This is a 127-day study with a cross-over design, divided into three metabolic periods (P1, P2, and P3). For the first 14 days (P1), all subjects will receive two placebo beverages and will be asked to consume one each with breakfast and dinner. Then in metabolic period 2 (P2), subjects will be randomly assigned to one of two groups (Group 1 and Group 2). For the next 56 days, Group 1 will continue to consume two placebo beverages per day, while Group 2 will consume two beverages containing limonoids (250 mg/beverage). During the final 56 days (P3), the beverages provided to Group 1 will contain limonoids, and beverages provided to Group 2 will be placebo. Both the placebo and limonoid beverages will be 12-oz buffered, sterile, orange flavored, artificially sweetened beverage, containing 60 mg vitamin C, 11 mg riboflavin and zero calories. Subjects are instructed that they must drink all the beverage provided each day. Beverages will contain a biomarker (riboflavin), and the biomarker is assayed in urine samples collected every 2 weeks at the beverage pickup appointments to monitor compliance. The subjects will be informed that they are being monitored for compliance. Limonin glucoside is obtained from citrus waste materials utilizing chromatographic methods that employ food grade approved media and solvents. The final pure limonin glucoside is fractionally crystallized from a concentrated water solution of a chromatographically purified extract. The crystalline material is separated from the mother liquor, dried and subjected to mass spectral and nuclear magnetic resonance assessment. The spectral data is compared to data acquired for a pure limonin glucoside standard to establish final purity which is better than 95%.

Blood samples (approximately 70 ml, less than five tablespoons) will be drawn after a 12 hour overnight fast on study days 1, 15, 71 and 127 by venipuncture. These blood samples will be used to determine serum limonoids, complete blood cell count (CBC), and comprehensive chemistry panel (CCP), serum lipids, markers of inflammation, lymphocyte and monocytes functions. In addition to the fasting blood draws on days 15 (Group 2) and day 71 (Group 1), repeated blood samples (5 ml each time, approximately one teaspoon) will be drawn at 2, 4, 6, 8, and 24 hr after taking two 12-oz limonoid beverages (total limonoids 500mg) to determine the absorption and metabolism of limonoids. The investigators note that the blood samples drawn 24-h after the limonoid intake will be on study day 16 for Group 2 and day 72 for Group 1. The total amount of blood drawn will be less than 500 ml (2 cups) in 127 days. A spot urine sample will be collected at the same visit as the fasting blood draws, and every two weeks at the beverage pickup appointments. Repeated blood draws at 0, 2, 4, 6, and 8 hr after the limonoid supplement will be accompanied by the collection of urine samples. No food will be allowed during the 8 hrs; water intake will be monitored and restricted to one liter. Subjects will be served two standardized meals during this time, each representing 35% of their daily caloric intake, one after the 0 hr blood draw and the other after the 8 hr blood draw.

Subjects will be instructed not to change their diets, exercise or lifestyle during the course of the study. They will also be instructed not to consume any citrus fruit/juice (orange, grape fruit) throughout the study. Three 24-hour dietary recalls will be collected by telephone during the last week of each metabolic period (P1, P2, P3). A standardized diet will be served for all three meals for each day prior to the blood draws.