Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Vitamin D status has a linear association with seasonal infections and lung function in British adults. Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults Vitamin D supplementation for severe pneumonia — A randomized controlled trial Vitamin D supplementation and upper respiratory tract infections in adolescent swimmers: a randomized controlled trial. Vitamin D supplementation during rehabilitation in COPD: a secondary analysis of a randomized trial Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease The impact of vitamin A supplementation given during a pneumonia episode on the subsequent morbidity of children. Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Respiratory infections reduce the growth response to vitamin A supplementation in a randomized controlled trial. Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation
BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often have vitamin D deficiency , which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation . Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking . We therefore investigated whether vitamin D3 ( colecalciferol ) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections . METHODS We did a r and omised , double-blind , placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practice s and four Acute National Health Service Trust clinics in London , UK . Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block r and omisation . Participants and study staff were masked to treatment assignment . Co primary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection . Analysis was by intention to treat . A prespecified subgroup analysis was done to assess whether effects of the intervention on the co primary outcomes were modified by baseline vitamin D status . This trial is registered with Clinical Trials.gov , number NCT00977873 . FINDINGS 240 patients were r and omly allocated to the vitamin D3 group ( n=122 ) and placebo group ( n=118 ) . Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation ( adjusted hazard ratio 0·86 , 95 % CI 0·60 - 1·24 , p=0·42 ) or time to first upper respiratory infection ( 0·95 , 0·69 - 1·31 , p=0·75 ) . Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L ( 0·57 , 0·35 - 0·92 , p=0·021 ) , but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L ( 1·45 , 0·81 - 2·62 , p=0·21 ; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status ) . Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection ( pinteraction=0·41 ) . INTERPRETATION Vitamin D3 supplementation protected against moderate or severe exacerbation , but not upper respiratory infection , in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation . FUNDING UK National Institute for Health Research Higher vitamin D concentrations have been proposed as a protective ' seasonal stimulus ' against influenza , and there are suggestions for associations with other aspects of respiratory health . The aim of the present study was to investigate the relationship of current vitamin D status ( measured by 25-hydroxyvitamin D , 25(OH)D ) with  respiratory infections and lung function .  We used cross-sectional data from 6789 participants in the nationwide 1958 British birth cohort who had measurements of 25(OH)D , lung function ( forced expiratory volume in 1 s ( FEV1 ) and forced vital capacity ( FVC ) ) and respiratory infections available from the age of 45 years . In this population , the prevalence of respiratory infections had a strong seasonal pattern in the opposite direction to the pattern for 25(OH)D concentrations . Each 10 nmol/l increase in 25(OH)D was associated with a 7 % lower risk of infection ( 95 % CI 3 , 11 % ) after adjustment for adiposity , lifestyle and socio-economic factors . For FEV1 and FVC , each 10 nmol/l increase in 25(OH)D was associated with 8 ( 95 % CI 3 , 13 ) ml and 13 ( 95 % CI 7 , 20 ) ml higher volume , respectively , after controlling for covariates . Associations of 25(OH)D with FEV1 and FVC were only slightly attenuated after further adjustment for infection and other respiratory illness . In conclusion , vitamin D status had a linear relationship with respiratory infections and lung function . R and omised controlled trials are warranted to investigate the role of vitamin D supplementation on respiratory health and to establish the underlying mechanisms Background Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections . This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections . Methodology / Findings In this prospect i ve cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults , blinded to the nature of the substance being measured . The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations . The incidence of infection in participants with different concentrations of vitamin D was determined . One hundred ninety-five ( 98.5 % ) of the enrolled participants completed the study . Light skin pigmentation , lean body mass , and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant ( p<0.0001 ) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill . Conclusions / Significance Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby , at least during the fall and winter in temperate zones . The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections , including influenza , in the general population and in sub population s with lower 25-hydroxyvitamin D concentrations , such as pregnant women , dark skinned individuals , and the obese Objective To determine the role of oral vitamin D supplementation for resolution of severe pneumonia in under-five children . Design R and omized , double blind , placebo-controlled trial . Setting In patients from a tertiary care hospital . Participants Two hundred children [ mean ( SD ) age : 13.9 ( 11.7 ) months ; boys : 120 ] between 2 months to 5 years with severe pneumonia . Pneumonia was diagnosed in the presence of fever , cough , tachypnea ( as per WHO cut-offs ) and crepitations . Children with pneumonia and chest indrawing or at least one of the danger sign ( inability to feed , lethargy , cyanosis ) were diagnosed as having severe pneumonia . The two groups were comparable for baseline characteristics including age , anthropometry , socio-demographic profile , and clinical and laboratory parameters . InterventionOral vitamin D ( 1000 IU for < 1 year and 2000 IU for > 1 year ) ( n=100 ) or placebo ( lactose ) ( n=100 ) once a day for 5 days , from enrolment . Both the groups received antibiotics as per the Indian Academy of Pediatrics guidelines , and supportive care ( oxygen , intravenous fluids and monitoring ) . Outcome variables Primary : time to resolution of severe pneumonia . Secondary : duration of hospitalization and time to resolution of tachypnea , chest retractions and inability to feed . Results Median duration ( SE , 95 % CI ) of resolution of severe pneumonia was similar in the two groups [ vitamin D : 72 ( 3.7 , 64.7–79.3 ) hours ; placebo : 64 ( 4.5 , 55.2–72.8 ) hours ] . Duration of hospitalization and time to resolution of tachypnea , chest retractions , and inability to feed were also comparable between the two groups . ConclusionS hort-term supplementation with oral vitamin D ( 1000–2000 IU per day for 5 days ) has no beneficial effect on resolution of severe pneumonia in under-five children . Further studies need to be conducted with higher dose of Vitamin D or longer duration of supplementation to corroborate these findings Observational studies identified associations between vitamin D insufficiency ( serum 25(OH)D < 30ng·ml-1 ) and risk of upper respiratory infection ( URI ) .  Swimmers are highly prone to URIs , which might hinder their performance . The aim of this study was to examine if vitamin D3 supplementation reduces URI burden in vitamin D-insufficient swimmers . Fifty-five competitive adolescent swimmers with vitamin D insufficiency were r and omized to receive vitamin D3 ( 2,000IU·d-1 ) or placebo for 12 winter weeks . A URI symptom question naire was completed weekly . Serum 25(OH)D concentrations were measured by radio-immunoassay before and after supplementation . We used linear regression to examine the relation between the change in 25(OH)D concentrations during the trial , and the duration and severity of URIs . There were no between-group differences in the frequency , severity , or duration of URIs . Exploratory analyses revealed that in the placebo group only , the change in 25(OH)D concentrations during the trial was highly associated with the duration of URIs ( r = -0.90,p < .001 ) , and moderately associated with the severity of URIs ( r = -0.65,p = .043 ) . The between-group differences for duration  were highly significant . Vitamin D3 supplementation in adolescent swimmers with vitamin D insufficiency did not reduce URI burden . However , larger decreases in serum 25(OH)D concentrations were associated with significantly longer and more severe URI episodes Rationale Pulmonary rehabilitation is an important treatment for patients with Chronic Obstructive Pulmonary Disease , who are often vitamin D deficient . As vitamin D status is linked to skeletal muscle function , we aim ed to explore if high dose vitamin D supplementation can improve the outcomes of rehabilitation in Chronic Obstructive Pulmonary Disease . Material and methods This study is a post-hoc subgroup analysis of a larger r and omized trial comparing a monthly dose of 100.000 IU of vitamin D with placebo to reduce exacerbations . 50 Subjects who followed a rehabilitation program during the trial are included in this analysis . We report changes from baseline in muscle strength and exercise performance between both study arms after 3 months of rehabilitation . Results Vitamin D intervention result ed in significantly higher median vitamin D levels compared to placebo ( 51 [ 44 - 62 ] ng/ml vs 15 [ 13 - 30 ] ng/ml ; p < 0.001 ) . Patients receiving vitamin D had significantly larger improvements in inspiratory muscle strength ( -11±12 cmH2O vs 0±14 cmH2O ; p = 0.004 ) and maximal oxygen uptake ( 110±211 ml/min vs -20±187 ml/min ; p = 0.029 ) . Improvements in quadriceps strength ( 15±16 Nm ) or six minutes walking distance ( 40±55 meter ) were not significantly different from the effects in the placebo group ( 7±19 Nm and 11±74 meter ; p>0.050 ) . Conclusion High dose vitamin D supplementation during rehabilitation may have mild additional benefits to training BACKGROUND R and omized controlled trials testing the association between vitamin D status and upper respiratory tract infection ( URTI ) have given mixed results . During a multicenter , r and omized controlled trial of colorectal adenoma chemoprevention , we tested whether 1000 IU/day vitamin D(3 ) supplementation reduced winter episodes and duration of URTI and its composite syndromes , influenza-like illness ( ILI ; fever and ≥2 of sore throat , cough , muscle ache , or headache ) and colds ( no fever , and ≥2 of runny nose , nasal congestion , sneezing , sore throat , cough , swollen or tender neck gl and s ) . METHODS The 2259 trial participants were aged 45 - 75 , in good health , had a history of colorectal adenoma , and had a serum 25-hydroxyvitamin D level ≥12 ng/mL. They were r and omized to vitamin D(3 ) ( 1000 IU/day ) , calcium ( 1200 mg/day ) , both , or placebo . Of these , 759 participants completed daily symptom diaries . Secondary data included semiannual surveys of all participants . RESULTS Among those who completed symptom diaries , supplementation did not significantly reduce winter episodes of URTI ( rate ratio [ RR ] , 0.93 ; 95 % confidence interval [ CI ] , .79 - 1.09 ) including colds ( RR , 0.93 ; 95 % CI , .78 - 1.10 ) or ILI ( RR , 0.95 ; 95 % CI , .62 - 1.46 ) , nor did it reduce winter days of illness ( RR , 1.13 ; 95 % CI , .90 - 1.43 ) . There was no significant benefit according to adherence , influenza vaccination , body mass index , or baseline vitamin D status . Semiannual surveys of all participants ( N = 2228 ) identified no benefit of supplementation on ILI ( odds ratio [ OR ] , 1.14 ; 95 % CI , .84 - 1.54 ) or colds ( OR , 1.03 ; 95 % CI , .87 - 1.23 ) . CONCLUSIONS Supplementation with 1000 IU/day vitamin D(3 ) did not significantly reduce the incidence or duration of URTI in adults with a baseline serum 25-hydroxyvitamin D level ≥12 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 serum levels of 25-hydroxyvitamin D3 are associated with an increased risk of respiratory tract infections ( RTIs ) . Clinical trials with vitamin D3 against various infections have been carried out but data are so far not conclusive . Thus , there is a need for additional r and omised controlled trials of effects of vitamin D3 on infections . Objective To investigate if supplementation with vitamin D3 could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs . Design A double-blind r and omised controlled trial . Setting Karolinska University Hospital , Huddinge . Participants 140 patients with antibody deficiency ( selective IgA subclass deficiency , IgG subclass deficiency , common variable immune disorder ) and patients with increased susceptibility to RTIs ( > 4 bacterial RTIs/year ) but without immunological diagnosis . Intervention Vitamin D3 ( 4000 IU ) or placebo was given daily for 1 year . Primary and secondary outcome measures The primary endpoint was an infectious score based on five parameters : symptoms from respiratory tract , ears and sinuses , malaise and antibiotic consumption . Secondary endpoints were serum levels of 25-hydroxyvitamin D3 , microbiological findings and levels of antimicrobial peptides ( LL-37 , HNP1–3 ) in nasal fluid . Results The overall infectious score was significantly reduced for patients allocated to the vitamin D group ( 202 points ) compared with the placebo group ( 249 points ; adjusted relative score 0.771 , 95 % CI 0.604 to 0.985 , p=0.04 ) . Limitations A single study centre , small sample size and a selected group of patients . The sample size calculation was performed using p=0.02 as the significance level whereas the primary and secondary endpoints were analysed using the conventional p=0.05 as the significance level . Conclusions Supplementation with vitamin D3 may reduce disease burden in patients with frequent RTIs BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) OBJECTIVE To evaluate the impact of large-dose vitamin A supplementation given to infants > 6 months old ( 200000 IU ) and to preschool children aged 1 - 4 years ( 400000 IU ) during a pneumonia episode , on their subsequent morbidity and severe morbidity . METHOD In a r and omized , double-blind , placebo controlled trial , the children were followed-up with 2-weekly visits at home for 16 weeks , with the first visit 2 weeks after treatment for pneumonia was initiated . The field workers asked about the presence of morbidity on the day of the visit and in the previous two weeks and about the occurrence and number of clinic attendances and hospital admissions since the last visit . They also measured the patients respiratory rate and temperature and assessed the children for the presence of cyanosis , chest indrawing and wheezing . RESULTS Except for the prevalence of diet refusal which was higher in the vitamin A group , no differences between the study groups were observed , either in the prevalence of morbidity or in the incidence of clinic attendances and hospital admissions . CONCLUSION No evidence was found for a beneficial effect of vitamin A given during acute pneumonia on the subsequent morbidity and severe morbidity of children in a population with marginal vitamin A deficiency Importance Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections . However , whether winter supplementation of vitamin D reduces the risk among children is unknown . Objective To determine whether high-dose vs st and ard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children . Design , Setting , and Participants A r and omized clinical trial was conducted during the winter months between September 13 , 2011 , and June 30 , 2015 , among children aged 1 through 5 years enrolled in TARGet Kids ! , a multisite primary care practice –based research network in Toronto , Ontario , Canada . Interventions Three hundred forty-nine participants were r and omized to receive 2000 IU/d of vitamin D oral supplementation ( high-dose group ) vs 354 participants who were r and omized to receive 400 IU/d ( st and ard-dose group ) for a minimum of 4 months between September and May. Main Outcome Measures The primary outcome was the number of laboratory-confirmed viral upper respiratory tract infections based on parent-collected nasal swabs over the winter months . Secondary outcomes included the number of influenza infections , noninfluenza infections , parent-reported upper respiratory tract illnesses , time to first upper respiratory tract infection , and serum 25-hydroxyvitamin D levels at study termination . Results Among 703 participants who were r and omized ( mean age , 2.7 years , 57.7 % boys ) , 699 ( 99.4 % ) completed the trial . The mean number of laboratory-confirmed upper respiratory tract infections per child was 1.05 ( 95 % CI , 0.91 - 1.19 ) for the high-dose group and 1.03 ( 95 % CI , 0.90 - 1.16 ) for the st and ard-dose group , for a between-group difference of 0.02 ( 95 % CI , −0.17 to 0.21 ) per child . There was no statistically significant difference in number of laboratory-confirmed infections between groups ( incidence rate ratio [ RR ] , 0.97 ; 95 % CI , 0.80 - 1.16 ) . There was also no significant difference in the median time to the first laboratory-confirmed infection : 3.95 months ( 95 % CI , 3.02 - 5.95 months ) for the high-dose group vs 3.29 months ( 95 % CI , 2.66 - 4.14 months ) for the st and ard-dose group , or number of parent-reported upper respiratory tract illnesses between groups ( 625 for high-dose vs 600 for st and ard-dose groups , incidence RR , 1.01 ; 95 % CI , 0.88 - 1.16 ) . At study termination , serum 25-hydroxyvitamin D levels were 48.7 ng/mL ( 95 % CI , 46.9 - 50.5 ng/mL ) in the high-dose group and 36.8 ng/mL ( 95 % CI , 35.4 - 38.2 ng/mL ) in the st and ard-dose group . Conclusions and Relevance Among healthy children aged 1 to 5 years , daily administration of 2000 IU compared with 400 IU of vitamin D supplementation did not reduce overall wintertime upper respiratory tract infections . These findings do not support the routine use of high-dose vitamin D supplementation in children for the prevention of viral upper respiratory tract infections . Trial Registration clinical trials.gov Identifier : Vitamin D has been shown to be an important immune system regulator . Vitamin D insufficiency during winter may cause increased susceptibility to upper respiratory tract infections ( URIs ) . To determine whether vitamin D supplementation during the winter season prevents or decreases URI symptoms , 162 adults were r and omized to receive 50 microg vitamin D3 ( 2000 IU ) daily or matching placebo for 12 weeks . A bi-weekly question naire was used to record the incidence and severity of URI symptoms . There was no difference in the incidence of URIs between the vitamin D and placebo groups ( 48 URIs vs. 50 URIs , respectively , P=0.57 ) . There was no difference in the duration or severity of URI symptoms between the vitamin D and placebo groups [ 5.4+/-4.8 days vs. 5.3+/-3.1 days , respectively , P=0.86 ( 95 % CI for the difference in duration -1.8 to 2.1 ) ] . The mean 25-hydroxyvitamin D level at baseline was similar in both groups ( 64.3+/-25.4 nmol/l in the vitamin D group ; 63.0+/-25.8 nmol/l in the placebo group ; n.s . ) . After 12 weeks , 25-hydroxyvitamin D levels increased significantly to 88.5+/-23.2 nmol/l in the vitamin D group , whereas there was no change in vitamin D levels in the placebo group . There was no benefit of vitamin D3 supplementation in decreasing the incidence or severity of symptomatic URIs during winter . Further studies are needed to determine the role of vitamin D in infection Summary Background Vitamin D has a role in regulating immune function , and its deficiency is a suggested risk factor for childhood pneumonia . Our aim was to assess whether oral supplementation of vitamin D3 ( cholecalciferol ) will reduce the incidence and severity of pneumonia in a high-risk infant population . Methods We did a r and omised placebo-controlled trial to compare oral 100 000 IU ( 2·5 mg ) vitamin D3 with placebo given to children aged 1–11 months in Kabul , Afghanistan . R and omisation was by use of a computer-generated list . Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months . Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically . Our primary outcome was the first or only episode of radiologically confirmed pneumonia . Our analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00548379 . Findings 1524 children were assigned to receive vitamin D3 and 1522 placebo .  There was no significant difference between the incidence of first or only pneumonia between the vitamin D ( 0·145 per child per year , 95 % CI 0·129–0·164 ) and the placebo group ( 0.137 , 0·121–0·155 ) ; the incidence rate ratio was 1·06 ( 95 % CI 0·89–1·27 ) . From 652 children during five separate periods of testing serum calcifediol , only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group — a toxic level . Interpretations Quarterly bolus doses of oral vitamin D3 supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting . Funding Wellcome Trust and British Council A r and omised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections ( bronchitis and bronchopneumonia ) . Patients were assessed clinical ly and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day , or placebo . This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection . Using a clinical scoring system based on major symptoms of the respiratory condition , patients supplemented with the vitamin fared significantly better than those on placebo . This was particularly the case for those commencing the trial most severely ill , many of whom had very low plasma and white cell vitamin C concentrations on admission . Various mechanisms by which vitamin C could assist this type of patient are discussed BACKGROUND Studies on the effect of vitamin A supplementation on growth have yielded various results . It is possible that such growth is dependent on the burden of infectious diseases in the population . METHODS We analysed data from a r and omized , double-masked , placebo-controled trial to examine the role of respiratory infections and diarrhoea in modifying the growth response to vitamin A supplementation . A single high dose of vitamin A or placebo was given every 4 months to 1405 children aged 6 - 48 months , and 4430 child treatment cycles were used in this analysis . RESULTS Vitamin A supplementation modestly improved linear but not ponderal growth of children who experienced little respiratory infection and especially of those who had vitamin A intake below the normative requirement ( < 400 RE/day ) . Children who received vitamin A and were free of respiratory infection grew 0.22 cm/4 months ( 95 % CI : 0.08 , 0.37 ) more in height than the placebo group , but those with > or = 21.5 % of days of respiratory infection did not show a significant growth response to vitamin A supplementation . Children who experienced no respiratory infection and had vitamin A intake < 400 RE/day benefited most , gaining 0.31 cm/4 months ( 95 % CI : 0.10 , 0.52 ) more in height compared to the placebo group . Diarrhoea was associated with poorer growth , but did not significantly modify the effect of  vitamin A supplementation  on growth . CONCLUSIONS Vitamin A supplementation improves the linear growth of children who have a low intake of vitamin A but this impact is muted with increasing levels of respiratory infections Patients with cystic fibrosis ( CF ) suffer from chronic lung infection and inflammation leading to respiratory failure . Vitamin D deficiency is common in patients with CF , and correction of vitamin D deficiency may improve innate immunity and reduce inflammation in patients with CF . We conducted a double-blinded , placebo-controlled , r and omized clinical trial of high-dose vitamin D to assess the impact of vitamin D therapy on antimicrobial peptide concentrations and markers of inflammation . We r and omized 30 adults with CF hospitalized with a pulmonary exacerbation to 250 000 IU of cholecalciferol or placebo  , and evaluated changes in plasma concentrations of inflammatory markers and the antimicrobial peptide LL-37 at baseline and 12 weeks post intervention . In the vitamin D group , there was a 50.4 % reduction in tumor necrosis factor-α ( TNF-α ) at 12 weeks ( P<0.01 ) , and there was a trend for a 64.5 % reduction in interleukin-6 ( IL-6 ) ( P=0.09 ) . There were no significant changes in IL-1β , IL-8 , IL-10 , IL-18BP and NGAL ( neutrophil gelatinase-associated lipocalin ) . We conclude that a large bolus dose of vitamin D is associated with reductions in two inflammatory cytokines , IL-6 and TNF-α . This study supports the concept that vitamin D may help regulate inflammation in CF , and that further research is needed to eluci date the potential mechanisms involved and the impact on clinical outcomes
Conclusions Vitamin D supplementation  was safe and it protected against acute respiratory tract infection overall .
Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit .
Objectives To assess the overall effect of vitamin D supplementation on  risk of acute respiratory tract infection  , and to identify factors modifying this effect .