***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: The objective of this study was to assess synergistic antioxidant properties of vitamin C and isoflavones . The design was a placebo-controlled crossover trial : 500 mg vitamin C , 5 mg/kg body weight isoflavones , 500 mg vitamin C plus 5 mg/kg body weight isoflavones , or placebo .  Total lipid peroxides , plasma vitamin C , and blood pressure were measured . Eight of 10 healthy postmenopausal women completed the study . A multiple analysis of variance was performed and least-squares difference post-hoc test utilized to determine where differences occurred . Significance was defined as P < .05 . There was a significant reduction in total lipid peroxides between baseline and isoflavone treatments ( 3.22+/-0.72 vs 2.47+/-0.82 nmol/mL , P < .05 ) . Mean systolic blood pressure was higher during isoflavone intervention than placebo ( 117+/-14 vs 125+/-15 mm Hg , P= .042 ) . Supplementation with vitamin C and isoflavones did not produce a synergistic antioxidant effect . A slight but significant increase in systolic blood pressure occurred with isoflavone supplementation . A larger study should be conducted to fully explore the potential interactions between these antioxidants The objectives of the study were to clarify the relationship between blood pressure and mortality from stroke , heart disease , cardiovascular diseases and all causes of death among representative population of Japanese and to estimate category-specific excess mortality from stroke due to blood pressure ( BP ) level . The study design comprised a retrospective cohort study using the 1980 National Survey on Cardiovascular Diseases and identification of underlying causes of death using national vital statistics data . In 1994 , a 14-year follow-up cohort study was conducted among participants of the National Survey on Cardiovascular Diseases in 1980 , r and omly selected from the Japanese population . With a collaboration of 300 public health centres , which had conducted the original survey in 1980 , 91.4 % of the participants of the original survey could be followed up . Total observed person-years were 53 948 for men and 70 932 for women . During follow-up , 1327 deaths were observed . BP levels were significantly related to mortality from strokes , cardiovascular diseases and all causes of death for both sexes ( P<0.001 ) . Heart disease mortality was significantly related to BP levels among men ( P<0.05 ) while not among women . Estimated excess mortality was 130 % for men and 42 % for women and chiefly observed among moderate hypertensives ( 48 % for men and 16 % for women ) . In conclusion , high blood pressure was a risk factor for mortality from all causes as well as those from cardiovascular diseases , stroke and heart disease among Japanese . Since the major part of excess mortality was due to mild hypertension , a population strategy to reduce blood pressure should be encouraged BACKGROUND a small number of reports exist on the cognitive effects of soy isoflavones , the findings from which are mixed . Isoflavone efficacy is dependent upon conversion of glycosides contained in soy foods and supplements to the biologically active aglycons . Of particular interest is the production of the metabolite , equol , which is dependent upon intestinal microflora and an integrous digestive system , both being altered by age and age-associated conditions . Unfortunately , few studies enrolled adults over the age of 70 , and none included older men . OBJECTIVE we examined safety , feasibility and cognitive efficacy of soy isoflavone administration in older nondemented men and women ( age 62 - 89 years ) . DESIGN AND METHODS in this r and omised , placebo-controlled , double-blind pilot study , subjects ingested either 100 mg/day soy isoflavones ( glycoside weight ) or matching placebo tablets for 6 months . RESULTS active and placebo-treated subjects exhibited a comparable side-effect profile . Plasma levels of genistein and daidzein ( P < 0.001 ) , but not equol , increased with isoflavone administration . While similar at baseline , the two groups differed across 6 months of treatment on 8 of 11 cognitive tests administered . Isoflavone-treated subjects improved on tests of visual-spatial memory ( P < 0.01 ) and construction ( P = 0.01 ) , verbal fluency ( P < 0.01 ) and speeded dexterity ( P = 0.04 ) . Placebo-treated participants were faster than isoflavone-treated subjects on two tests of executive function ( P < 0.05 ) . CONCLUSIONS these data suggest that administration of 100 mg/day of isoflavones was well tolerated . Plasma genistein and daidzein levels , but not equol , increased with isoflavone administration . Finally , data support the potential cognitive effects of soy isoflavones in older adults BACKGROUND Soy foods contain several components ( isoflavones and amino acids ) that potentially affect bone . Few long-term , large clinical trials of soy as a means of improving bone mineral density ( BMD ) in late postmenopausal women have been conducted . OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and /or soy isoflavone consumption on skeletal health in late postmenopausal women . DESIGN We conducted a r and omized , double-blind , placebo-controlled clinical trial in 131 healthy ambulatory women aged > 60 y. Ninety-seven women completed the trial . After a 1-mo baseline period , subjects were r and omly assigned into 1 of 4 intervention groups : soy protein ( 18 g ) + isoflavone tablets ( 105 mg isoflavone aglycone equivalents ) , soy protein + placebo tablets , control protein + isoflavone tablets , and control protein + placebo tablets . RESULTS Consumption of protein powder and isoflavone pills did not differ between groups , and compliance with the study powder and pills was 80 - 90 % . No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers . However , there were significant negative correlations between total dietary protein ( per kg ) and markers of bone turnover ( P < 0.05 ) . CONCLUSIONS Because soy protein and isoflavones ( either alone or together ) did not affect BMD , they should not be considered as effective interventions for preserving skeletal health in older women . The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover . This trial was registered at Clinical Trials.gov as NCT00668447 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 Background and Purpose We estimated the incidence of first-ever cerebral infa rct ion in regard to its subtypes and analyzed their risk factors separately in a community-based prospect i ve cohort study in Japan . Methods Stroke-free subjects ( n=1621 ) aged ≥40 years were followed up for 32 years from 1961 . During this period , 298 cerebral infa rct ions occurred and were divided into 167 lacunar , 62 atherothrombotic , 56 cardioembolic , and 13 undetermined subtypes of infa rct ion on the basis of clinical information including brain imaging and autopsy findings . Results The age-adjusted incidence of lacunar infa rct ion ( 3.8 per 1000 person-years for men and 2.0 for women ) was higher than that of atherothrombotic infa rct ion ( 1.2 , 0.7 ) and cardioembolic infa rct ion ( 1.3 , 0.5 ) in both sexes . Time-dependent Cox ’s proportional hazard analysis revealed systolic blood pressure as well as age to be independent risk factors for all subtypes of cerebral infa rct ion except for cardioembolic infa rct ion in men . Additionally , ST depression on ECG , glucose intolerance , and smoking in men and left ventricular hypertrophy on ECG and body mass index in women remained significant risk factors for lacunar infa rct ion . ST depression was also significantly related to events of atherothrombotic infa rct ion in women . The risk of atrial fibrillation for cardioembolic infa rct ion was outst and ingly high in both sexes , and left ventricular hypertrophy and lower total cholesterol were additional risk factors for cardioembolic infa rct ion in women . Conclusions In this Japanese population , lacunar infa rct ion was the most common subtype of cerebral infa rct ion and had a greater variety of risk factors , including not only hypertension but also ECG abnormalities , diabetes , obesity , and smoking , than did atherothrombotic infa rct ion or cardioembolic infa rct ion The phytoestrogen genistein improves endothelial dysfunction in ovariectomized rats through a nitric oxide-dependent mechanism . We investigated whether genistein alters the balance between the nitric oxide products and endothelin-1 and influences endothelium-dependent vasodilation in postmenopausal women . Sixty healthy postmenopausal women were enrolled in the study . A double-blind , placebo controlled , r and omized design was employed . After a 4-week stabilization on a st and ard fat-reduced diet , participants to the study were r and omly assigned to receive either genistein ( n=30 ; 54 mg/day ) or placebo ( n=30 ) . Flow-mediated , endothelium-dependent vasodilation of the brachial artery , plasma nitric oxide breakdown products and endothelin-1 levels were measured at baseline and after 6 months of genistein therapy . The mean baseline level of nitrites/nitrates was 22+/-10 micromol/l and increased to 41+/-10 micromol/ml after 6 months of treatment . The mean baseline plasma endothelin-1 level was 14+/-4 pg/ml and decreased to 7+/-1 pg/ml following 6 months of treatment with genistein . The mean baseline ratio of nitric oxide to endothelin also significantly increased at the end of treatment . Flow-mediated , endothelium-dependent vasodilation of the brachial artery was 3.9+/-0.8 mm at baseline and increased to 4.4+/-0.7 mm after 6 months of treatment . Placebo-treated women showed no changes in plasma nitrites/nitrates , endothelin-1 levels and flow-mediated vasodilation . Genistein therapy improves flow-mediated endothelium dependent vasodilation in healthy postmenopausal women . This improvement may be mediated by a direct effect of genistein on the vascular function and could be the result of an increased ratio of nitric oxide to endothelin OBJECTIVE To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100‐mg soy isoflavone in postmenopausal women . METHODS In this double‐blind , placebo‐controlled study , 80 women were r and omly assigned to isoflavone ( n = 40 ) and placebo ( n = 40 ) treatment . The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment . Cardiovascular risk factors were assessed by evaluating plasma lipid levels , body mass index , blood pressure , and glucose levels in the 
    Output:
    
The effect was not lost on sensitivity analysis .
Subgroup analyses suggest greater effects in studies longer than 3 months , in Western population s , at lower doses , and in studies at lower risk of bias .
Soy isoflavone extracts significantly decreased SBP but not  DBP in adult humans , and no dose-response relationship was observed .