***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 red grape constituent resveratrol possesses cancer chemopreventive properties in rodents . The hypothesis was tested that , in healthy humans , p.o . administration of resveratrol is safe and results in measurable plasma levels of resveratrol . A phase I study of oral resveratrol ( single doses of 0.5 , 1 , 2.5 , or 5 g ) was conducted in 10 healthy volunteers per dose level .  Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-t and em mass spectrometry and quantitated by high-performance liquid chromatography-UV . Consumption of resveratrol did not cause serious adverse events . Resveratrol and six metabolites were recovered from plasma and urine . Peak plasma levels of resveratrol at the highest dose were 539 ± 384 ng/mL ( 2.4 μmol/L , mean ± SD ; n = 10 ) , which occurred 1.5 h post-dose . Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold higher . The area under the plasma concentration curve ( AUC ) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol . Urinary excretion of resveratrol and its metabolites was rapid , with 77 % of all urinary agent-derived species excreted within 4 h after the lowest dose . Cancer chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 μmol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with cancer chemopreventive efficacy . However , the high systemic levels of resveratrol conjugate metabolites suggest that their cancer chemopreventive properties warrant investigation . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1246–52 Despite extensive research , the cardiovascular effects of coffee consumption in humans remain controversial . Our aim was to investigate the excretion of coffee phenols and the effects of filtered coffee consumption on oxidative stress and plasma homocysteine ( tHcy ) concentration in humans . The study consisted of a multiple-dose clinical supplementation trial and a single-dose study . In the long-term trial , 43 healthy nonsmoking men optionally consumed daily either no coffee , 3 cups ( 450 mL ) , or 6 cups ( 900 mL ) of filtered coffee for 3 weeks , while in the short-term study 35 subjects consumed a single dose of 0 , 1 ( 150 mL ) , or 2 cups ( 300 mL ) of coffee . Long-term consumption of coffee increased the urinary excretion of caffeic and ferulic acid . The change in the total excretion of phenolic acids in 3 and 6 cups groups represented 3.8 and 2.5 % of the amount ingested daily . Plasma tHcy concentrations increased nonsignificantly , but the consumption of coffee had neither short-nor long-term effects on lipid peroxidation or the activity of measured antioxidant enzymes . In conclusion , the consumption of filtered coffee does not have any detectable effects on lipid peroxidation in healthy nonsmoking men . The effect of coffee consumption on tHcy concentrations needs further investigation Subjects of this study consisted of 333 women ( aged 45 - 75 years ) drawn from a large United Kingdom prospect i ve study of diet and cancer , the European Prospect i ve Investigation of Cancer and Nutrition-Norfolk study . Using newly developed gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry methods incorporating triply (13)C-labeled st and ards , seven phytoestrogens ( daidzein , genistein , glycitein , O-desmethylangolensin , equol , enterodiol , and enterolactone ) were measured in 114 spot urines and 97 available serum sample s from women who later developed breast cancer . Results were compared with those from 219 urines and 187 serum sample s from healthy controls matched by age and date of recruitment .  Dietary levels were low , but even so , mean serum levels of phytoestrogens were up to 600 times greater than postmenopausal estradiol levels . Phytoestrogen concentrations in spot urine ( adjusted for urinary creatinine ) correlated strongly with that in serum , with Pearson correlation coefficients > 0.8 . There were significant relationships ( P < 0.02 ) between both urinary and serum concentrations of isoflavones across increasing tertiles of dietary intakes . Urinary enterodiol and enterolactone and serum enterolactone were significantly correlated with dietary fiber intake ( r = 0.13 - 0.29 ) . Exposure to all isoflavones was associated with increased breast cancer risk , significantly so for equol and daidzein . For a doubling of levels , odds ratios increased by 20 - 45 % [ log(2 ) odds ratio = 1.34 ( 1.06 - 1.70 ; P = 0.013 ) for urine equol , 1.46 ( 1.05 - 2.02 ; P = 0.024 ) for serum equol , and 1.22 ( 1.01 - 1.48 ; P = 0.044 ) for serum daidzein ] . These estimates of risk are similar to those established for estrogens and and rogens in postmenopausal breast cancer but need confirmation in larger studies 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 aim ed 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 r and omized 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 Green tea has been shown to exhibit cancer-preventive activities in pre clinical studies . Its principal active components include epigallocatechin gallate ( EGCG ) , epigallocatechin ( EGC ) , epicatechin ( EC ) , and epicatechin gallate , of which EGCG is the most abundant and possesses the most potent antioxidative activity . We performed a Phase I pharmacokinetic study to determine the systemic availability of green tea catechins after single oral dose administration of EGCG and Polyphenon E ( decaffeinated green tea catechin mixture ) .  Twenty healthy subjects ( five subjects/dose level ) were r and omly assigned to one of the dose levels ( 200 , 400 , 600 , and 800 mg based on EGCG content ) . All subjects were r and omly crossed-over to receive the two catechin formulations at the same dose level . Blood and urine sample s were collected for up to 24 h after oral administration of the study medication . Tea catechin concentrations in plasma and urine sample s were determined using high-performance liquid chromatography with the coulometric electrode array detection system . After EGCG versus Polyphenon E administration , the mean area under the plasma concentration-time curves ( AUC ) of unchanged EGCG were 22.5 versus 21.9 , 35.4 versus 52.2 , 101.9 versus 79.7 , and 167.1 versus 161.4 min x microg/ml at the 200- , 400- , 600- , and 800-mg dose levels , respectively . EGC and EC were not detected in plasma after EGCG administration and were present at low/undetectable levels after Polyphenon E administration . High concentrations of EGC and EC glucuronide/sulfate conjugates were found in plasma and urine sample s after Polyphenon E administration . There were no significant differences in the pharmacokinetic characteristics of EGCG between the two study medications . The AUC and maximum plasma concentration ( Cmax ) of EGCG after the 800-mg dose of EGCG were found to be significantly higher than those after the 200- and 400-mg dose . The AUC and Cmax of EGCG after the 800-mg dose of Polyphenon E were significantly higher than those after the three lower doses . We conclude that the two catechin formulations result ed in similar plasma EGCG levels . EGC and EC were present in the body after the Polyphenon E administration ; however , they were present predominantly in conjugated forms . The systemic availability of EGCG increased at higher doses , possibly due to saturable presystemic elimination of orally administered green tea polyphenols Dietary estrogens , such as lignans , are similar in structure to endogenous sex steroid hormones and may act in vivo to alter hormone metabolism and subsequent cancer risk . The objective of this study was to examine the effect of dietary intake of a lignan-rich plant food ( flaxseed ) on urinary lignan excretion in postmenopausal women . This r and omized , cross-over trial consisted of three 7-week feeding periods during which 31 healthy postmenopausal women , ages 52 - 82 years , consumed their habitual diets plus 0 , 5 , or 10 grams of ground flaxseed per day . Urine sample s collected for 2 consecutive days during the last week of each feeding period were analyzed for lignan content ( enterodiol , enterolactone , and matairesinol ) by isotope dilution gas chromatography/mass spectrometry . Compared with the 0-gram flaxseed diet , consumption of 5 or 10 grams of flaxseed significantly increased excretion of enterodiol by 1,009 and 2,867 nmol/day , respectively ; significantly increased excretion of enterolactone by 21,242 and 52,826 nmol/day , respectively ; and significantly increased excretion of total lignans ( enterodiol + enterolactone + matairesinol ) by 24,333 and 60,640 nmol/day , respectively . Excretion of matairesinol was not significantly altered by flaxseed consumption . Consumption of flax , a significant source of dietary estrogens , in addition to their habitual diets increased excretion of enterodiol and enterolactone , but not matairesinol , in a dose-dependent manner in this group of postmenopausal women .  Urinary excretion of lignan metabolites is a dose-dependent biomarker of flaxseed intake within the context of a habitual diet Estimation of dietary intake of polyphenols is difficult , due to limited availability of food composition data and bias inherent to dietary assessment methods . The aim of the present study was to evaluate the associations between the intake of polyphenol-rich foods and the urinary excretion of several phenolic compounds and therefore explore whether these phenolic compounds could be used as a biomarker of intake . Fifty-three participants of the SU.VI.MAX study ( a r and omised primary -prevention trial evaluating the effect of daily antioxidant supplementation on chronic diseases ) collected a 24 h urine and a spot urine sample and filled a dietary record during a 2 d period . Thirteen polyphenols and metabolites , chlorogenic acid , caffeic acid , m-coumaric acid , gallic acid , 4-O-methylgallic acid , quercetin , isorhamnetin , kaempferol , hesperetin , naringenin , phloretin , enterolactone and enterodiol , were measured using HPLC-electrospray ionisation-MS-MS . In spot sample s apple consumption was positively correlated to phloretin , grapefruit consumption to naringenin , orange to hesperetin , citrus fruit consumption to both naringenin and hesperetin , with r coefficients ranging from 0.31 to 0.57 ( P < 0.05 ) . The combination of fruits and /or fruit juices was positively correlated to gallic acid and 4-O-methylgallic acid , isorhamnetin , kaempferol , hesperetin , naringenin and phloretin ( r 0.24 - 0 
    Output:
    
These data confirm the value of certain urinary polyphenols as biomarkers of intake .