Effect of vitamin D supplementation on inflammation and nuclear factor kappa-B activity in overweight/obese adults: a randomized placebo-controlled trial Effects of a 1-year supplementation with cholecalciferol on interleukin-6, tumor necrosis factor-alpha and insulin resistance in overweight and obese subjects. Vitamin D supplementation during exercise training does not alter inflammatory biomarkers in overweight and obese subjects Effect of vitamin D supplementation on inflammation: protocol for a systematic review Large Doses of Vitamin D Fail to Increase 25-Hydroxyvitamin D Levels or to Alter Cardiovascular Risk Factors in Obese Adolescents: A Pilot Study. Antioxidant supplements reduced oxidative stress and stabilized liver function tests but did not reduce inflammation in a randomized controlled trial in obese children and adolescents. Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial. Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial Effect of moderate-dose vitamin D supplementation on insulin sensitivity in vitamin D-deficient non-Western immigrants in the Netherlands: a randomized placebo-controlled trial. Daily Cholecalciferol Supplementation during Pregnancy Alters Markers of Regulatory Immunity, Inflammation, and Clinical Outcomes in a Randomized Controlled Trial. Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults. Yeast β–Glucan Modulates Inflammation and Waist Circumference in Overweight and Obese Subjects Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial. Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: Results from the ComparED study. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Consumption of sucrose-sweetened soft drinks increases plasma levels of uric acid in overweight and obese subjects: a 6-month randomised controlled trial Effects of oral vitamin C supplementation on oxidative stress and inflammation status in haemodialysis patients. Effects of low-fat dairy consumption on markers of low-grade systemic inflammation and endothelial function in overweight and obese subjects: an intervention study. Effects of low- and high-glycemic index/glycemic load diets on coronary heart disease risk factors in overweight/obese men. Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease Effects of acute ingestion of different fats on oxidative stress and inflammation in overweight and obese adults
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 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 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 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 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 Oxidative stress and low- grade systemic inflammation may contribute to the pathogenesis of obesity-induced comorbidities , including nonalcoholic fatty liver disease . Increasing intake of dietary antioxidants might be beneficial , but there are few data in obese children . To examine the effect of antioxidant supplementation on biomarkers of oxidative stress , inflammation , and liver function , we r and omly assigned overweight or obese children and adolescents ( n = 44 ; mean ± SD age : 12.7 ± 1.5 y ) participating in a lifestyle modification program to a 4-mo intervention with daily antioxidants ( vitamin E , 400 IU ; vitamin C , 500 mg ; selenium , 50 μg ) or placebo . We measured anthropometrics , antioxidant status , oxidative stress ( F(2)-isoprostanes , F(2)-isoprostane metabolites ) , inflammation , liver enzymes , fasting insulin and glucose , and lipid profile at baseline and endpoint . There was a significant treatment effect of antioxidant supplementation on antioxidant status [ α-tocopherol , β = 23.2 ( 95 % CI : 18.0 , 28.4 ) ; ascorbic acid , β = 70.6 ( 95 % CI : 51.7 , 89.4 ) ; selenium , β = 0.07 ( 95 % CI : 0.01 , 0.12 ) ] and oxidative stress [ 8-iso-prostagl and in F2α , β = -0.11 ( 95 % CI : -0.19 , -0.02 ) ] but not on any of the inflammatory markers measured . There was a significant treatment effect on alanine aminotransferase [ β = -0.13 ( 95 % CI : -0.23 , -0.03 ) ] , a trend toward a significant effect on aspartate aminotransferase [ β = -0.04 ( 95 % CI : -0.09 , 0.01 ) ] , and no significant effect on γ-glutamyltransferase [ β = -0.03 ( 95 % CI : -0.11 , 0.06 ) ] . In  summary , antioxidant supplementation for 4 mo improved antioxidant-oxidant balance and modestly improved liver function tests ; however , it did not reduce markers of systemic inflammation despite significant baseline correlations between oxidative stress and inflammation . The study was registered at clinical trials.gov as NCT01316081 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 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 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 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 BACKGROUND Low serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with insulin resistance , the metabolic syndrome , and type 2 diabetes . Because many non-Western immigrants in the Netherl and s are vitamin D deficient , obese , and at high risk of diabetes , vitamin D supplementation may contribute to prevent diabetes and insulin resistance . OBJECTIVE We examined the effect of vitamin D supplementation on insulin sensitivity and β cell function in overweight , vitamin D-deficient , non-Western immigrants at high risk of diabetes . DESIGN The study was a 16-wk , r and omized , placebo-controlled trial . A total of 130 non-Western immigrants with prediabetes ( fasting glucose concentration > 5.5 mmol/L or r and om glucose concentration from 7.8 to 11.1 mmol/L ) and vitamin D deficiency ( serum 25[OH]D concentration < 50 nmol/L ) were r and omly assigned after stratification by sex to receive either cholecalciferol ( 1200 IU/d ) or a placebo for 16 wk . All participants received 500 mg Ca/d as calcium carbonate . The primary outcome was the difference in the area under the curve of insulin and glucose after a 75-g oral-glucose-tolerance test after 4 mo of treatment . Secondary outcomes were insulin-sensitivity variables , β cell-function variables , and metabolic syndrome . RESULTS Mean serum 25(OH)D concentrations increased significantly in the vitamin D compared with placebo groups . After 4 mo of therapy , the mean between-group difference was 38 nmol/L ( 95 % CI : 32.1 , 43.9 nmol/L ; P < 0.001 ) . There was no significant effect on insulin sensitivity and β cell function . In a post hoc analysis , when patients with diabetes at baseline were excluded , a significant increase in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L ( P = 0.040 ) . CONCLUSIONS Vitamin D supplementation in non-Western vitamin D-deficient immigrants with prediabetes did not improve insulin sensitivity or β cell function or change the incidence of metabolic syndrome . However , after the exclusion of diabetic subjects , an improvement in the insulinogenic index was observed in participants who obtained a 25(OH)D concentration ≥60 nmol/L. This trial was registered at trialregister.nl as NTR1827 BACKGROUND Vitamin D deficiency is widespread in pregnancy and has been associated with adverse health conditions in mothers and infants .  Vitamin D supplementation in pregnancy may support the maintenance of pregnancy by its effects on innate and adaptive immunity . OBJECTIVE We assessed the effects of vitamin D supplementation during pregnancy on vitamin D status and markers of immune function associated with adverse pregnancy outcomes . METHODS We conducted a r and omized , controlled , double-blind intervention of 2 doses of cholecalciferol ( 400 and 2000 IU/d ) from < 20 wk to delivery in 57 pregnant women .  Vitamin D status , regulatory and inflammatory T cells , markers of innate immunity and systemic inflammation , and clinical outcomes including maternal blood pressure and birth weight were assessed at 26 and 36 wk of pregnancy . RESULTS Supplementation with 2000 IU/d vitamin D had a greater effect on the change in vitamin D status over pregnancy ( P < 0.0001 ) and the final value at 36 wk ( P < 0.0001 ) than 400 IU/d , increasing serum 25-hydroxyvitamin D from 81.1 nmol/L at baseline to 116 nmol/L at 36 wk and from 69.6 nmol/L at baseline to 85.6 nmol/L at 36 wk , respectively . The 2000-IU/d group had 36 % more interleukin-10 + regulatory CD4 + T cells at 36 wk than did the 400-IU/d group ( P < 0.007 ) . The daily intake of 2000 compared with 400 IU/d tended to dampen the pregnancy-related increase in diastolic blood pressure by 1.3-fold ( P = 0.06 ) and increase birth weight by 8.6 % ( P = 0.06 ) , but these differences were not statistically significant . CONCLUSIONS Supplementation with 2000 IU/d is more effective at increasing vitamin D status in pregnant women than 400 IU/d and is associated with increased regulatory T cell immunity that may prevent adverse outcomes caused by excess inflammation . This trial was registered at clinical trials.gov as NCT01417351 Fish oils containing both EPA and DHA have been shown to have beneficial cardiovascular effects , but less is known about the independent effects of DHA . This study was design ed to examine the effects of DHA on plasma lipid and lipoprotein concentrations and other biomarkers of cardiovascular risk in the absence of weight loss . In this r and omized , controlled , double-blind trial , 36 overweight or obese adults were treated with 2 g/d of algal DHA or placebo for 4.5 mo . Markers of cardiovascular risk were assessed before and after treatment . In the DHA-supplemented group , the decrease in mean VLDL particle size ( P ≤ 0.001 ) and increases in mean LDL ( P ≤ 0.001 ) and HDL ( P ≤ 0.001 ) particle sizes were significantly greater than changes in the placebo group . DHA supplementation also increased the concentrations of large LDL ( P ≤ 0.001 ) and large HDL particles ( P = 0.001 ) and decreased the concentrations of small LDL ( P = 0.009 ) and medium HDL particles ( P = 0.001 ) . As calculated using NMR-derived data , DHA supplementation reduced VLDL TG ( P = 0.009 ) and total TG concentrations ( P = 0.006 ) . Plasma IL-10 increased with DHA supplementation to a greater extent than placebo ( P = 0.021 ) , but no other significant changes were observed in glucose metabolism , insulin sensitivity , blood pressure , or markers of inflammation with DHA . In summary , DHA supplementation result ed in potentially beneficial changes in some markers of cardiometabolic risk , whereas other markers were unchanged ABSTRACT Increased inflammation occurs with excessive adiposity and yeast β-glucan modulates immune responses . This study investigated the potential effect of yeast β-glucan on inflammatory cytokines in overweight/obese people . A r and omized , double blinded , placebo-controlled , clinical trial design enrolled 44 overweight/obese participants with body mass index ≥23 kg/m2 , r and omized to two groups  receiving β – glucan 477 mg/capsule ( n = 22 ) or placebo ( n = 22 ) orally for six weeks . At weeks one to two , participants received 1 β – glucan or placebo capsule/day and at four weeks two tablets/day . Anthropometric changes , lipid profiles , liver and renal functions , and inflammatory cytokines were measured . β-glucan  reduced waist circumference ( p = 0.037 ) and blood pressure ( p = 0.006 ) compared with controls after six weeks of intervention . No statistical significance between groups was observed for triglyceride , cholesterol , lipid profile , liver and renal function , or energy and nutrient intake compared with controls at week six . β-glucan increased interlukin-10 ( IL-10 ) , an anti-inflammatory cytokine , by 23.97 % from baseline at week two ( p < 0.001 ) and 31.12 % at week six ( p < 0.001 ) and was significantly increased compared with controls at week two ( p < 0.001 ) until week six ( p < 0.001 ) . β-glucan reduced pro-inflammatory cytokines IL-6 at week six ( p = 0.005 ) and tumor necrosis factor-α at week two ( p = 0.037 ) compared with controls . Supplementation of yeast β-glucan for six weeks modulated pro-cytokines that accelerate overweight/obese comorbidities and reduced blood pressure as well as waist circumference , the strong risk factors for cardiovascular disease , in overweight/obese subjects .  Thus , β-glucan might have the potential to decrease comorbid conditions associated with overweight/ obesity 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 BACKGROUND AND AIMS Whether EPA and DHA exert similar anti-inflammatory effects through modulation of gene expression in immune cells remains unclear . The aim of the study was to compare the impact of EPA and DHA supplementation on inflammatory gene expression in subjects at risk for cardiometabolic diseases . METHODS In this r and omized double-blind crossover trial , 154 men and women with abdominal obesity and low- grade inflammation were subjected to three 10-wk supplementation phases : 1 ) EPA ( 2.7 g/d ) ; 2 ) DHA ( 2.7 g/d ) ; 3 ) corn oil ( 3 g/d ) , separated by a 9-wk washout .  Pro- and anti-inflammatory gene expression was assessed in whole blood cells by RT-qPCR after each treatment in a representative sample of 44 participants . RESULTS No significant difference was observed between EPA and DHA in the expression of any of the genes investigated . Compared with control , EPA  enhanced TRAF3 and PPARA expression and lowered CD14 expression ( p < 0.01 ) whereas DHA  increased expression of PPARA and TNFA and decreased CD14 expression ( p < 0.05 ) . Variations in gene expression after EPA and after DHA were strongly correlated for PPARA ( r = 0.73 , p < 0.0001 ) and TRAF3 ( r = 0.66 , p < 0.0001 ) and less for TNFA ( r = 0.46 , p < 0.005 ) and CD14 ( r = 0.16 , p = 0.30 ) . CONCLUSIONS High-dose supplementation with either EPA or DHA has similar effects on the expression of many inflammation-related genes in immune cells of men and women at risk for cardiometabolic diseases . The effects of EPA and of DHA on anti-inflammatory gene expression may be more consistent than their effects on expression of pro-inflammatory genes in whole blood cells BACKGROUND Persistent , low- grade inflammation is an independent predictor of several chronic diseases and all-cause mortality . OBJECTIVE The intention of this study was to determine the independent and combined effects of diet-induced weight loss and exercise on markers of chronic inflammation . DESIGN Three hundred sixteen community-dwelling , older ( > or = 60 y ) , overweight or obese [ body mass index ( in kg/m2 ) > or = 28 ] , sedentary men and women with radiographic evidence of knee osteoarthritis were r and omly assigned to four 18-mo treatments : healthy lifestyle control , diet-induced weight loss , exercise , and diet plus exercise . The exercise intervention consisted of combined weight training and walking for 1 h 3 times/wk . The weight-loss intervention consisted of a weekly session with a registered dietitian to provide education and support for lowering energy intake . RESULTS The diet-induced weight-loss intervention result ed in significantly greater reductions in concentrations of C-reactive protein ( P = 0.01 ) , interleukin 6 ( P = 0.009 ) , and soluble tumor necrosis factor alpha receptor 1 ( P = 0.007 ) than did no weight-loss treatment . Changes in soluble tumor necrosis factor alpha receptor 1 but not in C-reactive protein or interleukin 6 correlated with changes in body weight .  Exercise training did not have a significant effect on these inflammatory biomarkers , and there was no significant interaction between weight loss and exercise training . CONCLUSIONS These findings provide evidence from a r and omized controlled trial that a dietary intervention design ed to elicit weight loss reduces overall inflammation in older , obese persons . Additional studies are needed to assess the effects of different modes and intensities of exercise on inflammation Background / Objectives : Sucrose-sweetened soft drinks ( SSSDs ) are associated with the development of metabolic disorders . Fructose is a major component of SSSDs and is demonstrated to induce uric acid ( UA ) production and stimulate fat accumulation independent of excess caloric intake . UA induce insulin resistance and low- grade inflammation , suggesting that UA may have a causal role in the development of metabolic complications . The objective of this study is to investigate the long-term effects of consuming SSSDs on circulating levels of UA in overweight and obese subjects . Subjects/ Methods : Using a previously published study , circulating UA levels were assessed at baseline and after 6 months using chromogenic enzymatic absorptiometry . The study included 47 overweight and obese subjects without diabetes , r and omised to consume 1 l daily of either SSSD ( regular cola ) , isocaloric semi-skimmed milk , diet cola or water for 6 months . Results : Circulating UA levels increased ~15 % ( P=0.02 ) after the 6-month intervention in the SSSD group with no change in the other groups . In the SSSD  group , circulating UA levels increased significantly after the intervention in both absolute ( P=0.005 ) and relative values ( P=0.004 ) . The change in UA after the intervention correlated with changes in liver fat ( P=0.005 ) , triglycerides ( P=0.02 ) and insulin ( P=0.002 ) . Conclusions : In this secondary analysis daily intake of 1 l SSSD for 6 months was found to increase circulating UA levels compared with isocaloric milk , diet cola and water . Thus , a high daily intake of SSSDs in overweight and obese subjects without overt diabetes may increase the risk of developing metabolic complications through the elevation of UA . This trial is registered at Clinical Trials.gov as NCT00777647 BACKGROUND There is increasing evidence for the presence of oxidative stress and vitamin C deficiency in dialysis patients . Limited data , however , are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in such patients . METHODS We ran a prospect i ve , r and omized , open-label trial to assess the effects of oral vitamin C supplementation ( 250 mg three times per week ) for 2 months on well-defined oxidative and inflammatory markers in 33 chronic haemodialysis ( HD ) patients . RESULTS Normalization of plasma total vitamin C and ascorbate levels by oral vitamin C supplementation did not modify plasma levels of carbonyls , C-reactive protein and albumin , or erythrocyte concentrations of reduced and oxidized glutathione . CONCLUSION Short-term oral vitamin C supplementation did not modify well-defined oxidative/antioxidative stress and inflammation markers in HD patients . Whether a higher oral dose or the intravenous route can modify these markers remains to be determined Although increased concentrations of plasma inflammatory markers are not one of the criteria to diagnose the metabolic syndrome , low- grade systemic inflammation is receiving large attention as a metabolic syndrome component and cardiovascular risk factor . As several epidemiological studies have suggested a negative relationship between low-fat dairy consumption and the metabolic syndrome , we decided to investigate the effects of low-fat dairy consumption on inflammatory markers and adhesion molecules in overweight and obese subjects in an intervention study . Thirty-five healthy subjects ( BMI > 27 kg/m² ) consumed , in a r and om order , low-fat dairy products ( 500 ml low-fat milk and 150 g low-fat yogurt ) or carbohydrate-rich control products ( 600 ml fruit juice and three fruit biscuits ) daily for 8 weeks . Plasma concentrations of TNF-α were decreased by 0.16 ( SD 0.50 ) pg/ml ( P = 0.070 ) , and soluble TNF-α receptor-1 ( s-TNFR-1 ) was increased by 110.0 ( SD 338.4 ) pg/ml ( P = 0.062 ) after the low-fat dairy period than after the control period . s-TNFR-2 was increased by 227.0 ( SD 449.0 ) pg/ml ( P = 0.020 ) by the dairy intervention . As a result , the TNF-α index , defined as the TNF-α : s-TNFR-2 ratio , was decreased by 0.000053 ( SD 0.00012 ) ( P = 0.015 ) after the dairy diet consumption . Low-fat dairy consumption had no effect on IL-6 , monocyte chemoattractant protein-1 , intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 concentrations . The present results indicate that in overweight and obese subjects , low-fat dairy consumption for 8 weeks may increase concentrations of s-TNFR compared with carbohydrate-rich product consumption , but that it has no effects on other markers of chronic inflammation and endothelial function Chronic insulin resistance contributes to sub clinical inflammation , thrombosis/impaired fibrinolysis , and dyslipidemia . The effect of dietary carbohydrate , specifically of glycemic index ( GI ) and glycemic load ( GL ) , on established and emerging coronary heart disease risk factors has not been eluci date d fully . We conducted a r and omized crossover feeding study of matched diets differing only in GI and GL in 24 overweight or obese but otherwise healthy men to investigate the effects on insulin sensitivity , inflammation , thrombosis/fibrinolysis , lipoproteins/lipids , and body composition .  All meals for the high- and low-GI/GL diets were prepared in a metabolic kitchen . Each participant consumed both diets in r and om order for 4 weeks each , with a 4-week washout period in between . Each participant underwent a frequently sample d intravenous glucose tolerance test for assessment of insulin sensitivity ; blood sampling for the measurement of inflammatory markers , coagulation factors , and lipoproteins/lipids ; and dual-energy x-ray absorptiometry for assessment of body composition at the beginning and end of each dietary period . There were no statistically significant differences in glucose metabolism factors , inflammatory markers , or coagulation factors after 4 weeks on the high- and low-GI/GL diets . The high-GI/GL diet result ed in a slightly greater reduction in fat mass and a slightly greater increase in lean mass compared with the low-GI/GL diet . The high-GI/GL diet result ed in significant , but unexpected , reductions in total and low-density lipoprotein cholesterol , whereas high-density lipoprotein cholesterol concentration was significantly reduced on the high-GI/GL diet compared with the low-GI/GL diet . Overall , high- and low-GI/GL diets of 4 weeks ' duration had no consistent effects on coronary heart disease risk factors in this group of overweight/obese men Background / objectives : Vitamin D has anti-inflammatory and immune-regulating properties . We aim ed to determine if high-dose cholecalciferol supplementation for 1 year in subjects with early chronic kidney disease ( CKD ) improved circulating markers of inflammation and immunity . Subjects/ methods : In this double-blind , r and omized , placebo-controlled trial , 46 subjects with early CKD ( stages 2 and 3 ) were supplemented with oral cholecalciferol ( 50 000 IU weekly for 12 weeks followed by 50 000 IU every other week for 40 weeks ) or a matching placebo for 1 year . Serum tumor necrosis factor-α , interleukin-6 , monocyte chemoattractant protein-1 ( MCP-1 ) , interferon gamma-induced protein-10 and neutrophil gelatinase-associated lipocalin were measured at baseline , 12 weeks and 1 year . Serum cathelicidin ( LL-37 ) was measured at baseline and 12 weeks . An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide ( LPS ) and Pseudomonas aeruginosa . Results : By 12 weeks , serum MCP-1 decreased in the cholecalciferol group ( 66.2±2.5 to 60.8±2.6 pg/ml , group-by-time interaction P=0.02 ) but was not different from baseline at 1 year . Other markers of inflammation and immunity did not change . In vitro , LPS- and Pseudomonas-activated monocytes treated with 1,25(OH)2D3 had significantly less MCP-1 secretion compared with untreated cells . Conclusions : High-dose cholecalciferol  decreased serum MCP-1 concentrations by 12 weeks in patients with early CKD , although the decrease was not maintained for the remainder of the year . In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes 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
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 .