Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial. High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis’ The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment Effect of vitamin D supplementation in type 2 diabetes patients with pulmonary tuberculosis. Rationale and design of a randomized controlled trial of the effect of retinol and vitamin D supplementation on treatment in active pulmonary tuberculosis patients with diabetes Vitamin D supplementation during rehabilitation in COPD: a secondary analysis of a randomized trial L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial Nutrient supplementation as adjunct therapy in pulmonary tuberculosis. Adjunctive micronutrient supplementation for pulmonary tuberculosis. Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. The effect of vitamin A and zinc supplementation on treatment outcomes in pulmonary tuberculosis: a randomized controlled trial. Serum 25-hydroxy-vitamin D3 concentrations increase during tuberculosis treatment in Tanzania.
RATIONALE Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis . OBJECTIVES To test whether vitamin D supplementation of patients with tuberculosis ( TB ) improved clinical outcome and reduced mortality . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau . We included 365 adult patients with TB starting antituberculosis treatment ; 281 completed the 12-month follow-up . The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment . MEASUREMENTS AND MAIN RESULTS The primary outcome was reduction in a clinical severity score ( TBscore ) for all patients with pulmonary TB . The secondary outcome was 12-month mortality . No serious adverse effects were reported ; mild hypercalcemia was rare and present in both arms . Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo .  Overall mortality was 15 % ( 54 of 365 ) at 1 year of follow-up and similar in both arms ( 30 of 187 for vitamin D treated and 24 of 178 for placebo ; relative risk , 1.19 [ 0.58 - 1.95 ] ) . HIV infection was seen in 36 % ( 131 of 359 ) : 21 % ( 76 of 359 ) HIV-1 , 10 % ( 36 of 359 ) HIV-2 , and 5 % ( 19 of 357 ) HIV-1 + 2 . CONCLUSIONS Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB ; it is possible that the dose used was insufficient . Clinical trial registered with www.controlled-trials.com/is rct n ( IS RCT N35212132 ) BACKGROUND Tuberculosis , including multidrug-resistant tuberculosis ( MDR-TB ) , is a major global health problem . Individuals with tuberculosis disease commonly exhibit vitamin D deficiency , which may adversely affect immunity and the response to therapy . OBJECTIVE We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease . DESIGN The study was a double-blind , r and omized , placebo-controlled , intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi , Georgia . Subjects were r and omly assigned to receive oral vitamin D3 [ 50,000 IUs ( 1.25 mg ) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk ] or a placebo concomitant with st and ard first-line antituberculosis drugs . The primary outcome was the time for the conversion of a Mycobacterium tuberculosis ( Mtb ) sputum culture to negative . RESULTS Baseline characteristics between groups were similar . Most subjects ( 74 % ) were vitamin D deficient ( plasma 25-hydroxyvitamin D [ 25(OH)D ] concentration < 50 nmol/L ) . With vitamin D3 , plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16 . Adverse events and plasma calcium concentrations were similar between groups . In 192 subjects with culture-confirmed tuberculosis , an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [ 29 and 27 d , respectively ; HR : 0.86 ; 95 % CI : 0.63 , 1.18 ; P = 0.33 ) . Eight-week culture-conversion rates were also similar ( 84.0 % and 82.1 % for vitamin D3 and placebo , respectively ; P = 0.99 ) . CONCLUSION A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort . This trial was registered at clinical trials.gov at NCT00918086 BACKGROUND Vitamin D was used to treat tuberculosis in the pre-antibiotic era , and its metabolites induce antimycobacterial immunity in vitro . Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent . METHODS We undertook a multicentre r and omised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London , UK . 146 patients were allocated to receive  2·5 mg vitamin D(3 ) or placebo at baseline and 14 , 28 , and 42 days after starting st and ard tuberculosis treatment . The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion . Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor , and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D(3 ) . This trial is registered with Clinical Trials.gov number NCT00419068 . FINDINGS 126 patients were included in the primary efficacy analysis ( 62 assigned to intervention , 64 assigned to placebo ) . Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group ( adjusted hazard ratio 1·39 , 95 % CI 0·90 - 2·16 ; p=0.14 ) . TaqI genotype modified the effect  of vitamin D supplementation on time to sputum culture conversion ( p(interaction)=0·03 ) , with enhanced response seen only in patients with the tt genotype ( 8·09 , 95 % CI 1·36 - 48·01 ; p=0·02 ) . FokI genotype did not modify the effect of vitamin D supplementation ( p(interaction)=0·85 ) . Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group ( 95 % CI for difference 68·6 - 88·2 ; p<0·0001 ) . INTERPRETATION Administration of four doses of 2·5 mg vitamin D(3 ) increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis . Vitamin D did not significantly affect time to sputum culture conversion in the whole study population , but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism . FUNDING British Lung Foundation Background Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma ( IFN-g ) and reducing disease associated inflammation in the host . The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis ( TB ) could influence recovery . Methods Two hundred and fifty nine patients with pulmonary TB were r and omized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses . Assessment s were performed at 4 , 8 and 12 weeks . Early secreted and T cell activated 6 kDa ( ESAT6 ) and Mycobacterium tuberculosis sonicate ( MTBs ) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks . Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student ’s t-test and Chi2 tests . Results After 12 weeks , the vitamin D supplemented arm demonstrated significantly greater mean weight gain ( kg ) + 3.75 , ( 3.16 – 4.34 ) versus + 2.61 ( 95 % CI 1.99 – 3.23 ) p 0.009 and lesser residual disease by chest radiograph ; number of zones involved 1.35 v/s 1.82 p 0.004 ( 95 % CI 0.15 , 0.79 ) and 50 % or greater reduction in cavity size 106 ( 89.8 % ) v/s 111 ( 94.8 % ) , p 0.035 . Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline ‘ Deficient ’ 25-hydroxyvitamin D serum levels ( p 0.021 ) . Conclusions Supplementation with high doses of vitamin D accelerated clinical , radiographic improvement in all TB patients and increased host immune activation in patients with baseline ‘ Deficient ’ serum vitamin D levels . These results suggest a therapeutic role for vitamin D in the treatment of TB.Trial registration Clinical Trials.gov ; No. NCT01130311 ; URL : clinical AIM to compare the vitamin D group of pulmonary tuberculosis patients with a placebo group in terms of clinical improvement , nutritional status , sputum conversion , and radiological improvement . METHODS sixty seven tuberculosis patient visiting the Pulmonary Clinic , of Cipto Mangunkusumo Hospital , Jakarta , from January 1st to August 31st , 2001 were included in this study . The subjects were r and omised to receive vitamin D ( 0.25 mg/day ) or placebo in a double blind method , during the 6th initial week of Tb treatment . The rate of sputum conversion , complete blood counts , blood chemistry as well as radiologic examination were evaluated . RESULTS there were more male patients than females ( 39:28 ) , 78.7 % were in the productive age group , 71.6 % had low nutritional status , 62.4 % with low education level , and 67.2 % with low income . One hundred percent of the vitamin D group and only 76.7 % of the placebo group had sputum conversion . This difference is statistically significant ( p=0.002 ) . CONCLUSION the sputum conversion had no correlation with the hemoglobin level , blood clotting time , calcium level , lymphocyte count , age , sex , and nutritional status . There were more subjects with radiological improvement in the vitamin D group 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 AIM Diabetes and vitamin D deficiency are widely prevalent in India . Studies have proven correlation between low vitamin D levels and pulmonary tuberculosis ( PTB ) and low vitamin D levels and insulin resistance . We evaluated the effects of vitamin D supplementation on type 2 diabetes mellitus patients with pulmonary tuberculosis ( PTB ) . METHODS Forty-five subjects ( M : F=34:11 ) were screened . Inclusion criteria were age > 15 years , newly diagnosed PTB cases with uncontrolled diabetes , serum vitamin D<20 ng/ml . The patients with vitamin D level<20 ng/ml were r and omly assigned to 2 groups . Group 1 subjects received oral cholecalceferol ( 60,000 units/week ) and calcium carbonate ( 1g/day ) along with anti tubercular treatment ( ATT ) , while group 2 subjects did not .  Sputum was checked at interval of 2 weeks for 12 weeks . Primary end point was time to achieve sputum smear conversion . RESULTS Fifteen patients having vitamin D>20 ng/ml were excluded . Age of the patients was 42.9±13.2 years and serum vitamin D levels were 18.4±15.3 ng/ml . Sputum smear conversion was 6 weeks in group 1 versus 8 weeks in group 2 ( p=0.067 ) . Glycated hemoglobin levels reduced from 11.1±1.3 to 7.7±0.9 in group 1 versus 10.3±1.2 to 7.8±1.1 ( p>0.1 ) . CONCLUSION Vitamin D can serve as adjuvant treatment of tuberculosis in diabetics with vitamin D deficiency . Further studies are required to vali date this observation and define a cut off for vitamin D level to prevent immunological alterations Background The association between pulmonary tuberculosis ( PTB ) and diabetes mellitus ( DM ) has been previously attracted much attention . Diabetes alters immunity to tuberculosis , leading to more frequent treatment failure in TB patients with DM . Moreover , TB and DM often coincide with micronutrients deficiencies , such as retinol and vitamin D , which are especially important to immunity of the body and may influence pancreas β-cell function . However , the effects of retinol and vitamin D supplementation in active TB patients with diabetes on treatment outcomes , immune and nutrition state are still uncertain . We are conducting a r and omized controlled trial of vitamin A and /or D in active PTB patients with DM in a network of 4 TB treatment clinics to determine whether the supplementation could improve the outcome in the patients . Methods / design This is a 2 × 2 factorial trial . We plan to enroll 400 active PTB patients with DM , and r and omize them to VA ( 2000 IU daily retinol ) ; VD ( 400 IU daily cholecalciferol ) ; VAD ( 2000 IU daily retinol plus 400 IU cholecalciferol ) or control ( placebo ) group . Our primary outcome measure is the efficacy of anti-tuberculosis treatment and ameliorating of glucose metabolism , and the secondary outcome measure being immune and nutrition status of the subjects . Of the first 37 subjects enrolled : 8 have been r and omized to VA , 10 to VD , 9 to VAD and 10 to control . To date , the sample is 97.3 % Han Chinese and 91.9 % female . The average fasting plasma glucose level is 12.19 mmol/L. Discussion This paper describes the design and rationale of a r and omized clinical trial comparing VA and /or VD supplementation to active pulmonary TB patients with DM . Our trial will allow rigorous evaluation of the efficacy of the supplementation to active TB and DM therapy for improving clinical outcomes and immunological condition . This detailed description of trial methodology can serve as a template for the development of future treatment scheme for active TB patient with DM.Trial registration 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 Vitamin D ( vitD ) and L-arginine have important antimycobacterial effects in humans . Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis ( TB ) . Methods In a 4-arm r and omised , double-blind , placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis ( PTB ) in Timika , Indonesia , we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo , and L-arginine 6.0 g daily or matching placebo , for 8 weeks , on proportions of participants with negative 4-week sputum culture , and on an 8-week clinical score ( weight , FEV1 , cough , sputum , haemoptysis ) . All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned . Adults with new smear-positive PTB were eligible . The trial was registered at Clinical Trials.gov NCT00677339 . Results 200 participants were enrolled , less than the intended sample size : 50 received L-arginine + active vitD , 49 received L-arginine + placebo vit D , 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model , 99 people received arginine , 101 placebo arginine , 101 vitamin D , 99 placebo vitamin D. Results for the primary endpoints were available in 155 ( 4-week culture ) and 167 ( clinical score ) participants . Sputum culture conversion was achieved by week 4 in 48/76 ( 63 % ) participants in the active L-arginine versus 48/79 ( 61 % ) in placebo L-arginine arms ( risk difference −3 % , 95 % CI −19 to 13 % ) , and in 44/75 ( 59 % ) in the active vitD versus 52/80 ( 65 % ) in the placebo vitD arms ( risk difference 7 % , 95 % CI −9 to 22 % ) . The mean clinical outcome score also did not differ between study arms . There were no effects of the interventions on adverse event rates including hypercalcaemia , or other secondary outcomes . Conclusion Neither vitD nor L-arginine supplementation , at the doses administered and with the power attained , affected TB outcomes . Registry Clinical Trials.gov . Registry number : The study examined the effect of supplementation with multivitamins and trace elements on microbiological and radiological recovery in patients with pulmonary tuberculosis . Forty-four patients aged 28 - 50 years were diagnosed with active pulmonary tuberculosis based on X-ray of the chest and smear examination of the sputum for the presence of acid-fast bacilli . They were all treated for six months with a st and ard anti-tuberculosis regimen that has been found to be effective worldwide for disease control . The subjects were r and omized to receive either a multivitamin-trace element supplement or a placebo containing calcium . The two groups were matched on all relevant confounding variables . At two months into the treatment , the group that was supplemented with a multivitamin-trace element preparation showed a significant reduction in the number of individuals with sputum smear positive for acid-fast bacillus : two out of 22 individuals , compared with seven out of 22 among placebo-treated controls ( p = 0.028 , Fisher 's test ) . It is concluded that patients with tuberculosis should be supplemented with a suitable micronutrient preparation that contains optimum amounts of all vitamins and trace elements that have been documented to enhance the immune response OBJECTIVE To assess the effect of micronutrient supplementation on tuberculosis ( TB ) patient outcomes . MATERIAL AND METHODS The r and omized , double-blinded , placebo-controlled study was conducted in pulmonary TB patients undergoing directly observed treatment short course/ tratamiento acortado estrictamente supervisado ( TAES/ DOTS ) at IMSS in Ciudad Juarez , Chihuahua , Mexico , who were recruited during August 2005-July 2006 . Consecutive patients received zinc and vitamin A supplements or matched placebo for four months . Dietary intake , blood zinc and vitamin A , immune response ( IFN-gamma , TNF-alpha , and IL-10 mRNA ) , and sputum smear conversion were measured . RESULTS The proportion of micronutrient compared to placebo group subjects with a negative sputum smear by month 3 was significantly increased ( p= 0.03 ) . This occurred subsequent to increased TNF-alpha and IFN-gamma and decreased IL-10 observed at month 2 . Micronutrient supplementation appeared to accelerate the beneficial therapeutic effect of chemotherapy . CONCLUSIONS The earlier elimination of bacilli from sputum was associated with improved zinc status and Th1 immune response . The therapeutic effect of vitamin A was less evident BACKGROUND Vitamin D has immunomodulatory effects that might aid clearance of mycobacterial infection . We aim ed to assess whether vitamin D supplementation would reduce time to sputum culture conversion in patients with active tuberculosis . METHODS We did this r and omised , double-blind , placebo-controlled , superiority trial at 13 sites in India . Treatment-naive patients who were sputum-smear positive , HIV negative , and had pulmonary tuberculosis were r and omly assigned ( 1:1 ) , with central ly labelled , serially numbered bottles , to receive st and ard active tuberculosis treatment with either supplemental high-dose oral vitamin D3 ( four doses of 2·5 mg at weeks 0 , 2 , 4 , and 6 ) or placebo . Neither the patients nor the clinical and laboratory investigators and personnel were aware of treatment assignment . The primary efficacy outcome was time to sputum culture conversion . Analysis was by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT00366470 . FINDINGS Between Jan 20 , 2010 , and Aug 23 , 2011 , we r and omly assigned 247 participants to the vitamin D group ( n=121 ) or the placebo group ( n=126 ) , of whom 211 participants ( n=101 and n=110 , respectively ) were included in the primary efficacy  analysis . Median time to culture conversion in the vitamin D group was 43·0 days ( 95 % CI 33·3 - 52·8 ) versus 42·0 days ( 33·9 - 50·1 ) in the placebo group ( log-rank p=0·95 ) . Three ( 2 % ) patients died in the vitamin D group and one ( 1 % ) patient died in the placebo group ; no death was considered attributable to the study intervention . No patients had hypercalcaemia . INTERPRETATION Our findings show that vitamin D supplementation did not reduce time to sputum culture conversion . Further studies should investigate the role of vitamin D in prevention or reactivation of tuberculosis infection . FUNDING Dalhousie University and Infectious Diseases Training and Research Centre Objectives Vitamin D is an immunomodulator and can alter response to tuberculosis ( TB ) treatment , though r and omised trials have been inconclusive to date . We present one of the first comprehensive analysis of the associations between vitamin D status and TB treatment , T-cell counts and nutritional outcomes by HIV status . Design Cohort study . Setting Outpatient clinics in Tanzania . Participants 25-hydroxyvitamin D levels were assessed in a cohort of 677 patients with TB ( 344 HIV infected ) initiating anti-TB treatment at enrolment in a multivitamin supplementation ( excluding vitamin D ) trial ( Clinical trials.gov identifier : NCT00197704 ) . Primary and secondary outcome measures Information on treatment outcomes such as failure and relapse , HIV disease progression , T-cell counts and anthropometry was collected routinely , with a median follow-up of 52 and 30 months for HIV-uninfected and HIV-infected patients , respectively . Cox and binomial regression , and generalised estimating equations were used to assess the association of vitamin D status with these outcomes . Results Mean 25-hydroxyvitamin D concentrations at enrolment were 69.8 ( ±21.5 ) nmol/L ( 27.9 ( ±8.6 ) ng/mL ) . Vitamin D insufficiency ( < 75 nmol/L ) was associated with a 66 % higher risk of relapse ( 95 % CI 4 % to 164 % ; 133 % higher risk in HIV-uninfected patients ) . Each unit higher 25-hydroxyvitamin D levels at baseline were associated with a decrease of 3 ( p=0.004 ) CD8 and 3 ( p=0.01 ) CD3 T-cells/µL during follow-up in patients with HIV infection . Vitamin D insufficiency was also associated with a greater decrease of body mass index ( BMI ; –0.21 kg/m2 ; 95 % CI −0.39 to −0.02 ) , during the first 8 months of follow-up . No association was observed  for vitamin D status with mortality or HIV disease progression . Conclusions Adequate vitamin D status is associated with a lower risk of relapse and with improved nutritional indicators such as BMI in patients with TB , with or without HIV infection . Further research is needed to determine the optimal dose of vitamin D and effectiveness of daily vitamin D supplementation among patients with TB 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 BACKGROUND Low serum concentrations of vitamin A and zinc are common in tuberculosis and may have an adverse effect on host cell-mediated responses . The role of adjunctive micronutrient supplementation on treatment outcomes is uncertain . OBJECTIVE The objective was to assess the efficacy of vitamin A and zinc supplementation on sputum smear and culture conversion and time to culture detection in adults with sputum smear-positive pulmonary tuberculosis . DESIGN Participants attending a primary care tuberculosis clinic in Cape Town , South Africa , were r and omly assigned to receive micronutrients ( single dose of 200,000 IU retinyl palmitate plus 15 mg Zn/d for 8 wk ) or matching placebo . Sputum was collected weekly for 8 wk for auramine staining and culture on liquid media ( BACTEC MGIT 960 ; Becton Dickinson , Sparks , MD ) . Performance status , chest radiographs , and anthropometric measures were assessed at baseline and again at 8 wk . RESULTS The participants ( n = 154 ) were r and omly assigned to the micronutrient ( n = 77 ) or placebo ( n = 77 ) group . Twenty participants were HIV infected ( 13 % ) , and 12 participants had an unknown HIV status ( 8 % ) . No differences in time to smear or culture conversion were observed between the treatment groups by Kaplan-Meier analysis ( P = 0.15 and P = 0.38 , respectively ; log-rank test ) . Log-logistic regression analysis found no significant group interaction effect in time to culture detection over the 8-wk period ( P = 0.32 ) . No significant differences in weight gain ( 2.3 ± 3.5 compared with 2.2 ± 2.4 kg , P = 0.68 ) or radiologic resolution were observed between the treatment groups . CONCLUSION Supplementation with vitamin A and zinc did not affect treatment outcomes in participants with pulmonary tuberculosis at 8 wk . This trial was registered at controlled-trials.com as IS RCT N80852505 SETTING Vitamin D deficiency is associated with susceptibility to active tuberculosis ( TB ) in many setting s. In vitro studies and studies on human volunteers showed that two of the first-line anti-tuberculosis drugs , isoniazid and rifampicin , reduce 25-hydroxy vitamin D ( 25[OH]D ) concentrations . OBJECTIVE To study changes in vitamin D status during treatment of Tanzanian hospitalised patients with pulmonary TB ( PTB ) . DESIGN We compared serum 25[OH]D concentrations in 81 Tanzanian PTB patients before and after 2 months of treatment . RESULTS Median serum 25[OH]D concentrations increased from 91 nmol/l at baseline to 101 nmol/l after 2 months of TB treatment ( median increase 6.0 nmol/l , IQR -0.7 - 25.0 , P = 0.001 ) . Median serum parathyroid hormone concentrations increased from 1.6 to 2.0 pmol/l ( median increase 0.46 , IQR -0.2 - 1.1 , P < 0.001 ) . CONCLUSION 25[OH]D serum concentrations increased during the first 2 months of TB treatment in 81 PTB patients in northern Tanzania . Improved dietary intake and increased sunlight exposure may have contributed to the increased 25[OH]D concentrations
Conclusion Vitamin D supplementation showed no influence on the improvement of sputum smear-negative conversion rates and BMI , as well as the decrease in ESR
Background Vitamin D might be promising to serve as an adjunctive therapy for pulmonary tuberculosis ( TB ) .
However , the results remained controversial .
We conducted a systematic review and meta- analysis to evaluate the efficacy and safety of vitamin D in patients with pulmonary TB .