Timing of supplementation of selenium and isoflavones determines prostate cancer risk factor reduction in rats.
BACKGROUND
High dietary intake of selenium or isoflavones reduces risk factors for prostate cancer. We tested whether combined supplementation of these two dietary components would reduce prostate cancer risk factors in rats more than supplementation of each component individually.


METHODS
Male Noble rat pups were exposed from conception to diets containing an adequate (0.33-0.45 mg/kg diet) or high (3.33-3.45 mg/kg) concentration of selenium as Se-methylselenocysteine and a low (10 mg/kg) or high (600 mg/kg) level of isoflavones in a 2 x 2 factorial design. Pups consumed their respective diets until sacrifice at 35, 100, or 200 days. Male Noble rat breeders, whose exposure to the diets began after puberty, were sacrificed at 336 days. Rats were weighed biweekly. Blood was collected at the time of sacrifice and body fat and prostates were dissected and weighed. Serum levels of leptin, IGF-1, and testosterone were determined using ELISA kits. Serum levels of isoflavones were assayed by GC/MS. Liver activity of selenium-dependent glutathione peroxidase 1 was measured as an indicator of selenium status.


RESULTS
Serum isoflavone concentrations were nearly 100-fold higher at 35 days of age (1187.1 vs. 14.4 ng/mL, mean +/- SD) in pups fed the high vs. low isoflavone diets, and remained so at 100 and 200 days, and in breeders. There were no dietary differences in liver glutathione peroxidase activity in pups or breeders. High isoflavone intake significantly (p = 0.001-0.047) reduced body weight in rat pups from 35 days onward, but not in breeders. Body fat and leptin were likewise significantly reduced by high isoflavones in pups while effects in breeders were less pronounced but still significant. High intake of Se and isoflavones each decreased serum IGF-1 in pups at 100 and 200 days, but not in breeders. No consistent dietary effects were observed on serum testosterone or relative weights of prostates. In pups, the combination of high isoflavones and high selenium produced the lowest weight gain, the lowest serum leptin, and the lowest serum IGF-1 concentrations of all four diets.


CONCLUSIONS
Combined intake of high selenium and high isoflavones may achieve greater chemopreventive effects than either compound individually. The timing of supplementation may determine the significance of its effects.
Tolman
Jessica R
JR
Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, Utah 84602, USA.
Lephart
Edwin D
ED
Department of Physiology, Developmental Biology and the Neuroscience Center, Brigham Young University, Provo, Utah 84602, USA.
Setchell
Kenneth Dr
KD
Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Eggett
Dennis L
DL
Department of Statistics, Brigham Young University, Provo, Utah 84602, USA.
Christensen
Merrill J
MJ
Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, Utah 84602, USA.|Cancer Research Center, Brigham Young University, Provo, Utah 84602, USA.