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PubMed1997

Measurement and metabolism of isoflavonoids and lignans in the human male.

Asian men, who consume a low fat/high fibre soya-based diet, have very much lower incidence of prostate cancer than men from North America and Europe. The soya bean is a rich source of the isoflavonic phyto-oestrogens, daidzein, genistein and equol, compounds which may be cancer-protective in Asian populations. The lignans, enterolactone and enterodiol, plant oestrogens derived from cereals and vegetables, may act in a similar manner in vegetarian men. We report here on the measurement of isoflavonoids and lignans, by gas chromatography-mass spectrometry, in prostatic fluid of men from Asia and Europe and also on the metabolism of these compounds in Western men following dietary supplementation.

Adult↗
PubMed2002

High-throughput quantification of soy isoflavones in human and rodent blood using liquid chromatography with electrospray mass spectrometry and tandem mass spectrometry detection.

Soy-containing foods and dietary supplements are widely consumed for putative health benefits (e.g., cancer chemoprevention, beneficial effects on serum lipids associated with cardiovascular health, reduction of osteoporosis, relief of menopausal symptoms). However, studies of soy isoflavones in experimental animals suggest possible adverse effects as well (e.g., enhancement of reproductive organ cancer, modulation of endocrine function, anti-thyroid effects). This paper describes the development and validation of a sensitive high throughput method for quantifying isoflavones in blood from experimental animal and human studies. Serum samples containing genistein, daidzein, and equol were processed using reverse phase solid-phase extraction in the 96-well format for subsequent LC-ES/MS/MS or LC-ES/MS analysis using isotope dilution in conjunction with labeled internal standards. The method was validated by repetitive analysis of spiked blank serum and the intra-day and inter-day accuracy (88-99%) and precision (relative standard deviations from 3 to 13%) of measurement determined. The lower limit of quantification for all isoflavones was approximately 0.005 micro M using MS/MS detection, and 0.03 micro M using MS for genistein and daidzein. The degree of method performance, with respect to throughput, sensitivity and selectivity, makes this approach practical for analysis of large sample sets generated from mechanistic animal studies and human clinical trials of soy isoflavones.

Animals↗
PubMed2005

Experimental determination of octanol-water partition coefficients of quercetin and related flavonoids.

Octanol-water partition coefficient (log P) values were determined for flavonoids from the flavone, flavonol, flavanone, and isoflavonoid subclasses. Each flavonoid was dissolved in an octanol-water system and allowed to equilibrate, and then both fractions were analyzed by high-performance liquid chromatography. log P was calculated as log[ratio of the concentration in the octanol phase to the concentration in the aqueous phase at pH 7.4]. The aglycons were more lipophilic than any conjugate. The conjugate moiety had a more significant effect on log P than the aglycon moiety. Quercetin was the least lipophilic aglycon (log P = 1.82 +/- 0.32) and, together with kaempferol (log P = 3.11 +/-0.54), gave the most variable results. The isoflavones genistein and daidzein and the isoflavone metabolite equol gave relatively high log P values (3.04 +/- 0.02, 2.51 +/- 0.06, and 3.20 +/- 0.13, respectively), while glycitein had an unexpectedly low value of 1.97 +/- 0.05. The conjugation characteristics and hydroxylation pattern were the most important determinants of log P in general, and log P was highly variable within the flavonoid subclass. The results are discussed in terms of further understanding of the in vivo fate of the flavonoids as important dietary bioactives.

Chemical Phenomena↗
PubMed2005

Identification of urolithin a as a metabolite produced by human colon microflora from ellagic acid and related compounds.

Dietary ellagic acid and related polyphenols are metabolized in humans to dibenzopyran-6-one derivatives, and the microbial origin of these metabolites has been suggested. However, this has not been demonstrated so far. Fecal samples donated by six volunteers were incubated under anaerobic conditions, and aliquots were used to evaluate the fecal metabolism of ellagic acid, the ellagitannin punicalagin, and an ellagitannin rich extract from walnuts. The isoflavone daidzein was also incubated with the same fecal samples to follow the production of the microbial metabolites previously reported (dihydrogenistein, O-demethylangolensin, and equol) as a positive control of the system and to evaluate similarities between isoflavone and ellagic acid fecal flora metabolism. After fermentation the metabolite "urolithin A" (3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one) was produced from ellagic acid, punicalagin, and the ellagitannin extract in all the fecal cultures from different volunteers, but with very different production rates and concentrations. This large variability in the concentration of metabolite and kinetics of metabolite production is consistent with the large variability found in the excretion of these metabolites in urine in vivo after human consumption of ellagitannins, and with differences in the composition of the fecal microflora. No correlation between isoflavone and ellagic acid metabolism by fecal microflora was observed. The present study confirms the microbial origin of the recently reported in vivo generated hydroxy-6H-dibenzo[b,d]pyran-6-one derivatives in humans and is a further step in the study of the bioavailability and metabolism of ellagic acid and ellagitannins.

Bacteria↗
PubMed2005

Metabolism of glycitein (7,4'-dihydroxy-6-methoxy-isoflavone) by human gut microflora.

Gut microbial disappearance and metabolism of the soy isoflavone glycitein, 7,4'-dihydroxy-6-methoxyisoflavone, were investigated by incubating glycitein anaerobically with feces from 12 human subjects. The subjects' ages ranged from 24 to 53 years with a body mass index (BMI) of 20.9-25.8 kg/m(2) (mean BMI = 24.0 +/- 1.1 kg/m(2)). Glycitein disappearance followed an apparent first-order rate loss. Fecal glycitein disappearance rates for the subjects segregated into three different groups described as high (k = 0.67 +/- 0.14/h), moderate (k = 0.34 +/- 0.04/h), and low (k = 0.15 +/- 0.07/h) glycitein degraders (p < 0.0001). There was no dose effect on the disappearance rates for each subject from 10 to 250 microM glycitein (average k = 0.32 +/- 0.03/h, p > 0.05). Four putative glycitein metabolites, characterized by liquid chromatography-mass spectrometry (electrospray ionization using positive ionization mode), were dihydroglycitein, dihydro-6,7,4'-trihydroxyisoflavone, and 5'-O-methyl-O-desmethylangolensin. Two subjects produced a metabolite tentatively identified as 6-O-methyl-equol, and one subject produced daidzein as an additional metabolite of glycitein. These results show that glycitein is metabolized by human gut microorganisms and may follow metabolic pathways similar to other soy isoflavones.

Adult↗
PubMed2000

Synthesis of haptens and conjugates for ELISAs of phytoestrogens. Development of the immunological tests.

Seven carboxylic acid haptens of isoflavonoids were synthesized, with the spacer arm on the oxygen atom at the C7 position for one series, with formononetin, daidzein, equol, biochanin A, and genistein, and at the C8 position for a second series, with only formononetin and daidzein. The different haptens were coupled to bovine serum albumin (BSA) and to swine thyroglobulin (Thyr). Polyclonal antibodies were generated against the BSA conjugates. Enzyme-linked immunosorbent assays (ELISAs) were developed based on competition between free phytoestrogens and the Thyr-hapten conjugates for specific antibodies. IC(50) values of the standard curves ranged between 0.8 and 20 ng/mL that is, 0.3 and 9.2 pmol/well. The antibodies obtained should be useful for assays in vegetable matter as well as in biological fluids after a separation step. These ELISAs should be valuable also in the food industry to control phytoestrogen concentrations prior to and after processing.

Animals↗
PubMed2004

Prediction of ligand binding affinity and orientation of xenoestrogens to the estrogen receptor by molecular dynamics simulations and the linear interaction energy method.

Exposure to environmental estrogens has been proposed as a risk factor for disruption of reproductive development and tumorigenesis of humans and wildlife (McLachlan, J. A.; Korach, K. S.; Newbold, R. R.; Degen, G. H. Diethylstilbestrol and other estrogens in the environment. Fundam. Appl. Toxicol. 1984, 4, 686-691). In recent years, many structurally diverse environmental compounds have been identified as estrogens. A reliable computational method for determining estrogen receptor (ER) binding affinity is of great value for the prediction of estrogenic activity of such compounds and their metabolites. In the presented study, a computational model was developed for prediction of binding affinities of ligands to the ERalpha isoform, using MD simulations in combination with the linear interaction energy (LIE) approach. The linear interaction energy approximation was first described by Aqvist et al. (Aqvist, J.; Medina, C.; Samuelsson, J. E. A new method for predicting binding affinity in computer-aided drug design. Protein Eng. 1994, 7, 385-391) and relies on the assumption that the binding free energy (DeltaG) depends linearly on changes in the van der Waals and electrostatic energy of the system. In the present study, MD simulations of ligands in the ERalpha ligand binding domain (LBD) (Shiau, A. K.; Barstad, D.; Loria, P. M.; Cheng, L.; Kushner, P. J.; Agard, D. A.; Greene, G. L. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 1998, 95, 927-937), as well as ligands free in water, were carried out using the Amber 6.0 force field (http://amber.scripps.edu/). Contrary to previous LIE methods, we took into account every possible orientation of the ligands in the LBD and weighted the contribution of each orientation to the total binding affinity according to a Boltzman distribution. The training set (n = 19) contained estradiol (E2), the synthetic estrogens diethylstilbestrol (DES) and 11beta-chloroethylestradiol (E2-Cl), 16alpha-hydroxy-E2 (estriol, EST), the phytoestrogens genistein (GEN), 8-prenylnaringenin (8PN), and zearalenon (ZEA), four derivatives of benz[a]antracene-3,9-diol, and eight estrogenic monohydroxylated PAH metabolites. We obtained an excellent linear correlation (r(2) = 0.94) between experimental (competitive ER binding assay) and calculated binding energies, with K(d) values ranging from 0.15 mM to 30 pM, a 5 000 000-fold difference in binding affinity. Subsequently, a test set (n = 12) was used to examine the predictive value of our model. This set consisted of the synthetic estrogen 5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol (THC), daidzein (DAI), equol (EQU) and apigenin (API), chlordecone (KEP), progesterone (PRG), several mono- and dihydroxylated PAH metabolites, and two brominated biphenyls. The predicted binding affinities of these estrogenic compounds were in very good agreement with the experimental values (average deviation of 0.61 +/- 0.4 kcal/mol). In conclusion, our LIE model provides a very good method for prediction of absolute ligand binding affinities, as well as binding orientation of ligands.

Animals↗
PubMedDate not supplied

Isolation and identification of "diazepam-like" compounds from bovine urine.

Attempts to isolate the putative endogenous ligand for the benzodiazepine receptor from bovine urine resulted in the identification of three isoflavans: equol (1), 3',7-dihydroxyisoflavan (2), and 4'-hydroxy-7-methoxyisoflavan (9), as "diazepam-like" compounds. 3-Chloro-9H-carbazole (17) was found to enhance the binding of diazepam in the benzodiazepine receptor binding assay. Pinosylvine monomethyl ether (18), indigo (20), and indirubin (21) were isolated as inactive compounds.

Animals↗
PubMed1995

Metabolism of daidzein and genistein by intestinal bacteria.

The isoflavones daidzein [1] and genistein [2] were fermented with human fecal bacteria under anaerobic conditions. Dihydrodaidzein [3], benzopyran-4,7-diol,3-(4-hydroxyphenyl) [4], and equol [5] were isolated from the fermentation broth of 1. Only one metabolite, dihydrogenistein [6], was isolated and characterized from the fermentation broth of 2. Metabolites 3-6 were identified by spectral methods.

Bacteria↗
PubMed1998

Detection of weak estrogenic flavonoids using a recombinant yeast strain and a modified MCF7 cell proliferation assay.

A newly developed recombinant yeast strain, in which the human estrogen receptor has been stably integrated into the genome of the yeast, was used to gain information on the estrogenic activity of a large series of dietary flavonoids. Among 23 flavonoids investigated, 8 were found to markedly stimulate the transcriptional activity of the human estrogen receptor in the yeast assay increasing transcriptional activity 5-13-fold above background level, corresponding to EC50 values between 0.1 and 25 microM. Five compounds increased the transcriptional activity 2-5-fold over the control, with EC50 values ranging from 84 to 102 microM, whereas the remaining flavonoids were devoid of activity. The most potent flavonoid estrogens tested were naringenin, apigenin, kaempferol, phloretin, and the four isoflavonoids equol, genistein, daidzein, and biochanin A. With the exception of biochanin A, the main feature required to confer estrogenicity was the presence of a single hydroxyl group in the 4'-position of the B-ring of the flavan nucleus, corresponding to the 4-position on phloretin. The estrogenic potency of the flavonoids was found to be 4 000-4 000 000 times lower than that observed for 17beta-estradiol, when compared on the basis of EC50 values. The estrogenic activity of the dietary flavonoids was further investigated in estrogen-dependent human MCF7 breast cancer cells. In this system several of the flavonoids were likewise capable of mimicking natural estrogens and thereby induce cell proliferation. Similar structural requirements for estrogenic activity were found for the two assays. The present results provide evidence that several of the flavo-estrogens possess estrogenic properties comparable in activity to the well-established isoflavonoid estrogens. The use of Alamar Blue, a vital dye which is metabolically reduced by cellular enzymes to a fluorescent product, was found to greatly simplify the MCF7 cell-based estrogen screen, making this mammalian assay applicable as a large-scale screening tool for estrogenic compounds.

Breast Neoplasms↗
PubMed2003

Urinary and serum concentrations of seven phytoestrogens in a human reference population subset.

Diets rich in naturally occurring plant estrogens (phytoestrogens) are strongly associated with a decreased risk for cancer and heart disease in humans. Phytoestrogens have estrogenic and, in some cases, antiestrogenic and antiandrogenic properties, and may contribute to the protective effect of some diets. However, little information is available about the levels of these phytoestrogens in the general US population. Therefore, levels of phytoestrogens were determined in urine (N=199) and serum (N=208) samples taken from a nonrepresentative subset of adults who participated in NHANES III, 1988-1994. The phytoestrogens quantified were the lignans (enterolactone, enterodiol, matairesinol); the isoflavones (genistein, daidzein, equol, O-desmethylangolensin); and coumestrol (urine only). Phytoestrogens with the highest mean urinary levels were enterolactone (512 ng/ml), daidzein (317 ng/ml), and genistein (129 ng/ml). In serum, the concentrations were much less and the relative order was reversed, with genistein having the highest mean level (4.7 ng/ml), followed by daidzein (3.9 ng/ml) and enterolactone (3.6 ng/ml). Highly significant correlations of phytoestrogen levels in urine and serum samples from the same persons were observed for enterolactone, enterodiol, genistein, and daidzein. Determination of phytoestrogen concentrations in large study populations will give a better insight into the actual dietary exposure to these biologically active compounds in the US population.

Adult↗
PubMed1972

The formation of glucosides of isoflavones and of some other phenols by rabbit liver microsomal fractions.

1. Rabbit liver microsomal fractions in vitro effected the transfer of glucuronic acid from UDP-glucuronic acid to biochanin A, formononetin, daidzein, genistein and equol. Only monoglucuronides were formed. 2. The same isoflavones were converted into monoglucosides when UDP-[6-(3)H]glucose was substituted for UDP-glucuronic acid in the incubation medium in vitro. The glucosides were formed in much lesser yield than were the glucuronides. 3. The glucoside of genistein was identified as genistin (genistein 7-glucoside) by Sephadex chromatography and reverse isotope dilution. 4. The specificity of the glucuronyl- and glucosyl-transfer mechanisms was compared for a series of steroids and other phenols in addition to the isoflavones. It was concluded that separate transferases were responsible for the formation of the two types of glycosides.

Animals↗
PubMed1998

Isoflavone content of infant foods and formulas.

OBJECTIVE: The purpose of this study was to investigate the phytoestrogen content of different foods, formulas and drinks that may be consumed by infants during their first year of life in an attempt to define levels of exposure on different feeding regimens. METHODOLOGY: High performance liquid chromatography (HPLC) was used to determine the levels of genistein, daidzein, biochanin A, formononetin and equol in samples purchased from Australian supermarkets. Single lots of duplicate or triplicate samples of soy beverages, cow's milks, infant formulas and infant yoghurts were analysed. RESULTS: All foods tested contained isoflavones, at varying levels, suggesting that exposure to these compounds is almost ubiquitous. Casein-based infant formulas contained between 0.001 and 0.03 mg L(-1). Soy-based infant formulas ranged from 17.2 to 21.9 mg L(-1) with the values detected in yoghurt at similar levels to that of cow's milk. For comparison, the soy-based beverages (which are not recommended for use under 12 months of age) contained levels of isoflavones from 22.9 to 71.5 mg L(-1). CONCLUSIONS: Given the relatively broad choice of infant foods becoming available, exposure to dietary isoflavones during the first year of life is virtually ubiquitous. The exposure may be higher if soy infant formulas are consumed, however, the levels attained appear to fall within normal physiological boundaries.

Analysis of Variance↗
PubMed2003

Phytoestrogens: recent developments.

Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Based on their chemical structure, phytoestrogens can be classified into four main groups, i. e., isoflavonoids, flavonoids, stilbenes, and lignans. For each group, the chemistry, dietary sources and biotransformation of the most interesting compounds will be discussed. Since phytoestrogens are structurally very similar to the estrogen 17beta-estradiol, they may exhibit selective estrogen receptor modulating activities. Therefore, special attention will be given to the hormonal effects of various isoflavonoids, including genistein, daidzein, coumestrol and equol, several prenylated flavonoids, especially 8-prenylnaringenin, and the stilbene resveratrol. Furthermore, their non-hormonal effects will be discussed briefly. Finally, the latest developments on the potential protective properties of phytoestrogens and phytoestrogen-containing foods against hormone-dependent breast and prostate cancers and cardiovascular diseases, and as estrogen replacement therapy for postmenopausal women will be discussed.

Antineoplastic Agents, Phytogenic↗
PubMed1999

The bioavailability of non-nutrient plant factors: dietary flavonoids and phyto-oestrogens.

The bioavailability in human subjects of non-nutrient plant factors, including dietary flavonoids and phyto-oestrogens, is of great importance relative to their reported health protective effects. These effects include protection against heart disease, and also in the case of the phyto-oestrogens, hormone-dependent cancers. Epidemiological studies have shown flavonoid intake (mostly quercetin) to be inversely associated with mortality from CHD. Quercetin is a potent antioxidant in vitro, and protection against the oxidative damage to LDL implicated in atherogenesis has been suggested as a possible mechanism. Human subjects can absorb significant amounts of quercetin (particularly in the glucoside form) and it would appear to be sufficiently bioavailable to act as an antioxidant in vivo; however, following our recent study (J O'Reilly, TAB Sanders and H Wiseman, unpublished results), it is currently less clear whether quercetin really can act as an antioxidant in vivo. The isoflavone phyto-oestrogens genistein and daidzein are much less effective antioxidants than quercetin in vitro, however, they are well-absorbed by human subjects and appear to be sufficiently bioavailable to act as antioxidants in vivo. In our recent study (O'Reilly et al. 1998) lower plasma isoprostane concentrations and increased resistance of LDL to oxidation were observed following the high-isoflavone dietary phase compared with the low-isoflavone dietary phase. Considerable inter-individual variation in isoflavone metabolite excretion has been observed, in particular the production of equol (the gut bacterial metabolite of daidzein; a more potent antioxidant and more oestrogenic than daidzein), and this appears to be influenced by habitual diet. Further studies on the bioavailability of these non-nutrient plant factors and related influencing factors are clearly still required.

Biological Availability↗
PubMed1999

Effects of chemoprotective agents on the metabolic activation of the carcinogenic arylamines PhIP and 4-aminobiphenyl in human and rat liver microsomes.

Carcinogenic aromatic amines, including the heterocyclic amines, may pose a significant health risk to humans. To determine the potential for chemoprotective intervention against the carcinogenicity of these arylamines and to better understand their mechanism of action, a range of agents, most of them natural dietary constituents, was examined in vitro for their ability to modulate the N-hydroxylation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 4-aminobiphenyl (ABP), an initial step in their bioactivation. Experiments were conducted with rat and human liver microsomes. The agents (diallyl sulfide, indole-3-carbinol, alpha-angelicalactone, cafestol/kahweol palmitates, cafestol, kahweol, benzylisothiocyanate, genistin, formononetin, daidzin, equol, biochanin A, Oltipraz, tannic acid, quercetin, ethoxyquin, green tea, and black tea) comprised a variety of chemical classes that included sulfur-containing compounds, antioxidants, flavonoids, phytoestrogens, diterpenes, and polyphenols. Several of these agents, quercetin, ethoxyquin, and black tea, were found to strongly inhibit PhIP N-hydroxylation in rat liver microsomes, resulting in a nearly 85-90% decrease in activity at 100 microM or 0.2%. Tannic acid and green tea, in addition to these agents, were also strong inhibitors of ABP N-hydroxylation. In human liver microsomes, each of these agents was strongly inhibitory (approx 85-95% at 100 microM or 0.02%) of PhIP and ABP N-hydroxylation. Theaflavins and polyphenols were judged to be the primary inhibiting components in the teas, the theaflavins showing the most potent effect. These results demonstrate that chemoprotective agents can inhibit the bioactivation of carcinogenic arylamines, and this is likely to be one of the mechanisms of protection.

Aminobiphenyl Compounds↗
PubMed1999

Usual dietary consumption of soy foods and its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai.

Soy foods and certain soy constituents, particularly isoflavones, have been suggested to have potential cancer-inhibitory effects in laboratory and epidemiological studies. Chinese women in Shanghai consume high levels of soy foods and have low incidence rates of breast and other hormone-related cancers. To assess the usual dietary consumption of soy foods and evaluate the correlation of soy food consumption with the urinary excretion of isoflavonoids in overnight urine samples in this population, we analyzed data from 60 healthy women included in an ongoing population-based case-control study of breast cancer in Shanghai. Usual consumption of soy foods in the previous five-year period was assessed using a food-frequency questionnaire, and urinary excretion of daidzein, genistein, glycitein, equol, and O-desmethylangolensin was measured from overnight urine samples collected at the time of dietary assessment. Virtually all women (96.7%) in Shanghai consumed soy foods at least once a week. The median intake of soy food was 100.6 g/day, with 25th and 75th percentiles of 36.8 and 238.2 g, respectively. The median intake of isoflavones was 39.26 mg/day, and there was a nearly fourfold difference between the 25th and 75th percentiles of this measurement. With the increasing intake of soy foods, urinary excretion rates of total isoflavonoids and all individual major isoflavonoids were increased in a dose-response manner (trend test p < or = 0.05). At individual levels the urinary excretion rate of total isoflavonoids was correlated closely with dietary soy food intake, with a correlation coefficient of around 0.5 (p < 0.001). These results indicate that the urinary excretion rate of total isoflavonoids measured from overnight urine samples may reflect reasonably well the usual intake of soy foods in a population with a high level of soy food consumption.

Adult↗
PubMed2006

Randomised, controlled, cross-over trial of soy protein with isoflavones on blood pressure and arterial function in hypertensive subjects.

OBJECTIVE: To examine the effects of dietary soy/isoflavones on 24 hr blood pressure profiles and arterial function [systemic arterial compliance (SAC), pulse wave velocity (PWV) and brachial arterial flow mediated vasodilation (FMD)] compared to non legume-based plant protein without isoflavones, in hypertensive subjects. DESIGN: In a 6 month double-blind, placebo controlled, cross-over trial, 41 hypertensive subjects (26 men, 15 postmenopausal women), 30-75 years, received soy cereal (40 g soy protein, 118 mg isoflavones) and gluten placebo cereal, each for 3 months. RESULTS: Thirty-eight subjects completed protocol with results expressed as mean or mean change (+/-SEM) with each intervention. Soy increased urinary isoflavones (daidzein: 8-fold; genistein: 8-fold; equol: 9-fold; ODMA: 18-fold) with no change during gluten placebo. There was no difference in the change in individual 24 hr ambulatory BP parameters (SBP: 2 +/- 2 vs -1 +/- 1 mmHg, p = 0.21; DBP: 1 +/- 1 vs -1 +/- 1 mmHg, p = 0.06) central BP (cSBP: -4 +/- 2 vs 0 +/- 2 mmHg, p = 0.2) or the change in arterial function (FMD: 0.3 +/- 0.5 vs -0.2 +/- 0.5%, p = NS; SAC: 0.02 +/- 0.02 vs -0.02 +/- 0.02 U/mmHg, p = NS; PWV central: -0.2 +/- 0.2 vs 0.0 +/- 0.2 m/sec, p = NS; PWV peripheral: 0.01 +/- 0.3 vs -0.4 +/- 0.4 m/sec, p = NS) noted between interventions. Analysis of the area under curve of 24 hr BP outputs demonstrated that soy protein compared to gluten protein resulted in higher 24 hr systolic BP by 2.3 mmHg (p = 0.003), a higher daytime systolic BP by 3.4 mmHg (p = 0.0002) and a higher daytime diastolic BP by 1.4 mmHg (p = 0.008). Overall 24 hr diastolic BP, night systolic BP and night diastolic BP were not significantly different between groups. Furthermore, soy protein compared to gluten protein resulted in higher 24 hr heart rates by 3.5 bpm (p < 0.0001). CONCLUSIONS: In hypertensive subjects, compared to gluten placebo, soy dietary supplementation containing isoflavones had no effect on arterial function, on average 24 hr ambulatory blood pressure parameters or central blood pressure in men and women with hypertension. Area under the curve of 24 hr profiles demonstrated that daytime BP was higher after soy compared to gluten.

Adult↗