title: High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease 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 Treatment of Vitamin D Deficiency Increases Lower Limb Muscle Strength in Institutionalized Older People Independently of Regular Physical Activity: A Randomized Double-Blind Controlled Trial Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial 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. Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Vitamin D supplementation did not prevent influenza-like illness as diagnosed retrospectively by questionnaires in subjects participating in randomized clinical trials Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. A randomized controlled trial of vitamin D3 supplementation for the prevention of symptomatic upper respiratory tract infections. Vitamin D supplementation for severe pneumonia — A randomized controlled trial Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis.
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 ) 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 Aims : To investigate the effects of a 6-month supplementation with calcium and cholecalciferol on biochemical parameters and muscle strength of institutionalized elderly . Methods : This prospect i ve , double-blind , placebo-controlled , r and omized trial included Brazilian institutionalized people ≥60 years of age receiving a 6-month supplementation ( December to May ) of daily calcium plus monthly placebo ( calcium/placebo group ) or daily calcium plus oral cholecalciferol ( 150,000 IU once a month during the first 2 months , followed by 90,000 IU once a month for the last 4 months ; calcium/vitamin D group ) . Fasting blood sample s for 25(OH)D , PTH and calcium determination were collected ( n = 56 ) and muscle tests were performed ( n = 46 ) to measure the strength of hip flexors ( SHF ) and knee extensors ( SKE ) before ( baseline ) and after the 6-month intervention ( 6 months ) . Results : Due to seasonal variations , serum 25(OH)D significantly enhanced in both groups after treatment , but the calcium/vitamin D group had significantly higher 25 (OH)D levels than the calcium/placebo group ( 84 vs. 33 % , respectively ; p < 0.0001 ) . No cases of hypercalcemia were observed . While the calcium/placebo group showed no improvement in SHF and SKE at 6 months ( p = 0.93 and p = 0.61 , respectively ) , SHF was increased in the calcium/vitamin D group by 16.4 % ( p = 0.0001 ) and SKE by 24.6 % ( p = 0.0007 ) . Conclusions : The suggested cholecalciferol supplementation was safe and efficient in enhancing 25(OH)D levels and lower limb muscle strength in the elderly , in the absence of any regular physical exercise practice 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 Calcidiol , the major circulating metabolite of vitamin D , supports induction of pleiotropic antimicrobial responses in vitro . Vitamin D supplementation elevates circulating calcidiol concentrations , and thus has a potential role in the prevention and treatment of infection . The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported . To characterize these effects , we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were r and omized to receive adjunctive high-dose vitamin D or placebo in a clinical trial , and who fulfilled criteria for per- protocol analysis . Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia , monocytosis , hypercytokinaemia , and hyperchemokinaemia . Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses , but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4 , CC chemokine lig and 5 , and IFN-α . We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment . Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community  Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33 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 Care of elderly patients after hip fracture is not well established . METHODS We enrolled 173 patients with acute hip fracture who were 65 years or older ( 79.2 % women ; mean age , 84 years ; 77.4 % living at home ) . Using a factorial design , we r and omly allocated patients to extended physiotherapy ( PT ) ( supervised 60 min/d during acute care plus an unsupervised home program ) vs st and ard PT ( supervised 30 min/d during acute care plus no home program ; single-blinded ) , and to cholecalciferol therapy , 2000 vs 800 IU/d ( double-blinded ) . Primary outcome was rate of falls ; secondary outcome was rate of hospital readmissions during the 12-month follow-up . All analyses included 173 individuals and used multivariate Poisson regression analyses . RESULTS At baseline , 50.9 % of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7 % of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions . Because this was a factorial design trial , all analyses tested the main effect of each treatment while controlling for the other in 173 participants . Extended vs st and ard PT reduced the rate of falls by 25 % ( 95 % confidence interval [ CI ] , -44 % to -1 % ) . Cholecalciferol treatment , 2000 vs 800 IU/d , did not reduce falls ( 28 % ; 95 % CI , -4 % to 68 % ) , but reduced the rate of hospital readmissions by 39 % ( 95 % CI , -62 % to -1 % ) . CONCLUSIONS Extended PT was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000 IU/d , was successful in reducing hospital readmission but not falls . Thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture 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 : Vitamin D deficiency has been associated with a number of diseases , including influenza . Whether or not this reflects a causal relationship is unknown . We therefore wanted to examine if supplementation with vitamin D would affect the incidence and severity of influenza-like disease  . Methods : Question naires on influenza were sent to subjects participating in ongoing placebo-controlled intervention studies with vitamin D supplementation , up until the end of April 2010 . Results : Five hundred and sixty-nine subjects from 10 different clinical trials were included in the study , of whom 289 were r and omized to receive vitamin D ( 1111–6800 IU/day ) and 280 to receive placebo .  Influenza-like disease during the previous fall/winter was reported in 38 subjects in the vitamin D group and 42 in the placebo group ( non-significant ) , of whom 25 and 26 subjects , respectively , fulfilled our clinical criteria for influenza . In these latter subjects , the duration of illness was significantly longer among those in the vitamin D group than among those in the placebo group ( median 7 ( range 2–60 ) days vs median 4 ( range 2–18 ) days ; p = 0.007 ) . However , this difference was not statistically significant if all 38 ( vitamin D ) and 42 ( placebo ) subjects who reported symptoms were included . Conclusion : Our results do not support the hypothesis that high doses of vitamin D supplementation will have a pronounced effect on influenza-like disease in population s not targeted for high influenza risk 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 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 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 CONTEXT The active metabolite of vitamin D , 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] , is a potent modulator of immune cells in vitro . OBJECTIVE Our objective was to determine whether the sun-dependent nutrient , cholecalciferol , can alter disease-associated cellular immune abnormalities in patients with multiple sclerosis ( MS ) . DESIGN This was an open-label , 12-month , r and omized controlled trial . SETTING Patients with MS were recruited from the MS Clinic at St. Michael 's Hospital , Toronto . PATIENTS Forty-nine patients were matched ( for age , sex , disease duration , disease-modifying drug , and disability ) and enrolled ( treated n = 25 ; control n = 24 ) . Four patients were lost to follow-up ( n = 2 from each group ) . INTERVENTION Treated patients received increasing doses of cholecalciferol ( 4,000 - 40,000 IU/d ) plus calcium ( 1200 mg/d ) , followed by equilibration to a moderate , physiological intake ( 10,000 IU/d ) . Control patients did not receive supplements . MAIN OUTCOME MEASURES At enrollment and at 12 months , peripheral blood mononuclear cell ( P BMC ) proliferative responses to disease-associated , MS-relevant , and control antigens were measured , along with selected serum biochemical markers . RESULTS At 12 months , mean serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations were 83 ± 35 nmol/liter and 179 ± 76 nmol/liter in control and treated participants , respectively ( paired t , P < 0.001 ) . Serum 1,25(OH)(2)D did not differ between baseline and 1 yr . In treated patients , 12-month P BMC proliferative responses to neuron antigens myelin basic protein and exon-2 were suppressed ( P = 0.002 ) . In controls , there were no significant changes in disease-associated P BMC responsiveness . There were no significant differences between groups in levels of selected biomarkers . INTERPRETATION MS-associated , abnormal T cell reactivities were suppressed in vivo by cholecalciferol at serum 25(OH)D concentrations higher than 100 nmol/liter
target: INTERPRETATION Results indicate that vitamin D has a protective effect against RTI , and dosing once-daily seems most effective .
background: BACKGROUND Low levels of 25-OH vitamin D are associated with  respiratory tract infection ( RTI ) .
  However , results from r and omized controlled trials are inconclusive .
  Therefore , we performed a systematic review and meta- analysis to assess the preventive effect of vitamin D supplementation on RTI .