Bioavailability Of Isoflavones Research Articles

Overnight urinary excretion of isoflavones as an indicator for dietary isoflavone intake in Korean girls of pubertal age

Little is known about the bioavailability of isoflavones in children. Previous studies have shown that children excrete more isoflavone in urine compared with adults. Thus we examined the relationship between usual dietary isoflavone intake and the urinary excretion of isoflavonoids in Korean girls of pubertal age. Twelve girls each were selected from the lowest and the highest quartiles of isoflavone intake among 252 Korean girls aged 8-11 years. Age, BMI and sexual maturation stage were matched between the two groups. Dietary intakes for 3 d by diet record and overnight urine samples were collected at baseline and at 6 and 12 months. Total and individual isoflavone (daidzein, genistein and glycitein) intakes were calculated from diet records. The parent isoflavone compounds (daidzein, genistein and glycitein) and their metabolites (equol, O-desmethylangolensin (O-DMA), dihydrodaidzein and dihydrogenistein) present in the urine samples were analysed using liquid chromatography-MS. Intake levels of total and individual isoflavone compounds were significantly higher in the high isoflavone (HI) group than the levels in the low isoflavone (LI) group (P < 0.05). Urinary excretion of all isoflavone parent compounds was significantly higher in the HI group than in the LI group (P < 0.0001). Among isoflavone metabolites, only O-DMA and total metabolites were significantly different (P < 0.05). Total isoflavone intake was highly correlated with the urinary excretion of total parent compounds (r 0.68; P < 0.01), parent compounds plus their metabolites (r 0.66-0.69; P < 0.01) and total isoflavonoids (r 0.72; P < 0.0001). In conclusion, overnight urinary excretion of total isoflavonoids is a reliable biomarker of usual isoflavone intake in Korean girls of pubertal age.

Combination of Genistin and Fructooligosaccharides Prevents Bone Loss in Ovarian Hormone Deficiency

We have reported that soy isoflavones are capable of preventing loss of bone mineral density (BMD) in rats due to ovariectomy. The intestinal microflora is important in rendering soy isoflavones bioavailability by facilitating their conversion to equol. Hence, substances that can modulate the intestinal microflora could affect the bioavailability of isoflavones. The purpose of this study was to examine whether combination of genistin and fructooligosaccharides (FOS), a prebiotic, can enhance the effects of soy isoflavones on bone in ovariectomized (OVX) female rats. Forty-eight 90-day-old female Sprague-Dawley rats were either sham-operated (Sham; one group) or Ovx (three groups) and were placed on dietary treatment for 50 days. The Sham and one Ovx group received a control diet, and the remaining Ovx groups received genistin-rich isoflavones diet (Ovx+G) or genistin-rich isoflavones and FOS diet (Ovx+G+FOS). After 50 days, blood and bone specimens were collected for analysis. The genistin-rich isoflavones diet was able to significantly increase the whole-body, right femur, and fourth lumbar BMD by 1.6%, 1.48%, and 1.3%, respectively in comparison with the Ovx control. The combination of genistin-rich isoflavones diet and 5% FOS further increased whole-body, right femur, and fourth lumbar BMD more compared to the genistin-rich isoflavones diet. Our findings suggest that although a genistin-rich isoflavones diet can increase the BMD in rats with Ovx-induced bone loss, combination of genistin-rich isoflavones and FOS had greater effect in preventing bone loss in this rat model.

Effects of the β‐glycosidase reaction on bio‐conversion of isoflavones and quality during tofu processing

Isoflavones are the most common group of phytoestrogens which are present in significantly large amounts in soybean and soy products such as tofu. Isoflavones occur naturally in glycoside forms having lower bioavailability than their aglycone forms. beta-Glycosidase acts as a bio-catalyst for the conversion of isoflavone glycosides to isoflavone aglycones, raising the bioavailability of isoflavones; therefore, it can be used to improve the quality of tofu. We need to establish process conditions for the optimal outcome of the enzyme reaction in tofu. By using the beta-glycosidase (0.02% w/v) reaction at 55 degrees C for 30 min, a maximum 84.5% conversion of isoflavone glycoside to isoflavone aglycone was obtained. The enzyme reaction caused no significant effects on the sensory acceptability of soft tofu. The hardness of enzyme-treated hard tofu increased with the coagulant amount whereas prolonged heating resulted in decrease of hardness. Incorporation of enzyme reaction before the coagulation process during soft tofu processing provided a sufficient bio-conversion of isoflavones at optimal conditions. beta-Glycosidase can be effectively used for the bioconversion of isoflavones in soft tofu manufacturing process at optimal reaction conditions before the onset of coagulation process.

The red clover isoflavone irilone is largely resistant to degradation by the human gut microbiota

Intestinal bacteria may influence bioavailability and physiological activity of dietary isoflavones. We therefore investigated the ability of human intestinal microbiota to convert irilone and genistein in vitro. In contrast to genistein, irilone was largely resistant to transformation by fecal slurries of ten human subjects. The fecal microbiota converted genistein to dihydrogenistein, 6'-hydroxy-O-desmethylangolensin, and 2-(4-hydroxyphenyl)-propionic acid. However, considerable interindividual differences in the rate of genistein degradation and the pattern of metabolites formed from genistein were observed. Only one metabolite, namely dihydroirilone, was formed from irilone in minor amounts. In further experiments, Eubacterium ramulus, a prevalent flavonoid-degrading species of the human gut, was tested for transformation of irilone. In contrast to genistein, irilone was not converted by E. ramulus. Irilone only differs from genistein by a methylenedioxy group attached to the A-ring of the isoflavone skeleton. This substitution obviously restricts the degradability of irilone by human intestinal bacteria.

Influence of ethnic origin (Asian v. Caucasian) and background diet on the bioavailability of dietary isoflavones

Soya isoflavones: genistein and daidzein are increasingly consumed in Western countries. Their beneficial effects are discussed considering nutrition and health in Asia. The present study aimed to check whether chronic ingestions, ethnic origin and dietary context can influence soya phyto-oestrogen bioavailability. Two prospective trials were carried out to blindly assess the pharmacokinetics after acute and chronic intake of soya-based cheese (45.97 (sd1.57) mg isoflavones) taken once a day for 10 d. Twelve healthy young Asians immersed for 2 months in France were randomised in a cross-over design to compare the influence of a Western v. Asian dietary context. The second trial partly nested in the first one, compared Asians under the Western diet to twelve healthy young male Caucasians under the same diet. All volunteers were non-equol producers. After an acute intake of soya in Western diet, Asians exhibited higher maximum concentration measured in plasma (Cmax) and area under the plasma concentration-time curve (AUC) for genistein and daidzein than Caucasians (P = 0.005, 0.006, 0.032 and 0.008, respectively). In Caucasians under Western diet, AUC and Cmax values significantly increased after chronic intake. This was not the case for daidzein in Asians whatever the dietary context. For the first time, it is evidenced that on acute intake of soya cheese, Asians absorb soya phyto-oestrogens better than Caucasians, regardless of whether the background diet is Western or Asian. On chronic ingestions, AUC and Cmax values were increased for daidzein and genistein in Caucasians but not in Asians. There are ethnic differences in isoflavone pharmacokinetic and bioavailability. This may influence health outcomes.

Apparent bioavailability of isoflavones after intake of liquid and solid soya foods

Isoflavone (IFL) intake may provide numerous health benefits, but IFL bioavailability differences among soya foods remains uncertain. Urinary IFL excretion (UIE) was shown to provide a reliable surrogate for systemic IFL exposure and therefore can be used as a measure of 'apparent bioavailability' (AB). We investigated the AB of IFL in fourteen healthy adults, consuming two liquid and two solid soya foods in a crossover designed study. Volunteers consumed the foods with a self-selected breakfast, which was kept identical for all four soya items (soya nuts, soya milk, soya protein bar and soya protein powder drink in water; average 23.7 mg IFL, 88-96 % glycosides, by HPLC analysis) and collected all urine up to 26 h. Liquid foods showed initially higher UIE values than solid foods, but this difference was considerably reduced or disappeared entirely after 24-26 h. Conclusive AB results were obtained only after 24-26 h; earlier collections were not reliable. At 26 h, adjusted UIE values for daidzein (DE) were 20 micromol in the milk and bar and 17 micromol for the nut and powder; urinary genistein excretion was the highest in the milk group (10 micromol) followed by the nut, bar (both 6 micromol) and powder groups (5 micromol); the UIE for glycitein was the highest for bars (4 micromol), followed by powder and nuts (3 micromol), and milk (2 micromol). DE makes the largest contribution to urinary total IFL. The AB of IFL was found to be variable depending on the analyte and soya food consumed.

Effect of glycosidation of isoflavones on their bioavailability and pharmacokinetics in aged male rats

There are limited reports on the bioavailability and pharmacokinetics of isoflavones in elderly humans and aged animals. The present study was conducted to assess the effect of glycosidation of isoflavones on their bioavailability and pharmacokinetics in aged (20 month old) male Fischer-344 (F-344) rats. The F-344 rat, developed by the National Institute on Aging, is an inbred rat model that is commonly used for aging studies and resembles many features of aging humans. Three sources of isoflavones; Novasoy (a commercial supplement), a mixture of synthetic aglycons (daidzein, genistein and glycitein), and a mixture of synthetic glucosides (daidzin, genistin, and glycitin) were tested. Following administration, blood samples were collected at different times (0-48 h post-oral gavage and 0-8 h post-IV dosing). Plasma isoflavones and 7-hydroxy-3-(4'-hydroxyphenyl)-chroman (a metabolite of daidzein) were measured by LC/MS. The extent of absorption was determined by comparing the area under the curve (AUC) of the plasma-concentration time curve after intravenous (IV) administration with that following oral administration. The extent of bioavailability was then calculated as: %bioabailability = (AUC(or)/AUC(IV))x(Dose(IV)/Dose(or))x100. Bioavailabilities for genistein were significantly (p = 0.013) higher for the aglycon (35 +/- 9%) compared with the glucoside forms (11 +/- 3%). In contrast, the bioavailabilities for glycitein were significantly (p = 0.011) higher in Novasoy (27 +/- 13%) and the glucoside form (21 +/- 10%) compared with the aglycon (8 +/- 3%). No significant differences in the bioavailability of daidzein were observed in aged rats dosed with aglycon, glucoside or Novasoy. However, aged rats were able to produce equol as early as 8 h post-dosing. In summary, the source of isoflavones had significant effects on genistein and glycitein bioavailability in aged male rats.

Soybean isoflavones regulate dendritic cell function: implications in food allergy (79.16)

Abstract Peanuts and tree nuts are the most allergenic foods in children and adults in the U.S. Several allergens in peanut and soy share amino acid similarity by as much as 60%, yet soy allergy is less common and less severe compared to peanut allergy. Unlike peanuts, soybeans are rich in isoflavones such as genistein, daidzein and glycitein and are the most common source of isoflavones in the human food supply. Isoflavones are known to have anti-inflammatory and anti-oxidant properties. The maximum bioavailability of isoflavones is from the gut since they are quickly converted to inactive forms before entering the circulation. Therefore, we hypothesize that the active-isoflavones in the gut milieu are capable of modulating the initiation of immune responses to dietary-antigens by regulating DC function. In vitro, isoflavones inhibited lipopolysachharide (LPS) or cholera toxin (CT)-induced cell-surface expression of CD83, CD80 and CD86 in a dose dependent manner in human monocyte derived dendritic cells (MDDC). Isoflavone treatment augmented CT induced up-regulation of CXCR4 and CCR7. Isoflavone treated MDDC inhibited T cell proliferation in a mixed lymphocyte reaction and inhibited the secretion of Th2 cytokines. We hypothesize that these changes in DC function could induce tolerance to food allergens. Studies are underway to test this hypothesis in a peanut allergic mouse model.

Food matrix and isoflavones bioavailability in early post menopausal women: An European clinical study

The estrogenic effects of soy isoflavones (IF) on symptoms of menopause are of particular interest. The aim of the present study was to improve compliance of IF in two IF-enriched foods providing the same IF circulating levels in postmenopausal women. Forty-two healthy postmenopausal women (mean age: 53.28 years) were recruited for a randomized, crossover, multicenter trial conducted in the Netherlands, Italy and France. Over 18 days, volunteers were assigned to two groups and supplemented with two different IF-enriched foods (100 mg IF aglycones/two servings). The first group had to eat two biscuits daily for three days. After a wash-out period (11 d), they received cereal bars for three days. The second group started with the cereal bars and finished with biscuits. After IF intake, plasma and urinary levels of genistein, daidzein, O desmethyl angolensin and equol significantly increased and returned to baseline level after the washout period. There was no difference between biscuits and cereals bars intake, as shown by group values at each end of experimental period (day 4 or day 18). Both matrixes are comparable in terms of IF-circulating levels and could be used independently.

Orally Administered Isoflavones Are Present as Glucuronides in the Human Prostate

Better knowledge of the bioavailability and metabolism of isoflavones in prostate tissue is needed to further investigate their mechanisms of action in the context of prostate cancer prevention. A total of 12 men with benign prostatic hyperplasia received soy extract supplementation (3 Evestrel® capsules, providing a total of 112.5 mg isoflavones aglycone eq/day) for 3 days before prostate surgery. Blood and prostate tissues were sampled and metabolites were identified using electrospray ionization liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) and chemically synthesized standards of glucuronidated isoflavones. The main metabolites were the same in prostate tissue and in plasma, namely, 2 monoglucuronides of daidzein and 2 monoglucuronides of genistein. Concentrations of total isoflavones measured in prostate reached 1.05 ± 0.62 nmol/g tissue (range 0.30–2.23) at the time of sampling, 12 h after the last isoflavone supplementation. At that time point, prostate concentrations were lower than plasma concentrations in all volunteers: 0.47 nmol/g vs. 0.66 μ M for daidzein and 0.58 nmol/g vs. 0.78 μ M for genistein. Isoflavone mechanisms of action should thus be investigated in in vitro cell studies using physiological conditions, intracellular concentrations below 5 nmol/g and no intracellular deconjugation of the monoglucuronide metabolites.

Pharmacokinetics of the soybean isoflavone daidzein in its aglycone and glucoside form: a randomized, double-blind, crossover study

BackgroundThere are conflicting results in the literature on the bioavailability of isoflavones in the aglycone and the glucoside forms. ObjectiveThe objective was to investigate the pharmacokinetics of the soy isoflavone daidzein (DAI) on oral administration of both the aglycone and glucoside form in a human intervention study. In addition, the pharmacokinetics of the bacterial and oxidative metabolites of DAI was assessed. DesignSeven German men aged 22–30 y participated in a randomized, double-blind study in a crossover design. After ingestion of pure DAI or pure daidzein-7-O-β-d-glucoside (DG) (1 mg DAI aglycone equivalent/kg body weight), blood samples were drawn before isoflavone administration and 1, 2, 3, 4.5, 6, 8, 10, 12, 24, and 48 h after the dose. Urine was collected before and 0–6, 6–12, and 12–24 h after the intake of the isoflavones. The concentrations of DAI and its major bacterial and oxidative metabolites in plasma and urine were measured with isotope dilution capillary gas chromatography–mass spectrometry. ResultsThe systemic bioavailability (area under the curve; AUCinf), the maximal plasma concentration (Cmax), and the cumulative recovery of DAI in urine after administration of DG were 3–6 times greater than after the ingestion of DAI. Except for equol, which was formed by only one volunteer, all other quantified metabolites exhibited 2–12 times greater AUCinf, Cmax, and urinary recoveries after consumption of DG. ConclusionOur results show that DG exhibits a greater bioavailability than its aglycone when ingested in an isolated form.

Isoflavones and the prevention of breast and prostate cancer: new perspectives opened by nutrigenomics

Epidemiological evidence together with preclinical data from animal and in vitro studies strongly support a correlation between soy isoflavone consumption and protection towards breast and prostate cancers. The biological processes modulated by isoflavones, and especially by genistein, have been extensively studied, yet without leading to a clear understanding of the cellular and molecular mechanisms of action involved. This review discusses the existing gaps in our knowledge and evaluates the potential of the new nutrigenomic approaches to improve the study of the molecular effects of isoflavones. Several issues need to be taken into account for the proper interpretation of the results already published for isoflavones. Too often knowledge on isoflavone bioavailability is not taken into account; supra-physiological doses are frequently used. Characterization of the individual variability as defined by the gut microflora composition and gene polymorphisms may also help to explain the discrepancies observed so far in the clinical studies. Finally, the complex inter-relations existing between tissues and cell types as well as cross-talks between metabolic and signalling pathways have been insufficiently considered. By appraising critically the abundant literature with these considerations in mind, the mechanisms of action that are the more likely to play a role in the preventive effects of isoflavones towards breast and prostate cancers are reviewed. Furthermore, the new perspectives opened by the use of genetic, transcriptomic, proteomic and metabolomic approaches are highlighted.

Isoflavones in children and adults consuming soy

Soy and their isoflavones (IFLs) are believed to protect against breast cancer, particularly when exposure occurs during childhood. Little is known about the bioavailability of IFLs in children and how this is affected by oral antibiotics (OABX). We measured IFLs by LC/MS and found that the urinary IFL excretion rate (UIER) reflects circulating IFLs accurately when area-under-curve (AUC) and identical time intervals are used ( r = 0.93; p < 0.001). UIER in children and adults was determined when healthy and when on OABX by collecting urine in pairs of baseline and overnight specimen before and after consuming soy nuts, respectively. Compared to when healthy, children on OABX showed significantly decreased UIER but adults on OABX showed increased UIER ( p < 0.05). All 37 healthy children showed significantly higher UIERs compared to all 34 healthy adults. UIER is an adequate surrogate for determining IFL bioavailability and for measuring soy or IFL exposure in epidemiologic and other studies.

Higher bioavailability of isoflavones after a single ingestion of a soya-based supplement than a soya-based food in young healthy males

Soya isoflavones, genistein and daidzein, are the focus of numerous studies investigating their potential effects on health and results remain controversial. Bioavailability is clearly a crucial factor influencing their bioefficacy and could explain these discrepancies. This study aimed at assessing: (1) the isoflavone content of sixty-nine European soya-derivative products sold on the French market; (2) the bioavailability of isoflavones comparing supplement with food. Twelve healthy volunteers were recruited in a randomized two-way crossover trial and received 35 mg isoflavones equivalent aglycone either through supplements or through cheese, both containing different patterns of isoflavone conjugates and different daidzein:genistein ratios. A specific ELISA method was used to assess the plasma and urinary concentrations of isoflavones and thus the pharmacokinetic parameters, which were then normalized to mg of each isoflavone ingested. Results showed that the normalized Cmax of daidzein (P = 0.002) and similarly the normalized AUC0 --> infinity and Cmax of genistein (P = 0.002) from soya-based capsules were higher than that from soya-based cheese. In conclusion, this work completes studies on isoflavone bioavailability and presents new data regarding isoflavone concentrations in soya-derivative products. Assuming that isoflavone conjugation patterns do not influence isoflavone bioavailability, this study shows that isoflavones contained in capsules are more bioavailable than those contained in soya-based cheese. Although the supplement is more bioavailable, the relative importance of this is difficult to interpret as there is little evidence that supplements are biologically active in human subjects to date and further studies will be necessary for this specific supplement to prove its efficacy.

Low activities of intestinal lactase suppress the early phase absorption of soy isoflavones in Japanese adults

The contribution of lactase to isoflavone bioavailability has not been clarified. We evaluated the association between lactase activity and the bioavailability of isoflavone glucosides in Japanese adults. Twenty-six Japanese adult participants completed a study that included tests of breath hydrogen after a lactose load, orocecal transit time, and isoflavone glucoside absorption. Lactose malabsorbers were defined as those with an increase in breath hydrogen level (DeltaH(2)) of more than 20 ppm after a load of lactose (20 g). Participants ingested 200 ml soymilk, and serum isoflavones were analyzed until 480 min. Serum daidzein and genistein levels increased rapidly until 60 min, then slowly increased. The increases of serum isoflavones in the early phase, but not the later phase, were suppressed in lactose malabsorbers. DeltaH(2 max) after a load of lactose inversely correlated with serum daidzein levels at 30 min. The percentage of equol producers tended to be greater among lactose malabsorbers (P=0.067). Lactase may be involved in absorption of isoflavone glucosides in the small intestine, but the bacterial deglycosylation in the large intestine compensates the reduction of isoflavone absorption. The beneficial effect of isoflavones may not be impaired by low lactase activity.

骨粗鬆症の予防における大豆イソフラボンの生体利用性に関する研究

[in Japanese]

Characteristics of fermentation and bioavailability of isoflavones in Korean soybean paste (doenjang) with application of Bacillus sp. KH‐15

SummaryWe attempted to increase the fibrinolytic activity and aglycone contents of isoflavone in doenjang prepared with Bacillus sp. KH‐15. An initial rapid increase of viable cells was observed in the first 30 days followed by a gradual decrease to 1.78 × 108 CFU g−1 wet weight. The amino type nitrogen sharply was increased after 15 days, and showed the highest level (788.7 mg%) after 90 days. The total nitrogen was increased from 2.21% to 2.52% of final content after 90 days. Soluble carbohydrate was increased to 32.9 mg g−1 for 60 days, and after 60 days, the content was slowly decreased to 29.5 mg g−1. A rapid increase in fibrinolytic and caseinolytic activities were observed in the first 30 and 45 days of fermentation followed by a gradual decrease to 2.54 and 144.5 U g−1, respectively. β‐Glucosidase activity also showed a similar change pattern of the caseinolytic and fibrinoytic activities. Daidzein and genistein were increased to the maximum level of 764.5 and 561.4 mg kg−1 at day 30, respectively. At day 90, the contents of daidzein and genistein were 661.5 and 524.9 mg kg−1, respectively. The rats were fed a diet supplemented with either doenjang powder prepared with Bacillus sp. KH‐15 (D‐1 group) or commercial doenjang powder (D‐2 group) for 40 days. The level of serum total isoflavones in the D‐1 group was significantly higher than that in the D‐2 group.

Dietary combination of soy with a probiotic or prebiotic food significantly reduces total and LDL cholesterol in mildly hypercholesterolaemic subjects

We hypothesized that a dietary combination of soy with either a probiotic (yoghurt) or a prebiotic (resistant starch) would result in enhanced lipid-lowering effects compared with a control soy diet, possibly via improvements in isoflavone bioavailability. Mildly hypercholesterolaemic subjects (men and post-menopausal women) older than 45 years were recruited via the local media. Thirty-six subjects commenced the study; five withdrew. Soy+probiotic significantly decreased total cholesterol (4.7+/-2.0%; P=0.038) and soy+prebiotic significantly decreased total and low-density lipoprotein cholesterol (5.5+/-1.6%; P=0.003 and 7.3+/-2.2%; P=0.005, respectively). The bioavailabilities of daidzein, genistein or equol were not affected by probiotic or prebiotic consumption or associated with lipid changes. Dietary combination of soy with either a probiotic or a prebiotic resulted in significant lipid lowering, not related to isoflavone bioavailability.

Increased probiotic yogurt or resistant starch intake does not affect isoflavone bioavailability in subjects consuming a high soy diet

Objective Probiotics and prebiotics that affect gut microflora balance and its associated enzyme activity may contribute to interindividual variation in isoflavone absorption after soy intake, possibly enhancing isoflavone bioavailability. This study examined the effects of the consumption of bioactive yogurt (a probiotic) or resistant starch (a known prebiotic) in combination with high soy intake on soy isoflavone bioavailability. Methods Using a crossover design, chronic soy consumption was compared with soy plus probiotic yogurt or resistant starch in older male and postmenopausal females ( n = 31). Isoflavone bioavailability was assessed at the beginning and end of each 5-wk dietary period by sampling plasma and urine after a standardized soy meal. Results Chronic soy intake did not significantly affect plasma or urinary isoflavones after the soy meal and there were no significant effects of probiotic or resistant starch treatment. However, there were trends for increased circulating plasma daidzein and genistein after the probiotic treatment and for increased plasma daidzein and genistein 24 h after soy intake with resistant starch treatment. Neither treatment induced or increased equol production, although there was a trend for increased plasma equol in “equol-positive” subjects ( n = 12) after probiotic treatment. Conclusion The weak or absence of effects of probiotic yogurt or resistant starch supplement to a chronic soy diet suggests that gut microflora were not modified in a manner that significantly affected isoflavone bioavailability or metabolism.

Bioavailability of soy isoflavones in rats Part I: Application of accurate methodology for studying the effects of gender and source of isoflavones

There are limited and controversial reports about the effects of gender and source of isoflavones on their bioavailability. Moreover, several previous studies have not used appropriate methodology to determine the bioavailability of soy isoflavones, which requires comparing the area under the plasma concentration-time curve after both oral and intravenous injection (IV) administration. Therefore, the present study was conducted to determine the bioavailability of isoflavones from different sources following both oral and IV administration in male and female rats. Three sources of isoflavones; Novasoy (a commercial supplement), a mixture of synthetic aglycones (daidzein, genistein and glycitein) and a mixture of synthetic glucosides (daidzin, genistin and glycitin) were tested. Following administration, blood samples were collected at several time points (0, 10, 30 min and 1, 2, 8, 24, 48 h post oral gavage and 0, 10, 30, 45 min and 1, 2, 3, 4, 8 h post-IV dosing) and plasma isoflavones were measured by LC/MS. Bioavailability values for daidzein, genistein and glycitein were significantly (p <0.05) higher (up to sevenfold) in Novasoy and the glucoside forms of isoflavones compared with those of the aglycone forms. Moreover, significant (p <0.05) gender differences in the bioavailability of 7-hydroxyl-3-(4'-hydroxyphenyl)-chroman (a metabolite of daidzein), glycitein and daidzein were observed for Novasoy, with higher values in male rats. In summary, the source of isoflavones and the sex of rats had significant effects on isoflavone bioavailability.