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 Statins are at the forefront of strategies to manage hypercholesterolemia . However 10 % to 15 % of patients are intolerant to any statin drugs , even at low daily doses and almost one-third of statin users discontinue therapy within 1 year . Some nutraceuticals are prescribed as lipid-lowering substances , but doubts remain about their efficacy and tolerability . Objectives We aim ed to investigate the efficacy and the safety of a nutraceutical combination consisting mainly of 200 mg red yeast rice extract ( equivalent to 3 mg monacolins ) , 500 mg berberine , and 10 mg policosanols ( MBP-NC ) in patients with low-moderate risk hypercholesterolemia . Methods In this single centre , r and omized , double-blind , placebo-controlled study 60 consecutive out patients ( 29 men and 31 women ; age range = 18–60 years ) , with newly diagnosed primary hypercholesterolemia not previously treated , after a run-in period of 3 weeks on a stable hypolipidic diet , were r and omized to receive a pill of MBP-NC ( n = 30 ) or placebo ( n = 30 ) once a day after dinner , in addition to the hypolipidic diet . The efficacy and the tolerability of the proposed nutraceutical treatment were fully assessed after 4 , 12 , and 24 weeks of treatment . Results In the MBP-NC group both total cholesterol and LDL-C already showed a significant reduction at Week 4 ( –30.3 % ± 33.9 % and –29.4 % ± 35.3 % , respectively ) that remained substantially unchanged at Week 12 ( –26.7 % ± 33.1 % and –25.6 % ± 31.5 % , respectively ) and at Week 24 ( –24.6 % ± 32.1 % and –23.7 % ± 32.6 % , respectively ) . The between-groups differences were significant at all time points for both total cholesterol and LDL-C. There were no significant changes in HDL-C , fasting glucose , and triglyceride serum levels in either group . MBP-NC  was also safe and well tolerated . Conclusions In patients with low- to moderate-risk hypercholesterolemia  a nutraceutical combination in association with a hypolipidic diet  significantly reduced total cholesterol and LDL-C levels and may favor the reaching the recommended cholesterol targets . Clinical Trials.gov identifier : NCT02078167 Patients with diabetes show an increased vascular morbidity and mortality that reduces their life expectancy by ~5–15 years ( depending on the age at diagnosis ) ( 1 ) . There is convincing evidence from epidemiological and pathophysiological studies that hyperglycemia per se is largely responsible for the harmful effects of the disease . As recently shown by clinical trials , treatment of this condition may reduce cardiovascular events and mortality , and several therapies should be considered : initiating early and individualized treatment and avoiding hypoglycemia . As shown in the Multiple Risk Factor Intervention Trial , at any given level of major cardiovascular risk factors , diabetes is associated with an odds ratio of 2–4 for cardiovascular mortality compared with nondiabetic subjects ( 2 ) . These results were confirmed by the European Prospect i ve Investigation of Cancer and Nutrition ( EPIC Norfolk ) study ( 3 ) and a recent analysis of the Atherosclerosis Risk in Communities ( ARIC ) study ( 4 ) . Furthermore , a recently published 18-year follow-up study from Finl and demonstrated a similar impact of type 1 and type 2 diabetes on cardiovascular mortality . The adjusted hazard ratios compared with age-matched subjects without diabetes were 5.2 and 4.9 for type 1 and type 2 diabetes , respectively ( 5 ) . Thus , today evidence exists on long-term follow-up population -based studies in patients with type 1 and type 2 diabetes . This evidence clearly suggests that hyperglycemia is a key risk factor not only for diabetes-related disease , but also for cardiovascular and all-cause mortality . On the basis of these long-term observations , one can assume an increment of cardiovascular disease per increase of 1 unit ( % ) A1C of ~18 % ( 6 ) . As shown in numerous prospect i ve studies , the deleterious effects of dysglycemia ( fasting and postpr and ial hyperglycemia ) develop before diabetes is diagnosed . In the Glucose Tolerance in Acute Myocardial Infa rct ion study of patients with acute coronary syndrome  , abnormal glucose tolerance was the strongest independent Berberine ( BERB ) and a combination ( COMB ) of berberine ( CAS 2086 - 83 - 1 ) with policosanol ( CAS 557 - 61 - 9 ) , red yeast extract ( containing monacolin , CAS 557 - 61 - 9 ) , folic acid and astaxanthin were orally administered daily for 4 weeks to 40 subjects with moderate dyslipidemias divided in two parallel groups each of 20 subjects .  Total cholesterol ( TC ) , LDL , HDL , Non HDL , ApoB , ApoA , Lp(a ) and triglycerides ( TG ) were measured before and at the end of treatments . BERB and COMB significantly reduced TC ( respectively by 16 % and 20 % ) , LDL ( by 20 % and 25 % ) , ApoB ( by 15 % and 29 % ) and TG ( by 22 % and 26 % ) , and increased HDL ( by 6.6 % and 5.1 % ) . Adverse events or impairments of liver transaminases or of CPK were not observed . In conclusion , food supplements containing natural products such as berberine , policosanol , red yeast extracts , folic acid and astaxanthin could be a useful support to diet and life style changes to correct dyslipidemias and to reduce cardiovascular risk in subjects with moderate mixed dyslipidemias BACKGROUND Astaxanthin has been reported to improve dyslipidemia and metabolic syndrome in animals , but such effects in humans are not well known . METHODS Placebo-controlled astaxanthin administration at doses of 0 , 6 , 12 , 18 mg/day for 12 weeks was r and omly allocated to 61 non-obese subjects with fasting serum triglyceride of 120 - 200mg/dl and without diabetes and hypertension , aged 25 - 60 years . RESULTS In before and after tests , body mass index ( BMI ) and LDL-cholesterol were unaffected at all doses , however , triglyceride decreased , while HDL-cholesterol increased significantly . Multiple comparison tests showed that 12 and 18 mg/day doses significantly reduced triglyceride , and 6 and 12 mg doses significantly increased HDL-cholesterol . Serum adiponectin was increased by astaxanthin ( 12 and 18 mg/day ) , and changes of adiponectin correlated positively with HDL-cholesterol changes independent of age and BMI . CONCLUSIONS This first-ever r and omized , placebo-controlled human study suggests that astaxanthin consumption ameliorates triglyceride and HDL-cholesterol in correlation with increased adiponectin in humans Efficacy of a new patented proprietary combination of natural nutraceuticals ( PN ) containing natural hypolipidemic as red yeast , policosanol and berberine was tested in a large study on dyslipidemic patients in clinical practice . A parallel , controlled , r and omized , multicenter study was design ed . After 2 weeks on a stable dietary regimen , the patients were r and omized to PN 1 tablet/day associated with diet ( PN + D ) or diet alone ( D ) for 16 weeks . Entry criteria were : Tot-Chol > 200 mg/dL or LDL-Chol > 150 mg/dL without a clear indication for statins , or plasma triglycerides > 150 mg/dL.  Lipid pattern and CV parameters were evaluated at baseline and monthly . 1,751 patients were enrolled in 248 Italian units , 933 patients on PN + D and 818 on D. The baseline lipid values were : Tot-Chol 255.4 versus 243.1 mg/dL , LDL-Chol 170.1 versus 162.2 mg/dL , HDL-Chol 50.0 versus 48.8 mg/dL , and TG 190.5 versus 184.4 mg/dL. PN constantly and significantly improved lipid parameters versus D group : at 16 weeks −19.1 versus −9.4 % for Tot-Chol ( p < 0.001 ) , −23.5 versus −10.8 % for LDL-Chol ( p < 0.001 ) , + 11.6 versus + 4.0 % for HDL-Chol ( p < 0.001 ) , −17.9 versus −11.3 % for TG ( p < 0.001 ) . In conclusions , PN plus diet allows an effective improvement of blood lipids with a significant reduction of global CV risk , suggesting a role for PN in CHD prevention A dietary supplement ( AP , Armolipid Plus ) that combines red yeast rice extract , policosanol , berberine , folic acid , coenzyme Q10 and asthaxantine can have beneficial effects on cardiovascular disease ( CVD ) biomarkers . The aim of this study was to assess whether the intake of AP , in combination with dietary recommendations , reduces serum low density lipoprotein cholesterol ( LDL-c ) concentrations and other CVD biomarkers in patients with hypercholesterolemia . Eligible patients were recruited from the outpatient clinics of six Spanish hospitals Hospital Virgen del Rocío ( Sevilla ) ; Hospital San Jorge ( Huesca ) ; Hospital San Pedro ( Logroño ) ; Hospital Gregorio Marañón ( Madrid ) , Hospital la Fe ( Valencia ) and Hospital Universitari Sant Joan ( Reus ) as recruiting and coordinating center . 102 participants ( mean age ± SD ; 50.91±11.61 ; 32 men ) with low CVD , with mild-to-moderately elevated LDL-c ( between 3.35 mmol/L and 4.88 mmol/L ) without hypolipemic therapy were r and omized in a double-blind , parallel , controlled , multicenter trial commencing January 2012 and ending December 2012 . Among the exclusion criteria were any concomitant chronic disease , triglycerides ( TG ) > 3.97 mmol/L , pregnant or lactating , and history of CVD . At 12 weeks , compared to placebo , AP reduced LDL-c by −6.9 % , apolipoprotein ( Apo ) B-100 by −6.6 % and total cholesterol/HDL-c ratio by −5.5 % , the ApoB/ApoA1 ratio by −8.6 % , while increasing ApoA1 by + 2.5 % ( p<0.05 ) . AP consumption was associated with modest mean weight loss of −0.93 kg ( 95%CI : -1.74 to -0.12 ; P = 0.02 ) compared with control group while dietary composition remained unchanged in the AP group . The AP product was well tolerated . In conclusion , AP , combined with dietary recommendations , reduced LDL-c levels as well as total cholesterol/HDL-c and ApoB/ApoA1 ratios , while increasing Apo A1 , all of which are improvements in CVD risk indicators . AP is a product which could benefit patients having moderate hyperlipidemia and excess body weight . Trial Registration Clinical Trials.gov Introduction Statins are at the forefront of strategies to manage dyslipidemia , although they are not always well tolerated . At 6–7 months after the drug was supplied , discontinuation rates averaged 30 % . Alternate agents to statins have been studied . Some nutraceuticals demonstrated an efficacy in reducing cholesterol concentrations . However , there are no data regarding the use of nutraceuticals in elderly dyslipidemic patients . The purpose of this study was to examine the efficacy , safety , and tolerability of a nutraceutical-based protocol in elderly hypercholesterolemic patients previously intolerant to statins . Methods This study was performed as a r and omized , prospect i ve , parallel group , single-blind study . Patients were included in the study if they had high total cholesterolemia , high low-density lipoprotein cholesterol ( LDL-C ) , > 75 years of age , statin-intolerant , and were refusing other pharmaceutical treatments for hypercholesterolemia . At the baseline visit , eligible patients were r and omized to either nutraceutical-combined pill ( containing berberine 500 mg , policosanol 10 mg , red yeast rice 200 mg , folic acid 0.2 mg , coenzyme Q10 2.0 mg , and astaxanthin 0.5 mg ) or placebo , and the first dose was dispensed . The efficacy , safety , and tolerability of the proposed treatment were fully assessed after 3 , 6 , and 12 months of treatment . Results Out of 106 consecutive patients screened , 80 eligible patients were r and omized to receive either 
    Output:
    
agent
NComb-induced amelioration of lipid profile was not affected by duration of supplementation nor by baseline lipid levels ; conversely , a greater glucose-lowering effect of NComb was found with higher baseline glucose levels and longer duration s of supplementation .
In conclusion , the present results suggest that NComb supplementation is associated with improvement of lipid and glucose profile .
Short-term beneficial effects of NComb supplementation appear to be maintained in the long term
***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 Statins are at the forefront of strategies to manage hypercholesterolemia . However 10 % to 15 % of patients are intolerant to any statin drugs , even at low daily doses and almost one-third of statin users discontinue therapy within 1 year . Some nutraceuticals are prescribed as lipid-lowering substances , but doubts remain about their efficacy and tolerability . Objectives We aim ed to investigate the efficacy and the safety of a nutraceutical combination consisting mainly of 200 mg red yeast rice extract ( equivalent to 3 mg monacolins ) , 500 mg berberine , and 10 mg policosanols ( MBP-NC ) in patients with low-moderate risk hypercholesterolemia . Methods In this single centre , r and omized , double-blind , placebo-controlled study 60 consecutive out patients ( 29 men and 31 women ; age range = 18–60 years ) , with newly diagnosed primary hypercholesterolemia not previously treated , after a run-in period of 3 weeks on a stable hypolipidic diet , were r and omized to receive a pill of MBP-NC ( n = 30 ) or placebo ( n = 30 ) once a day after dinner , in addition to the hypolipidic diet . The efficacy and the tolerability of the proposed nutraceutical treatment were fully assessed after 4 , 12 , and 24 weeks of treatment . Results In the MBP-NC group both total cholesterol and LDL-C already showed a significant reduction at Week 4 ( –30.3 % ± 33.9 % and –29.4 % ± 35.3 % , respectively ) that remained substantially unchanged at Week 12 ( –26.7 % ± 33.1 % and –25.6 % ± 31.5 % , respectively ) and at Week 24 ( –24.6 % ± 32.1 % and –23.7 % ± 32.6 % , respectively ) . The between-groups differences were significant at all time points for both total cholesterol and LDL-C. There were no significant changes in HDL-C , fasting glucose , and triglyceride serum levels in either group . MBP-NC  was also safe and well tolerated . Conclusions In patients with low- to moderate-risk hypercholesterolemia  a nutraceutical combination in association with a hypolipidic diet  significantly reduced total cholesterol and LDL-C levels and may favor the reaching the recommended cholesterol targets . Clinical Trials.gov identifier : NCT02078167 Patients with diabetes show an increased vascular morbidity and mortality that reduces their life expectancy by ~5–15 years ( depending on the age at diagnosis ) ( 1 ) . There is convincing evidence from epidemiological and pathophysiological studies that hyperglycemia per se is largely responsible for the harmful effects of the disease . As recently shown by clinical trials , treatment of this condition may reduce cardiovascular events and mortality , and several therapies should be considered : initiating early and individualized treatment and avoiding hypoglycemia . As shown in the Multiple Risk Factor Intervention Trial , at any given level of major cardiovascular risk factors , diabetes is associated with an odds ratio of 2–4 for cardiovascular mortality compared with nondiabetic subjects ( 2 ) . These results were confirmed by the European Prospect i ve Investigation of Cancer and Nutrition ( EPIC Norfolk ) study ( 3 ) and a recent analysis of the Atherosclerosis Risk in Communities ( ARIC ) study ( 4 ) . Furthermore , a recently published 18-year follow-up study from Finl and demonstrated a similar impact of type 1 and type 2 diabetes on cardiovascular mortality . The adjusted hazard ratios compared with age-matched subjects without diabetes were 5.2 and 4.9 for type 1 and type 2 diabetes , respectively ( 5 ) . Thus , today evidence exists on long-term follow-up population -based studies in patients with type 1 and type 2 diabetes . This evidence clearly suggests that hyperglycemia is a key risk factor not only for diabetes-related disease , but also for cardiovascular and all-cause mortality . On the basis of these long-term observations , one can assume an increment of cardiovascular disease per increase of 1 unit ( % ) A1C of ~18 % ( 6 ) . As shown in numerous prospect i ve studies , the deleterious effects of dysglycemia ( fasting and postpr and ial hyperglycemia ) develop before diabetes is diagnosed . In the Glucose Tolerance in Acute Myocardial Infa rct ion study of patients with acute coronary syndrome  , abnormal glucose tolerance was the strongest independent Berberine ( BERB ) and a combination ( COMB ) of berberine ( CAS 2086 - 83 - 1 ) with policosanol ( CAS 557 - 61 - 9 ) , red yeast extract ( containing monacolin , CAS 557 - 61 - 9 ) , folic acid and astaxanthin were orally administered daily for 4 weeks to 40 subjects with moderate dyslipidemias divided in two parallel groups each of 20 subjects .  Total cholesterol ( TC ) , LDL , HDL , Non HDL , ApoB , ApoA , Lp(a ) and triglycerides ( TG ) were measured before and at the end of treatments . BERB and COMB significantly reduced TC ( respectively by 16 % and 20 % ) , LDL ( by 20 % and 25 % ) , ApoB ( by 15 % and 29 % ) and TG ( by 22 % and 26 % ) , and increased HDL ( by 6.6 % and 5.1 % ) . Adverse events or impairments of liver transaminases or of CPK were not observed . In conclusion , food supplements containing natural products such as berberine , policosanol , red yeast extracts , folic acid and astaxanthin could be a useful support to diet and life style changes to correct dyslipidemias and to reduce cardiovascular risk in subjects with moderate mixed dyslipidemias BACKGROUND Astaxanthin has been reported to improve dyslipidemia and metabolic syndrome in animals , but such effects in humans are not well known . METHODS Placebo-controlled astaxanthin administration at doses of 0 , 6 , 12 , 18 mg/day for 12 weeks was r and omly allocated to 61 non-obese subjects with fasting serum triglyceride of 120 - 200mg/dl and without diabetes and hypertension , aged 25 - 60 years . RESULTS In before and after tests , body mass index ( BMI ) and LDL-cholesterol were unaffected at all doses , however , triglyceride decreased , while HDL-cholesterol increased significantly . Multiple comparison tests showed that 12 and 18 mg/day doses significantly reduced triglyceride , and 6 and 12 mg doses significantly increased HDL-cholesterol . Serum adiponectin was increased by astaxanthin ( 12 and 18 mg/day ) , and changes of adiponectin correlated positively with HDL-cholesterol changes independent of age and BMI . CONCLUSIONS This first-ever r and omized , placebo-controlled human study suggests that astaxanthin consumption ameliorates triglyceride and HDL-cholesterol in correlation with increased adiponectin in humans Efficacy of a new patented proprietary combination of natural nutraceuticals ( PN ) containing natural hypolipidemic as red yeast , policosanol and berberine was tested in a large study on dyslipidemic patients in clinical practice . A parallel , controlled , r and omized , multicenter study was design ed . After 2 weeks on a stable dietary regimen , the patients were r and omized to PN 1 tablet/day associated with diet ( PN + D ) or diet alone ( D ) for 16 weeks . Entry criteria were : Tot-Chol > 200 mg/dL or LDL-Chol > 150 mg/dL without a clear indication for statins , or plasma triglycerides > 150 mg/dL.  Lipid pattern and CV parameters were evaluated at baseline and monthly . 1,751 patients were enrolled in 248 Italian units , 933 patients on PN + D and 818 on D. The baseline lipid values were : Tot-Chol 255.4 versus 243.1 mg/dL , LDL-Chol 170.1 versus 162.2 mg/dL , HDL-Chol 50.0 versus 48.8 mg/dL , and TG 190.5 versus 184.4 mg/dL. PN constantly and significantly improved lipid parameters versus D group : at 16 weeks −19.1 versus −9.4 % for Tot-Chol ( p < 0.001 ) , −23.5 versus −10.8 % for LDL-Chol ( p < 0.001 ) , + 11.6 versus + 4.0 % for HDL-Chol ( p < 0.001 ) , −17.9 versus −11.3 % for TG ( p < 0.001 ) . In conclusions , PN plus diet allows an effective improvement of blood lipids with a significant reduction of global CV risk , suggesting a role for PN in CHD prevention A dietary supplement ( AP , Armolipid Plus ) that combines red yeast rice extract , policosanol , berberine , folic acid , coenzyme Q10 and asthaxantine can have beneficial effects on cardiovascular disease ( CVD ) biomarkers . The aim of this study was to assess whether the intake of AP , in combination with dietary recommendations , reduces serum low density lipoprotein cholesterol ( LDL-c ) concentrations and other CVD biomarkers in patients with hypercholesterolemia . Eligible patients were recruited from the outpatient clinics of six Spanish hospitals Hospital Virgen del Rocío ( Sevilla ) ; Hospital San Jorge ( Huesca ) ; Hospital San Pedro ( Logroño ) ; Hospital Gregorio Marañón ( Madrid ) , Hospital la Fe ( Valencia ) and Hospital Universitari Sant Joan ( Reus ) as recruiting and coordinating center . 102 participants ( mean age ± SD ; 50.91±11.61 ; 32 men ) with low CVD , with mild-to-moderately elevated LDL-c ( between 3.35 mmol/L and 4.88 mmol/L ) without hypolipemic therapy were r and omized in a double-blind , parallel , controlled , multicenter trial commencing January 2012 and ending December 2012 . Among the exclusion criteria were any concomitant chronic disease , triglycerides ( TG ) > 3.97 mmol/L , pregnant or lactating , and history of CVD . At 12 weeks , compared to placebo , AP reduced LDL-c by −6.9 % , apolipoprotein ( Apo ) B-100 by −6.6 % and total cholesterol/HDL-c ratio by −5.5 % , the ApoB/ApoA1 ratio by −8.6 % , while increasing ApoA1 by + 2.5 % ( p<0.05 ) . AP consumption was associated with modest mean weight loss of −0.93 kg ( 95%CI : -1.74 to -0.12 ; P = 0.02 ) compared with control group while dietary composition remained unchanged in the AP group . The AP product was well tolerated . In conclusion , AP , combined with dietary recommendations , reduced LDL-c levels as well as total cholesterol/HDL-c and ApoB/ApoA1 ratios , while increasing Apo A1 , all of which are improvements in CVD risk indicators . AP is a product which could benefit patients having moderate hyperlipidemia and excess body weight . Trial Registration Clinical Trials.gov Introduction Statins are at the forefront of strategies to manage dyslipidemia , although they are not always well tolerated . At 6–7 months after the drug was supplied , discontinuation rates averaged 30 % . Alternate agents to statins have been studied . Some nutraceuticals demonstrated an efficacy in reducing cholesterol concentrations . However , there are no data regarding the use of nutraceuticals in elderly dyslipidemic patients . The purpose of this study was to examine the efficacy , safety , and tolerability of a nutraceutical-based protocol in elderly hypercholesterolemic patients previously intolerant to statins . Methods This study was performed as a r and omized , prospect i ve , parallel group , single-blind study . Patients were included in the study if they had high total cholesterolemia , high low-density lipoprotein cholesterol ( LDL-C ) , > 75 years of age , statin-intolerant , and were refusing other pharmaceutical treatments for hypercholesterolemia . At the baseline visit , eligible patients were r and omized to either nutraceutical-combined pill ( containing berberine 500 mg , policosanol 10 mg , red yeast rice 200 mg , folic acid 0.2 mg , coenzyme Q10 2.0 mg , and astaxanthin 0.5 mg ) or placebo , and the first dose was dispensed . The efficacy , safety , and tolerability of the proposed treatment were fully assessed after 3 , 6 , and 12 months of treatment . Results Out of 106 consecutive patients screened , 80 eligible patients were r and omized to receive either 
    Output:
    