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: BACKGROUND Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans . METHODS We assessed prospect ively whether plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations are associated with risk of coronary heart disease . A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study ; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection . The blood sample s were returned between April 1 , 1993 , and November 30 , 1999 ; 99 % were received between April 1 , 1993 , and November 30 , 1995 . During 10 years of follow-up , 454 men developed nonfatal myocardial infa rct ion or fatal coronary heart disease . Using risk set sampling , controls ( n = 900 ) were selected in a 2:1 ratio and matched for age , date of blood collection , and smoking status . RESULTS After adjustment for matched variables , men deficient in 25(OH)D ( < or=15 ng/mL [ to convert to nanomoles per liter , multiply by 2.496 ] ) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D ( > or=30 ng/mL ) ( relative risk [ RR ] , 2.42 ; 95 % confidence interval [ CI ] , 1.53 - 3.84 ; P < .001 for trend ) . After additional adjustment for family history of myocardial infa rct ion , body mass index , alcohol consumption , physical activity , history of diabetes mellitus and hypertension , ethnicity , region , marine omega-3 intake , low- and high-density lipoprotein cholesterol levels , and triglyceride levels , this relationship remained significant ( RR , 2.09 ; 95 % CI , 1.24 - 3.54 ; P = .02 for trend ) . Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels ( 22.6 - 29.9 ng/mL : RR , 1.60 [ 95 % CI , 1.10 - 2.32 ] ; and 15.0 - 22.5 ng/mL : RR , 1.43 [ 95 % CI , 0.96 - 2.13 ] , respectively ) . CONCLUSION Low levels of 25(OH)D are associated with higher risk of myocardial infa rct ion in a grade d manner , even after controlling for factors known to be associated with coronary artery disease Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels < 50 nmol/L ( 20 ng/mL ) received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P<0.001 ) and maintained this increase at 20 weeks . The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896 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 BACKGROUND Studies suggest that vitamin D deficiency is a risk factor for cardiovascular disease and diabetes . Vitamin D deficiency is prevalent in HIV patients but the effect of vitamin D supplementation on cardiovascular risk in this population is unknown . METHODS We conducted a r and omized , double-blind , placebo-controlled trial among 45 HIV-infected adults in Clevel and ( OH , USA ) on stable antiretroviral therapy with durable virological suppression and a baseline serum 25-hydroxyvitamin D level of ≤20 ng/ml . Participants were r and omized 2:1 to vitamin D3 4,000 IU daily or placebo  for 12 weeks . The primary outcome was a change in flow-mediated brachial artery dilation ( FMD ) . RESULTS Baseline demographics were similar except for age ( vitamin D versus placebo , mean ±sd 47 ±8 versus 40 ±10 years ; P=0.009 ) . Both groups had reduced FMD at baseline ( median values 2.9 % [ IQR 1.6 - 4.8 ] for vitamin D versus 2.5 % [ IQR 1.7 - 6.4 ] for placebo ; P=0.819 ) . Despite an increase in the concentration of serum 25-hydroxyvitamin D from baseline to 12 weeks ( 5.0 ng/ml [ IQR -0.9 - 7.4 ] versus -1.9 ng/ml [ IQR -4.0 - 0.1 ] for vitamin D versus placebo , respectively ; P=0.003 ) , there was no difference in FMD change ( 0.55 % [ IQR -1.05 - 2.13 ] versus 0.29 % [ IQR -1.61 - 1.77 ] ; P=0.748 ) . Vitamin D supplementation was associated with a decrease in total and non-high-density lipoprotein cholesterol , and an increase in indices of insulin resistance . CONCLUSIONS Among HIV-infected individuals with vitamin D deficiency , supplementation with 4,000 IU vitamin D3 daily for 12 weeks modestly improved vitamin D status and cholesterol but worsened insulin resistance without change in endothelial function . The mechanisms of resistance to st and ard doses of vitamin D and the complex role of vitamin D in glucose metabolism in this population require further investigation BACKGROUND Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure ( CHF ) . In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines . OBJECTIVE We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF . DESIGN One hundred twenty-three patients r and omly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [ D(+ ) group ] or placebo plus 500 mg Ca/d [ D(- ) group ] for 9 mo . Biochemical variables were assessed at baseline and after 9 mo . The survival rate was calculated for a follow-up period of 15 mo . RESULTS Ninety-three patients completed the study . Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D ( P = 0.001 ) , parathyroid hormone ( P = 0.007 ) , tumor necrosis factor alpha ( P = 0.006 ) , and interleukin 10 ( P = 0.042 ) . 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+ ) group but increased only by 3.6 ng/mL in the D(- ) group . Compared with baseline , parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+ ) group after 9 mo . The proinflammatory cytokine tumor necrosis factor alpha increased in the D(- ) group but remained constant in the D(+ ) group . The survival rate did not differ significantly between the study groups during the follow-up period . CONCLUSIONS Vitamin D(3 ) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease . Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF BACKGROUND Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [ 25(OH)D ] 
    Output:
    
agent
Evidence from the studies included in this systematic review did not demonstrate that vitamin D supplementation in adults , results in an improvement in circulating inflammatory and endothelial function biomarkers/parameters .
This systematic review does not therefore support the use of vitamin D supplementation as a therapeutic or preventative measure for CVD in this respect
***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 Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans . METHODS We assessed prospect ively whether plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations are associated with risk of coronary heart disease . A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study ; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection . The blood sample s were returned between April 1 , 1993 , and November 30 , 1999 ; 99 % were received between April 1 , 1993 , and November 30 , 1995 . During 10 years of follow-up , 454 men developed nonfatal myocardial infa rct ion or fatal coronary heart disease . Using risk set sampling , controls ( n = 900 ) were selected in a 2:1 ratio and matched for age , date of blood collection , and smoking status . RESULTS After adjustment for matched variables , men deficient in 25(OH)D ( < or=15 ng/mL [ to convert to nanomoles per liter , multiply by 2.496 ] ) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D ( > or=30 ng/mL ) ( relative risk [ RR ] , 2.42 ; 95 % confidence interval [ CI ] , 1.53 - 3.84 ; P < .001 for trend ) . After additional adjustment for family history of myocardial infa rct ion , body mass index , alcohol consumption , physical activity , history of diabetes mellitus and hypertension , ethnicity , region , marine omega-3 intake , low- and high-density lipoprotein cholesterol levels , and triglyceride levels , this relationship remained significant ( RR , 2.09 ; 95 % CI , 1.24 - 3.54 ; P = .02 for trend ) . Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels ( 22.6 - 29.9 ng/mL : RR , 1.60 [ 95 % CI , 1.10 - 2.32 ] ; and 15.0 - 22.5 ng/mL : RR , 1.43 [ 95 % CI , 0.96 - 2.13 ] , respectively ) . CONCLUSION Low levels of 25(OH)D are associated with higher risk of myocardial infa rct ion in a grade d manner , even after controlling for factors known to be associated with coronary artery disease Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels < 50 nmol/L ( 20 ng/mL ) received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P<0.001 ) and maintained this increase at 20 weeks . The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896 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 BACKGROUND Studies suggest that vitamin D deficiency is a risk factor for cardiovascular disease and diabetes . Vitamin D deficiency is prevalent in HIV patients but the effect of vitamin D supplementation on cardiovascular risk in this population is unknown . METHODS We conducted a r and omized , double-blind , placebo-controlled trial among 45 HIV-infected adults in Clevel and ( OH , USA ) on stable antiretroviral therapy with durable virological suppression and a baseline serum 25-hydroxyvitamin D level of ≤20 ng/ml . Participants were r and omized 2:1 to vitamin D3 4,000 IU daily or placebo  for 12 weeks . The primary outcome was a change in flow-mediated brachial artery dilation ( FMD ) . RESULTS Baseline demographics were similar except for age ( vitamin D versus placebo , mean ±sd 47 ±8 versus 40 ±10 years ; P=0.009 ) . Both groups had reduced FMD at baseline ( median values 2.9 % [ IQR 1.6 - 4.8 ] for vitamin D versus 2.5 % [ IQR 1.7 - 6.4 ] for placebo ; P=0.819 ) . Despite an increase in the concentration of serum 25-hydroxyvitamin D from baseline to 12 weeks ( 5.0 ng/ml [ IQR -0.9 - 7.4 ] versus -1.9 ng/ml [ IQR -4.0 - 0.1 ] for vitamin D versus placebo , respectively ; P=0.003 ) , there was no difference in FMD change ( 0.55 % [ IQR -1.05 - 2.13 ] versus 0.29 % [ IQR -1.61 - 1.77 ] ; P=0.748 ) . Vitamin D supplementation was associated with a decrease in total and non-high-density lipoprotein cholesterol , and an increase in indices of insulin resistance . CONCLUSIONS Among HIV-infected individuals with vitamin D deficiency , supplementation with 4,000 IU vitamin D3 daily for 12 weeks modestly improved vitamin D status and cholesterol but worsened insulin resistance without change in endothelial function . The mechanisms of resistance to st and ard doses of vitamin D and the complex role of vitamin D in glucose metabolism in this population require further investigation BACKGROUND Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure ( CHF ) . In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines . OBJECTIVE We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF . DESIGN One hundred twenty-three patients r and omly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [ D(+ ) group ] or placebo plus 500 mg Ca/d [ D(- ) group ] for 9 mo . Biochemical variables were assessed at baseline and after 9 mo . The survival rate was calculated for a follow-up period of 15 mo . RESULTS Ninety-three patients completed the study . Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D ( P = 0.001 ) , parathyroid hormone ( P = 0.007 ) , tumor necrosis factor alpha ( P = 0.006 ) , and interleukin 10 ( P = 0.042 ) . 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+ ) group but increased only by 3.6 ng/mL in the D(- ) group . Compared with baseline , parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+ ) group after 9 mo . The proinflammatory cytokine tumor necrosis factor alpha increased in the D(- ) group but remained constant in the D(+ ) group . The survival rate did not differ significantly between the study groups during the follow-up period . CONCLUSIONS Vitamin D(3 ) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease . Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF BACKGROUND Indirect evidence suggests that optimal vitamin D status is achieved with a serum 25-hydroxyvitamin D [ 25(OH)D ] 
    Output:
    