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 Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol The effects of vitamin D and omega-3 fatty acids co-supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in patients with gestational diabetes A Randomized Controlled Clinical Trial Investigating the Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Biomarkers of Oxidative Stress, Inflammation and Pregnancy Outcomes in Gestational Diabetes. The effects of synbiotic supplementation on hormonal status, biomarkers of inflammation and oxidative stress in subjects with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial The Effects of Vitamin D-K-Calcium Co-Supplementation on Endocrine, Inflammation, and Oxidative Stress Biomarkers in Vitamin D-Deficient Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Effect of alpha-lipoic acid and vitamin E supplementation on oxidative stress, inflammation, and malnutrition in hemodialysis patients. The vitamin E debate: implications for ongoing trials of pre‐eclampsia prevention Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. Does short-term vitamin C reduce cardiovascular risk in type 2 diabetes? 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. A systematic review of randomized controlled trials on curative and health enhancement effects of forest therapy The Effects of Chromium Supplementation on Endocrine Profiles, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial Effects of oral vitamin C supplementation on oxidative stress and inflammation status in haemodialysis patients. Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients. Mendelian randomization studies of biomarkers and type 2 diabetes Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - The "RISTOMED project": Randomized controlled trial in healthy older people. Effects of alpha-tocopherol and mixed tocopherol supplementation on markers of oxidative stress and inflammation in type 2 diabetes. Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome. The effects of probiotic supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes in gestational diabetes Effects of combination tocopherols and alpha lipoic acid therapy on oxidative stress and inflammatory biomarkers in chronic kidney disease. FISH OIL AND VITAMIN E CHANGE LIPID PROFILES AND ANTI-LDL-ANTIBODIES IN TWO DIFFERENT ETHNIC GROUPS OF WOMEN TRANSITIONING THROUGH MENOPAUSE. Effect of daily supplementation of fruits on oxidative stress indices and glycaemic status in type 2 diabetes mellitus.
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 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 Background This study was carried out to determine the effects of vitamin D and omega-3 fatty acids co- supplementation on biomarkers of inflammation , oxidative stress and pregnancy outcomes  in gestational diabetes ( GDM ) patients . Methods This r and omized , double-blind , placebo-controlled trial was conducted among 120 GDM women . Participants were r and omly divided into four groups to receive : 1 ) 1000 mg omega-3 fatty acids containing 180 mg eicosapentaenoic acid ( EPA ) and 120 mg docosahexaenoic acid ( DHA ) twice a day + vitamin D placebo ( n = 30 ) ; 2 ) 50,000 IU vitamin D every 2 weeks + omega-3 fatty acids placebo ( n = 30 ) ; 3 ) 50,000 IU vitamin D every 2 weeks + 1000 mg omega-3 fatty acids twice a day ( n = 30 ) and 4 ) vitamin D placebo + omega-3 fatty acids placebo ( n = 30 ) for 6 weeks . Results Subjects who received vitamin D plus omega-3 fatty acids supplements compared with vitamin D , omega-3 fatty acids and placebo had significantly decreased high-sensitivity C-reactive protein ( −2.0 ± 3.3 vs. -0.8 ± 4.4 , −1.3 ± 2.4 and + 0.9 ± 2.7 mg/L , respectively , P = 0.008 ) , malondialdehyde ( −0.5 ± 0.5 vs. −0.2 ± 0.5 , −0.3 ± 0.9 and + 0.5 ± 1.4 μmol/L , respectively , P < 0.001 ) , and increased total antioxidant capacity ( + 92.1 ± 70.1 vs. + 55.1 ± 123.6 , + 88.4 ± 95.2 and + 1.0 ± 90.8 mmol/L , respectively , P = 0.001 ) and glutathione ( + 95.7 ± 86.7 vs. + 23.0 ± 62.3 , + 30.0 ± 66.5 and −7.8 ± 126.5 μmol/L , respectively , P = 0.001 ) . In addition , vitamin D and omega-3 fatty acids co-supplementation , compared with vitamin D , omega-3 fatty acids and placebo , result ed in lower incidences of newborns ’ hyperbilirubinemiain ( P = 0.037 ) and newborns ’ hospitalization ( P = 0.037 ) . Conclusion Overall , vitamin D and omega-3 fatty acids co-supplementation for 6 weeks among GDM women had beneficial effects on some biomarkers of inflammation , oxidative stress and pregnancy outcomes OBJECTIVES Limited data are available for assessing the effects of omega-3 fatty acids and vitamin E co-supplementation on metabolic profiles and pregnancy outcomes in gestational diabetes ( GDM ) . This study was design ed to determine the effects of omega-3 fatty acids and vitamin E co-supplementation on biomarkers of oxidative stress , inflammation and pregnancy outcomes in women with GDM . METHODS This r and omized , double-blind , placebo-controlled clinical trial was conducted in 60 patients with GDM who were not taking oral hypoglycemic agents . Patients were r and omly allocated to intake either 1000 mg omega-3 fatty acids from flaxseed oil plus 400 IU vitamin E supplements ( n=30 ) or placebo ( n=30 ) for 6 weeks . Fasting blood sample s were obtained from the women at the beginning of the study and after the 6-week intervention to quantify related markers . RESULTS After 6 weeks of intervention , omega-3 fatty acids and vitamin E co-supplementation , compared with the placebo , result ed in a significant rise in total antioxidant capacity ( TAC ) ( + 187.5±224.9 vs. -32.5±136.1 mmol/L ; p<0.001 ) ; nitric oxide ( NO ) ( + 5.0±7.7 vs. -12.0±28.0 µmol/L ; p=0.002 ) and a significant decrease in plasma malondialdehyde ( MDA ) concentrations ( -0.1±0.9 vs. + 0.6±1.4 µmol/L ; p=0.03 ) . Co-supplementation with omega-3 fatty acids and vitamin E showed no detectable changes in plasma glutathione and serum high-sensitivity C-reactive protein levels . Joint omega-3 fatty acids and vitamin E supplementation result ed in lower incidences of hyperbilirubinemia in newborns ( 10.3 % vs. 33.3 % ; p=0.03 ) . CONCLUSIONS Overall , omega-3 fatty acids and vitamin E co-supplementation for 6 weeks in women with GDM had beneficial effects on plasma TAC , MDA and NO and on the incidence of the newborns ' hyperbilirubinemia Background To our knowledge , no reports are available indicating the effects of synbiotic supplementation on hormonal status , biomarkers of inflammation and oxidative stress in subjects with polycystic ovary syndrome ( PCOS ) . This research was done to assess the effects of synbiotic supplementation on hormonal status , biomarkers of inflammation and oxidative stress in subjects with PCOS . Methods This r and omized double-blind , placebo-controlled trial was conducted on 60 subjects diagnosed with PCOS according to the Rotterdam criteria . Subjects were r and omly assigned into two groups to take either synbiotic ( n = 30 ) or placebo ( n = 30 ) for 12 weeks . Endocrine , inflammation and oxidative stress biomarkers were quantified at baseline and after the 12-week intervention . Results After the 12-week intervention , compared with the placebo , synbiotic supplementation significantly increased serum sex hormone-binding globulin ( SHBG ) ( changes from baseline in synbiotic group : + 19.8 ± 47.3 vs. in placebo group : + 0.5 ± 5.4 nmol/L , p = 0.01 ) , plasma nitric oxide ( NO ) ( changes from baseline in synbiotic group : + 5.5 ± 4.8 vs. in placebo group : + 0.3 ± 9.1 μmol/L , p = 0.006 ) , and decreased modified Ferriman Gallwey ( mF-G ) scores ( changes from baseline in synbiotic group : − 1.3 ± 2.5 vs. in placebo group : − 0.1 ± 0.5 , p = 0.01 ) and serum high-sensitivity C-reactive protein ( hs-CRP ) ( changes from baseline in synbiotic group : − 950.0 ± 2246.6 vs. in placebo group : + 335.3 ± 2466.9 ng/mL , p = 0.02 ) . We did not observe any significant effect of synbiotic supplementation on other hormonal status and biomarkers of oxidative stress . Conclusions Overall , synbiotic supplementation for 12 weeks in PCOS women had beneficial effects on SHBG , mFG scores , hs-CRP and NO levels , but did not affect other hormonal status and biomarkers of oxidative stress . Trial registration This study was retrospectively registered in the Iranian website ( www.i rct .ir ) for registration of clinical trials ( I RCT 201509115623N53 ) , on 2015–09 - 27 The current study was conducted to assess the effects of vitamin D-K-calcium co-supplementation on endocrine , inflammation , and oxidative stress biomarkers in vitamin D-deficient women with polycystic ovary syndrome ( PCOS ) . This r and omized double-blind , placebo-controlled trial was performed on 60 vitamin D-deficient women diagnosed with PCOS aged 18 - 40 years old . Participants were r and omly allocated into 2 groups to intake either 200 IU vitamin D , 90 μg vitamin K plus , 500 mg calcium supplements ( n=30 ) , or placebo ( n=30 ) twice a day for 8 weeks . Endocrine , inflammation , and oxidative stress biomarkers were quantified at the beginning and the end of the study . After 8 weeks of intervention , compared with the placebo , vitamin D-K-calcium co-supplementation result ed in a significant reduction in serum-free testosterone ( - 2.1±1.6 vs.+0.1±1.0 pg/ml , p<0.001 ) and dehydroepi and rosterone sulfate ( DHEAS ) levels ( - 0.8±1.0 vs.-0.1±0.5 μg/ml , p=0.006 ) . In addition , a significant increase in plasma total antioxidant capacity ( TAC ) ( + 75.7±126.1 vs.-80.4±242.8 mmol/l , p=0.005 ) and a significant difference in plasma malondialdehyde ( MDA ) concentrations ( + 0.03±0.6 vs.+1.4±2.4 μmol/l , p=0.005 ) was observed following the supplementation with vitamin D-K-calcium compared with the placebo . A trend toward a greater decrease in luteinizing hormone was observed in vitamin D-K-calcium co-supplement group compared to placebo group ( - 7.0 vs.-1.2 IU/l , p=0.09 ) . We did not find any significant effect of vitamin D-K-calcium co-supplementation  on prolactin , follicle-stimulating hormone , 17-OH progesterone , inflammatory markers , and glutathione levels . Overall , vitamin D-K-calcium co-supplementation for 8 weeks among vitamin D-deficient women with PCOS had beneficial effects on serum DHEAS , free testosterone , plasma TAC , and MDA levels 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 A potential role for oxidative stress in the pathophysiology of pre-eclampsia was first proposed by Stark in 1993 . Synthesis of free radicals by a dysfunctional placenta , and possibly by maternal leucocytes and endothelium , seems to play a central role in this association . Free radicals , through oxidative damage of biomolecules and lipid peroxidation , can initiate maternal vascular endothelial dysfunction and leucocyte activation . A comprehensive review of the role of oxidative stress in pre-eclampsia has been recently published . Antioxidants such as vitamin C and vitamin E have been proposed as potential therapeutic or prophylactic treatment for pre-eclampsia .  This suggestion was supported by the observation that women with pre-eclampsia have lower plasma vitamin C concentrations . Both in vitro and in vivo studies suggest that there is an interaction between vitamin C and vitamin E , with vitamin C possibly exerting a ‘ redox ’ recycling effect on oxidised vitamin E within lipoproteins and membranes . The vitamin C to E ratio may be of central importance in protecting against the damaging effects of reactive oxygen species . To date , three placebo-controlled trials have assessed the effect of vitamins C and E on  pre-eclampsia .  Although no benefits were found when supplementation was given to women with diagnosed pre-eclampsia , a combination of 1 g/day of vitamin C and 400 IU/day of vitamin E given as prophylaxis to high risk women demonstrated a reduction in the risk of pre-eclampsia from 17 % in the control group to 8 % in the active treatment group . In this same double-masked r and omised controlled trial , women receiving vitamins C and E showed a reduction in biological markers of oxidative stress . Since this report , a number of multicentre r and omised clinical trials have been initiated both in low risk and in high risk population s , with the goal of testing the hypothesis that antioxidants reduce the incidence of pre-eclampsia ( Table 1 ) . In the UK , a multicentre trial is currently recruiting pregnant women with diabetes . The NIH has funded two antioxidant trials , one that is under way in Brazil and the second that is being conducted among nulliparous women in the NICHD Maternal Fetal Medicine Network . The International Trial of Antioxidants for the Prevention of Preeclampsia ( INTAPP ) , funded by the Canadian Institutes of Health Research , is enrolling nulliparas without additional risk factors ( Stratum I ) and multiparas and nulliparas with clinical risk factors for gestational hypertension ( Stratum II ) . Collectively , these trials should provide an answer to the question of the role of antioxidants in the prevention of pre-eclampsia and its related disorders . Recently , a meta- analysis of 19 clinical trials of  vitamin E  , for the most part secondary prevention trials , conducted in elderly population s at increased risk for a number of diseases ranging from lung or gastrointestinal cancer to cardiovascular disease , Alzheimer ’s disease or cataract , was published in the Annals of Internal Medicine . The authors of the meta- analysis concluded that high doses of vitamin E may be associated with an increased risk of all-cause mortality . What are the implication s of this meta- analysis for the ongoing pre-eclampsia prevention trials ? It is the responsibility of the Principal Investigators , the Steering Committees and Data Safety Monitoring Committees ( DSMC ) of ongoing clinical trials to take into account information generated from studies that arise in the course of their trial . They must assess the quality of the new evidence and determine how this information influences the balance of risks to benefits of the ongoing trials . In the case of the Canadian trial , both the DSMC and the hospital Ethics Committee have review ed the information and made their recommendations to the trial Steering Committee . The following is our evaluation of the quality of the evidence of the meta- analysis by Miller et al. , and its implication s for ongoing clinical trials of antioxidants in the prevention of pre-eclampsia BACKGROUND Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial . The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus ( DM ) . METHODS In a double-blind , placebo-controlled trial , we r and omized 100 type 2 DM patients to vitamin D supplement  ( 5000 IU/day , n = 50 ) or placebo ( controls , n = 50 ) for 12 weeks . Assessment of vascular function with brachial artery flow-mediated dilatation ( FMD ) , circulating levels of endothelial progenitor cells ( EPCs ) and brachial-ankle pulse wave velocity , and metabolic parameter , high-sensitivity C-reactive protein ( hsCRP ) and oxidative stress markers were performed before and after the supplementation . RESULTS After 12 weeks , vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [ 25(OH)D ] concentration ( treatment effect 34.7 ng/mL , 95 % CI 26.4 - 42.9 , P < 0.001 ) and serum ionized calcium ( treatment effect 0.037 mmol/L , 95 % CI 0.007 - 0.067 , P = 0.018 ) ; decreased serum parathyroid hormone concentration ( treatment effect -0.55 pmol/L , 95 % CI -1.08 to -0.02 , P = 0.042 ) compared to patients who received placebo . Nevertheless , vitamin D supplementation did not improve vascular function as determined by FMD , circulating EPC count or baPWV ( all P > 0.05 ) . Furthermore , hsCRP , oxidative stress markers , low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups ( all P > 0.05 ) . CONCLUSION In patients with type 2 DM , 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress . CLINICAL TRIAL NUMBER HKCTR-867 , www.hk clinical trials.com 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 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 Objective To summarize the evidence for curative and health enhancement effects through  forest therapy  and to assess the quality of studies based on a review of r and omized controlled trials ( RCTs ) . Study design A systematic review based on RCTs . Methods Studies were eligible if they were RCTs . Studies included one treatment group in which forest therapy was applied .  The following data bases – from 1990 to November 9 , 2010 – were search ed : MEDLINE via PubMed , CINAHL , Web of Science , and Ichushi- Web . All Cochrane data bases and Campbell Systematic Review s were also search ed up to November 9 , 2010 . Results Two trials met all inclusion criteria . No specific diseases were evaluated , and both studies reported significant effectiveness in one or more outcomes for health enhancement . However , the results of evaluations with the CONSORT ( Consoli date d St and ards of Reporting Trials ) 2010 and CLEAR NPT ( A Checklist to Evaluate a Report of a Nonpharmacological Trial ) checklists generally showed a remarkable lack of description in the studies . Furthermore , there was a problem of heterogeneity , thus a meta- analysis was unable to be performed . Conclusion Because there was insufficient evidence on forest therapy due to poor method ological and reporting quality and heterogeneity of RCTs , it was not possible to offer any conclusions about the effects of this intervention . However , it was possible to identify problems with current RCTs of forest therapy , and to propose a strategy for strengthening study quality and stressing the importance of study feasibility and original check items based on characteristics of forest therapy as a future research agenda Limited data are available indicating the effects of chromium administration on endocrine profiles , biomarkers of inflammation , and oxidative stress among women with polycystic ovary syndrome ( PCOS ) . This study was done to assess the effects of chromium administration on endocrine profiles , biomarkers of inflammation , and oxidative stress in women with PCOS . Participants of this r and omized , double-blind , placebo-controlled trial consisted of 60 patients with PCOS who received either 200 μg chromium supplements  ( n = 30 )  or placebo daily ( n = 30 ) for 8 weeks . Endocrine profiles , inflammatory factors , and biomarkers of oxidative stress were assessed at study baseline and at the end of intervention . After 8 weeks of intervention , pregnancy rate in chromium group was higher than that in the placebo group : 16.7 % ( 5/30 ) vs. 3.3 % ( 1/30 ) , P = 0.08 . In addition , prevalence of acne ( 20.0 vs. 3.3 % , P = 0.04 ) decreased following the administration of chromium supplements compared with the placebo . Taking chromium led to a significant reduction in hirsutism ( −1.8 ± 2.5 vs. −0.2 ± 0.8 , P = 0.002 ) , serum high-sensitivity C-reactive protein ( hs-CRP ) ( −717.0 ± 1496.1 vs. + 227.1 ± 1669.6 ng/mL , P = 0.02 ) , plasma malondialdehyde ( MDA ) ( −0.1 ± 0.7 vs. + 1.1 ± 1.5 μmol/L , P < 0.001 ) , and a significant increase in plasma total antioxidant capacity ( TAC ) concentrations ( + 250.7 ± 265.2 vs. + 13.0 ± 201.6 mmol/L , P < 0.001 ) . We failed to find any significant effect of chromium administration on endocrine profiles and nitric oxide ( NO ) and glutathione ( GSH ) levels . Overall , taking chromium for 8 weeks among women with PCOS had beneficial effects on acne , hirsutism , hs-CRP , TAC , and MDA levels , but it did not affect endocrine profiles , NO , and GSH . Clinical trial registration number : I RCT 201506105623N44 ( www.i rct .ir 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 BACKGROUND Atherosclerotic cardiovascular disease is the most common cause of death among hemodialysis patients ; it has been attributed to increased oxidative stress , dyslipidemia , malnutrition , and chronic inflammation . Activation of neutrophils is a well-recognized feature in dialysis patients , and superoxide-anion production by neutrophil NADPH oxidase may contribute significantly to oxidative stress . OBJECTIVE The aim of the study was to compare the effects of dietary supplementation with concentrated red grape juice ( RGJ ) , a source of polyphenols , and vitamin E on neutrophil NADPH oxidase activity and other cardiovascular risk factors in hemodialysis patients . DESIGN Thirty-two patients undergoing hemodialysis were recruited and r and omly assigned to groups to receive dietary supplementation with RGJ , vitamin E , or both or a control condition without supplementation or placebo . Blood was obtained at baseline and on days 7 and 14 of treatment . RESULTS RGJ consumption but not vitamin E consumption reduced plasma concentrations of total cholesterol and apolipoprotein B and increased those of HDL cholesterol . Both RGJ and vitamin E reduced plasma concentrations of oxidized LDL and ex vivo neutrophil NADPH oxidase activity . These effects were intensified when the supplements were used in combination ; in that case , reductions in the inflammatory biomarkers intercellular adhesion molecule 1 and monocyte chemoattractant protein 1 also were observed . CONCLUSIONS Regular ingestion of concentrated RGJ by hemodialysis patients reduces neutrophil NADPH-oxidase activity and plasma concentrations of oxidized LDL and inflammatory biomarkers to a greater extent than does that of vitamin E. This effect of RGJ consumption may favor a reduction in cardiovascular risk Many biomarkers are associated with type 2 diabetes ( T2D ) risk in epidemiological observations . The aim of this study was to identify and summarize current evidence for causal effects of biomarkers on T2D . A systematic literature search in PubMed and EMBASE ( until April 2015 ) was done to identify Mendelian r and omization studies that examined potential causal effects of biomarkers on T2D . To replicate the findings of identified studies , data from two large-scale , genome-wide association studies ( GWAS ) were used : DIAbetes  Genetics Replication And Meta- analysis  ( DIAGRAMv3 ) for T2D and the Meta-Analyses of Glucose and Insulin-related traits Consortium ( MAGIC ) for glycaemic traits . GWAS summary statistics were extracted for the same genetic variants ( or proxy variants ) , which were used in the original Mendelian r and omization studies . Of the 21 biomarkers ( from 28 studies ) , ten have been reported to be causally associated with T2D in Mendelian r and omization . Most biomarkers were investigated in a single cohort study or population . Of the ten biomarkers that were identified , nominally significant associations with T2D or glycaemic traits were reached for those genetic variants related to bilirubin , pro-B-type natriuretic peptide , delta-6 desaturase and dimethylglycine based on the summary data from DIAGRAMv3 or MAGIC . Several Mendelian r and omization studies investigated the nature of associations of biomarkers with T2D . However , there were only a few biomarkers that may have causal effects on T2D . Further research is needed to broadly evaluate the causal effects of multiple biomarkers on T2D and glycaemic traits using data from large-scale cohorts or GWAS including many different genetic variants OBJECTIVES To assess the impact of a personalized diet , with or without addition of VSL#3 preparation , on biomarkers of inflammation , nutrition , oxidative stress and intestinal microbiota in 62 healthy persons aged 65 - 85 years . DESIGN Open label , r and omized , multicenter study . PRIMARY ENDPOINT High-sensitivity C-reactive protein . SETTING Community . INTERVENTIONS Eight week web-based dietary advice ( RISTOMED platform ) alone or with supplementation of VSL#3 ( 2 capsules per day ) . The RISTOMED diet was optimized to reduce inflammation and oxidative stress . MEASUREMENTS Blood and stool sample s were collected on days 1 and 56 . RESULTS Diet alone reduced ESR ( p = 0.02 ) , plasma levels of cholesterol ( p < 0.01 ) and glucose ( p = 0.03 ) . Addition of VSL#3  reduced ESR ( p = 0.05 ) and improved folate ( p = 0.007 ) , vitamin B12 ( p = 0.001 ) and homocysteine ( p < 0.001 ) plasma levels . Neither intervention demonstrated any further effects on inflammation . Subgroup analysis showed 40 participants without signs of low- grade inflammation ( hsCRP<3 mg/l , subgroup 1 ) and 21 participants with low- grade inflammation at baseline ( hsCRP≥3 mg/l , subgroup 2 ) . In subgroup 2 addition of VSL#3  increased bifidobacteria ( p = 0.005 ) in more participants and improved both folate ( p = 0.015 ) and vitamin B12 ( p = 0.035 ) levels compared with subgroup 1 . The increases were positively correlated to the change in the bifidobacteria concentration for folate ( p = 0.023 ) and vitamin B12 ( p = 0.001 ) . As expected change in homocysteine correlated negatively to change in folate ( r = -0.629 , p = 0.002 ) and vitamin B12 ( r = -0.482 , p = 0.026 ) . CONCLUSIONS Addition of VSL#3  increased bifidobacteria and supported adequate folate and vitamin B12 concentrations in subjects with low- grade inflammation . Decrease in homocysteine with VSL#3 was clinical ly relevant . suggesting protective potentials for aging-associated conditions , e.g. cardiovascular or neurological diseases . Clinical Trials.gov : NCT01069445-NCT01179789 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 Selenium supplementation could be effective on reproductive outcomes , biomarkers of inflammation , and oxidative stress among women with polycystic ovary syndrome ( PCOS ) . The aim of the study was to determine the effects of selenium supplementation on reproductive outcomes , biomarkers of inflammation , and oxidative stress in PCOS patients . The present r and omized double-blind , placebo-controlled trial was conducted on 64 women aged 18 - 40 years old with PCOS at the clinic affiliated to Ardabil University of Medical Sciences , Ardabil , Iran . The participants were r and omly assigned to 2 groups receiving either 200 μg selenium daily ( n=32 ) or placebo ( n=32 ) for 8 weeks . Hormonal profiles , biomarkers of inflammation , and oxidative stress were measured and compared both before and after the treatment . After 8 weeks of intervention , pregnancy rate in the selenium group was higher than in the placebo group : 18.8 ( 6/32 ) vs. 3.1 % ( 1/32 ) , p=0.04 . In addition , alopecia ( 40.6 vs. 9.4 % , p=0.004 ) and acne ( 46.9 vs. 12.5 % , p=0.003 ) decreased following the consumption of selenium supplements compared with placebo . Additionally , patients who received selenium supplements had significantly decreased serum dehydroepi and rosterone ( DHEA ) levels ( p=0.02 ) , hirsutism ( modified Ferriman-Gallwey scores ) ( p<0.001 ) , serum high sensitivity C-reactive protein ( hs-CRP ) ( p=0.02 ) , and plasma malondialdehyde ( MDA ) levels ( p=0.01 ) compared with placebo . We did not observe any significant effects of taking selenium supplements on other hormonal profiles , nitric oxide ( NO ) , and other biomarkers of oxidative stress . Taken together , selenium supplementation for 8 weeks among PCOS women had beneficial effects on reproductive outcomes , DHEA , hs-CRP , and MDA levels . Supporting Information for this article is available online at http://www.thieme-connect.de/products Abstract Objective : This study was design ed to evaluate the effects of probiotic supplementation on biomarkers of inflammation , oxidative stress and pregnancy outcomes  among subjects with gestational diabetes ( GDM ) . Methods : This r and omized , double-blind , placebo-controlled clinical trial was done among 60 subjects with GDM who were not on oral hypoglycemic agents . Patients were r and omly allocated to intake either probiotic capsule containing Lactobacillus acidophilus , Lactobacillus casei and Bifidobacterium bifidum ( 2 × 109 CFU/g each ) ( n = 30 ) or placebo ( n = 30 ) for six weeks . Results : Compared with the placebo , probiotic supplementation result ed in significant decreases in fasting plasma glucose ( FPG ) ( −5.3 ± 6.7 vs. + 0.03 ± 9.0 mg/dL , p = .01 ) , serum high-sensitivity C-reactive protein ( hs-CRP ) ( −2.2 ± 2.7 vs. + 0.5 ± 2.4 μg/mL , p < .001 ) , plasma malondialdehyde ( MDA ) concentrations ( −0.1 ± 0.8 vs. + 0.5 ± 1.5 μmol/L , p = .03 ) and MDA/TAC ratio ( −0.0003 ± 0.0008 vs. + 0.0009 ± 0.002 , p = .004 ) , and a significant increase in total antioxidant capacity ( TAC ) levels ( + 65.4 ± 103.3 vs. −37.2 ± 143.7 mmol/L , p = .002 ) . Probiotic supplementation did not affect pregnancy outcomes . Conclusions : Overall , probiotic supplementation among women with GDM for six weeks had beneficial effects on FPG , serum hs-CRP , plasma TAC , MDA and oxidative stress index , but did not affect pregnancy outcomes OBJECTIVE Although increased oxidative stress and inflammation are highly prevalent in chronic kidney disease ( CKD ) , few studies have investigated whether oral antioxidant therapy can alter markers of inflammation or oxidative stress in patients with CKD . The purpose of this study was to investigate whether a combination of mixed tocopherols and alpha lipoic acid ( ALA ) would alter biomarkers of oxidative stress and inflammation in subjects with stage 3 to 4 CKD . METHODS This was a prospect i ve , r and omized , double-blind , placebo-controlled pilot trial . In all , 62 subjects were enrolled and were r and omly assigned to receive a combination of mixed tocopherols 666 IU/day , in addition to ALA 600 mg/day , or their matching placebos for a total of 8 weeks . Plasma F(2)-isoprostane and protein thiol concentration were measured as biomarkers of oxidative stress , and C-reactive protein and interleukin-6 concentration as biomarkers of systemic inflammation . RESULTS There were no significant differences in demographics , diabetic status , or estimated glomerular filtration rate between study treatment and placebo groups at baseline . Of the 62 r and omized subjects , 58 ( 93 % ) completed the study protocol . After 2 months of treatment , there were no significant changes in the concentrations of F(2)-isoprostanes , protein thiols , C-reactive protein , and interleukin-6 with respect to treatment with mixed tocopherols and ALA as compared with matching placebos , whether analyzed as intention to treat or as treated . Diabetic status and baseline body mass index did not influence the results . CONCLUSIONS Combination of oral mixed tocopherols and ALA treatment for 2 months does not influence biomarkers of oxidative stress and inflammation in patients with stage 3 to 4 CKD BACKGROUND studies have investigated the relationship between the transition through menopause and cardiovascular diseases . White population , generally , have lower levels of traditional coronary heart risk factors , particularly dyslipidemia , hypertension , obesity , and diabetes , and lower rates of coronary heart disease mortality , than black population . Furthermore many studies have shown the cardioprotective and anti-inflammatory effects of omega-3 polyunsaturated fatty acids ( eicosapentaenoic acid and docosahexaenoic acid ) of marine origin . The aim of this study was to investigate the effect of omega-3 supplementation , combined or not with vitamin E , on oxidative biomarkers and lipid profiles in nonwhite and white women with dyslipidemia transitioning through menopause . METHODS a r and omized , double-blind , placebo-controlled trial was conducted . Seventy-four eligible women were assigned to receive : fish oil , fish oil plus vitamin E and placebo for three months . At baseline , 45 and 90 days blood sample for biochemical variables and biomarkers of oxidative stress were taken . Socioeconomic and lifestyle variables were collected with st and ardized question naires . RESULTS after 90 days the fish oil plus vitamin E treated group had a significant decrease in total cholesterol and LDL-C. Furthermore , there was a decrease in anti- LDL- autoantibodies after 45 days . Plasma TBARS concentrations were increased after 90 days in the group receiving only fish oil when compared to the placebo and fish oil-vitamin E groups . All of the effects observed were independent of ethnic group . CONCLUSION supplementation with fish oil and vitamin E reduced total cholesterol and LDL-C , but had opposite effects on oxidative stress compared to supplementation with fish oil alone This study sought to examine whether consumption of two low-calorie fruit/day for 3-months can effectively improve oxidative stress , anthropometry , blood pressure and glycaemic control in type 2 diabetes mellitus . Study involved 123 patients who were assigned to receive either st and ard care or with additional dietary therapy .  Dietary intervention result ed in significant reduction in malondialdehyde , plasma glucose , glycated haemoglobin and improvement in antioxidants like vitamin C and reduced glutathione when compared to controls . Mean plasma levels of vitamin C increased by 64 % ( p < 0.001 ) . There were no differences in waist circumference , waist-to-hip ratio , blood pressure , vitamin E and superoxide dismutase in the intervention group at follow-up . Diet rich in fruits can improve some antioxidants which are likely to reduce oxidative stress in type 2 diabetes . Regular consumption of fruits can lower the glycaemic status in these patients . The study supports the usefulness of plasma vitamin C as a biomarker for fruit intake
Overall , this meta- analysis shows that in diabetic patients , taking vitamin D had significant effects on hs-CRP and MDA levels , and significantly increased NO , TAC and GSH levels
In this systematic review and meta- analysis of r and omized controlled trials ( RCTs ) , the effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress in diabetic patients are summarized .