title: Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients How confidence intervals become confusion intervals Effect of treatment with dydrogesterone or calcium plus vitamin D on the severity of premenstrual syndrome. Randomized Trial of Vitamin D Supplementation and Risk of Acute Respiratory Infection in Mongolia Serum vitamin D and falls in older women in residential care in Australia. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Annual high-dose vitamin D3 and mental well-being: randomised controlled trial. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Calcium and vitamin D supplementation and incident rheumatoid arthritis: the Women’s Health Initiative Calcium plus Vitamin D trial Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women Annual high-dose oral vitamin D and falls and fractures in older women: a randomized 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 A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study. Effects of Vitamin D Supplementation on Cognitive and Emotional Functioning in Young Adults – A Randomised Controlled Trial Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. Vitamin D3 enhances mood in healthy subjects during winter Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Efficacy of Vitamin D in patients with active rheumatoid arthritis receiving methotrexate therapy The Effect of 2 Different Single Injections of High Dose of Vitamin D on Improving the Depression in Depressed Patients With Vitamin D Deficiency: A Randomized Clinical Trial Serum parathyroid hormone predicts time to fall independent of vitamin D status in a frail elderly population. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. Therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Vitamin D supplementation and depression in the women's health initiative calcium and vitamin D trial. Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. Effects of large doses of calciferol on patients with rheumatoid arthritis. A double-blind clinical trial. Seasonal mood changes in 250 normal women Correlation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: a randomized controlled trial. Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms Low serum 25-hydroxyvitamin D levels are associated with increased all-cause mortality risk in a general population: the Tromsø study.
abstract: Background For adults , vitamin D intake of 100 mcg ( 4000 IU)/day is physiologic and safe . The adequate intake ( AI ) for older adults is 15 mcg ( 600 IU)/day , but there has been no report focusing on use of this dose . Methods We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded , r and omized trial . In Study 1 , 64 out patients ( recruited if summer 2001 25(OH)D < 61 nmol/L ) were given 15 or 100 mcg/day vitamin D in December 2001 . Biochemical responses were followed at subsequent visits that were part of clinical care ; 37 patients completed a wellbeing question naire in December 2001 and February 2002 . Subjects for Study 2 were recruited if their 25(OH)D was < 51 nmol/L in summer 2001 . 66 out patients were given vitamin D ;  51 completed a wellbeing question naire in both December 2002 and February 2003 . Results In Study 1 , basal summer 25-hydroxyvitamin D [ 25(OH)D ] averaged 48 ± 9 ( SD ) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group , and 112 ± 41 nmol/L for the 100 mcg/day group . Both doses lowered plasma parathyroid hormone with no effect on plasma calcium . Between December and February , wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group ( 1-tail Mann-Whitney p = 0.036 ) . In Study 2 , 25(OH)D averaged 39 ± 9 nmol/L , and winter wellbeing scores improved with both doses of vitamin D ( two-tail p < 0.001 ) . Conclusion The highest AI for vitamin D  brought summertime 25(OH)D to > 40 nmol/L , lowered PTH , and its use was associated with improved wellbeing . The 100 mcg/day dose produced greater responses . Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients , we can not rule out a placebo wellbeing response , particularly for those on the lower dose . This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin Background Controversies are common in medicine . Some arise when the conclusions of research publications directly contradict each other , creating uncertainty for frontline clinicians . Discussion In this paper , we review how research ers can look at very similar data yet have completely different conclusions based purely on an over-reliance of statistical significance and an unclear underst and ing of confidence intervals . The dogmatic adherence to statistical significant thresholds can lead authors to write dichotomized absolute conclusions while ignoring the broader interpretations of very consistent findings . We describe three examples of controversy around the potential benefit of a medication , a comparison between new medications , and a medication with a potential harm . The examples include the highest levels of evidence , both meta-analyses and r and omized controlled trials . We will show how in each case the confidence intervals and point estimates were very similar . The only identifiable differences to account for the contrasting conclusions arise from the serendipitous finding of confidence intervals that either marginally cross or just fail to cross the line of statistical significance . Summary These opposing conclusions are false disagreements that create unnecessary clinical uncertainty . We provide helpful recommendations in approaching conflicting conclusions when they are associated with remarkably similar results OBJECTIVE To compare the effects of dydrogesterone and calcium plus vitamin D in women with severe premenstrual syndrome ( PMS ) . METHOD In this r and omized , double-blind , placebo-controlled study , 180 Shiraz University students with PMS used question naires daily to rate their symptoms for 2 menstrual cycles . Then , the students were r and omly assigned to take a tablet containing either 5 mg of dydrogesterone , 500 mg of calcium plus 200 mg of vitamin D , or a placebo twice daily from the 15th to the 24th day of the cycle for 2 more cycles , and to use the same question naires during the intervention cycles . The collected data were then analyzed by repeated-measurement design and multilevel modeling tests . RESULT Treatment with dydrogesterone or calcium plus vitamin D  decreased symptom severity in a similar way ( by 4.64 % and 4.20 % , respectively ) and placebo was associated with a 3.42 % decrease . CONCLUSION Treatment with dydrogesterone or calcium plus vitamin D had a similar effect on symptom severity in women with PMS OBJECTIVE : Observational studies suggest that serum levels of 25-hydroxyvitamin D ( 25[OH]D ) are inversely associated with acute respiratory infections ( ARIs ) . We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs . METHODS : By using cluster r and omization , classrooms of 744 Mongolian schoolchildren were r and omly assigned to different treatments in winter ( January – March ) . This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk ( control ; n = 104 ) or milk fortified with 300 IU of vitamin D3 ( n = 143 ) . This comparison was double-blinded . The primary outcome was the number of parent-reported ARIs over the past 3 months . RESULTS : At baseline , the median serum 25(OH)D level was 7 ng/mL ( interquartile range : 5–10 ng/mL ) . At the end of the trial , follow-up was 99 % ( n = 244 ) , and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different ( 7 vs 19 ng/mL ; P < .001 ) . Compared with controls , children receiving vitamin D reported significantly fewer ARIs during the study period ( mean : 0.80 vs 0.45 ; P = .047 ) , with a rate ratio of 0.52 ( 95 % confidence interval : 0.31–0.89 ) . Adjusting for age , gender , and history of wheezing , vitamin D continued to halve the risk of ARI ( rate ratio : 0.50 [ 95 % confidence interval : 0.28–0.88 ] ) . Similar results were found among children either below or above the median 25(OH)D level at baseline ( rate ratio : 0.41 vs 0.57 ; Pinteraction = .27 ) . CONCLUSIONS : Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency OBJECTIVES To determine the prevalence of vitamin D deficiency in older people in residential care and the influence that the level of vitamin D may have on their incidence of falls . DESIGN Prospect i ve cohort . SETTING Residential care facilities for older people in several states of Australia . PARTICIPANTS Six hundred sixty-seven women in low-level care and 952 women in high-level care , mean age 83.7 years . MEASUREMENTS  Serum 25-hydroxyvitamin D ( 25D ) levels and recognized risk factors for falls including current medication use , a history of previous fractures , weight , tibial length ( as a surrogate for height ) , cognitive function , walking ability , and frequency of going outdoors were determined . The women in low-level care and high-level care were followed for an average of 145 and 168 days , respectively . Falls were recorded prospect ively in diaries completed monthly by residential care staff . RESULTS  Vitamin D deficiency ( defined as a serum 25D level below 25 nmol/L ) was present in 144 ( 22 % ) women in low-level care and 428 ( 45 % ) in high-level care . After excluding 358 bed-bound residents and adjusting for weight , cognitive status , psychotropic drug use , previous Colles fracture , and the presence of w and ering behavior , log serum 25D level remained independently associated with time to first fall . The adjusted hazards ratio was 0.74 ( 95 % confidence interval=0.59 - 0.94 ; P=.01 ) , implying a 20 % reduction in the risk of falling with a doubling of the vitamin D level . CONCLUSION Vitamin D deficiency is common in residential care in Australia . A low level of serum vitamin D is an independent predictor of incident falls BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk  of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces  all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women 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 To determine whether calcium plus vitamin D supplementation ( CaD ) affects incidence of  rheumatoid arthritis ( RA ) . Participants enrolled in the Women ’s Health Initiative CaD trial ( n = 36,282 ) were r and omized to 1,000 mg calcium carbonate plus 400 IU of vitamin D3 daily or to placebo . Incident RA cases were identified via self-report and vali date d rheumatic medication use . Cox proportional hazards models were used to compare RA incidence in the treatment versus placebo groups . The analysis included 32,435 women without the history of RA , of which 163 incident RA cases were identified over an average of 5.1 years . No significant differences in demographics , total personal vitamin D intake [ P = 0.36 ] , or solar irradiance [ P = 0.68 ] were seen between the groups . In intention-to-treat analyses , no differences were observed in RA incidence [ HR 1.04 , 95 % CI 0.76 , 1.41 ] . No significant modifying effects were seen for stratum of age , solar irradiance , or total vitamin D intake , overall or when adjusted for adherence . Significant effect modifications were seen between  CaD  and total vitamin D  intake and CaD and solar irradiance that suggest increased RA incidence with high vitamin D exposure . CaD supplementation did not demonstrate a significant effect on RA incidence  in postmenopausal women . Modifying effects between CaD and both solar irradiance and dietary vitamin D intake are suggestive that multiple high vitamin D exposures may increase RA incidence . Further research is needed to fully explore the benefits and possible adverse effects of vitamin D supplementation on RA Objectives : Vitamin D has immune-modulating effects and may protect against the development of systemic lupus erythematosus ( SLE ) and rheumatoid arthritis ( RA ) . Methods : We identified incident cases of SLE and RA among 186 389 women followed from 1980 to 2002 in the Nurses ’ Health Study and Nurses ’ Health Study II cohorts . We excluded subjects where SLE or RA was not confirmed by medical record review , and those who failed to return question naires . Semi-quantitative food frequency question naires assessed  vitamin D intake from food and supplements .  We used cumulative-up date d total energy-adjusted dietary exposures for each 2-year cycle . Relationships between vitamin D  intake and incident SLE and RA were examined in age-adjusted and Cox proportional hazards models , adjusted for confounders . Results were pooled using meta- analysis r and om effects models . Results : We confirmed 190 incident cases of SLE and 722 of RA with dietary information . Increasing levels of  vitamin D  intake had no relationship to the relative risk of developing either SLE or RA . Conclusions : Vitamin D intake was not associated with risk of SLE or RA in these large prospect i ve cohorts of women CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 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 Objective : Low vitamin D status has been associated with multiple sclerosis ( MS ) prevalence and risk , but the therapeutic potential of vitamin D in established MS has not been explored . Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical , immunologic , and clinical outcomes in patients with MS prospect ively . Methods : An open-label r and omized prospect i ve controlled 52-week trial matched patients with MS for demographic and disease characteristics , with r and omization to treatment or control groups . Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [ 25(OH)D ] rapidly and assess tolerability , followed by 10,000 IU/day ( 12 weeks ) , and further downtitrated to 0 IU/day . Calcium ( 1,200 mg/day ) was given throughout the trial . Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups . Secondary endpoints included 25(OH)D and other biochemical measures , immunologic biomarkers , relapse events , and Exp and ed Disability Status Scale ( EDSS ) score . Results : Forty-nine patients ( 25 treatment , 24 control ) were enrolled [ mean age 40.5 years , EDSS 1.34 , and 25(OH)D 78 nmol/L ] . All calcium-related measures within and between groups were normal . Despite a mean peak 25(OH)D of 413nmol/L , no significant adverse events occurred . Although there may have been confounding variables in clinical outcomes , treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls . Conclusions : High-dose vitamin D ( ∼10,000 IU/day ) in multiple sclerosis is safe , with evidence of immunomodulatory effects . Classification of evidence : This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation . The trial , however , lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures ( relapses and Exp and ed Disability Status Scale scores ) , providing only Class level IV evidence for these outcomes OBJECTIVE Vitamin D is a potent regulator of calcium homeostasis and may have immunomodulatory effects . The influence of vitamin D on human autoimmune disease has not been well defined . The purpose of this study was to evaluate the association of dietary and supplemental vitamin D intake with rheumatoid arthritis ( RA ) incidence . METHODS We analyzed data from a prospect i ve cohort study of 29,368 women of ages 55 - 69 years without a history of RA at study baseline in 1986 . Diet was ascertained using a self-administered , 127-item vali date d food frequency question naire that included supplemental vitamin D use . Risk ratios ( RRs ) and 95 % confidence intervals ( 95 % CIs ) were estimated using Cox proportional hazards regression , adjusting for potential confounders . RESULTS Through 11 years of followup , 152 cases of RA were vali date d against medical records . Greater intake ( highest versus lowest tertile ) of vitamin D  was inversely associated with risk of RA ( RR 0.67 , 95 % CI 0.44 - 1.00 , P for trend = 0.05 ) . Inverse associations were apparent for both dietary ( RR 0.72 , 95 % CI 0.46 - 1.14 , P for trend = 0.16 ) and supplemental ( RR 0.66 , 95 % CI 0.43 - 1.00 , P for trend = 0.03 )  vitamin D.  No individual food item high in vitamin D content and /or calcium was strongly associated with RA risk , but a composite measure of milk products was suggestive of an inverse association with risk of RA ( RR 0.66 , 95 % CI 0.42 - 1.01 , P for trend = 0.06 ) . CONCLUSION Greater intake of vitamin D may be associated with a lower risk of RA in older women , although this finding is hypothesis generating Background Epidemiological research links vitamin D status to various brain-related outcomes . However , few trials examine whether supplementation can improve such outcomes and none have examined effects on cognition . This study examined whether Vitamin D supplementation led to improvements in diverse measures of cognitive and emotional functioning , and hypothesised that supplementation would lead to improvements in these outcomes compared to placebo . Methods /Principal Findings Healthy young adults were recruited to a parallel-arm , double-blind trial conducted at The University of Queensl and . Participants were r and omly allocated to receive Vitamin D ( one capsule daily , containing 5000 IU cholecalciferol ) or identical placebo capsule for six weeks . All participants and outcome assessors were blinded to group assignment . Primary outcome measures assessed at baseline and 6 weeks were working memory , response inhibition and cognitive flexibility . Secondary outcomes were : hallucination-proneness , psychotic-like experiences , and ratings of depression , anxiety and anger .  128 participants were recruited , r and omised and included in primary analyses ( vitamin D n = 63 ; placebo n = 65 ) . Despite significant increases in vitamin D status in the active group , no significant changes were observed in working memory ( F = 1.09 ; p = 0.30 ) , response inhibition ( F = 0.82 ; p = 0.37 ) , cognitive flexibility ( F = 1.37 ; p = 0.24 ) or secondary outcomes . No serious adverse effects were reported . Conclusions Our findings indicate that vitamin D supplementation does not influence cognitive or emotional functioning in healthy young adults . Future controlled trials in targeted population s of interest are required to determine whether supplementation can improve functioning in these domains . Australian and New Zeal and Clinical Trials Registry ; ACTRN12610000318088 BACKGROUND Seasonal Affective Disorder ( SAD ) is a sub-type of depression that only occurs during the winter months . A reduction in vitamin D may be linked to SAD . Since vitamin D deficiency has been reported to be common in older people , vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group . OBJECTIVE To assess the effect of vitamin D supplementation on the mental health of older women . SETTING Primary care in three areas of the UK ( Herts , Newcastle , York ) . SUBJECTS Women aged 70 years or more recruited to the trial in the months May-October . INTERVENTION Eligible women were r and omised to receive calcium and vitamin D supplementation or no supplementation . OUTCOME MEASURE At baseline and the six monthly assessment the mental component score ( MCS ) , calculated from the SF-12 question naire was used to assess participants ' subjective psychological well-being . RESULTS A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October ( 1205 woman in the control group and 912 women in the intervention group ) . Of these women , 1621 had a  MCS score at baseline and six months . Comparison of the six month mean MCS scores , adjusting for baseline MCS score and age , showed there was no significant difference between the two scores ( p = 0.262 ) . CONCLUSIONS Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores OBJECTIVES The objective of the present study was to examine the cross-sectional relation between serum 25-hydroxyvitamin D [ 25-(OH ) D ] levels and  depression in overweight and obese subjects and to assess the effect of vitamin D supplementation on depressive symptoms . DESIGN Cross-sectional study and r and omized double blind controlled trial of 20,000 or 40,000 IU vitamin D per week versus placebo for 1 year . SETTING A total of 441 subjects ( body mass index 28 - 47 kg m(-2 ) , 159 men and 282 women , aged 21 - 70 years ) recruited by advertisements or from the out-patient clinic at the University Hospital of North Norway . MAIN OUTCOME MEASURES Beck Depression Inventory ( BDI ) score with subscales 1 - 13 and 14 - 21 . RESULTS Subjects with serum 25(OH)D levels < 40 nmol L(-1 ) scored significantly higher ( more depressive traits ) than those with serum 25(OH)D levels > or = 40 nmol L(-1 ) on the BDI total [ 6.0 ( 0 - 23 ) versus 4.5 ( 0 - 28 ) ( median and range ) ] and the BDI subscale 1 - 13 [ 2.0 ( 0 - 15 ) versus 1.0 ( 0 - 29.5 ) ] ( P < 0.05 ) . In the two groups given vitamin D , but not in the placebo group , there was a significant improvement in BDI scores after 1 year . There was a significant decrease in serum parathyroid hormone in the two vitamin D groups without a concomitant increase in serum calcium . CONCLUSIONS It appears to be a relation between serum levels of 25(OH)D and symptoms of depression . Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship Abstract Mood changes synchronised to the seasons exist on a continuum between individuals , with anxiety and depression increasing during the winter months . An extreme form of seasonality is manifested as the clinical syndrome of seasonal affective disorder ( SAD ) with carbohydrate craving , hypersomnia , lethargy , and changes in circadian rhythms also evident . It has been suggested that seasonality and the symptoms of SAD may be due to changing levels of vitamin D3 , the hormone of sunlight , leading to changes in brain serotonin . Forty-four healthy subjects were given 400 IU , 800 IU , or no vitamin D3 for 5 days during late winter in a r and om double-blind study . Results on a self-report measure showed that vitamin D3 significantly enhanced positive affect and there was some evidence of a reduction in negative affect . Results are discussed in terms of their implication s for seasonality , SAD , serotonin , food preference , sleep , and circadian rhythms 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 To determine the efficacy of oral vitamin D [ 25(OH)D ] in patients with active rheumatoid arthritis ( RA ) who are in methotrexate ( MTX ) therapy , patients receiving stable doses of MTX  were r and omized to one of two dose groups and received 12 weeks of double-blind vitamin D[25(OH)D ] ( 50,000 IU per week ) or matching placebo . The moderate and major efficacy measure was the proportion of patients with > 0.6 and > 1.2 improvement in RA based on the Disease Activity Score 28(DAS 28 ) at 12 weeks . Safety measures included adverse events and laboratory assessment s. On a background of MTX , the percentage of patients with a moderate/major DAS 28 response at week 12 in the vitamin D groups ( 76/44 % ) was not significantly different from placebo ( 64.6/33.4 % ) . Adverse events were typically mild and included small hepatic enzyme elevation ; we did not have any undesirable events result ing in discontinuation of study drug . In patients with active RA receiving stable doses of MTX , vitamin D showed non-significant improvement in efficacy outcomes compared to placebo Abstract The correlation between vitamin D deficiency and depression has recently been put forward and result ed in controversial findings . The present study was conducted to find out the effect of 2 single injections of 150,000 and 300,000 IU of vitamin D on improving the depression in depressed patients with vitamin D deficiency . This clinical trial study was carried out during 2011–2012 in Yazd , Islamic Republic of Iran . A total of 120 patients who had a Beck Depression Inventory II score of 17 + and were affected with vitamin D deficiency were r and omly assigned to 3 groups of 40 . They included G300 , G150 , and NTG . G300 and G150 received an intramuscular single dose of 300,000 and 150,000 IU of vitamin D , respectively , and the NTG group received nothing . After 3 months of intervention , the depression state , serum vitamin D , calcium , phosphorus , and parathormone were measured . The median of serum vitamin D after intervention were 60.2 , 54.6 , and 28.2 nmol/L ( P < 0.001 ) for the G300 , G150 , and NTG , respectively . Percentages of vitamin D deficiency after intervention were 18 , 20 , and 91.2 for the groups , respectively . The serum calcium mean showed a statistically significant increase in just the 2 test groups receiving vitamin D. There was only significant difference in mean of Beck Depression Inventory II test score between G300 and NTG ( P = 0.003).The results of the study revealed that first , the correction of vitamin D deficiency improved the depression state , and second , a single injection dose of 300,000 IU of vitamin D was safe and more effective than a 150,000-IU dose Very frail older people constitute an increasing proportion of ageing population s and often have vitamin D deficiency . Falls are frequent in this population and have usually been associated with vitamin D deficiency . In this prospect i ve study we measured serum 25-hydroxyvitamin D ( 25OHD ) , serum PTH , and falls in 637 ambulatory subjects living in institutional aged care facilities ( intermediate-care hostels or nursing homes ) . The study sample comprised 121 men ( mean age , 82.1 yr ) and 516 women ( mean age , 86.7 yr ) . Two hundred and seventy-four subjects fell one or more times over a mean duration of follow-up of 10.2 months . Vitamin D deficiency , defined as a serum 25OHD level below 39 nmol/liter was present in 73.6 % . Baseline serum 25OHD and PTH were significantly associated with falls in univariate analyses . In multivariate analyses that also corrected for balance and health status , PTH remained a significant predictor of falls independent of 25OHD . Serum PTH is a predictor of time to first fall in the frail elderly independent of vitamin D status and measures of general health 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 Seasonal Affective Disorder ( SAD ) is prevalent when vitamin D stores are typically low . Broad-spectrum light therapy includes wavelengths between 280 - 320 nm which allow the skin to produce vitamin D. This study was design ed to test the hypothesis that vitamin D deficiency might play a role in SAD . A prospect i ve , r and omized controlled trial was conducted in a group of 15 subjects with SAD . Eight subjects received 100,000 I.U. of vitamin D and seven subjects received phototherapy . At the onset of treatment and after 1 month of therapy subjects were administered the Hamilton Depression scale , the SIGH-SAD , and the SAD-8 depression scale . All subjects also had serum levels of 25-hydroxyvitamin D ( 25-OH D ) measured before and 1 week after intervention therapy . All subjects receiving vitamin D improved in all outcome measures . The phototherapy group showed no significant change in depression scale measures . Vitamin D status improved in both groups ( 74 % vitamin D group , p < 0.005 and 36 % phototherapy group , p < 0.01 ) . Improvement in 25-OH D was significantly associated with improvement in depression scale scores ( r2=0.26 ; p=0.05 ) . Vitamin D may be an important treatment for SAD . Further studies will be necessary to confirm these findings Objective : To compare the therapeutic effects of vitamin D3 plus fluoxetine and fluoxetine alone in patients with major depressive disorder . Methods : In the present double-blind , r and omized , placebo-controlled trial , 42 patients with a diagnosis of major depressive disorder based on DSM-IV criteria were r and omly assigned into two groups to receive daily either 1500 IU vitamin D3 plus 20 mg fluoxetine or fluoxetine alone for 8 weeks . Depression severity was assessed at 2-week intervals using the 24-item Hamilton Depression Rating Scale ( HDRS ) as a primary outcome measure and the 21-item Beck Depression Inventory ( BDI ) as a secondary outcome measure . Serum 25(OH ) vitamin D was measured at baseline and after intervention . Results : Forty patients completed the trial . A two-way repeated- measures analysis of variance showed that depression severity based on HDRS and BDI decreased significantly after intervention , with a significant difference between the two groups . The vitamin D + fluoxetine combination was significantly better than fluoxetine alone from the fourth week of treatment . Conclusions : In the present 8-week trial , the vitamin D + fluoxetine combination was superior to fluoxetine alone in controlling depressive symptoms OBJECTIVES Low trauma fractures in older people incur enormous physical , social and economic costs . Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group . This strategy requires validation in a population setting . METHODS R and omized , double-blind , placebo-controlled trial of 300,000 IU intramuscular ( i.m . ) vitamin D2 ( ergocalciferol ) injection or matching placebo every autumn over 3 years . 9440 people ( 4354 men and 5086 women ) aged 75 yrs and over were recruited from general practice registers in Wessex , Engl and . Primary outcome measure was all non-vertebral fracture . Secondary outcomes were hip and wrist fractures , and all falls . RESULTS 585 subjects had incident non-spine fractures  ( hip 110 , wrist 116 , ankle 37 ) . Hazard ratios ( HRs ) for fracture in the vitamin D group were : 1.09 [ 95 % confidence interval ( CI ) 0.93 - 1.28 , P = 0.29 ] for any first fracture , 1.49 ( 95 % CI 1.02 - 2.18 , P = 0.04 ) for hip and 1.22 ( 95 % CI 0.85 - 1.76 , P = 0.28 ) for wrist . There was no effect on falls : HR 0.98 ( 0.93 - 1.04 ) . No protective effect was observed in any subgroup when the cohort was stratified by sex , age , previous fracture or mobility . CONCLUSIONS An annual i.m . injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population While observational studies have suggested that vitamin D deficiency increases risk of depression , few clinical trials have tested whether vitamin D supplementation affects the occurrence of depression symptoms . The authors evaluated the impact of daily supplementation with 400 IU of vitamin D(3 ) combined with 1,000 mg of elemental calcium on measures of depression in a r and omized , double-blinded US trial comprising 36,282 postmenopausal women . The Burnam scale and current use of antidepressant medication were used to assess depressive symptoms at r and omization ( 1995 - 2000 ) . Two years later , women again reported on their antidepressant use , and 2,263 completed a second Burnam scale . After 2 years , women r and omized to receive vitamin D and calcium had an odds ratio for experiencing depressive symptoms ( Burnam score ≥0.06 ) of 1.16 ( 95 % confidence interval : 0.86 , 1.56 ) compared with women in the placebo group . Supplementation was not associated with antidepressant use ( odds ratio = 1.01 , 95 % confidence interval : 0.92 , 1.12 ) or continuous depressive symptom score . Results stratified by  baseline vitamin D and calcium intake , solar irradiance , and other factors were similar . The findings do not support a relation between supplementation with 400 IU/day of vitamin D(3 ) along  with calcium and depression in older women . Additional trials testing higher doses of vitamin D are needed to determine whether this nutrient may help prevent or treat depression OBJECTIVES To evaluate the association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and mortality in a representative U.S. sample of older adults . DESIGN Prospect i ve cohort from the Third National Health and Nutrition Examination Survey ( NHANES III ) and linked mortality files . SETTING Noninstitutionalized U.S. civilian population . PARTICIPANTS Three thous and four hundred eight NHANES III participants aged 65 and older enrolled from 1988 to 1994 and followed for mortality through 2000 . MEASUREMENTS Primary exposure was  serum 25(OH)D level  at enrollment . Primary and secondary outcomes were all-cause and cardiovascular disease ( CVD ) mortality , respectively . RESULTS During the median 7.3 years of follow-up , there were 1,493 ( 44 % ) deaths , including 767 CVD-related deaths . Median 25(OH)D level was 66 nmol/L. Adjusting for demographics , season , and cardiovascular risk factors , baseline 25(OH)D levels were inversely associated with all-cause mortality risk ( adjusted hazard ratio (HR)=0.95 , 95 % confidence interval (CI)=0.92 - 0.98 , per 10 nmol/L 25[OH]D ) . Compared with subjects with 25(OH)D levels of 100 nmol/L or higher , the adjusted HR for subjects with levels less than 25.0 nmol/L was 1.83 ( 95 % CI=1.14 - 2.94 ) and for levels of 25.0 to 49.9 nmol/L was 1.47 ( 95 % CI=1.09 - 1.97 ) . The association appeared stronger for CVD mortality ( adjusted HR=2.36 , 95 % CI=1.17 - 4.75 , for subjects with 25[OH]D levels<25.0 nmol/L vs those > or = 100.0 nmol/L ) than for non-CVD mortality ( adjusted HR=1.42 , 95 % CI=0.73 - 2.79 , for subjects with 25[OH]D levels<25.0 nmol/L vs those > or = 100.0 nmol/L ) . CONCLUSION In noninstitutionalized older adults , a group at high risk for all-cause mortality , serum 25(OH)D levels had an independent , inverse association with CVD and all-cause mortality . R and omized controlled trials of vitamin D supplementation in older adults are warranted to determine whether this association is causal and reversible In a double-blind clinical trial on 49 patients with rheumatoid arthritis , calciferol was given in a dose of 100 000 IU per day for 1 year to 24 patients , while the remaining 25 received placebo .  Objective and subjective improvement was noted in 67 % of the calciferol group and in 36 % of the control group , while objective and subjective deterioration was noted in 4 % of the calciferol group and in 32 % of the control group . The mean values for sedimentation rate and a2-globulin decreased and the mean hemoglobin level increased in the calciferol group . The consumption of analgesics and antiinflammatory medicines  decreased significantly in the calciferol group and after 1 year morning stiffness had eased and h and strength had increased in this group A 1-year prospect i ve study of seasonal mood changes was conducted in 250 female Boston area residents , aged 43 to 72 , who were participants in a study of vitamin D supplementation .  Each woman completed the Profile of Mood States question naire at four study visits . There were significant changes over the year in scores for Tension-Anxiety , Depression-Dejection , Anger-Hostility , Fatigue-Inertia , and Confusion-Bewilderment . These scores were all highest or " worst " in the fall and lowest in the spring or summer . Worse mood scores were associated with fewer hours of sleep . Serum thyroxine was positively associated with higher Depression-Dejection scores in August through November and with higher ( better ) Vigor-Activity scores in February through May. Supplementation with 400 IU of vitamin D did not appear to affect levels or changes in mood scores OBJECTIVE To examine the association of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment in a r and omized , double-blind , placebo-controlled trial . METHODS Adult primary care patients in Duluth , Minnesota , were screened for vitamin D deficiency in February 2007 . Participants completed question naires pertaining to a variety of symptoms , vitamin D intake , and selected medical conditions . Patients with mild to moderate vitamin D deficiency ( 25-hydroxyvitamin D [ 25(OH)D ] , 10 - 25 ng/mL ) participated in a r and omized controlled trial ( RCT ) of vitamin D replacement and its effect on symptoms . Participants were r and omly assigned to receive 50 000 units of cholecalciferol ( vitamin D3 ) weekly or placebo for 8 weeks . Patients with severe vitamin D deficiency ( 25[OH]D < 10 ng/mL ) were treated in an unblinded fashion , and symptoms were reevaluated post treatment . RESULTS A total of 610 patients underwent initial screening , and 100 patients with mild to moderate vitamin D deficiency participated in the RCT . Thirty-eight severely deficient patients were treated in an unblinded fashion . On initial screening , 46.2 % of participants were deficient in vitamin D. Self-reported vitamin D supplementation , milk intake , celiac disease , gastric bypass , and chronic pancreatitis were predictive of vitamin D status . Severely deficient participants reported increased musculoskeletal symptoms , depression ( including seasonal ) , and higher ( worse ) scores on a fibromyalgia assessment question naire . In the RCT , the treated group showed significant improvement in fibromyalgia assessment scores ( P = 0.03 ) , whereas the placebo-treated participants did not . Severely deficient patients did not show symptom improvement over the 8-week trial period or when followed up 1 year later . CONCLUSIONS Compared with participants in the placebo group , patients in the treatment group showed mild short-term improvement in the overall fibromyalgia impact score , but did not show significant improvement in most musculoskeletal symptoms or in activities of daily living Objective The aim of this study was to examine the effect of hormone therapy and calcitriol on  depression in older postmenopausal women and to determine whether the response was associated with polymorphisms of estrogen receptor & agr ; and vitamin D receptor . Methods In a double-blind placebo-controlled prospect i ve trial involving 489 postmenopausal older women , a secondary analysis of depression was done . The Geriatric Depression Scale was used to screen for depression . We used binary logistic regression to examine the effect of treatment on depression and one-way analysis of variance to find a relationship between gene polymorphisms and depression . Results There was no effect of hormone therapy ( odds ratio [ OR ] , 1.65 ; 95 % CI , 0.66 - 4.12 ; P = 0.277 ) , calcitriol ( OR , 1.15 ; 95 % CI , 0.43 - 3.11 ; P = 0.772 ) , or hormone therapy with calcitriol ( OR , 1.01 ; 95 % CI , 0.36 - 2.80 ; P = 0.979 ) on depression . Neither the polymorphisms of estrogen receptor & agr ; ( XbaI-&bgr ; = 0.093 ; CI , −0.337 to 1.350 ; P = 0.239 and PvuII-&bgr ; = −0.064 ; CI , −1.171 to 0.491 , P = 0.421 ) nor those of vitamin D receptor ( BsmI-&bgr ; = 0.044 , CI −2.546 to 3.030 , P = 0.865 and TaqI-&bgr ; = −0.015 , CI −2.900 to 2.738 , P = 0.955 ) were associated with depression . Conclusion In older postmenopausal women , there was no effect of hormone therapy and calcitriol either individually or in combination with depression . Estrogen receptor & agr ; and vitamin D receptor polymorphisms are not associated with depression or the response to intervention in older postmenopausal women . Additional trials are required to confirm these findings OBJECTIVE Ecologic and observational studies have suggested an association between serum 25-hydroxyvitamin D ( 25(OH)D ) levels and cardiovascular disease ( CVD ) risk factors , CVD mortality , and cancer mortality . Based on this , low serum 25(OH)D levels should be associated with higher all-cause mortality in a general population . This hypothesis was tested in the present study . DESIGN The Tromsø study is a longitudinal population -based multi purpose study initiated in 1974 with focus on lifestyle-related diseases . Our data are based on the fourth Tromsø study carried out in 1994 - 1995 . METHODS Information about death and cause of death was registered by obtaining information from the National Directory of Residents and the Death Cause Registry .  Serum 25(OH)D  was measured in 7161 participants in the fourth Tromsø study . Results are presented for smokers ( n=2410 ) and non-smokers ( n=4751 ) separately as our immunoassay seems to overestimate 25(OH)D levels for smokers . RESULTS During a mean 11.7 years of follow-up , 1359 ( 19.0 % ) participants died . In multivariate regression models , there was a significantly increased risk of all-cause mortality ( hazard ratio ( HR ) 1.32 , confidence interval ( CI ) 1.07 - 1.62 ) among non-smoking participants in the lowest 25(OH)D quartile when compared with participants in the highest quartile . Equivalent results for smokers were not significant ( HR 1.06 , CI 0.83 - 1.35 ) . CONCLUSIONS Low serum 25(OH)D levels were associated with increased all-cause mortality for non-smokers , but the results did not reach statistical significance for smokers . However , low 25(OH)D levels are known to be associated with impaired general health , and r and omized controlled studies are needed to address the question of causality
target: The evidence shows that vitamin D supplementation provides some benefit in fracture prevention ( likely ∼10–15 % relative reduction ) , particularly at a dose ≥800 IU and with calcium ; a likely benefit in the rate of falls , though it is less clear whether the number of fallers changes ; and a possible small ( ∼5 % ) relative reduction in mortality .
  Evidence does not support the use of vitamin D supplementation for the prevention of cancer , respiratory infections or rheumatoid arthritis .
  Similarly , evidence does not support vitamin D supplementation for the treatment of multiple sclerosis and rheumatoid arthritis or for improving depression/mental well-being .
  Regular testing of 25-hydroxyvitamin D is generally not required , and mega-doses ( ≥300,000 IU ) appear to increase harms .
background: Over the past decade , a large body of observational evidence has suggested an association between  lower vitamin D status ( 25-hydroxyvitamin D ) and multiple acute and chronic disorders , including cancer , multiple sclerosis , depression and respiratory tract infections .
  This evidence has fostered the hypothesis that increasing vitamin D intake may treat and prevent such disorders .
  Our objective was to perform a critical analysis of the highest-level evidence for ten common beliefs regarding vitamin D for the prevention of falls , fractures and respiratory tract infections , the reduction of cancer incidence/mortality and overall mortality , and the prevention or treatment of depression/mental well-being , rheumatoid arthritis and multiple sclerosis , as well as maximum dosing and regular testing .