human
***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: Tissue levels of n-3 fatty acids reflect dietary intake , but quantitative data about rate of incorporation and levels as a function of intake are scarce . We fed 58 men 0 , 3 , 6 , or 9 g/d of fish oil for 12 months and monitored fatty acids in serum cholesteryl esters , erythrocytes , and subcutaneous fat during and after supplementation .  Eicosapentaenoic acid ( EPA ) in cholesteryl esters plateaued after 4 - 8 weeks ; the incorporation half-life was 4.8 days . Steady-state levels increased by 3.9 + /- 0.3 mass % points ( + /- SE ) for each extra gram of EPA eaten per day . Incorporation of docosahexaenoic acid ( DHA ) was erratic ; plateau values were 1.1 + /- 0.1 mass % higher for every g/d ingested . Incorporation of EPA into erythrocyte membranes showed a half-life of 28 days ; a steady state was reached after 180 days . Each g/d increased levels by 2.1 + /- 0.1 mass % . C22:5n-3 levels increased markedly . Changes in DHA were erratic and smaller . EPA levels in adipose tissue rose also ; the change after 6 months was 67 % of that after 12 months in gluteal and 75 % in abdominal fat . After 12 months each gram per day caused an 0.11 + /- 0.01 mass % rise in gluteal fat for EPA , 0.53 + /- 0.07 for C22:5n-3 , and 0.14 + /- 0.03 for DHA . Thus , different ( n-3 ) fatty acids were incorporated with different efficiencies , possibly because of interconversions or different affinities of the enzymatic pathways involved . EPA levels in cholesteryl esters reflect intake over the past week or two , erythrocytes over the past month or two , and adipose tissue over a period of years . These findings may help in assessing the intake of ( n-3 ) fatty acids in epidemiological studies Background Whether and how n-3 and n-6 polyunsaturated fatty acids ( PUFAs ) are related to type 2 diabetes ( T2D ) is debated . Objective ly measured plasma PUFAs can help to clarify these associations . Methods and Findings Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries .  Country-specific hazard ratios ( HRs ) were estimated using Prentice-weighted Cox regression and pooled by r and om-effects meta- analysis . We also systematic ally review ed published prospect i ve studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct . In EPIC-InterAct , among long-chain n-3 PUFAs , α-linolenic acid ( ALA ) was inversely associated with T2D ( HR per st and ard deviation [ SD ] 0.93 ; 95 % CI 0.88–0.98 ) , but eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) were not significantly associated . Among n-6 PUFAs , linoleic acid ( LA ) ( 0.80 ; 95 % CI 0.77–0.83 ) and eicosadienoic acid ( EDA ) ( 0.89 ; 95 % CI 0.85–0.94 ) were inversely related , and arachidonic acid ( AA ) was not significantly associated , while significant positive associations were observed with γ-linolenic acid ( GLA ) , dihomo-GLA , docosatetraenoic acid ( DTA ) , and docosapentaenoic acid ( n6-DPA ) , with HRs between 1.13 to 1.46 per SD . These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases . Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs . Conclusions These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA ( ALA ) but no convincing association of marine-derived n3 PUFAs ( EPA and DHA ) with T2D . Moreover , they highlight that the most abundant n6-PUFA ( LA ) is inversely associated with T2D . The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class Background : Epidemiologic evidence of an association between fish intake and  type 2 diabetes ( T2D )  is inconsistent and unresolved . Objective : The objective was to examine the association between total and type of fish intake and  T2D in 8 European countries . Design : This was a case-cohort study , nested within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study , with 3.99 million person-years of follow-up , 12,403 incident diabetes cases , and a r and om subcohort of 16,835 individuals from 8 European countries . Habitual fish intake ( lean fish , fatty fish , total fish , shellfish , and combined fish and shellfish ) was assessed by country-specific dietary question naires . HRs were estimated in each country by using Prentice-weighted Cox regression models and pooled by using a r and om-effects meta- analysis . Results : No overall association was found between combined fish and shellfish intake and incident T2D per quartile ( adjusted HR : 1.00 ; 95 % CI : 0.94 , 1.06 ; P-trend = 0.99 ) . Total fish , lean fish , and shellfish intakes separately were also not associated with T2D , but fatty fish intake was weakly inversely associated with T2D : adjusted HR per quartile 0.97 ( 0.94 , 1.00 ) , with an HR of 0.84 ( 0.70 , 1.01 ) , 0.85 ( 0.76 , 0.95 ) , and 0.87 ( 0.78 , 0.97 ) for a comparison of the second , third , and fourth quartiles with the lowest quartile of intake , respectively ( P-trend = 0.06 ) . Conclusions : These findings suggest that lean fish , total fish , and shellfish intakes are not associated with incident diabetes but that fatty fish intake may be weakly inversely associated . Replication of these findings in other population s and investigation of the mechanisms underlying these associations are warranted . Meanwhile , current public health recommendations on fish intake should remain unchanged Background Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids ( n-3 LC PUFAs ) and better cognitive outcomes in older adults . To date , only two r and omised , controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy population s. Of these trials only one found a benefit , in the subgroup carrying the ApoE-ε4 allele . The benefits of n-3 LC PUFA supplementation on cognitive function in older normal population s thus still remain unclear . The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people , and included ApoE-ε4 allele carriage as a potential moderating factor . The detailed methodology of the trial is reported herein . Methods The study was a parallel , 18-month , r and omised , double-blind , placebo-controlled intervention with assessment at baseline and repeated 6-monthly . Participants ( N = 391 , 53.7 % female ) aged 65 - 90 years , English-speaking and with normal cognitive function , were recruited from metropolitan Adelaide , South Australia . Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules . The primary outcome is rate of change in cognitive performance , as measured by latent variables for the cognitive constructs ( encompassing Reasoning , Working Memory , Short-term Memory , Retrieval Fluency , Inhibition , Simple and Choice-Reaction Time , Perceptual Speed , Odd-man-out Reaction Time , Speed of Memory Scanning , and Psychomotor Speed ) and assessed by latent growth curve modeling . Secondary outcomes are change in the Mini-mental State Examination , functional capacity and well-being ( including health status , depression , mood , and self-report cognitive functioning ) , blood pressure , and biomarkers of n-3 LC PUFA status , glucose , lipid metabolism , inflammation , oxidative stress , and DNA damage . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : Background The benefit of n-3 polyunsaturated fatty acids ( PUFA ) supplementation for mortality and cardiovascular events after myocardial infa rct ion is well documented , but the effect of n-3 PUFA in Caucasians without established cardiovascular disease is not known . Our aim was to examine the influence of supplementation with eicosapentaenoic acid and docosahexaenoic acid on all-cause mortality and cardiovascular events in elderly men at high-risk of cardiovascular disease . Design In the Diet and Omega-3 Intervention Trial , 563 Norwegian men , 64–76-year old and 72 % without overt cardiovascular disease , were r and omized to a 3-year 2 × 2 factorial design ed clinical trial of diet counseling and /or 2.4 g n-3 PUFA supplementation . The n-3 PUFA arm was placebo-controlled ( corn oil ) . Methods Demographic parameters and classical risk factors were obtained at baseline . Deaths and cardiovascular events were recorded through 3 years , and the effects of n-3 PUFA-intervention on these outcomes were evaluated in pooled groups of the n-3 PUFA-arm . Results There were 38 deaths and 68 cardiovascular events . The unadjusted hazard ratios of all-cause mortality and cardiovascular events were 0.57 ( 95 % confidence interval : 0.29–1.10 ) and 0.86 ( 0.57–1.38 ) , respectively . Adjusted for baseline age , current smoking , hypertension , body mass index and serum glucose , hazard ratios were 0.53 ( 0.27–1.04 , P = 0.063 ) and 0.89 ( 0.55–1.45 , P = 0.641 ) , respectively . Conclusion We observed a tendency toward reduction in all-cause mortality in the n-3 PUFA groups that , despite a low number of participants , reached borderline statistical significance . The magnitude of risk-reduction suggests that a larger trial should be considered in similar population BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary ar 
    Output:
    
agent
***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: Tissue levels of n-3 fatty acids reflect dietary intake , but quantitative data about rate of incorporation and levels as a function of intake are scarce . We fed 58 men 0 , 3 , 6 , or 9 g/d of fish oil for 12 months and monitored fatty acids in serum cholesteryl esters , erythrocytes , and subcutaneous fat during and after supplementation .  Eicosapentaenoic acid ( EPA ) in cholesteryl esters plateaued after 4 - 8 weeks ; the incorporation half-life was 4.8 days . Steady-state levels increased by 3.9 + /- 0.3 mass % points ( + /- SE ) for each extra gram of EPA eaten per day . Incorporation of docosahexaenoic acid ( DHA ) was erratic ; plateau values were 1.1 + /- 0.1 mass % higher for every g/d ingested . Incorporation of EPA into erythrocyte membranes showed a half-life of 28 days ; a steady state was reached after 180 days . Each g/d increased levels by 2.1 + /- 0.1 mass % . C22:5n-3 levels increased markedly . Changes in DHA were erratic and smaller . EPA levels in adipose tissue rose also ; the change after 6 months was 67 % of that after 12 months in gluteal and 75 % in abdominal fat . After 12 months each gram per day caused an 0.11 + /- 0.01 mass % rise in gluteal fat for EPA , 0.53 + /- 0.07 for C22:5n-3 , and 0.14 + /- 0.03 for DHA . Thus , different ( n-3 ) fatty acids were incorporated with different efficiencies , possibly because of interconversions or different affinities of the enzymatic pathways involved . EPA levels in cholesteryl esters reflect intake over the past week or two , erythrocytes over the past month or two , and adipose tissue over a period of years . These findings may help in assessing the intake of ( n-3 ) fatty acids in epidemiological studies Background Whether and how n-3 and n-6 polyunsaturated fatty acids ( PUFAs ) are related to type 2 diabetes ( T2D ) is debated . Objective ly measured plasma PUFAs can help to clarify these associations . Methods and Findings Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries .  Country-specific hazard ratios ( HRs ) were estimated using Prentice-weighted Cox regression and pooled by r and om-effects meta- analysis . We also systematic ally review ed published prospect i ve studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct . In EPIC-InterAct , among long-chain n-3 PUFAs , α-linolenic acid ( ALA ) was inversely associated with T2D ( HR per st and ard deviation [ SD ] 0.93 ; 95 % CI 0.88–0.98 ) , but eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) were not significantly associated . Among n-6 PUFAs , linoleic acid ( LA ) ( 0.80 ; 95 % CI 0.77–0.83 ) and eicosadienoic acid ( EDA ) ( 0.89 ; 95 % CI 0.85–0.94 ) were inversely related , and arachidonic acid ( AA ) was not significantly associated , while significant positive associations were observed with γ-linolenic acid ( GLA ) , dihomo-GLA , docosatetraenoic acid ( DTA ) , and docosapentaenoic acid ( n6-DPA ) , with HRs between 1.13 to 1.46 per SD . These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases . Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs . Conclusions These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA ( ALA ) but no convincing association of marine-derived n3 PUFAs ( EPA and DHA ) with T2D . Moreover , they highlight that the most abundant n6-PUFA ( LA ) is inversely associated with T2D . The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class Background : Epidemiologic evidence of an association between fish intake and  type 2 diabetes ( T2D )  is inconsistent and unresolved . Objective : The objective was to examine the association between total and type of fish intake and  T2D in 8 European countries . Design : This was a case-cohort study , nested within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study , with 3.99 million person-years of follow-up , 12,403 incident diabetes cases , and a r and om subcohort of 16,835 individuals from 8 European countries . Habitual fish intake ( lean fish , fatty fish , total fish , shellfish , and combined fish and shellfish ) was assessed by country-specific dietary question naires . HRs were estimated in each country by using Prentice-weighted Cox regression models and pooled by using a r and om-effects meta- analysis . Results : No overall association was found between combined fish and shellfish intake and incident T2D per quartile ( adjusted HR : 1.00 ; 95 % CI : 0.94 , 1.06 ; P-trend = 0.99 ) . Total fish , lean fish , and shellfish intakes separately were also not associated with T2D , but fatty fish intake was weakly inversely associated with T2D : adjusted HR per quartile 0.97 ( 0.94 , 1.00 ) , with an HR of 0.84 ( 0.70 , 1.01 ) , 0.85 ( 0.76 , 0.95 ) , and 0.87 ( 0.78 , 0.97 ) for a comparison of the second , third , and fourth quartiles with the lowest quartile of intake , respectively ( P-trend = 0.06 ) . Conclusions : These findings suggest that lean fish , total fish , and shellfish intakes are not associated with incident diabetes but that fatty fish intake may be weakly inversely associated . Replication of these findings in other population s and investigation of the mechanisms underlying these associations are warranted . Meanwhile , current public health recommendations on fish intake should remain unchanged Background Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids ( n-3 LC PUFAs ) and better cognitive outcomes in older adults . To date , only two r and omised , controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy population s. Of these trials only one found a benefit , in the subgroup carrying the ApoE-ε4 allele . The benefits of n-3 LC PUFA supplementation on cognitive function in older normal population s thus still remain unclear . The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people , and included ApoE-ε4 allele carriage as a potential moderating factor . The detailed methodology of the trial is reported herein . Methods The study was a parallel , 18-month , r and omised , double-blind , placebo-controlled intervention with assessment at baseline and repeated 6-monthly . Participants ( N = 391 , 53.7 % female ) aged 65 - 90 years , English-speaking and with normal cognitive function , were recruited from metropolitan Adelaide , South Australia . Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules . The primary outcome is rate of change in cognitive performance , as measured by latent variables for the cognitive constructs ( encompassing Reasoning , Working Memory , Short-term Memory , Retrieval Fluency , Inhibition , Simple and Choice-Reaction Time , Perceptual Speed , Odd-man-out Reaction Time , Speed of Memory Scanning , and Psychomotor Speed ) and assessed by latent growth curve modeling . Secondary outcomes are change in the Mini-mental State Examination , functional capacity and well-being ( including health status , depression , mood , and self-report cognitive functioning ) , blood pressure , and biomarkers of n-3 LC PUFA status , glucose , lipid metabolism , inflammation , oxidative stress , and DNA damage . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : Background The benefit of n-3 polyunsaturated fatty acids ( PUFA ) supplementation for mortality and cardiovascular events after myocardial infa rct ion is well documented , but the effect of n-3 PUFA in Caucasians without established cardiovascular disease is not known . Our aim was to examine the influence of supplementation with eicosapentaenoic acid and docosahexaenoic acid on all-cause mortality and cardiovascular events in elderly men at high-risk of cardiovascular disease . Design In the Diet and Omega-3 Intervention Trial , 563 Norwegian men , 64–76-year old and 72 % without overt cardiovascular disease , were r and omized to a 3-year 2 × 2 factorial design ed clinical trial of diet counseling and /or 2.4 g n-3 PUFA supplementation . The n-3 PUFA arm was placebo-controlled ( corn oil ) . Methods Demographic parameters and classical risk factors were obtained at baseline . Deaths and cardiovascular events were recorded through 3 years , and the effects of n-3 PUFA-intervention on these outcomes were evaluated in pooled groups of the n-3 PUFA-arm . Results There were 38 deaths and 68 cardiovascular events . The unadjusted hazard ratios of all-cause mortality and cardiovascular events were 0.57 ( 95 % confidence interval : 0.29–1.10 ) and 0.86 ( 0.57–1.38 ) , respectively . Adjusted for baseline age , current smoking , hypertension , body mass index and serum glucose , hazard ratios were 0.53 ( 0.27–1.04 , P = 0.063 ) and 0.89 ( 0.55–1.45 , P = 0.641 ) , respectively . Conclusion We observed a tendency toward reduction in all-cause mortality in the n-3 PUFA groups that , despite a low number of participants , reached borderline statistical significance . The magnitude of risk-reduction suggests that a larger trial should be considered in similar population BACKGROUND Epidemiological and clinical evidence suggests that an increased intake of long-chain n-3 fatty acids protects against mortality from coronary artery disease . We aim ed to test the hypothesis that long-term use of eicosapentaenoic acid ( EPA ) is effective for prevention of major coronary events in hypercholesterolaemic patients in Japan who consume a large amount of fish . METHODS 18 645 patients with a total cholesterol of 6.5 mmol/L or greater were recruited from local physicians throughout Japan between 1996 and 1999 . Patients were r and omly assigned to receive either 1800 mg of EPA daily with statin ( EPA group ; n=9326 ) or statin only ( controls ; n=9319 ) with a 5-year follow-up . The primary endpoint was any major coronary event , including sudden cardiac death , fatal and non-fatal myocardial infa rct ion , and other non-fatal events including unstable angina pectoris , angioplasty , stenting , or coronary artery bypass grafting . Analysis was by intention-to-treat . The study was registered at Clinical Trials.gov , number NCT00231738 . FINDINGS At mean follow-up of 4.6 years , we detected the primary endpoint in 262 ( 2.8 % ) patients in the EPA group and 324 ( 3.5 % ) in controls-a 19 % relative reduction in major coronary events ( p=0.011 ) . Post-treatment LDL cholesterol concentrations decreased 25 % , from 4.7 mmol/L in both groups . Serum LDL cholesterol was not a significant factor in a reduction of risk for major coronary events . Unstable angina and non-fatal coronary events were also significantly reduced in the EPA group . Sudden cardiac death and coronary death did not differ between groups . In patients with a history of coronary artery disease who were given EPA treatment , major coronary events were reduced by 19 % ( secondary prevention subgroup : 158 [ 8.7 % ] in the EPA group vs 197 [ 10.7 % ] in the control group ; p=0.048 ) . In patients with no history of coronary ar 
    Output:
    