title: Lowering of oxidative stress improves endothelial function in healthy subjects with habitually low intake of fruit and vegetables: a randomized controlled trial of antioxidant- and polyphenol-rich blackcurrant juice. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. The Effect of Vitamin C Supplementation on Diabetic Hyperlipidaemia: a Double Blind, Crossover Study Megadose of vitamin C delays insulin response to a glucose challenge in normoglycemic adults. Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial Supplementation of Vitamin C Reduces Blood Glucose and Improves Glycosylated Hemoglobin in Type 2 Diabetes Mellitus: A Randomized, Double-Blind Study Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon. Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers. High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance. Lowered risks of hypertension and cerebrovascular disease after vitamin/mineral supplementation: the Linxian Nutrition Intervention Trial. Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer--Norfolk prospective study. Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer--Norfolk (EPIC-Norfolk) study: a population-based study. Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: Findings of a randomized controlled study. Vitamin C may have similar beneficial effects to Gemfibrozil on serum high-density lipoprotein-cholesterol in type 2 diabetic patients Unchanged renal haemodynamics following high dose ascorbic acid administration in normoalbuminuric IDDM patients. Effects of vitamins C and E and beta-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial. PRETREATMENT WITH INTRAVENOUS ASCORBIC ACID PRESERVES ENDOTHELIAL FUNCTION DURING ACUTE HYPERGLYCAEMIA (R1) The effect of aspirin and vitamins C and E on HbA1c assays. FFA-induced endothelial dysfunction can be corrected by vitamin C. Does short-term vitamin C reduce cardiovascular risk in type 2 diabetes? Effect of ascorbic acid on surgical stress response in gynecologic surgery.
abstract: 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-related diseases . Smoking cessation should still be considered the most effective way to prevent smoking-related diseases Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress . Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal . Thus endothelial dysfunction may worsen insulin resistance . Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes . In the present study , we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes .  Plasma vitamin C levels in 109 diabetic subjects were lower than healthy ( 36 + /- 2 microM ) levels . Thirty-two diabetic subjects with low plasma vitamin C ( < 40 microM ) were subsequently enrolled in a r and omized , double-blind , placebo-controlled study of vitamin C ( 800 mg/day for 4 wk ) . Insulin sensitivity ( determined by glucose clamp ) and forearm blood flow in response to ACh , sodium nitroprusside ( SNP ) , or insulin ( determined by plethysmography ) were assessed before and after 4 wk of treatment . In the placebo group ( n = 17 subjects ) , plasma vitamin C ( 22 + /- 3 microM ) , fasting glucose ( 159 + /- 12 mg/dl ) , insulin ( 19 + /- 7 microU/ml ) , and SI(Clamp ) [ 2.06 + /- 0.29 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] did not change significantly after placebo treatment . In the  vitamin C  group ( n = 15 subjects ) , basal plasma vitamin C ( 23 + /- 2 microM ) increased to 48 + /- 6 microM ( P < 0.01 ) after treatment , but this was significantly less than that expected for healthy subjects ( > 80 microM ) . No significant changes in fasting glucose ( 156 + /- 11 mg/dl ) , insulin ( 14 + /- 2 microU/ml ) , SI(Clamp ) [ 2.71 + /- 0.46 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] , or forearm blood flow in response to ACh , SNP , or insulin were observed after vitamin C treatment . We conclude that high-dose oral vitamin C therapy , result ing in incomplete replenishment of vitamin C levels , is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes A total of 3,318 men and women from a region in rural China were r and omized to receive daily either a multiple vitamin/mineral supplement or a placebo . Deaths that occurred in the participants were ascertained and classified according to cause over the 6-year period from 1985 to 1991 . At the end of supplementation , blood pressure readings were taken , and the prevalence of hypertension was determined . There was a slight reduction in overall mortality in the supplement group ( relative risk ( RR ) = 0.93 , 95 percent confidence interval ( CI ) 0.75 - 1.16 ) , with the decreased relative risk most pronounced for cerebrovascular disease deaths ( RR = 0.63 , 95 percent CI 0.37 - 1.07 ) . This benefit was greater for men ( RR = 0.42 , 95 percent CI 0.19 - 0.93 ) than for women ( RR = 0.93 , 95 percent CI 0.44 - 1.98 ) . Among the survivors , the presence of elevations in both systolic and diastolic blood pressures was less common in those who received the supplement ( RR for men = 0.43 , 95 % CI 0.28 - 0.65 ; RR for women = 0.92 , 95 percent CI 0.68 - 1.24 ) . This study indicates that supplementation with a multivitamin/mineral combination may have reduced mortality from cerebrovascular disease and the prevalence of hypertension in this rural population with a micronutrient-poor diet BACKGROUND Epidemiologic studies suggest that greater consumption of fruit and vegetables may decrease the risk of diabetes mellitus , but the evidence is limited and inconclusive . Plasma vitamin C level is a good biomarker of fruit and vegetable intake , but , to our knowledge , no prospect i ve studies have examined its association with diabetes risk . This study aims to examine whether fruit and vegetable intake and plasma vitamin C level are associated with the risk of incident type 2 diabetes . METHODS We administered a semiquantitative food frequency question naire to men and women from a population -based prospect i ve cohort ( European Prospect i ve Investigation of Cancer-Norfolk ) study who were aged 40 to 75 years at baseline ( 1993 - 1997 ) when plasma vitamin C level was determined and habitual intake of fruit and vegetables was assessed . During 12 years of follow-up between February 1993 and the end of December 2005 , 735 clinical ly incident cases of diabetes were identified among 21 831 healthy individuals . We report the odds ratios of diabetes associated with sex-specific quintiles of fruit and vegetable intake and of plasma vitamin C levels . RESULTS A strong inverse association was found between plasma vitamin C level and diabetes risk . The odds ratio of diabetes in the top quintile of plasma vitamin C was 0.38 ( 95 % confidence interval , 0.28 - 0.52 ) in a model adjusted for demographic , lifestyle , and anthropometric variables . In a similarly adjusted model , the odds ratio of diabetes in the top quintile of fruit and vegetable consumption was 0.78 ( 95 % confidence interval , 0.60 - 1.00 ) . CONCLUSIONS Higher plasma vitamin C level and , to a lesser degree , fruit and vegetable intake were associated with a substantially decreased risk of diabetes . Our findings highlight a potentially important public health message on the benefits of a diet rich in fruit and vegetables for the prevention of diabetes OBJECTIVE To examine the cross-sectional association between plasma vitamin C , self-reported diabetes , and HbA1c . RESEARCH DESIGN AND METHODS Data from a population -based study of diet , cancer , and chronic disease were analyzed . A total of 2,898 men and 3,560 women 45 - 74 years of age who were registered with general practice s in Norfolk , U.K. , were recruited to the European Prospect i ve Investigation Into Cancer-Norfolk study between 1995 and 1998 . RESULTS Mean plasma vitamin C levels were significantly higher in individuals with HbA1c levels < 7 % than in those with self-reported diabetes or prevalent undiagnosed hyperglycemia ( HbA1c > or = 7 % ) . An inverse gradient of mean plasma vitamin C was found in both sexes across quintiles of HbA1c distribution < 7 % . The odds ratio ( 95 % CI ) of having prevalent undiagnosed hyperglycemia per 20 micromol/l ( or 1 SD ) increase in plasma vitamin C was 0.70 ( 0.52 - 0.95 ) ( adjusted for sex , age , BMI , waist-to-hip ratio , tertiary education , any use of dietary supplements , vegetarian diet , alcohol consumption , physical activity , dietary vitamin E , dietary fiber , dietary saturated fat , and smoking history ) . The unadjusted change in HbA1c per 20 micromol/l increase in vitamin C estimated by linear regression was -0.12 % ( -0.14 to -0.09 ) in men and -0.09 % ( -0.11 to -0.07 ) in women . After adjusting for the possible confounders , these values were -0.08 % ( -0.11 to -0.04 ) in men and -0.05 % ( -0.07 to -0.03 ) in women . CONCLUSIONS An inverse association was found between plasma vitamin C and HbA1c .  Dietary measures to increase  plasma vitamin C  may be an important public health strategy for reducing the prevalence of diabetes AIM /HYPOTHESIS Skeletal muscle insulin resistance and oxidative stress are characteristic metabolic disturbances in people with type 2 diabetes . Studies in insulin resistant rodents show an improvement in skeletal muscle insulin sensitivity and oxidative stress following antioxidant supplementation . We therefore investigated the potential ameliorative effects of antioxidant ascorbic acid ( AA ) supplementation on skeletal muscle insulin sensitivity and oxidative stress in people with type 2 diabetes . METHODS Participants with stable glucose control commenced a r and omized cross-over study involving four months of AA ( 2 × 500 mg/day ) or placebo supplementation . Insulin sensitivity was assessed using a hyperinsulinaemic , euglycaemic clamp coupled with infusion of 6,6-D2 glucose . Muscle biopsies were measured for AA concentration and oxidative stress markers that included basal measures ( 2',7'-dichlorofluorescin [ DCFH ] oxidation , ratio of reduced-to-oxidized glutathione [ GSH/GSSG ] and F2-Isoprostanes ) and insulin-stimulated measures ( DCFH oxidation ) . Antioxidant concentrations , citrate synthase activity and protein abundances of sodium-dependent vitamin C transporter 2 ( SVCT2 ) , total Akt and phosphorylated Akt ( ser473 ) were also measured in muscle sample s. RESULTS AA supplementation significantly increased insulin-mediated glucose disposal ( delta rate of glucose disappearance ; ∆Rd ) ( p=0.009 ) , peripheral insulin-sensitivity index ( p=0.046 ) , skeletal muscle AA concentration ( p=0.017 ) and muscle SVCT2 protein expression ( p=0.008 ) ; but significantly decreased skeletal muscle DCFH oxidation during hyperinsulinaemia ( p=0.007 ) when compared with  placebo . Total superoxide dismutase activity was also lower following AA supplementation when compared with placebo ( p=0.006 ) . Basal oxidative stress markers , citrate synthase activity , endogenous glucose production , HbA1C and muscle Akt expression were not significantly altered by AA supplementation . CONCLUSIONS /INTERPRETATION In summary , oral AA supplementation ameliorates skeletal muscle oxidative stress during hyperinsulinaemia and improves insulin-mediated glucose disposal in people with type 2 diabetes . Findings implicate AA supplementation as a potentially inexpensive , convenient , and effective adjunct therapy in the treatment of insulin resistance in people with type 2 diabetes Objective : Type 2 diabetes mellitus ( DM-T2 ) is commonly associated with increased triglycerides ( TG ) , low-density lipoprotein cholesterol ( LDL-C ) and low high-density lipoprotein cholesterol ( HDL-C ) levels . Fibrates like gemfibrozil are frequently used in diabetic patients to decrease TG and increase HDL-C levels . We compared the efficacy of Vitamin C , an antioxidant vitamin , with gemfibrozil on serum HDL-C in diabetic patients . Methods : Type 2 diabetic patients , referred to our out-patient clinic were r and omly divided into three groups . After 1 month of lifestyle and diet modifications , groups A , B , and C were prescribed 1000 mg Vitamin C , 600 mg gemfibrozil and combination of both , respectively . Before the study initiation and after 6th week of drug prescription , the blood sample s were taken and analyzed for total cholesterol ( Total-C ) , HDL-C , TG , fasting blood sugar ( FBS ) , and hemoglobin A1c ( HbA1c ) levels . Findings : Sixty-seven patients entered , and 50 patients ( 18 male , 32 female ) finished the study . Overall , serum HDL-C increased significantly from 39.8 to 45.2 mg/dL in the participants ( P = 0.001 ) . HDL-C increased 6.3 , 4.4 and 5.0 mg/dL in groups A , B and C , respectively ( related significance s were 0.017 , 0.022 and 0.033 , respectively ) . Significant decrease of serum TG and Total-C occurred in gemfibrozil and combination groups , but not in Vitamin C group . Changes in serum HDL-C between three groups were not significant ( P = 0.963 ) . We found a significant decrease in TG and Total-C in the groups B and C ( P < 0.05 ) , but no significant changes of TG , Total-C , LDL-C , FBS and HbA1c in group A ( P > 0.05 ) . Conclusion : The results demonstrated that Vitamin C may have beneficial effects on HDL-C in diabetic patients without significant effects on plasma glucose or other lipid parameters ; however , its role for the treatment of low HDL-C patients should be evaluated in larger studies The object of the study was to test whether high dose ascorbic acid ( AA ) could normalize glomerular hyperfiltration in insulin-dependent diabetes mellitus ( IDDM ) patients . A prospect i ve , double-blind , r and omized , placebo ( tartaric acid , TA ) controlled study design was used , with parallel treatment lasting 4 weeks . Measurements were made before and after treatment , on 24 normoalbuminuric , normotensive male IDDM patients , who were r and omized to ascorbic acid ( n = 12 , age 35 years ( 18 - 39 ) , diabetes duration 12 years ( 2 - 12 ) , BP 128/82 mmHg ( SD 14/6 ) ) , or to placebo ( TA ) ( n = 12 , age 30 years ( 19 - 36 ) , diabetes duration 8 years ( 2 - 17 ) , BP 119/75 mmHg ( SD 9/7 ) . The intervention consisted of 6 enterosoluble tablets of 500 mg AA or 213 mg TA , twice a day , being daily doses of 6 g AA or 2.55 g TA . No significant differences in any of the parameters measured were seen , when comparing results following AA or placebo treatment . The glomerular filtration rate ( GFR , clearance of 125I-iothalamate ) was unchanged while effective renal plasma flow ( ERPF , clearance of 131I-hippuran ) tended to decline in both groups . The GFRs before and after treatment in the AA-treated group were 141 ( SD 15 ) and 134 ( SD 12 ) ml min-1 1.73 m-2 ; NS ( 2p = 0.09 ) . In the TA-treated group they were 142 ( SD 19 ) and 137 ( SD 16 ) ml min-1 1.73 m-2 ; NS ( 2p = 0.20 ) . The ERPFs in the AA group were 584 ( SD 93 ) and 545 ( SD 47 ) ml min-1 1.73 m-2 ; ( 2p = 0.06 ) . In the TA group they were 618 ( SD 108 ) and 574 ( SD 98 ) ml min-1 1.73 m-2 ( 2p = 0.03 ) . The filtration fractions ( FFs ) in the AA group were 0.244 and 0.246 NS . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Vitamin C , vitamin E , and beta-carotene are major antioxidants and as such may protect against the development of type 2 diabetes via reduction of oxidative stress . OBJECTIVE The purpose of this study was to investigate the long-term effects of supplementation with vitamin C , vitamin E , and beta-carotene for primary prevention of type 2 diabetes . DESIGN In the Women 's Antioxidant Cardiovascular Study , a r and omized trial that occurred between 1995 and 2005 , 8171 female health professionals aged > or = 40 y with either a history of cardiovascular disease ( CVD ) or > or =3 CVD risk factors were r and omly assigned to receive vitamin C ( ascorbic acid , 500 mg every day ) , vitamin E ( RRR-alpha-tocopherol acetate , 600 IU every other day ) , beta-carotene ( 50 mg every other day ) , or their respective placebos . RESULTS During a median follow-up of 9.2 y , a total of 895 incident cases occurred among 6574 women who were free of diabetes at baseline . There was a trend toward a modest reduction in diabetes risk in women assigned to receive vitamin C compared with those assigned to receive placebo [ relative risk ( RR ) : 0.89 ; 95 % CI : 0.78 , 1.02 ; P = 0.09 ] , whereas a trend for a slight elevation in diabetes risk was observed for vitamin E treatment ( RR : 1.13 ; 95 % CI : 0.99 , 1.29 ; P = 0.07 ) . However , neither of these effects reached statistical significance . No significant effect was observed for beta-carotene treatment ( RR : 0.97 ; 95 % CI : 0.85 , 1.11 ; P = 0.68 ) . CONCLUSION Our r and omized trial data showed no significant overall effects of vitamin C , vitamin E , and beta-carotene on risk of developing type 2 diabetes in women at high risk of CVD . This trial was registered at clinical trials.gov as NCT00000541 1 . Acute hyperglycaemia may impair endothelial function .  Ascorbic acid ( AA ) , administered intra‐arterially , has been reported to improve endothelium‐dependent vasodilatation during a forearm hyperglycaemic clamp . Using a r and omized , double‐blind , placebo‐controlled , cross‐over study , we investigated the potential for intravenous ascorbic acid to modify the endothelial response to acute systemic hyperglycaemia in humans BACKGROUND Aspirin ( ASA ) and vitamins C and E may inhibit non-enzymatic glycation in vivo and may also interfere with HbA(1c ) assays , masking true results . We investigated the effect of usual doses of ASA , vitamin C and E on HbA1c levels in a group of non-diabetic volunteers . METHODS A r and omized clinical trial was performed with 28 healthy non-diabetic individuals . Subjects were allocated to take ASA 200 mg/day , vitamin C 1 g/day , vitamin E 400 mg/day , or to a control group , for a period of 4 months . Blood sample s were collected at baseline and at monthly intervals for HbA1c analysis by HPLC Variant II ( BioRad ) , HPLC L-9100 ( Merck - Hitachi ) and Tina Quant HbA(1c ) II immunoassay ( Roche ) . RESULTS HbA(1c ) levels of the control , vitamin C and E groups did not change throughout the study , independently of the method used . HbA(1c ) measured by Hitachi L-9100 HPLC increased significantly ( P=0.033 ) at 4 months after ASA intake , although this increase was of only 0.17 % . CONCLUSIONS Treatment with vitamins C and E in pharmacological doses does not have any impact on HbA1c measurements in non-diabetic patients with the three methods employed . ASA induces a modest , not clinical ly relevant , increase in HbA1c levels with one of the methods Insulin resistance is associated with an inappropriate elevation of plasma FFA and endothelial dysfunction . FFA could stimulate formation of reactive oxygen species , which could be responsible for vascular impairment . In this r and omized , double-blind , cross-over study in 10 healthy volunteers ( 24 + /- 3 yr old ) , forearm blood flow ( FBF ) responses to intraarterial acetylcholine ( ACh ) and glyceryl trinitrate were assessed with coadministration of vitamin C ( 24 mg/ml ) or placebo , respectively , in the presence of increased plasma FFA induced by Intralipid/heparin infusion . The rise in plasma FFA from 320 + /- 64 to 1852 + /- 232 micromol/liter was associated with a reduced response of FBF to ACh by 55 % ( P < 0.01 ) . During coadministration of vitamin C , the impaired responsiveness of FBF to ACh was completely reversed and not different from that observed under baseline conditions . Vitamin C did not affect plasma FFA concentrations . Glyceryl trinitrate responsiveness was unchanged during FFA elevation , with or without vitamin C. These data suggest that FFA-induced vascular oxidative stress could contribute to endothelial dysfunction in insulin-resistant patients . High concentrations of antioxidants are able to reverse the local effects of FFA on endothelium-dependent vasodilation OBJECTIVE Vitamin C is a powerful antioxidant that is potentially useful in the prevention of atherosclerosis in diabetic individuals . However , the mechanism(s ) of vitamin C 's anti-atherosclerotic effects in vivo are unresolved , and clinical trials in nondiabetic individuals have yielded conflicting results . Therefore , we performed 32 studies in a r and omized , crossover , dose-response trial in 8 volunteers with type 2 diabetes to determine the effects of vitamin C on serum vitamin C levels , lipids , inflammation , and coagulation . METHODS Well-controlled , type 2 volunteers received , in r and omized order for 2-week periods , each of the following : 1 ) no supplemental vitamin C , 2 ) low-dose vitamin C ( 250 mg/day ) , 3 ) medium-dose vitamin C ( 500 mg/day ) , and 4 ) high-dose vitamin C ( 1,000 mg/day ) . A high-caloric content lunch was ingested during each study arm to enhance oxidative stress . Serum vitamin C levels and atherosclerotic risk factors including lipids and markers of oxidative stress , inflammation , and hypercoagulation were determined . RESULTS Serum vitamin C levels increased significantly at all dosages . In addition , the high-caloric content meal result ed in acute elevations of glucose , insulin , and triglycerides for several hours postmeal . However , no significant effect of vitamin C was observed on lipid parameters or any of the surrogate markers of oxidative stress , inflammation , or hypercoagulability . CONCLUSION Our study suggests that if vitamin C does have anti-atherosclerotic effects in diabetes , it does not exert them through the traditional pathways identifiable by established surrogate markers of cardiovascular risk Surgical stress may cause neural , endocrine , metabolic and humoral responses depending on the severity of the procedure . In this study , we aim ed to study the effect of the preoperatively given ascorbic acid ( AA ) , which is an antioxidant , and its role in the bio synthesis of neuropituitary hormones on the surgical stress response . Twenty-two American Society of Anaesthesiologists I and II patients ageing between 18 and 40 , who have no endocrine and metabolic disease , and undergoing abdominal operation for non-malignant diseases were allocated to the study . These non-premedicated patients were divided into two groups in r and om : Group I , etomi date group ; and Group II , AA plus etomi date group . AA was given to patients in Group II 20min before etomi date injection . After monitoring the patient , anaesthetic induction was applied by giving 0.3 mg/kg of etomi date , 2 microg/kg of fentanyl and 0.1 mg/kg of vecuronium . Anaesthesia was continued with 1 - 0.7 % isoflurane and N2O/O2 ( 67 and 37 % , respectively ) . Tramadol was given for the management of post-operative analgesia . Blood sample s were obtained from all patients before the operation and at second , sixth , twelfth and twenty-forth hours after the beginning of operation for cortisol , adrenocorticotropic hormone ( ACTH ) , osteocalcin , insulin and blood glucose level analyses . There was no statistically significant difference in cortisol , osteocalcin , insulin and glucose levels in both groups , when compared to the control levels . Whereas , patients in Group II had higher levels of cortisol than the control group at sixth hour , which were in normal limits , and there was no decrease in osteocalcin concentration . ACTH level was increased at the second and sixth hours , which was statistically significant , but at twelfth and twenty-forth hours , they were close to control group levels . As a result , we conclude that AA given before anaesthesia achieved by etomi date is not sufficient for the prevention of surgical stress response and that AA induction before anaesthesia should be preferred , particularly for the prevention of decrease in osteocalcin levels
target: 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 .
background: R and omised controlled trials ( RCTs ) have observed contrasting results on the effects of vitamin C on circulating biomarkers of glycaemic and insulin regulation .