. These include botanical nonsteroidal anti-inflammatory drugs (NSAIDs), tannins, flavonoids, phenyl propanoids, terpenes, and S-compounds.

But consistency is a problem. Searching a local market for competing brands of tofu, a product now touted for the isoflavones it contains, is revealing. “You can do very well with one product on one day, but on another day with another box, the contents are not necessarily the same,” he said. The desired constituents may vary widely with the season, growing temperature, water, and other environmental factors.

Existing conventional chemopreven-tive agents, like NSAIDs or estrogen, are single compounds with by-now familiar properties, absorption rates, formulation, routes of administration, drug interactions, safety, toxicity, and stability. Thus, it is possible to compare one product with another with some validity, Dr. Go said.

However, such standards are not in place for evaluating dietary supplements, he said. “Many compounds contain multiple active ingredients, and there may be many different formulations,” he said. “This makes interpretation of results difficult.”

Testing these compounds would require a standardized extract, based on the kind of consistent good manufacturing practices (GMP) which the FDA mandates for the foods and drugs under its control. Only then, Dr. Go said, would it be possible to reliably test for physicochemical profiles, biomarkers, solubility, stability, absorption, excretion, and metabolism.

The Dietary Supplements Health and Education Act (DSHEA) passed by Congress in 1994 established an Office of Dietary Supplements Research within the National Institutes of Health, and called for research centers to be set up around the country. Two of those centers have been established, at the University of Illinois-Chicago and UCLA.

Dr. Go said that the UCLA center will identify active compounds, assess their biological activity and availability, and conduct preclinical studies.

Dr. Go cited several examples of forthcoming research. His lab has developed in vitro cell lines to assay phytoestrogens found in soy products for the chemicals that bind to two different estrogen receptors. While some isoflavones found in soy, like genistein, have received much attention, the percentage of genistein in any given soy powder may vary, and genistein is not the only isoflavone present in soy.

“No one swallows pure genistein,” he said. “They eat soy protein, and the observed effect could be due to some other compound.”

PC-SPES, a proprietary mixture of eight Chinese herbs used for their antiproliferative effects in prostate cancer, raises the issue of how to test a product with multiple ingredients. Dr. Go said that markers are needed for both the intended use of the product and possible side effects—and for all the ingredients individually.

Green tea is another area of current interest in the marketplace, due to the potent antioxidative properties of the catechins it contains. However, he said, the catechin content of the teas found in stores is not the same as that of the extracts used in the lab. “We need controlled levels of the catechins or the trials are worthless,” he said. “Also, patients cannot drink green tea on their own during a trial; it will confound the data.”