***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 7-Hydroxy-3-(4'-hydroxyphenyl)-chroman ( S-equol ) is a specific end-metabolite formed in the biotransformation of the dietary soy isoflavones daidzin and daidzein by intestinal bacteria . The frequency of equol production varies among individuals and population s , and it is suggested that the efficacy of soy foods differs depending on the ability of an individual to produce equol . To develop a st and ardized approach to define equol-producer status that can be universally adopted to differentiate these 2 distinct population s , we measured isoflavones in serum and urine collected from a cohort of 41 healthy adults , comprising 29 vegetarians and 12 nonvegetarians , after consuming 2 x 250 mL/d soy milk on 3 consecutive days .  Serum and urinary daidzein and S-equol concentrations were analyzed by MS . Serum S-equol and daidzein concentrations ranged from 10.3 - 139 nmol/L ( 2.5 - 33.6 microg/L ) and 16 - 1401 nmol/L ( 4.0 - 356 microg/L ) , respectively , whereas in urine the corresponding concentrations ranged from 16 - 12,574 nmol/L ( 4 - 3043 microg/L ) and 539 - 26,834 nmol/L ( 137 - 6816 microg/L ) , respectively . The log10-transformed urinary S-equol : daidzein ratio provided a clearer distinction of equol-producer status than the absolute serum or urinary S-equol concentrations because it is independent of isoflavone intake and minimizes interindividual variation in isoflavone pharmacokinetics or differences in analytical method ologies . A threshold value for the log10-transformed urinary S-equol : daidzein ratio of -1.75 provided a demarcation to define equol-producer status . The frequency of equol producers in the vegetarians was 59 % , similar to the reported frequency in Japanese adults consuming soy , and much higher than for nonvegetarian adults ( 25 % ) , suggesting that dietary components other than soy influence S-equol synthesis by intestinal bacteria OBJECTIVES It has been suggested that isoflavones protect the cardiovascular system , in part by improving lipid profile . The purpose of the present research was to examine the effect of a 12-week soy isoflavone supplementation on lipoprotein status and platelet thromboxane A2 receptor density . METHODS Twenty-nine healthy postmenopausal women were invited to take part in a r and omised study to receive either 100 mg/day isoflavone supplement ( n=15 ) or identical placebo capsules ( n=14 ) . Blood sample s obtained at baseline and after 12 weeks were analysed for isoflavones , total cholesterol , high density lipoprotein cholesterol , triglycerides , glucose , insulin , estradiol , testosterone , gonadotrophins , sex hormone-binding globulin ( SHBG ) and platelet thromboxane A2 receptor density . Blood pressure measurements , body mass index , subcutaneous fat at entrance and at the end of treatment were also registered . Changes in variables between groups were compared by ANOVA for repeated measures . RESULTS Blood pressure , body mass index , subcutaneous fat , insulin , serum lipoprotein , sex hormones and SHBG did not differ among groups . However , platelet thromboxane A2 receptor density declined significantly ( from 181.9+/-30.9 to 115.2+/-16.2 fmol/10(8 ) platelets ) in the experimental group , remaining mostly unchanged in the placebo group ( 176.3+/-27.3 to 170.4+/-28.2 fmol/10(8 ) platelets ) . The dissociation constant ( Kd ) values were unchanged . The change in platelet thromboxane A2 receptors correlated negatively with isoflavones serum concentration ( r=-0.59 , p<0.001 ) . CONCLUSIONS In this study we demonstrated that the beneficial effects of isoflavones in menopausal women could be more related to platelet function than to improving classical cardiovascular risk factors Objective : The phytoestrogen genistein has been shown to be the most efficacious in clinical and experimental studies . We studied whether genistein treatment affects some cardiovascular risk markers in postmenopausal women . Design : Sixty healthy postmenopausal women , who were 52 to 60 years of age , were enrolled in a 6-month double-blind , placebo-controlled , r and omized study . After a 4-week stabilization on a st and ard fat-reduced diet , participants were r and omly assigned to receive either genistein ( n = 30 ; 54 mg/d ) or placebo ( n = 30 ) . At baseline and after a 6-month treatment , we measured fasting glucose , insulin , insulin resistance ( HOMA-IR ) , osteoprotegerin ( OPG ) , fibrinogen , and sex hormone-binding globulin ( SHBG ) . Results : By comparison with placebo , genistein treatment decreased significantly fasting glucose  ( genistein = −8.7 ± 2.3 % ; placebo = 3.2 ± 2.3 % ; P < 0.001 ) , fasting insulin ( genistein = −12 ± 3.33 % ; placebo = 36 ± 3.29 % ; P < 0.001 ) , and HOMA-IR  ( genistein = −14 ± 5.8 % ; placebo = 42 ± 0.6 % ; P < 0.001 ) . After genistein-treatment , fibrinogen decreased ( genistein = 3.18 ± 0.12 g/L ; placebo = 3.83 ± 0.04 g/L ; P < 0.001 ) with respect to placebo . In the genistein group , serum OPG was lower ( −2 ± 0.3 % ) than in placebo ( 9 ± 1.5 % ; P < 0.001 ) , and serum SHBG was higher ( 63 ± 3.8 nmol/L ) compared with placebo ( 53 ± 2.9 nmol/L ; P < 0.05 ) . Conclusion : Our study suggests that genistein may have a favorable effect on some cardiovascular markers Objective : To investigate whether 6 months of exercise combined with isoflavone supplementation could improve clinical risk factors that predispose to cardiovascular disease in obese postmenopausal women . Design : This was a r and omized , double-blind , controlled trial in which 50 healthy obese postmenopausal women were divided into two groups and assigned to isoflavone supplementation ( n = 25 ) or a placebo ( n = 25 ) for 1 year . For the last 6 months , both groups participated in an exercise program ( three times per week ) , at the end of which cardiovascular disease risk factors were compared between groups . Body composition ( using dual-energy x-ray absorptiometry ) , metabolic profile ( blood lipids , fasting insulin , fasting glucose , sex hormone-binding globulin , C-reactive protein ) were determined at baseline and at 6 and 12 months . Results : We observed a significant effect of exercise and isoflavone supplementation on body weight , total and abdominal fat mass ( kilograms and percentage ) , body mass index , appendicular fat-free mass , fat-free mass/fat mass ratio , and sex hormone-binding globulin , but not with exercise alone . No difference was observed for other biochemical characteristics , although the quantitative insulin sensitivity check index increased equally in both groups . Conversely , although not significant , we observed a tendency for a treatment effect on body mass index ( P = 0.07 ) and on absolute ( kilograms ) ( P = 0.07 ) and percentage of ( P = 0.053 ) abdominal fat mass , whereas no effect of treatment was found for other variables using the Mann-Whitney test . Conclusions : Compared to an aerobic exercise program alone , 70 mg/day of isoflavones combined with exercise may promote significant improvements in body composition parameters that are known to influence cardiovascular disease risk in postmenopausal women OBJECTIVE To determine whether a supplement of soy protein improves body composition , body fat distribution , and glucose and insulin metabolism in postmenopausal women without diabetes compared with an isocaloric casein placebo . DESIGN R and omized , double-blind , placebo-controlled 3-month trial . SETTING Clinical Research Center . PATIENT(S ) Fifteen postmenopausal women . INTERVENTION(S ) Computed tomographic scans at L4/L5 , dual energy x-ray absorptiometry , hyperglycemic clamps . MAIN OUTCOME MEASURE(S ) Total fat , total abdominal fat , visceral fat , subcutaneous abdominal fat , and insulin secretion . RESULT ( S ) Weight by dual energy x-ray absorptiometry did not change between groups ( + 1.38 + /- 2.02 kg for placebo vs. + 0.756 + /- 1.32 kg for soy , mean + /- SD ) . Total and subcutaneous abdominal fat increased more in the placebo group than in the soy group ( for differences between groups in total abdominal fat : + 38.62 + /- 22.84 cm(2 ) for placebo vs. -11.86 + /- 31.48 cm(2 ) for soy ; subcutaneous abdominal fat : + 22.91 + /- 28.58 cm(2 ) for placebo vs. -14.73 + /- 22.26 cm(2 ) for soy ) . Insulin secretion , visceral fat , total body fat , and lean mass did not differ between groups . Isoflavone levels increased more in the soy group . CONCLUSION ( S ) A daily supplement of soy protein prevents the increase in subcutaneous and total abdominal fat observed with an isocaloric casein placebo in postmenopausal women Results from a pilot project indicate that isoflavones and exercise could have an additive effect on body composition and clinical risk factors of CVD in postmenopausal women . The objective of the present study was to assess the combined effect of exercise and isoflavones in overweight-to-obese postmenopausal women . In this double-blind r and omised controlled trial , 100 overweight-to-obese ( BMI 29·9 ( sd 3·2 ) kg/m2 ) postmenopausal women were assigned to four groups : ( 1 ) placebo ( PLA ) ; ( 2 ) isoflavones ( ISO ) ; ( 3 ) exercise and placebo ( Ex+PLA ) ; ( 4 ) exercise and isoflavones ( Ex+ISO ) . The supplementation contained 70 mg/d of isoflavones . Exercise consisted of three weekly sessions of resistance training and aerob 
    Output:
    
Soy isoflavones were found to show great significance for the improvement of glucose metabolism , though marked heterogeneity was found between studies .
Although the results displayed a significant tendency in favor of soy isoflavones , it appears that genistein alone played an important role in improving glucose metabolism due to its low heterogeneity