Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer. Vitamin D status and the risk of cardiovascular disease death. The inverse association between serum 25-hydroxyvitamin D and mortality may be modified by vitamin A status and use of vitamin A supplements Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). Sun, vitamin D, and cardiovascular disease. Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease Parathyroid hormone and vitamin D--markers for cardiovascular and all cause mortality in heart failure. Vitamin D and overall cancer risk and cancer mortality: a Mendelian randomization study Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary Angiography Prospective association of vitamin D concentrations with mortality in postmenopausal women: results from the Women's Health Initiative (WHI). Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men. Association of Serum Level of Vitamin D at Diagnosis With Breast Cancer Survival: A Case-Cohort Analysis in the Pathways Study Circulating 25-Hydroxyvitamin D3 and Survival after Diagnosis with Kidney Cancer Vitamin D, PTH and the risk of overall and disease-specific mortality: Results of the Longitudinal Aging Study Amsterdam Effect of a single, oral, high-dose vitamin D supplementation on endothelial function in patients with peripheral arterial disease: a randomised controlled pilot study.
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 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 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 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 CONTEXT Vitamin D or calcium supplementation may have effects on  vascular disease and cancer .  OBJECTIVE Our objective was to investigate whether vitamin D or calcium supplementation affects mortality , vascular disease , and cancer in older people . DESIGN AND SETTING The study included long-term follow-up of participants in a two by two factorial , r and omized controlled trial from 21 orthopedic centers in the United Kingdom . PARTICIPANTS Participants were 5292 people ( 85 % women ) aged at least 70 yr with previous low-trauma fracture . INTERVENTIONS Participants were r and omly allocated to daily vitamin D(3 ) ( 800 IU ) , calcium ( 1000 mg ) , both , or placebo for 24 - 62 months , with a follow-up of 3 yr after intervention . MAIN OUTCOME MEASURES All-cause mortality , vascular disease mortality , cancer mortality , and cancer incidence were evaluated . RESULTS In intention-to-treat analyses , mortality [ hazard ratio ( HR ) = 0.93 ; 95 % confidence interval ( CI ) = 0.85 - 1.02 ] , vascular disease mortality ( HR = 0.91 ; 95 % CI = 0.79 - 1.05 ) , cancer mortality ( HR = 0.85 ; 95 % CI = 0.68 - 1.06 ) , and cancer incidence ( HR = 1.07 ; 95 % CI = 0.92 - 1.25 ) did not differ significantly between participants allocated vitamin D and those not . All-cause mortality ( HR = 1.03 ; 95 % CI = 0.94 - 1.13 ) , vascular disease mortality ( HR = 1.07 ; 95 % CI = 0.92 - 1.24 ) , cancer mortality ( HR = 1.13 ; 95 % CI = 0.91 - 1.40 ) , and cancer incidence ( HR = 1.06 ; 95 % CI = 0.91 - 1.23 ) also did not differ significantly between participants allocated calcium and those not . In a post hoc statistical analysis adjusting for compliance , thus with fewer participants , trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated , although all results remain nonsignificant . CONCLUSIONS Daily vitamin D or calcium supplementation did not affect mortality , vascular disease , cancer mortality , or cancer incidence 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 The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers ( VDPP ) brought together 10 cohorts to conduct a prospect i ve study of the association between vitamin D status , measured as serum concentrations of 25-hydroxyvitamin D ( 25(OH)D ) , and the development of 7 rarer cancer sites : endometrial , esophageal , gastric , kidney , non-Hodgkin lymphoma , ovarian , and pancreatic cancers . The cohorts come from 3 continents , with participants from a wide range of latitude who are racially diverse . Across each cancer site , there was no evidence of a protective association between higher concentrations of 25-hydroxyvitamin D ( > 75 nmol/L ) and cancer outcome . An increased risk at very high levels ( ≥100 nmol/L ) was noted for pancreatic cancer , confirming previous reports . The articles included in this issue detail the overall design and governance of the project , correlates of vitamin D status , and results from the cancer site-specific investigations . The Vitamin D Pooling Project realizes a major goal of consortium efforts , namely , to rigorously test hypotheses for rarer cancer outcomes that may not be adequately addressed in any one prospect i ve cohort study . The results of this study have application for the planning and conduct of intervention trials , especially in determining potential risks 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 . 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 & 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 Accumulating evidence suggests that vitamin D may protect against cancer , but results from epidemiologic studies are inconclusive so far , and other studies looking into the prospect i ve association of total cancer mortality and serum 25-hydroxyvitamin D [ 25(OH)D ] levels , which are considered to be the best indicator of vitamin D status , are scarce . We measured 25(OH)D and 1,25-dihydroxyvitamin D in 3,299 patients from the Ludwigshafen Risk and Cardiovascular Health study . The baseline examination was done between July 1997 and January 2000 and included a fasting blood sampling in the morning before coronary angiography . During a median follow-up period of 7.75 years , 95 patients died due to cancer . After adjustment for possible confounders , the Cox proportional hazard ratio ( 95 % confidence interval ) of the fourth 25(OH)D quartile was 0.45 ( 0.22 - 0.93 ) when compared with the first quartile and the hazard ratio per increase of 25 nmol/L in serum 25(OH)D concentrations was 0.66 ( 0.49 - 0.89 ) . We found no association between serum 1,25-dihydroxyvitamin D levels and fatal cancer . In summary , our data suggest that low levels of 25(OH)D are associated with increased risk of fatal cancer in patients referred to coronary angiography and that the maintenance of a sufficient vitamin D status might therefore be a promising approach for the prevention and /or treatment of cancer . ( Cancer Epidemiol Biomarkers Prev 2008;17(5):1228–33 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 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 Importance There are long-st and ing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality , yet data from prospect i ve cohort studies are limited . Objective To investigate a serum biomarker of vitamin D status , 25-hydroxyvitamin D ( 25OHD ) measured at the time of breast cancer diagnosis , to determine the association with prognosis . Design , Setting , and Participants The Pathways Study is a prospect i ve cohort study of breast cancer survivors established in 2006 . Enrollment was completed in 2013 ; follow-up is ongoing . The cohort was established in Kaiser Permanente Northern California , a large integrated health care delivery system in northern California . Women with a diagnosis of incident invasive breast cancer were typically consented and enrolled within 2 months of diagnosis . The overall enrollment rate was 46 % ( 4505 of 9820 ) . Participants are followed for health outcomes and comorbidities at 12 , 24 , 48 , 72 , and 96 months after baseline interview . A case-cohort design was used for efficiency assay of 25OHD , selecting 1666 cohort members with serum sample s and ensuring representation in the subcohort of races and clinical subtypes . The data analysis was performed from January 5 , 2014 , to March 15 , 2015 . Main Outcomes and Measures Primary outcomes are breast cancer recurrence , second primary cancer , and death .  Results Mean ( SD ) age was 58.7 ( 12.4 ) years . Serum 25OHD concentrations were lower in women with advanced-stage tumors , and the lowest in premenopausal women with triple-negative cancer . Levels were also inversely associated with hazards of disease progression and death . Compared with the lowest tertile , women with the highest tertile of 25OHD levels had superior overall survival ( OS ) . This association remained after adjustment for clinical prognostic factors ( hazard ratio [ HR ] , 0.72 ; 95 % CI , 0.54 - 0.98 ) . Among premenopausal women , the association with OS was stronger , and there were also associations with breast cancer – specific survival and invasive disease – free survival ( OS : HR , 0.45 ; 95 % CI , 0.21 - 0.96 ; breast cancer – specific survival : HR , 0.37 ; 95 % CI , 0.15 - 0.93 ; invasive disease – free survival : HR , 0.58 ; 95 % CI , 0.34 - 1.01 ; all after full adjustment ) . Conclusions and Relevance Serum 25OHD levels were independently associated with breast cancer prognostic characteristics and patient prognosis , most prominently among premenopausal women . Our findings from a large , well-characterized prospect i ve cohort provide compelling observational evidence on associations of vitamin D with lower risk of breast cancer morbidity and mortality Prospect i ve cohort studies have provided some evidence that circulating vitamin D is associated with risk of , and survival from , renal cell carcinoma ( RCC ) , but it is unclear whether concentrations of vitamin D at the time of diagnosis of RCC are associated with prognosis . We conducted a case – cohort study of 630 RCC cases , including 203 deaths , from a multicenter case – control study in Eastern Europe .  Vitamin D was assessed as 25-hydroxyvitamin D3 [ 25(OH)D3 ] , and we used weighted Cox models to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) by categories of season-adjusted 25(OH)D3 . Higher concentrations of 25(OH)D3 were associated with lower risk of death after adjusting for stage , age , sex , and country ( HR highest vs. lowest category 0.57 ; 95 % CI , 0.34–0.97 ) . The inverse associations of 25(OH)D3 with death were most notable among those who died from non-RCC causes and those diagnosed with early-stage disease . In summary , 25(OH)D3 concentration at diagnosis of RCC was inversely associated with all-cause mortality rates , but not specifically with RCC outcome . Cancer Epidemiol Biomarkers Prev ; 24(8 ) ; 1277–81 . © 2015 AACR 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 OBJECTIVE Apart from its role in bone metabolism , vitamin D may also influence cardiovascular disease . The objective of this study was : ( 1 ) to determine the effect of a single , oral , high-dose vitamin D supplementation on endothelial function and arterial stiffness in patients with peripheral arterial disease ( PAD ) and ( 2 ) to investigate the impact of this supplementation on coagulation and inflammation parameters . METHODS In this double-blind , placebo-controlled , interventional pilot study , we screened 76 Caucasian patients with PAD for vitamin D deficiency . Sixty-two were r and omised to receive a single , oral supplementation of 100,000 IU vitamin D3 or placebo . At baseline and after 1 month , we measured serum vitamin D and parathormone levels , and surrogate parameters for cardiovascular disease . RESULTS Sixty-five of 76 patients ( 86 % ) had low 25-hydroxyvitamin D levels ( < 30 ng ml(-1 ) ) ; of those , 62 agreed to participate in the study . At baseline , only parathormone was related to vitamin D. In supplemented patients , vitamin D levels increased from 16.3 ± 6.7 to 24.3 ± 6.2 ng ml(-1 ) ( P < 0.001 ) , with wide variations between single patients ; in the placebo group vitamin levels did not change . Seasonal factors accounted for a decrease of vitamin D levels by 8 ng ml(-1 ) between summer and winter . After 1 month , none of the measured parameters was influenced by vitamin substitution . CONCLUSION In this pilot study , most patients with PAD were vitamin D deficient . Vitamin D supplementation  increased serum 25-hydroxyvitamin D without influencing endothelial function , arterial stiffness , coagulation and inflammation parameters , although the study was underpowered for definite conclusions
Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements .
The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics .
However , for vitamin D2 supplementation , increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods .
Conclusions Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease , cancer , and other causes .
Objective To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with  mortality from cardiovascular , cancer , or other conditions  , under various circumstances .