Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs) Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial Maternal vitamin D supplementation during pregnancy Effect of Vitamin D Supplementation on Moderate to Severe Bronchial Asthma Vitamin D status has a linear association with seasonal infections and lung function in British adults. Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma. Supplementation with vitamin A early in life and subsequent risk of asthma Effect of vitamin D supplementation on inflammation: protocol for a systematic review The Vitamin D Antenatal Asthma Reduction Trial (VDAART): rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. Vitamin D status in irritable bowel syndrome and the impact of supplementation on symptoms: what do we know and what do we need to know? Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial. Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial Effect of dietary interventions in mild cognitive impairment: a systematic review. Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial. Vitamin D levels, lung function, and steroid response in adult asthma. Does vitamin D intake during infancy promote the development of atopic allergy? Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants.
Rationale Asthma exacerbations are commonly precipitated by viral upper respiratory infections ( URIs ) . Vitamin D insufficiency associates with susceptibility to URI in patients with asthma . Trials of vitamin D in adults with asthma with incidence of exacerbation and URI as primary outcome are lacking . Objective To conduct a r and omised controlled trial of vitamin D3 supplementation for the prevention of asthma exacerbation and URI ( co primary outcomes ) . Measurements and methods 250 adults with asthma in London , UK were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 ( n=125 ) or placebo ( n=125 ) over 1 year . Secondary outcomes included asthma control test and St George 's Respiratory Question naire scores , fractional exhaled nitric oxide and concentrations of inflammatory markers in induced sputum . Subgroup analyses were performed to determine whether effects of supplementation were modified by baseline vitamin D status or genotype for 34 single nucleotide polymorphisms in 11 vitamin D pathway genes . Main results 206/250 participants ( 82 % ) were vitamin D insufficient at baseline . Vitamin D3 did not influence time to first severe exacerbation ( adjusted HR 1.02 , 95 % CI 0.69 to 1.53 , p=0.91 ) or first URI ( adjusted HR 0.87 , 95 % CI 0.64 to 1.16 , p=0.34 ) . No clinical ly important effect of vitamin D3 was seen on any of the secondary outcomes listed above . The influence of vitamin D3 on co primary outcomes was not modified by baseline vitamin D status or genotype . Conclusions Bolus-dose vitamin D3 supplementation did not influence time to exacerbation or URI in a population of adults with asthma with a high prevalence of baseline vitamin D insufficiency . Trial registration number NCT00978315 ( Clinical Trials.gov ) BACKGROUND Asthma exacerbations , most often caused by respiratory tract infections , are the leading causes of asthma morbidity and comprise a significant proportion of asthma-related costs . Vitamin D status might play a role in preventing asthma exacerbations . OBJECTIVES We sought to assess the relationship between serum vitamin D levels and subsequent severe asthma exacerbations . METHODS We measured  25-hydroxyvitamin D levels in sera collected from 1024 children with mild-to-moderate persistent asthma at the time of enrollment in a multicenter clinical trial of children r and omized to receive budesonide , nedocromil , or placebo ( as-needed beta-agonists ) : the Childhood Asthma Management Program . Using multivariable modeling , we examined the relationship between baseline vitamin D levels and the odds of any hospitalization or emergency department visit over the 4 years of the trial . RESULTS Thirty-five percent of all subjects were  vitamin D insufficient , as defined by a level of 30 ng/mL or less 25-hydroxyvitamin D. Mean vitamin D levels were lowest in African American subjects and highest in white subjects . After adjusting for age , sex , body mass index , income , and treatment group , insufficient vitamin D status was associated with a higher odds of any hospitalization or emergency department visit ( odds ratio , 1.5 ; 95 % CI , 1.1 - 1.9 ; P = .01 ) . CONCLUSION Vitamin D insufficiency is common in this population of North American children with mild-to-moderate persistent asthma and is associated with higher odds of severe exacerbation over a 4-year period RATIONALE Restoration of vitamin D sufficiency may reduce asthma exacerbations , events that are often associated with respiratory tract infections and cold symptoms . OBJECTIVES To determine whether vitamin D supplementation reduces cold symptom occurrence and severity in adults with mild to moderate asthma and vitamin D insufficiency . METHODS Colds were assessed in the AsthmaNet VIDA ( Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness ) trial , in which 408 adult patients were r and omized to receive placebo or cholecalciferol ( 100,000 IU load plus 4,000 IU/d ) for 28 weeks as add-on therapy . The primary outcome was cold symptom severity , which was assessed using daily scores on the 21-item Wisconsin Upper Respiratory Symptom Survey . MEASUREMENTS AND MAIN RESULTS A total of 203 participants experienced at least one cold .  Despite achieving 25-hydroxyvitamin D levels of 41.9 ng/ml ( 95 % confidence interval [ CI ] , 40.1 - 43.7 ng/ml ) by 12 weeks , vitamin D supplementation had no effect on the primary outcome : the average peak WURSS-21 scores ( 62.0 [ 95 % CI , 55.1 - 68.9 ; placebo ] and 58.7 [ 95 % CI , 52.4 - 65.0 ; vitamin D ] ; P = 0.39 ) . The rate of colds did not differ between groups ( rate ratio [ RR ] , 1.2 ; 95 % CI , 0.9 - 1.5 ) ; however , among African Americans , those receiving vitamin D versus placebo had an increased rate of colds ( RR , 1.7 ; 95 % CI , 1.1 - 2.7 ; P = 0.02 ) . This was also observed in a responder analysis of all subjects achieving vitamin D sufficiency , regardless of treatment assignment ( RR , 1.4 ; 95 % CI , 1.1 - 1.7 ; P = 0.009 ) . CONCLUSIONS Our findings in patients with mild to moderate asthma undergoing an inhaled corticosteroid dose reduction do not support the use of vitamin D supplementation for the purpose of reducing cold severity or frequency BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often have vitamin D deficiency , which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation . Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking . We therefore investigated whether vitamin D3 ( colecalciferol ) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections . METHODS We did a r and omised , double-blind , placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practice s and four Acute National Health Service Trust clinics in London , UK . Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block r and omisation . Participants and study staff were masked to treatment assignment . Co primary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection . Analysis was by intention to treat . A prespecified subgroup analysis was done to assess whether effects of the intervention on the co primary outcomes were modified by baseline vitamin D status . This trial is registered with Clinical Trials.gov , number NCT00977873 . FINDINGS 240 patients were r and omly allocated to the vitamin D3 group ( n=122 ) and placebo group ( n=118 ) . Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation ( adjusted hazard ratio 0·86 , 95 % CI 0·60 - 1·24 , p=0·42 ) or time to first upper respiratory infection ( 0·95 , 0·69 - 1·31 , p=0·75 ) . Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L ( 0·57 , 0·35 - 0·92 , p=0·021 ) , but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L ( 1·45 , 0·81 - 2·62 , p=0·21 ; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status ) . Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection ( pinteraction=0·41 ) . INTERPRETATION Vitamin D3 supplementation protected against moderate or severe exacerbation , but not upper respiratory infection , in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation . FUNDING UK National Institute for Health Research Background Vitamin D levels are alarmingly low ( < 75 nmol/L ) in 65 - 70 % of North American children older than 1 year . An increased risk of viral upper respiratory tract infections ( URTI ) , asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations , two of the most common and costly illnesses of early childhood . The objectives of this study are : 1 ) to compare the effect of ‘ high dose ’ ( 2000 IU/day ) vs. ‘ st and ard dose ’ ( 400 IU/day ) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children ; and 2 ) to assess the effect of ‘ high dose ’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI . Methods / Design This study is a pragmatic r and omized controlled trial . Over 4 successive winters we will recruit 750 healthy children 1–5 years of age . Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be r and omized to the ‘ st and ard dose ’ or ‘ high dose ’ oral supplemental vitamin D for a minimum of 4 months ( 200 children per group ) . Parents will obtain a nasal swab from their child with each URTI , report the number of asthma exacerbations and complete symptom checklists . Unscheduled physician visits for URTIs and asthma exacerbations will be recorded . By May , a blood sample will be drawn to determine vitamin D serum levels . The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model . Secondary analyses will compare  vitamin D serum levels , asthma exacerbations and the frequency of specific viral agents between groups . Discussion Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs . This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers 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 Objective To define the therapeutic role of vitamin D in children with moderate to severe bronchial asthma as an adjunct to st and ard treatment . Methods Hundred asthmatic children of either sex , attending the respiratory and asthma clinic were enroled in the study . Diagnosis was made on the basis of history and clinical examination . R and omization was done using sealed opaque envelop method . In addition to the treatment as per GINA guidelines , one group received oral vitamin D3 ( Cholecalciferol ) 60,000 IU per month for 6 mo and the other group received placebo powder in the form of glucose sachet with a double blinded design . Monthly follow up of every patient was done and during every visit change in severity , level of control , Peak expiratory flow rate ( PEFR ) , steroid dosage , number of exacerbations and number of emergency visits were assessed . Results Monthly doses of 60,000 IU vitamin D significantly reduced the number of exacerbations as compared to placebo ( p = 0.011 ) . PEFR significantly increased in the treatment group ( p = 0.000 ) . Monthly doses of vitamin D significantly reduced the requirement of steroids ( p = 0.013 ) and emergency visits ( p = 0.015 ) . Control of asthma was achieved earlier in patients who received monthly vitamin D. Vitamin D significantly reduced the level of severity of asthma patients over 6 mo of treatment ( p = 0.016 ) . Conclusions Vitamin D has a definite role in the management of moderate to severe persistent bronchial asthma as an adjunct to st and ard treatment Higher vitamin D concentrations have been proposed as a protective ' seasonal stimulus ' against influenza , and there are suggestions for associations with other aspects of respiratory health . The aim of the present study was to investigate the relationship of current vitamin D status ( measured by 25-hydroxyvitamin D , 25(OH)D ) with  respiratory infections and lung function .  We used cross-sectional data from 6789 participants in the nationwide 1958 British birth cohort who had measurements of 25(OH)D , lung function ( forced expiratory volume in 1 s ( FEV1 ) and forced vital capacity ( FVC ) ) and respiratory infections available from the age of 45 years . In this population , the prevalence of respiratory infections had a strong seasonal pattern in the opposite direction to the pattern for 25(OH)D concentrations . Each 10 nmol/l increase in 25(OH)D was associated with a 7 % lower risk of infection ( 95 % CI 3 , 11 % ) after adjustment for adiposity , lifestyle and socio-economic factors . For FEV1 and FVC , each 10 nmol/l increase in 25(OH)D was associated with 8 ( 95 % CI 3 , 13 ) ml and 13 ( 95 % CI 7 , 20 ) ml higher volume , respectively , after controlling for covariates . Associations of 25(OH)D with FEV1 and FVC were only slightly attenuated after further adjustment for infection and other respiratory illness . In conclusion , vitamin D status had a linear relationship with respiratory infections and lung function . R and omised controlled trials are warranted to investigate the role of vitamin D supplementation on respiratory health and to establish the underlying mechanisms BACKGROUND Low levels of vitamin D are associated with asthma severity , airway remodeling , and exacerbation rate increase , especially in nonatopic asthma . Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms . OBJECTIVE We sought to evaluate the effect of vitamin D supplementation on eosinophilic and neutrophilic airway inflammation in patients with nonatopic asthma . METHODS In a double-blind , r and omized , placebo-controlled trial , we investigated the effect of long-acting vitamin D3 ( 400,000 IU ) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic ( ≥53 % ) and /or eosinophilic ( ≥3 % ) airway inflammation . Sputum induction was performed at baseline and after 9 weeks . Other measurements included question naires , blood sample s , and pulmonary function . RESULTS Treatment with vitamin D did not significantly affect sputum neutrophils or eosinophils compared with treatment with placebo in the total group . Regarding sputum eosinophils , the effect of vitamin D appeared to be dependent on baseline sputum eosinophil levels ( interaction P = .015 ) . In patients with eosinophil levels  of 26.2 % or more ( median in patients with sputum eosinophilia , > 3 % ) , eosinophils decreased from a median of 41.0 % to 11.8 % after vitamin D treatment as compared with an increase from 51.8 % to 63.3 % in patients receiving placebo ( P = .034 ) . Vitamin D treatment also result ed in slightly better Asthma Control Question naire scores ( P = .08 ) . CONCLUSIONS Vitamin D supplementation  reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation , but did not affect sputum neutrophils . Also , a small effect on asthma control was observed . These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma Animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness , and may predispose to an increased risk of asthma .  We examined the long-term effects of vitamin A supplementation early in life on later  asthma risk . In 2006–2008 , we revisited participants from two cohorts in rural Nepal who were enrolled in r and omised trials of vitamin A supplementation . The first cohort received  vitamin A or placebo  for < 16 months during their pre-school years ( 1989–1991 ) . The second cohort was born to mothers who received vitamin A , & bgr;-carotene or placebo before , during and after pregnancy ( 1994–1997 ) . At follow-up , we asked about asthma symptoms and performed spirometry .  Out of 6,421 subjects eligible to participate , 5,430 ( 85 % ) responded to our respiratory survey . Wheezing prevalence during the previous year was 4.8 % in participants aged 9–13 yrs and 6.6 % in participants aged 14–23 yrs . We found no differences between the vitamin A supplemented and placebo groups from either trial in the prevalence of lifetime or current asthma and wheeze or in spirometric indices of obstruction ( p≥0.12 for all comparisons ) . Vitamin A supplementation early in life was not associated with a decreased risk of asthma  in an area with chronic vitamin A deficiency 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 There is intense interest in the role of vitamin D in the development of asthma and allergies . However , studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies . To address this uncertainty , the Vitamin D Antenatal Asthma Reduction Trial ( VDAART ) was developed . VDAART is a r and omized , double-blind , placebo-controlled trial of vitamin D supplementation  in pregnant women to determine whether prenatal supplementation can prevent the development of  asthma and allergies in women 's offspring . A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications , such as preeclampsia , preterm birth , and gestational diabetes .  Women were r and omized to the treatment arm of 4000IU/day of vitamin D3 plus a daily multivitamin that contained 400IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400IU daily of vitamin D3 . Women who were between the gestational ages of 10 and 18 weeks were r and omized from three clinical centers across the United States - Boston Medical Center , Washington University in St. Louis , and Kaiser Permanente Southern California Region ( San Diego , CA ) . Supplementation took place throughout pregnancy . Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events . Offspring are being evaluated quarterly through question naires and yearly during in-person visits until the 3rd birthday of the child . Ancillary studies will investigate neonatal T-regulatory cell function , maternal vaginal flora , and maternal and child intestinal flora IMPORTANCE In asthma and other diseases , vitamin D insufficiency is associated with adverse outcomes . It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency . OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS The VIDA ( Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma ) r and omized , double-blind , parallel , placebo-controlled trial study ing adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart , Lung , and Blood Institute 's AsthmaNet network , with enrollment starting in April 2011 and follow-up complete by January 2014 . After a run-in period that included treatment with an inhaled corticosteroid , 408 patients were r and omized . INTERVENTIONS Oral vitamin D3 ( 100,000 IU once , then 4000 IU/d for 28 weeks ; n = 201 ) or placebo ( n = 207 ) was added to inhaled ciclesonide ( 320 µg/d ) . If asthma control was achieved after 12 weeks , ciclesonide was tapered to 160 µg/d for 8 weeks , then to 80 µg/d for 8 weeks if asthma control was maintained . MAIN OUTCOMES AND MEASURES The primary outcome was time to first asthma treatment failure ( a composite outcome of decline in lung function and increases in use of β-agonists , systemic corticosteroids , and health care ) . RESULTS Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks ( 28 % [ 95 % CI , 21%-34 % ] with vitamin D3 vs 29 % [ 95 % CI , 23%-35 % ] with placebo ; adjusted hazard ratio , 0.9 [ 95 % CI , 0.6 - 1.3 ] ) . Of 14 prespecified secondary outcomes , 9 were analyzed , including asthma exacerbation ; of those 9 , the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control ( 111.3 µg/d [ 95 % CI , 102.2 - 120.4 µg/d ] in the vitamin D3 group vs 126.2 µg/d [ 95 % CI , 117.2 - 135.3 µg/d ] in the placebo group ; difference of 14.9 µg/d [ 95 % CI , 2.1 - 27.7 µg/d ] ) . CONCLUSIONS AND RELEVANCE Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency . These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01248065 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 CONTEXT Immune response in elderly individuals has been reported to improve after micronutrient supplementation . However , efficacy trials evaluating infectious diseases as outcomes are scarce and inconclusive . OBJECTIVE To investigate the effect of daily multivitamin-mineral and vitamin E supplementation on incidence and severity of acute respiratory tract infections in elderly individuals . DESIGN A r and omized , double blind , placebo-controlled , 2 x 2 factorial trial . SETTING AND PARTICIPANTS A total of 652 noninstitutionalized individuals aged 60 years or older enrolled from 2 community-based sampling strategies in the Wageningen area of the Netherl and s , conducted from 1998 to 2000 . At baseline , 6 % of participants had suboptimal ascorbic acid and 1.3 % had suboptimal alpha-tocopherol plasma concentration . INTERVENTION Physiological doses of multivitamin-minerals , 200 mg of vitamin E , both , or placebo . MAIN OUTCOME MEASURES Incidence and severity of self-reported acute respiratory tract infections at 15 months , as assessed by a nurse ( telephone contact ) , home visits , and microbiological and serological testing in subsets of patients . RESULTS During a median observation period of 441 days , 443 ( 68 % ) of 652 participants recorded 1024 respiratory tract infection episodes . The incidence rate ratio of acute respiratory tract infection for multivitamin-mineral supplementation was 0.95 ( 95 % confidence interval , 0.75 - 1.15 ; P = .58 ) and for vitamin E supplementation , 1.12 ( 95 % confidence interval , 0.88 - 1.25 ; P = .21 ) . Severity of infections was not influenced by multivitamin-mineral supplementation . For vitamin E vs no vitamin E , severity was worse : median ( interquartile range ) for illness- duration was 19 ( 9 - 37 ) vs 14 ( 6 - 29 ) days , P = .02 ; number of symptoms , 6 ( 3 - 8 ) vs 4 ( 3 - 8 ) , P = .03 ; presence of fever , 36.7 % vs 25.2 % , P = .009 ; and restriction of activity , 52.3 % vs 41.1 % , P = .02 . CONCLUSIONS Neither daily multivitamin-mineral supplementation at physiological dose nor 200 mg of vitamin E showed a favorable effect on incidence and severity of acute respiratory tract infections in well-nourished noninstitutionalized elderly individuals . Instead we observed adverse effects of vitamin E on illness severity Background Low vitamin D status is associated with risk of colorectal cancer and has been implicated in inflammatory bowel disease . Irritable bowel syndrome ( IBS ) is a chronic , relapsing , functional bowel disorder . A nascent literature suggests a role for vitamin D in IBS , but this has not been collated or critiqued . To date , seven studies have been published : four observational studies and three r and omised controlled trials ( RCTs ) . All observational studies reported that a substantial proportion of the IBS population was vitamin D deficient . Two intervention studies reported improvement in IBS symptom severity scores and quality of life ( QoL ) with vitamin D supplementation . There are limited data around the role of vitamin D in IBS . Conclusions The available evidence suggests that low vitamin D status is common among the IBS population and merits assessment and rectification for general health reasons alone . An inverse correlation between serum vitamin D and IBS symptom severity is suggested and vitamin D interventions may benefit symptoms . However , the available RCTs do not provide strong , generalisable evidence ; larger and adequately powered interventions are needed to establish a case for therapeutic application of vitamin D in IBS IMPORTANCE Maternal smoking during pregnancy adversely affects offspring lung development , with lifelong decreases in pulmonary function and increased asthma risk . In a primate model , vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function . OBJECTIVE To determine if newborns of pregnant smokers r and omized to receive daily vitamin C would have improved results of pulmonary function tests ( PFTs ) and decreased wheezing compared with those r and omized to placebo . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011 . One hundred fifty-nine newborns of r and omized pregnant smokers ( 76 vitamin C treated and 83 placebo treated ) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs . Follow-up assessment including wheezing was assessed through age 1 year , and PFTs were performed at age 1 year . INTERVENTIONS Pregnant women were r and omized to receive vitamin C ( 500 mg/d ) ( n = 89 ) or placebo ( n = 90 ) . MAIN OUTCOMES AND MEASURES The primary outcome was measurement of newborn pulmonary function ( ratio of the time to peak tidal expiratory flow to expiratory time [ TPTEF : TE ] and passive respiratory compliance per kilogram [ Crs/kg ] ) within 72 hours of age . Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year . A subgroup of pregnant smokers and nonsmokers had genotyping performed . RESULTS Newborns of women r and omized to vitamin C ( n = 76 ) , compared with those r and omized to placebo ( n = 83 ) , had improved pulmonary function as measured by TPTEF : TE ( 0.383 vs 0.345 [ adjusted 95 % CI for difference , 0.011 - 0.062 ] ; P = .006 ) and Crs/kg ( 1.32 vs 1.20 mL/cm H2O/kg [ 95 % CI , 0.02 - 0.20 ] ; P = .01 ) . Offspring of women r and omized to vitamin C had significantly decreased wheezing through age 1 year ( 15/70 [ 21 % ] vs 31/77 [ 40 % ] ; relative risk , 0.56 [ 95 % CI , 0.33 - 0.95 ] ; P = .03 ) . There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups . The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor ( rs16969968 ) ( P < .001 for interaction ) . CONCLUSIONS AND RELEVANCE Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring . Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00632476 Background : Increased dietary vitamin E intake is associated with a reduced incidence of asthma , and combinations of antioxidant supplements including vitamin E are effective in reducing ozone induced bronchoconstriction . A study was undertaken to investigate the effect of supplementation with vitamin E for 6 weeks on bronchial hyperresponsiveness in atopic adults with asthma . Methods : 72 participants from a clinical trial register of adults with asthma were r and omised to receive 500 mg natural vitamin E or matched placebo for 6 weeks in a placebo controlled , double blind parallel group clinical trial . Inclusion criteria included age 18–60 years , maintenance treatment of at least one dose of inhaled corticosteroid per day , a positive skin prick test to one of three common allergens , and bronchial hyperresponsiveness to methacholine ( defined as a dose provoking a 20 % fall in forced expiratory volume in 1 second ( FEV1 ) ( PD20 ) of 12.25 μmol ) . Secondary outcomes were FEV1 , forced vital capacity , mean morning and evening peak flow , symptom scores , bronchodilator use , and serum immunoglobulin E levels . Results : In the primary intention to treat analysis the change in PD20 was similar in the vitamin E and placebo groups with a mean difference of + 0.25 doubling doses of methacholine ( 95 % confidence interval −0.67 to + 1.16 greater with vitamin E ) . There was no effect of vitamin E supplementation on any other measure of asthma control , either in the intention to treat or per protocol analysis . There was also no effect of vitamin E supplementation on serum immunoglobulin levels . Conclusion : Dietary supplementation with vitamin E adds no benefit to current st and ard treatment in adults with mild to moderate asthma Diet has been investigated in relation to its ability to promote cognitive function . However , evidence is currently limited and has rarely been systematic ally review ed , particularly in a mild cognitive impairment ( MCI ) population . This review examined the effect of diet on cognitive outcomes in MCI patients . A total of five data bases were search ed to find r and omised controlled trial ( RCT ) studies , with diet as the main focus , in MCI participants . The primary outcome was incident dementia and /or Alzheimer 's disease ( AD ) and secondary outcomes included cognitive function across different domains using vali date d neuropsychological tests .  Sixteen studies met the inclusion criteria . There was a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured , thus making study comparisons difficult . Supplementation with vitamin E ( one study , n 516 ) , ginkgo biloba ( one study , n 482 ) or Fortasyn Connect ( one study , n 311 ) had no significant effect on progression from MCI to dementia and /or AD . For cognitive function , the findings showed some improvements in performance , particularly in memory , with the most consistent results shown by B vitamins , including  folic acid  ( one study , n 266 ) ,  folic acid alone  ( one study , n 180 ) ,  DHA and EPA  ( two studies , n 36 and n 86 ) ,  DHA  ( one study , n 240 ) and  flavonol supplementation  ( one study , n 90 ) . The findings indicate that dietary factors may have a potential benefit for cognitive function in MCI patients . Further well- design ed trials are needed , with st and ardised and robust measures of cognition to investigate the influence of diet on cognitive status IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring , but the preventive effect of vitamin D supplementation to pregnant women is unknown . OBJECTIVE To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring . DESIGN , SETTING , AND PARTICIPANTS A double-blind , single-center , r and omized clinical trial conducted within the Copenhagen Prospect i ve Studies on Asthma in Childhood 2010 cohort . Enrollment began March 2009 with a goal of 708 participants , but due to delayed ethical approval , only 623 women were recruited at 24 weeks of pregnancy . Follow-up of the children ( N = 581 ) was completed when the youngest child reached age 3 years in March 2014 . INTERVENTIONS Vitamin D3 ( 2400 IU/d ; n = 315 ) or matching placebo tablets ( n = 308 ) from pregnancy week 24 to 1 week postpartum . All women received 400 IU/d of vitamin D3 as part of usual pregnancy care . MAIN OUTCOMES AND MEASURES Age at onset of persistent wheeze in the first 3 years of life . Secondary outcomes included number of episodes of troublesome lung symptoms , asthma , respiratory tract infections , and neonatal airway immunology . Adverse events were assessed . RESULTS Of the 581 children ,  persistent wheeze  was diagnosed during the first 3 years of life in 47 children ( 16 % ) in the  vitamin D3 group and 57 children ( 20 % ) in the  control group .  Vitamin D3 supplementation was not associated with the risk of persistent wheeze , but the number of episodes of troublesome lung symptoms was reduced , and the airway immune profile was up-regulated ( principal component analysis , P = .04 ) . There was no effect on additional end points . Intrauterine death was observed in 1 fetus ( < 1 % ) in the vitamin D3 group vs 3 fetuses ( 1 % ) in the control group and congenital malformations in 17 neonates ( 5 % ) in the vitamin D3 group vs 23 neonates ( 8 % ) in the control group . [ table : see text ] . CONCLUSIONS AND RELEVANCE The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years . However , interpretation of the study is limited by a wide CI that includes a clinical ly important protective effect . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00856947 RATIONALE Patients with asthma exhibit variable response to inhaled corticosteroids ( ICS ) . Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid ( GC ) response in asthma . OBJECTIVES To determine the effect of vitamin D levels on phenotype and GC response in asthma . METHODS Nonsmoking adults with asthma were enrolled in a study assessing the relationship between serum 25(OH)D ( vitamin D ) concentrations  and lung function , airway hyperresponsiveness ( AHR ) , and GC response , as measured by dexamethasone-induced expression of mitogen-activated protein kinase phosphatase (MKP)-1 by peripheral blood mononuclear cells . MEASUREMENTS AND MAIN RESULTS A total of 54 adults with asthma ( FEV(1 ) , 82.9 + /- 15.7 % predicted [ mean + /- SD ] , serum  vitamin D  levels of 28.1 + /- 10.2 ng/ml ) were enrolled . Higher vitamin D levels were associated with greater lung function , with a 22.7 ( + /-9.3 ) ml ( mean + /- SE ) increase in FEV(1 ) for each nanogram per milliliter increase in vitamin D ( P = 0.02 ) . Participants with vitamin D insufficiency ( < 30 ng/ml ) demonstrated increased AHR , with a provocative concentration of methacholine inducing a 20 % fall in FEV(1 ) of 1.03 ( + /-0.2 ) mg/ml versus 1.92 ( + /-0.2 ) mg/ml in those with vitamin D of 30 ng/ml or higher ( P = 0.01 ) . In ICS-untreated participants , dexamethasone-induced MKP-1 expression increased with higher vitamin D levels , with a 0.05 (+/-0.02)-fold increase ( P = 0.02 ) in MKP-1 expression observed for each nanogram per milliliter increase in vitamin D , a finding that occurred in the absence of a significant increase in IL-10 expression . CONCLUSIONS In asthma , reduced vitamin D levels are associated with impaired lung function , increased AHR , and reduced GC response , suggesting that supplementation of vitamin D levels in patients with asthma may improve multiple parameters of asthma severity and treatment response . Clinical trials registered with www . clinical trials.gov ( NCT00495157 , NCT00565266 , and NCT00557180 ) The active metabolite of vitamin D , 1,25-(OH)2D3 , has immunomodulatory properties in addition to its more established action on bone and calcium metabolism . Recently vitamin D has been proposed as one of several environmental factors responsible for the increase in atopic diseases during the last decades . The objective of this study was to determine whether the estimated dose of dietary vitamin D3 during the first year of life is associated with atopic diseases up to the age of 6 years . In a prospect i ve birth cohort study 123 six-year-old children were investigated for the cumulative incidence of atopic dermatitis , allergic rhinitis or asthma by means of a postal question naire . Their vitamin D3 intake during infancy was recorded in a previous study and the relationship between lower or higher vitamin D3 intake and atopic illness later in childhood was assessed . Atopic manifestations were more prevalent in the group with higher intake of vitamin D3 . Although small , this study supports previous investigations suggesting a role of vitamin D intake during infancy in the development of atopic allergy later in childhood . If these findings are confirmed in prospect i ve controlled clinical trials , prevention through modified vitamin D3 supplementation in infancy could be discussed to reduce the burden of atopic illnesses To evaluate whether acute effects of ozone , nitrogen dioxide , and particulates with mass median diameter less than 10 micro m could be attenuated by antioxidant vitamin supplementation , we conducted a r and omized trial using a double-blinded design . Children with asthma ( n = 158 ) who were residents of Mexico City were r and omly given a daily supplement of vitamins ( 50 mg/day of vitamin E and 250 mg/day of vitamin C ) or a placebo and were followed from October 1998 to April 2000 . Pulmonary function tests were carried out twice a week in the morning . During the follow-up observation period , the mean 1-hour maximum ozone level was 102 ppb ( SD = 47 ) , and the mean 24-hour average PM(10 ) level was 56.7 micro g/m(3 ) ( SD = 27.4 ) . In children with moderate and severe asthma , ozone levels 1 day before spirometry were inversely associated significantly with forced expiratory flow ( FEF(25 - 75 ) ) ( -13.32 ml/second/10 ppb ; p = 0.000 ) , FEV(1 ) ( -4.59 ml/10 ppb ; p = 0.036 ) , and peak expiratory flow ( PEF ) ( -15.01 ml/second/10 ppb ; p = 0.04 ) in the placebo group after adjusting for potential confounding factors . No association between ozone and lung functions was observed in the supplement group . We observed significant differences in lung function decrements between groups for FEF(25 - 75 ) and PEF . Our results suggest that supplementation with antioxidants might modulate the impact of ozone exposure on the small airways of children with moderate to severe asthma
Available evidence from this systematic review suggests that high dose vitamin D may prevent  asthma exacerbation .
CONTEXT Observational studies have suggested a relationship between vitamin D status and asthma-related respiratory outcomes .
The benefit of vitamin D supplementation for pulmonary function , symptoms and exacerbations is not well established .
OBJECTIVE To systematic ally review paediatric clinical trials investigating the role of vitamin D on asthma-related respiratory outcomes .