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: Inadequate intake of the recommended five-a-day fruit and vegetable portions might contribute to increased cardiovascular disease risk . We assessed the effects of dietary intake of a blackcurrant juice drink , rich in vitamin C and polyphenols , on oxidative stress and vascular function . This was a double-blind , placebo-controlled , parallel group study of 66 healthy adults who habitually consume < 2 portions of fruit and vegetables per day . Participants were r and omly allocated to consume 250ml of placebo ( flavored water ) or low or high blackcurrant juice drink four times a day for 6 weeks . Flow-mediated dilation ( FMD ) and plasma concentrations of F2-isoprostanes and vitamin C were measured . In the high blackcurrant juice drink group FMD increased significantly ( 5.8±3.1 to 6.9±3.1 % , P=0.022 ) compared with the placebo group ( 6.0±2.2 to 5.1±2.4 % ) . Plasma vitamin C concentration increased significantly in the low ( 38.6±17.6 to 49.4±21.0µmol/L , P<0.001 ) and high ( 34.6±20.4 to 73.8±23.3µmol/L , P<0.001 ) blackcurrant juice drink groups compared with the placebo group ( 38.1±21.0 to 29.0±17.6µmol/L ) . F2-isoprostane concentrations were significantly lower in the high blackcurrant juice drink group ( 225±64pg/ml ) compared with the low blackcurrant juice drink ( 257±69pg/ml , P=0.002 ) and placebo group ( 254±59pg/ml , P=0.003 ) . At follow-up , changes in plasma vitamin C correlated significantly with changes in FMD ( r=0.308 , P=0.044 ) . Consumption of blackcurrant juice drink high in vitamin C and polyphenols can decrease oxidative stress and improve vascular health in individuals with habitually low dietary fruit and vegetable intake BACKGROUND Loss of endothelium-derived nitric oxide ( EDNO ) contributes to the clinical expression of coronary artery disease ( CAD ) . Increased oxidative stress has been linked to impaired endothelial vasomotor function in atherosclerosis , and recent studies demonstrated that short-term ascorbic acid treatment improves endothelial function . METHODS AND RESULTS In a r and omized , double-blind , placebo-controlled study , we examined the effects of single-dose ( 2 g PO ) and long-term ( 500 mg/d ) ascorbic acid treatment on EDNO-dependent flow-mediated dilation of the brachial artery in patients with angiographically established CAD .  Flow-mediated dilation was examined by high-resolution vascular ultrasound at baseline , 2 hours after the single dose , and 30 days after long-term treatment in 46 patients with CAD .  Flow-mediated dilation improved from 6.6+/-3.5 % to 10.1+/-5.2 % after single-dose treatment , and the effect was sustained after long-term treatment ( 9 . 0+/-3.7 % ) , whereas flow-mediated dilation was 8.6+/-4.7 % at baseline and remained unchanged after single-dose ( 7.8+/-4.4 % ) and long-term ( 7.9+/-4.5 % ) treatment with placebo ( P=0.005 by repeated- measures ANOVA ) . Plasma ascorbic acid concentrations increased from 41.4+/-12 . 9 to 115.9+/-34.2 micromol/L after single-dose treatment and to 95 . 0+/-36.1 micromol/L after long-term treatment ( P<0.001 ) . CONCLUSIONS In patients with CAD , long-term ascorbic acid treatment has a sustained beneficial effect on EDNO action . Because endothelial dysfunction may contribute to the pathogenesis of cardiovascular events , this study indicates that ascorbic acid treatment may benefit patients with CAD Fifty diabetic patients took part in a four‐month , double‐blind crossover study comparing 500 mg of vitamin C daily with placebo . No significant difference was observed between vitamin C and placebo therapy in fasting whole blood glucose , serum cholesterol , triglycerides , and glycosylated haemoglobin levels The effect of a megadose of ascorbic acid ( AA ) on glucose and insulin responses after an oral-glucose-tolerance test ( OGTT ) is unknown . With a double-blind , placebo-controlled design , nine normoglycemic subjects ( 22 + /- 1 y , mean + /- SEM ) consumed AA  ( 2 g/d ) or placebo for 2 wk after a 2-wk washout period with placebo , and an OGTT was performed after an overnight fast . This 4-wk protocol was repeated in a crossover fashion . Plasma glucose was significantly elevated 1-h postpr and ial in vitamin C-saturated subjects vs those taking a placebo . The plasma insulin response curve was shifted rightward in vitamin C-saturated subjects relative to baseline : plasma insulin was significantly depressed at 0.5 h postpr and ial but significantly elevated at 2 h postpr and ial . These data indicate that elevated plasma AA delays the insulin response to a glucose challenge in normoglycemic adults , thereby prolonging the postpr and ial hyperglycemia . These effects might be partially explained by the competitive inhibition of glucose transfer into pancreatic beta cells by high concentrations of circulating AA Abstract Aims /hypothesis Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction , which has important implication s for the progression of disease . Thus , in the present study , we design ed a r and omised double-blind , placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus . Methods All data were collected from hospitalised diabetic patients . The electron paramagnetic resonance spectroscopic detection of spin-trapped α-phenyl-tert-butylnitrone ( PBN ) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes ( HbA1c 7.9 ± 1 % , n = 12 ) and healthy controls ( HbA1c 4.6 ± 0.5 % , n = 14 ) . Following participant r and omisation using numbers in a sealed envelope , venous blood sample s were obtained at rest , after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo . Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments . Primary outcome was the difference in changes in free radicals following ascorbate ingestion . Results Six diabetic patients and seven healthy control participants were r and omised to each of the placebo and ascorbate groups . Diabetic patients ( n = 12 ) exhibited an elevated concentration of PBN adducts ( p < 0.05 vs healthy , n = 14 ) , which were confirmed as secondary , lipid-derived oxygen-centred alkoxyl ( RO · ) radicals ( anitrogen = 1.37 mT and aβhydrogen = 0.18 mT ) . Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene ( p < 0.05 vs healthy ) . Vitamin C supplementation  increased plasma vitamin C concentration to a similar degree in both groups ( p < 0.05 vs pre-supplementation ) and attenuated the exercise-induced oxidative stress response ( p < 0.05 vs healthy).There were no selective treatment differences between groups in the primary outcome variable . Conclusions /interpretationThese findings are the first to suggest that oral vitamin C supplementation provides an effective prophylaxis against exercise-induced free radical-mediated lipid peroxidation in human diabetic blood . Clinical trials registration number : IS RCT N96164937 Funding : No external funding No study has ever examined the effect of vitamin C with metformin on fasting ( FBS ) and postmeal blood glucose ( PMBG ) as well as glycosylated hemoglobin ( HbA1c ) in the treatment of type 2 diabetes mellitus ( DM ) . The goal was to examine the effect of oral vitamin C with metformin on FBS , PMBG , HbA1c , and plasma ascorbic acid level ( PAA ) with type 2 DM . Seventy patients with type 2 DM participated in a prospect i ve , double-blind , placebo-controlled , 12-week study . The patients with type 2 DM were divided r and omly into placebo and vitamin C group of 35 each . Both groups received the treatment for twelve weeks . Decreased PAA levels were found in patients with type 2 diabetes mellitus . This level was reversed significantly after treatment with vitamin C along with metformin compared to placebo with metformin . FBS , PMBG , and HbA1c levels showed significant improvement after 12 weeks of treatment with vitamin C. In conclusion , oral supplementation of vitamin C with metformin  reverses ascorbic acid levels , reduces FBS , PMBG , and improves HbA1c . Hence , both the drugs in combination may be used in the treatment of type 2 DM to maintain good glycemic control The purpose of this r and omized study was to measure the influence of  vitamin C ( n = 15 runners ) compared with  placebo ( n = 13 runners )  supplementation on oxidative and immune changes in runners competing in an ultramarathon race . During the 7-day period before the race and on race day , subjects ingested in r and omized , double-blind fashion 1,500 mg/day vitamin C or placebo . On race day , blood sample s were collected 1 h before race , after 32 km of running , and then again immediately after race . Subjects in both groups maintained an intensity of approximately 75 % maximal heart rate throughout the ultramarathon race and ran a mean of 69 km ( range : 48 - 80 km ) in 9.8 h ( range : 5 - 12 h ) . Plasma ascorbic acid was markedly higher in the vitamin C compared with placebo group prerace and rose more strongly in the vitamin C group during the race ( postrace : 3.21 + /- 0.29 and 1.28 + /- 0.12 microg/100 microl , respectively , P < 0.001 ) . No significant group or interaction effects were measured for lipid hydroperoxide , F2-isoprostane , immune cell counts , plasma interleukin (IL)-6 , IL-10 , IL-1-receptor antagonist , or IL-8 concentrations , or mitogen-stimulated lymphocyte proliferation and IL-2 and IFN-gamma production . These data indicate that vitamin C supplementation in carbohydrate-fed runners does not serve as a countermeasure to oxidative and immune changes during or after a competitive ultramarathon race Free radicals in cigarette smoke ( CS ) cause oxidative damage to proteins , DNA , and lipids , contributing to the pathobiology of atherosclerosis , heart disease , and cancer . In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS . It is hypothesized that a combination of antioxidants is more effective than a single antioxidant , due to their interactions . To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination , we conducted an intervention study in smokers . In a r and omized double-blind placebo-controlled trial , we investigated whether vitamin C or an antioxidant mixture containing vitamin C , alpha-lipoic acid , and vitamin E decreases plasma F(2)-isoprostane levels , an index of oxidant stress , in smokers . Plasma of 126 smokers ( mean age , 46 years ; age range , 20 - 78 years ) was analyzed for F(2)-isoprostanes at baseline and after intervention with antioxidants and placebo . In smokers with a body mass index ( BMI ) above the median , 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F(2)-isoprostane levels by 28.8 pmol/liter when compared with the placebo group ( P = 0.001 ) ; levels in the mixture group were 7.45 pmol/liter lower after treatment , but this difference was not statistically significant ( P = 0.14 ) . There was no treatment effect in smokers with a low BMI .  BMI was significantly positively associated with plasma F(2)-isoprostane levels ( trend P = 0.001 ) . Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI . Our results do not indicate that an antioxidant combination is more effective than vitamin C alone . The intake of antioxidants may help prevent smoking 
    Output:
    
agent
Overall , vitamin C did not modify glucose , HbA1c and insulin concentrations .
Meta-regression analyses showed that age was a modifier of the effect of vitamin C on insulin concentration .
Furthermore , the effect size was associated with baseline BMI and plasma glucose levels , and with the duration of the intervention .
In conclusion , greater reduction in glucose concentrations observed in patients with diabetes , older individuals and with more prolonged supplementation .
***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: Inadequate intake of the recommended five-a-day fruit and vegetable portions might contribute to increased cardiovascular disease risk . We assessed the effects of dietary intake of a blackcurrant juice drink , rich in vitamin C and polyphenols , on oxidative stress and vascular function . This was a double-blind , placebo-controlled , parallel group study of 66 healthy adults who habitually consume < 2 portions of fruit and vegetables per day . Participants were r and omly allocated to consume 250ml of placebo ( flavored water ) or low or high blackcurrant juice drink four times a day for 6 weeks . Flow-mediated dilation ( FMD ) and plasma concentrations of F2-isoprostanes and vitamin C were measured . In the high blackcurrant juice drink group FMD increased significantly ( 5.8±3.1 to 6.9±3.1 % , P=0.022 ) compared with the placebo group ( 6.0±2.2 to 5.1±2.4 % ) . Plasma vitamin C concentration increased significantly in the low ( 38.6±17.6 to 49.4±21.0µmol/L , P<0.001 ) and high ( 34.6±20.4 to 73.8±23.3µmol/L , P<0.001 ) blackcurrant juice drink groups compared with the placebo group ( 38.1±21.0 to 29.0±17.6µmol/L ) . F2-isoprostane concentrations were significantly lower in the high blackcurrant juice drink group ( 225±64pg/ml ) compared with the low blackcurrant juice drink ( 257±69pg/ml , P=0.002 ) and placebo group ( 254±59pg/ml , P=0.003 ) . At follow-up , changes in plasma vitamin C correlated significantly with changes in FMD ( r=0.308 , P=0.044 ) . Consumption of blackcurrant juice drink high in vitamin C and polyphenols can decrease oxidative stress and improve vascular health in individuals with habitually low dietary fruit and vegetable intake BACKGROUND Loss of endothelium-derived nitric oxide ( EDNO ) contributes to the clinical expression of coronary artery disease ( CAD ) . Increased oxidative stress has been linked to impaired endothelial vasomotor function in atherosclerosis , and recent studies demonstrated that short-term ascorbic acid treatment improves endothelial function . METHODS AND RESULTS In a r and omized , double-blind , placebo-controlled study , we examined the effects of single-dose ( 2 g PO ) and long-term ( 500 mg/d ) ascorbic acid treatment on EDNO-dependent flow-mediated dilation of the brachial artery in patients with angiographically established CAD .  Flow-mediated dilation was examined by high-resolution vascular ultrasound at baseline , 2 hours after the single dose , and 30 days after long-term treatment in 46 patients with CAD .  Flow-mediated dilation improved from 6.6+/-3.5 % to 10.1+/-5.2 % after single-dose treatment , and the effect was sustained after long-term treatment ( 9 . 0+/-3.7 % ) , whereas flow-mediated dilation was 8.6+/-4.7 % at baseline and remained unchanged after single-dose ( 7.8+/-4.4 % ) and long-term ( 7.9+/-4.5 % ) treatment with placebo ( P=0.005 by repeated- measures ANOVA ) . Plasma ascorbic acid concentrations increased from 41.4+/-12 . 9 to 115.9+/-34.2 micromol/L after single-dose treatment and to 95 . 0+/-36.1 micromol/L after long-term treatment ( P<0.001 ) . CONCLUSIONS In patients with CAD , long-term ascorbic acid treatment has a sustained beneficial effect on EDNO action . Because endothelial dysfunction may contribute to the pathogenesis of cardiovascular events , this study indicates that ascorbic acid treatment may benefit patients with CAD Fifty diabetic patients took part in a four‐month , double‐blind crossover study comparing 500 mg of vitamin C daily with placebo . No significant difference was observed between vitamin C and placebo therapy in fasting whole blood glucose , serum cholesterol , triglycerides , and glycosylated haemoglobin levels The effect of a megadose of ascorbic acid ( AA ) on glucose and insulin responses after an oral-glucose-tolerance test ( OGTT ) is unknown . With a double-blind , placebo-controlled design , nine normoglycemic subjects ( 22 + /- 1 y , mean + /- SEM ) consumed AA  ( 2 g/d ) or placebo for 2 wk after a 2-wk washout period with placebo , and an OGTT was performed after an overnight fast . This 4-wk protocol was repeated in a crossover fashion . Plasma glucose was significantly elevated 1-h postpr and ial in vitamin C-saturated subjects vs those taking a placebo . The plasma insulin response curve was shifted rightward in vitamin C-saturated subjects relative to baseline : plasma insulin was significantly depressed at 0.5 h postpr and ial but significantly elevated at 2 h postpr and ial . These data indicate that elevated plasma AA delays the insulin response to a glucose challenge in normoglycemic adults , thereby prolonging the postpr and ial hyperglycemia . These effects might be partially explained by the competitive inhibition of glucose transfer into pancreatic beta cells by high concentrations of circulating AA Abstract Aims /hypothesis Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction , which has important implication s for the progression of disease . Thus , in the present study , we design ed a r and omised double-blind , placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus . Methods All data were collected from hospitalised diabetic patients . The electron paramagnetic resonance spectroscopic detection of spin-trapped α-phenyl-tert-butylnitrone ( PBN ) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes ( HbA1c 7.9 ± 1 % , n = 12 ) and healthy controls ( HbA1c 4.6 ± 0.5 % , n = 14 ) . Following participant r and omisation using numbers in a sealed envelope , venous blood sample s were obtained at rest , after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo . Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments . Primary outcome was the difference in changes in free radicals following ascorbate ingestion . Results Six diabetic patients and seven healthy control participants were r and omised to each of the placebo and ascorbate groups . Diabetic patients ( n = 12 ) exhibited an elevated concentration of PBN adducts ( p < 0.05 vs healthy , n = 14 ) , which were confirmed as secondary , lipid-derived oxygen-centred alkoxyl ( RO · ) radicals ( anitrogen = 1.37 mT and aβhydrogen = 0.18 mT ) . Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene ( p < 0.05 vs healthy ) . Vitamin C supplementation  increased plasma vitamin C concentration to a similar degree in both groups ( p < 0.05 vs pre-supplementation ) and attenuated the exercise-induced oxidative stress response ( p < 0.05 vs healthy).There were no selective treatment differences between groups in the primary outcome variable . Conclusions /interpretationThese findings are the first to suggest that oral vitamin C supplementation provides an effective prophylaxis against exercise-induced free radical-mediated lipid peroxidation in human diabetic blood . Clinical trials registration number : IS RCT N96164937 Funding : No external funding No study has ever examined the effect of vitamin C with metformin on fasting ( FBS ) and postmeal blood glucose ( PMBG ) as well as glycosylated hemoglobin ( HbA1c ) in the treatment of type 2 diabetes mellitus ( DM ) . The goal was to examine the effect of oral vitamin C with metformin on FBS , PMBG , HbA1c , and plasma ascorbic acid level ( PAA ) with type 2 DM . Seventy patients with type 2 DM participated in a prospect i ve , double-blind , placebo-controlled , 12-week study . The patients with type 2 DM were divided r and omly into placebo and vitamin C group of 35 each . Both groups received the treatment for twelve weeks . Decreased PAA levels were found in patients with type 2 diabetes mellitus . This level was reversed significantly after treatment with vitamin C along with metformin compared to placebo with metformin . FBS , PMBG , and HbA1c levels showed significant improvement after 12 weeks of treatment with vitamin C. In conclusion , oral supplementation of vitamin C with metformin  reverses ascorbic acid levels , reduces FBS , PMBG , and improves HbA1c . Hence , both the drugs in combination may be used in the treatment of type 2 DM to maintain good glycemic control The purpose of this r and omized study was to measure the influence of  vitamin C ( n = 15 runners ) compared with  placebo ( n = 13 runners )  supplementation on oxidative and immune changes in runners competing in an ultramarathon race . During the 7-day period before the race and on race day , subjects ingested in r and omized , double-blind fashion 1,500 mg/day vitamin C or placebo . On race day , blood sample s were collected 1 h before race , after 32 km of running , and then again immediately after race . Subjects in both groups maintained an intensity of approximately 75 % maximal heart rate throughout the ultramarathon race and ran a mean of 69 km ( range : 48 - 80 km ) in 9.8 h ( range : 5 - 12 h ) . Plasma ascorbic acid was markedly higher in the vitamin C compared with placebo group prerace and rose more strongly in the vitamin C group during the race ( postrace : 3.21 + /- 0.29 and 1.28 + /- 0.12 microg/100 microl , respectively , P < 0.001 ) . No significant group or interaction effects were measured for lipid hydroperoxide , F2-isoprostane , immune cell counts , plasma interleukin (IL)-6 , IL-10 , IL-1-receptor antagonist , or IL-8 concentrations , or mitogen-stimulated lymphocyte proliferation and IL-2 and IFN-gamma production . These data indicate that vitamin C supplementation in carbohydrate-fed runners does not serve as a countermeasure to oxidative and immune changes during or after a competitive ultramarathon race Free radicals in cigarette smoke ( CS ) cause oxidative damage to proteins , DNA , and lipids , contributing to the pathobiology of atherosclerosis , heart disease , and cancer . In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS . It is hypothesized that a combination of antioxidants is more effective than a single antioxidant , due to their interactions . To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination , we conducted an intervention study in smokers . In a r and omized double-blind placebo-controlled trial , we investigated whether vitamin C or an antioxidant mixture containing vitamin C , alpha-lipoic acid , and vitamin E decreases plasma F(2)-isoprostane levels , an index of oxidant stress , in smokers . Plasma of 126 smokers ( mean age , 46 years ; age range , 20 - 78 years ) was analyzed for F(2)-isoprostanes at baseline and after intervention with antioxidants and placebo . In smokers with a body mass index ( BMI ) above the median , 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F(2)-isoprostane levels by 28.8 pmol/liter when compared with the placebo group ( P = 0.001 ) ; levels in the mixture group were 7.45 pmol/liter lower after treatment , but this difference was not statistically significant ( P = 0.14 ) . There was no treatment effect in smokers with a low BMI .  BMI was significantly positively associated with plasma F(2)-isoprostane levels ( trend P = 0.001 ) . Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI . Our results do not indicate that an antioxidant combination is more effective than vitamin C alone . The intake of antioxidants may help prevent smoking 
    Output:
    