title: High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Effect of weekly vitamin D supplements on mortality, morbidity, and growth of low birthweight term infants in India up to age 6 months: randomised controlled trial Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Infection in Mongolia High‐Dose Monthly Vitamin D for Prevention of Acute Respiratory Infection in Older Long‐Term Care Residents: A Randomized Clinical Trial Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Vitamin D₃ Supplementation in Batswana Children and Adults with HIV: A Pilot Double Blind Randomized Controlled Trial Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Vitamin D3 and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs) Vitamin D Supplementation Reduces the Risk of Acute Otitis Media in Otitis-prone Children Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults. Effect of vitamin D supplementation on antibiotic use: a randomized controlled trial. Effects of vitamin D supplements on influenza A illness during the 2009 H1N1 pandemic: a randomized controlled trial. A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Vitamin D supplementation and upper respiratory tract infections in adolescent swimmers: a randomized controlled trial. Improved control of childhood asthma with low‐dose, short‐term vitamin D supplementation: a randomized, double‐blind, placebo‐controlled trial Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial.
abstract: 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 ) 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 Objective To investigate whether vitamin D supplementation can decrease the mortality and morbidity of low birthweight infants in low income countries . Design R and omised controlled trial . Setting Large government hospital in New Delhi , India . Participants 2079 low birthweight infants born at term ( > 37 weeks ’ gestation ) . Main outcome measures Primary outcome was admission to hospital or death during the first six months of life . Main secondary outcome was growth . Interventions Weekly vitamin D supplements for six months at a dose of one recommended nutrient intake per day ( 35 µg/week ) . Infants were visited weekly at home for observed supplementation and were brought to the clinic monthly for clinical examination and anthropometric measurements . Results Between group differences were not significant for death or hospital admissions ( 92 among 1039 infants in the vitamin D group v 99 among 1040 infants in the placebo group ; adjusted rate ratio 0.93 , 95 % confidence interval 0.68 to 1.29 ; P=0.68 ) , or referral to the outpatient clinic for moderate morbidity  . Vitamin D supplementation result ed in better vitamin D status as assessed by plasma calcidiol levels at six months . In adjusted analyses , vitamin D treatment significantly increased st and ard deviation ( z ) scores at six months for weight , length , and arm circumference and decreased the proportion of children with stunted growth ( length for age z score ≤2 ) or with arm circumference z scores of 2 or less . Conclusion A weekly dose of vitamin D result ed in better vitamin D status and benefited the classic vitamin D function of bone growth but did not decrease the incidence of severe morbidity or death among young low birthweight infants . Trial registration Clinical Trials.gov NCT00415402 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 OBJECTIVE : Observational studies suggest that serum levels of 25-hydroxyvitamin D ( 25[OH]D ) are inversely associated with acute respiratory infections ( ARIs ) . We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs . METHODS : By using cluster r and omization , classrooms of 744 Mongolian schoolchildren were r and omly assigned to different treatments in winter ( January – March ) . This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk ( control ; n = 104 ) or milk fortified with 300 IU of vitamin D3 ( n = 143 ) . This comparison was double-blinded . The primary outcome was the number of parent-reported ARIs over the past 3 months . RESULTS : At baseline , the median serum 25(OH)D level was 7 ng/mL ( interquartile range : 5–10 ng/mL ) . At the end of the trial , follow-up was 99 % ( n = 244 ) , and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different ( 7 vs 19 ng/mL ; P < .001 ) . Compared with controls , children receiving vitamin D reported significantly fewer ARIs during the study period ( mean : 0.80 vs 0.45 ; P = .047 ) , with a rate ratio of 0.52 ( 95 % confidence interval : 0.31–0.89 ) . Adjusting for age , gender , and history of wheezing , vitamin D continued to halve the risk of ARI ( rate ratio : 0.50 [ 95 % confidence interval : 0.28–0.88 ] ) . Similar results were found among children either below or above the median 25(OH)D level at baseline ( rate ratio : 0.41 vs 0.57 ; Pinteraction = .27 ) . CONCLUSIONS : Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency OBJECTIVES To determine the efficacy and safety of high-dose vitamin D supplementation for prevention of acute respiratory infection ( ARI ) in older long-term care residents . DESIGN R and omized controlled trial investigating high-dose vs st and ard-dose vitamin D from 2010 to 2014 . SETTING Colorado long-term care facilities . PARTICIPANTS Long-term care residents aged 60 and older ( n = 107 ) . INTERVENTION The high-dose group received monthly supplement of vitamin D3 100,000 IU , the st and ard-dose group received a monthly placebo ( for participants taking 400 - 1,000 IU/d as part of usual care ) or a monthly supplement of 12,000 IU of vitamin D3 ( for participants taking < 400 IU/d as part of usual care ) . MEASUREMENTS The primary outcome was incidence of ARI during the 12-month intervention . Secondary outcomes were falls and fractures , 25-hydroxyvitamin D levels , hypercalcemia , and kidney stones . RESULTS Participants ( 55 high dose , 52 st and ard dose ) were r and omized and included in the final analysis . The high-dose group had 0.67 ARIs per person-year and the st and ard-dose group had 1.11 ( incidence rate ratio ( IRR ) = 0.60 , 95 % confidence interval ( CI ) = 0.38 - 0.94 , P = .02 ) . Falls were more common in the high-dose group ( 1.47 per person-year vs 0.63 in st and ard-dose group ; IRR = 2.33 , 95 % CI = 1.49 - 3.63 , P < .001 ) . Fractures were uncommon and similar in both groups ( high dose 0.10 vs st and ard dose 0.19 per person-year ; P = .31 ) . Mean trough 25-hydroxyvitamin D levels during the trial were 32 . ng/mL in the high-dose group and 25.1 ng/mL in the st and ard-dose group . There was no hypercalcemia or kidney stones in either group . CONCLUSION Monthly high-dose vitamin D3 supplementation reduced the incidence of ARI in older long-term care residents but was associated with a higher rate of falls without an increase in fractures BACKGROUND To our knowledge , no rigorously design ed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza . OBJECTIVE We investigated the effect of vitamin D supplements on the incidence of  seasonal influenza A in schoolchildren . DESIGN From December 2008 through March 2009 , we conducted a r and omized , double-blind , placebo-controlled trial comparing vitamin D(3 ) supplements ( 1200 IU/d ) with placebo  in schoolchildren . The primary outcome was the incidence of influenza A , diagnosed with influenza antigen testing with a nasopharyngeal swab specimen . RESULTS Influenza A occurred in 18 of 167 ( 10.8 % ) children in the vitamin D(3 ) group compared with 31 of 167 ( 18.6 % ) children in the  placebo  group [ relative risk ( RR ) , 0.58 ; 95 % CI : 0.34 , 0.99 ; P = 0.04 ] . The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements ( RR : 0.36 ; 95 % CI : 0.17 , 0.79 ; P = 0.006 ) and who started nursery school after age 3 y ( RR : 0.36 ; 95 % CI : 0.17 , 0.78 ; P = 0.005 ) . In children with a previous diagnosis of asthma , asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D(3 ) compared with 12 children receiving placebo ( RR : 0.17 ; 95 % CI : 0.04 , 0.73 ; P = 0.006 ) . CONCLUSION This study suggests that vitamin D(3 ) supplementation during the winter may reduce the incidence of influenza A , especially in specific subgroups of schoolchildren . This trial was registered at https://center.umin.ac.jp as UMIN000001373 Objectives Since vitamin D insufficiency is common worldwide in people with HIV , we explored safety and efficacy of high dose cholecalciferol ( D₃ )  in Botswana , and evaluated potential modifiers of serum 25 hydroxy vitamin D change ( Δ25D ) . Design Prospect i ve r and omized double-blind 12-week pilot trial of subjects ages 5.0–50.9 years . Methods Sixty subjects r and omized within five age groups to either 4000 or 7000IU per day of D₃  and evaluated for vitamin D , parathyroid hormone , HIV , safety and growth status . Efficacy was defined as serum 25 hydroxy vitamin D ( 25D ) ≥32ng/mL , and safety as no simultaneous elevation of serum calcium and 25D . Also assessed were HIV plasma viral RNA viral load ( VL ) , CD4 % , anti-retroviral therapy ( ART ) regime , and height-adjusted ( HAZ ) , weight-adjusted ( WAZ ) and Body Mass Index ( BMI Z ) Z scores . Results Subjects were 50 % male , age ( mean±SD ) 19.5±11.8 years , CD4 % 31.8±10.4 , with baseline VL log₁₀ range of < 1.4 to 3.8 and VL detectable ( > 1.4 ) in 22 % . From baseline to 12 weeks , 25D increased from 36±9ng/ml to 56±18ng/ml ( p<0.0001 ) and 68 % and 90 % had 25D ≥32ng/ml , respectively ( p = 0.02 ) . Δ25D was similar by dose . No subjects had simultaneously increased serum calcium and 25D . WAZ and BMI Z improved by 12 weeks ( p<0.04 ) . HAZ and CD4 % increased and VL decreased in the 7000IU/d group ( p<0.04 ) . Younger ( 5–13y ) and older ( 30–50y ) subjects had greater Δ25D than those 14–29y ( 26±17 and 28±12 vs. 11±11ng/ml , respectively , p≤0.001 ) . Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment ( 22±12 , 27±17 , vs. 13±10 , respectively , p≤0.03 ) . Conclusions In a pilot study in Botswana , 12-week high dose D₃ supplementation was safe and improved vitamin D , growth and HIV status ; age and ART regimen were significant effect modifiers . Trial Registration Clinical Trials.gov CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 Background We undertook a 2X2 factorial , r and omized controlled trial ( RCT ) to assess whether vitamin D3 supplementation ( 10,000 international units per week ) versus placebo and gargling versus no gargling could prevent  viral  ,  clinical upper respiratory tract infection ( URTI ) in university students . Methods We r and omized 600 students into 4 treatment arms : 1 ) vitamin D3 and gargling , 2 ) placebo and gargling , 3 ) vitamin D3 and no gargling , and 4 ) placebo and no gargling . Students completed weekly electronic surveys and su bmi tted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011 . Symptomatic students also completed an electronic symptom diary . The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively . Results Of 600 participants , 471 ( 78.5 % ) completed all surveys while 43 ( 7.2 % ) completed none ; 150 ( 25.0 % ) reported clinical URTI . Seventy participants ( 23.3 % ) r and omized to vitamin D3 reported clinical URTI compared to 80 ( 26.7 % ) r and omized to placebo ( RR:0.79 , CI95:0.61 - 1.03 , p = 0.09 ) . Eighty-five participants ( 28.3 % ) r and omized to gargling reported clinical URTI compared to 65 participants ( 21.7 % ) r and omized to the no gargling arm ( RR:1.3 , CI95:0.92 - 1.57 , p = 0.19 ) . Laboratory testing identified 70 infections ( 46.7 per 100 URTIs ) . Vitamin D3 treatment was associated with a significantly lower risk for laboratory confirmed URTI ( RR : 0.54 , CI95:0.34 - 0.84 , p = 0.007 ) and with a significantly lower mean viral load measured as log10 viral copies/mL ( mean difference : -0.89 , CI95 : -1.7 , -0.06 , p = 0.04 ) . Fewer students assigned to gargling experienced laboratory confirmed URTI , however this was not statistically significant ( RR:0.82 , CI95:0.53 - 1.26 , p = 0.36 ) . Conclusions These results suggest that vitamin D3 is a promising intervention for the prevention of URTI . Vitamin D3 significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections . Trial registration Clinical Trials Registration : NCT01158560 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 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 OBJECTIVES To determine whether ( i ) supplementation of oral 100,000 iu of vitamin D(3 ) ( cholecalciferol ) along with antibiotics will reduce the duration of illness in children with pneumonia ; ( ii ) supplementation will reduce the risk of repeat episodes . METHODS Double-blind individually r and omised placebo-controlled trial in an inner-city hospital in Kabul , of 453 children aged 1 - 36 months , diagnosed with non-severe or severe pneumonia at the outpatient clinic . Children with rickets , other concurrent severe diseases , very severe pneumonia or wheeze , were excluded . Children were given vitamin D(3 ) or placebo drops additional to routine pneumonia treatment . RESULTS Two hundred and twenty-four children received vitamin D(3 ; ) and 229 received placebo .  There was no significant difference in the mean number of days to recovery between the vitamin D(3 ) ( 4.74 days ; SD 2.22 ) and placebo arms ( 4.98 days ; SD 2.89 ; P = 0.17 ) . The risk of a repeat episode of pneumonia within 90 days of supplementation was lower in the intervention ( 92/204 ; 45 % ) than the placebo group [ 122/211 ; ( 58 % ; relative risk 0.78 ; 95 % CI 0.64 , 0.94 ; P = 0.01 ] . Children in the vitamin D(3 ) group survived longer without experiencing a repeat episode ( 72 days vs. 59 days ; HR 0.71 ; 95 % CI 0.53 - 0.95 ; P = 0.02 ) . CONCLUSION A single high-dose oral vitamin D(3 ) supplementation to young children along with antibiotic treatment for pneumonia could reduce the occurrence of repeat episodes of pneumonia BACKGROUND Recent studies suggest a role for vitamin D in innate immunity , including the prevention of respiratory tract infections ( RTIs ) . We hypothesize that serum 25-hydroxyvitamin D ( 25[OH]D ) levels are inversely associated with self-reported recent upper RTI ( URTI ) . METHODS We performed a secondary analysis of the Third National Health and Nutrition Examination Survey , a probability survey of the US population conducted between 1988 and 1994 . We examined the association between 25(OH)D level  and  recent URTI in 18 883 participants 12 years and older . The analysis adjusted for demographics and clinical factors ( season , body mass index , smoking history , asthma , and chronic obstructive pulmonary disease ) . RESULTS The median serum 25(OH)D level was 29 ng/mL ( to convert to nanomoles per liter , multiply by 2.496 ) ( interquartile range , 21 - 37 ng/mL ) , and 19 % ( 95 % confidence interval [ CI ] , 18%-20 % ) of participants reported a recent URTI . Recent URTI was reported by 24 % of participants with 25(OH)D levels less than 10 ng/mL , by 20 % with levels of 10 to less than 30 ng/mL , and by 17 % with levels of 30 ng/mL or more ( P < .001 ) . Even after adjusting for demographic and clinical characteristics , lower 25(OH)D levels were independently associated with recent URTI ( compared with 25[OH]D levels of > or = 30 ng/mL : odds ratio [ OR ] , 1.36 ; 95 % CI , 1.01 - 1.84 for < 10 ng/mL and 1.24 ; 1.07 - 1.43 for 10 to < 30 ng/mL ) . The association between 25(OH)D level and URTI seemed to be stronger in individuals with asthma and chronic obstructive pulmonary disease ( OR , 5.67 and 2.26 , respectively ) . CONCLUSIONS Serum 25(OH)D levels are inversely associated with recent URTI . This association may be stronger in those with respiratory tract diseases . R and omized controlled trials are warranted to explore the effects of vitamin D supplementation on RTI 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 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 : The aim of this study was to evaluate whether a deficit in vitamin D ( VD ) is associated with an increased risk of recurrent acute otitis media ( AOM ) and whether VD supplementation is effective in reducing the number of AOM episodes in otitis-prone children . Methods : A total of 116 children with a history of recurrent AOM ( ≥3 episodes in preceding 6 months or ≥4 episodes in preceding 12 months ) were prospect ively and blindly r and omized to receive oral VD 1000 IU/d or placebo for 4 months . Episodes of AOM were monitored for 6 months . Results : Fifty-eight children received placebo and 58 with similar characteristics were treated with VD . The number of children experiencing ≥1 AOM episode during the study period was significantly lower in the treatment group ( 26 versus 38 ; P = 0.03 ) . There was a marked difference in the number of children who developed uncomplicated AOM ( P < 0.001 ) , but no difference in the number of children with ≥1 episode of spontaneous otorrhea . The likelihood of AOM was significantly reduced in the patients whose serum VD concentrations were ≥30 ng/mL. Conclusions : VD hypovitaminosis is common in children with recurrent AOM and associated with an increase in the occurrence of AOM when serum 25(OH)D levels are < 30 ng/mL. The administration of VD in a dosage of 1000 IU/d restores serum values of ≥30 ng/mL in most cases and is associated with a significant reduction in the risk of uncomplicated AOM CONTEXT Observational studies have reported an inverse association between serum 25-hydroxyvitamin D ( 25-OHD ) levels and incidence of upper respiratory tract infections ( URTIs ) . However , results of clinical trials of vitamin D supplementation have been inconclusive . OBJECTIVE To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch , New Zeal and . INTERVENTION Participants were r and omly assigned to receive an initial dose of 200,000 IU oral vitamin D3 , then 200,000 IU 1 month later , then 100,000 IU monthly ( n = 161 ) , or placebo administered in an identical dosing regimen ( n = 161 ) , for a total of 18 months . MAIN OUTCOME MEASURES The primary end point was number of URTI episodes . Secondary end points were duration of URTI episodes , severity of URTI episodes , and number of days of missed work due to URTI episodes . RESULTS The mean baseline 25-OHD level of participants was 29 ( SD , 9 ) ng/mL. Vitamin D supplementation result ed in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study . There were 593 URTI episodes in the vitamin D group and 611 in the placebo group , with no statistically significant differences in the number of URTIs per participant ( mean , 3.7 per person in the vitamin D group and 3.8 per person in the placebo group ; risk ratio , 0.97 ; 95 % CI , 0.85 - 1.11 ) , number of days of missed work as a result of URTIs ( mean , 0.76 days in each group ; risk ratio , 1.03 ; 95 % CI , 0.81 - 1.30 ) , duration of symptoms per episode ( mean , 12 days in each group ; risk ratio , 0.96 ; 95 % CI , 0.73 - 1.25 ) , or severity of URTI episodes . These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels . CONCLUSION In this trial , monthly administration of 100,000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12609000486224 CONTEXT AND OBJECTIVE Suboptimal vitamin D status can be corrected by vitamin D supplementation , but individual responses to supplementation vary . We aim ed to examine genetic and nongenetic determinants of change in serum 25-hydroxyvitamin D ( 25(OH)D ) after supplementation . DESIGN AND PARTICIPANTS We used data from a pilot r and omized controlled trial in which 644 adults aged 60 to 84 years were r and omly assigned to monthly doses of placebo , 30 000 IU , or 60 000 IU vitamin D3 for 12 months . Baseline characteristics were obtained from a self-administered question naire . Eighty-eight single-nucleotide polymorphisms ( SNPs ) in 41 c and i date genes were genotyped using Sequenom MassArray technology . Serum 25(OH)D levels before and after the intervention were measured using the Diasorin Liaison platform immunoassay . We used linear regression models to examine associations between genetic and nongenetic factors and change in serum 25(OH)D levels . RESULTS Supplement dose and baseline 25(OH)D level explained 24 % of the variability in response to supplementation . Body mass index , self-reported health status , and ambient UV radiation made a small additional contribution . SNPs in CYP2R1 , IRF4 , MC1R , CYP27B1 , VDR , TYRP1 , MCM6 , and HERC2 were associated with change in 25(OH)D level , although only CYP2R1 was significant after adjustment for multiple testing . Models including SNPs explained a similar proportion of variability in response to supplementation as models that included personal and environmental factors . CONCLUSION Stepwise regression analyses suggest that genetic variability may be associated with response to supplementation , perhaps suggesting that some people might need higher doses to reach optimal 25(OH)D levels or that there is variability in the physiologically normal level of BACKGROUND Observational data suggested that supplementation with vitamin D could reduce risk of infection , but trial data are inconsistent . OBJECTIVE We aim ed to examine the effect of oral vitamin D supplementation on antibiotic use . DESIGN We conducted a post hoc analysis of data from pilot D-Health , which is a r and omized trial carried out in a general community setting between October 2010 and February 2012 . A total of 644 Australian residents aged 60 - 84 y were r and omly assigned to receive monthly doses of a placebo ( n = 214 ) or 30,000 ( n = 215 ) or 60,000 ( n = 215 ) IU oral cholecalciferol for ≤12 mo . Antibiotics prescribed during the intervention period were ascertained by linkage with pharmacy records through the national health insurance scheme ( Medicare Australia ) . RESULTS People who were r and omly assigned 60,000 IU cholecalciferol had nonsignificant 28 % lower risk of having antibiotics prescribed at least once than did people in the placebo group ( RR : 0.72 ; 95 % CI : 0.48 , 1.07 ) . In analyses stratified by age , in subjects aged ≥70 y , there was a significant reduction in antibiotic use in the high-dose vitamin D compared with placebo groups ( RR : 0.53 ; 95 % CI : 0.32 , 0.90 ) , whereas there was no effect in participants aged < 70 y ( RR : 1.07 ; 95 % CI : 0.58 , 1.97 ) ( P-interaction = 0.1 ) . CONCLUSION Although this study was a post hoc analysis and statistically nonsignificant , this trial lends some support to the hypothesis that supplementation with 60,000 IU vitamin D/mo is associated with lower risk of infection , particularly in older adults . The trial was registered at the Australian New Zeal and Clinical Trials Registry ( anzctr.org.au ) as ACTRN12609001063202 In a prior r and omized trial , we found that the incidence of influenza A was less in the vitamin D3 group than among those on placebo , but the total incidence of either influenza A or B did not differ between groups . In this trial , the incidence of influenza A or B was less in the vitamin D3 group than in the placebo group only during the first half of the study . To eluci date whether vitamin D3 has preventive actions against influenza A , we conducted another trial during the 2009 p and emic of the H1N1 subtype of influenza A. Students ( n = 247 ) of a Japanese high school were r and omly assigned to receive vitamin D3 supplements ( n = 148 ; 2000 IU per day ) or a placebo ( n = 99 ) in a double-blind study for 2 months . The primary outcome was incidence of influenza A diagnosed by a rapid influenza diagnostic test by medical doctors . Influenza A was equally likely in the vitamin D3 group ( 20/148 : 13.5 % ) compared with the placebo group ( 12/99 : 12.1 % ) . By post hoc analysis , influenza A occurred significantly less in the vitamin D3 group ( 2/148 : 1.4 % ) compared with the placebo group ( 8/99 : 8.1 % ) ( risk ratio , 0.17 ; 95 % confidence interval , 0.04 to 0.77 ; P = 0.009 ) in the first month . However , during the second month , the vitamin D3 group experienced more events and effectively caught up with the placebo group . Vitamin D3 supplementation did not lower the overall incidence of influenza A during the 2009 H1N1 p and emic . A post hoc analysis suggests that the initial benefit during the first month of treatment was lost during the second month 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 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 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 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
target: 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 .
background: Objectives To assess the overall effect of vitamin D supplementation on  risk of acute respiratory tract infection  , and to identify factors modifying this effect .