***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 There are very limited data regarding the effects of blueberry flavonoid intake on vascular function in healthy humans . OBJECTIVES We investigated the impact of blueberry flavonoid intake on endothelial function in healthy men and assessed potential mechanisms of action by the assessment of circulating metabolites and neutrophil NADPH oxidase activity . DESIGN Two r and omized , controlled , double-blind , crossover human-intervention trials were conducted with 21 healthy men . Initially , the impact of blueberry flavonoid intake on flow-mediated dilation ( FMD ) and polyphenol absorption and metabolism was assessed at baseline and 1 , 2 , 4 , and 6 h after consumption of blueberry containing 766 , 1278 , and 1791 mg total blueberry polyphenols or a macronutrient- and micronutrient-matched control drink ( 0 mg total blueberry polyphenols ) . Second , an intake-dependence study was conducted ( from baseline to 1 h ) with 319 , 637 , 766 , 1278 , and 1791 mg total blueberry polyphenols and a control . RESULTS We observed a biphasic time-dependent increase in FMD , with significant increases at 1 - 2 and 6 h after consumption of blueberry polyphenols . No significant intake-dependence was observed between 766 and 1791 mg . However , at 1 h after consumption , FMD increased dose dependently to ≤766 mg total blueberry polyphenol intake , after which FMD plateaued . Increases in FMD were closely linked to increases in circulating metabolites and by decreases in neutrophil NADPH oxidase activity at 1 - 2 and 6 h. CONCLUSIONS Blueberry intake acutely improves vascular function in healthy men in a time- and intake-dependent manner . These benefits may be mechanistically linked to the actions of circulating phenolic metabolites on neutrophil NADPH oxidase activity . This trial was registered at clinical trials.gov as NCT01292954 and NCT01829542 SCOPE Blueberries are a rich source of flavonoids and phenolic acids . Currently , little information is available regarding the impact of processing on the bioavailability and the bioactivity of blueberry (poly)phenols . METHODS AND RESULTS In a r and omized , controlled crossover trial , ten healthy volunteers consumed ( a )  blueberry-containing baked products  , ( b ) an unprocessed blueberry drink containing the same amount of freeze-dried blueberry powder as used in the baked products , and ( c ) matched control baked products .  Endothelial function was measured as flow-mediated dilation ( FMD ) and plasma sample s taken at baseline and at 1 , 2 , 4 , and 6 h postconsumption . Although processing did not significantly change the total (poly)phenolic amount , the processed products contained significantly less anthocyanins ( -42 % ) , more chlorogenic acid ( 23 % ) , no flavanol nonamers or decamers , and significantly more flavanol dimers and trimers ( 36 % and 28 % , respectively ) . FMD increased after 1 , 2 , and 6 h consumption of the baked products to a similar degree as the unprocessed blueberries , despite significant differences in the levels of individual plasma metabolites . No changes were observed after the consumption of the control product . CONCLUSION Careful processing can preserve important biological activities of blueberries despite changing the blueberry (poly)phenol composition and plasma metabolite profile SCOPE Underst and ing the metabolic fate of polyphenols from plant foods can aid in developing dietary recommendations that maximize their health benefits . Wild blueberries ( WBB ) provide a distinctive composition of dietary anthocyanins and chlorogenic acid ( CGA ) . METHODS AND RESULTS This is a single blind , r and omized , two-arm crossover controlled study . Human subjects ingested a WBB beverage ( 25 g freeze dried WBB powder ) or placebo beverage with a meal and plasma was collected over 24 h. Anthocyanins , CGA and their metabolites were characterized and quantified in beverages and in plasma using targeted and non-targeted mass analyses . Bioavailability of WBB anthocyanins and 3-CGA was 1.1 and 0.2 % , respectively . Parent anthocyanins and 3-CGA peaked ≈2 h post ingestion , while phase II metabolites , including glucuronide conjugates of peonidin , delphinidin , cyanidin and petunidin peaked ≈ 2.6 , 6.3 , 7 and 8.8 h , respectively . Phenolic acids ( metabolites ) peaked between 0.5 and 24 h. Biphasic responses were evident suggesting preferential enterohepatic recycling for some compounds . CONCLUSION The data indicate bioavailability of early and late phase WBB metabolites peaking at different times during the 24 h period , which may be important for maximizing their biological activity Using a r and omized , double-blinded , placebo-controlled , parallel group design , this investigation determined if the combination of two weeks of flavonoid supplementation ( 329 mg/day , quercetin , anthocyanins , flavan-3-ols mixture ) and a 45-minute walking bout ( 62.2 ± 0.9 % VO2max ( maximal oxygen consumption rate ) ) enhanced the translocation of gut-derived phenolics into circulation in a group of walkers ( n = 77 ) . The walkers ( flavonoid , placebo groups ) were r and omized to either sit or walk briskly on treadmills for 45 min ( thus , four groups : placebo – sit , placebo – walk , flavonoid – sit , flavonoid – walk ) . A comparator group of runners ( n = 19 ) ingested a double flavonoid dose for two weeks ( 658 mg/day ) and ran for 2.5 h ( 69.2 ± 1.2 % VO2max ) . Four blood sample s were collected ( pre- and post-supplementation , immediately post- and 24 h post-exercise/rest ) . Of the 76 metabolites detected in this targeted analysis , 15 increased after the 2.5 h run , and when grouped were also elevated post-exercise ( versus placebo – sit ) for the placebo– and flavonoid – walking groups ( p < 0.05 ) . A secondary analysis showed that pre- study plasma concentrations of gut-derived phenolics in the runners were 40 % higher compared to walkers ( p = 0.031 ) . These data indicate that acute exercise bouts ( brisk walking , intensive running ) are linked to an increased translocation of gut-derived phenolics into circulation , an effect that is amplified when combined with a two-week period of increased flavonoid intake or chronic training as a runner 
    Output:
    
However , significant within-group effects for change from baseline were prevalent , suggesting that high inter-individual variability precluded significant treatment effects .
Berry consumption in general appears to cause a fluctuation in the pools of small molecule metabolites already present at baseline , rather than the appearance of unique berry-derived metabolites , which likely reflects the ubiquitous nature of (poly)phenols in the background diet