Isoflavone excretion phenotypes influence plasma cholesterol in golden Syrian hamsters

We hypothesized that hamsters sorted into high and low isoflavone excreter phenotypic categories would show significant differences in plasma cholesterol status, the high isoflavone excreters having lower cholesterol. One-year-old hamsters were fed either 1.18 mmol of total isoflavones per kilogram diet (5 males and 5 females) or 1.77 mmol of total isoflavones per kilogram diet (5 males and 4 females) for 10 days. Urine and feces were collected for 24 hours in metabolic cages, and blood collected at euthanasia after 16 hours of fast. According to a cluster analysis, hamsters were sorted into 2 distinct urinary isoflavone phenotypes: high and low excreters with mean total isoflavone excretion of 44% ± 5% vs 14% ± 7%; daidzein excretion of 30% ± 7% vs 8% ± 3%; glycitein excretion of 84% ± 6% vs 28% ± 13%; and genistein excretion of 35% ± 7% vs 8% ± 4% of the ingested dose. Urinary excretion of all isoflavones was strongly correlated (0.93 < r < 0.98; P < .001). Fasting plasma total cholesterol was significantly lower in high vs low excreters (eg, based upon total isoflavones, 6.1 ± 1.9 vs 8.3 ± 1.5 mmol/L, respectively), regardless of sex. Although females had significantly better bioavailability than males for total isoflavones (33% ± 18% vs 17% ± 9%), daidzein (24% ± 14% vs 11% ± 6%) and genistein (27% ± 15% vs 10% ± 6%), cholesterol concentrations were not significantly different by sex, probably because of the lesser difference in bioavailability between sexes than between urinary isoflavone excretion clusters. These data support our hypothesis. Golden Syrian hamsters may be good models to study the link between bioavailability and cholesterol-lowering effects of isoflavones because they sort into isoflavone bioavailability clusters similar to that noted previously in humans.