Effect of vitamin D supplementation on inflammation: protocol for a systematic review Supplementation with vitamin A early in life and subsequent risk of asthma Randomized trial of vitamin D supplementation for winter-related atopic dermatitis in children. Allergen immunotherapy for the treatment of allergic rhinitis and/or asthma: an umbrella review. Effect of vitamin D and inhaled corticosteroid treatment on lung function in children. Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial Antioxidant supplementation and nasal inflammatory responses among young asthmatics exposed to high levels of ozone Does vitamin D intake during infancy promote the development of atopic allergy? The effects of vitamin D supplementation on airway functions in mild to moderate persistent asthma. Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Vitamin D Oral magnesium and vitamin C supplements in asthma: a parallel group randomized placebo‐controlled trial Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Should measurement of vitamin D and treatment of vitamin D insufficiency be routine in New Zealand? Maternal vitamin D intake during pregnancy and early childhood wheezing. Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The VDAART Randomized Clinical Trial. Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma. Vitamin D supplementation in pregnancy, prenatal 25(OH)D levels, race, and subsequent asthma or recurrent wheeze in offspring: Secondary analyses from the Vitamin D Antenatal Asthma Reduction Trial Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial The association of vitamin D, cathelicidin, and vitamin D binding protein with acute asthma attacks in children. Trends and mortality effects of vitamin A deficiency in children in 138 low-income and middle-income countries between 1991 and 2013: a pooled analysis of population-based surveys. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs)
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 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 BACKGROUND Epidemiologic and pre clinical data , and a small r and omized trial in Boston , suggest that vitamin D supplementation may improve winter-related atopic dermatitis ( AD ) . OBJECTIVE To determine the effect of vitamin D supplementation on winter-related AD . METHODS We performed a r and omized , double-blind , placebo-controlled trial of Mongolian children with winter-related AD ( clinical trials.gov identifier : NCT00879424 ) . Baseline eligibility included age 2 to 17 years , AD score 10 to 72 using the Eczema Area and Severity Index ( EASI ) , and winter-related AD ( eg , history of AD worsening during the fall-to-winter transition ) . Subjects were enrolled in Ulaanbaatar during winter and r and omly assigned to oral cholecalciferol ( 1000 IU/day ) versus placebo for 1 month . All children and parents received emollient and patient education about AD and basic skin care . The main outcomes were changes in EASI score and in Investigator 's Global Assessment . RESULTS The 107 enrolled children had a mean age of 9 years ( SD 5 ) , and 59 % were male . Their median age of AD onset was 3 months ( interquartile range 2 months to 1 year ) and mean EASI score at baseline 21 ( SD 9 ) . One-month follow-up data were available for 104 ( 97 % ) children . Compared with placebo , vitamin D supplementation for 1 month produced a clinical ly and statistically significant improvement in EASI score ( adjusted mean change : -6.5 vs -3.3 , respectively ; P = .04 ) . Moreover , change in Investigator 's Global Assessment favored vitamin D over placebo ( P = .03 ) . There were no adverse effects in either group . CONCLUSION Vitamin D supplementation improved winter-related AD among Mongolian children , a population likely to have vitamin D deficiency in winter BACKGROUND Allergic rhinitis and asthma are important public health concerns , yet there is no consensus about the benefits and harms of allergen-specific immunotherapy to treat these conditions . We performed an umbrella review of systematic review s summarizing the current evidence for the benefits and harms of subcutaneous immunotherapy ( SCIT ) and sublingual immunotherapy ( SLIT ) . METHODS We search ed MEDLINE , Embase , the Cochrane Library and the grey literature from Jan. 1 , 2010 to Nov. 20 , 2016 for systematic review s of r and omized controlled trials or prospect ively controlled studies involving children or adults with allergic rhinitis or asthma . Outcomes were summarized narratively ( benefits : total combined symptom-medication score , symptom score , medication score , disease-specific quality of life , adherence ; harms : anaphylaxis , death , local and systemic reactions ) . RESULTS Twenty-three systematic review s were included . SCIT and SLIT were more effective than placebo for most outcomes . SCIT was better than SLIT at improving medication and symptom scores , with no differences in quality of life ; however , data were limited for this comparison . Anaphylaxis and death were infrequently reported . Few review s assessed benefits or harms among children . INTERPRETATION Allergen immunotherapy appears to be effective among patients with allergic rhinitis and asthma . The safety of allergen immunotherapy is not conclusively established , although death and anaphylaxis appear to be rare . PROSPERO no. : CRD42015024590 RATIONALE Low vitamin D levels are associated with asthma and decreased airway responsiveness . Treatment with inhaled corticosteroids improves airway responsiveness and asthma control . OBJECTIVES To assess the effect of vitamin D levels on prebronchodilator FEV(1 ) , bronchodilator response , and responsiveness to methacholine ( PC(20 ) , provocative concentration of methacholine producing a 20 % decline in FEV(1 ) ) in patients with asthma treated with inhaled corticosteroids . METHODS We measured  25-hydroxyvitamin D levels  in the serum of children with persistent asthma at the time of enrollment in the Childhood Asthma Management Program . We divided subjects into the vitamin D sufficiency ( > 30 ng/ml ) , insufficiency ( 20 - 30 ng/ml ) , and deficiency ( < 20 ng/ml ) groups . Covariates included age , treatment , sex , body mass index , race , history of emergency department visits , hospitalizations , and season that vitamin D specimen was drawn . Our main outcome measures were change in prebronchodilator FEV(1 ) , bronchodilator response , and PC(20 ) from enrollment to 8 - 12 months . MEASUREMENTS AND MAIN RESULTS Of the 1,024 subjects , 663 ( 65 % ) were vitamin D sufficient , 260 ( 25 % ) were insufficient , and 101 ( 10 % ) were deficient . Vitamin D-deficient subjects were more likely to be older , African American , and have a higher body mass index compared with the vitamin D-sufficient and insufficient subjects . In the inhaled corticosteroid treatment group , prebronchodilator FEV(1 ) increased from r and omization to 12 months by 140 ml in the vitamin D-deficient group and prebronchodilator FEV(1 ) increased by 330 ml in the vitamin D insufficiency group and by 290 ml in the vitamin D sufficiency group ( P = 0.0072 ) , in adjusted models . CONCLUSIONS In children with asthma treated with inhaled corticosteroids , vitamin D deficiency is associated with poorer lung function than in children with vitamin D insufficiency or sufficiency 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 The inflammatory response to ozone in atopic asthma suggests that soluble mediators of inflammation are released in response to oxidant stress . Antioxidants may alleviate additional oxidative stress associated with photochemical oxidant pollution . This study investigates the impact of antioxidant supplementation on the nasal inflammatory response to ozone exposure in atopic asthmatic children . We conducted a r and omized trial using a double‐blinded design . Children with asthma ( n = 117 ) , residents of Mexico City , were given r and omly a daily supplement of vitamins ( 50 mg/day of vitamin E and 250 mg/day of vitamin C ) or placebo . Nasal lavages were performed three times during the 4‐month follow‐up and analysed for content of interleukin‐6 ( IL‐6 ) , IL‐8 , uric acid and glutathione ( GSx ) . IL‐6 levels in the nasal lavage were increased significantly in the placebo group after ozone exposure while no increase was observed in the supplement group . The difference in response to ozone exposure between the two groups was significant ( P = 0·02 ) . Results were similar for IL‐8 , but with no significant difference between the groups ( P = 0·12 ) . GSx decreased significantly in both groups . Uric acid decreased slightly in the placebo group . Our data suggest that vitamin C and E supplementation above the minimum dietary requirement in asthmatic children with a low intake of vitamin E might provide some protection against the nasal acute inflammatory response to ozone 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 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 Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . This is a grade I recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found poor evidence to determine whether supplementation with these vitamins reduces the risk for cardiovascular disease or cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) The available evidence from r and omized trials is either inadequate or conflicting , and the influence of confounding variables on observed outcomes in observational studies can not be determined . As a result , the USPSTF could not determine the balance of benefits and harms of routine use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . The USPSTF recommends against the use of beta-carotene supplements , either alone or in combination , for the prevention of cancer or cardiovascular disease . This is a grade D recommendation . The USPSTF found good evidence that -carotene supplementation provides no benefit in the prevention of cancer or cardiovascular disease in middle-aged and older adults . In two trials restricted to heavy smokers , -carotene supplementation was associated with higher incidence of lung cancer and higher all-cause mortality . The USPSTF concludes that -carotene supplements are unlikely to provide important benefits and might cause harm in some groups . Clinical Considerations The USPSTF did not review evidence regarding vitamin supplementation for patients with known or potential nutritional deficiencies , including pregnant and lactating women , children , elderly persons , and people with chronic illnesses .  Dietary supplements may be appropriate for people whose diet does not provide the recommended dietary intake of specific vitamins . Individuals may wish to consult a health care provider to discuss whether dietary supplements are appropriate . With the exception of vitamins for which there is compelling evidence of net harm ( for example , beta-carotene supplementation in smokers ) , there is little reason to discourage people from taking vitamin supplements . Patients should be reminded that taking vitamins does not replace the need to eat a healthy diet . All patients should receive information about the benefits of a diet high in fruits and vegetables , as well as information on other foods and nutrients that should be emphasized or avoided in their diet ( see the 2002 USPSTF recommendations on counseling to promote a healthy diet [ 1 ] ) . Patients who choose to take vitamins  should be encouraged to adhere to the dosages recommended in the Dietary Reference Intakes of the Institute of Medicine . Some vitamins , such as A and D , may be harmful in higher doses ; therefore , doses greatly exceeding the Recommended Dietary Allowance or Adequate Intake should be taken with care while considering whether potential harms outweigh potential benefits . Vitamins and minerals sold in the United States are classified as dietary supplements , and there is a degree of quality control over content if they have a U.S. Pharmacopeia seal ( 2 ) . Nevertheless , imprecision in the content and concentration of ingredients could pose a theoretical risk not reflected in clinical trials using calibrated compounds . The adverse effects of beta-carotene on smokers have been observed primarily in those taking large supplemental doses . There is no evidence to suggest that beta-carotene is harmful to smokers at levels occurring naturally in foods . The USPSTF did not review evidence supporting folic acid supplementation among pregnant women to reduce neural tube defects . In 1996 , the USPSTF recommended folic acid for all women who are planning , or capable of , pregnancy ( see the 1996 USPSTF chapter on screening for neural tube defects [ 3 ] ) . Clinicians and patients should discuss the possible need for vitamin supplementation when taking certain medications ( for example , folic acid supplementation for patients taking methotrexate ) . Scientific Evidence The USPSTF review s ( 4 - 6 ) focused on the quality of the evidence regarding the effect of routine supplementation with certain vitamins on primary prevention of cancer and cardiovascular disease . These review s were undertaken because of the growing epidemiologic evidence that dietary factors may play a role in the etiology of these diseases ( 7 - 9 ) . The review s focused on prospect i ve trials of vitamin supplementation and observational studies of associations between the use of specific supplements and the risk for cancer or cardiovascular disease . The value of vitamins naturally occurring in food , the use of vitamin supplements for the prevention of other conditions ( for example , neural tube defects ) , and the use of vitamin supplements for the secondary prevention of complications in patients with existing disease were outside the scope of these review s. Vitamin A No prospect i ve trials have examined the effect of vitamin A supplements alone on the risk for cancer . Observational studies provide no evidence that such supplements prevent cancer in men . In women , observational studies have reported a statistically significant inverse association between use of vitamin A supplements and risk for colon and breast cancer ( 10 , 11 ) . Despite efforts to adjust for confounding variables , the observational , nonr and om design of these studies makes it difficult to assess the extent to which the reduced cancer risk is attributable to vitamin A or to other characteristics of women who take vitamin A supplements .  No evidence from prospect i ve trials is available regarding the benefits of vitamin A alone in preventing cardiovascular disease . One good- quality cohort study found no effect of vitamin A supplementation in reducing cardiovascular disease mortality ( 12 ) . Vitamin C No primary prevention trial of the effect of vitamin C supplementation alone on cancer or cardiovascular disease has been reported . Observational studies have generally shown no statistically significant associations between use of vitamin C supplements and risk for cancer of the breast , prostate , colon , or lung ( 12 - 14 ) . The observational cohort studies examining the effects of vitamin C on cardiovascular disease have produced inconsistent results ( 12 , 15 , 16 ) . Vitamin E Only a few trials have examined the effects of vitamin E on the primary prevention of cancer or cardiovascular disease . A r and omized , controlled trial ( RCT ) involving Finnish male smokers found that vitamin E supplementation is not protective against lung cancer but may have a beneficial impact on prostate cancer ( 14 ) . Because prostate cancer was not a primary end point of the trial and the trial had other limitations , further evidence is needed to confirm this finding . Observational studies have shown no statistically significant association between use of vitamin E supplements and risk for prostate , lung , or breast cancer ( 5 ) . One study suggested that vitamin E protects against colon cancer , but the influence of confounding variables can not be fully excluded ( 17 ) . Among primary prevention trials , two good- quality trials ( 14 , 18 ) and one fair- quality trial ( 19 ) found no statistically significant benefit of vitamin E supplementation in preventing cardiovascular disease ( 20 ) . Only one of seven trials of vitamin E supplementation for secondary prevention demonstrated a statistically significant reduction in cardiac events ( 4 ) . Some prospect i ve cohort studies have suggested a significant benefit , but the results are mixed and the influence of confounding variables can not be excluded ( 4 ) . -Carotene A consistent body of evidence from clinical trials suggests that beta-carotene supplementation does not decrease the risk for lung , prostate , colon , breast , or nonmelanoma skin cancer ( 14 , 21 - 25 ) . -Carotene supplements were associated with an increased risk for lung cancer among smokers , especially heavy smokers , in two RCTs ( 14 , 25 ) . Results from four RCTs demonstrated no reduced risk for cardiovascular events or death after beta-carotene supplementation ( 14 , 21 , 22 , 26 - 28 ) . Antioxidant Vitamin Combinations Studies of the effects of antioxidant vitamin combinations to prevent cancer have yielded mixed results . A recent RCT reported no statistically significant effect of daily supplementation with a combination of antioxidants : vitamin E , vitamin C , and beta-carotene ( 29 ) . Some studies have suggested an adverse effect of antioxidant combinations on cancer , but the results may have been confounded by the inclusion of beta-carotene ( 5 ) . Some observational studies of antioxidant vitamin combinations have suggested a benefit in preventing cardiovascular disease ( 13 , 30 , 31 ) , but other studies , including well- design ed RCTs , have shown no benefit ( 29 , 32 , 33 ) . One secondary prevention trial showed an increase in all-cause mortality among women taking antioxidant supplements  ( 34 ) . Multiple Vitamin Combinations The incremental benefit of taking supplemental doses of folic acid and B vitamins has been examined by comparing the outcomes of observational studies while controlling for the total intake of antioxidant vitamin supplements ( 35 ) . In these analyses , folic acid supplementation was associated with significantly decreased risk for colon cancer , but the protective effect requires confirmation in prospect i ve trials . There is conflicting evidence regarding the use of multivitamins and the risk for cardiovascular disease . Among cohort studies , one good- quality study reported a statistically significant reduction in coronary events ( 36 ) , two good- quality studies reported no statistically significant effect on mortality ( 16 , 37 ) , and one 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 Epidemiological studies suggest that higher intakes of dietary vitamin C and magnesium may be associated with a reduced risk of 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 Epidemiological studies have reported associations between lower vitamin D levels and a great variety of diseases , prompting calls for widespread treatment of individuals with low vitamin D levels . Most of New Zeal and 's population have vitamin D levels for at least part of the year that are considered insufficient ( 25-hydroxyvitamin D < 50 - 80 nmol/L ) . However , evidence for benefits of vitamin D supplementation in such population s is controversial and there is some evidence of harmful effects . Until adequately powered , r and omised , controlled trials of vitamin D supplementation demonstrate safe improvements in health , clinicians should not focus on detecting/treating individuals with vitamin D insufficiency , instead treating those at high risk of vitamin D deficiency ( 25-hydroxyvitamin D < 25 nmol/L ) , such as the frail elderly , and those with specific clinical indications . Treatment for such individuals does not require vitamin D measurements . Requests for vitamin D measurements in Auckl and have nearly quadrupled in the past decade , from 8500 in the year 2000 to 32,800 in 2010 , with substantial increases in cost . Vitamin D measurement is often inaccurate and imprecise , and the vast majority of tests performed currently do not reveal vitamin D deficiency . Therefore , a move away from  routine vitamin D measurements  seems sensible , though they are still indicated when investigating suspected metabolic bone disease or hypocalcaemia BACKGROUND Maternal intake of vitamin D in pregnancy is a potentially modifiable but understudied risk factor for the development of asthma in children . OBJECTIVE We investigated whether maternal vitamin D intake in pregnancy is associated with decreased risks of  wheezing symptoms in young children . DESIGN Subjects were from a birth cohort recruited in utero with the primary objective of identifying associations between maternal diet during pregnancy and asthma and allergies in children . A r and om sample of 2000 healthy pregnant women was recruited while attending antenatal clinics at the Aberdeen Maternity Hospital , Scotl and , at approximately 12 wk gestation . Maternal vitamin D intake was ascertained from a food-frequency question naire completed at 32 wk of gestation . The main outcome measures were wheezing symptoms , spirometry , bronchodilator response , atopic sensitization , and exhaled nitric oxide at 5 y. RESULTS Respiratory details through 5 y and maternal food-frequency- question naire data were available for 1212 children . In models adjusted for potential confounders , including the children 's vitamin D intake , a comparison of the highest and lowest quintiles of maternal total vitamin D intake conferred lower risks for ever wheeze [ odds ratio ( OR ) : 0.48 ; 95 % CI : 0.25 , 0.91 ] , wheeze in the previous year ( OR : 0.35 ; 95 % CI : 0.15 , 0.83 ) , and persistent wheeze ( OR : 0.33 ; 95 % CI : 0.11 , 0.98 ) in 5-y-old children . In addition , lower maternal total vitamin D intakes in pregnancy were also associated with decreased bronchodilator response ( P = 0.04 ) . No associations were observed between maternal  vitamin D intakes and spirometry or exhaled nitric oxide concentrations . CONCLUSION Increasing maternal vitamin D intakes during pregnancy may decrease the risk of wheeze symptoms in early childhood 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 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 Background Nutrient trials differ from drug trials because participants have varying circulating levels at entry into the trial . Objective We sought to study the effect of a vitamin D intervention in pregnancy between subjects of different races and the association between 25‐hydroxyvitamin D3 ( 25[OH]D ) levels in pregnancy and the risk of asthma/recurrent wheeze in offspring . Methods The Vitamin D Antenatal Asthma Reduction Trial is a r and omized trial of pregnant women at risk of having children with asthma r and omized to 4400 international units/d vitamin D or placebo plus 400 international units/d vitamin D. Asthma and  recurrent wheezing until age 3 years were recorded . Results African American ( AA ) women ( n = 312 ) had lower initial levels of 25(OH)D ( mean [ SD ] , 17.6 ng/mL [ 8.3 ng/mL ] ) compared with non‐AA women ( n = 400 ; 27.1 ng/mL [ 9.7 ng/mL ] , P < .001 ) . No racial difference was found from vitamin D supplementation in pregnancy on asthma/recurrent wheezing in offspring ( P for interaction = .77 ) . Having an initial level of greater than 30 ng/mL and being r and omized to the intervention group was associated with the lowest risk for asthma/recurrent wheeze by age 3 years compared with having an initial level of less than 20 ng/mL and receiving placebo ( adjusted odds ratio , 0.42 ; 95 % CI , 0.19‐0.91 ) . Conclusions We did not find differences between AA and non‐AA mothers in the effect of maternal vitamin D supplementation and asthma/recurrent wheeze in offspring at 3 years . Maternal supplementation of vitamin D , particularly in mothers with initial 25(OH)D levels of greater than 30 ng/mL , reduced asthma/recurrent wheeze in the offspring through age 3 years , suggesting that higher vitamin D status beginning in early pregnancy is necessary for asthma/recurrent wheeze prevention in early life . Graphical abstract Figure . No Caption available 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 & NA ; Figure . No caption available . Background : Programming of the immune system during fetal development can influence asthma‐related risk factors and outcomes in later life . Vitamin D is a well‐recognized immune modulator , and deficiency of this nutrient during pregnancy is hypothesized to influence disease development in offspring . Objective : We sought to investigate the effect on neonatal immunity of maternal supplementation with 4400 IU/d vitamin D3 during the second and third trimesters of pregnancy by using a subset of cord blood sample s from a r and omized , double‐blind , placebo‐controlled clinical trial ( the Vitamin D Antenatal Asthma Reduction Trial ) . Methods : Cord blood sample s from neonates born to mothers supplemented with 4400 IU/d ( n = 26 ) or 400 IU/d ( n = 25 ) of vitamin D3  were analyzed for immune cell composition by flow cytometry , Toll‐like receptor ( TLR ) expression by quantitative PCR , and cytokine secretion after stimulation with mitogenic , TLR , and T‐cell stimuli by cytometric bead array . Responsiveness to the glucocorticoid dexamethasone was determined . Results : Supplementation of mothers with 4400 IU of vitamin D3 result ed in an enhanced broad‐spectrum proinflammatory cytokine response of cord blood mononuclear cells to innate and mitogenic stimuli ( P = .0009 ) , with an average 1.7‐ to 2.1‐fold increase in levels of several proinflammatory cytokines ( GM‐CSF , IFN‐&ggr ; , IL‐1&bgr ; , IL‐6 , and IL‐8 ) across stimuli , a higher gene expression level of TLR2 ( P = .02 ) and TLR9 ( P = .02 ) , a greater than 4‐fold increase in IL‐17A ( P = .03 ) production after polyclonal T‐cell stimulation , and an enhanced IL‐10 response of cord blood mononuclear cells to dexamethasone treatment in culture ( P = .018 ) . Conclusion : Vitamin D exposure during fetal development influences the immune system of the neonate , which can contribute to protection from asthma‐related , including infectious , outcomes in early life BACKGROUND Recent evidence about the various effects of vitamin D ( vit D ) on innate and adaptive immunity has led to a search for the role of vit D in asthma . It is postulated that a decrease in cathelicidin , a multifunctional host defense molecule , production due to low vit D status may predispose to infectious complications in children with asthma . OBJECTIVE The aim of this study was to determine the association of vit D , vit D-binding protein ( VDBP ) and cathelicidin with acute asthma attacks among children with allergic asthma . METHODS This prospect i ve study included 35 patients with acute asthma attack and 32 children with controlled asthma , and all were matched by sampling season , sensitization to mites , and previous severity of asthma . A comprehensive question naire about risk factors , blood sampling for 25-hydroxyvitamin D vit D , VDBP , and cathelicidin levels ; spirometric indices were used . Factors that influence serum vit D and cathelicidin levels and the development of asthma attacks were evaluated with multivariate analysis . RESULTS The mean serum vit D levels of the attack group was significantly lower than that of the controlled asthma group ( p < 0.001 ) . The mean cathelicidin level was significantly higher in the acute asthma group than with the controlled subjects with asthma ( p = 0.002 ) . There was no difference between the acute and controlled asthma groups in terms of markers of allergy and serum VDBP levels . Risk factors that may influence vit D levels revealed that body mass index ( BMI ) ( p = 0.038 ) , duration of sun exposure ( p < 0.001 ) , and amount of dietary vit D ( p < 0.001 ) independently affected serum vit D levels . Risk factors that may result in acute asthma showed that low serum levels of vit D were significantly related to the risk of asthma attacks ( p < 0.001 , adjusted odds ratio 16.11 ) . Cathelicidin levels showed a significant positive association with asthma attacks and BMI . CONCLUSIONS Vit D deficiency showed a significant relationship to the development of asthma attacks independent of cathelicidin deficiency and other factors associated with the severity of chronic asthma BACKGROUND Vitamin A deficiency is a risk factor for blindness and for mortality from measles and diarrhoea in children aged 6 - 59 months . We aim ed to estimate trends in the prevalence of vitamin A deficiency between 1991 and 2013 and its mortality burden in low-income and middle-income countries . METHODS We collated 134 population -representative data sources from 83 countries with measured serum retinol concentration data . We used a Bayesian hierarchical model to estimate the prevalence of vitamin A deficiency , defined as a serum retinol concentration lower than 0·70 μmol/L. We estimated the relative risks ( RRs ) for the effects of vitamin A deficiency on mortality from measles and diarrhoea by pooling effect sizes from r and omised trials of vitamin A supplementation . We used information about prevalences of deficiency , RRs , and number of cause-specific child deaths to estimate deaths attributable to vitamin A deficiency . All analyses included a systematic quantification of uncertainty . FINDINGS In 1991 , 39 % ( 95 % credible interval 27 - 52 ) of children aged 6 - 59 months in low-income and middle-income countries were vitamin A deficient . In 2013 , the prevalence of deficiency was 29 % ( 17 - 42 ; posterior probability [ PP ] of being a true decline=0·81 ) . Vitamin A deficiency significantly declined in east and southeast Asia and Oceania from 42 % ( 19 - 70 ) to 6 % ( 1 - 16 ; PP>0·99 ) ; a decline in Latin America and the Caribbean from 21 % ( 11 - 33 ) to 11 % ( 4 - 23 ; PP=0·89 ) also occurred . In 2013 , the prevalence of deficiency was highest in sub-Saharan Africa ( 48 % ; 25 - 75 ) and south Asia ( 44 % ; 13 - 79 ) . 94 500 ( 54 200 - 146 800 ) deaths from diarrhoea and 11 200 ( 4300 - 20 500 ) deaths from measles were attributable to vitamin A deficiency in 2013 , which accounted for 1·7 % ( 1·0 - 2·6 ) of all deaths in children younger than 5 years in low-income and middle-income countries . More than 95 % of these deaths occurred in sub-Saharan Africa and south Asia . INTERPRETATION Vitamin A deficiency remains prevalent in south Asia and sub-Saharan Africa . Deaths attributable to this deficiency have decreased over time worldwide , and have been almost eliminated in regions other than south Asia and sub-Saharan Africa . This new evidence for both prevalence and absolute burden of vitamin A deficiency should be used to reconsider , and possibly revise , the list of priority countries for high-dose vitamin A supplementation such that a country 's priority status takes into account both the prevalence of deficiency and the expected mortality benefits of supplementation . FUNDIN Bill & Melinda Gates Foundation , Gr and Challenges Canada , UK Medical Research Council 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 )
Conclusions The available very low to low quality evidence does not confirm or rule out beneficial effects of vitamin D supplementation in children with asthma .
Background Epidemiologic studies suggest an association between vitamin D deficiency and atopic diseases , including asthma .
The objective of this study was to systematic ally review the benefits and harms of vitamin D supplementation in children with asthma .