title: The association between serum 25-hydroxyvitamin D3 concentration and risk of disease death in men: modification by magnesium intake Total 25-Hydroxyvitamin D Concentration as a Predictor for All-Cause Death and Cardiovascular Event Risk among Ethnic Chinese Adults: A Cohort Study in a Taiwan Community Circulating 25OHD, dietary vitamin D, PTH, and calcium associations with incident cardiovascular disease and mortality: the MIDSPAN Family Study. Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up. Effect of follow-up time on the relation between prediagnostic serum 25-hydroxyvitamin D and all-cause mortality rate Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults The effect of vitamin D and frailty on mortality among non-institutionalized US older adults Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland Prospective study of serum 25-hydroxyvitamin D concentration and mortality in a Chinese population. Serum 25-hydroxyvitamin D level, chronic diseases and all-cause mortality in a population-based prospective cohort: the HUNT Study, Norway A prospective study of serum 25-hydroxyvitamin d levels and mortality among African Americans and non-African Americans. Circulating calcitriol concentrations and total mortality. Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men. Genetically low vitamin D concentrations and increased mortality: mendelian randomisation analysis in three large cohorts Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents. Vitamin D status and the risk of cardiovascular disease death. 25-hydroxyvitamin D and increased all-cause mortality in very old women: the Newcastle 85+ study A Reverse J-Shaped Association Between Serum 25-Hydroxyvitamin D and Cardiovascular Disease Mortality: The CopD Study. Vitamin d, parathyroid hormone, and cardiovascular mortality in older adults: the Rancho Bernardo study. 25-Hydroxyvitamin D, parathyroid hormone, and mortality in black and white older adults: the health ABC study. Prospective association of vitamin D with frailty status and all-cause mortality in older adults: Results from the KORA-Age Study. Low vitamin D status is an independent predictor of increased frailty and all-cause mortality in older men: the Health in Men Study. The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer. Update on the Vitamin D and OmegA-3 trial (VITAL) Vitamin D deficiency in elderly people in Swedish nursing homes is associated with increased mortality. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Associations between serum 25-hydroxyvitamin D concentrations and multiple health conditions, physical performance measures, disability, and all-cause mortality: the Concord Health and Ageing in Men Project. Association Between Hypovitaminosis D in Elderly Women and Long- and Short-Term Mortality-Results from the Osteoporotic Prospective Risk Assessment Cohort. Serum 25‐hydroxyvitamin D as a predictor of mortality and cardiovascular events: A 20‐year study of a community‐based cohort 25-Hydroxyvitamin D concentration and all-cause mortality: the Melbourne Collaborative Cohort Study. Low Serum Vitamin D is Not Associated with an Increase in Mortality in Oldest Old Subjects: The Octabaix Three-Year Follow-Up Study Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men. Estimation of the optimum dose of vitamin D for disease prevention in older people: Rationale, design and baseline characteristics of the BEST-D trial Vitamin D, PTH and the risk of overall and disease-specific mortality: Results of the Longitudinal Aging Study Amsterdam Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. Vitamin D for health: a global perspective. Does liver damage explain the inverse association between vitamin D status and mortality? Low serum 25-hydroxyvitamin D concentrations are associated with greater all-cause mortality in older community-dwelling women. The inverse association between serum 25-hydroxyvitamin D and mortality may be modified by vitamin A status and use of vitamin A supplements Bone Mineral Density and Parathyroid Hormone as Independent Risk Factors for Mortality in Community-Dwelling Older Adults: A Population-Based Prospective Cohort Study in Brazil. The São Paulo Ageing & Health (SPAH) Study. Prospective association of vitamin D concentrations with mortality in postmenopausal women: results from the Women's Health Initiative (WHI). Nutritional status and subsequent all-cause mortality in men and women aged 75 years or over living in the community. Contributions of 25-hydroxyvitamin D, co-morbidities and bone mass to mortality in Japanese postmenopausal women. Monthly High-Dose Vitamin D Supplementation and Cancer Risk: A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease Vitamin D and overall cancer risk and cancer mortality: a Mendelian randomization study Low serum 25-hydroxyvitamin D levels are associated with increased all-cause mortality risk in a general population: the Tromsø study. Vitamin D insufficiency and health outcomes over 5 y in older women.
abstract: Low vitamin D status increases the risk of death . Magnesium plays an essential role in vitamin D metabolism and low magnesium intake may predispose to vitamin D deficiency and potentiate the health problems . We investigated whether magnesium intake modifies the serum 25(OH)D3 concentration and its associations with mortality in middle-aged and older men . We included 1892 men aged 42–60 years without cardiovascular disease or cancer at baseline in 1984–1989 from the prospect i ve , population -based Kuopio Ischaemic Heart Disease Risk Factor Study .  Serum 25(OH)D3 was measured with the high-performance liquid chromatography using coulometric electrode array detection . Magnesium intake was assessed with 4-day food recording .  Deaths were ascertained by a computer linkage to the national cause of death register . Deaths due accidents and suicides were excluded . Cox proportional hazards regression models were used to analyze the associations . The multivariate-adjusted hazard ratio ( HR ) for death in the lowest ( < 32.1 nmol/L ) versus the highest ( > 49.4 nmol/L ) serum 25(OH)D3 tertile was 1.31 ( 95 % CI 1.07–1.60 , Ptrend = 0.01 ) . Stratified by the magnesium intake , the higher risk was observed only in the lower magnesium intake median ( < 414 mg/day ) ; HR = 1.60 ( 95 % CI 1.19–2.13 , Ptrend = 0.002 ) in the lowest versus the highest 25(OH)D3 tertile , whereas the corresponding HR = 1.07 , 95 % CI 0.75–1.36 , Ptrend = 0.63 ) in the higher magnesium intake median , P for interaction = 0.08 . In this cohort of middle-aged and older men  low serum 25(OH)D3 concentration was associated with increased risk of death mainly in those with lower magnesium intake Background Evidence of an inverse association between serum  25-hydoroxyvitamin D [ 25(OH)D ] and the risk of all-cause death and cardiovascular disease from prospect i ve studies is inconsistent . We tested the relationship between 25(OH)D and the risk among adult ethnic Chinese in Taiwan . Methods We conducted a community-based cohort study of 1816 participants ( age 60.2±10.2 yrs , 45.0 % women ) in the Chin-Shan Community Cardiovascular Cohort Study who were free of cardiovascular diseases at baseline and provided 25(OH)D measurements . Results During a median 9.6 ( interquartile range , 8.8- 10.5 ) years ’ follow-up period , totally 263 cases developed cardiovascular death events and 559 participants were documented to death from any cause . As 25(OH)D concentration increased , the incidence rates of cardiovascular events and all-cause death decreased progressively . 25(OH)D was inversely associated with all-cause death : the adjusted hazard ratio was 0.49 ( 95 % confidence interval [ CI ] , 0.25 - 0.97 ) for the third quartile and a significant J-shape relationship was found . The performance measures by integrated discriminative improvement showed significant improvement after adding 25(OH)D information ( 0.14 % , 95 % CI , 0.03 - 0.31 , P=0.050 , for all-cause death and 0.32 % , 95 % CI , 0.02 - 0.62 , P=0.018 for cardiovascular events ) . Conclusion These findings suggested a modest inverse association between 25(OH)D and the risk of all-cause death among diabetic participants and a good predictive factor in the community . Further studies to investigate the mechanism of vitamin D role on health effect are warranted CONTEXT Observational studies relating circulating 25-hydroxyvitamin D ( 25OHD ) and dietary vitamin D intake to cardiovascular disease ( CVD ) have reported conflicting results . OBJECTIVE Our objective was to investigate the association of 25OHD , dietary vitamin D , PTH , and adjusted calcium  with  CVD and mortality in a Scottish cohort . DESIGN AND SETTING The MIDSPAN Family Study is a prospect i ve study of 1040 men and 1298 women from the West of Scotl and recruited in 1996 and followed up for a median 14.4 yr . PARTICIPANTS Locally resident adult offspring of a general population cohort were recruited from 1972 - 1976 . MAIN OUTCOME MEASURES CVD events ( n = 416 ) and all-cause mortality ( n = 100 ) were evaluated . RESULTS 25OHD was measured using liquid chromatography-t and em mass spectrometry in available plasma ( n = 2081 ) . Median plasma 25OHD was 18.6 ng/ml , and median vitamin D intake was 3.2 μg/d ( 128 IU/d ) . Vitamin D deficiency ( 25OHD < 15 ng/ml ) was present in 689 participants ( 33.1 % ) . There was no evidence that dietary vitamin D intake , PTH , or adjusted calcium were associated with CVD events or with mortality . Vitamin D deficiency was not associated with CVD ( fully adjusted hazard ratio = 1.00 ; 95 % confidence interval = 0.77 - 1.31 ) . Results were similar after excluding patients who reported an activity-limiting longst and ing illness at baseline ( 18.8 % ) and those taking any vitamin supplements ( 21.7 % ) . However , there was some evidence vitamin D deficiency was associated with all-cause mortality ( fully adjusted hazard ratio = 2.02 ; 95 % confidence interval = 1.17 - 3.51 ) . CONCLUSION Vitamin D deficiency was not associated with risk of CVD in this cohort with very low 25OHD . Future trials of vitamin D supplementation in middle-aged cohorts should be powered to detect differences in mortality outcomes as well as CVD BACKGROUND AND AIMS Emerging evidence suggests that low levels of vitamin D may be an important risk factor for multiple chronic diseases and mortality , but the evidence is mixed . Vitamin D levels are associated with sun exposure , diet , and metabolic status . One potential explanation for the lack of consistent findings amongst various studies is that low vitamin levels may be associated with poor diets or other risk factors that we were not adequately controlled for in different analyses . METHODS Prospect i ve analysis of adults over the age of 35 in NHANES III data ( 1988 - 1994 ) with 20 year mortality follow-up . Sequential Cox proportional hazard models quartiles of 25OH vitamin D adjusted for age , season , geography , sociodemographic ( SD ) , CVD risk factors ( CVD ) and nutritional factors ( NF ) were performed . RESULTS Gender , race , diabetes , anti-hypertensive meds , income , taking  vitamin D supplements , physical activity , alcohol consumption , region , body mass index , blood pressure , creatinine , albumin , CRP , thyroxine , iron , RBC folate , vitamin A , E , alpha-carotene , and lycopene were all associated with different quartiles of vitamin D and as well as CHD and all-cause mortality and thus are important potential confounders of this relationship . Adjusting for the confounding factors , higher levels of vitamin D demonstrate an inverse relationship with all-cause mortality , but only the top quartile of vitamin D shows an inverse relationship with CHD mortality . CONCLUSIONS The highest quartile compared to the lowest quartile of 25OH vitamin D levels is inversely associated with CHD and all-cause mortality adjusting for multiple confounders . Whether supplementation of individuals with low vitamin D will result in similar benefits will require a r and omized clinical trial Evidence continues to mount that vitamin D reduces the risk and mortality rates of many types of disease . However , evidence from prospect i ve cohort studies is sometimes weaker than that from case – control and ecological studies . A suggested reason for this discrepancy is that , because serum levels of 25-hydroxyvitamin D [ 25(OH)D ] change over time , a single 25(OH)D concentration measurement taken at study enrollment does not reliably indicate 25(OH)D concentration related to the health outcome . To evaluate this suggestion further , this paper plots results from 12 prospect i ve cohort studies of all-cause mortality rate vs. follow-up time . The regression fit to the hazard ratio per 20-nmol/l increase in serum 25(OH)D concentration vs. time increased from 0.82 ( 95 % CI , 0.67–1.02 ) for 6 y to 0.96 ( 95 % CI , 0.90–1.01 ) for 14 y. The value extrapolated for zero follow-up time was 0.72 ( 95 % CI , 0.50–1.03 ) , giving a hazard ratio reduction 3.5 times higher than the st and ard result from the meta- analysis [ 0.92 ( 95 % CI , 0.89–0.95 ) ] . Using the example of the Vitamin D Pooling Project of Rarer Cancers , this paper also discusses follow-up time ’s effect in interpreting prospect i ve cohort studies of cancer outcome . This paper recommends that meta-analyses of prospect i ve cohort studies account for follow-up time and , if possible , that studies measure serum 25(OH)D concentration every 2–4 Background / Objectives : Vitamin D deficiency is associated with cardiovascular disease , osteoporosis , poor muscle strength , falls , fractures and mortality . Although older adults are at a higher risk of vitamin D deficiency , the relationship of serum 25-hydroxyvitamin D ( 25(OH)D ) with all-cause and cardiovascular disease mortality has not been well characterized in the elderly . We hypothesized that low serum 25(OH)D levels predicted mortality in older adults . Subjects/ Methods : Serum 25(OH)D  as well as all-cause and cardiovascular disease mortality were examined in 1006 adults , aged ⩾65 years , who participated in the InCHIANTI ( Invecchiare in Chianti , Aging in the Chianti Area ) study , a population -based , prospect i ve cohort study of aging in Tuscany , Italy . Serum 25(OH)D levels were measured at the time of enrollment in 1998–1999 , and participants were followed up for mortality . Results : During 6.5 years of follow-up , 228 ( 22.7 % ) participants died , of whom 107 died due to cardiovascular diseases . Compared with participants in the highest quartile of serum 25(OH)D ( > 26.5 ng/ml ) ( to convert to nmol/l , multiply by 2.496 ) , those in the lowest quartile ( < 10.5 ng/ml ) had increased risk of all-cause mortality ( Hazard Ratio ( H.R. ) 2.11 , 95 % Confidence Interval ( 95 % C.I. ) : 1.22–3.64 , P=0.007 ) and cardiovascular disease mortality ( H.R. 2.64 , 95 % C.I. : 1.14–4.79 , P=0.02 ) , in multivariate Cox proportional hazards models that adjusted for age , sex , education , season , physical activity and other potential confounders . Conclusions : Older community-dwelling adults with low serum 25(OH)D levels are at higher risk of all-cause and cardiovascular disease mortality BACKGROUND / OBJECTIVES : Although both frailty and low vitamin D have been separately associated with an increased risk for adverse health , their joined effects on mortality have not been reported . The current study examined prospect ively the effects of frailty and vitamin D status on mortality in US older adults . SUBJECTS/ METHODS : Participants aged ⩾60 years in The Third National Health and Nutrition Examination Survey with 12 years of mortality follow-up were included in the analysis ( n=4731 ) . Frailty was defined as meeting three or more criteria and pre-frailty as meeting one or two of the five frailty criteria ( low body mass index ( BMI ) , slow walking , weakness , exhaustion and low physical activity )  . Vitamin D status  was assessed by serum 25-hydroxyvitamin D ( 25(OH)D )  and categorized into quartiles . Analyses were adjusted for gender , race , age , smoking , education , latitude and other comorbid conditions . RESULTS : Serum 25(OH)D concentrations were lowest in participants with frailty , intermediate in participants with pre-frailty and highest in participants without frailty . The odds of frailty in the lowest quartile of serum 25(OH)D was 1.94 times the odds in the highest quartile ( 95 % confidence interval ( CI ) : 1.09–3.44 ) . Mortality was positively associated with frailty , with the risk among participants who were frail and had low serum 25(OH)D being significantly higher than those who were not frail and who had high concentrations of serum 25(OH)D ( hazards ratio 2.98 ; 95 % CI : 2.01–4.42 ) . CONCLUSION : Our results suggest that low serum 25(OH)D is associated with frailty , and there is additive joint effects of serum 25(OH)D and frailty on all-cause mortality in older adults Purpose To investigate the association between serum 25-hydroxyvitamin D [ 25(OH)D ] concentration , a marker of vitamin D status , and risk of all-cause and cardiovascular mortality in a general older population with relatively low average serum 25(OH)D concentrations . Methods The study population included 552 men and 584 women aged 53–73 years who were free of CVD and cancer at baseline in 1998–2001 from the prospect i ve , population -based Kuopio Ischaemic Heart Disease Risk Factor ( KIHD ) Study . Deaths were ascertained by a computer linkage to the national cause of death register . All deaths that occurred from the study entry to December 31 , 2008 , were included . Cox proportional hazards regression models were used to analyze the association between serum 25(OH)D and risk of death . Results The mean serum 25(OH)D concentration was 43.7 nmol/L ( SD 17.8 ) , with a strong seasonal variation . During the average follow-up of 9.1 years , 87 participants died , 35 from cardiovascular disease ( CVD ) . After multivariable-adjustments , the hazard ratios ( HR ) for all cause death in the tertiles of serum 25(OH)D were 1 , 1.68 ( 95 % CI : 0.92 , 3.07 ) and 2.06 ( 95 % CI : 1.12 , 3.80 ) , p for trend = 0.02 . Conclusions Our study supports the accumulating evidence from epidemiological studies that vitamin D deficiency is associated with increased risk of death . Large-scale primary prevention trials with vitamin D supplementation are warranted Prospect i ve epidemiologic data on the association between vitamin D and mortality are limited , particularly in Asian population s. Among subjects in Linxian , China , the authors aim ed to test whether baseline serum 25-hydroxyvitamin D ( 25(OH)D ) concentrations in a prospect i ve cohort were associated with all-cause mortality and cause-specific mortality rates over 24 years of follow-up ( 1986 - 2010 ) .  Serum 25(OH)D concentrations  were measured in 1,101 subjects  using an immunoassay .  Hazard ratios and 95 % confidence intervals were calculated using Cox regression models that were adjusted for age , sex , tobacco smoking , alcohol drinking , and hypertension . The 25th , 50th , and 75th percentile concentrations of 25(OH)D were 19.6 , 31.9 , and 48.4 nmol/L , respectively . During follow-up , 793 subjects died  , including 279 who died of cerebrovascular accident  , 217 who died of cancer  , and 200 cardiovascular disease deaths . All-cause mortality was not associated with 25(OH)D concentrations using continuous models ( for every 15 nmol/L , hazard ratio = 1.01 , 95 % confidence interval : 0.97 , 1.05 ) or quartile models ( fourth vs. first quartiles , hazard ratio = 1.06 , 95 % confidence interval : 0.87 , 1.30 ; P for trend = 0.731 ) . The authors also found no association with the cause-specific mortality outcomes . Results were similar for men and women . This study showed that prediagnostic serum 25(OH)D concentrations were not associated with all-cause or cause-specific mortality rates in this Chinese population who had low levels of vitamin Objective To investigate the association of vitamin D status with  all-cause mortality in a Norwegian population and the potential influences of existing chronic diseases on the association . Design A population -based prospect i ve cohort study . Setting Nord-Trøndelag County , Norway . Participants A r and om sample ( n=6613 ) of adults aged 20 years or older in a cohort . Methods  Serum 25-hydroxyvitamin D ( 25(OH)D ) levels were measured in blood sample s collected at baseline ( n=6377 ) .  Mortality was ascertained from the Norwegian National Registry . Cox regression models were applied to estimate the HRs with 95 % CIs for all-cause mortality in association with serum 25(OH)D levels after adjustment for a wide spectrum of confounding factors as well as chronic diseases at baseline . Results The median follow-up time was 18.5 years , during which 1539 subjects died . The HRs for all-cause mortality associated with the first quartile level of 25(OH)D ( < 34.5 nmol/L ) as compared with the fourth quartile ( ≥58.1 nmol/L ) before and after adjustment for chronic diseases at baseline were 1.30 ( 95 % CI 1.11 to 1.51 ) and 1.27 ( 95 % CI 1.09 to 1.48 ) , respectively . In the subjects without chronic diseases at baseline and with further exclusion of the first 3 years of follow-up , the corresponding adjusted HR was 1.34 ( 95 % CI 1.09 to 1.66 ) . Conclusions Low serum 25(OH)D level was associated with increased all-cause mortality  in a general Norwegian population . The association was not notably influenced by existing chronic diseases The beneficial biologic effects attributed to vitamin D suggest a potential to influence overall mortality . Evidence addressing this hypothesis is limited , especially for African Americans who have a high prevalence of vitamin D insufficiency . The authors conducted a nested case-control study within the prospect i ve Southern Community Cohort Study to relate baseline serum levels of 25-hydroxyvitamin D ( 25(OH)D ) with subsequent mortality .  Cases were 1,852 participants who enrolled from 2002 to 2009 and died > 12 months postenrollment . Controls ( n = 1,852 ) were matched on race , sex , age , enrollment site , and blood collection date . The odds ratios for quartile 1 ( < 10.18 ng/mL ) versus quartile 4 ( > 21.64 ng/mL ) levels of 25(OH)D were 1.60 ( 95 % confidence interval ( CI ) : 1.20 , 2.14 ) for African Americans and 2.11 ( 95 % CI : 1.39 , 3.21 ) for non-African Americans . The effects were strongest for circulatory disease death , where quartile 1 versus quartile 4 odds ratios were 2.53 ( 95 % CI : 1.44 , 4.46 ) and 3.25 ( 95 % CI : 1.33 , 7.93 ) for African Americans and non-African Americans , respectively . The estimated odds of total mortality were minimized in the 25(OH)D range of 35 - 40 ng/mL. These findings provide support for the hypothesis that vitamin D status may have an important influence on mortality for both African Americans and non-African Americans BACKGROUND Evidence is accumulating that vitamin D supplementation of patients with low 25-hydroxyvitamin D concentrations is associated with lower cardiovascular morbidity and total mortality during long-term follow-up . Little is known , however , about the effect of low concentrations of the vitamin D hormone calcitriol on total mortality . We therefore evaluated the predictive value of circulating calcitriol for midterm mortality in patients of a specialized heart center . METHODS This prospect i ve cohort study included 510 patients , 67.7 % with heart failure ( two-thirds in end stage ) , 64.3 % hypertension , 33.7 % coronary heart disease , 20.2 % diabetes , and 17.3 % renal failure . We followed the patients for up to 1 year after blood collection . For data analysis , the study cohort was stratified into quintiles of circulating calcitriol concentrations . RESULTS Patients in the lowest calcitriol quintile were more likely to have coronary heart disease , heart failure , hypertension , diabetes , and renal failure compared to other patients . They also had low 25-hydroxyvitamin D concentrations and high concentrations of creatinine , C-reactive protein , and tumor necrosis factor alpha . Eighty-two patients ( 16.0 % ) died during follow-up . Probability of 1-year survival was 66.7 % in the lowest calcitriol quintile , 82.2 % in the second quintile , 86.7 % in the intermediate quintile , 88.8 % in the fourth quintile , and 96.1 % in the highest quintile ( P < 0.001 ) . Discrimination between survivors and nonsurvivors was best when a cutoff value of 25 ng/L was applied ( area under the ROC curve 0.72 ; 95 % CI 0.66 - 0.78 ) . CONCLUSIONS Decreased calcitriol levels are linked to excess midterm mortality in patients of a specialized heart center BACKGROUND vitamin D deficiency has been associated with an increased risk of mortality , but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain . Our objective was to determine whether endogenous 25-hydroxyvitamin D ( 25(OH)D ) , 1,25-dihydroxyvitamin D ( 1,25(OH)2D ) and parathyroid hormone ( PTH ) levels predicted all-cause , cardiovascular and cancer mortality independently of health and lifestyle factors . SETTING : prospect i ve cohort analysis within the European Male Ageing Study . PARTICIPANTS : 2,816 community-dwelling men aged 40 - 79 years at baseline . METHODS : Cox regression was used to examine the association of all-cause mortality with 25(OH)D , 1,25(OH)2D and PTH ;  cardiovascular and cancer mortality were modelled using competing-risks regression . Results were expressed as hazard ratios ( HR ) and 95 % confidence intervals ( CIs ) for Cox models ; sub-hazard ratios ( SHR ) and 95 % CIs for competing-risks models . RESULTS : a total of 187 men died  during a median of 4.3 years of follow-up . Serum levels of 25(OH)D ( per 1 SD decrease : HR = 1.45 ; 95 % CI = 1.16 , 1.81 ) and 1,25(OH)2D ( per 1 SD decrease : HR = 1.20 ; 95 % CI = 1.00 , 1.44 ) were associated with an increased risk of all-cause mortality after adjusting for age , centre , smoking , self-reported morbidities , physical activity and functional performance . Only levels of 25(OH)D < 25 nmol/l predicted cancer mortality ( SHR = 3.33 ; 95 % CI = 1.38 , 8.04 ) . CONCLUSION : lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men . Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here Objective To test the hypothesis that genetically low 25-hydroxyvitamin D concentrations are associated with increased mortality . Design Mendelian r and omisation analysis . Setting Copenhagen City Heart Study , Copenhagen General Population Study , and Copenhagen Ischemic Heart Disease Study . Participants 95 766 white participants of Danish descent from three cohorts , with median follow-up times of 19.1 , 5.8 , and 7.9 years , genotyped for genetic variants in DHCR7 and CYP2R1 affecting plasma 25-hydroxyvitamin D concentrations ; 35 334 also had plasma 25-hydroxyvitamin D measurements . Participants were followed from study entry through 2013 , during which time 10 349 died . Main outcome measures All cause mortality and cause specific mortality , adjusted for common risk factors for all cause mortality based on the World Health Organization ’s global health status . Results The multivariable adjusted hazard ratios for a 20 nmol/L lower plasma 25-hydroxyvitamin D concentration were 1.19 ( 95 % confidence interval 1.14 to 1.25 ) for all cause mortality , 1.18 ( 1.09 to 1.28 ) for cardiovascular mortality , 1.12 ( 1.03 to 1.22 ) for cancer mortality , and 1.27 ( 1.15 to 1.40 ) for other mortality . Each increase in DHCR7/CYP2R1 allele score was associated with a 1.9 nmol/L lower plasma 25-hydroxyvitamin D concentration and with increased all cause , cancer , and other mortality but not with cardiovascular mortality . The odds ratio for a genetically determined 20 nmol/L lower plasma 25-hydroxyvitamin D concentration was 1.30 ( 1.05 to 1.61 ) for all cause mortality , with a corresponding observational multivariable adjusted odds ratio of 1.21 ( 1.11 to 1.31 ) . Corresponding genetic and observational odds ratios were 0.77 ( 0.55 to 1.08 ) and 1.13 ( 1.03 to 1.24 ) for cardiovascular mortality , 1.43 ( 1.02 to 1.99 ) and 1.10 ( 1.02 to 1.19 ) for cancer mortality , and 1.44 ( 1.01 to 2.04 ) and 1.17 ( 1.06 to 1.29 ) for other mortality . The results were robust in sensitivity analyses . Conclusions Genetically low 25-hydroxyvitamin D concentrations were associated with increased all cause mortality , cancer mortality , and other mortality but not with increased cardiovascular mortality . These findings are compatible with the notion that genetically low 25-hydroxyvitamin D concentrations may be causally associated with cancer and other mortality but also suggest that the observational association with cardiovascular mortality could be the result of confounding CONTEXT Vitamin D deficiency contributes to skeletal diseases and is highly prevalent among institutionalized elderly patients . Whether low 25-hydroxyvitamin D ( 25[OH]D ) concentrations are an independent risk factor for mortality in these patients is , however , unclear . OBJECTIVE We aim ed to evaluate whether 25(OH)D concentrations are associated with mortality . DESIGN , SETTING , AND PARTICIPANTS This is a prospect i ve cohort study among elderly female patients ( age > 70 yr ) recruited from 95 nursing homes in Austria . MAIN OUTCOME MEASURES We calculated Cox proportional hazard ratios ( HR ) for all-cause mortality according to 25(OH)D quartiles . RESULTS We examined 961 study participants ( age 83.7 ± 6.1 yr ) . Median 25(OH)D concentration was 17.5 ( interquartile range 13.7 - 25.5 ) nmol/liter , and 93 % of our cohort had 25(OH)D levels below 50 nmol/liter . During a mean follow-up time of 27 ± 8 months , 284 patients died . Compared with the fourth quartile ( 25[OH]D > 25.5 nmol/liter ) , the age-adjusted HR ( with 95 % confidence interval ) was 1.49 ( 1.07 - 2.10 ) in the first 25(OH)D quartile ( 25[OH]D < 14.0 nmol/liter ) , and this association remained significant after multivariate adjustments ( HR = 1.56 ; 95 % confidence interval = 1.01 - 2.40 ) . CONCLUSIONS This Austrian study suggests that the majority of institutionalized female patients are vitamin D deficient during winter and that there was an inverse association of 25(OH)D and mortality . These data underscore the urgent need for effective strategies for the prevention and treatment of vitamin D deficiency , in particular in the setting of nursing homes Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases . The authors aim ed to investigate whether serum 25-hydroxyvitamin D ( 25(OH)D ) level predicts mortality from cardiovascular disease ( CVD ) . The study was based on the Mini-Finl and Health Survey and included 6,219 men and women aged > or = 30 years who were free from CVD at baseline ( 1978 - 1980 ) . During follow-up through 2006 , 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified . Levels of 25(OH)D were determined from serum collected at baseline .  Cox 's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death . After adjustment for potential confounders , the hazard ratio for total CVD death was 0.76 ( 95 % confidence interval ( 95 % CI ) : 0.60 , 0.95 ) for the highest quintile of 25(OH)D level versus the lowest . The association was evident for cerebrovascular death ( hazard ratio = 0.48 , 95 % CI : 0.31 , 0.75 ) but not coronary death ( hazard ratio = 0.91 , 95 % CI : 0.70 , 1.18 ) . A low vitamin D level may be associated with higher risk of a fatal CVD event , particularly cerebrovascular death . These findings need to be replicated in other population s. To demonstrate a causal link between vitamin D and CVD , r and omized controlled trials are required Objective To investigate the associations between low and high concentrations of baseline serum 25-hydroxyvitamin D [ 25(OH)D ] and all-cause mortality in very old ( ≥85 years ) men and women over 6 years . Design , setting and subjects Prospect i ve mortality data from 775 participants in the Newcastle 85 + Study were analysed for survival in relation to 25(OH)D ( season-specific quartiles and predefined cut-off values ) and sex using Cox proportional hazards models . The models were fitted to the entire and restricted ( nonusers of vitamin D-containing supplements and medication ) cohorts . Results For the entire cohort , mortality was higher in both the lowest and highest 25(OH)D season-specific quartiles [ SQ1 : hazard ratio ( HR ) 1.31 , 95 % confidence interval ( CI ) 1.01–1.69 , P = 0.04 ; SQ4 : HR 1.44 , 95 % CI 1.12–1.85 , P = 0.004 ] compared with the combined middle quartiles ( SQ2 + SQ3 ) , after adjustment for sociodemographic factors . The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables ( SQ4 : HR 1.37 , 95 % CI 1.06–1.77 , P = 0.02 ) and was seen only in women in sex-specific analyses . Similarly , in sensitivity analyses with predefined 25(OH)D cut-off values , the highest 25(OH)D concentration ( ≥75 nmol L−1 ) was associated with a 2.4-fold increased risk of mortality in women ( restricted cohort ) after adjusting for all covariates . Conclusion Low and high season-specific 25(OH)D quartiles were associated with increased risks of mortality over 6 years in the very old ; this effect was particularly noticeable in women , including those who reported taking vitamin D-containing supplements/medication CONTEXT Cardiovascular disease is the major cause of death in the Western world , but the association between 25-hydroxyvitamin D [ 25(OH)D ] levels and the risk of cardiovascular disease mortality remains unclear . OBJECTIVE The objective of the study was to determine the association between cardiovascular , stroke , and acute myocardial infa rct mortality and serum levels of 25(OH)D.  DESIGN This was an observational cohort study , the Copenhagen vitamin D study , data from a single laboratory center in Copenhagen , Denmark . Follow-up was from 2004 to 2011 . SETTING  Serum 25(OH)D  was analyzed from 247 574 subjects from the Copenhagen general practice sector . PARTICIPANTS Examination of the association 25(OH)D levels and mortality from cardiovascular disease , stroke , and acute myocardial infa rct was performed among 161 428 women and 86 146 men . MAIN OUTCOME MEASURES A multivariate Cox regression analysis was used to compute hazard ratios for cardiovascular , stroke , and acute myocardial infa rct mortality . RESULTS Of 247 574 subjects , a total of 16 645 subjects died  in the ensuing 0 - 7 years . A total of 5454 died from cardiovascular disease including 1574 from stroke and 702 from acute myocardial infa rct . The 25(OH)D level of 70 nmol/L was associated with the lowest cardiovascular disease mortality risk . Compared with that level , the hazard ratio for cardiovascular disease mortality was 2.0 [ 95 % confidence interval ( CI ) 1.8 - 2.1 ] at the lower extreme ( ∼ 12.5 nmol/L ) with a higher risk for men [ 2.5 ( 95 % CI 2.2 - 2.9 ) ] than for women [ 1.7 ( 95 % CI 1.5 - 1.9 ) ] . At the higher extreme ( ∼ 125 nmol/L ) , the hazard ratio of cardiovascular disease mortality was 1.3 ( 95 % CI 1.2 - 1.4 ) , with a similar risk among men and women . Results were similar for stroke and acute myocardial subgroups . CONCLUSIONS In this large observational study , low and high levels of 25(OH)D were associated with cardiovascular disease , stroke , and acute myocardial mortality in a nonlinear , reverse J-shaped manner , with the highest risk at lower levels . Whether this was a causal or associational finding can not be determined from our data . There is a need for r and omized clinical trials that include information on the effects of 25(OH)D levels greater than 100 BACKGROUND recent systematic review s have cast doubt on the association between vitamin D and cardiovascular disease . No prior studies have investigated the association between 25-hydroxyvitamin D ( 25[OH]D ) , 1,25-dihydroxyvitamin D ( 1,25[OH](2)D ) , or intact parathyroid hormone and cardiovascular mortality in a temperate climate . METHODS a total of 1073 community-dwelling older adults were evaluated in 1997 - 1999 ; serum levels of 25(OH)D ( mean 42 ng/mL ) , 1,25(OH)(2)D ( median 29 pg/mL ) , and intact parathyroid hormone ( median 46 pg/mL ) were measured ; mean estimated glomerular filtration rate was 74 mL/min/1.73 m(2 ) . Participants were followed up to 10.4 ( mean 6.4 ) years with 111 cardiovascular deaths . RESULTS in unadjusted Cox proportional hazards models , higher levels of 1,25(OH)(2)D were protective against cardiovascular mortality , whereas higher levels of intact parathyroid hormone predicted increased risk of cardiovascular death . After adjusting for age alone or multiple covariates , there was no significant association between 25(OH)D , 1,25(OH)(2)D , or intact parathyroid hormone and cardiovascular mortality ; results did not differ by an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m(2 ) or<60 mL/min/1.73 m(2 ) . CONCLUSION in this prospect i ve study of Caucasian , middle-income , community-dwelling older adults living in sunny southern California , serum levels of 25(OH)D , 1,25(OH)(2)D , and intact parathyroid hormone were not independently associated with cardiovascular mortality CONTEXT Previous 25-hydroxyvitamin D [ 25(OH)D ] and mortality studies have included mostly individuals of European descent . Whether the relationship is similar in Blacks and to what extent differences in 25(OH)D explain racial disparities in mortality is unclear . OBJECTIVE The objective of the study was to examine the relationship between 25(OH)D , PTH , and mortality in Black and white community-dwelling older adults over 8.5 yr of follow-up . DESIGN AND SETTING Health ABC is a prospect i ve cohort study conducted in Memphis , TN , and Pittsburgh , PA . PARTICIPANTS Well-functioning Blacks and whites aged 71 - 80 yr with measured 25(OH)D and PTH ( n = 2638 ; 49 % male , 39 % Black ) were included in the study . MAIN OUTCOME MEASURE Multivariate-adjusted proportional hazards models estimated the hazard ratios ( HR ) for all-cause , cardiovascular , cancer , and noncancer , noncardiovascular mortality ( n = 691 deaths ) . RESULTS Mean 25(OH)D concentrations were higher in whites than in Blacks [ mean ( sd ) : 29.0 ( 9.9 ) and 20.8 ( 8.7 ) ng/ml , respectively ; P < 0.001 ] . Serum 25(OH)D by race interactions were not significant , however . Lower 25(OH)D concentrations were associated with higher mortality in Blacks and whites combined [ HR ( 95 % confidence interval [ CI ] 2.27 ( 1.59 - 3.24 ) , 1.48 ( 1.20 - 1.84 ) , and 1.25 ( 1.02 - 1.52 ) for < 10 , 10 to < 20 , and 20 to < 30 vs. ≥30 ng/ml ] . In the multivariate model without 25(OH)D , Blacks had 22 % higher mortality than whites [ HR ( 95 % CI ) 1.22 ( 1.01 , 1.48 ) ] ; after including 25(OH)D in the model , the association was attenuated [ 1.09 ( 0.90 - 1.33 ) ] . The mortality population attributable risks ( 95 % CI ) for 25(OH)D concentrations less than 20 ng/ml and less than 30 ng/ml in Blacks were 16.4 % ( 3.1 - 26.6 % ) and 37.7 % ( 11.6 - 55.1 % ) and in whites were 8.9 % ( 3.9 - 12.7 % ) and 11.1 % ( -2.7 to 22.0 % ) , respectively . PTH was also associated with mortality [ HR ( 95 % CI ) 1.80 ( 1.33 - 2.43 ) for ≥70 vs. < 23 pg/ml ] . CONCLUSIONS Low 25(OH)D and high PTH concentrations were associated with increased mortality  in Black and white community-dwelling older adults . Because 25(OH)D concentrations were much lower in Blacks , the potential impact of remediating low 25(OH)D concentrations was greater in Blacks than whites OBJECTIVE To assess the prospect i ve association of serum 25-hydroxyvitamin D [ 25(OH)D ] levels with frailty status and all-cause mortality in a cohort of community-dwelling participants of the population -based KORA [ Cooperative Health Research in the Region of Augsburg]-Age Study . METHODS 727 non-frail participants , aged ≥65years , with 25(OH)D measurement at baseline in 2009 , were followed for 2.9±0.1years . Participants were classified as pre-frail or frail if they met 1 - 2 or ≥3 , respectively , of the following five criteria : weight loss , exhaustion , physical inactivity , low walking speed , weakness . The association between 25(OH)D and mortality was assessed in 954 participants . Multivariable adjusted logistic regression models were calculated for each outcome . RESULTS The incidence of pre-frailty and frailty was 21.2 % and 3.9 % respectively . After multivariable adjustment , participants with very low 25(OH)D levels ( < 15ng/ml vs. ≥30ng/ml ) had a significantly higher odds for pre-frailty ( OR=2.43 [ 95 % CI : 1.17 - 5.03 ] ) and pre-frailty/frailty combined ( OR=2.53 [ 95 % CI : 1.23 - 5.22 ] ) , but not for frailty alone ( OR=2.63 [ 95 % CI : 0.39 - 17.67 ] ) . The association between 25(OH)D and mortality ( OR=3.39 [ 95 % CI : 1.08 - 10.65 ] ) was partly mediated by frailty status . CONCLUSION Very low 25(OH)D levels were independently associated with incident pre-frailty , pre-frailty/frailty combined and all-cause mortality CONTEXT AND OBJECTIVE Hypovitaminosis D and frailty are common in the older population . We aim ed to determine whether 25-hydroxyvitamin D [ 25(OH)D ] concentrations are associated with frailty and mortality . DESIGN We conducted a prospect i ve cohort study . SETTING AND PARTICIPANTS Participants included 4203 older men aged 70 - 88 years in Perth , Western Australia . MAIN OUTCOME MEASURES 25(OH)D was measured by immunoassay  . Frailty was assessed with the 5-point FRAIL ( fatigue , resistance , ambulation , illness , and loss of weight ) scale . Mortality was determined from the death registry via the Western Australian Data Linkage System . RESULTS At baseline , 676 ( 16.1 % ) men were frail , as defined by having ≥3 deficits ( FRAIL scale ≥ 3 ) . In multivariate cross-sectional analysis , low vitamin D status , defined by the lowest quartile of 25(OH)D values ( < 52.9 nmol/L ) , was associated with increased prevalent frailty ( odds ratio , 1.96 ; 95 % confidence interval [ CI ] , 1.52 to 2.52 ) in comparison to the highest quartile of 25(OH)D values ( > 81.6 nmol/L ) . After a mean period of 5.3 years , the adjusted odds ratio of being frail at follow-up for men with low vitamin D and having zero deficit at baseline ( FRAIL scale = 0 ) was 1.56 ( 95 % CI , 1.07 to 2.27 ) . Low vitamin D also predicted all-cause mortality over a period of up to 9.2 years ( hazard ratio , 1.20 ; 95 % CI , 1.02 to 1.42 ) , independent of baseline frailty and other covariates . CONCLUSION Hypovitaminosis D is associated with prevalent and incident frailty in older men . Hypovitaminosis D also predicts all-cause mortality , independent of frailty . The association between vitamin D and mortality is not solely dependent on the occurrence of frailty BACKGROUND Vitamin D , specifically serum 25(OH)D has been associated with mortality , cancer and multiple other health endpoints in observational studies , but there is a paucity of clinical trial evidence sufficient to determine the safety and effectiveness of population -wide supplementation . We have therefore launched the D-Health Trial , a r and omized trial of vitamin D supplementation for prevention of mortality and cancer . Here we report the methods and describe the trial cohort . METHODS The D-Health Trial is a r and omized placebo-controlled trial , with planned intervention for 5years and a further 5years of passive follow-up through linkage with health and death registers . Participants aged 65 - 84years were recruited from the general population of Australia . The intervention is monthly oral doses of 60,000IU of cholecalciferol or matching placebo . The primary outcome is all-cause mortality . Secondary outcomes are total cancer incidence and colorectal cancer incidence . RESULTS We recruited 21,315 participants to the trial between February 2014 and May 2015 . The participants in the two arms of the trial were well-balanced at baseline . Comparison with Australian population statistics shows that the trial participants were less likely to report being in fair or poor health , to be current smokers or to have diabetes than the Australian population . However , the proportion overweight or with health conditions such as arthritis and angina was similar . CONCLUSIONS Observational data can not be considered sufficient to support interventions delivered at a population level . Large-scale r and omized trials such as the D-Health Trial are needed to inform public health policy and practice Despite continued appreciation of the potential role of vitamin D and omega-3 fatty acids in the prevention of cancer and cardiovascular disease ( CVD ) , there remain no completed large-scale , r and omized trials of these agents for the primary prevention of cancer or CVD in a population that has not been selected on the basis of elevated risk . The VITamin D and OmegA-3 TriaL ( VITAL ) is a 2 × 2 factorial r and omized , double-blind , placebo-controlled trial of the benefits and risks of vitamin D ( vitamin D3 [ cholecalciferol ] , 2000 IU/d ) and marine omega-3 fatty acids ( Omacor ( ® ) fish oil , a 1 g/d ) in the primary prevention of cancer and CVD among 25,875 men and women , aged ≥50 and ≥55 years , respectively . R and omization began in November 2011 and was completed in March 2014 . This report will describe the rationale for the trial and currently available r and omized trial data , summarize related ongoing large-scale trials , and provide a brief overview of study design , and an up date on r and omization milestones , racial/ethnic diversity , biorepository activities , in-depth phenotyping of a subcohort , and ancillary studies OBJECTIVE Institutionalised elderly people at northern latitudes may be at elevated risk for vitamin D deficiency . In addition to osteoporosis-related disorders , vitamin D deficiency may influence several medical conditions conferring an increased mortality risk . The aim of this study was to explore the prevalence of vitamin D deficiency and its association with mortality . DESIGN The Study of Health and Drugs in the Elderly ( SHADES ) is a prospect i ve cohort study among elderly people ( > 65 years ) in 11 nursing homes in Sweden . METHODS We analysed the levels of 25-hydroxyvitamin D₃ ( 25(OH)D₃ ) at baseline . Vital status of the subjects was ascertained and hazard ratios ( HRs ) for mortality according to 25(OH)D₃ quartiles were calculated . RESULTS We examined 333 study participants with a mean follow-up of 3 years . A total of 147 ( 44 % ) patients died within this period . Compared with the subjects in Q4 ( 25(OH)D₃ > 48 nmol/l ) , HR ( with 95 % CI ) for mortality was 2.02 ( 1.31 - 3.12 ) in Q1 ( 25(OH)D₃ < 29 nmol/l ) ( P<0.05 ) ; 2.03 ( 1.32 - 3.14 ) in Q2 ( 25(OH)D₃ 30 - 37 nmol/l ) ( P<0.05 ) and 1.6 ( 1.03 - 2.48 ) in Q3 ( 25(OH)D₃ 38 - 47 nmol/l ) ( P<0.05 ) . The mean 25(OH)D₃ concentration was 40.2 nmol/l ( S.D. 16.0 ) and 80 % had 25(OH)D₃ below 50 nmol/l . The vitamin D levels decreased from baseline to the second and third measurements . CONCLUSIONS Vitamin D deficiency was highly prevalent and associated with increased mortality among the elderly in Swedish nursing homes . Strategies are needed to prevent , and maybe treat , vitamin D deficiency in the elderly in nursing homes and the benefit of vitamin D supplementation should be evaluated in r and omised clinical trials BACKGROUND In cross-sectional studies , low serum levels of 25-hydroxyvitamin D are associated with higher prevalence of cardiovascular risk factors and disease . This study aim ed to determine whether endogenous 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are related to all-cause and cardiovascular mortality . METHODS Prospect i ve cohort study of 3258 consecutive male and female patients ( mean [ SD ] age , 62 [ 10 ] years ) scheduled for coronary angiography at a single tertiary center . We formed quartiles according to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels within each month of blood drawings . The main outcome measures were all-cause and cardiovascular deaths . RESULTS During a median follow-up period of 7.7 years , 737 patients ( 22.6 % ) died , including 463 deaths from cardiovascular causes . Multivariate-adjusted hazard ratios ( HRs ) for patients in the lower two 25-hydroxyvitamin D quartiles ( median , 7.6 and 13.3 ng/mL [ to convert 25-hydroxyvitamin D levels to nanomoles per liter , multiply by 2.496 ] ) were higher for all-cause mortality ( HR , 2.08 ; 95 % confidence interval [ CI ] , 1.60 - 2.70 ; and HR , 1.53 ; 95 % CI , 1.17 - 2.01 ; respectively ) and for cardiovascular mortality ( HR , 2.22 ; 95 % CI , 1.57 - 3.13 ; and HR , 1.82 ; 95 % CI , 1.29 - 2.58 ; respectively ) compared with patients in the highest 25-hydroxyvitamin D quartile ( median , 28.4 ng/mL ) . Similar results were obtained for patients in the lowest 1,25-dihydroxyvitamin D quartile . These effects were independent of coronary artery disease , physical activity level , Charlson Comorbidity Index , variables of mineral metabolism , and New York Heart Association functional class . Low 25-hydroxyvitamin D levels were significantly correlated with variables of inflammation ( C-reactive protein and interleukin 6 levels ) , oxidative burden ( serum phospholipid and glutathione levels ) , and cell adhesion ( vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels ) . CONCLUSIONS Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular mortality . A causal relationship has yet to be proved by intervention trials using vitamin OBJECTIVES To explore associations between serum  25-hydroxyvitamin D ( 25(OH)D ) levels and a wide range of health conditions , physical performance measures , disability , and mortality in a large epidemiological study to identify an optimum range for 25(OH)D concentrations . DESIGN Cross-sectional study , with additional prospect i ve data on falls and mortality . SETTING Concord Health and Ageing in Men Project , Sydney , Australia . PARTICIPANTS Community-dwelling men aged 70 and older ( N = 1,659 ) . MEASUREMENTS  Serum 25(OH)D levels , general health status , self-reported diseases , physical performance measures , disability ( activities of daily living and instrumental activities of daily living ) and falls . RESULTS Fair , poor , and very poor health ; self-reported diabetes mellitus ; hyperglycemia ; depression ; muscle weakness ; poor balance ; and all-cause mortality were all associated with serum 25(OH)D levels less than 50 nmol/L , even after adjustment for confounding . The findings also suggest that , in older men , for a wide range of health conditions , physical performance measures , disability , falls , and mortality , the optimum range of 25(OH)D is between 50.0 and 74.9 nmol/L , with no additional benefit for 25(OH)D levels of 75.0 nmol/L or greater . CONCLUSION Programs aim ed at achieving an optimum range of serum 25(OH)D at levels between 50.0 and 74.9 nmol/L may have overall health benefits and such levels are adequate for older men OBJECTIVES To investigate the association between low vitamin D levels ( < 50 nmol/L ) and 10-year mortality in women aged 75 and older . DESIGN Prospect i ve with 15 years of follow-up . SETTING Malmö , Sweden . PARTICIPANTS Population -based cohort of 75-year-old women ( N = 1,044 ) . MEASUREMENTS  Serum 25-hydroxyvitamin D ( 25(OH)D ) levels  at age 75 ( n = 1,011 ) , 80 ( n = 642 ) , and 85 ( n = 348 ) were categorized as low ( < 50 nmol/L ) , intermediate ( 50 - 75 nmol/L ) and high ( > 75 nmol/L ) at all ages . Hazard ratios ( HRs ) for all-cause mortality between ages 75 and 90 were calculated according to 25(OH)D category . RESULTS Between ages 80 and 90 , all-cause mortality ( HR = 1.8 , 95 % confidence interval ( CI ) = 1.3 - 2.4 , P < .001 ; adjusted for comorbidities ( aHR ) = 1.9 , 95 % CI = 1.4 - 2.6 , P < .001 ) was significantly higher in women with low 25(OH)D levels than in those with high levels . Osteoporosis had the greatest effect on mortality , but even after excluding women with osteoporotic fracture during the risk of dying associated with low 25(OH)D remained greater ( HR = 1.8 , 95 % CI = 1.2 - 2.7 , P = .002 ; aHR = 1.7 , 95 % CI = 1.2 - 2.5 , P = .006 ) . CONCLUSION In this observational study of women aged 75 and older , 25(OH)D levels of less than 50 nmol/L were associated with greater all-cause mortality for up to 10 years . This difference was at least partially independent of comorbidities and fracture , indicating that low 25(OH)D not only is an indicator of impaired health , but also plays a role in disease outcome Prospect i ve studies , mostly from Europe and North America , suggest that serum 25‐hydroxyvitamin D ( 25(OH)D ) is inversely associated with mortality and cardiovascular disease ( CVD ) risk . Data from other regions are limited , and threshold levels for adverse cardiovascular outcomes are uncertain . We examined serum 25(OH)D  as a predictor of total mortality and cardiovascular outcomes in an Australian cohort OBJECTIVE To investigate relationships between mortality and circulating 25-hydroxyvitamin D ( 25(OH)D ) , 25-hydroxycholecalciferol ( 25(OH)D3 ) and 25-hydroxyergocalciferol ( 25(OH)D2 ) . DESIGN Case-cohort study within the Melbourne Collaborative Cohort Study ( MCCS ) . We measured 25(OH)D2 and 25(OH)D3 in archived dried blood spots by LC-MS/MS . Cox regression was used to estimate mortality hazard ratios ( HR ) , with adjustment for confounders . SETTING General community . SUBJECTS The MCCS included 29 206 participants , who at recruitment in 1990 - 1994 were aged 40 - 69 years , had dried blood spots collected and no history of cancer . For the present study we selected participants who died by 31 December 2007 ( n 2410 ) and a r and om sample ( sub-cohort , n 2996 ) . RESULTS The HR per 25 nmol/l increment in concentration of 25(OH)D and 25(OH)D3 were 0·86 ( 95 % CI 0·78 , 0·96 ; P=0·007 ) and 0·85 ( 95 % CI 0·77 , 0·95 ; P=0·003 ) , respectively . Of 5108 participants , sixty-three ( 1·2 % ) had detectable 25(OH)D2 ; their mean 25(OH)D concentration was 11·9 ( 95 % CI 7·3 , 16·6 ) nmol/l higher ( P<0·001 ) . The HR for detectable 25(OH)D2 was 1·80 ( 95 % CI 1·09 , 2·97 ; P=0·023 ) ; for those with detectable 25(OH)D2 , the HR per 25 nmol/l increment in 25(OH)D was 1·06 ( 95 % CI 0·87 , 1·29 ; P interaction=0·02 ) . HR were similar for participants who reported being in good , very good or excellent health four years after recruitment . CONCLUSIONS Total 25(OH)D and 25(OH)D3 concentrations were inversely associated with mortality . The finding that the inverse association for 25(OH)D was restricted to those with no detectable 25(OH)D2 requires confirmation in population s with higher exposure to ergocalciferol Background : Poor vitamin D status , i.e. low serum levels of 25-hydroxyvitamin D [ 25(OH)D ] , is common in the general population . Prospect i ve epidemiologic data on the association between vitamin D and mortality in oldest old subjects are limited . Objective : This study aim ed to determine whether 25(OH)D concentrations were prospect ively and independently associated with cardiovascular disease ( CVD ) mortality and all-cause mortality in oldest old subjects . Methods : A total of 312 subjects aged 85 years old at baseline ( Octabaix study ) were followed for 3 years . Sociodemographic and overall geriatric assessment data were collected . Serum 25(OH)D concentrations were used to assess vitamin D status . Data on overall and cardiovascular mortality were collected . Results : The mean serum 25(OH)D levels were 28 ± 30 ng/ml . During the follow-up period , 58 subjects ( 18.5 % ) died . Twenty-five of the deaths ( 8 % ) were related to CVD . There were no differences in mortality rates according to the different quartiles of vitamin D ( p = 0.41 for total mortality and p = 0.86 for CVD mortality ) . Conclusion : In community-dwelling oldest old subjects  , serum 25(OH)D levels were not associated with overall or CVD mortality after a 3-year follow-up CONTEXT Low 25-hydroxyvitamin D [ 25(OH)D ] and high PTH may contribute to increased mortality risk in older adults . OBJECTIVE The aim of the study was to test the association between 25(OH)D , PTH , and mortality in older men . DESIGN AND SETTING The prospect i ve Osteoporotic Fractures in Men ( MrOS ) study was conducted at six U.S. clinical centers . PARTICIPANTS We studied community-dwelling men at least 65 yr old ( n = 1490 ) . MAIN OUTCOME MEASURE Multivariate-adjusted proportional hazards models estimated the hazard ratio ( HR ) for mortality ; cause of death was classified as cancer , cardiovascular , and other by central review of death certificates . RESULTS During 7.3 yr of follow-up , 330 ( 22.2 % ) participants died : 97 from cancer , 110 from cardiovascular disease , and 106 from other causes . The adjusted HR per sd decrease in 25(OH)D for all-cause mortality was 1.01 ( 95 % CI , 0.89 , 1.14 ) ; no association between 25(OH)D and cardiovascular or other-cause mortality was seen . Unexpectedly , lower 25(OH)D levels were modestly associated with a decreased risk of cancer mortality ( adjusted HR per sd decrease , 0.80 ; 95 % CI , 0.64 , 0.99 ) . Analyzing 25(OH)D as a categorical variable did not alter these results . Higher PTH levels ( log-transformed ) were associated with an increased risk of all-cause mortality ( adjusted HR per sd increase , 1.15 ; 95 % CI , 1.03 , 1.29 ) and cardiovascular mortality ( adjusted HR per sd increase in PTH , 1.21 ; 95 % CI , 1.00 , 1.45 ) . CONCLUSIONS In contrast to previous studies , lower 25(OH)D levels were not associated with an increased risk of all-cause or cause-specific  mortality in older men . Higher PTH levels were associated with a modest increase in mortality risk Highlights • The BEST-D ( Biochemical Efficacy and Safety Trial of vitamin D ) trial will compare the biochemical and other effects of daily dietary supplementation with 100 μg or 50 μg vitamin D3 or placebo , when administered for 12 months , in 305 ambulant community-dwelling older people living in Oxfordshire , Engl and .• The primary analyses will compare 12-month mean plasma concentrations of 25(OH)D as well as the proportion of participants with a 12-month concentration > 90 nmol/L between participants allocated 100 μg and participants allocated 50 μg daily . Secondary analyses will compare the two active doses ( both separately and when combined ) with placebo.• Additional end-points include biochemical assessment s of safety , blood pressure , arterial stiffness , falls , fractures , heel and wrist bone density , grip strength and physical performance and echocardiographic assessment s of cardiac function in a r and om sample of participants .• The results of this trial will help determine the optimum dose of vitamin D to test in a larger trial investigating whether vitamin D supplementation can reduce the risk of fractures , cardiovascular disease or cancer Observational studies suggest that low concentrations of serum 25-hydroxyvitamin D ( 25(OH)D ) and high concentrations of parathyroid hormone ( PTH ) are associated with a higher risk of mortality . The aim of this study was to examine whether 25(OH)D and PTH concentrations are independently associated with overall and disease-specific ( cardiovascular and cancer-related ) mortality in a large , prospect i ve population -based cohort of older adults . Data from 1317 men and women ( 65 - 85 years ) of the Longitudinal Aging Study Amsterdam were used . Cox proportional hazard analyses were used to examine whether 25(OH)D and PTH at baseline were associated with overall mortality ( with a follow-up of 18 years ) and disease-specific mortality ( with a follow-up of 13 years ) . Compared to persons in the reference category of ≥75nmol/L , persons with serum 25(OH)D < 25nmol/L ( HR 1.46 ; 95 % CI : 1.12 - 1.91 ) and 25 - 49.9nmol/L ( HR 1.24 ; 95 % CI : 1.01 - 1.53 ) had a significantly higher risk of overall mortality , as well as men with baseline PTH concentrations ≥7pmol/L ( HR 2.54 ( 95 % CI : 1.58 - 4.08 ) ) , compared to the reference category of < 2.33pmol/L. The relationship of 25(OH)D with overall mortality was partly mediated by PTH . Furthermore , men with PTH concentrations of ≥7pmol/L ( HR 3.22 ; 95 % CI : 1.40 - 7.42 ) had a higher risk of cardiovascular mortality , compared to the reference category . No significant associations of 25(OH)D or PTH with cancer-related mortality were observed . Both 25(OH)D and PTH should be considered as important health markers 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 It is now generally accepted that vitamin D deficiency is a worldwide health problem that affects not only musculoskeletal health but also a wide range of acute and chronic diseases . However , there remains cynicism about the lack of r and omized controlled trials to support the association studies regarding the nonskeletal health benefits of vitamin D. This review was obtained by search ing English- language studies published up to April 1 , 2013 , in PubMed , MEDLINE , and the Cochrane Central Register of Controlled Trials ( search terms : vitamin D and supplementation ) and focuses on recent challenges regarding the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D concentrations from dietary sources , supplements , and sun exposure . The effect of vitamin D on fetal programming epigenetics and gene regulation could potentially explain why vitamin D has been reported to have such wide-ranging health benefits throughout life . There is potentially a great upside to increasing the vitamin D status of children and adults worldwide for improving musculoskeletal health and reducing the risk of chronic illnesses , including some cancers , autoimmune diseases , infectious diseases , type 2 diabetes mellitus , neurocognitive disorders , and mortality PURPOSE Several observational studies have linked vitamin D deficiency with an increased risk of all cause mortality .  Vitamin D deficiency is common among patients with liver diseases . In a r and om sample of the general population , we investigated whether the inverse association between vitamin D status and all-cause mortality could be explained by liver damage as reflected by increased levels of liver enzymes . METHODS We included a total of 2649 persons examined in 1993e1994 . Vitamin D status was assessed as serum 25-hydroxyvitamin D and liver enzyme levels were measured . Information on all-cause mortality was obtained from the Danish Central Personal Register until July 2011 . Median follow-up time was 17.0 years , and there were 736 deaths . RESULTS Multivariable Cox regression analyses with age as underlying time axis and delayed entry showed lower mortality risk with higher vitamin D levels and this was essentially unaffected by adjustment for liver enzyme levels with hazard ratio , 0.96 ( 95 % confidence interval , 0.93e0.99 ) for a 10 nmol/L higher vitamin D level . CONCLUSIONS The present study did not support our hypothesis that the well-known association between low vitamin D status and mortality is explained by liver damage as reflected by levels of liver enzymes Vitamin D deficiency is associated with osteoporosis , poor muscle strength , falls , and fractures . The relationship between serum vitamin D concentrations and mortality in older community-dwelling women has not been well characterized . We hypothesized that women with lower 25-hydroxyvitamin D ( 25[OH]D ) concentrations were at higher risk of mortality . We examined the association between serum 25[OH]D concentrations and all-cause mortality in a prospect i ve , population -based study of 714 community-dwelling women , aged 70 to 79 years , the Women 's Health and Aging Studies I and II in Baltimore , Md. The studies were originally design ed to evaluate the causes and course of physical disability in older women living in the community .  Vital status was determined through follow-up interviews and matching with the National Death Index . During a median of 72 months of follow-up , 100 ( 14 % ) of 714 women died . Women in the lowest quartile of 25(OH)D ( < 15.3 ng/mL or 38.2 nmol/L ) were at higher risk of death ( hazards ratio , 2.45 ; 95 % confidence interval , 1.12 - 5.36 ; P = .02 ) compared to women in the highest quartile ( > 27.0 ng/mL or 67.4 nmol/L ) of 25(OH)D in a multivariate Cox proportional hazards model adjusting for demographics , season , and conventional risk factors . Older community-dwelling women with low 25(OH)D levels are at an increased risk of death Background Low serum 25-hydroxyvitamin D [ 25(OH)D ] levels have been associated with higher risk of many diseases that affect mortality , including cardiovascular disease ( CVD ) and cancer . The inverse association between serum 25(OH)D and mortality may be modified by excess circulating vitamin A , due to interactions of vitamin A at the level of the vitamin D nuclear receptor . In this prospect i ve cohort study , we investigated whether the association of 25(OH)D with all-cause , cancer , and CVD mortality  was modified by circulating vitamin A or preformed vitamin A intake from supplements . Methods We analyzed 15,998 adults in the Third National Health and Nutrition Examination Survey ( NHANES III ) , 1988–1994 . Mortality data for all-cause ( n = 3890 ) , cancer ( n = 844 ) , and CVD mortality ( n = 1715 ) were assessed through December 2006 .  Serum 25(OH)D was measured using a radioimmunoassay kit , vitamin A biomarkers were measured by HPLC , and information on supplement use was obtained by self-report . Multivariable hazard ratios ( HRs ) and corresponding 95 % confidence intervals ( CI ) were estimated by proportional hazards regression . Results Serum 25(OH)D was significantly inversely associated with all-cause mortality ( HR 0.93 , 95 % CI 0.89 , 0.97 , per 10 ng/mL increase ) and also with CVD mortality and mortality due to non-cancer/non-cardiovascular causes , but not with cancer mortality . The observed inverse associations remained statistically significant only among participants with serum retinyl esters < 7.0 μg/dL. High intake ( > 5000 IU/day ) of preformed vitamin A from supplements attenuated the inverse association of 25(OH)D with overall mortality . The observed interactions were not statistically significant . Conclusions 25(OH)D was inversely associated with overall mortality , CVD mortality , and mortality due to non-cancer/non-CVD causes , but not with cancer mortality . A possible interaction between vitamin A exposure and 25(OH)D concentration appears to be associated with an attenuation of the inverse association between risk of death and quartile of 25(OH)D concentration Previous studies have shown a relationship between osteoporosis and increased mortality risk . However , none of these studies performed a concomitant evaluation of the parathyroid hormone (PTH)-calcium-vitamin D axis and bone mass to accurately determine the contribution of each of these parameters to survival in older subjects . Thus , we sought to investigate the association between bone parameters and mortality in a longitudinal , prospect i ve , population -based cohort of 839 elderly subjects . Clinical data ( including history of fractures and cardiovascular events ) were assessed using a specific question naire . Laboratory exams , including serum 25OHD and PTH  , were also performed .  Bone mineral density ( BMD ) at the lumbar spine and hip were evaluated using DXA . All analyses were performed at baseline ( 2005 to 2007 ) . Mortality was recorded during follow-up . Multivariate Cox proportional regression was used to compute hazard ratios for all-cause and cardiovascular mortality . Over a mean 4.06 ± 1.07 years , there were 132 ( 15.7 % ) deaths . These individuals were compared to 707 subjects who were alive at the end of the coverage period for mortality data collection . In a multivariate Cox proportional hazards model , age ( HR 1.32 ; 95 % CI , 1.13 to 1.55 ; p = 0.001 , for each 5-year increase ) , male gender ( HR 1.90 ; 95 % CI , 1.30 to 2.79 ; p = 0.001 ) , recurrent falls ( more than two in the previous year ; HR 1.65 ; 95 % CI , 1.06 to 2.56 ; p = 0.026 ) , diabetes mellitus ( HR 2.17 ; 95 % CI , 1.46 to 3.21 ; p < 0.001 ) , low physical activity score ( HR 1.78 ; 95 % CI , 1.14 to 2.79 ; p = 0.011 ) , prior cardiovascular event ( HR 1.76 ; 95 % CI , 1.18 to 2.63 ; p = 0.006 ) , total hip BMD ( HR 1.41 ; 95 % CI , 1.15 to 1.72 ; p = 0.001 , per each 1 SD decrease ) , and intact PTH ( iPTH ) ( HR 1.06 ; 95 % CI , 1.04 to 1.08 ; p < 0.001 , per each 10 pg/mL increase ) were independently associated with all-cause mortality . The subjects in the highest quartile of PTH ( > 49 pg/mL ) were at a higher risk of cardiovascular death ( HR 3.09 ; 95 % CI , 1.36 to 6.99 ; p = 0.007 ) compared with the subjects in the lowest quartile ( < 26 pg/mL ) . Low BMD and higher PTH were significantly associated with mortality  in community-dwelling older adults . These findings support the notion that careful screening of these bone parameters might lead to better management of older patients and improve outcomes in this population . © 2016 American Society for Bone and Mineral Research BACKGROUND Prospect i ve epidemiologic data on the association between vitamin D and all-cause and cause-specific mortality are limited . OBJECTIVE This study aim ed to determine whether 25-hydroxyvitamin D [ 25(OH)D ]  concentrations were prospect ively and independently associated with cardiovascular disease ( CVD ) , cancer , and all-cause mortality in postmenopausal women . DESIGN A sub study in 2429 postmenopausal women within the Women 's Health Initiative ( WHI ) with measured baseline 25(OH)D concentrations were followed for 10 y for death from CVD , cancer , and all-cause mortality . Proportional hazards models were performed to evaluate quartiles of month-adjusted 25(OH)D concentrations , with adjustment for potential confounders . Sequential model building and analysis for multiplicative interaction were performed to evaluate the effects of central adiposity on the association of low 25(OH)D with all-cause mortality . RESULTS Of the 2429 women , 224 deaths occurred , with 79 deaths from CVD and 62 deaths from cancer . Multivariate-adjusted HRs that compared quartiles 1 ( lowest ) to 4 ( highest ) of 25(OH)D for all-cause mortality ( HR : 1.25 ; 95 % CI : 0.80 , 1.95 ) , CVD mortality ( HR : 1.27 ; 95 % CI : 0.81 , 1.99 ) , and cancer mortality ( HR : 1.39 ; 95 % CI : 0.88 , 2.19 ) were not significant . There was a potential interaction ( P = 0.08 ) between abdominal obesity and low 25(OH)D concentrations that showed an increased risk of the lowest quartile of 25(OH)D concentrations ( HR : 1.85 ; 95 % CI : 1.00 , 3.44 ) with increased mortality in women with a normal waist circumference but no increased risk in women with abdominal obesity ( HR : 0.96 ; 95 % CI : 0.52 , 1.76 ) . CONCLUSION Body fat distribution may play an important role in the modulation of the effect of low vitamin D concentrations on health . This trial was registered at clinical trials.gov as NCT 00000611 We prospect ively investigated relationships between blood markers of Fe , vitamin B12 , folate , vitamin C and vitamin D status and subsequent  all-cause mortality  in 208 men and 191 women aged 75 years or over living in the community in Aberdeen , Scotl and . The participants had been recruited for a cross-sectional study in 1999 - 2000 when they completed health and lifestyle question naires  and had blood sample s taken for analysis of serum ferritin , serum vitamin B12 , erythrocyte folate , plasma vitamin C and serum 25-hydroxycholecalciferol .  Mortality was ascertained on national data bases up to December 2005 , with a median time of follow up of 69.2 ( range 1.0 - 79.9 ) months . Participants were divided into sex-specific quintiles of baseline levels for each nutrient , and hazard ratios were estimated with Cox proportional hazard models adjusted for age and sex with the significance of linear trends in the associations assessed by logistic regression . There was no significant association between blood markers of Fe , vitamin B12 or folate status at baseline and mortality , but  vitamin D status at baseline was inversely related to mortality ( P for trend < 0.001 ) . For vitamin C there was no evidence of a linear trend but participants in the lowest quintile of plasma levels had a significantly higher risk of death than those in the highest quintile . R and omized controlled trials of lifestyle changes which improve vitamin status are needed to assess whether these associations could be causal It was reported that low bone mineral density ( BMD ) , osteoporotic fractures and low serum 25-hydroxyvitamin D ( 25-OHVD ) levels increase the risk of mortality in elderly Caucasian people . However , there is no data available on the relationship between bone mineral density or 25-OHVD levels and mortality in elderly Asian women . To determine whether or not low bone mineral density ( BMD ) or low 25-OHVD levels contribute to increased mortality risk , we conducted a prospect i ve observational study in 1232 ambulatory postmenopausal female volunteers . Information was obtained from the subjects on baseline BMD , the serum levels of biochemical indices including 25-OHVD , prevalent fractures , co-morbidities and lifestyle variables .  The participants were observed for a total of 6.9+/-3.6 years ( mean+/-SD ) and a total of 107 participants ( 8.7 % ) were dead during the observation . Mortality was assessed and confirmed on the certificates or hospital records or information from their family . In addition to traditional risks for mortality , such as age ( Hazard ratio , 1.73 , 95 % CI , 1.51 - 1.98 , P<0.01 ) , 25-OHVD level < 50 nmol/l ( HR 2.17 , 1.27 - 3.72 , P=0.01 ) , prevalent malignancies ( HR 5.60 , 3.36 - 9.31 , P<0.01 ) and existing osteoporosis ( HR 2.14 , 1.22 - 3.75 , P=0.01 ) were found to be significant independent risk factors for all-cause mortality by using multivariate Cox 's regression analysis . It is suggested that prevalent osteoporosis , prevalent malignancy or lower levels of 25-OHVD represent powerful risk factors for mortality Importance Previous r and omized clinical trials have reported inconsistent results on the effect of vitamin D supplementation on cancer incidence . Objective To examine whether high-dose vitamin D supplementation received monthly , without calcium , is associated with a reduction in  cancer incidence and cancer mortality in the general population . Design , Setting , and Participants This is a post hoc analysis of data from the Vitamin D Assessment ( ViDA ) study , a r and omized , double-blind , placebo-controlled trial that recruited participants from family practice s and community groups in Auckl and , New Zeal and , from April 5 , 2011 , through November 6 , 2012 , with follow-up completed December 31 , 2015 . Participants were adult community residents 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 withdrew consent , and all others ( n = 5108 ) were included in the primary analysis . Data analysis was by intention to treat . Interventions Oral vitamin D3 , in an initial bolus dose of 200 000 IU and followed 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 Post hoc primary outcome was the number of all primary invasive and in situ malignant neoplasms ( excluding nonmelanoma skin cancers ) diagnosed from r and omization until the study medication was discontinued on July 31 , 2015 . Results Of the 5108 participants included in the analysis , the mean ( SD ) age was 65.9 ( 8.3 ) years , 58.1 % were male , and 4253 ( 83.3 % ) were of European or another race/ethnicity , with the remainder being Polynesian or South Asian .  Mean ( SD ) baseline deseasonalized 25-hydroxyvitamin D concentration was 26.5 ( 9.0 ) ng/mL. In a r and om sample of 438 participants , the mean follow-up 25-hydroxyvitamin D concentration consistently was greater than 20 ng/mL higher in the vitamin D group than in the placebo group . The primary outcome of cancer comprised 328 total cases of cancer ( 259 invasive and 69 in situ malignant neoplasms ) and occurred in 165 of 2558 participants ( 6.5 % ) in the vitamin D group and 163 of 2550 ( 6.4 % ) in the placebo group , yielding an adjusted hazard ratio of 1.01 ( 95 % CI , 0.81 - 1.25 ; P = .95 ) . Conclusions and Relevance High-dose vitamin D supplementation prescribed monthly for up to 4 years without calcium may not prevent cancer . This study suggests that daily or weekly dosing for a longer period may require further study . Trial Registration anzctr.org.au Identifier : BACKGROUND It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease , and data from r and omized trials are limited . METHODS We conducted a nationwide , r and omized , placebo‐controlled trial , with a two‐by‐two factorial design , of vitamin D3 ( cholecalciferol ) at a dose of 2000 IU per day and marine n‐3 ( also called omega‐3 ) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States . Primary end points were invasive cancer of any type and major cardiovascular events ( a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes ) . Secondary end points included site‐specific cancers , death from cancer , and additional cardiovascular events . This article reports the results of the comparison of vitamin D with placebo . RESULTS A total of 25,871 participants , including 5106 black participants , underwent r and omization . Supplementation with vitamin D was not associated with a lower risk of either of the primary end points . During a median follow‐up of 5.3 years , cancer was diagnosed in 1617 participants ( 793 in the vitamin D group and 824 in the placebo group ; hazard ratio , 0.96 ; 95 % confidence interval [ CI ] , 0.88 to 1.06 ; P=0.47 ) . A major cardiovascular event occurred in 805 participants ( 396 in the vitamin D group and 409 in the placebo group ; hazard ratio , 0.97 ; 95 % CI , 0.85 to 1.12 ; P=0.69 ) . In the analyses of secondary end points , the hazard ratios were as follows : for death from cancer ( 341 deaths ) , 0.83 ( 95 % CI , 0.67 to 1.02 ) ; for breast cancer , 1.02 ( 95 % CI , 0.79 to 1.31 ) ; for prostate cancer , 0.88 ( 95 % CI , 0.72 to 1.07 ) ; for colorectal cancer , 1.09 ( 95 % CI , 0.73 to 1.62 ) ; for the exp and ed composite end point of major cardiovascular events plus coronary revascularization , 0.96 ( 95 % CI , 0.86 to 1.08 ) ; for myocardial infa rct ion , 0.96 ( 95 % CI , 0.78 to 1.19 ) ; for stroke , 0.95 ( 95 % CI , 0.76 to 1.20 ) ; and for death from cardiovascular causes , 1.11 ( 95 % CI , 0.88 to 1.40 ) . In the analysis of death from any cause ( 978 deaths ) , the hazard ratio was 0.99 ( 95 % CI , 0.87 to 1.12 ) . No excess risks of hypercalcemia or other adverse events were identified . CONCLUSIONS Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo . ( Funded by the National Institutes of Health and others ; VITAL Clinical Trials.gov number , NCT01169259 . & NA ; There is considerable debate regarding the role that 25‐hydroxyvitamin D [ 25(OH)D ] concentrations play in cancer risk or mortality , with earlier studies drawing mixed conclusions . Using data from the UK Biobank ( UKB ) , we evaluate whether genetically predicted 25(OH)D concentrations are associated with overall cancer susceptibility and cancer mortality using five 25(OH)D genetic markers . Data comprised 438 870 white British UKB participants aged 37‐73 , including 46 155 cancer cases and 6998 cancer‐specific deaths . Participants with keratinocyte cancers and /or benign tumors were excluded from the analysis . Odds ratios were calculated per 20 nmol/L increase in genetically predicted 25(OH)D for cancer risk and cancer mortality . For individual cancer risks , estimates were meta‐analyzed with publicly available data using a fixed‐effect inverse‐variance‐weighted model . We demonstrated that genetically low plasma 25(OH)D concentrations were not associated with increased cancer risk nor cancer mortality . Stratification by sex or cancer types did not reveal any meaningful differences albeit wider confidence intervals . Fixed‐effect meta‐ analysis of our individual cancer risk estimates with those derived from publicly available cancer consortia data and previous studies further reinforced our null Mendelian r and omization findings on prostate , lung , colorectal and breast cancers with tight confidence intervals ; for ovarian and pancreatic cancers , our estimates were less precise despite being not statistically significant . Taken altogether , our results provide no genetic evidence for an association  between vitamin D  and overall cancer outcomes , with tight confidence intervals to exclude all but very small effect sizes 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 BACKGROUND Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies . However , some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [ 25(OH)D ] . OBJECTIVE We sought to determine the effect of vitamin D status on health outcomes . DESIGN Healthy community-dwelling women ( n = 1471 ) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation .  25(OH)D was measured at baseline in all women .  Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline . RESULTS Fifty percent of women had a seasonally adjusted 25(OH)D concentration < 50 nmol/L. These women were significantly older , heavier , and less physically active and had more comorbidities than women with a seasonally adjusted 25(OH)D concentration > or = 50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L had an increased incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities . Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at increased risk of adverse consequences for any musculoskeletal outcome , including fracture , falls , bone density , or grip strength or any nonskeletal outcomes , including death , myocardial infa rct ion , cancer , heart failure , diabetes , or adverse changes in blood pressure , weight , body composition , cholesterol , or glucose . CONCLUSIONS Vitamin D insufficiency is more common in older , frailer women . Community-dwelling older women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at risk of adverse outcomes over 5 y after control for comorbidities . R and omized placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes . This trial was registered at www.anzctr.org.au as ACTRN 012605000242628
target: The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality .
  This association appeared to be non-linear , with progressively lower mortality with increasing 25(OH)D up to a point , beyond which there was no further decrease .
  There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases , while for cardiovascular mortality , there is weak evidence of an association in observational studies , which is not supported by the data from intervention or Mendelian r and omization studies .
background: Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality , but it is unclear whether this is explained by reverse causation , and if there are specific causes of death for which vitamin D might be important .