Large Doses of Vitamin D Fail to Increase 25-Hydroxyvitamin D Levels or to Alter Cardiovascular Risk Factors in Obese Adolescents: A Pilot Study. Effects of a 1-year supplementation with cholecalciferol on interleukin-6, tumor necrosis factor-alpha and insulin resistance in overweight and obese subjects. Effect of vitamin D supplementation on inflammation and nuclear factor kappa-B activity in overweight/obese adults: a randomized placebo-controlled trial Effect of vitamin D supplementation on inflammation: protocol for a systematic review Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial. Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation Effect of short-term vitamin D supplementation on markers of vascular health in South Asian women living in the UK--a randomised controlled trial. Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-beta-glycan consumption in overweight humans. Prospective Association Between the Dietary Inflammatory Index and Cardiovascular Diseases in the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Cohort Vitamin D supplementation during exercise training does not alter inflammatory biomarkers in overweight and obese subjects Vitamin D and inflammatory markers: cross-sectional analyses using data from the English Longitudinal Study of Ageing (ELSA) Effects of acute ingestion of different fats on oxidative stress and inflammation in overweight and obese adults Impact of Vitamin D Supplementation on Inflammatory Markers in African Americans: Results of a Four-Arm, Randomized, Placebo-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 a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: a randomised controlled pilot study. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects.
PURPOSE Vitamin D deficiency and cardiometabolic risk factors are common in obese adolescents . Observational studies demonstrate an inverse relationship among serum 25-hydroxyvitamin D ( 25OHD ) and obesity , insulin resistance , and inflammatory cytokines . This pilot study explores if vitamin D supplementation could reduce serum concentrations of inflammatory cytokines ( interleukin [ IL ] 6 , IL-10 , tumor necrosis factor α ) , adiponectin , lipids , hemoglobin A1C , and high-sensitivity C-reactive protein ( hs-CRP ) . A secondary aim was to determine the associations between baseline serum 25OHD concentrations and body mass index ( BMI ) , hs-CRP , inflammatory cytokines , and lipids . METHODS Overweight and obese adolescents enrolled in this 24-week , r and omized , double-blind study were given 150,000 IU ergocalciferol or placebo at baseline and 12 weeks . Outcome measurements included serum 25OHD , inflammatory cytokines , adiponectin , hs-CRP , lipids , hemoglobin A1C , and BMI at baseline , 12 , and 24 weeks . RESULTS Of 40 participants , 31 ( 78 % ) completed the study . Mean ± st and ard error 25OHD levels were similar in vitamin D and placebo groups at baseline ( 19.6 ± 5.3 vs. 25.8 ± 10.8 ng/mL ) and 24 weeks ( 20.1 ± 3.4 vs. 24.6 ± 8.4 ng/mL ) . Inflammatory and cardiovascular markers were not significantly different between groups at 24 weeks . Serum 25OHD at baseline was associated with BMI ( r = -.44 [ 95 % confidence interval , -.66 to -.15 ] ) but not with other outcome measures . CONCLUSIONS Supplementation with vitamin D at 150,000 IU every 3 months failed to increase serum 25OHD or alter inflammatory markers and lipids in overweight and obese youth . Further studies are needed to establish the dose of vitamin D required to increase 25OHD and determine potential effects on metabolic risk factors in obese teens Insufficient vitamin D status has been linked to autoimmune diseases , cancer and metabolic disorders , like obesity and insulin resistance . In vitro and animal studies suggest that vitamin D may play a crucial role in immune activation and inflammation . The relation between vitamin D and pro-inflammatory cytokines is not completely established . Furthermore , it is not known if the effect of vitamin D on entities of metabolic syndrome is mediated through its effect on cytokines or other biomarkers . The objectives of this study were to investigate if there is a relationship between vitamin D status and such pro-inflammatory cytokines as tumor necrosis factor-alpha ( TNF-α ) , interleukin 6 ( IL-6 ) and high sensitive C-reactive protein ( hs-CRP ) in patients with overweigh and obesity . We also proposed that the intervention with high dose of cholecalciferol may have effect on the cytokine levels and result in corresponding changes in the measures of insulin resistance ( HOMA-IR and QUICKI ) . Serum levels of IL-6 , TNF-α and hs-CRP were measured in 332 overweight and obese subjects who completed a 1-year r and omised intervention with either 40,000 IU vitamin D ( cholecalciferol ) per week or 20,000 IU vitamin D per week  ,  or placebo .  We found significant associations between IL-6 , TNF-α , vitamin D and insulin resistance indices at baseline . One year intervention with vitamin D  decreased serum IL-6 levels ; however hs-CRP levels were significantly increased . Neither measures of insulin resistance , nor TNF-α were influenced by a 1-year vitamin D supplementation 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 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 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 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 Patients with cystic fibrosis ( CF ) suffer from chronic lung infection and inflammation leading to respiratory failure . Vitamin D deficiency is common in patients with CF , and correction of vitamin D deficiency may improve innate immunity and reduce inflammation in patients with CF . We conducted a double-blinded , placebo-controlled , r and omized clinical trial of high-dose vitamin D to assess the impact of vitamin D therapy on antimicrobial peptide concentrations and markers of inflammation . We r and omized 30 adults with CF hospitalized with a pulmonary exacerbation to 250 000 IU of cholecalciferol or placebo  , and evaluated changes in plasma concentrations of inflammatory markers and the antimicrobial peptide LL-37 at baseline and 12 weeks post intervention . In the vitamin D group , there was a 50.4 % reduction in tumor necrosis factor-α ( TNF-α ) at 12 weeks ( P<0.01 ) , and there was a trend for a 64.5 % reduction in interleukin-6 ( IL-6 ) ( P=0.09 ) . There were no significant changes in IL-1β , IL-8 , IL-10 , IL-18BP and NGAL ( neutrophil gelatinase-associated lipocalin ) . We conclude that a large bolus dose of vitamin D is associated with reductions in two inflammatory cytokines , IL-6 and TNF-α . This study supports the concept that vitamin D may help regulate inflammation in CF , and that further research is needed to eluci date the potential mechanisms involved and the impact on clinical outcomes OBJECTIVE Low vitamin D levels and risk factors for vascular disease are both common in South Asian women . This trial evaluated whether vitamin D supplementation could improve markers of vascular health in South Asian women with low 25-hydroxyvitamin D levels . METHODS Parallel-group , double-blind , r and omised placebo-controlled trial . Healthy South Asian women with baseline serum 25-hydroxyvitamin D levels of < 75 nmol/L were r and omised to receive a single dose of 100,000 units oral vitamin D3 or matching placebo . Outcomes were measured at baseline , 4 and 8 weeks . The primary outcome was change in endothelial function measured using brachial artery flow-mediated dilatation . Secondary outcomes included blood pressure , arterial stiffness , microvascular function measured using laser Doppler iontophoresis , insulin resistance , serum lipids , circulating markers of inflammation , thrombosis and adipokines . RESULTS 50 women were r and omised , 25 to each group . Mean age was 41 years ; mean baseline 25-hydroxyvitamin D level was 27 nmol/L.  25-Hydroxyvitamin D levels rose in the vitamin D group relative to the placebo group by 4 weeks ( 16 nmol/L , 95 % CI 11 to 21 , p < 0.001 ) . There was no improvement in flow-mediated dilatation in the vitamin D group relative to placebo at 4 weeks ( 0.1 % , 95 % CI -0.9 to 1.1 , p = 0.84 ) or 8 weeks ( 0.0 % , 95 % CI -1.4 to 1.4 , p = 0.98 ) . There was no improvement in cholesterol , insulin resistance or markers of inflammation . Both platelet activation inhibitor-1 and tissue plasminogen activator levels fell significantly in the vitamin D group relative to placebo at 8 weeks . CONCLUSION A single large dose of vitamin D3 did not improve blood pressure or endothelial function in South Asian women with low baseline 25-hydroxyvitamin D levels . TRIAL REGISTRATION IS RCT N75081811 Obesity-induced insulin resistance has been suggested to be a systemic inflammatory condition with activation of the innate immune system . Animal studies indicate that certain dietary fibers such as (1,3)(1,6)-beta-D-glycans ( BDG ) have potent effects on immune activity such as increasing the antiinflammatory cytokine interleukin-10 ( IL-10 ) and reducing the secretion of inflammatory factors . Therefore , we hypothesized that BDG consumption improves inflammatory markers and insulin sensitivity in overweight and obese subjects with moderately increased levels of C-reactive protein , indicating sub clinical inflammation . We screened 180 overweight and obese subjects for moderately increased C-reactive protein levels on 2 or more occasions , in the absence of any signs of acute infection . Twelve of the subjects met all inclusion criteria and were investigated in a r and omized , double-blind , placebo-controlled , crossover design for 2 x 4 weeks ( washout > or = 4 weeks ) . Subjects ingested capsules containing 3 x 0.5 g of highly purified BDG or 3 x 0.5 g of placebo ( waxy maize starch ) daily . Maintenance of the normal diet of the participants and the correct intake of the capsules were monitored , using 6 x 3-day food recording and counting of the provided capsules . Predefined outcome measures were BDG-induced changes in pro and antiinflammatory markers in circulating blood and gene expression in adipose tissue and peripheral insulin sensitivity expressed as M value . The BDG consumption for 4 weeks significantly increased both circulating levels and adipose tissue messenger RNA ( mRNA ) expression of the antiinflammatory cytokine IL-10 in overweight and obese humans .  Insulin sensitivity as well as circulating levels and mRNA expression of proinflammatory cytokines were unaffected by BDG treatment . Increased IL-10 after BDG consumption might be a contributing factor to the known beneficial effects of dietary fiber intake Background Cardiovascular diseases ( CVD ) are the leading cause of death in the world , and diet plays a major role in CVD incidence , especially through lipid oxidation mechanisms . This , in turn , leads to tissue inflammation and formation of atheromatous plaques . Methods and Results Our objective was to evaluate the association between the inflammatory potential of the diet and the incidence of overall CVD or its subclasses . We included 7743 participants from the Supplémentation en Vitamines et Minéraux AntioXydants ( SU.VI.MAX ) cohort . All cardiovascular events were recorded using self‐reported information or clinical visits , and were vali date d. The dietary inflammatory index ( DII ) was computed using repeated 24‐hour dietary records ( mean=9.5±3.4 records/subject ) . Hazard ratio and 95 % CI for outcomes ( CVD and subclasses ) were estimated across sex‐specific quartiles of the DII using Cox proportional hazard models . A total of 292 cardiovascular events were recorded and vali date d during an average of 11.4 years of follow‐up : 93 myocardial infa rct ions , 58 strokes , 128 angina pectoris and revascularization interventions , and 13 sudden deaths . When considering CVD subclasses , a diet with pro‐inflammatory properties , as expressed by higher DII scores , was significantly associated with a higher risk of myocardial infa rct ion ( hazard ratioQuartile 4 versus Quartile 1=2.24 , 95 % CI : 1.08–4.67 ) . No significant association was observed between the DII score and stroke or both angina pectoris and revascularization intervention . Conclusions A pro‐inflammatory diet , as measured by a higher DII score , was prospect ively associated with a higher risk of myocardial infa rct ion . Promotion of a diet exhibiting anti‐inflammatory properties may help prevent myocardial infa rct ions The purpose of this study was to examine the effects of vitamin D supplementation on inflammatory biomarkers in overweight and obese adults participating in a progressive resistance exercise training program . Twenty-three ( 26.1 ± 4.7 years ) overweight and obese ( BMI 31.3 ± 3.2 kg/m2 ) adults were r and omized into a double-blind vitamin D supplementation ( Vit D 4,000 IU/day ; female 5 , male 5 ) or placebo ( PL , female 7 ; male 6 ) intervention trial . Both groups performed 12 weeks ( 3 days/week ) of progressive resistance exercise training ( three sets of eight exercises ) at 70–80 % of one repetition maximum . Whole-blood lipopolysaccharide (LPS)-stimulated tumor necrosis factor ( TNF ) α production as well as circulating C-reactive protein ( CRP ) , TNFα , interleukin 6 ( IL-6 ) , and alanine aminotransferase ( ALT ) were assessed at baseline and after the 12-week intervention . No main effects of group or time were detected for circulating CRP , TNFα , IL-6 , and ALT . As expected , when PL and Vit D groups were combined , there was a significant correlation between percent body fat and CRP at baseline ( r = 0.45 , P = 0.04 ) , and between serum 25OHD and CRP at 12 weeks ( r = 0.49 , P = 0.03 ) . The PL group had a significant increase in 25 μg/ml LPS + polymixin B-stimulated TNFα production ( P = 0.04 ) , and both groups had a significant reduction in unstimulated TNFα production ( P < 0.05 ) after the 12-week intervention . Vitamin D supplementation in healthy , overweight , and obese adults participating in a resistance training intervention did not augment exercise-induced changes in inflammatory biomarkers Recent evidence suggests that low vitamin D concentrations are associated with increased levels of inflammatory markers . However , there are limited studies investigating associations between vitamin D levels and inflammatory markers in the general population and much of this evidence in older adults is inconclusive . Therefore , this study investigates the cross-sectional association of  serum 25-hydroxyvitamin D ( 25(OH)D ) levels with inflammatory markers in 5870 older English adults from wave 6 ( 2012–2013 ) of the English Longitudinal Study of Ageing ( ELSA ) . ELSA is a large prospect i ve observational study of community-dwelling people aged 50 years and over in Engl and . Serum 25(OH)D levels , C-reactive protein ( CRP ) levels , plasma fibrinogen levels , white blood cell count ( WBC ) , age , season of blood collection , waist circumference , total non-pension household wealth , measures of health and health behaviours that included depression , number of cardiovascular , non-cardiovascular conditions and difficulties in activities of daily living , smoking , and physical activity were measured . There was a significant negative association between low 25(OH)D levels ( ≤30 nmol/l ) and CRP ( OR 1·23 , 95 % CI 1·00 , 1·51 ) and WBC ( OR 1·35 , 95 % CI 1·13 , 1·60 ) that remained after adjustment for a wide range of covariates of clinical significance . However , for fibrinogen , the association did not remain significant when waist circumference was entered in the final model . Our findings showed that 25(OH)D levels were associated with two out the three inflammatory markers investigated . The independent and inverse association between serum 25(OH)D levels and inflammation suggests a potential anti-inflammatory role for vitamin D in older English individuals from the general population Background Studies show that obese individuals have prolonged elevations in postpr and ial lipemia and an exacerbated inflammatory response to high fat meals , which can increase risk for cardiovascular diseases . As epidemiological studies indicate an association between type of fat and circulating inflammatory markers , the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals . Methods Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat ( MFA ) , saturated fat ( SFA ) , or long-chain omega 3 polyunsaturated fat ( O3FA ) in r and om order . Blood sample s collected at baseline , 1 , 2 , 4 , and 6 hours postpr and ial were analyzed for markers of inflammation ( soluble intercellular adhesion molecule-1 ( ICAM-1 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) , tumor necrosis factor- α ( TNF-α ) , and C-reactive protein ( CRP ) ) , oxidative stress ( 8-epi-prostagl and in-F2α ( 8-epi ) and nuclear factor-κB ( NF-κB ) ) , and metabolic factors ( glucose , insulin , non-esterified free fatty acids , and triglycerides ( TG ) ) . Results O3FA enhanced NF-kB activation compared to SFA , but did not increase any inflammatory factors measured . Conversely , SFA led to higher ICAM-1 levels than MFA ( p = 0.051 ) , while MFA increased TG more than SFA ( p < 0.05 ) . CRP increased while TNF-α and 8-epi decreased with no difference between treatments . Conclusions While most of the inflammatory factors measured had modest or no change following the meal , ICAM-1 and NF-κB responded differently by meal type . These results are provocative and suggest that type of fat in meals may differentially influence postpr and ial inflammation and endothelial activation 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 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 OBJECTIVE Apart from its role in bone metabolism , vitamin D may also influence cardiovascular disease . The objective of this study was : ( 1 ) to determine the effect of a single , oral , high-dose vitamin D supplementation on endothelial function and arterial stiffness in patients with peripheral arterial disease ( PAD ) and ( 2 ) to investigate the impact of this supplementation on coagulation and inflammation parameters . METHODS In this double-blind , placebo-controlled , interventional pilot study , we screened 76 Caucasian patients with PAD for vitamin D deficiency . Sixty-two were r and omised to receive a single , oral supplementation of 100,000 IU vitamin D3 or placebo . At baseline and after 1 month , we measured serum vitamin D and parathormone levels , and surrogate parameters for cardiovascular disease . RESULTS Sixty-five of 76 patients ( 86 % ) had low 25-hydroxyvitamin D levels ( < 30 ng ml(-1 ) ) ; of those , 62 agreed to participate in the study . At baseline , only parathormone was related to vitamin D. In supplemented patients , vitamin D levels increased from 16.3 ± 6.7 to 24.3 ± 6.2 ng ml(-1 ) ( P < 0.001 ) , with wide variations between single patients ; in the placebo group vitamin levels did not change . Seasonal factors accounted for a decrease of vitamin D levels by 8 ng ml(-1 ) between summer and winter . After 1 month , none of the measured parameters was influenced by vitamin substitution . CONCLUSION In this pilot study , most patients with PAD were vitamin D deficient . Vitamin D supplementation  increased serum 25-hydroxyvitamin D without influencing endothelial function , arterial stiffness , coagulation and inflammation parameters , although the study was underpowered for definite conclusions CONTEXT Vitamin D receptors are present in many tissues . Hypovitaminosis D is considered to be a risk factor for atherosclerosis . OBJECTIVE This study explores the effects of vitamin D replacement on insulin sensitivity , endothelial function , inflammation , oxidative stress , and leptin in vitamin D-deficient subjects . DESIGN , SETTING , AND PATIENTS Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [ 25(OH)D ] levels below 25 nmol/liter were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter . The vitamin D-deficient group received 300,000 IU i m monthly for 3 months . The following parameters were evaluated before and after treatment : vitamin D metabolites , leptin , endothelial function by brachial artery flow mediated dilatation ( FMD ) , insulin sensitivity index based on oral glucose tolerance test , and lipid peroxidation as measures of thiobarbituric acid reactive substances ( TBARS ) . RESULTS FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls ( P = 0.001 ) and improved after replacement therapy ( P = 0.002 ) . Posttreatment values of TBARS were significantly lower than pretreatment levels ( P < 0.001 ) . A positive correlation between FMD and 25(OH)D ( r = 0.45 ; P = 0.001 ) and a negative correlation between FMD and TBARS ( r = -0.28 ; P < 0.05 ) were observed . There was a significant increase in leptin levels after therapy , and the leptin levels were positively correlated with 25(OH)D levels ( r = 0.45 ; P < 0.05 ) . CONCLUSIONS This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation . Replacement of vitamin D has favorable effects on endothelial function . Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis . Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter
Baseline serum VD possibly influences the effect of VD repletion on inflammatory markers .
Risk of bias was present in most studies , thus supporting the need for higher quality studies in this area to more conclusively underst and the role VD supplementation has on inflammatory pathways
BACKGROUND Obesity induced low- grade chronic inflammation disrupts proper immune and metabolic function .
Vitamin D deficiency increases inflammation , which is associated with cardiometabolic risk .
This systematic review examines the association between oral vitamin D ( VD ) supplementation and circulating inflammatory biomarkers and glycemic outcomes from r and omized controlled trials ( RCTs ) of overweight and /or obese adults .