Estrogenic and antiestrogenic activities of commercial dietary supplements containing herbal ingredients and isoflavones

Phytoestrogens, non‐steroidal polyphenolic compounds resembling the structure of the mammalian estrogen 17β‐estradiol, are present in dietary supplements that are widely marketed as natural alternatives to hormone replacement therapy. This study aimed to assess the estrogenic and antiestrogenic activities of five commercial dietary supplements: Alfalfa (Solgar Inc.), Solaray®'s Black Cohosh (Nutraceutical Corp.), EstroPause Menopause Support (Irwin Naturals), Advanced Therapeutics Isoflavone Rx‐Phytoestrogen® (Natural Organics Laboratories, Inc.), and MenoCare for Menopausal Comfort® (Himalaya Drug Co.). All dietary supplements were extracted with either 80% methanol or distilled water. A steroid‐regulated transcription system in S. cerevisiae containing a human estrogen receptor alpha expression plasmid and a β‐galactosidase gene reporter plasmid was employed to assess the estrogenic and antiestrogenic activities of supplement extracts. The estrogenic activities of methanolic extracts ranked as follows: Alfalfa > EstroPause > Isoflavone Rx‐Phytoestrogen > MenoCare > Black Cohosh and of water extracts: EstroPause > Black Cohosh > Isoflavone Rx‐Phytoestrogen > MenoCare. The highest estrogenic activities were detected in methanol (2342.5 ± 20.83 MU) and water (1225.6 ± 20.6 MU) extracts of Alfalfa supplement (400 estradiol equivalents). Supplement extracts showed antiestrogenic properties by lowering the transcriptional activity induced by estradiol in transgenic yeast. The antiestrogenic activities of methanolic extracts ranked as follows: EstroPause and Isoflavone Rx‐Phytoestrogen > MenoCare and Alfalfa and of water extracts: EstroPause and Alfalfa > MenoCare > Black Cohosh and Isoflavone Rx‐Phytoestrogen. The highest antiestrogenic activity was detected in the methanol extract of Solaray®'s Black Cohosh, which inhibited estradiol activity by 76.5 %. Black cohosh plants contain formononetin, which is the phytoestrogens responsible for the antiestrogenic activity of Solaray®'s Black Cohosh extract. Both estrogenic and antiestrogenic activities increased with increasing concentrations of supplement extracts. Except for Solaray®'s Black Cohosh extract, all other supplements showed higher estrogenic activities as methanolic extracts than water extracts. Except for Alfalfa and EstroPause, all other supplements displayed higher antiestrogenic activities as methanolic extracts than water extracts. Isoflavone Rx‐Phytoestrogen contains glycosidic phytoestrogens, which are less active than the corresponding aglycones and therefore the extracts showed lower estrogenic and antiestrogenic activities in transgenic yeast as compared to other supplement extracts. The β‐glycosidic bonds of the phytoestrogenic isoflavones are cleaved in the digestive tract and thus aglycones exert their biological effects. Future study will assess the estrogenic and antiestrogenic activities of dietary supplement extracts after acid hydrolysis and will focus on the identity, concentration and potential biological significance to the consumer of phytoestrogens in a dietary supplements.