Effect of vitamin D supplementation on inflammation: protocol for a systematic review Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies The Effectiveness of Psychosocial Interventions as Adjuncts to Orthopaedic Surgery: A Systematic Review Protocol Role of Vitamin D in Insulin Secretion and Insulin Sensitivity for Glucose Homeostasis A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial. Maternal vitamin D supplementation during pregnancy Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial
Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 Background 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 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 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 AIMS Pain and anxiety are commonly reported among those undergoing orthopaedic surgery . Improvement in anxiety and pain control might be achieved by supplementing st and ard care with psychological interventions . However , the effectiveness of adjunctive psychosocial interventions in anxiety and pain control have not been addressed sufficiently by previous systematic review s in orthopaedic surgeries . The present study aim ed to assess the effectiveness of adjunctive psychosocial techniques to improve perioperative clinical care in orthopaedic surgery , to identify the most effective intervention types and to evaluate potential moderators . METHODS We will perform a systematic review and meta- analysis to address the study aims . PubMed , PsycINFO , CINAHL and ProQuest Dissertations & Theses will be search ed between 1980 and 2015 . Prospect i ve controlled clinical trials completed in adults , contrasting st and ard care and st and ard care supplemented with psychosocial methods  , will be eligible for inclusion . Effectiveness will be assessed through the outcomes of postoperative pain intensity , analgesic requirement , perioperative anxiety , quality of life and postoperative recovery . The results of a r and om-effect meta- analysis will be reported . To aid implementation of best practice , moderating effects of the type and timing of psychosocial intervention , type of surgical intervention and type of anaesthesia will be evaluated through meta-regression . Sensitivity analyses and subgroup contrasts will follow as necessary . DISCUSSION Recommendations will be made to improve medical care in orthopaedic procedures . The quality of evidence will be rated using GRADE criteria . Copyright © 2016 John Wiley & Sons , Vitamin D functions are not limited to skeletal health benefits and may extend to preservation of insulin secretion and insulin sensitivity . This review summarizes the literature related to potential vitamin D influences on glucose homeostasis and insulin sensitivity . Cross-sectional data provide some evidence that circulating 25-hydroxyvitamin D ( 25(OH)D ) is inversely associated with insulin resistance , although direct measurements of insulin sensitivity are required for confirmation . Reported associations with insulin secretion , however , are contradictory . Available prospect i ve studies support a protective influence of high 25(OH)D concentrations on type 2 diabetes mellitus risk . There is a general lack of consistency in vitamin D intervention outcomes on insulin secretion and sensitivity , likely due to differences in subject population s , length of interventions , and forms of vitamin D supplementation . Vitamin D receptor gene polymorphisms and vitamin D interactions with the insulin like growth factor system may further influence glucose homeostasis . The ambiguity of optimal vitamin D dosing regimens and optimal therapeutic concentrations of serum 25(OH)D limit available intervention studies . Future studies , including cross-sectional and prospect i ve , should be performed in population s at high risk for both vitamin D deficiency and type 2 diabetes mellitus . Well- design ed , placebo-controlled , r and omized intervention studies are required to establish a true protective influence of  vitamin D on glucose homeostasis AIM To determine the short-term effect of vitamin D(3 ) supplementation on insulin sensitivity in apparently healthy , middle-aged , central ly obese men . SUBJECTS AND METHODS A double-blind r and omized controlled trial was conducted at a tertiary care facility in which 100 male volunteers aged > or = 35 years received three doses of vitamin D(3 ) ( 120,000 IU each ; supplemented group ) fortnightly or placebo ( control group ) . Hepatic fasting insulin sensitivity [ homeostasis model assessment ( HOMA ) , quantitative insulin-sensitivity check index , HOMA-2 ] , postpr and ial insulin sensitivity [ oral glucose insulin sensitivity ( OGIS ) ] , insulin secretion ( HOMA%B , HOMA2-%B ) , lipid profile and blood pressure were measured at baseline and at 6 weeks ' follow-up . RESULTS Seventy-one of the recruited subjects completed the study ( 35 in supplemented group , 36 in control group ) . There was an increase in OGIS with supplementation by per protocol analysis ( P = 0.038 ; intention-to-treat analysis P = 0.055 ) . The age- and baseline 25-hydroxyvitamin D level-adjusted difference in change in OGIS was highly significant ( mean difference 41.1 + /- 15.5 ; P = 0.01 ) . No changes in secondary outcome measures ( insulin secretion , basal indices of insulin sensitivity , blood pressure or lipid profile ) were found with supplementation . CONCLUSION The trial indicates that vitamin D(3 ) supplementation improves postpr and ial insulin sensitivity ( OGIS ) in apparently healthy men likely to have insulin resistance ( central ly obese but non-diabetic ) 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 Introduction Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring . A wealth of observational studies have reported on both obstetric outcomes and complications , including pre-eclampsia , gestational diabetes , mode and timing of delivery . Many foetal and childhood outcomes are also linked to vitamin D status , including measures of foetal size , body composition and skeletal mineralization , in addition to later childhood outcomes , such as asthma . Sources of data Synthesis of systematic and narrative review s. Areas of agreement and controversy The findings are generally inconsistent in most areas , and , at present , there is a lack of data from high- quality intervention studies to confirm a causal role for vitamin D in these outcomes . In most areas , the evidence tends towards maternal vitamin D being of overall benefit , but often does not reach statistical significance in meta-analyses . Growing points and areas timely for developing research The most conclusive evidence is in the role of maternal vitamin D supplementation in the prevention of neonatal hypocalcaemia ; as a consequence the UK department of health recommends that pregnant women take 400 IU vitamin D daily . High- quality r and omized placebo-controlled trials , such as the UK-based MAVIDOS trial , will inform the potential efficacy and safety of vitamin D supplementation in pregnancy across a variety of outcomes Objectives To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity , insulin secretion , β-cell function , inflammation and metabolic markers . Design 6-month r and omized , placebo-controlled trial . Participants Ninety-five adults with serum 25-hydroxyvitamin D [ 25(OH)D ] ≤55 nmol/L at risk of type 2 diabetes ( with prediabetes or an AUSDRISK score ≥15 ) were r and omized . Analyses included participants who completed the baseline and final visits ( treatment n = 35 ; placebo n = 45 ) . Intervention Daily calcium carbonate ( 1,200 mg ) and cholecalciferol [ 2,000–6,000 IU to target 25(OH)D > 75 nmol/L ] or matching placebos for 6 months .  Measurements Insulin sensitivity ( HOMA2%S , Matsuda index ) , insulin secretion ( insulinogenic index , area under the curve ( AUC ) for C-peptide ) and β-cell function ( Matsuda index x AUC for C-peptide ) derived from a 75 g 2-h OGTT ; anthropometry ; blood pressure ; lipid profile ; hs-CRP ; TNF-α ; IL-6 ; adiponectin ; total and undercarboxylated osteocalcin . Results Participants were middle-aged adults ( mean age 54 years ; 69 % Europid ) at risk of type 2 diabetes ( 48 % with prediabetes ) . Compliance was > 80 % for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group ( 91 % achieved > 75 nmol/L ) , but remained unchanged in controls . There were no significant changes in insulin sensitivity , insulin secretion and β-cell function , or in inflammatory and metabolic markers between or within the groups , before or after adjustment for potential confounders including waist circumference and season of recruitment . In a post hoc analysis restricted to participants with prediabetes , a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity ( HOMA%S and Matsuda ) was observed . Conclusions Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity , insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes . However , in participants with prediabetes , supplementation with vitamin D and calcium may improve insulin sensitivity . Trial Registration Australian New Zeal and Clinical Trials Registry
Vitamin K supplementation did not affect insulin sensitivity as measured by homeostasis model assessment of insulin resistance , fasting plasma glucose , fasting plasma insulin , C-reactive protein , adiponectin , leptin , and interleukin-6 levels .
Our analysis suggests no effect of vitamin K supplementation on insulin sensitivity
OBJECTIVE To perform a systematic review and meta- analysis of r and omized , placebo-controlled trials to assess the effect of vitamin K supplementation on insulin sensitivity .