Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up. Low levels of vitamin D are associated with increased mortality in patients attending a university hospital in Denmark Vitamin D status and the risk of cardiovascular disease death. Prospective association of vitamin D concentrations with mortality in postmenopausal women: results from the Women's Health Initiative (WHI). Low vitamin D status is an independent predictor of increased frailty and all-cause mortality in older men: the Health in Men Study. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Sun, vitamin D, and cardiovascular disease. Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland Does liver damage explain the inverse association between vitamin D status and mortality? Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. Parathyroid hormone and vitamin D--markers for cardiovascular and all cause mortality in heart failure. The inverse association between serum 25-hydroxyvitamin D and mortality may be modified by vitamin A status and use of vitamin A supplements Low serum 25-hydroxyvitamin D concentrations are associated with greater all-cause mortality in older community-dwelling women. Low Serum Vitamin D is Not Associated with an Increase in Mortality in Oldest Old Subjects: The Octabaix Three-Year Follow-Up Study Vitamin D deficiency in elderly people in Swedish nursing homes is associated with increased mortality. Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents. The effect of vitamin D and frailty on mortality among non-institutionalized US older adults
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 Abstract Introduction . Increased mortality in patients with low serum concentrations of S-25(OH)D  has been described , though no causal relationship has been shown . The aim of this cohort study was to investigate the possible association between S-25(OH)D status and  all-cause mortality in 5,147 patients attending a university hospital in Denmark from 2003–2008 . Methods . Serum was analyzed for ionized calcium ( S-Ca2 + ) , parathyroid hormone ( S-PTH ) and S-25(OH)D. Kaplan-Meier curves were used to analyze the association between S-25(OH)D quartiles , S-PTH-quartiles and all-cause mortality . Cox regression analyzed associations of age , gender , concentrations of ionized calcium , S-PTH and S-25(OH)D with all-cause mortality . Results . Log rank tests for both S-25(OH)D and S-PTH quartiles showed a significant difference across the quartiles . The Cox regression analysis showed a hazard ratio ( HR ) for death of 1.02 ( 95 % CI : 1.01 ; 1.03 ) for S-PTH per pmol/L increase , 1.07 ( 95 % CI : 1.05 ; 1.10 ) for S-25(OH)D per 10 nmol/L decrease and 0.54 ( 95 % CI : 0.24 ; 1.20 ) for S-Ca2 + per mmol/L increase . Discussion . This study supports growing evidence , that low serum concentrations of 25(OH)D are associated with an increased all-cause mortality ; however the nature of the study prevents the finding of a causal relationship . In the Cox regression analysis S-25(OH)D concentrations in the blood were inversely associated with all-cause mortality . Prospect i ve controlled studies are needed to confirm a causal relationship between low S-25(OH)D concentrations and mortality 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 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 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 Vitamin D recently has been proposed to play an important role in a broad range of organ functions , including cardiovascular ( CV ) health ; however , the CV evidence -base is limited . We prospect ively analyzed a large electronic medical records data base to determine the prevalence of vitamin D deficiency and the relation of vitamin D levels to prevalent and incident CV risk factors and diseases , including mortality . The data base contained 41,504 patient records with at least one measured vitamin D level . The prevalence of vitamin D deficiency ( ≤30 ng/ml ) was 63.6 % , with only minor differences by gender or age . Vitamin D deficiency was associated with highly significant ( p < 0.0001 ) increases in the prevalence of diabetes , hypertension , hyperlipidemia , and peripheral vascular disease . Also , those without risk factors but with severe deficiency had an increased likelihood of developing diabetes , hypertension , and hyperlipidemia . The vitamin D levels were also highly associated with coronary artery disease , myocardial infa rct ion , heart failure , and stroke ( all p < 0.0001 ) , as well as with incident death , heart failure , coronary artery disease/myocardial infa rct ion ( all p < 0.0001 ) , stroke ( p = 0.003 ) , and their composite ( p < 0.0001 ) . In conclusion , we have confirmed a high prevalence of  vitamin D deficiency in the general healthcare population and an association between vitamin D levels and prevalent and incident CV risk factors and outcomes . These observations lend strong support to the hypothesis that vitamin D might play a primary role in CV risk factors and disease . Given the ease of vitamin D measurement and replacement , prospect i ve studies of vitamin D supplementation to prevent and treat CV disease are urgently needed Globally , cardiovascular disease ( CVD ) is the number one cause of death , being responsible for approximately 30 % of deaths worldwide . Urbanization and a westernized lifestyle are thought to play a major role in the development of CVD . There is accumulating evidence that vitamin D is a nonclassical risk factor for CVD . The active vitamin D metabolite , 1,25-dihydroxyvitamin D , which is synthesized from its precursor 25-hydroxyvitamin D ( 25[OH]D ) , down-regulates several negative and up-regulates various protective pathways in the heart and vasculature . First r and omized trials demonstrate that vitamin D supplementation leads to vasodilatation and suppresses cardiovascular risk markers such as triglycerides and the inflammation marker tumor necrosis factor-α . Solar UV-B radiation is the major source of vitamin D for humans . Consequently , the vitamin D status is largely influenced by season , geographic latitude , daily outdoor activities , and the percentage of body surface exposed to solar UV-B. A significant proportion of individuals in Europe and North America have  vitamin D concentrations in the deficiency range ( 25[OH]D<25 nmol/l ) . Available data indicate that low solar UV-B exposure and /or low 25(OH)D concentrations are associated with an increased risk of CVD . Large nonr and omized studies indicate that CVD mortality is more than twice as high in older individuals with deficient 25(OH)D concentrations compared with those individuals who have adequate 25(OH)D concentrations ( > 75 nmol/l ) . Together , experimental and epidemiological evidence does support a plausible role for improving vitamin D status in CVD prevention in the population at large . Nevertheless , future r and omised clinical trials are needed to evaluate whether vitamin D is effective with respect to primary , secondary , and /or tertiary prevention of CVD 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 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 BACKGROUND Vitamin D has potent anticancer properties , especially against digestive-system cancers . Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure . Here , we considered multiple determinants of vitamin D exposure ( dietary and supplementary vitamin D , skin pigmentation , adiposity , geographic residence , and leisure-time physical activity-to estimate sunlight exposure ) in relation to cancer risk in the Health Professionals Follow-Up Study . METHODS Among 1095 men of this cohort , we quantified the relation of these six determinants to plasma  25-hydroxy-vitamin D [ 25(OH)D ] level by use of a multiple linear regression model . We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics . We then prospect ively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models . RESULTS From 1986 through January 31 , 2000 , we documented 4286 incident cancers ( excluding organ-confined prostate cancer and nonmelanoma skin cancer ) and 2025 deaths from cancer . From multivariable models , an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17 % reduction in total cancer incidence ( multivariable relative risk [ RR ] = 0.83 , 95 % confidence interval [ CI ] = 0.74 to 0.92 ) , a 29 % reduction in total cancer mortality ( RR = 0.71 , 95 % CI = 0.60 to 0.83 ) , and a 45 % reduction in digestive-system cancer mortality ( RR = 0.55 , 95 % CI = 0.41 to 0.74 ) . The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile ; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality . Results were similar when we controlled further for body mass index or physical activity level . CONCLUSIONS Low levels of vitamin D may be associated with increased cancer incidence and mortality in men , particularly for digestive-system cancers . The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day AIMS To investigate levels of vitamin D and parathyroid hormone ( PTH ) in a population of heart failure ( HF ) patients , and to evaluate whether vitamin D and PTH are related to prognosis . METHODS AND RESULTS This was a prospect i ve study of 148 HF out patients ( mean age 68 years , 102 men ) with follow-up for mortality after 3½ years . Levels of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , PTH , 25-hydroxyvitamin D ( 25-OHD ) , and several other biomarkers were examined . Mortality and cardiovascular mortality were analysed in multivariable regression analyses adjusting for other independent prognostic variables . Vitamin D deficiency ( ≤50 nmol/L ) was prevalent in 43 % of the population ; 26 % had elevated PTH levels ; none had primary hyperparathyroidism . We found a strong and independent significant association of both PTH and vitamin D  to mortality , which was independent of other clinical ly important parameters [ NT-proBNP , estimated glomerular filtration rate ( eGFR ) , age , and left ventricular ejection fraction ( LVEF ) ] . Both PTH and vitamin D were also significantly associated with all cause mortality . In an adjusted model , we found a hazard ratio of 1.9 ( confidence interval 1.1 - 3.4 ) for vitamin D deficiency and 2.0 ( 1.0 - 3.8 ) for the upper median of PTH , respectively . CONCLUSION In this relatively small prospect i ve study , PTH and vitamin D were independently associated with all cause and cardiovascular mortality in patients with HF . This was independent of other known risk factors such as eGFR , LVEF , NT-proBNP , and age 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 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 : 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 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 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 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
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 .
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 .