Red Clover Botanical Dietary Supplements - Metabolism and Safety in Women

At the start of a study, subjects will be administered low doses of a mixture of four
FDA-approved drugs (caffeine, tolbutamide, dextromethorphan, and alprazolam), and serial
blood samples will be drawn and analyzed for the concentration of each drug over time.
Afterwards, participants will take the red clover dietary supplement twice daily for 14 days
to allow for potential inhibition or induction of drug metabolizing enzymes and transporters.
Thereafter, the same drugs will be taken again to obtain a second measure of drug
concentrations in blood over time. Changes in the concentration-time curve values for each
probe drug obtained before and after ingestion of the supplement would indicate that
metabolism of the probe drugs is impacted by the red clover dietary supplement.

Inclusion Criteria:

- healthy peri- and post-menopausal women ages 40 - 79

- non-smokers

- no-significant medical conditions as assessed by subject-reported medical history,
physical examination and blood and urine chemistry screens

- no medical condition that requires chronic use of medication

Exclusion Criteria:

- known allergies or hypersensitivity to caffeine, dextromethorphan, sulfonylureas
(tolbutamide), benzodiazepines, or red clover

- positive pregnancy test

- use of hormone therapy within 8 weeks of study initiation for oral agents, 4 weeks for
transdermal or other topical agents

- use of caffeine products 7 days before study participation or during the study

- use of citrus products 7 days before study participation or during the study

- other prescription (with the exception of the Mirena® IUD) or non-prescription
medicines within the 2 weeks prior to study initiation or during the study

- chronic diseases, such as inflammatory bowel disease, that could alter the absorption
or metabolism of the probe substrates

- unwillingness to comply with study requirements

- current participation in another clinical trial

- CYP2D6 deficiency based on phenotyping at screening

- smoker

- red clover or soy intake (whether as a botanical dietary supplement, food, drink or
otherwise) within the previous two weeks and during the study

- use of any dietary supplements within the last 2 weeks prior to study initiation and
during the study

- extreme obesity (defined as >40 BMI)

- alcohol or drug abuse

- chronic diseases such as diabetes.