***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 Nrf2/ARE pathway is a major cellular defense mechanism that prevents damage by reactive oxygen species through induction of antioxidative phase II enzymes . However , the activity of the Nrf2/ARE system is not uniform with variability in response presumed to be dependent on the Nrf2 genotype . We recently completed a pilot human coffee intervention trial with healthy humans , where large interindividual differences in the antioxidative response to the study coffee were examined . Here , we address the question whether differences in the modulation of Nrf2 gene transcription , assessed as an induction of Nrf2 gene transcription by Q-PCR , might be correlated with specific Nrf2 genotypes . To date , nine single nucleotide polymorphisms ( SNPs ) have been identified in the Nrf2 ( NFE2L2 ) gene . Two of these , the −617C/A and −651G/A SNPs are located within the promoter region and have previously been reported to influence the activity of the Nrf2/ARE pathway by reducing Nrf2 transcriptional activity . Sequencing of the critical Nrf2 gene promoter region not only confirmed the existence of these SNPs within the participants of the trial at the expected frequency ( 33 % carrying the −617C/A , 17 % the −651G/A and 56 % the −653A/G SNP ) but also indicated reduced Nrf2 gene transcription associated with a normal diet if the SNPs at position −617 , −651 or −653 were present . Of note , the data also indicated the study coffee  increased Nrf2 gene transcription even in SNP carriers . This further highlights the relevance of genotype-dependent induction of Nrf2 gene transcription that appears to be largely influenced by dietary factors Background The relationship between  coffee consumption and mortality in diverse European population s with variable coffee preparation methods is unclear . Objective To examine whether coffee consumption is associated with all-cause and cause-specific mortality . Design Prospect i ve cohort study . Setting 10 European countries . Participants 521 330 persons enrolled in EPIC ( European Prospect i ve Investigation into Cancer and Nutrition ) . Measurements Hazard ratios ( HRs ) and 95 % CIs estimated using multivariable Cox proportional hazards models . The association of coffee consumption with serum biomarkers of liver function , inflammation , and metabolic health was evaluated in the EPIC Biomarkers subcohort ( n = 14 800 ) . Results During a mean follow-up of 16.4 years , 41 693 deaths occurred . Compared with nonconsumers , participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality ( men : HR , 0.88 [ 95 % CI , 0.82 to 0.95 ] ; P for trend < 0.001 ; women : HR , 0.93 [ CI , 0.87 to 0.98 ] ; P for trend = 0.009 ) . Inverse associations were also observed for digestive disease mortality for men ( HR , 0.41 [ CI , 0.32 to 0.54 ] ; P for trend < 0.001 ) and women ( HR , 0.60 [ CI , 0.46 to 0.78 ] ; P for trend < 0.001 ) . Among women , there was a statistically significant inverse association of coffee drinking with circulatory disease mortality ( HR , 0.78 [ CI , 0.68 to 0.90 ] ; P for trend < 0.001 ) and cerebrovascular disease mortality ( HR , 0.70 [ CI , 0.55 to 0.90 ] ; P for trend = 0.002 ) and a positive association with ovarian cancer mortality ( HR , 1.31 [ CI , 1.07 to 1.61 ] ; P for trend = 0.015 ) . In the EPIC Biomarkers subcohort , higher coffee consumption was associated with lower serum alkaline phosphatase ; alanine aminotransferase ; aspartate aminotransferase ; γ-glutamyltransferase ; and , in women , C-reactive protein , lipoprotein(a ) , and glycated hemoglobin levels . Limitations Reverse causality may have biased the findings ; however , results did not differ after exclusion of participants who died within 8 years of baseline . Coffee-drinking habits were assessed only once . Conclusion Coffee drinking was associated with reduced risk for death from various causes . This relationship did not vary by country . Primary Funding Source European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer Recent results from prospect i ve cohort studies have shown that moderate  coffee consumption is associated with a reduced risk for diabetes mellitus type II or Alzheimer 's disease . Since reactive oxygen species ( ROS ) are believed to be involved in the pathogenesis of these diseases , antioxidants in coffee might contribute to this risk reduction . We aim ed at elucidating whether a dark roast coffee beverage ( CB ) rich in N-methylpyridinium ions ( NMP : 785 μmol/L ) and low in chlorogenic acids ( CGA : 523 μmol/L ) has stronger antioxidant effects on human erythrocytes than a CB prepared from a light roast with opposite proportions ( CGA : 4538 μmol/L ; NMP : 56 μmol/L ) . Following a 2-wk wash out period , 500 mL of the respective CB was administered to 30 subjects daily for 4-wk . Blood and spot urine sample s were collected at the beginning and at the end of each intervention . Intake of the dark roast CB most effectively improved the antioxidant status of erythrocytes : superoxide dismutase and glutathione peroxidase activity decreased by 5.8 and 15 % , respectively , whereas tocopherol and total glutathione concentrations increased by 41 and 14 % , respectively . Furthermore , administration of the NMP-rich CB led to a significant body weight reduction in pre-obese subjects , whereas the CGA-rich CB did not BACKGROUND Coffee consumption has been associated with a lower risk of diabetes , but little is known about the mechanisms responsible for this association , especially related to the time when coffee is consumed . OBJECTIVE We examined the long-term effect of coffee , globally and according to the accompanying meal , and of tea , chicory , and caffeine on  type 2 diabetes risk . DESIGN This was a prospect i ve cohort study including 69,532 French women , aged 41 - 72 y from the E3N/EPIC ( Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale/European Prospect i ve Investigation into Cancer and Nutrition ) cohort study , without diabetes at baseline .  Food and drink intakes per meal were assessed by using a vali date d diet-history question naire in 1993 - 1995 . RESULTS During a mean follow-up of 11 y , 1415 new cases of diabetes  were identified . In multivariable Cox regression models , the hazard ratio in the highest category of coffee consumption [ > or =3 cups ( 375 mL)/d ] was 0.73 ( 95 % CI : 0.61 , 0.87 ; P for trend < 0.001 ) , in comparison with no coffee consumption . This inverse association was restricted to coffee consumed at lunchtime ( hazard ratio : 0.66 ; 95 % CI : 0.57 , 0.76 ) when comparing > 1.1 cup ( 125 mL)/meal with no intake . At lunchtime , this inverse association was observed for both regular and decaffeinated coffee and for filtered and black coffee , with no effect of sweetening . Total caffeine intake was also associated with a statistically significantly lower risk of diabetes . Neither tea nor chicory consumption was associated with diabetes risk . CONCLUSIONS Our data support an inverse association between coffee consumption and diabetes and suggest that the time of drinking coffee plays a distinct role in glucose metabolism BACKGROUND Consumption of caffeinated beverages such as coffee and tea has been associated with a lower risk of  type 2 diabetes ( T2D ) . Paradoxically , short-term metabolic studies have shown that caffeine impairs postpr and ial glycemic control . OBJECTIVE The objective was to prospect ively examine the association of caffeinated compared with caffeine-free beverages , including coffee , tea , sugar-sweetened beverages ( SSBs ) , and carbonated artificially sweetened beverages ( ASBs ) , with T2D risk . DESIGN We prospect ively observed 74,749 women from the Nurses ' Health Study ( NHS , 1984 - 2008 ) and 39,059 men from the Health Professionals Follow-Up Study ( HPFS , 1986 - 2008 ) who were free of diabetes , cardiovascular diseases , and cancer at baseline . RESULTS We documented 7370 incident cases of T2D during 24 y of follow-up in the NHS and 2865 new cases during 22 y of follow-up in the HPFS . After major lifestyle and dietary risk factors were controlled for , caffeinated and caffeine-free SSB intake was significantly associated with a higher risk of T2D in the NHS ( RR per serving : 13 % for caffeinated SSBs , 11 % for caffeine-free SSBs ; P < 0.05 ) and in the HPFS ( RR per serving : 16 % for caffeinated SSBs , 23 % for caffeine-free SSBs ; P < 0.01 ) . Only  caffeine-free ASB  intake in NHS participants was associated with a higher risk of T2D ( RR : 6 % per serving ; P < 0.001 ) . Conversely , the consumption of caffeinated and decaffeinated coffee was associated with a lower risk of T2D [ RR per serving : 8 % for both caffeinated and decaffeinated coffee in the NHS ( P < 0.0001 ) and 4 % for caffeinated and 7 % for decaffeinated coffee in the HPFS ( P < 0.01 ) ] . Only caffeinated tea was associated with a lower T2D risk among NHS participants ( RR per serving : 5 % ; P < 0.0001 ) . CONCLUSION Irrespective of the caffeine content , SSB intake was associated with a higher risk of T2D , and coffee intake was associated with a lower risk of T2D OBJECTIVE We evaluated the influence of coffee consumption on diabetes incidence among the Hawaii component of the Multiethnic Cohort ( MEC ) . DESIGN Prospect i ve cohort . SETTING Population -based sample residing in Hawaii . SUBJECTS After exclusions , 75 140 men and women of Caucasian , Japanese American and Native Hawaiian ancestry aged 45 - 75 years were part of the current analysis . All participants provided information on diet and lifestyle through an FFQ . After 14 years of follow-up 8582 incident diabetes cases were identified using self-reports , medication question naires and health plan linkages . Hazard ratios ( HR ) and 95 % confidence intervals were calculated using Cox regression while adjusting for known covariates . RESULTS The risk for diabetes associated with total coffee consumption differed by sex ( P interaction < 0·0001 ) . Women consuming ≥3 cups of any type of coffee daily had a significantly lower risk ( HR = 0·66 ; 95 % CI 0·58 , 0·77 ; P trend < 0·0001 ) than those reporting < 1 cup/d , whereas the relationship in men was borderline ( HR = 0·89 ; 95 % CI 0·80 , 0·99 ; P trend = 0·09 ) . The same difference by sex was seen  for regular coffee consumption , with HR of 0·65 ( 95 % CI 0·54 , 0·78 ; P trend < 0·0001 ) and 0·86 ( 95 % CI 0·75 , 0·98 ; P trend = 0·09 ) in men and women , respectively . No significant association with diabetes was apparent  for decaffeinated coffee in women ( HR = 0·85 ; 95 % CI 0·72 , 1·01 ; P trend = 0·73 ) or men ( HR = 1·07 ; 95 % CI 0·93 , 1·23 ; P trend = 0·71 ) . Despite small differences by ethnicity , the interaction terms between coffee intake and ethnicity were not significant . CONCLUSIONS In this multiethnic population , regular , but not decaffeinated , coffee intake was much more protective against diabetes in women of all ethnic groups than in men BACKGROUND The long-term effects of caffeine intake on weight have not been examined prospect ively . OBJECTIVE The objective was to assess the relation between caffeine intake and 12-y weight change . DESIGN We conducted a prospect i ve study of 18 417 men and 39 740 women , with no chronic diseases at baseline , who were followed from 1986 to 1998 .  Caffeine intake was assessed repeatedly every 2 - 4 y. Weight change was calculated as the difference between the self-reported weight in 1986 and in 
    Output:
    
Conclusions Available evidence indicates that coffee consumption is inversely associated with risk of T2D .