Effect of vitamin D supplementation on inflammation: protocol for a systematic review A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial Does short-term vitamin C reduce cardiovascular risk in type 2 diabetes? Calcium-vitamin D cosupplementation influences circulating inflammatory biomarkers and adipocytokines in vitamin D-insufficient diabetics: a randomized controlled clinical trial. Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Supplementation with orange and blackcurrant juice, but not vitamin E, improves inflammatory markers in patients with peripheral arterial disease. Serum IL-18 and hsCRP correlate with insulin resistance without effect of calcitriol treatment on type 2 diabetes. Effects of alpha-tocopherol and mixed tocopherol supplementation on markers of oxidative stress and inflammation in type 2 diabetes. Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial Effect of vitamin D supplementation on inflammation and nuclear factor kappa-B activity in overweight/obese adults: a randomized placebo-controlled trial Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial. Effect of Vitamin D Supplementation on Glucose Control and Inflammatory Response in Type II Diabetes: A Double Blind, Randomized Clinical Trial Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies Effect of alpha-lipoic acid and vitamin E supplementation on oxidative stress, inflammation, and malnutrition in hemodialysis patients. Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes. Impact of Vitamin D Supplementation on Inflammatory Markers in African Americans: Results of a Four-Arm, Randomized, Placebo-Controlled Trial Systemic inflammatory load in humans is suppressed by consumption of two formulations of dried, encapsulated juice concentrate. Improvements in peripheral vascular function with vitamin D treatment in deficient adolescents with type 1 diabetes The Diabetes and Pre-eclampsia Intervention Trial. Improvement of vitamin D status via daily intake of fortified yogurt drink either with or without extra calcium ameliorates systemic inflammatory biomarkers, including adipokines, in the subjects with type 2 diabetes. Long-term use of supplemental vitamins and minerals does not reduce the risk of urothelial cell carcinoma of the bladder in the VITamins And Lifestyle study. Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial.
Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 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 Background Despite Australia ’s sunny climate , low vitamin D levels are increasingly prevalent . Sun exposure is limited by long working hours , an increase in time spent indoors , and sun protection practice s , and there is limited dietary vitamin D fortification . While the importance of vitamin D for bone mineralization is well known , its role as a protective agent against chronic diseases , such as type 2 diabetes and cardiovascular disease , is less understood . Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion , mainly via its anti-inflammatory properties , thereby decreasing the risk of development and progression of type 2 diabetes . The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D ( 25(OH)D ) , obtained through vitamin D supplementation , will increase insulin sensitivity and insulin secretion . A secondary aim is to determine whether these relationships are mediated by a reduction in underlying sub clinical inflammation associated with obesity . Methods / Design Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old , with low vitamin D levels ( 25(OH)D < 50 nmol/l ) , will be r and omly assigned to intervention or placebo . At baseline , participants will undergo a medical review and anthropometric measurements , including dual X-ray absorptiometry , an intravenous glucose tolerance test , muscle and fat biopsies , a hyperinsulinemic euglycemic clamp  , and question naires assessing diet , physical activity , sun exposure , back and knee pain , and depression . The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D ( cholecalciferol ) daily , while the placebo group will receive apparently identical capsules , both for a period of 16 weeks . All measurements will be repeated at follow-up , with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group . Secondary outcome measures will compare changes in anthropometry , cardiovascular risk factors , and inflammatory markers . Discussion The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms , which are relevant for the prevention and management of type 2 diabetes . Trial registration Clinical trials.gov ID : NCT02112721 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 CONTEXT To the best of our knowledge , no study has examined the effects of vitamin D-calcium cosupplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient type 2 diabetics . OBJECTIVE This study was performed to assess the effects of vitamin D and calcium supplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient people with type 2 diabetes . METHODS Totally , 118 diabetic patients were enrolled in this r and omized , placebo-controlled clinical trial . After matching for age , sex , body mass index , type and dose of hypoglycemic agents , and duration of diabetes , subjects were r and omly assigned into 4 groups receiving the following : 1 ) 50000 IU/wk vitamin D + calcium placebo ; 2 ) 1000 mg/d calcium + vitamin D placebo ; 3 ) 50 000 IU/wk vitamin D + 1000 mg/d calcium ; or 4 ) vitamin D placebo + calcium placebo for 8 weeks . Blood sampling was done for the quantification of inflammatory biomarkers and adipocytokines at the study baseline and after 8 weeks of intervention . RESULTS Calcium ( changes from baseline : -75 ± 19 ng/ml , P = .01 ) and vitamin D alone ( -56 ± 19 ng/mL , P = .01 ) and joint calcium-vitamin D supplementation ( -92 ± 19 ng/mL , P = .01 ) result ed in a significant reduction in serum leptin levels compared with placebo ( -9 ± 18 ng/mL ) . This was also the case for serum IL-6 , such that calcium ( -2 ± 1 pg/mL , P < .001 ) and vitamin D alone ( -4 ± 1 pg/mL , P < .001 ) and their combination ( -4 ± 1 pg/mL , P < .001 ) led to significant reductions compared with placebo ( 3 ± 1 pg/mL ) . After adjustment for potential confounders , individuals in the calcium ( -3.1 ± 1.3 , P < .05 ) , vitamin D ( -3.1 ± 1.3 , P < .05 ) , and joint calcium-vitamin D groups ( -3.4 ± 1.3 , P < .05 ) had greater reductions in serum TNF-α concentrations compared with placebo ( 0.1 ± 1.2 ) . Individuals who received joint calcium-vitamin D supplements tended to have a decrease in serum high-sensitivity C-reactive protein levels compared with placebo after controlling for baseline levels ( -1.14 ± 0.25 vs 0.02 ± 0.24 ng/mL , P = .09 ) . CONCLUSION Joint calcium-vitamin D supplementation might improve systemic inflammation through decreasing IL-6 and TNF-α concentrations in vitamin D-insufficient people with type 2 diabetes Background The role of vitamin D in management of depression is unclear . Results from observational and emerging r and omized controlled trials ( RCTs ) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association . Methods / Design The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors ’ original definition . Secondary aims include assessing the change in quality of life , adverse events and treatment discontinuation . We will conduct the systematic review and meta- analysis according to the recommendations of the Cochrane H and book for Systematic Review s of Interventions . We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( 1966 to present ) , EMBASE ( 1980 to present ) , CINAHL ( 1982 to present ) , PsychINFO ( 1967 to present ) and Clinical Trials.gov . Unpublished work will be identified by search ing two major conferences : the International Vitamin Conference , the Anxiety Disorders and Depression Conference , while grey literature will be acquired by contacting authors of included studies . We will use the r and om-effects meta- analysis to synthesize the data by pooling the results of included studies . Discussion The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant setting s. Study registration Unique identifier : CRD42013003849 Inflammation and endothelial activation are associated with an increased risk of CVD and epidemiological evidence suggests an association between levels of markers of inflammation or endothelial activation and the intake of fruit . Also , vitamin E , a fat-soluble antioxidant , has anti-inflammatory properties . We performed a r and omised 2 x 2 factorial , crossover trial to determine the effect of orange and blackcurrant juice ( 500 ml/d ) and vitamin E ( 15 mg RRR-alpha-tocopherol/d ) supplementation on markers of inflammation and endothelial activation in forty-eight patients with peripheral arterial disease . Patients were r and omly allocated to two dietary supplements from the four possible combinations of juice and vitamin E : juice+vitamin E ; juice+placebo ; reference beverage ( sugar drink)+vitamin E ; and reference beverage+placebo . The supplementations were given for 28 d , separated by a 4-week wash-out period . Analysis of main effects showed that juice decreased C-reactive protein ( CRP ) by 11 % and fibrinogen by 3 % while the reference drink increased CRP by 13 % and fibrinogen by 2 % ( P<0.008 and P<0.002 , respectively ) . No significant differences were measured for IL-6 and the endothelial activation markers von Willebr and factor , tissue-plasminogen activator and plasmin activator inhibitor-1 .  Vitamin E supplementation had no significant effects on the various markers . We observed no significant interaction between juice and vitamin E. In this study , orange and blackcurrant juice reduced markers of inflammation , but not markers of endothelial activation , in patients with peripheral arterial disease , relative to sugar drinks BACKGROUND Chronic low- grade systemic inflammation presented in Type 2 diabetes mellitus plays a major role in disease progression as well as development of micro- and macro-vascular complications of diabetes . Therefore , reducing inflammation can be beneficial in prevention of diabetes complications . OBJECTIVES To investigate the association between insulin resistance and inflammatory markers , and assessing the effects of oral Calcitriol on inflammatory cytokines in type 2 diabetic patients . METHODS In this double-blind r and omized placebo-controlled trial , 70 participants with type-2 diabetes were r and omly divided to two groups . One group received two capsules of Calcitriol ( 0.25 μg 1,25-dihydroxy cholecalciferol per each capsule ) per day . The second group received placebo tablets . At the beginning of the study , we assessed insulin resistance and its relation to inflammatory profile . Serum high sensitive C-reactive protein ( hs CRP ) , interleukin-6 and interleukin-18 were also measured at the beginning and the end of the 12-week supplementation trial . RESULTS Mean calcium , phosphorus and vitamin D concentrations in the study participants were 8.98 ± 0.79 mg/dL , 3.86 ± 0.50 mg/dL and 40.91 ± 30.9 ng/mL , respectively . IL-18 and hsCRP had significant positive associations with insulin resistance markers and negative associations with insulin sensitivity markers . At the end of the 12-week supplementation trial , no significant difference was seen in serum levels of hsCRP , IL-6 and IL-18 between the two groups , while these values were adjusted for baseline values . CONCLUSION Inflammation was associated with insulin resistance in diabetic patients . No anti-inflammatory effect of Calcitriol in terms of decreasing hsCRP , IL-6 and IL-18 detected BACKGROUND Vitamin E isomers may protect against atherosclerosis . The aim of this study was to compare the effects of supplementation with either alpha-tocopherol ( alphaT ) or mixed tocopherols rich in gamma-tocopherol ( gammaT ) on markers of oxidative stress and inflammation in patients with type 2 diabetes . METHODS In a double-blind , placebo-controlled trial , 55 patients with type 2 diabetes were r and omly assigned to receive ( 500 mg/day ) ( a ) alphaT , ( b ) mixed tocopherols , or ( c ) placebo for 6 weeks . Cellular tocopherols , plasma and urine F(2)-isoprostanes , erythrocyte antioxidant enzyme activities , plasma inflammatory markers , and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation . RESULTS Neutrophil alphaT and gammaT increased ( both P < 0.001 ) with mixed tocopherol supplementation , whereas alphaT ( P < 0.001 ) increased and gammaT decreased ( P < 0.005 ) after alphaT supplementation . Both alphaT and mixed tocopherol supplementation result ed in reduced plasma F(2)-isoprostanes ( P < 0.001 and P = 0.001 , respectively ) but did not affect 24-h urinary F(2)-isoprostanes or erythrocyte antioxidant enzyme activities . Neither alphaT nor mixed tocopherol supplementation affected plasma C-reactive protein , interleukin 6 , tumor necrosis factor-alpha , or monocyte chemoattractant protein-1 . Stimulated neutrophil leukotriene B(4 ) production decreased significantly in the mixed tocopherol group ( P = 0.02 ) but not in the alphaT group ( P = 0.15 ) . CONCLUSIONS The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes . In population s with well-controlled type 2 diabetes , supplementation with either alphaT or mixed tocopherols rich in gammaT is unlikely to confer further benefits in reducing inflammation Objectives To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity , insulin secretion , β-cell function , inflammation and metabolic markers . Design 6-month r and omized , placebo-controlled trial . Participants Ninety-five adults with serum 25-hydroxyvitamin D [ 25(OH)D ] ≤55 nmol/L at risk of type 2 diabetes ( with prediabetes or an AUSDRISK score ≥15 ) were r and omized . Analyses included participants who completed the baseline and final visits ( treatment n = 35 ; placebo n = 45 ) . Intervention Daily calcium carbonate ( 1,200 mg ) and cholecalciferol [ 2,000–6,000 IU to target 25(OH)D > 75 nmol/L ] or matching placebos for 6 months .  Measurements Insulin sensitivity ( HOMA2%S , Matsuda index ) , insulin secretion ( insulinogenic index , area under the curve ( AUC ) for C-peptide ) and β-cell function ( Matsuda index x AUC for C-peptide ) derived from a 75 g 2-h OGTT ; anthropometry ; blood pressure ; lipid profile ; hs-CRP ; TNF-α ; IL-6 ; adiponectin ; total and undercarboxylated osteocalcin . Results Participants were middle-aged adults ( mean age 54 years ; 69 % Europid ) at risk of type 2 diabetes ( 48 % with prediabetes ) . Compliance was > 80 % for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group ( 91 % achieved > 75 nmol/L ) , but remained unchanged in controls . There were no significant changes in insulin sensitivity , insulin secretion and β-cell function , or in inflammatory and metabolic markers between or within the groups , before or after adjustment for potential confounders including waist circumference and season of recruitment . In a post hoc analysis restricted to participants with prediabetes , a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity ( HOMA%S and Matsuda ) was observed . Conclusions Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity , insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes . However , in participants with prediabetes , supplementation with vitamin D and calcium may improve insulin sensitivity . Trial Registration Australian New Zeal and Clinical Trials Registry In-vitro studies suggest that vitamin D reduces inflammation by inhibiting nuclear factor kappa-B ( NFκB ) activity . Yet , no trials have examined the effects of vitamin D supplementation on NFκB activity in-vivo in humans . We conducted a double-blind r and omized trial ( RCT ) examining effects of vitamin D supplementation on inflammatory markers and NFκB activity in peripheral blood mononuclear cells ( P BMC s ) . Sixty-five overweight/obese , vitamin D-deficient ( 25-hydroxyvitamin D [ 25(OH)D ] ≤ 50 nmol/L ) adults were r and omized to a single 100,000 IU bolus followed by 4,000 IU daily cholecalciferol or matching placebo for 16 weeks . We measured BMI , % body fat , serum 25(OH)D , high-sensitivity C-reactive protein ( hsCRP ) , tumour necrosis factor ( TNF ) , monocyte chemoattractant protein-1 ( MCP-1 ) , interferon-gamma ( IFN-γ ) , several interleukins , and NFκB activity in P BMC s. Fifty-four participants completed the study . Serum 25(OH)D concentrations  increased with vitamin D supplementation compared to placebo ( p < 0.001 ) . Vitamin D and placebo groups did not differ in any inflammatory markers or NFκB activity ( all p > 0.05 ) . Results remained non-significant after adjustment for age , sex , and % body fat , and after further adjustment for sun exposure , physical activity , and dietary vitamin D intake . Although in-vitro studies report anti-inflammatory effects  of vitamin D , our RCT data show no effect of vitamin D supplementation on inflammatory markers or NFκB activity in-vivo in humans BACKGROUND Vitamin-D deficiency and vitamin-D receptor genotype ( VDR ) are risk factors for several disorders with inflammatory components , including coronary heart disease ( CHD ) and diabetes , though the mechanisms involved are unclear . AIM To examine the hypothesis that vitamin D status modulates the matrix metalloproteinase ( MMP ) system in a population with a high prevalence of vitamin D deficiency , a situation affecting susceptibility to CHD and diabetes . DESIGN Prospect i ve cross-sectional , interventional and embedded studies . METHODS Circulating MMP2,9 , the inhibitor TIMP-1 and C-reactive protein ( CRP ) were measured during studies of vitamin-D deficiency as a risk factor for type 2 diabetes and CHD in 171 healthy British Bangladeshi adults , free of known diabetes or major illness .  Vitamin D status , VDR genotype , body-build , blood pressure , lipid and insulin profiles , glucose tolerance , fibrinogen , PAI-1 , folate and homocysteine were measured . Vitamin-D-deficient subjects were re-assessed after 1 years ' supplementation .  MMP , TIMP-1 and CRP levels were measured in 41 subjects halfway through 5-year follow-up . Independent determinants of circulating concentrations of MMP9 , TIMP-1 and CRP were assessed by multiple regression analysis . RESULTS Vitamin D status was the sole determinant of circulating MMP9 ( inversely ) and an independent determinant of CRP ( inversely ) . Determinants of TIMP-1 were MMP9 , systolic blood-pressure ( directly ) and VDR genotype ( TaqI ) . Significant reductions in MMP9 ( -68 % ) , TIMP-1 ( -38 % ) and CRP ( -23 % ) concentrations followed vitamin-D supplementation . DISCUSSION Vitamin-D insufficiency is associated with increased circulating MMP2,9 and CRP , correctable by supplementation . This finding provides a possible mechanism for tissue damage in chronic inflammatory conditions , including CHD and diabetes BACKGROUND Obese adolescents are at a greater risk of vitamin D deficiency because vitamin D is thought to be sequestered by excess adipose tissue . Poor vitamin D status has been associated with a higher prevalence of the metabolic syndrome , type 2 diabetes , or both in adults and adolescents . OBJECTIVE The objective was to determine in obese adolescents the efficacy and safety of 4000 IU vitamin D3/d and whether subsequent increased circulating concentrations of 25-hydroxyvitamin D [ 25(OH)D ] are associated with improved markers of insulin sensitivity and resistance and reduced inflammation . DESIGN Obese adolescent patients [ n = 35 ; mean ± SD age : 14.1 ± 2.8 y ; BMI ( in kg/m(2 ) ) : 39.8 ± 6.1 ; 25(OH)D : 19.6 ± 7.1 ng/mL ] were recruited from the University of Missouri Adolescent Diabetes and Obesity Clinic and were r and omly assigned to receive either vitamin D3 ( 4000 IU/d ) or placebo as part of their st and ard care . Anthropometric measurements , inflammatory markers ( IL-6 , TNF-α , C-reactive protein ) , adipokines ( leptin , adiponectin ) , fasting glucose , fasting insulin , and HOMA-IR values were measured at baseline and at 2 follow-up visits ( 3 and 6 mo ) . RESULTS After 6 mo , there were no significant differences in BMI , serum inflammatory markers , or plasma glucose concentrations between groups . Participants supplemented with vitamin D3 had increases in serum 25(OH)D concentrations ( 19.5 compared with 2.8 ng/mL for placebo ; P < 0.001 ) , fasting insulin ( -6.5 compared with + 1.2 μU/mL for placebo ; P = 0.026 ) , HOMA-IR ( -1.363 compared with + 0.27 for placebo ; P = 0.033 ) , and leptin-to-adiponectin ratio ( -1.41 compared with + 0.10 for placebo ; P = 0.045 ) . Inflammatory markers remained unchanged . CONCLUSION The correction of poor vitamin D status through dietary supplementation may be an effective addition to the st and ard treatment of obesity and its associated insulin resistance . This trial was registered at clinical trials.gov as NCT00994396 Background : Diabetes mellitus ( DM ) and vitamin D deficiency are major health concerns around the world . Evidence suggests a possible role of vitamin D in improvement of insulin secretion and sensitivity . Objectives : We assessed whether vitamin D supplementation could be used in vitamin D deficient-type II diabetes to improve glucose metabolism , components of metabolic syndrome ( MetS ) and specific inflammatory biomarkers . Patients and Methods : A double blind , r and omized clinical trial was conducted in King Khalid University Hospital , Saudi Arabia to evaluate the effect of cholecalciferol supplementation on glycemic control , MetS components and specific inflammatory biomarkers including tumor necrosis factor-alpha ( TNF-α ) , Interleukin ( IL-6 ) , leptin , adiponectin and vascular cell adhesion molecule-1 ( VCAM-1 ) . Twenty-two patients with type II diabetes with insulin resistance , glycated hemoglobin ( HbA1c ) ≥ 6 ( 42 mmol/mol ) and serum 25(OH)D < 50 nmol/L were r and omized using a computer program to receive either supplementation with cholecalciferol ( 5000 IU/day ) or placebo for 12 weeks . The primary outcome was change in HbA1c levels from baseline . Results : Median [ IQR ] 25(OH)D levels increased significantly in the vitamin D group as 58.1 [ 48 , 67.3 ] nmol/L ( P = 0.002 ) . There was no significant difference in the change of HbA1c between the groups ( P = 0.5 ) with a decrease of -0.1 % [ -1 , 0.5 ] in the vitamin D group and an increase of 0.15 % [ 0.1 , 0.2 ] in the placebo group . A significant improvement was observed in the homeostasis model of assessment of β-cell activity ( HOMA-%B ) ( P = 0.03 ) with vitamin D supplementation compared to baseline . Conclusions : Vitamin D repletion for 12 weeks increased serum vitamin D concentrations and improved β-cell activity in vitamin D-deficient type II diabetes with no significant changes in HbA1c or insulin sensitivity Background Diabetes and vitamin D deficiency are global epidemics . Research ers have long been exploring the role of potentially modifiable factors to manage type 2 diabetes . We conducted a systematic review of prospect i ve studies and r and omized controlled trials that involved vitamin D supplementation and specifically intended to study glycemic outcomes related to type 2 diabetes . Methods Two authors independently search ed Medline and PubMed for longitudinal studies that had assessed the effect of vitamin D supplements on glycemic control , insulin resistance and beta-cell dysfunction in patients with diabetes . Results Seventeen r and omized control trials and seven longitudinal studies with a minimum follow-up of one month were included . Results of the various short-term studies ( follow up ≤ 3 months ) suggested that vitamin D supplementation had a positive impact on glycemic control and metabolic parameters such as insulin resistance and beta cell dysfunction . However , the evidence was weak due to the low method ological quality of the studies . There was no significant effect on HbA1c , beta cell function and insulin resistance in the long-term studies ( follow up > 3 months ) . There existed heterogeneity in the methodology of the studies , inclusion criteria , mode of supplementation of vitamin D and the duration of follow up . Conclusions Current evidence based on r and omized controlled trials and longitudinal studies do not support the notion that vitamin D supplementation can improve hyperglycemia , beta cell secretion or insulin sensitivity in patients with type 2 diabetes . Large-scale trials with proper study design , optimal vitamin D supplementation and longer follow up need to be conducted INTRODUCTION Increased oxidative stress , inflammation , and malnutrition are present in hemodialysis patients and these factors exacerbate cardiovascular comorbidities . Vitamin E and alpha-lipoic acid ( ALA ) may have a protective role against cardiovascular disease risk factors via anti-oxidative and anti-inflammatory properties . The aim of this study was to evaluate the effect of ALA and vitamin E administration ( alone or combined ) on hemodialysis-induced stress oxidation , inflammation , and malnutrition . MATERIAL S AND METHODS In a r and omized placebo-controlled trial , we examined the effects of 2-month supplementation by vitamin E and ALA ( alone or combined ) on biomarkers of lipid peroxidation ( malondialdehyde ) , inflammation ( high-sensitivity C-Reactive protein and interleukin-6 ) , and malnutrition ( Subjective Global Assessment and body mass index ) in 85 hemodialysis patients receiving ALA ( 600 mg ) , vitamin E ( 400 IU ) , ALA and vitamin E , and placebo .  RESULTS After supplementation , no significant changes were observed in malondialdehyde level ; however , there was a decrease in the ALA and vitamin E group during the period of the study . Also , a nonsignificant decrease was seen in the high-sensitivity C-Reactive protein concentration of the interventional groups . Supplementation of vitamin E with and without ALA significantly reduced interleukin-6 concentration . A significant improvement was observed in malnutrition status of all groups . CONCLUSIONS Vitamin E and ALA supplementation , especially their combination , might improve inflammation and malnutrition status , which suggest it as a potential preventive strategy against CVD among end-stage renal disease patients OBJECTIVE To compare the effects of short-term dietary supplementation with tomato juice , vitamin E , and vitamin C on susceptibility of LDL to oxidation and circulating levels of C-reactive protein ( C-RP ) and cell adhesion molecules in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS There were 57 patients with well-controlled type 2 diabetes aged < 75 years treated with placebo for 4 weeks and then r and omized to receive tomato juice ( 500 ml/day ) , vitamin E ( 800 U/day ) , vitamin C ( 500 mg/day ) , or continued placebo treatment for 4 weeks . Susceptibility of LDL to oxidation ( lag time ) and plasma concentrations of lycopene , vitamin E , vitamin C , C-RP , vascular cell adhesion molecule 1 , and intercellular adhesion molecule 1 were measured at the beginning of the study , after the placebo phase , and at the end of the study . RESULTS Plasma lycopene levels increased nearly 3-fold ( P = 0.001 ) , and the lag time in isolated LDL oxidation by copper ions increased by 42 % ( P = 0.001 ) in patients during supplementation with tomato juice . The magnitude of this increase in lag time was comparable with the corresponding increase during supplementation with vitamin E ( 54 % ) . Plasma C-RP levels decreased significantly ( -49 % , P = 0.004 ) in patients who received vitamin E.  Circulating levels of cell adhesion molecules and plasma glucose did not change significantly during the study . CONCLUSIONS This study indicates that consumption of commercial tomato juice increases plasma lycopene levels and the intrinsic resistance of LDL to oxidation almost as effectively as supplementation with a high dose of vitamin E , which also decreases plasma levels of C-RP , a risk factor for myocardial infa rct ion , in patients with diabetes . These findings may be relevant to strategies aim ed at reducing risk of myocardial infa rct ion in patients with diabetes African Americans have a disproportionate burden of inflammation-associated chronic diseases such as cancer and lower circulating levels of 25-hydroxyvitamin D [ 25(OH)D ] . The effect of vitamin D3 ( cholecalciferol ) supplementation on inflammatory markers is uncertain . We conducted a r and omized , double-blind , placebo-controlled trial of supplemental oral vitamin D ( placebo , 1,000 , 2,000 , or 4,000 IU/day of vitamin D3 orally for 3 months ) in 328 African Americans ( median age , 51 years ) of public housing communities in Boston , MA , who were enrolled over three consecutive winter periods ( 2007–2010 ) . Change from 0 to 3 months of plasma levels of 25(OH)D , high-sensitivity C-reactive protein ( CRP ) , interleukin (IL)-6 , IL-10 , and soluble TNF-α receptor type 2 ( sTNF-R2 ) in 292 ( 89 % ) participants were measured . Overall , no statistically significant changes in CRP , IL-6 , IL-10 , and sTNF-R2 were observed after the vitamin D supplementation period . Baseline CRP was significantly inversely associated with the baseline 25(OH)D level ( P < 0.001 ) in unadjusted and adjusted models . An interaction between baseline 25(OH)D and vitamin D supplementation was observed for outcome change in log CRP ( month 3–month 0 ; P for interaction = 0.04 ) . Within an unselected population of African Americans , short-term exposure to vitamin D supplementation produced no change in circulating inflammatory markers . This study confirms the strong independent association of CRP with 25(OH)D status even after adjusting for body mass index . Future studies of longer supplemental vitamin D3 duration are necessary to examine the complex influence of vitamin D3 on CRP and other chronic inflammatory cytokines for possible reduction of cancer health disparities in African Americans . Cancer Prev Res ; 7(2 ) ; 218–25 . © 2013 AACR Chronic inflammation contributes to an increased risk for developing chronic conditions such as cardiovascular disease , diabetes , and cancer . A high " inflammatory load " is defined as elevated inflammation markers in blood or other tissues . We evaluated several markers of systemic inflammation from healthy adults and tested the hypothesis that two formulations of encapsulated fruit and vegetable juice powder concentrate with added berry powders ( FVB ) or without ( FV ) could impact markers of inflammatory load . Using a double-blind , placebo-controlled approach , 117 subjects were r and omly assigned to receive placebo , FV , or FVB capsules . Blood was drawn at baseline and after 60 d of capsule consumption . We measured inflammatory markers ( high sensitivity C-Reactive Protein , Monocyte Chemotactic Protein-1 , Macrophage Inflammatory Protein 1-β , and Regulated upon Activation , Normal T cell Expressed and Secreted ) , superoxide dismutase , and micronutrients ( β-carotene , vitamin C , and vitamin E ) . Results showed Monocyte Chemotactic Protein-1 , Macrophage Inflammatory Protein 1-β , and RANTES levels were significantly reduced and superoxide dismutase and micronutrient levels were significantly increased in subjects consuming both FV and FVB , relative to placebo . Data suggest a potential health benefit by consuming either formulation of the encapsulated juice concentrates through their anti-inflammatory properties BACKGROUND Vitamin D ( VitD ) deficiency is prevalent in adolescents with type 1 diabetes ( T1D ) and is associated with diabetes-related vascular complications in adulthood . The objective of this clinical trial was to assess VitD treatment on endothelial function ( EF ) and markers of renal inflammation , in this patient group . METHODS Adolescents with T1D with suboptimal levels of VitD ( < 37.5 nmol/L ) were treated for 12 to 24 weeks with a VitD analog ( VitD3 ) at doses of 1000 or 2000 IU daily . The primary end-point assessed the change in reactive hyperemia index ( lnRHI ) , a measure of EF . Secondary end-points included changes in blood pressure , lipid profile , HbA1c and albumin creatinine ratio ( ACR ) . Urinary cytokine/chemokine inflammatory profile was also assessed in a subset of subjects posttreatment . RESULTS Two hundred and seventy-one subjects were screened for VitD status and 31 VitD deficient subjects with a mean age of 15.7 ± 1.4 years were enrolled and completed the study . Mean 25-OH-VitD levels significantly increased ( 33.0 ± 12.8 vs 67.0 ± 23.2 nmol/L , P < .01 ) with a significant improvement in EF  following VitD supplementation ( lnRHI 0.58 ± 0.20 vs 0.68 ± 0.21 , P = .03 ) . VitD supplementation did not significantly impact systolic blood pressure/diastolic blood pressure ( SBP/DBP ) , lipids , HbA1c and ACR and no adverse effects were seen . Several urinary inflammatory cytokines/chemokines : MCP-3 ( P < .01 ) , epidermal growth factor ( EGF ) ( P < .01 ) tumor necrosis factor β ( TNFβ ) ( P = .01 ) , interleukin-10 ( IL-10 ) ( P = .01 ) , also significantly decreased post-VitD-treatment . CONCLUSIONS Treatment with VitD was associated with an improvement in EF and reduced expression of urinary inflammatory markers in adolescents with T1D . This data is suggestive of an additional benefit of VitD supplementation on early markers of microvascular complications OBJECTIVE Rates of  pre-eclampsia  in women with type 1 diabetes are two to four times higher than in normal pregnancies . Diabetes is associated with antioxidant depletion and increased free radical production , and an increasing body of evidence suggests that oxidative stress and endothelial cell activation may be relevant to disease pathogenesis in pre-eclampsia . The Diabetes and Pre-eclampsia Intervention Trial ( DAPIT ) aims to establish if pregnant women with type 1 diabetes supplemented with vitamins C and E have lower rates of pre-eclampsia and endothelial activation compared with placebo treatment . METHODS DAPIT is a r and omised multicentre double-blind placebo-controlled trial that will recruit 756 pregnant women with type 1 diabetes from 20 metabolic-antenatal clinics in the UK over 4 years . Women are r and omised to daily vitamin C ( 1000 mg ) and vitamin E ( 400 IU ) or placebo at 8 - 22 weeks of gestation until delivery . Maternal venous blood is obtained at r and omisation , 26 and 34 weeks , for markers of endothelial activation and oxidative stress and to assess glycaemic control . The primary outcome of DAPIT is pre-eclampsia . Secondary outcomes include endothelial activation ( PAI-1/PAI-2 ) and birthweight centile CONTEXT Systemic inflammation is thought to have a central role in diabetic long-term complications . OBJECTIVE The aim of this study was to investigate the effects of vitamin D either with or without extra calcium on certain inflammatory biomarkers in the subjects with type 2 diabetes ( T2D ) . DESIGN , SETTING , AND PARTICIPANTS This was a double-blind , r and omized , controlled trial conducted over 12 wk in 90 T2D subjects aged 30 - 60 yr from both sexes . INTERVENTION Subjects were r and omly allocated to one of three groups to receive two 250-ml bottles a day of plain Persian yogurt drink or doogh ( PD , containing 150 mg calcium and no detectable vitamin D(3)/250 ml ) , vitamin D-fortified doogh ( DD , containing 500 IU vitamin D(3 ) and 150 mg calcium/250 ml ) , or calcium + vitamin D(3)-fortified doogh ( CDD , containing 500 IU vitamin D(3 ) and 250 mg calcium/250 ml ) . OUTCOME MEASURES The changes in inflammatory markers were evaluated . RESULTS Compared to the baseline values , highly sensitive C-reactive protein , IL-1β , IL-6 , fibrinogen , and retinol binding protein-4 concentrations significantly decreased in both the DD and CDD groups . Although the decrement in highly sensitive C-reactive protein and fibrinogen was more in CDD compared to DD ( -4.0 ± 8.5 vs. -1.3 ± 2.8 mg/liter , and -0.40 ± 0.74 and -0.20 ± 0.52 mg/liter , respectively ) , the differences were not significant . There was a significant increase in serum adiponectin in both the DD and CDD groups ( 51.3 ± 65.3 vs. 57.1 ± 33.8 μg/liter ; P < 0.05 ) . Mean adiponectin changes in CDD were significantly higher than in PD ( P = 0.021 ) . CONCLUSIONS Daily intake of vitamin D-fortified doogh improved inflammatory markers in T2D subjects , and extra calcium conferred additional benefit only for the antiinflammatory adipokine , i.e. adiponectin PURPOSE Urothelial carcinoma has the highest lifetime treatment cost of any cancer , making it an ideal target for preventative therapies . Previous work has suggested that certain vitamin and mineral supplements may reduce the risk of urothelial  carcinoma . We used the prospect i ve VITamins And Lifestyle cohort to examine the association of all commonly taken vitamin and mineral supplements as well as 6 common anti-inflammatory supplements with incident urothelial carcinoma in a United States population . MATERIAL S AND METHODS A total of 77,050 eligible VITAL participants completed a detailed question naire at baseline on supplement use and cancer risk factors . After 6 years of followup 330 incident urothelial carcinoma cases in the cohort were identified via linkage to the Seattle-Puget Sound SEER cancer registry . We analyzed use of supplemental vitamins ( multivitamins , beta-carotene , retinol , folic acid , and vitamins B1 , B3 , B6 , B12 , C , D and E ) , minerals ( calcium , iron , magnesium , zinc and selenium ) and anti-inflammatory supplements ( glucosamine , chondroitin , saw palmetto , ginkgo biloba , fish oil and garlic ) . For each supplement the hazard ratios ( risk ratios ) for urothelial carcinoma comparing each category of users to nonusers , and 95 % CIs , were determined using Cox proportional hazards regression , adjusted for potential confounders . RESULTS None of the vitamin , mineral or anti-inflammatory supplements was significantly associated with urothelial carcinoma risk in age adjusted or multivariate models . CONCLUSIONS The results of this study do not support the use of commonly taken vitamin or mineral supplements or 6 common anti-inflammatory supplements for the chemoprevention of urothelial carcinoma Background : Vitamin D supplementation has been proposed as a potential strategy to prevent  type 2 diabetes .  Existing clinical trials have been limited by short duration , low doses of vitamin D , variability in participants ' vitamin D-deficiency status , and the use of surrogate measures of body composition , insulin sensitivity , and insulin secretion . Objective : To address existing knowledge gaps , we conducted a double-blind , r and omized , placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-st and ard methods . We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo . Design : Sixty-five overweight or obese , vitamin D-deficient ( 25-hydroxyvitamin D [ 25(OH)D ] concentration ≤50 nmol/L ) adults were r and omly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk . Before and after the intervention , participants received gold-st and ard assessment s of body composition ( via dual X-ray absorptiometry ) , insulin sensitivity ( via hyperinsulinemic-euglycemic clamps ) , and insulin secretion [ via intravenous-glucose-tolerance tests ( IVGTTs ) ] . Results : Fifty-four participants completed the study [ 35 men and 19 women ; mean ± SD age : 31.9 ± 8.5 y ; body mass index ( in kg/m2 ) : 30.9 ± 4.4 ] . 25(OH)D increased with vitamin D supplementation compared with placebo ( 57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L , respectively ; P = 0.02 ) . Vitamin D and placebo groups did not differ in change in insulin sensitivity ( 0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg-1 · min-1 , respectively ; P = 0.9 ) or first-phase insulin secretion ( -21 ± 212 compared with 24 ± 184 mU/L , respectively ; P = 0.9 ) . Results remained nonsignificant after adjustment for age , sex , percentage of body fat , sun exposure , physical activity , and dietary vitamin D intake ( P > 0.1 ) . Conclusions : Vitamin D supplementation does not improve insulin sensitivity or secretion in vitamin D-deficient , overweight or obese adults , despite using high-dose vitamin D supplementation and robust endpoint measures . Therefore , it is unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk even in vitamin D-deficient population s. This trial was registered at clinical trials.gov as NCT02112721
Conclusions This meta‐ analysis provides level 1 evidence that vitamin D supplementation may reduce chronic low‐ grade inflammation in patients with type 2 diabetes .
Background Vitamin D has been proposed to have anti‐inflammatory properties ; however , the effect of vitamin D supplementation on inflammation in type 2 diabetes has not been established .
Objective The aim of this systematic review and meta‐ analysis was to examine the effect of vitamin D supplementation on inflammatory markers in patients with type 2 diabetes and to identify relevant gaps in knowledge .