title: A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial. A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk No Effect of High-Dose Vitamin D Supplementation on Glycemic Status or Cardiovascular Risk Factors in Subjects With Prediabetes Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. Vitamin D and health in adults in Australia and New Zealand: a position statement. Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial Vitamin d deficiency impacts on expression of toll-like receptor-2 and cytokine profile: a pilot study C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Risk of bias versus quality assessment of randomised controlled trials: cross sectional study Vitamin D and Serum Cytokines in a Randomized Clinical Trial Plasma 1,25(OH)2D levels decrease in postmenopausal women with hypovitaminosis D. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. Effects of vitamin D supplementation on markers of vascular function after myocardial infarction--a randomised controlled trial. Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes.
abstract: Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 Low serum 25-hydroxyvitamin D ( 25(OH)D ) has been shown to correlate with increased risk of type 2 diabetes . Small , observational studies suggest an action for vitamin D in improving insulin sensitivity and /or insulin secretion . The objective of the present study was to investigate the effect of improved vitamin D status on insulin resistance ( IR ) , utilising r and omised , controlled , double-blind intervention administering 100 microg ( 4000 IU ) vitamin D(3 ) ( n 42 ) or placebo ( n 39 ) daily for 6 months to South Asian women , aged 23 - 68 years , living in Auckl and , New Zeal and . Subjects were insulin resistant - homeostasis model assessment 1 (HOMA1)>1.93 and had serum 25(OH)D concentration < 50 nmol/l . Exclusion criteria included diabetes medication and vitamin D supplementation > 25 microg ( 1000 IU)/d . The HOMA2 computer model was used to calculate outcomes . Median ( 25th , 75th percentiles ) serum 25(OH)D(3 ) increased significantly from 21 ( 11 , 40 ) to 75 ( 55 , 84 ) nmol/l with supplementation . Significant improvements were seen in insulin sensitivity and IR ( P = 0.003 and 0.02 , respectively ) , and fasting insulin decreased ( P = 0.02 ) with supplementation compared with placebo . There was no change in C-peptide with supplementation . IR was most improved when endpoint serum 25(OH)D reached > or = 80 nmol/l . Secondary outcome variables ( lipid profile and high sensitivity C-reactive protein ) were not affected by supplementation . In conclusion , improving vitamin D status in insulin resistant women result ed in improved IR and sensitivity , but no change in insulin secretion . Optimal vitamin D concentrations for reducing IR were shown to be 80 - 119 nmol/l , providing further evidence for an increase in the recommended adequate levels . Registered Trial No. ACTRN12607000642482 Vitamin D ( VitD ) supplementation has been advocated for cardiovascular risk reduction ; however , supporting data are sparse . The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk . Subjects in this prospect i ve , r and omized , double-blind , placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations > 10 and < 60 ng/mL were r and omized to Vitamin D3 2500 IU or placebo , daily for 4 months . Primary endpoints were changes in brachial artery flow-mediated vasodilation ( FMD ) , carotid-femoral pulse wave velocity ( PWV ) , and aortic augmentation index ( AIx ) . The 114 subjects were mean ( st and ard deviation ) 63.9 ( 3.0 ) years old with a 25-hydroxyvitamin D level of 31.3 ( 10.6 ) ng/mL.  Low VitD ( < 30 ng/mL ) was present in 47 % and was associated with higher body-mass index , systolic blood pressure , glucose , CRP , and lower FMD ( all p<0.05 ) . After 4 months , 25-hydroxyvitamin D levels increased by 15.7 ( 9.3 ) ng/mL on vitamin D3 vs. −0.2 ( 6.1 ) ng/mL on placebo ( p<0.001 ) . There were no significant differences between groups in changes in FMD ( 0.3 [ 3.4 ] vs. 0.3 [ 2.6 ] % , p = 0.77 ) , PWV ( 0.00 [ 1.06 ] vs. 0.05 [ 0.92 ] m/s , p = 0.65 ) , AIx ( 2.7 [ 6.3 ] vs. 0.9 [ 5.6 ] % , p = 0.10 ) , or CRP ( 0.3 [ 1.9 ] vs. 0.3 [ 4.2 ] mg/L , p = 0.97 ) . Multivariable models showed no significant interactions between treatment group and low VitD status ( < 30 ng/mL ) for changes in FMD ( p = 0.65 ) , PWV ( p = 0.93 ) , AIx ( p = 0.97 ) , or CRP ( p = 0.26).In conclusion , VitD supplementation  did not improve endothelial function , arterial stiffness , or inflammation . These observations do not support use of VitD supplementation to reduce cardiovascular disease risk . Trial Registration Clinical Trials.gov NCT00690417 Trial Registration Clinical Trials.gov OBJECTIVE In observational studies , low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease . RESEARCH DESIGN AND METHODS We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose ( IFG ) and /or impaired glucose tolerance ( IGT ) r and omly assigned to 20,000 IU/week vitamin D3 or placebo .  An oral glucose tolerance test was performed at baseline and after 1 year . RESULTS Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups , respectively , and increased by 45.8 nmol/L and 3.4 nmol/L , respectively . With adjustment for baseline concentrations , no differences in measures of glucose metabolism , insulin secretion or sensitivity , blood pressure , or hs-CRP were found after 1 year . There was a slight , but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group , but as there was also a decrease in HDL cholesterol , the change in the total/HDL cholesterol ratio did not differ significantly . Only analyzing subjects with 25(OH)D < 50 nmol/L did not change the results . CONCLUSIONS This study shows that vitamin D supplementation does not improve glycemic indices , blood pressure , or lipid status in subjects with IFG and /or IGT CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P<0.001 , linear mixed model ) . Mean ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin The prevalence of vitamin D deficiency varies , with the groups at greatest risk including housebound , community-dwelling older and /or disabled people , those in residential care , dark-skinned people ( particularly those modestly dressed ) , and other people who regularly avoid sun exposure or work indoors . Most adults are unlikely to obtain more than 5%-10 % of their vitamin D requirement from dietary sources . The main source of vitamin D for people residing in Australia and New Zeal and is exposure to sunlight . A serum 25-hydroxyvitamin D ( 25-OHD ) level of ≥ 50 nmol/L at the end of winter ( 10 - 20 nmol/L higher at the end of summer , to allow for seasonal decrease ) is required for optimal musculoskeletal health . Although it is likely that higher serum 25-OHD levels play a role in the prevention of some disease states , there is insufficient evidence from r and omised controlled trials to recommend higher targets . For moderately fair-skinned people , a walk with arms exposed for 6 - 7 minutes mid morning or mid afternoon in summer , and with as much bare skin exposed as feasible for 7 - 40 minutes ( depending on latitude ) at noon in winter , on most days , is likely to be helpful in maintaining adequate vitamin D levels in the body . When sun exposure is minimal , vitamin D intake from dietary sources and supplementation of at least 600 IU ( 15 µg ) per day for people aged ≤ 70 years and 800 IU ( 20 µg ) per day for those aged > 70 years is recommended . People in high-risk groups may require higher doses . There is good evidence that vitamin D plus calcium supplementation  effectively reduces fractures and falls in older men and women The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases , insulin resistance , oxidative stress , and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease ( NAFLD ) . Fifty-three patients with NAFLD were enrolled in a parallel , double-blind , placebo-controlled study . The patients were r and omly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 ( n = 27 ) or a placebo ( n = 26 ) , every 14 days for 4 months . Serum aminotransferases , high-sensitive C-reactive protein ( hs-CRP ) , tumor necrosis factor α , malondialdehyde ( MDA ) , total antioxidant capacity , transforming growth factor β1 , as well as grade of hepatic steatosis and homeostasis model assessment of insulin resistance were assessed pre- and post-intervention . In patients who received vitamin D supplement compared to the controls , the median of serum 25(OH)D3 significantly increased ( 16.2 vs. 1.6 ng/ml , P < 0.001 ) . This increase accompanied by significant decrease in serum MDA ( −2.09 vs. −1.23 ng/ml , P = 0.03 ) and near significant changes in serum hs-CRP ( −0.25 vs. 0.22 mg/l , P = 0.06 ) . These between-group differences remained significant even after controlling for baseline covariates . Other variables showed no significant changes . Improved vitamin D status led to amelioration in serum hs-CRP and MDA in patients with NAFLD . This might be considered as an adjunctive therapy to attenuate systemic inflammation and lipid peroxidation alongside other treatments for NAFLD patients Background Vitamin D is believed to play an important role outside the endocrine system in the regulation of the immune system , and in cellular proliferation and differentiation . The aim of the study was to investigate the impact of vitamin D levels on innate immunity . Methods Participants for this prospect i ve , longitudinal study were recruited amongst otherwise healthy staff of a large hospital in Victoria , Australia . Those fulfilling the inclusion criteria , including a vitamin D level of < 50 nmol/L , were supplemented . Using flow cytometry , expression of the innate immune receptors TLR2 , TLR4 and CD86 was measured on peripheral blood mononuclear cells ( P BMC s ) collected prior to vitamin D treatment and then at 1 and 3 months . Additonally , P BMC s at each timepoint were stimulated with specific TLR lig and s and result ant supernatants were assayed for the cytokines TNFα , IL-6 , IFN-α and IP-10 . Results In participants whose vitamin D level was > 100 nmol/L post supplementation ( n=11 ) , TLR2 expression on P BMC s increased significantly , with no change noted in TLR4 or CD86 expression . Stimulation of vitamin D deficient sample s with TLR lig and s produced a number of proinflammatory cytokines , which were significantly reduced upon vitamin D normalisation . In patients whose levels returned to a deficient level at 3 months despite ongoing low-level supplementation , an increase in the pro-inflamamtory state returned . This suggests that vitamin D may play an important role in ensuring an appropriate baseline pro-inflammatory state . Conclusions This ex-vivo pilot study adds clinical evidence supporting a possibly important role for vitamin D in innate immunity . If confirmed , this unique clinical study has potentially significant implication s for the treatment of a variety of inflammatory conditions , where achieving optimal vitamin D levels may help reduce inflammation BACKGROUND Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events ; inflammation elsewhere is also associated with both atherogenesis generally and its thrombotic complications . Recent studies indicate that systemic markers of inflammation can identify subjects at high risk of coronary events . METHODS AND RESULTS We used a sensitive immunoradiometric assay to examine the association of serum C-reactive protein ( CRP ) with the incidence of first major coronary heart disease ( CHD ) event in 936 men 45 to 64 years of age . The subjects , who were sample d at r and om from the general population , participated in the first MONICA Augsburg survey ( 1984 to 1985 ) and were followed for 8 years . There was a positive and statistically significant unadjusted relationship , which was linear on the log-hazards scale , between CRP values and the incidence of CHD events ( n=53 ) . The hazard rate ratio ( HRR ) of CHD events associated with a 1-SD increase in log-CRP level was 1.67 ( 95 % CI , 1.29 to 2 . 17 ) . After adjustment for age , the HRR was 1.60 ( 95 % CI , 1.23 to 2 . 08 ) . Adjusting further for smoking behavior , the only variable selected from a variety of potential confounders by a forward stepping process with a 5 % change in the relative risk of CRP as the selection criterion , yielded an HRR of 1.50 ( 95 % CI , 1.14 to 1.97 ) . CONCLUSIONS These results confirm the prognostic relevance of CRP , a sensitive systemic marker of inflammation , to the risk of CHD in a large , r and omly selected cohort of initially healthy middle-aged men . They suggest that low- grade inflammation is involved in pathogenesis of atherosclerosis , especially its thrombo-occlusive complications Objectives To evaluate the risk of bias tool , introduced by the Cochrane Collaboration for assessing the internal validity of r and omised trials , for inter-rater agreement , concurrent validity compared with the Jadad scale and Schulz approach to allocation concealment , and the relation between risk of bias and effect estimates . Design Cross sectional study . Study sample 163 trials in children . Main outcome measures Inter-rater agreement between review ers assessing trials using the risk of bias tool ( weighted κ ) , time to apply the risk of bias tool compared with other approaches to quality assessment ( paired t test ) , degree of correlation for overall risk compared with overall quality scores ( Kendall ’s τ statistic ) , and magnitude of effect estimates for studies classified as being at high , unclear , or low risk of bias ( metaregression ) . Results Inter-rater agreement on individual domains of the risk of bias tool ranged from slight ( κ=0.13 ) to substantial ( κ=0.74 ) . The mean time to complete the risk of bias tool was significantly longer than for the Jadad scale and Schulz approach , individually or combined ( 8.8 minutes ( SD 2.2 ) per study v 2.0 ( SD 0.8 ) , P<0.001 ) . There was low correlation between risk of bias overall compared with the Jadad scores ( P=0.395 ) and Schulz approach ( P=0.064 ) . Effect sizes differed between studies assessed as being at high or unclear risk of bias ( 0.52 ) compared with those at low risk ( 0.23 ) . Conclusions Inter-rater agreement varied across domains of the risk of bias tool . Generally , agreement was poorer for those items that required more judgment . There was low correlation between assessment s of overall risk of bias and two common approaches to quality assessment : the Jadad scale and Schulz approach to allocation concealment . Overall risk of bias as assessed by the risk of bias tool differentiated effect estimates , with more conservative estimates for studies at low risk Background . The role of vitamin D in the body 's ability to fight influenza and URI 's may be dependent on regulation of specific cytokines that participate in the host inflammatory response . The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines . Subjects and Methods . This study was a 3-month prospect i ve placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [ Li-Ng et al. , 2009 ] . 162 volunteers were r and omized to receive either 50 μg/d ( 2000 IU ) of vitamin D3 or matching placebo . 25(OH)D and the levels of 10 different cytokines ( IL-2 , 4 , 5 , 6 , 8 , 10 , 13 , GM-CSF , IFN-γ , TNF-α ) were measured in the serum of participants at baseline and the final visit . There were 6 drop-outs from the active vitamin D group and 8 from the placebo group . Results . In the active vitamin D group , we found a significant median percent decline in levels of GM-CSF ( −62.9 % , P < .0001 ) , IFN-γ ( −38.9 % , P < .0001 ) , IL-4 ( −50.8 % , P = .001 ) , IL-8 ( −48.4 % , P < .0001 ) , and IL-10 ( −70.4 % , P < .0001 ) . In the placebo group , there were significant declines for GM-CSF ( −53.2 % , P = .0007 ) and IFN-γ ( −34.4 % , P = .0011 ) . For each cytokine , there was no significant difference in the rate of decline between the two groups . 25(OH)D levels increased in the active vitamin D group from a mean of 64.3 ± 25.4 nmol/L to 88.5 ± 23.2 nmol/L. Conclusions . The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults OBJECTIVE Although calcitriol ( 1,25(OH)2D ) is considered the biologically active vitamin D metabolite , several studies have shown that calcidiol ( 25OHD ) is the vitamin D metabolite that is most closely linked to parathyroid function and indices of calcium homeostasis . Moreover , low levels of 25OHD have been associated with increased risk of different diseases including cancer , diabetes , and myopathy . DESIGN Cross-sectional study . METHODS We studied relations between  plasma concentrations of 25OHD , 1,25(OH)2D , and parathyroid hormone ( PTH ) in fasting plasma sample s from 315 healthy postmenopausal women r and omly selected from the local background population . RESULTS P-1,25(OH)2D levels varied in a concentration-dependent manner with P-25OHD levels ( P<0.001 ) . Thus , P-1,25(OH)2D levels were the lowest in women with vitamin D insufficiency , i.e. , P-1,25(OH)2D levels were reduced by approximately one-third in subjects with P-25OHD levels below 25 nmol/l compared with levels above 80 nmol/l ( P<0.01 ) . The association was most pronounced at P-25OHD concentrations below 80 nmol/l , whereas no major increase in P-1,25(OH)2D was observed at P-25OHD concentrations above 80 nmol/l . In multiple regression analysis , PTH was a minor although significant predictor of P-1,25(OH)2D levels . CONCLUSIONS In normal postmenopausal women , the conversion of 25OHD to active vitamin D depends on the substrate concentration . Our data support that vitamin D insufficiency should be considered at P-25OHD levels below 80 nmol/l IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension . No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension , the most common pattern of hypertension in older people . OBJECTIVE To test whether high-dose , intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension . DESIGN Parallel group , double-blind , placebo-controlled  r and omized trial . SETTING Primary care clinics and hospital clinics . PARTICIPANTS Patients 70 years and older with isolated systolic hypertension ( supine systolic blood pressure > 140 mm Hg and supine diastolic blood pressure < 90 mm Hg ) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were r and omized into the trial from June 1 , 2009 , through May 31 , 2011 . INTERVENTIONS A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year . MAIN OUTCOMES AND MEASURES Difference in office blood pressure , 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , insulin resistance , and b-type natriuretic peptide level during 12 months . RESULTS A total of 159 participants were r and omized ( mean age , 77 years ) .  Mean baseline office systolic blood pressure was 163/78 mm Hg . Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group ( + 8 ng/mL at 1 year , P < .001 ) . No significant treatment effect was seen for mean ( 95 % CI ) office blood pressure ( −1 [ −6 to 4]/−2 [ −4 to 1 ] mm Hg at 3 months and 1 [ −2 to 4]/0 [ −2 to 2 ] mm Hg overall treatment effect ) . No significant treatment effect was evident for any of the secondary outcomes ( 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , glucose level , and walking distance ) . There was no excess of adverse events in the treatment group , and the total number of falls was nonsignificantly lower in the group receiving vitamin D ( 36 vs 46 , P = .24 ) . CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N92186858 BACKGROUND Low vitamin D levels are common , and are associated with a higher incidence of future vascular events . We tested whether vitamin D supplementation could improve endothelial function and other markers of vascular function in patients with a history of myocardial infa rct ion . METHODS Parallel group , placebo-controlled , double-blind r and omised trial . Patients with a history of myocardial infa rct ion were r and omised to receive 100,000 units of oral vitamin D3 or placebo at baseline , 2 months and 4 months . Outcomes were measured at baseline , 2 and 6 months . Reactive hyperaemia index on fingertip plethysmography was the primary outcome . Secondary outcome measures included blood pressure , cholesterol , C-reactive protein , von Willebr and factor , tumour necrosis factor alpha , E-selectin , B-type natriuretic peptide , thrombomodulin and 25-hydroxyvitamin D levels . RESULTS 75 patients were r and omised , mean age 66 years . 74/75 ( 99 % ) completed 6 month follow-up . 25 hydroxyvitamin D levels increased in the intervention group relative to placebo ( + 13 vs + 1 nmol/L , p=0.04 ) . There was no between-group difference in change in reactive hyperaemia index between baseline and 6 months ( -0.18 vs -0.07 , p=0.40 ) . Of the secondary outcomes , only C-reactive protein showed a significant decline in the intervention arm relative to placebo at 6 months ( -1.3 vs 2.0mg/L , p=0.03 ) . Systolic blood pressure ( + 1.4 vs + 2.3 mmHg , p=0.79 ) , diastolic blood pressure ( + 2.0 vs + 0.8 mmHg , p=0.54 ) and total cholesterol ( + 0.26 vs + 0.24 mmol/L , p=0.88 ) showed no between-group difference at 6 months . CONCLUSIONS Supplementation with vitamin D did not improve markers of vascular function in patients with a history of myocardial infa rct ion BACKGROUND Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial . The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus ( DM ) . METHODS In a double-blind , placebo-controlled trial , we r and omized 100 type 2 DM patients to vitamin D supplement  ( 5000 IU/day , n = 50 ) or placebo ( controls , n = 50 ) for 12 weeks . Assessment of vascular function with brachial artery flow-mediated dilatation ( FMD ) , circulating levels of endothelial progenitor cells ( EPCs ) and brachial-ankle pulse wave velocity , and metabolic parameter , high-sensitivity C-reactive protein ( hsCRP ) and oxidative stress markers were performed before and after the supplementation . RESULTS After 12 weeks , vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [ 25(OH)D ] concentration ( treatment effect 34.7 ng/mL , 95 % CI 26.4 - 42.9 , P < 0.001 ) and serum ionized calcium ( treatment effect 0.037 mmol/L , 95 % CI 0.007 - 0.067 , P = 0.018 ) ; decreased serum parathyroid hormone concentration ( treatment effect -0.55 pmol/L , 95 % CI -1.08 to -0.02 , P = 0.042 ) compared to patients who received placebo . Nevertheless , vitamin D supplementation did not improve vascular function as determined by FMD , circulating EPC count or baPWV ( all P > 0.05 ) . Furthermore , hsCRP , oxidative stress markers , low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups ( all P > 0.05 ) . CONCLUSION In patients with type 2 DM , 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress . CLINICAL TRIAL NUMBER HKCTR-867 , www.hk clinical trials.com
target: Available high- quality RCTs did not support a beneficial effect of cholecalciferol on systemic IL-6 and CRP .
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