title: Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Daily consumption of vitamin D- or vitamin D + calcium-fortified yogurt drink improved glycemic control in patients with type 2 diabetes: a randomized clinical trial. Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial 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 Sample size slippages in randomised trials: exclusions and the lost and wayward Implausible results in human nutrition research Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study: A Randomized Clinical Trial Modes of death in patients with heart failure and preserved ejection fraction. The effects of vitamin D supplementation on maternal and neonatal outcome: A randomized clinical trial The Effect of the Systemic Inflammatory Response on Plasma Vitamin 25 (OH) D Concentrations Adjusted for Albumin Vitamin D 20,000 IU per Week for Five Years Does Not Prevent Progression From Prediabetes to Diabetes. Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial 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 of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial Calcium plus vitamin D supplementation and the risk of colorectal cancer. Single data extraction generated more errors than double data extraction in systematic reviews. Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial. Risk of Heart Failure Among Postmenopausal Women: A Secondary Analysis of the Randomized Trial of Vitamin D Plus Calcium of the Women’s Health Initiative Prevention of urinary tract infections with vitamin D supplementation 20,000 IU per week for five years. Results from an RCT including 511 subjects Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). Sepsis-Associated Outcomes in Critically Ill Patients with Malignancies. Calcium plus vitamin D supplementation and mortality in postmenopausal women: the Women's Health Initiative calcium-vitamin D randomized controlled trial. A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial. Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The VDAART Randomized Clinical Trial.
abstract: 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 Low serum concentrations of 25-hydroxyvitamin D [ 25(OH)D ] have been associated with impaired glucose tolerance and diabetes . OBJECTIVE This study aim ed to compare the effects of daily intake of vitamin D- or vitamin D(3 ) + calcium-fortified yogurt drink on glycemic status in subjects with type 2 diabetes ( T2D ) . DESIGN Ninety diabetic subjects were r and omly allocated to 3 groups to consume plain yogurt drink ( PY ; containing no vitamin D and 150 mg Ca/250 mL ) , vitamin D-fortified yogurt drink ( DY ; containing 500 IU vitamin D(3 ) and 150 mg Ca/250 mL ) , or vitamin D + calcium-fortified yogurt drink ( DCY ; containing 500 IU vitamin D(3 ) and 250 mg Ca/250 mL ) twice per day for 12 wk . Fasting serum glucose ( FSG ) , glycated hemoglobin ( Hb A(1c ) ) , homeostasis model assessment of insulin resistance ( HOMA-IR ) , serum lipid profile , and percentage fat mass ( FM ) were assessed before ( baseline ) and after the intervention . RESULTS In both the DY and DCY groups , mean serum 25(OH)D(3 ) improved ( + 32.8 ± 28.4 and + 28.8 ± 16.1 nmol/L , respectively ; P < 0.001 for both ) , but FSG [ -12.9 ± 33.7 mg/dL ( P = 0.015 ) and -9.6 ± 46.9 mg/dL ( P = 0.035 ) ] , Hb A(1c ) [ -0.4 ± 1.2 % ( P < 0.001 ) and -0.4 ± 1.9 % ( P < 0.001 ) ] , HOMA-IR [ -0.6 ± 1.4 ( P = 0.001 ) and -0.6 ± 3.2 ( P < 0.001 ) ] , waist circumference ( -3.6 ± 2.7 and -2.9 ± 3.3 ; P < 0.001 for both ) , and body mass index [ in kg/m(2 ) ; -0.9 ± 0.6 ( P < 0.001 ) and -0.4 ± 0.7 ( P = 0.005 ) ] decreased significantly more than in the PY group . An inverse correlation was observed between changes in serum 25(OH)D(3 ) and FSG ( r = -0.208 , P = 0.049 ) , FM ( r = -0.219 , P = 0.038 ) , and HOMA-IR ( r = -0.219 , P = 0.005 ) . CONCLUSION Daily intake of a vitamin D-fortified yogurt drink , either with or without added calcium , improved glycemic status  in T2D patients . This trial was registered at clinical trials.gov as NCT01229891 Background Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing .  We examined the effect of prenatal vitamin D on childhood wheezing  in an interventional study . Methods We r and omised 180 pregnant women at 27 weeks gestation to either  no vitamin D , 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol  , in an ethnically stratified , r and omised controlled trial . Supplementation improved but did not optimise vitamin D status . Research ers blind to allocation assessed offspring at 3 years . Primary outcome was any history of wheeze assessed by vali date d question naire . Secondary outcomes included atopy , respiratory infection , impulse oscillometry and exhaled nitric oxide . Primary analyses used logistic and linear regression . Results We evaluated 158 of 180 ( 88 % ) offspring at age 3 years for the primary outcome . Atopy was assessed by skin test for 95 children ( 53 % ) , serum IgE for 86 ( 48 % ) , exhaled nitric oxide for 62 ( 34 % ) and impulse oscillometry of acceptable quality for 51 ( 28 % ) . We found no difference between supplemented and control groups in risk of wheeze  [ no vitamin D : 14/50 ( 28 % ) ; any vitamin D : 26/108 ( 24 % ) ( risk ratio 0.86 ; 95 % confidence interval 0.49 , 1.50 ; P = 0.69 ) ] . There was no significant difference in atopy , eczema risk , lung function or exhaled nitric oxide between supplemented groups and controls . Conclusion Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level , was not associated with decreased wheezing in offspring at age three years . Trial Registration Controlled-Trials.com IS RCT 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 Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity Definitive solutions wo n’t come from another million observational papers or small r and omized trials Importance Cohort studies have reported increased incidence of cardiovascular disease ( CVD ) among individuals with low vitamin D status . To date , r and omized clinical trials of vitamin D supplementation have not found an effect , possibly because of using too low a dose of vitamin D. Objective To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population . Design , Setting , and Participants The Vitamin D Assessment Study is a r and omized , double-blind , placebo-controlled trial that recruited participants mostly from family practice s in Auckl and , New Zeal and , from April 5 , 2011 , through November 6 , 2012 , with follow-up until July 2015 . Participants were community-resident adults aged 50 to 84 years . Of 47 905 adults invited from family practice s and 163 from community groups , 5110 participants were r and omized to receive vitamin D3 ( n = 2558 ) or placebo ( n = 2552 ) . Two participants retracted consent , and all others ( n = 5108 ) were included in the primary analysis . Interventions Oral vitamin D3 in an initial dose of 200 000 IU , followed a month later by monthly doses of 100 000 IU , or placebo for a median of 3.3 years ( range , 2.5 - 4.2 years ) . Main Outcomes and Measures The primary outcome was the number of participants with incident CVD and death , including a prespecified subgroup analysis in participants with vitamin D deficiency ( baseline deseasonalized 25-hydroxyvitamin D [ 25(OH)D ] levels < 20 ng/mL ) . Secondary outcomes were myocardial infa rct ion , angina , heart failure , hypertension , arrhythmias , arteriosclerosis , stroke , and venous thrombosis . Results Of the 5108 participants included in the analysis , the mean ( SD ) age was 65.9 ( 8.3 ) years , 2969 ( 58.1 % ) were male , and 4253 ( 83.3 % ) were of European or other ethnicity , with the remainder being Polynesian or South Asian .  Mean ( SD ) baseline deseasonalized 25(OH)D concentration was 26.5 ( 9.0 ) ng/mL , with 1270 participants ( 24.9 % ) being vitamin D deficient . In a r and om sample of 438 participants , the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group . The primary outcome of CVD occurred in 303 participants ( 11.8 % ) in the vitamin D group and 293 participants ( 11.5 % ) in the placebo group , yielding an adjusted hazard ratio of 1.02 ( 95 % CI , 0.87 - 1.20 ) . Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes . Conclusions and Relevance Monthly high-dose vitamin D supplementation does not prevent CVD . This result does not support the use of monthly vitamin D supplementation for this purpose . The effects of daily or weekly dosing require further study . Trial Registration clinical trials.gov Identifier : BACKGROUND Recent studies suggest that reduced right ventricular function is an important predictor of outcome in patients with heart failure and preserved ejection fraction ( HFpEF ) . Because affected patients suffer from a broad spectrum of non-cardiac co-morbidities , it remains unclear , whether they actually die from right heart failure ( RHF ) or as a consequence of other conditions . METHODS Consecutive patients with a confirmed diagnosis of HFpEF were enrolled in this prospect i ve registry . Local and external medical records , as well as telephone interviews with relatives were used to ascertain modes of death . RHF was accepted as a mode of death , if the following criteria were met : 1 . right ventricular dysfunction assessed by transthoracic echocardiography , and 2 . clinical signs of right heart decompensation at the time of death . RESULTS Out of 230 patients with complete follow-up , 16.5 % ( n=38 ) died after a mean of 30±17months . 60.5 % deaths were classified as cardiovascular and 34.2 % as non-cardiovascular . In 5.3 % patients , the reason for death remained unknown . Of the cardiovascular cases ( n=23 ) , 91.4 % of deaths were attributed to RHF , 4.3 % died from stroke and 4.3 % from sudden cardiac death . Of the non-cardiovascular deaths ( n=13 ) , 46.2 % of deaths were attributed to major infections and 38.4 % deaths were related to cancer . Other reasons for death included ileus ( 7.7 % ) and major bleeding ( 7.7 % ) . CONCLUSION In our well-characterised HFpEF cohort , more than half of all deaths could directly be attributed to RHF . The right ventricle seems to be a meaningful therapeutic target in a subset of patients Background : Vitamin D supplementation during pregnancy has been supposed to defend against adverse gestational outcomes . Objective : This r and omized clinical trial study was conducted to assess the effects of 50,000 IU of vitamin D every two weeks supplementation on the incidence of  gestational diabetes ( GDM ) , gestational hypertension , preeclampsia and preterm labor , vitamin D status at term and neonatal outcomes contrasted with pregnant women that received 400 IU vitamin D daily . Material s and Methods : 500 women with gestational age 12 - 16 weeks and serum 25 hydroxy vitamin D ( 25 ( OH ) D ) less than 30 ng/ml r and omly categorized in two groups . Group A received 400 IU vitamin D daily and group B 50,000 IU vitamin D every 2 weeks orally until delivery . Maternal and Neonatal outcomes were assessed in two groups . Results : The incidence of GDM in group B was significantly lower than group A ( 6.7 % versus 13.4 % ) and odds ratio ( 95 % Confidence interval ) was 0.46 ( 0.24 - 0.87 ) ( P=0.01 ) . The mean ± SD level of 25 ( OH ) D at the time of delivery in mothers in group B was significantly higher than A ( 37.9 ± 19.8 versus 27.2 ± 18.8 ng/ml , respectively ) ( P=0.001 ) . There were no differences in the incidence of preeclampsia , gestational hypertension , preterm labor , and low birth weight between two groups . The mean level of 25 ( OH ) D in cord blood of group B was significantly higher than group A ( 37.9 ± 18 versus 29.7 ± 19ng/ml , respectively ) . Anthropometric measures between neonates were not significantly different . Conclusion : Our study showed 50,000 IU vitamin D every 2 weeks decreased the incidence of GDM Background Plasma 25-hydroxyvitamin D ( 25(OH ) D ) deficiencies are associated with several diseases . The magnitude of systemic inflammatory response , as evidence d by C-reactive protein ( CRP ) , is a major factor associated with lower 25(OH)D. Other aspects of the systemic inflammatory response may be important in determining plasma 25 (OH)D concentrations . Aim To examine the relationship between plasma 25(OH)D , CRP and albumin concentrations in two patient cohorts . Methods 5327 patients referred for nutritional assessment and 117 patients with critical illness were examined .  Plasma 25 ( OH ) D concentrations were measured using st and ard methods . Intra and between assay imprecision was < 10 % . Result In the large cohort , plasma 25 ( OH ) D was significantly associated with CRP ( r s = −0.113 , p<0.001 ) and albumin ( r s = 0.192 , p<0.001 ) . 3711 patients had CRP concentrations ≤10 mg/L ; with decreasing albumin concentrations ≥35 , 25–34 and < 25 g/l , median concentrations of 25 ( OH ) D were significantly lower from 35 to 28 to 14 nmol/l ( p<0.001 ) . This decrease was significant when albumin concentrations were reduced between 25–34 g/L ( p<0.001 ) and when albumin < 25 g/L ( p<0.001 ) . 1271 patients had CRP concentrations between 11–80 mg/L ; with decreasing albumin concentrations ≥35 , 25–34 and < 25 g/l , median concentrations of 25 ( OH ) D were significantly lower from 31 to 24 to 19 nmol/l ( p<0.001 ) . This decrease was significant when albumin concentration were 25–34 g/L ( p<0.001 ) and when albumin < 25 g/L ( p<0.001 ) . 345 patients had CRP concentrations > 80 mg/L ; with decreasing albumin concentrations ≥35 , 25–34 and < 25 g/l , median concentrations of 25 ( OH ) D were not significantly altered varying from 19 to 23 to 23 nmol/l . Similar relationships were also obtained in the cohort of patients with critical illness . Conclusion Plasma concentrations of 25(OH ) D were independently associated with both CRP and albumin and consistent with the systemic inflammatory response as a major confounding factor in determining vitamin D status CONTEXT Vitamin D deficiency is associated with insulin resistance and risk of future diabetes . OBJECTIVE The objective of the study was to test whether supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes mellitus ( T2DM ) . DESIGN This was a r and omized controlled trial performed in 2008 through 2015 . SETTING The study was conducted at the clinical research unit at a teaching hospital . PATIENTS Five hundred eleven subjects ( mean age 62 y , 314 males ) with prediabetes diagnosed with an oral glucose tolerance test as part of the Tromsø Study 2007–2008 were included . A total of 256 were r and omized to vitamin D and 255 to placebo .  Twenty-nine subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events . INTERVENTIONS Interventions included vitamin D ( cholecalciferol ) 20 000 IU/wk vs placebo for 5 years . Annual oral glucose tolerance tests were performed . MAIN OUTCOME MEASURE Progression to T2DM was the main outcome measure . Secondary outcomes were change in glucose levels , insulin resistance , serum lipids , and blood pressure . RESULTS The mean baseline serum 25-hydroxyvitamin D level was 60 nmol/L ( 24 ng/mL ) . One hundred three in the vitamin D and 112 in the placebo group developed T2DM ( hazard risk 0.90 ; 95 % confidence interval 0.69–1.18 , Cox regression , P = .45 , intention to treat analysis ) . No consistent significant effects on the other outcomes were seen . Subgroup analyses in subjects with low baseline 25-hydroxyvitamin D yielded similar results . No serious side effects related to the intervention were recorded . CONCLUSIONS In subjects without vitamin D deficiency , vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes . Very large studies with inclusion of vitamin D-deficient subjects will probably be needed to show such a putative effect . This study tested if supplementation with  vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes ( T2DM ) Background Endothelial dysfunction has been proposed as the underlying cause of diabetic angiopathy that eventually leads to cardiovascular disease , the major cause of death in diabetes . We recently demonstrated the ameliorating effect of regular vitamin D intake on the glycemic status of patients with type 2 diabetes ( T2D ) . In this study , the effects of improvement of vitamin D status on glycemic status , lipid profile and endothelial biomarkers in T2D subjects were investigated . Methods Subjects with T2D were r and omly allocated to one of the two groups to receive either plain yogurt drink ( PYD ; containing 170 mg calcium and no vitamin D/250 mL , n1 = 50 ) or vitamin D3-fortified yogurt drink ( FYD ; containing 170 mg calcium and 500 IU/250 mL , n2 = 50 ) twice a day for 12 weeks . Anthropometric measures , glycemic status , lipid profile , body fat mass ( FM ) and endothelial biomarkers including serum endothelin-1 , E-selectin and matrix metalloproteinase (MMP)-9 were evaluated at the beginning and after the 12-week intervention period . Results The intervention result ed in a significant improvement in fasting glucose , the Quantitative Insulin Check Index ( QUICKI ) , glycated hemoglobin ( HbA1c ) , triacylglycerols , high-density lipoprotein cholesterol ( HDL-C ) , endothelin-1 , E-selectin and MMP-9 in FYD compared to PYD ( P < 0.05 , for all ) . Interestingly , difference in changes of endothelin-1 , E-selectin and MMP-9 concentrations in FYD compared to PYD ( -0.35 ± 0.63 versus -0.03 ± 0.55 , P = 0.028 ; -3.8 ± 7.3 versus 0.95 ± 8.3 , P = 0.003 and -2.3 ± 3.7 versus 0.44 ± 7.1 ng/mL , respectively , P < 0.05 for all ) , even after controlling for changes of QUICKI , FM and waist circumference , remained significant for endothelin-1 and MMP-9 ( P = 0.009 and P = 0.005 , respectively ) but disappeared for E-selectin ( P = 0.092 ) . On the contrary , after controlling for serum 25(OH)D , the differences disappeared for endothelin-1(P = 0.066 ) and MMP-9 ( P = 0.277 ) but still remained significant for E-selectin ( P = 0.011 ) . Conclusions Ameliorated vitamin D status was accompanied by improved glycemic status , lipid profile and endothelial biomarkers in T2D subjects . Our findings suggest both direct and indirect ameliorating effects of vitamin D on the endothelial biomarkers . Trial registration Clinical Trials.gov : 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 Importance Evidence suggests that low vitamin D status may increase the risk of cancer . Objective To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of  cancer among older women . Design , Setting , and Participants A 4-year , double-blind , placebo-controlled , population -based r and omized clinical trial in 31 rural counties ( June 24 , 2009 , to August 26 , 2015—the final date of follow-up ) . A total of 2303 healthy postmenopausal women 55 years or older were r and omized , 1156 to the treatment group and 1147 to the placebo group . Duration of treatment was 4 years . Interventions The treatment group ( vitamin D3 + calcium group ) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium ; the placebo group received identical placebos . Main Outcomes and Measures The primary outcome was the incidence of all-type cancer ( excluding nonmelanoma skin cancers ) , which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling . Results Among 2303 r and omized women ( mean age , 65.2 years [ SD , 7.0 ] ; mean baseline serum 25-hydroxyvitamin D level , 32.8 ng/mL [ SD , 10.5 ] ) , 2064 ( 90 % ) completed the study . At year 1 , serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group . A new diagnosis of cancer was confirmed in 109 participants , 45 ( 3.89 % ) in the vitamin D3 + calcium group and 64 ( 5.58 % ) in the placebo group ( difference , 1.69 % [ 95 % CI , −0.06 % to 3.46 % ] ; P = .06 ) . Kaplan-Meier incidence over 4 years was 0.042 ( 95 % CI , 0.032 to 0.056 ) in the vitamin D3 + calcium group and 0.060 ( 95 % CI , 0.048 to 0.076 ) in the placebo group ; P = .06 . In unadjusted Cox proportional hazards regression , the hazard ratio was 0.70 ( 95 % CI , 0.47 to 1.02 ) . Adverse events potentially related to the study included renal calculi ( 16 participants in the vitamin D3 + calcium group and 10 in the placebo group ) , and elevated serum calcium levels ( 6 in the vitamin D3 + calcium group and 2 in the placebo group ) . Conclusions and Relevance Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL , supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years . Further research is necessary to assess the possible role of vitamin D in cancer prevention . Trial Registration clinical trials.gov Identifier : BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo-controlled trial involving 36,282 postmenopausal women from 40 Women 's Health Initiative centers : 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [ corrected ] twice daily ( 1000 mg of elemental calcium and 400 IU of vitamin D3 ) and 18,106 received a matching placebo for an average of 7.0 years . The incidence of pathologically confirmed colorectal cancer was the design ated secondary outcome . Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study . RESULTS The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo ( 168 and 154 cases ; hazard ratio , 1.08 ; 95 percent confidence interval , 0.86 to 1.34 ; P=0.51 ) , and the tumor characteristics were similar in the two groups . The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups . There were no significant treatment interactions with baseline characteristics . CONCLUSIONS Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer  among postmenopausal women . The long latency associated with the development of colorectal cancer , along with the seven-year duration of the trial , may have contributed to this null finding . Ongoing follow-up will assess the longer-term effect of this intervention . ( Clinical Trials.gov number , NCT00000611 . ) BACKGROUND AND OBJECTIVE To conduct a pilot study to compare the frequency of errors that accompany single vs. double data extraction , compare the estimate of treatment effect derived from these methods , and compare the time requirements for these methods . METHODS Review ers were r and omized to the role of data extractor or data verifier , and were blind to the study hypothesis . The frequency of errors associated with each method of data extraction was compared using the McNemar test . The data set for each method was used to calculate an efficacy estimate by each method , using st and ard meta-analytic techniques . The time requirement for each method was compared using a paired t-test . RESULTS Single data extraction result ed in more errors than double data extraction ( relative difference : 21.7 % , P = .019 ) . There was no substantial difference between methods in effect estimates for most outcomes . The average time spent for single data extraction  was less than the average time for double data extraction ( relative difference : 36.1 % , P = .003 ) . CONCLUSION In the case that single data extraction is used in systematic review s , review ers and readers need to be mindful of the possibility for more errors and the potential impact these errors may have on effect estimates IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring , but the preventive effect of vitamin D supplementation to pregnant women is unknown . OBJECTIVE To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring . DESIGN , SETTING , AND PARTICIPANTS A double-blind , single-center , r and omized clinical trial conducted within the Copenhagen Prospect i ve Studies on Asthma in Childhood 2010 cohort . Enrollment began March 2009 with a goal of 708 participants , but due to delayed ethical approval , only 623 women were recruited at 24 weeks of pregnancy . Follow-up of the children ( N = 581 ) was completed when the youngest child reached age 3 years in March 2014 . INTERVENTIONS Vitamin D3 ( 2400 IU/d ; n = 315 ) or matching placebo tablets ( n = 308 ) from pregnancy week 24 to 1 week postpartum . All women received 400 IU/d of vitamin D3 as part of usual pregnancy care . MAIN OUTCOMES AND MEASURES Age at onset of persistent wheeze in the first 3 years of life . Secondary outcomes included number of episodes of troublesome lung symptoms , asthma , respiratory tract infections , and neonatal airway immunology . Adverse events were assessed . RESULTS Of the 581 children ,  persistent wheeze  was diagnosed during the first 3 years of life in 47 children ( 16 % ) in the  vitamin D3 group and 57 children ( 20 % ) in the  control group .  Vitamin D3 supplementation was not associated with the risk of persistent wheeze , but the number of episodes of troublesome lung symptoms was reduced , and the airway immune profile was up-regulated ( principal component analysis , P = .04 ) . There was no effect on additional end points . Intrauterine death was observed in 1 fetus ( < 1 % ) in the vitamin D3 group vs 3 fetuses ( 1 % ) in the control group and congenital malformations in 17 neonates ( 5 % ) in the vitamin D3 group vs 23 neonates ( 8 % ) in the control group . [ table : see text ] . CONCLUSIONS AND RELEVANCE The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years . However , interpretation of the study is limited by a wide CI that includes a clinical ly important protective effect . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00856947 Background —Vitamin D supplementation may be an inexpensive intervention to reduce heart failure ( HF ) incidence . However , there are insufficient data to support this hypothesis . This study evaluates whether vitamin D plus calcium ( CaD ) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF . Methods and Results —Analyses were restricted to 35 983 ( of original 36 282 ) women aged 50 to 79 years old in the Women ’s Health Initiative r and omized trial of CaD supplementation who were r and omized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo . Overall , 744 adjudicated incident HF cases ( intervention , 363 ; control , 381 ) occurred during a median follow-up of 7.1 ( interquartile range , 1.6 ) years . CaD supplementation , compared with placebo , was not associated with reduced HF risk in the overall population , hazard ratio , 0.95 ; P=0.46 . However , CaD supplementation had differential effects ( P interaction=0.005 ) in subgroups stratified by baseline risk status of HF defined by the presence ( high risk=17 449 ) or absence ( low risk=18 534 ) of pre-existing HF precursors including coronary heart diseases , diabetes mellitus , or hypertension : 37 % ( hazard ratio , 0.63 [ 95 % confidence interval , 0.46–0.87 ] ) lower risk of HF in the low-risk versus hazard ratio , 1.06 ; P=0.51 , in the high-risk subgroups . Conclusions —CaD supplementation did not significantly reduce HF incidence in the overall cohort , however , it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups . Additional studies are warranted to confirm these findings and investigate the underlying mechanism . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00000611 Abstract Background : In observational studies vitamin D deficiency is associated with increased risk of infections , whereas the effect of vitamin D supplementation in r and omized controlled trials is non-conclusive . Methods : Five hundred and eleven subjects with prediabetes were r and omized to vitamin D3 ( 20,000 IU per week ) versus placebo for five years . Every sixth month , a question naire on respiratory tract infections ( RTI ) ( common cold , bronchitis , influenza ) and urinary tract infection ( UTI ) was filled in . Results : Mean baseline serum 25-hydroxyvitamin D ( 25(OH)D ) level was 60 nmol/L. Two hundred and fifty-six subjects received vitamin D and 255 placebo . One hundred and sixteen subjects in the vitamin D and 111 in the placebo  group completed the five-year study . Eighteen subjects in the vitamin D group and 34 subjects in the placebo group reported UTI during the study ( p < 0.02 ) , whereas no significant differences were seen for RTI . The effect on UTI was most pronounced in males . The effect of vitamin D on UTI was unrelated to baseline serum 25(OH)D level . Conclusion : Supplementation with vitamin D might prevent UTI , but confirmatory studies are needed CONTEXT Vitamin D or calcium supplementation may have effects on  vascular disease and cancer .  OBJECTIVE Our objective was to investigate whether vitamin D or calcium supplementation affects mortality , vascular disease , and cancer in older people . DESIGN AND SETTING The study included long-term follow-up of participants in a two by two factorial , r and omized controlled trial from 21 orthopedic centers in the United Kingdom . PARTICIPANTS Participants were 5292 people ( 85 % women ) aged at least 70 yr with previous low-trauma fracture . INTERVENTIONS Participants were r and omly allocated to daily vitamin D(3 ) ( 800 IU ) , calcium ( 1000 mg ) , both , or placebo for 24 - 62 months , with a follow-up of 3 yr after intervention . MAIN OUTCOME MEASURES All-cause mortality , vascular disease mortality , cancer mortality , and cancer incidence were evaluated . RESULTS In intention-to-treat analyses , mortality [ hazard ratio ( HR ) = 0.93 ; 95 % confidence interval ( CI ) = 0.85 - 1.02 ] , vascular disease mortality ( HR = 0.91 ; 95 % CI = 0.79 - 1.05 ) , cancer mortality ( HR = 0.85 ; 95 % CI = 0.68 - 1.06 ) , and cancer incidence ( HR = 1.07 ; 95 % CI = 0.92 - 1.25 ) did not differ significantly between participants allocated vitamin D and those not . All-cause mortality ( HR = 1.03 ; 95 % CI = 0.94 - 1.13 ) , vascular disease mortality ( HR = 1.07 ; 95 % CI = 0.92 - 1.24 ) , cancer mortality ( HR = 1.13 ; 95 % CI = 0.91 - 1.40 ) , and cancer incidence ( HR = 1.06 ; 95 % CI = 0.91 - 1.23 ) also did not differ significantly between participants allocated calcium and those not . In a post hoc statistical analysis adjusting for compliance , thus with fewer participants , trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated , although all results remain nonsignificant . CONCLUSIONS Daily vitamin D or calcium supplementation did not affect mortality , vascular disease , cancer mortality , or cancer incidence RATIONALE Sepsis is a major cause of mortality among critically ill patients with cancer . Information about clinical outcomes and factors associated with increased risk of death in these patients is necessary to help physicians recognize those patients who are most likely to benefit from  ICU therapy  and identify possible targets for intervention . OBJECTIVES In this study , we evaluated cancer patients with sepsis chosen from a multicenter prospect i ve study to characterize their clinical characteristics and to identify independent risk factors associated with hospital mortality . METHODS Subgroup analysis of a multicenter prospect i ve cohort study conducted in 28 Brazilian intensive care units ( ICUs ) to evaluate adult cancer patients with severe sepsis and septic shock . We used logistic regression to identify variables associated with hospital mortality . MEASUREMENTS AND MAIN RESULTS Of the 717 patients admitted to the participating ICUs , 268 ( 37 % ) had severe sepsis ( n = 142 , 53 % ) or septic shock ( n = 126 , 47 % ) . These patients comprised the population of the present study . The mean score on the third version of the Simplified Acute Physiology Score was 62.9 ± 17.7 points , and the median Sequential Organ Failure Assessment score was 9 ( 7 - 12 ) points . The most frequent sites of infection were the lungs ( 48 % ) , intraabdominal region ( 25 % ) , bloodstream as primary infection ( 19 % ) , and urinary tract ( 17 % ) . Half of the patients had microbiologically proven infections , and Gram-negative bacteria were the most common pathogens causing sepsis ( 31 % ) . ICU and hospital mortality rates were 42 % and 56 % , respectively . In multivariable analysis , the number of acute organ dysfunctions ( odds ratio [ OR ] , 1.48 ; 95 % confidence interval [ CI ] , 1.16 - 1.87 ) , hematological malignancies ( OR , 2.57 ; 95 % CI , 1.05 - 6.27 ) , performance status 2 - 4 ( OR , 2.53 ; 95 % CI , 1.44 - 4.43 ) , and polymicrobial infections ( OR , 3.74 ; 95 % CI , 1.52 - 9.21 ) were associated with hospital mortality . CONCLUSIONS Sepsis is a common cause of critical illness in patients with cancer and remains associated with high mortality . Variables related to underlying malignancy , sepsis severity , and characteristics of infection are associated with a grim prognosis BACKGROUND Calcium and vitamin D ( CaD ) supplementation trials including the Women 's Health Initiative ( WHI ) trial of CaD have shown nonsignificant reductions in total mortality . This report examines intervention effects on total and cause-specific mortality by age and adherence . METHODS The WHI CaD trial was a r and omized , double-blind , placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51 - 82 years from 40 U.S. clinical centers . Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D(3 ) daily or placebo with average follow-up of 7.0 years . RESULTS The hazard ratio ( HR ) for total mortality was 0.91 ( 95 % confidence interval [ CI ] , 0.83 - 1.01 ) with 744 deaths in women r and omized to CaD versus 807 deaths in the placebo group . HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality , but near unity for coronary heart disease and other causes of death . HRs for total mortality were 0.89 in the 29,942 women younger than 70 years ( 95 % CI , 0.79 - 1.01 ) and 0.95 in the 6,340 women aged 70 and older ( 95 % CI , 0.80 - 1.12 ; p value for age interaction = .10 ) . No statistically significant interactions were observed for any baseline characteristics . Treatment effects did not vary significantly by season . CONCLUSIONS In the WHI CaD trial , supplementation did not have a statistically significant effect on mortality rates but the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women . These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality BACKGROUND Epidemiologic and pre clinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia . To further study the chemopreventive potential of these nutrients , we conducted a r and omized , double-blind , placebo-controlled trial of supplementation with vitamin D , calcium , or both for the prevention of colorectal adenomas . METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy . We r and omly assigned 2259 participants to receive daily vitamin D3 ( 1000 IU ) , calcium as carbonate ( 1200 mg ) , both , or neither in a partial 2 × 2 factorial design . Women could elect to receive calcium plus r and om assignment to vitamin D or placebo . Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations , according to the endoscopist 's recommendation . The primary end point was adenomas diagnosed in the interval from r and omization through the anticipated surveillance colonoscopy . RESULTS Participants who were r and omly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter , relative to participants given placebo . Overall , 43 % of participants had one or more adenomas diagnosed during follow-up . The adjusted risk ratios for recurrent adenomas were 0.99 ( 95 % confidence interval [ CI ] , 0.89 to 1.09 ) with vitamin D versus no vitamin D , 0.95 ( 95 % CI , 0.85 to 1.06 ) with calcium versus no calcium , and 0.93 ( 95 % CI , 0.80 to 1.08 ) with both agents versus neither agent . The findings for advanced adenomas were similar . There were few serious adverse events . CONCLUSIONS Daily supplementation with vitamin D3 ( 1000 IU ) , calcium ( 1200 mg ) , or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00153816 . ) IMPORTANCE Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill . It is unknown if this association is causal . OBJECTIVE To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs . DESIGN , SETTING , AND PARTICIPANTS A r and omized double-blind , placebo-controlled , single-center trial , conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency ( ≤20 ng/mL ) assigned to receive either vitamin D3 ( n = 249 ) or a placebo ( n = 243 ) . INTERVENTIONS Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months . MAIN OUTCOMES AND MEASURES The primary outcome was hospital length of stay . Secondary outcomes included , among others , length of ICU stay , the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7 , hospital mortality , and 6-month mortality . A predefined severe vitamin D deficiency ( ≤12 ng/mL ) subgroup analysis was specified before data unblinding and analysis . RESULTS A total of 475 patients were included in the final analysis ( 237 in the vitamin D3 group and 238 in the placebo  group ) . The median ( IQR ) length of hospital stay was not significantly different between groups ( 20.1 days [ IQR , 11.1 - 33.3 ] for vitamin D3 vs 19.3 days [ IQR , 11.1 - 34.9 ] for placebo ; P = .98 ) . Hospital mortality and 6-month mortality were also not significantly different ( hospital mortality : 28.3 % [ 95 % CI , 22.6%-34.5 % ] for vitamin D3 vs 35.3 % [ 95 % CI , 29.2%-41.7 % ] for placebo ; hazard ratio [ HR ] , 0.81 [ 95 % CI , 0.58 - 1.11 ] ; P = .18 ; 6-month mortality : 35.0 % [ 95 % CI , 29.0%-41.5 % ] for vitamin D3 vs 42.9 % [ 95 % CI , 36.5%-49.4 % ] for placebo ; HR , 0.78 [ 95 % CI , 0.58 - 1.04 ] ; P = .09 ) . For the severe vitamin D deficiency subgroup analysis ( n = 200 ) , length of hospital stay was not significantly different between the 2 study groups : 20.1 days ( IQR , 12.9 - 39.1 ) for vitamin D3 vs 19.0 days ( IQR , 11.6 - 33.8 ) for placebo . Hospital mortality was significantly lower with 28 deaths among 98 patients ( 28.6 % [ 95 % CI , 19.9%-38.6 % ] ) for vitamin D3 compared with 47 deaths among 102 patients ( 46.1 % [ 95 % CI , 36.2%-56.2 % ] ) for placebo ( HR , 0.56 [ 95 % CI , 0.35 - 0.90 ] , P for interaction = .04 ) , but not 6-month mortality ( 34.7 % [ 95 % CI , 25.4%-45.0 % ] for vitamin D3 vs 50.0 % [ 95 % CI , 39.9%-60.1 % ] for placebo ; HR , 0.60 [ 95 % CI , 0.39 - 0.93 ] , P for interaction = .12 ) . CONCLUSIONS AND RELEVANCE Among critically ill patients with vitamin D deficiency , administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay , hospital mortality , or 6-month mortality . Lower hospital mortality was observed in the severe vitamin D deficiency subgroup , but this finding should be considered hypothesis generating and requires further study . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01130181 IMPORTANCE Asthma and wheezing begin early in life , and prenatal vitamin D deficiency has been variably associated with these disorders in offspring . OBJECTIVE To determine whether prenatal vitamin D ( cholecalciferol ) supplementation can prevent  asthma or recurrent wheeze in early childhood . DESIGN , SETTING , AND PARTICIPANTS The Vitamin D Antenatal Asthma Reduction Trial was a r and omized , double-blind , placebo-controlled trial conducted in 3 centers across the United States . Enrollment began in October 2009 and completed follow-up in January 2015 . Eight hundred eighty-one pregnant women between the ages of 18 and 39 years at high risk of having children with asthma were r and omized at 10 to 18 weeks ' gestation . Five participants were deemed ineligible shortly after r and omization and were discontinued . INTERVENTIONS Four hundred forty women were r and omized to receive daily 4000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D , and 436 women were r and omized to receive a placebo plus a prenatal vitamin containing 400 IU vitamin D. MAIN OUTCOMES AND MEASURES Co primary outcomes of ( 1 ) parental report of physician-diagnosed asthma or recurrent wheezing through 3 years of age and ( 2 ) third trimester maternal 25-hydroxyvitamin D levels . RESULTS Eight hundred ten infants were born in the study , and 806 were included in the analyses for the 3-year outcomes . Two hundred eighteen children developed asthma or recurrent wheeze : 98 of 405 ( 24.3 % ; 95 % CI , 18.7%-28.5 % ) in the 4400-IU group vs 120 of 401 ( 30.4 % , 95 % CI , 25.7%-73.1 % ) in the 400-IU group ( hazard ratio , 0.8 ; 95 % CI , 0.6 - 1.0 ; P = .051 ) . Of the women in the 4400-IU group whose blood levels were checked , 289 ( 74.9 % ) had 25-hydroxyvitamin D levels of 30 ng/mL or higher by the third trimester of pregnancy compared with 133 of 391 ( 34.0 % ) in the 400-IU group ( difference , 40.9 % ; 95 % CI , 34.2%-47.5 % , P < .001 ) . CONCLUSIONS AND RELEVANCE In pregnant women at risk of having a child with asthma , supplementation with 4400 IU/d of vitamin D compared with 400 IU/d significantly increased vitamin D levels in the women . The incidence of asthma and recurrent wheezing in their children at age 3 years was lower by 6.1 % , but this did not meet statistical significance ; however , the study may have been underpowered . Longer follow-up of the children is ongoing to determine whether the difference is clinical ly important . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00920621
target: Recent meta-analyses reinforce the finding that 10 - 20 μg per day of vitamin D can reduce all-cause mortality and cancer mortality in middle-aged and older people .
  Although vitamin D doses were greater than those assessed in the past , we found no new evidence that supplementation could have an effect on most non-skeletal conditions , including cardiovascular disease , adiposity , glucose metabolism , mood disorders , muscular function , tuberculosis , and colorectal adenomas , or on maternal and perinatal conditions .
  The compilation of results from 83 trials showed that vitamin D supplementation had no significant effect on biomarkers of systemic inflammation .
  The main new finding highlighted by this systematic review is that vitamin D supplementation might help to prevent common upper respiratory tract infections and asthma exacerbations .
  There remains little evidence to suggest that vitamin D supplementation has an effect on most conditions , including chronic inflammation , despite use of increased doses of vitamin D , strengthening the hypothesis that low vitamin D status is a consequence of ill health , rather than its cause .
  We further hypothesise that vitamin D supplementation could exert immunomodulatory effects that strengthen resistance to acute infections , which would reduce the risk of death in debilitated individuals .
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