Nurses and their patients must be talking the same language.

I agree with the Nursing Standard readers panel (August 19) that nursing staff who work directly with the public should be able to speak English fluently.

S-(-)equol production is developmentally regulated and related to early diet composition.

S-(-)7-hydroxy-3-(4'-hydroxyphenyl)-chroman, or S-(-)equol, a biologically active intestinally derived bacterial metabolite of the soy isoflavones daidzin/daidzein, is not produced in neonatal life. Because its synthesis is dependent on equol-producing bacteria, we hypothesized that early nutrition may influence equol production. This prospective 2.5-year study determined the frequency of S-(-)equol production in healthy infants (n = 90) fed breast milk, soy infant formula, or cow's milk formula in their first year. Urinary S-(-)equol and daidzein were quantified by mass spectrometry after a standardized 3.5-day soy isoflavone challenge. Infants were tested at 6, 9, 12, 18, 24, and 36 months of age, and 3-day diet records were obtained at each visit to explore the effect of early and postweaning (>12 months) macronutrient and micronutrient dietary composition and S-(-)equol production. Use of antibiotics was also recorded. At age 6 months, none of the breast-fed infants produced S-(-)equol, whereas 3.8% and 6.0%, respectively, of soy and cow's milk formula-fed infants were equol producers. By age 3 years, 50% of the formula-fed infants were equol producers, compared with 25% of breast-fed infants. Use of antibiotics was prevalent among infants and may have impacted the stability of S-(-)equol production. No significant differences among the groups were observed in postweaning dietary intakes of total energy, carbohydrate, fiber, protein, fat, saturated fatty acids, or polyunsaturated fatty acids and the propensity to make S-(-)equol. In conclusion, S-(-)equol production is developmentally regulated and initially related to diet composition with the proportion of equol producers increasing over the first 3 years of life, with a trend for formula feeding favoring S-(-)equol production.

Metabolism of secoisolariciresinol-diglycoside the dietary precursor to the intestinally derived lignan enterolactone in humans.

Secoisolariciresinol-diglycoside (SDG), a natural dietary lignan of flaxseeds now available in dietary supplements, is converted by intestinal bacteria to the mammalian lignans enterodiol and enterolactone. High levels of these lignans in blood and urine are associated with reduced risk of many chronic diseases. Our objective was to determine the bioavailability and pharmacokinetics of SDG in purified flaxseed extracts under dose-ranging and steady-state conditions, and to examine whether differences in secoisolariciresinol-diglycoside purity influence bioavailability. Pharmacokinetic studies were performed on healthy postmenopausal women after oral intake of 25, 50, 75, 86 and 172 mg of secoisolariciresinol-diglycoside. Extracts differing in secoisolariciresinol-diglycoside purity were compared, and steady-state lignan concentrations measured after daily intake for one week. Blood and urine samples were collected at timed intervals and secoisolariciresinol, enterodiol and enterolactone concentrations measured by mass spectrometry. Secoisolariciresinol-diglycoside was efficiently hydrolyzed and converted to secoisolariciresinol. Serum concentrations increased rapidly after oral intake, peaking after 5-7 h and disappearing with a plasma elimination half-life of 4.8 h. Maximum serum concentrations of the biologically active metabolites, enterodiol and enterolactone were attained after 12-24 h and 24-36 h, respectively, and the half-lives were 9.4 h and 13.2 h. Linear dose-responses were observed and secoisolariciresinol bioavailability correlated (r(2) = 0.835) with cumulative lignan excretion. There were no significant differences in the pharmacokinetics of extracts differing in purity, and steady-state serum lignan concentrations were obtained after one-week of daily dosing. In conclusion, this study defines the pharmacokinetics of secoisolariciresinol-diglycoside and shows it is first hydrolyzed and then metabolized in a time-dependent sequence to secoisolariciresinol, enterodiol and ultimately enterolactone, and these metabolites are efficiently absorbed.

Dietary factors influence production of the soy isoflavone metabolite s-(-)equol in healthy adults.

S-(-)equol, an intestinally derived metabolite of the soy isoflavone daidzein, is proposed to enhance the efficacy of soy diets. Adults differ in their ability to produce equol when consuming soy foods for reasons that remain unclear. Therefore, we performed a comprehensive dietary analysis of 143 macro- and micronutrients in 159 healthy adults in the United States (n = 89) and Australia (n = 70) to determine whether the intake of specific nutrients favors equol production. Three-d diet records were collected and analyzed using Nutrition Data System for Research software and S-(-)equol was measured in urine by mass spectrometry. Additionally, in a subset of equol producers and nonproducers (n = 10/group), we examined the long-term stability of equol producer status by retesting 12, 18, and 24 mo later. Finally, the effect of oral administration of the antibiotic metronidazole (500 mg/d for 7 d) on equol production was examined in 5 adults monitored during a 4-mo follow-up period. Equol producers accounted for 30.3% and 28.6% of the United States and Australian participants, respectively (overall frequency, 29.6%). No significant differences were observed for total protein, carbohydrate, fat, saturated fat, or fiber intakes between equol producers and nonproducers. However, principal component analysis revealed differences in several nutrients, including higher intakes of polyunsaturated fatty acids (P = 0.039), maltose (P = 0.02), and vitamins A (P = 0.01) and E (P = 0.035) and a lower intake of total cholesterol (P = 0.010) in equol producers. During a 2-y period, equol producer status remained unchanged in all nonproducers and in 80% of equol producers, whereas metronidazole abolished equol production in only 20% of participants. In conclusion, these findings suggest that major differences in the macronutrient content of the diet appear not to influence equol production, but subtle differences in some nutrients may influence the ability to produce equol, which was a relatively stable phenomenon.

Cross-border use of food databases: equivalence of US and Australian databases for macronutrients.

When estimating dietary intake across multiple countries, the lack of a single comprehensive dietary database may lead researchers to modify one database to analyze intakes for all participants. This approach may yield results different from those using the country-specific database and introduce measurement error. We examined whether nutrient intakes of Australians calculated with a modified US database would be similar to those calculated with an Australian database. We analyzed 3-day food records of 68 Australian adults using the US-based Nutrition Data System for Research, modified to reflect food items consumed in Australia. Modification entailed identifying a substitute food whose energy and macronutrient content were within 10% of the Australian food or by adding a new food to the database. Paired Wilcoxon signed rank tests were used to compare differences in nutrient intakes estimated by both databases, and Pearson and intraclass correlation coefficients measured degree of association and agreement between intake estimates for individuals. Median intakes of energy, carbohydrate, protein, and fiber differed by <5% at the group level. Larger discrepancies were seen for fat (11%; P<0.0001) and most micronutrients. Despite strong correlations, nutrient intakes differed by >10% for an appreciable percentage of participants (35% for energy to 69% for total fat). Adding country-specific food items to an existing database resulted in similar overall macronutrient intake estimates but was insufficient for estimating individual intakes. When analyzing nutrient intakes in multinational studies, greater standardization and modification of databases may be required to more accurately estimate intake of individuals.

The estrogenic content of rodent diets, bedding, cages, and water bottles and its effect on bisphenol A studies.

The lowest observed adverse effect level for bisphenol A (BPA) in mice and rats is currently poorly defined due to inconsistent study designs and results in published studies. The objectives of the current study were to (1) compare the estrogenic content of rodent diets, bedding, cages, and water bottles to evaluate their impact on the estrogenic activity of BPA and (2) review the literature on BPA to determine the most frequently reported diets, beddings, cages, and water bottles used in animal studies. Our literature review indicated that low-dose BPA animal studies have inconsistent results and that factors contributing to this inconsistency are the uses of high-phytoestrogen diets and the different routes of exposure. In 44% (76 of 172) of all reports, rodents were exposed to BPA via the subcutaneous route. Our literature review further indicated that the type of diet, bedding, caging, and water bottles used in BPA studies were not always reported. Only 37% (64 of 172) of the reports described the diet used. In light of these findings, we recommend the use of a diet containing low levels of phytoestrogen (less than 20 µg/g diet) and metabolizable energy (approximately 3.1 kcal/g diet) and estrogen-free bedding, cages, and water bottles for studies evaluating the estrogenic activity of endocrine-disrupting compounds such as BPA. The oral route of BPA exposure should be used when results are to be extrapolated to humans.

Soy isoflavone phase II metabolism differs between rodents and humans: implications for the effect on breast cancer risk.

BACKGROUND: Human and animal studies have produced conflicting results with regard to the effect of soy isoflavones on breast cancer risk. This may be due to differences in isoflavone metabolism. OBJECTIVE: The objective of this study was to determine whether soy isoflavone phase II metabolism differs between humans and rodents. DESIGN: Circulating total and unconjugated isoflavone concentrations were determined by mass spectrometry in plasma samples from 7 separate studies: 1) in Sprague-Dawley rats and in 3 strains of mice fed commercial soy-containing diets; 2) in Sprague-Dawley rats gavaged with genistein; 3) in healthy adults who consumed single servings of soy nuts, soy milk, and tempeh; 4) in healthy adults subchronically given soy milk; 5) in healthy women orally administered 50 mg genistein; 6) in healthy women orally administered 20 mg pure S-(-)equol; and 7) in 6-mo-old infants fed soy infant formula and later, at age 3 y, a soy germ isoflavone supplement. RESULTS: The proportion of unconjugated genistein in plasma from adults and infants who consumed different soy foods, pure genistein, or an isoflavone supplement was <1% in steady state and <2% at peak concentrations. By contrast, rodents fed soy-containing diets conjugate isoflavones less efficiently. The plasma percentages of unconjugated genistein concentrations in Sprague-Dawley rats and C57BL/6, nude, and transgenic AngptL4B6 mice were 4.0 ± 0.6%, 4.6 ± 0.6%, 11.6 ± 0%, and 30.1 ± 4.3%, respectively, which represent 20, 23, 58, and 150 times that in humans. CONCLUSION: The markedly higher circulating concentrations of biologically active (unconjugated) genistein in certain strains of mice cast doubt on the value of the use of these rodents for gaining insight into the effects of isoflavones in humans, especially with regard to the effects on breast tissue.

Impact of perinatal exposure to equol enantiomers on reproductive development in rodents.

There is now considerable interest in the intestinally derived soy isoflavone metabolite, equol, which occurs in the enantiomeric forms, S-(-)equol and R-(+)equol, both differing in biological actions. Little is known about effects of either enantiomer on reproductive development, yet such knowledge is fundamental because of the recent commercialization of S-(-)equol as a dietary supplement. S-(-)equol and R-(+)equol were therefore investigated to determine their effects on reproductive development and fertility in the Sprague-Dawley rat. Neither enantiomer affected fertility, number of litters produced, number of pups per litter, number of male and female pups born, birth weight, anogenital distance, testicular descent or vaginal opening. Histological analysis showed no major abnormalities in ovary, testis, prostate or seminal vesicle tissue with dietary exposure to S-(-)equol or R-(+)equol, but both enantiomers triggered hyperplasia of uterine tissue. With R-(+)equol this stimulatory effect subsided after exposure was discontinued, but the effect of S-(-)equol was prolonged.

The chemopreventive action of equol enantiomers in a chemically induced animal model of breast cancer.

We describe for the first time the chemopreventive effects of S-(-)equol and R-(+)equol, diastereoisomers with contrasting affinities for estrogen receptors (ERs). S-(-)equol, a ligand for ERbeta, is an intestinally derived metabolite formed by many humans and by rodents consuming diets containing soy isoflavones. Whether the well-documented chemopreventive effect of a soy diet could be explained by equol's action was unclear because neither diastereoisomers had been tested in animal models of chemoprevention. Sprague-Dawley rats (n = 40-41 per group) were fed a soy-free AIN-93G diet or an AIN-93G diet supplemented with 250 mg/kg of S-(-)equol or R-(+)equol beginning day 35. On day 50, mammary tumors were induced by dimethylbenz[a]anthracene and thereafter, animals were palpated for number and location of tumors. On day 190, animals were killed and mammary tumors were removed and verified by histology, and the degree of invasiveness and differentiation was determined. S-(-)equol and R-(+)equol plasma concentrations measured on days 35, 100 and 190 by tandem mass spectrometry confirmed diet compliance and no biotransformation of either diastereoisomer. In this model, S-(-)equol had no chemopreventive action, nor was it stimulatory. In contrast, R-(+)equol compared with Controls reduced palpable tumors (P = 0.002), resulted in 43% fewer tumors (P = 0.004), increased tumor latency (88.5 versus 66 days, P = 0.003), and tumors were less invasive but showed no difference in pattern grade or mitosis. Both enantiomers had no effect on absolute uterine weight but caused a significant reduction in body weight gain. In conclusion, the novel finding that the unnatural enantiomer, R-(+)equol, was potently chemopreventive warrants investigation of its potential for breast cancer prevention and treatment.

The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers.

BACKGROUND: The nonsteroidal estrogen equol occurs as diastereoisomers, S-(-)equol and R-(+)equol, both of which have significant biological actions. S-(-)equol, the naturally occurring enantiomer produced by 20-30% of adults consuming soy foods, has selective affinity for estrogen receptor-beta, whereas both enantiomers modulate androgen action. Little is known about the pharmacokinetics of the diastereoisomers, despite current interest in developing equol as a nutraceutical or pharmaceutical agent. OBJECTIVE: The objective was to compare the pharmacokinetics of S-(-)equol and R-(+)equol by using [13C] stable-isotope-labeled tracers to facilitate the optimization of clinical studies aimed at evaluating the potential of these diastereoisomers in the prevention and treatment of estrogen- and androgen-dependent conditions. DESIGN: A randomized, crossover, open-label study in 12 healthy adults (6 men and 6 women) compared the plasma and urinary pharmacokinetics of orally administered enantiomeric pure forms of S-(-)[2-13C]equol, R-(+)[2-13C]equol, and the racemic mixture. Plasma and urinary [13C]R-equol and [13C]S-equol concentrations were measured by tandem mass spectrometry. RESULTS: Plasma [13C]equol concentration appearance and disappearance curves showed that both enantiomers were rapidly absorbed, attained high circulating concentrations, and had a similar terminal elimination half-life of 7-8 h. The systemic bioavailability and fractional absorption of R-(+)[2-13C]equol were higher than those of S-(-)[2-13C]equol or the racemate. The pharmacokinetics of racemic (+/-)[2-13C]equol were different from those of the individual enantiomers: slower absorption, lower peak plasma concentrations, and lower systemic bioavailability. CONCLUSIONS: The high bioavailability of both diastereoisomers contrasts with previous findings for the soy isoflavones daidzein and genistein, both of which have relatively poor bioavailability, and suggests that low doses of equol taken twice daily may be sufficient to achieve biological effects.

S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora.

BACKGROUND: The discovery of equol in human urine more than 2 decades ago and the finding that it is bacterially derived from daidzin, an isoflavone abundant in soy foods, led to the current nutritional interest in soy foods. Equol, unlike the soy isoflavones daidzein or genistein, has a chiral center and therefore can occur as 2 distinct diastereoisomers. OBJECTIVE: Because it was unclear which enantiomer was present in humans, our objectives were to characterize the exact structure of equol, to examine whether the S- and R-equol enantiomers are bioavailable, and to ascertain whether the differences in their conformational structure translate to significant differences in affinity for estrogen receptors. DESIGN: With the use of chiral-phase HPLC and mass spectrometry, equol was isolated from human urine and plasma, and its enantiomeric structure was defined. Human fecal flora were cultured in vitro and incubated with daidzein to ascertain the stereospecificity of the bacterial production of equol. The pharmacokinetics of S- and R- equol were determined in 3 healthy adults after single-bolus oral administration of both enantiomers, and the affinity of each equol enantiomer for estrogen receptors was measured. RESULTS: Our studies definitively establish S-equol as the exclusive product of human intestinal bacterial synthesis from soy isoflavones and also show that both enantiomers are bioavailable. S-equol has a high affinity for estrogen receptor beta (K(i) = 0.73 nmol/L), whereas R-equol is relatively inactive. CONCLUSIONS: Humans have acquired an ability to exclusively synthesize S-equol from the precursor soy isoflavone daidzein, and it is significant that, unlike R-equol, this enantiomer has a relatively high affinity for estrogen receptor beta.

Pharmacokinetics of a slow-release formulation of soybean isoflavones in healthy postmenopausal women.

Pharmacokinetic studies of soybean isoflavones have shown that following oral ingestion, the two major isoflavones, daidzin and genistin, are hydrolyzed in the intestine, rapidly absorbed into the peripheral circulation, and eliminated from the body with a terminal half-life of 7-8 h. These characteristics make maintenance of steady-state plasma isoflavone concentrations difficult to attain unless there is repeated daily ingestion of foods or supplements containing isoflavones. In an attempt to sustain more constant plasma isoflavone concentrations, a new slow-release formulation of a soybean isoflavone extract was prepared by microencapsulation with a mixture of hydroxypropylcellulose and ethylcellulose to alter its dissolution characteristics. In vitro experiments confirmed slow aqueous dissolution of isoflavones from this formulation when compared with the conventional isoflavone extract. The pharmacokinetics of this slow-release isoflavone extract was studied in 10 healthy postmenopausal women after oral administration of a single capsule containing the equivalent of 22.3 mg of genistein and 7.47 mg of daidzein expressed as aglycons. A comparison of the key pharmacokinetic parameters obtained in this study with those established in extensive studies performed previously in this laboratory indicated that the mean residence time of genistein and daidzein increased 2-fold with microencapsulation. These findings are indicative of a decreased rate of absorption, consistent with the observed slow in vitro dissolution rate. These findings show that it is feasible to employ polymer matrices that slow the aqueous dissolution for preparing sustained-release formulations of soy isoflavones. Further studies to optimize such formulations are warranted.

Tolerability of N-chlorotaurine in the guinea pig middle ear: a pilot study using an improved application system.

The tissue tolerance of N-chlorotaurine (NCT), a mild endogenous antimicrobial oxidant, has been investigated by application to the guinea pig middle ear. The animals were implanted with a novel cannula system that allows chronic external drug delivery to the round window niche. In the first part of the study, 3 animals each received 100 microL of 0.1% NCT (5.5 mmol/L) and 1% NCT, respectively, in aqueous solution twice daily for 8 days. In the second part, NCT was dissolved in phosphate-buffered saline solution to 300 milliosmolar (isotonic), and 27 microL was injected in 3 additional animals twice daily for 7 days. The guinea pigs injected with 100 microL of NCT developed immediate dizziness and nystagmus and did not thrive. Other reactions included mucosal thickening in the middle ear, rupture of the tympanic membrane, and blood and gelatinous material in the cochlea accompanied by hair cell loss and a 10- to 90-dB elevation of the hearing threshold as determined by auditory brain stem responses. The effects seemed to be dose-dependent, but the rate of variability was high across animals. In contrast, the guinea pigs treated with 27 microL of isotonic NCT showed no signs of discomfort, no or only moderate thickening of the middle ear mucosa, no shift of the hearing threshold, and no hair cell loss. Positive control animals injected with 10% neomycin sulfate developed extensive hair cell loss. Provided that the membranes of the inner ear are intact and that low single-dose volumes are used to avoid increased middle ear pressure, isotonic NCT seems to be well tolerated in the tympanic cavity. The new drug delivery system proved to be advantageous for ototoxicity studies.

Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes.

The pharmacokinetics of isoflavones in 10 healthy women were determined from serum appearance/disappearance concentration profiles and urinary excretions after single-bolus ingestion of 10, 20 or 40 g of soy nuts delivering increasing amounts of the conjugated forms of daidzein (6.6, 13.2 and 26.4 mg) and genistein (9.8, 19.6 and 39.2 mg). Peak serum daidzein and genistein concentrations were attained after 4-8 h, and elimination half-lives were 8.0 and 10.1 h, respectively. There were no differences in the pharmacokinetics of daidzein and genistein between pre- and postmenopausal women, indicating absorption and disposition of isoflavones to be independent of age or menopausal status. A curvilinear relationship was observed between the bioavailability of daidzein and genistein, apparent from the area under the curve to infinity (AUC(inf)) of the serum concentration-time profiles and the amount of isoflavones ingested. The mean fraction of the isoflavones excreted in urine decreased with increasing intake when expressed as a percentage of the administered dose (63.2 +/- 8.0, 54.4 +/- 8.1 and 44.0 +/- 4.3%, respectively, for daidzein, and correspondingly, 25.2 +/- 5.3, 13.4 +/- 2.1 and 15.8 +/- 2.7% for genistein), underscoring the trend toward nonlinear pharmacokinetics. Equol was identified as a metabolite in 30% of women; it was present consistently in urine and blood from the same subjects. Its delayed appearance was consistent with colonic synthesis. On the basis of the pharmacokinetics, optimum steady-state serum isoflavone concentrations would be expected from modest intakes of soy foods consumed regularly throughout the day rather than from a single highly enriched product.

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.

The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones.

Equol [7-hydroxy-3-(4'-hydroxyphenyl)-chroman] is a nonsteroidal estrogen of the isoflavone class. It is exclusively a product of intestinal bacterial metabolism of dietary isoflavones and it possesses estrogenic activity, having affinity for both estrogen receptors, ERalpha and ERbeta. Equol is superior to all other isoflavones in its antioxidant activity. It is the end product of the biotransformation of the phytoestrogen daidzein, one of the two main isoflavones found in abundance in soybeans and most soy foods. Once formed, it is relatively stable; however, equol is not produced in all healthy adults in response to dietary challenge with soy or daidzein. Several recent dietary intervention studies examining the health effects of soy isoflavones allude to the potential importance of equol by establishing that maximal clinical responses to soy protein diets are observed in people who are good "equol-producers." It is now apparent that there are two distinct subpopulations of people and that "bacterio-typing" individuals for their ability to make equol may hold the clue to the effectiveness of soy protein diets in the treatment or prevention of hormone-dependent conditions. In reviewing the history of equol, its biological properties, factors influencing its formation and clinical data, we propose a new paradigm. The clinical effectiveness of soy protein in cardiovascular, bone and menopausal health may be a function of the ability to biotransform soy isoflavones to the more potent estrogenic isoflavone, equol. The failure to distinguish those subjects who are "equol-producers" from "nonequol producers" in previous clinical studies could plausibly explain the variance in reported data on the health benefits of soy.

Evidence for lack of absorption of soy isoflavone glycosides in humans, supporting the crucial role of intestinal metabolism for bioavailability.

BACKGROUND: The isoflavones daidzein and genistein occur naturally in most soyfoods, conjugated almost exclusively to sugars. Controversy exists regarding the extent of bioavailability of isoflavone glycosides, and the mechanism of intestinal absorption of isoflavones in humans is unclear. Evidence from intestinal perfusion and in vitro cell culture studies indicates that isoflavone glycosides are poorly absorbed, yet isoflavones are bioavailable and appear in high concentrations in plasma, irrespective of whether they are ingested as aglycones or glycoside conjugates. OBJECTIVE: The objective was to determine whether isoflavone glycosides are absorbed from the intestine intact and reach the peripheral circulation unchanged. DESIGN: Plasma was collected at timed intervals before and after healthy adults ingested 50 mg of one of the isoflavone beta-glycosides (daidzin or genistin) or 250 mL soymilk containing mainly isoflavone glycosides. Electrospray ionization mass spectrometry was used to detect daidzin and genistin after solid-phase extraction of these conjugates from plasma. Bioavailability of isoflavones was confirmed by gas chromatography-mass spectrometry analysis. RESULTS: Specific and sensitive electrospray mass spectrometry failed to detect even traces of daidzin or genistin in plasma collected 1, 2, and 8 h after their ingestion as pure compounds or in a soyfood matrix. However, plasma was enriched in isoflavones that were hydrolyzable with a combined beta-glucuronidase and sulfatase enzyme preparation. CONCLUSION: Isoflavone glycosides are not absorbed intact across the enterocyte of healthy adults, and their bioavailability requires initial hydrolysis of the sugar moiety by intestinal beta-glucosidases for uptake to the peripheral circulation.