Maternal vitamin D supplementation during pregnancy Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Vitamin D Effect of vitamin D3 on mild to moderate persistent asthmatic patients: A randomized controlled pilot study Improved control of childhood asthma with low‐dose, short‐term vitamin D supplementation: a randomized, double‐blind, placebo‐controlled trial Effect of vitamin D supplementation on inflammation: protocol for a systematic review Effect of Vitamin D Supplementation on Moderate to Severe Bronchial Asthma DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. 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 Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The VDAART Randomized Clinical Trial. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs) The effects of vitamin D supplementation on airway functions in mild to moderate persistent asthma. Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Association Between Vitamin D Supplementation During Pregnancy and Offspring Growth, Morbidity, and Mortality Supplementation with vitamin A early in life and subsequent risk of asthma Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial. Early-life supplementation of vitamins A and D, in water-soluble form or in peanut oil, and allergic diseases during childhood. Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma. A systematic review protocol examining the effect of vitamin D supplementation on endothelial function
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 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 The prevalence of allergic diseases is approximately 10 % in infants whose parents and siblings do not have allergic diseases and 20–30 % in those with an allergic first-degree relative .  Vitamin D is involved in the regulation of the immune system and it may play a role in the development , severity and course of asthma and other allergic diseases . Objective The World Allergy Organization ( WAO ) convened a guideline panel to develop evidence -based recommendations addressing the use of vitamin D in primary prevention of allergic diseases . Methods Our WAO guideline panel identified the most relevant clinical questions and performed a systematic review of r and omized controlled trials and non-r and omized studies ( NRS ) , specifically cohort and case-control studies , of vitamin D supplementation for the prevention of allergic diseases . We also review ed the evidence about values and preferences , and re source requirements ( up to January 2015 , with an up date on January 30 , 2016 ) . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . Results Having review ed the currently available evidence , the WAO guideline panel found no support for the hypothesis that vitamin D supplementation reduces the risk of developing allergic diseases in children . The WAO guideline panel suggest not using vitamin D in pregnant women , breastfeeding mothers , or healthy term infants as a means of preventing the development of allergic diseases . This recommendation does not apply to those mothers and infants who have other indications for prophylactic or therapeutic use of vitamin D. The panel ’s recommendations are conditional and supported by very low certainty evidence . Conclusions WAO recommendations about vitamin D supplementation for the prevention of allergic diseases support parents , clinicians and other health care professionals in their decisions whether or not to use vitamin D in preventing allergic diseases in healthy , term infants Background : Asthma is a common chronic inflammatory disease of the bronchial airways . Well defined treatment options for asthma are very few . The role of vitamin D3 on asthma is still baffling . Aim : We have examined the effect of vitamin D3 supplementation in mild to moderate persistent asthma patients . Material s and Methods : We conducted an open labeled , r and omized comparative trial in 48 asthma patients . The study duration was about 90 days . The study had a run-in-period of 2 weeks . At the end of run-in-period , patients were divided into two groups : Usual care group ( n = 31 ) patients received budesonide and formoterol and intervention care group ( n = 32 ) patients received vitamin D3 supplementation along with their regular medicine . Results : The primary outcome of the study was to measure the improvement in forced expiratory volume in 1 second ( FEV1 ) . Patients in both groups had a significant improvement in FEV1 at the end of the study . The mean difference in percentage predicted FEV1 in usual care and intervention care group was 4.95 and 7.07 respectively . Conclusion : The study concluded that adjunctive therapy of vitamin D3 is effective in asthma patients . The present study will be an evidence based report ; however , future studies are warranted in longer duration of time to substantiate the present findings In our prior r and omized trial on preventing influenza , asthma attacks as a secondary outcome occurred less often in the vitamin D group than in the placebo group . We aim ed to clarify whether low‐dose , short‐term vitamin D supplementation , in addition to st and ard treatments , improves control of childhood asthma 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 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 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 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 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 Asthma and wheezing begin early in life , and prenatal vitamin D deficiency has been variably associated with these disorders in offspring . OBJECTIVE To determine whether prenatal vitamin D ( cholecalciferol ) supplementation can prevent  asthma or recurrent wheeze in early childhood . DESIGN , SETTING , AND PARTICIPANTS The Vitamin D Antenatal Asthma Reduction Trial was a r and omized , double-blind , placebo-controlled trial conducted in 3 centers across the United States . Enrollment began in October 2009 and completed follow-up in January 2015 . Eight hundred eighty-one pregnant women between the ages of 18 and 39 years at high risk of having children with asthma were r and omized at 10 to 18 weeks ' gestation . Five participants were deemed ineligible shortly after r and omization and were discontinued . INTERVENTIONS Four hundred forty women were r and omized to receive daily 4000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D , and 436 women were r and omized to receive a placebo plus a prenatal vitamin containing 400 IU vitamin D. MAIN OUTCOMES AND MEASURES Co primary outcomes of ( 1 ) parental report of physician-diagnosed asthma or recurrent wheezing through 3 years of age and ( 2 ) third trimester maternal 25-hydroxyvitamin D levels . RESULTS Eight hundred ten infants were born in the study , and 806 were included in the analyses for the 3-year outcomes . Two hundred eighteen children developed asthma or recurrent wheeze : 98 of 405 ( 24.3 % ; 95 % CI , 18.7%-28.5 % ) in the 4400-IU group vs 120 of 401 ( 30.4 % , 95 % CI , 25.7%-73.1 % ) in the 400-IU group ( hazard ratio , 0.8 ; 95 % CI , 0.6 - 1.0 ; P = .051 ) . Of the women in the 4400-IU group whose blood levels were checked , 289 ( 74.9 % ) had 25-hydroxyvitamin D levels of 30 ng/mL or higher by the third trimester of pregnancy compared with 133 of 391 ( 34.0 % ) in the 400-IU group ( difference , 40.9 % ; 95 % CI , 34.2%-47.5 % , P < .001 ) . CONCLUSIONS AND RELEVANCE In pregnant women at risk of having a child with asthma , supplementation with 4400 IU/d of vitamin D compared with 400 IU/d significantly increased vitamin D levels in the women . The incidence of asthma and recurrent wheezing in their children at age 3 years was lower by 6.1 % , but this did not meet statistical significance ; however , the study may have been underpowered . Longer follow-up of the children is ongoing to determine whether the difference is clinical ly important . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00920621 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 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 Vitamin D is hypothesized to have some roles in innate and adaptive immunity , inflammation reduction , and remodeling ; therefore , it is supposed to affect the asthma phenotype , severity , and response to inhaled corticosteroid ( ICS ) . OBJECTIVE To explore the synergistic effects of vitamin D supplementation in addition to asthma controllers ( ICS or ICS plus long-acting β-agonist ) on airway functions . METHODS A r and omized clinical trial was conducted in 130 individuals aged 10 to 50 years who lived in Tehran during a 24-week period . Data on age , sex , body mass index , stage of asthma , serum total IgE , history of allergic rhinitis , atopic dermatitis , food allergy , and urticaria were collected .  Spirometric parameters ( forced expiratory volume in 1 second [ FEV1 ] and ratio of FEV1 to forced vital capacity ) and serum vitamin D measurement were obtained before and 8 and 24 weeks after the intervention . Patients were divided in 2 groups r and omly . Both groups received asthma controllers ( budesonide or budesonide plus formoterol ) according to their stage , but the intervention group received vitamin D supplementation ( 100,000-U bolus intramuscularly plus 50,000 U orally weekly ) in addition to asthma controllers . RESULTS FEV1 improved significantly in both groups after 8 weeks , but no significant difference was found between the 2 groups at baseline ( P = .20 ) or after 8 weeks ( P = .99 ) ; however , a significant improvement was seen in the intervention group in the last 16 weeks , and FEV1 was significantly better in the intervention group than the other group after 24 weeks ( P < .001 ) . CONCLUSION Vitamin D supplementation associated with asthma controllers could significantly improve FEV1 in mild to moderate persistent asthma after 24 weeks . TRIAL REGISTRATION i rct .ir Identifier : I RCT 201302079608N1 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 BACKGROUND Vitamin D deficiency and asthma are common at higher latitudes . Although vitamin D has important immunologic effects , its relation with asthma is unknown . OBJECTIVE We hypothesized that a higher maternal intake of vitamin D during pregnancy is associated with a lower risk of  recurrent wheeze in children at 3 y of age . DESIGN The participants were 1194 mother-child pairs in Project Viva-a prospect i ve prebirth cohort study in Massachusetts . We assessed the maternal intake of vitamin D during pregnancy from a vali date d food-frequency question naire . The primary outcome was recurrent wheeze , ie , a positive asthma predictive index ( > or=2 wheezing attacks among children with a personal diagnosis of eczema or a parental history of asthma ) . RESULTS The mean ( + /-SD ) total vitamin D intake during pregnancy was 548 + /- 167 IU/d . By age 3 y , 186 children ( 16 % ) had recurrent wheeze . Compared with mothers in the lowest quartile of daily intake ( median : 356 IU ) , those in the highest quartile ( 724 IU ) had a lower risk of having a child with recurrent wheeze [ odds ratio ( OR ) : 0.39 ; 95 % CI : 0.25 , 0.62 ; P for trend < 0.001 ] . A 100-IU increase in vitamin D intake was associated with lower risk ( OR : 0.81 ; 95 % CI : 0.74 , 0.89 ) , regardless of whether vitamin D was from the diet ( OR : 0.81 ; 95 % CI : 0.69 , 0.96 ) or supplements ( OR : 0.82 ; 95 % CI : 0.73 , 0.92 ) . Adjustment for 12 potential confounders , including maternal intake of other dietary factors , did not change the results . CONCLUSION In the northeastern United States , a higher maternal intake of vitamin D during pregnancy may decrease the risk of recurrent wheeze in early childhood Importance Whether vitamin D supplementation during pregnancy is beneficial and safe for offspring is unclear . Objective To systematic ally review studies of the effects of vitamin D supplementation during pregnancy on offspring growth , morbidity  , and mortality . Data Sources Search es of Medline , Embase , and the Cochrane Data base of Systematic Review s were conducted up to October 31 , 2017 . Key search terms were vitamin D , pregnancy , r and omized controlled trials , and offspring outcomes . Study Selection R and omized clinical trials of vitamin D supplementation during pregnancy and offspring outcomes . Data Extraction and Synthesis Two authors independently extracted data , and the quality of the studies was assessed . Summary risk ratio ( RR ) , risk difference ( RD ) or mean difference ( MD ) , and 95 % CI were calculated using fixed-effects or r and om-effects meta- analysis . Main Outcomes and Measures Main outcomes were fetal or neonatal mortality , small for gestational age ( SGA ) , congenital malformation , admission to a neonatal intensive care unit , birth weight , Apgar scores , neonatal 25-hydroxyvitamin D ( 25[OH]D ) and calcium concentrations , gestational age , preterm birth , infant anthropometry , and respiratory morbidity during childhood . Results Twenty-four clinical trials involving 5405 participants met inclusion criteria . Vitamin D supplementation during pregnancy was associated with a lower risk of SGA ( RR , 0.72 ; 95 % CI , 0.52 to 0.99 ; RD , −5.60 % ; 95 % CI , −0.86 % to −10.34 % ) without risk of fetal or neonatal mortality ( RR , 0.72 ; 95 % CI , 0.47 to 1.11 ) or congenital abnormality ( RR , 0.94 ; 95 % CI , 0.61 to 1.43 ) . Neonates with prenatal vitamin D supplementation had higher 25(OH)D levels ( MD , 13.50 ng/mL ; 95 % CI , 10.12 to 16.87 ng/mL ) , calcium levels ( MD , 0.19 mg/dL ; 95 % CI , 0.003 to 0.38 mg/dL ) , and weight at birth ( MD , 75.38 g ; 95 % CI , 22.88 to 127.88 g ) , 3 months ( MD , 0.21 kg ; 95 % CI , 0.13 to 0.28 kg ) , 6 months ( MD , 0.46 kg ; 95 % CI , 0.33 to 0.58 kg ) , 9 months ( MD , 0.50 kg ; 95 % CI , 0.01 to 0.99 kg ) , and 12 months ( MD , 0.32 kg ; 95 % CI , 0.12 to 0.52 kg ) . Subgroup analysis by doses showed that low-dose vitamin D supplementation ( ⩽2000 IU/d ) was associated with a reduced risk of fetal or neonatal mortality ( RR , 0.35 ; 95 % CI , 0.15 to 0.80 ) , but higher doses ( > 2000 IU/d ) did not reduce this risk ( RR , 0.95 ; 95 % CI , 0.59 to 1.54 ) . Conclusions and Relevance Vitamin D supplementation during pregnancy is associated with a reduced risk of SGA and improved infant growth without risk of fetal or neonatal mortality or congenital abnormality . Vitamin D supplementation with doses of 2000 IU/d or lower during pregnancy may reduce the risk of fetal or neonatal mortality 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 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 BACKGROUND Early vitamin supplementation is given routinely to infants in many countries , but it is unclear whether this affects the risk of allergic diseases . OBJECTIVES We sought to study the association between early-life supplementation of vitamins A and D in water-soluble form or in peanut oil and allergic diseases up to 4 years of age . METHODS A prospect i ve birth cohort of 4089 newborn infants was followed for 4 years using parental question naires repeatedly to collect information on exposure and health . At 4 years , the response rate was 90 % , and allergen-specific IgE levels to food and airborne allergens were measured in 2614 of the participating children . RESULTS Vitamins A and D were given to 98 % of the children in infancy , and vitamins based in peanut oil dominated ( 90 % ) . Children supplemented with vitamins A and D in water-soluble form during the first year of life had an almost 2-fold increased risk of asthma ( adjusted odds ratio [ OD ] , 2.18 ; 95 % CI , 1.45 - 3.28 ) , food hypersensitivity ( adjusted OR , 1.89 ; 95 % CI , 1.33 - 2.65 ) , and sensitization to common food and airborne allergens ( adjusted OR , 1.88 ; 95 % CI , 1.34 - 2.64 ) at age 4 years compared with those receiving vitamins in peanut oil . No increased risk of IgE antibodies to peanut was seen in children receiving vitamins in peanut oil . CONCLUSION Supplementation of vitamins A and D in water-soluble form seems to increase the risk of allergic disease up to the age of 4 years compared with supplementation with the same vitamins given in peanut oil . CLINICAL IMPLICATION S Vitamins A and D in oil does not seem to increase the risk of allergic disease during childhood 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 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 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
There was no significant effect for asthma symptom scores and lung function .
Conclusions and Relevance R and omized controlled trials provide some low- quality evidence to support vitamin D supplementation for the reduction of asthma exacerbations .
Importance There is growing evidence that vitamin D plays a role in the pathogenesis of asthma but it is unclear whether supplementation during childhood may improve asthma outcomes .
Objectives The objective of this systematic review and meta- analysis was to evaluate the efficacy and safety of vitamin D supplementation as a treatment or adjunct treatment for asthma .