Factors affecting the bioavailability of soy isoflavones in humans after ingestion of physiologically relevant levels from different soy foods.

The precise role that isoflavones play in the health-related effects of soy foods, and their potential for adverse effects are controversial. This may be due in part to a lack of basic knowledge regarding their bioavailability and metabolism, particularly as it relates to the soy source. To date, there is little information concerning possible differences in the bioavailability of isoflavones derived from natural soy foods consumed at physiologically relevant intakes and whether age- or gender-related differences influence that bioavailability. In the current study of healthy adults [premenopausal (n = 21) and postmenopausal (n = 17) women and a group of men (n = 21)], we examined the effect of age, gender, and the food matrix on the bioavailability of isoflavones for both the aglycon and glucoside forms that are naturally present in 3 different soy foods, soy milk, textured vegetable protein, and tempeh. The study was designed as a random crossover trial so that all individuals received each of the 3 foods. The dose of isoflavones administered to each individual as a single bolus dose was 0.44 mg/kg body weight. Pharmacokinetic parameters were normalized to mg of each isoflavone ingested per kilogram body weight to account for differences in daidzein and genistein content between the diets. Serum isoflavone concentrations in all individuals and groups increased rapidly after the ingestion of each soy food; as expected, genistein concentrations exceeded daidzein concentrations in serum. In this small study, gender differences in peak concentrations of daidzein were observed, with higher levels attained in women. Consumption of tempeh (mainly isoflavone aglycon) resulted in higher serum peak levels of both daidzein (P < 0.001) and genistein (P < 0.01) and the associated area under the curve (P < 0.001 and P < 0.03, respectively) compared with textured vegetable protein (predominantly isoflavone glucosides). However, soy milk was absorbed faster and peak levels of isoflavones were attained earlier than with the other soy foods. Only 30% of the subjects were equol producers and no differences in equol production with age or gender were observed.

Urinary isoflavone kinetics: the effect of age, gender, food matrix and chemical composition.

Urinary isoflavone excretion is used to monitor compliance and examine biological effects. The present study determined if there were alterations in urinary isoflavone excretion following the ingestion of different soya foods and if age and gender potentially modified profiles. Twenty premenopausal women, seventeen post-menopausal women and twenty men received a defined single oral bolus dose (0.44 mg isoflavones/kg body weight) of soya milk, textured vegetable protein (TVP) or tempeh on three separate occasions. Baseline and four consecutive complete 24 h pooled urines were collected during each period. Urinary genistein recovery was influenced by gender and food matrix. For women the urinary genistein recovery was higher following soya-milk consumption compared with TVP (P<0.05). Tempeh consumption also resulted in an increased urinary genistein recovery relative to soya milk in premenopausal women (P<0.052). No differences in urinary genistein recoveries between soya foods were observed in the men. Although urinary daidzein excretion was similar across the foods studied and was not affected by age or gender, conversion to its intestinal metabolite, equol, resulted in potential matrix and chemical composition effects; urinary equol excretion was higher (P<0.01) following tempeh ingestion among equol producers. Together these data suggest that the fractional absorption of genistein is potentially different in men and women and is influenced by the food matrix and chemical composition. Furthermore, the data suggest that the metabolism of daidzein may be altered by the chemical composition of the isoflavones ingested. Further studies are required to examine the effect of higher intake and define the relative influence of these factors in elderly population groups.

Comparing the pharmacokinetics of daidzein and genistein with the use of 13C-labeled tracers in premenopausal women.

BACKGROUND: Despite significant interest in the risks and benefits of phytoestrogens to human health, few data exist on their pharmacokinetics in humans. OBJECTIVE: We investigated the pharmacokinetics of the (13)C isotopic forms of daidzein and genistein in healthy humans, specifically addressing intraindividual variability, effect of increasing intake, and influence of prolonged exposure to a soy food diet. DESIGN: Premenopausal women (n = 16) were administered 0.4 mg [(13)C]daidzein or [(13)C]genistein/kg body wt orally on 3 occasions, including once after eating soy foods for 7 d. On a further occasion the dose was doubled. Plasma and urinary [(13)C]isoflavone concentrations were measured by mass spectrometry. RESULTS: Serum concentrations of [(13)C]genistein and [(13)C]daidzein peaked after 5.5 and 7.4 h, respectively. The systemic bioavailability and maximum serum concentration of [(13)C]genistein were significantly greater than those of [(13)C]daidzein. The bioavailability of both isoflavones did not increase linearly when the dietary intake was doubled. The mean volume of distribution normalized to bioavailability (V(d)/F), clearance rate, and half-life of [(13)C]daidzein were 336.25 L, 30.09 L/h, and 7.75 h, respectively; the corresponding values for [(13)C]genistein were 258.76 L, 21.85 L/h, and 7.77 h. The average recovery of [(13)C]daidzein and [(13)C]genistein in urine was 30.1% and 9.0% of the dose ingested, respectively. CONCLUSIONS: The serum pharmacokinetics of [(13)C]daidzein and [(13)C]genistein were reproducible among healthy women, and genistein was more bioavailable than was daidzein. Pharmacokinetics were unaffected by chronic exposure to soy foods. Urinary isoflavone concentrations correlated poorly with maximal serum concentrations, indicating the limitations of urine measurements as a predictor of systemic bioavailability. The bioavailability of both isoflavones was nonlinear at higher intakes, suggesting that uptake is rate-limiting and saturable.