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: Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 Low serum 25-hydroxyvitamin D ( 25(OH)D ) has been shown to correlate with increased risk of type 2 diabetes . Small , observational studies suggest an action for vitamin D in improving insulin sensitivity and /or insulin secretion . The objective of the present study was to investigate the effect of improved vitamin D status on insulin resistance ( IR ) , utilising r and omised , controlled , double-blind intervention administering 100 microg ( 4000 IU ) vitamin D(3 ) ( n 42 ) or placebo ( n 39 ) daily for 6 months to South Asian women , aged 23 - 68 years , living in Auckl and , New Zeal and . Subjects were insulin resistant - homeostasis model assessment 1 (HOMA1)>1.93 and had serum 25(OH)D concentration < 50 nmol/l . Exclusion criteria included diabetes medication and vitamin D supplementation > 25 microg ( 1000 IU)/d . The HOMA2 computer model was used to calculate outcomes . Median ( 25th , 75th percentiles ) serum 25(OH)D(3 ) increased significantly from 21 ( 11 , 40 ) to 75 ( 55 , 84 ) nmol/l with supplementation . Significant improvements were seen in insulin sensitivity and IR ( P = 0.003 and 0.02 , respectively ) , and fasting insulin decreased ( P = 0.02 ) with supplementation compared with placebo . There was no change in C-peptide with supplementation . IR was most improved when endpoint serum 25(OH)D reached > or = 80 nmol/l . Secondary outcome variables ( lipid profile and high sensitivity C-reactive protein ) were not affected by supplementation . In conclusion , improving vitamin D status in insulin resistant women result ed in improved IR and sensitivity , but no change in insulin secretion . Optimal vitamin D concentrations for reducing IR were shown to be 80 - 119 nmol/l , providing further evidence for an increase in the recommended adequate levels . Registered Trial No. ACTRN12607000642482 Vitamin D ( VitD ) supplementation has been advocated for cardiovascular risk reduction ; however , supporting data are sparse . The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk . Subjects in this prospect i ve , r and omized , double-blind , placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations > 10 and < 60 ng/mL were r and omized to Vitamin D3 2500 IU or placebo , daily for 4 months . Primary endpoints were changes in brachial artery flow-mediated vasodilation ( FMD ) , carotid-femoral pulse wave velocity ( PWV ) , and aortic augmentation index ( AIx ) . The 114 subjects were mean ( st and ard deviation ) 63.9 ( 3.0 ) years old with a 25-hydroxyvitamin D level of 31.3 ( 10.6 ) ng/mL.  Low VitD ( < 30 ng/mL ) was present in 47 % and was associated with higher body-mass index , systolic blood pressure , glucose , CRP , and lower FMD ( all p<0.05 ) . After 4 months , 25-hydroxyvitamin D levels increased by 15.7 ( 9.3 ) ng/mL on vitamin D3 vs. −0.2 ( 6.1 ) ng/mL on placebo ( p<0.001 ) . There were no significant differences between groups in changes in FMD ( 0.3 [ 3.4 ] vs. 0.3 [ 2.6 ] % , p = 0.77 ) , PWV ( 0.00 [ 1.06 ] vs. 0.05 [ 0.92 ] m/s , p = 0.65 ) , AIx ( 2.7 [ 6.3 ] vs. 0.9 [ 5.6 ] % , p = 0.10 ) , or CRP ( 0.3 [ 1.9 ] vs. 0.3 [ 4.2 ] mg/L , p = 0.97 ) . Multivariable models showed no significant interactions between treatment group and low VitD status ( < 30 ng/mL ) for changes in FMD ( p = 0.65 ) , PWV ( p = 0.93 ) , AIx ( p = 0.97 ) , or CRP ( p = 0.26).In conclusion , VitD supplementation  did not improve endothelial function , arterial stiffness , or inflammation . These observations do not support use of VitD supplementation to reduce cardiovascular disease risk . Trial Registration Clinical Trials.gov NCT00690417 Trial Registration Clinical Trials.gov OBJECTIVE In observational studies , low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease . RESEARCH DESIGN AND METHODS We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose ( IFG ) and /or impaired glucose tolerance ( IGT ) r and omly assigned to 20,000 IU/week vitamin D3 or placebo .  An oral glucose tolerance test was performed at baseline and after 1 year . RESULTS Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups , respectively , and increased by 45.8 nmol/L and 3.4 nmol/L , respectively . With adjustment for baseline concentrations , no differences in measures of glucose metabolism , insulin secretion or sensitivity , blood pressure , or hs-CRP were found after 1 year . There was a slight , but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group , but as there was also a decrease in HDL cholesterol , the change in the total/HDL cholesterol ratio did not differ significantly . Only analyzing subjects with 25(OH)D < 50 nmol/L did not change the results . CONCLUSIONS This study shows that vitamin D supplementation does not improve glycemic indices , blood pressure , or lipid status in subjects with IFG and /or IGT CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P<0.001 , linear mixed model ) . Mean ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin The prevalence of vitamin D deficiency varies , with the groups at greatest risk including housebound , community-dwelling older and /or disabled people , those in residential care , dark-skinned people ( particularly those modestly dressed ) , and other people who regularly avoid sun exposure or work indoors . Most adults are unlikely to obtain more than 5%-10 % of their vitamin D requirement from dietary sources . The main source of vitamin D for people residing in Australia and New Zeal and is exposure to sunlight . A serum 25-hydroxyvitamin D ( 25-OHD ) level of ≥ 50 nmol/L at the end of winter ( 10 - 20 nmol/L higher at the end of summer , to allow for seasonal decrease ) is required for optimal musculoskeletal health . Although it is likely that higher serum 25-OHD levels play a role in the prevention of some disease states , there is insufficient evidence from r and omised controlled trials to recommend higher targets . For moderately fair-skinned people , a walk with arms exposed for 6 - 7 minutes mid morning or mid afternoon in summer , and with as much bare skin exposed as feasible for 7 - 40 minutes ( depending on latitude ) at noon in winter , on most days , is likely to be helpful in maintaining adequate vitamin D levels in the body . When sun exposure is minimal , vitamin D intake from dietary sources and supplementation of at least 600 IU ( 15 µg ) per day for people aged ≤ 70 years and 800 IU ( 20 µg ) per day for those aged > 70 years is recommended . People in high-risk groups may require higher doses . There is good evidence that vitamin D plus calcium supplementation  effectively reduces fractures and falls in older men and women The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases , insulin resistance , oxidative stress , and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease ( NAFLD ) . Fifty-three patients with NAFLD were enrolled in a parallel , double-blind , placebo-controlled study . The patients were r and omly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 ( n = 27 ) or a placebo ( n = 26 ) , every 14 days for 4 months . Serum aminotransferases , high-sensitive C-reactive protein ( hs-CRP ) , tumor necrosis factor α , malondialdehyde ( MDA ) , total antiox 
    Output:
    
agent
Available high- quality RCTs did not support a beneficial effect of cholecalciferol on systemic IL-6 and CRP .
***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: Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 Low serum 25-hydroxyvitamin D ( 25(OH)D ) has been shown to correlate with increased risk of type 2 diabetes . Small , observational studies suggest an action for vitamin D in improving insulin sensitivity and /or insulin secretion . The objective of the present study was to investigate the effect of improved vitamin D status on insulin resistance ( IR ) , utilising r and omised , controlled , double-blind intervention administering 100 microg ( 4000 IU ) vitamin D(3 ) ( n 42 ) or placebo ( n 39 ) daily for 6 months to South Asian women , aged 23 - 68 years , living in Auckl and , New Zeal and . Subjects were insulin resistant - homeostasis model assessment 1 (HOMA1)>1.93 and had serum 25(OH)D concentration < 50 nmol/l . Exclusion criteria included diabetes medication and vitamin D supplementation > 25 microg ( 1000 IU)/d . The HOMA2 computer model was used to calculate outcomes . Median ( 25th , 75th percentiles ) serum 25(OH)D(3 ) increased significantly from 21 ( 11 , 40 ) to 75 ( 55 , 84 ) nmol/l with supplementation . Significant improvements were seen in insulin sensitivity and IR ( P = 0.003 and 0.02 , respectively ) , and fasting insulin decreased ( P = 0.02 ) with supplementation compared with placebo . There was no change in C-peptide with supplementation . IR was most improved when endpoint serum 25(OH)D reached > or = 80 nmol/l . Secondary outcome variables ( lipid profile and high sensitivity C-reactive protein ) were not affected by supplementation . In conclusion , improving vitamin D status in insulin resistant women result ed in improved IR and sensitivity , but no change in insulin secretion . Optimal vitamin D concentrations for reducing IR were shown to be 80 - 119 nmol/l , providing further evidence for an increase in the recommended adequate levels . Registered Trial No. ACTRN12607000642482 Vitamin D ( VitD ) supplementation has been advocated for cardiovascular risk reduction ; however , supporting data are sparse . The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk . Subjects in this prospect i ve , r and omized , double-blind , placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations > 10 and < 60 ng/mL were r and omized to Vitamin D3 2500 IU or placebo , daily for 4 months . Primary endpoints were changes in brachial artery flow-mediated vasodilation ( FMD ) , carotid-femoral pulse wave velocity ( PWV ) , and aortic augmentation index ( AIx ) . The 114 subjects were mean ( st and ard deviation ) 63.9 ( 3.0 ) years old with a 25-hydroxyvitamin D level of 31.3 ( 10.6 ) ng/mL.  Low VitD ( < 30 ng/mL ) was present in 47 % and was associated with higher body-mass index , systolic blood pressure , glucose , CRP , and lower FMD ( all p<0.05 ) . After 4 months , 25-hydroxyvitamin D levels increased by 15.7 ( 9.3 ) ng/mL on vitamin D3 vs. −0.2 ( 6.1 ) ng/mL on placebo ( p<0.001 ) . There were no significant differences between groups in changes in FMD ( 0.3 [ 3.4 ] vs. 0.3 [ 2.6 ] % , p = 0.77 ) , PWV ( 0.00 [ 1.06 ] vs. 0.05 [ 0.92 ] m/s , p = 0.65 ) , AIx ( 2.7 [ 6.3 ] vs. 0.9 [ 5.6 ] % , p = 0.10 ) , or CRP ( 0.3 [ 1.9 ] vs. 0.3 [ 4.2 ] mg/L , p = 0.97 ) . Multivariable models showed no significant interactions between treatment group and low VitD status ( < 30 ng/mL ) for changes in FMD ( p = 0.65 ) , PWV ( p = 0.93 ) , AIx ( p = 0.97 ) , or CRP ( p = 0.26).In conclusion , VitD supplementation  did not improve endothelial function , arterial stiffness , or inflammation . These observations do not support use of VitD supplementation to reduce cardiovascular disease risk . Trial Registration Clinical Trials.gov NCT00690417 Trial Registration Clinical Trials.gov OBJECTIVE In observational studies , low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease . RESEARCH DESIGN AND METHODS We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose ( IFG ) and /or impaired glucose tolerance ( IGT ) r and omly assigned to 20,000 IU/week vitamin D3 or placebo .  An oral glucose tolerance test was performed at baseline and after 1 year . RESULTS Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups , respectively , and increased by 45.8 nmol/L and 3.4 nmol/L , respectively . With adjustment for baseline concentrations , no differences in measures of glucose metabolism , insulin secretion or sensitivity , blood pressure , or hs-CRP were found after 1 year . There was a slight , but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group , but as there was also a decrease in HDL cholesterol , the change in the total/HDL cholesterol ratio did not differ significantly . Only analyzing subjects with 25(OH)D < 50 nmol/L did not change the results . CONCLUSIONS This study shows that vitamin D supplementation does not improve glycemic indices , blood pressure , or lipid status in subjects with IFG and /or IGT CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P<0.001 , linear mixed model ) . Mean ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin The prevalence of vitamin D deficiency varies , with the groups at greatest risk including housebound , community-dwelling older and /or disabled people , those in residential care , dark-skinned people ( particularly those modestly dressed ) , and other people who regularly avoid sun exposure or work indoors . Most adults are unlikely to obtain more than 5%-10 % of their vitamin D requirement from dietary sources . The main source of vitamin D for people residing in Australia and New Zeal and is exposure to sunlight . A serum 25-hydroxyvitamin D ( 25-OHD ) level of ≥ 50 nmol/L at the end of winter ( 10 - 20 nmol/L higher at the end of summer , to allow for seasonal decrease ) is required for optimal musculoskeletal health . Although it is likely that higher serum 25-OHD levels play a role in the prevention of some disease states , there is insufficient evidence from r and omised controlled trials to recommend higher targets . For moderately fair-skinned people , a walk with arms exposed for 6 - 7 minutes mid morning or mid afternoon in summer , and with as much bare skin exposed as feasible for 7 - 40 minutes ( depending on latitude ) at noon in winter , on most days , is likely to be helpful in maintaining adequate vitamin D levels in the body . When sun exposure is minimal , vitamin D intake from dietary sources and supplementation of at least 600 IU ( 15 µg ) per day for people aged ≤ 70 years and 800 IU ( 20 µg ) per day for those aged > 70 years is recommended . People in high-risk groups may require higher doses . There is good evidence that vitamin D plus calcium supplementation  effectively reduces fractures and falls in older men and women The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases , insulin resistance , oxidative stress , and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease ( NAFLD ) . Fifty-three patients with NAFLD were enrolled in a parallel , double-blind , placebo-controlled study . The patients were r and omly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 ( n = 27 ) or a placebo ( n = 26 ) , every 14 days for 4 months . Serum aminotransferases , high-sensitive C-reactive protein ( hs-CRP ) , tumor necrosis factor α , malondialdehyde ( MDA ) , total antiox 
    Output:
    