title: High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease Serum vitamin D levels and survival of patients with colorectal cancer: Post-hoc analysis of a prospective cohort study 1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial. The Effects of Vitamin D Supplementation on Physical Function and Quality of Life in Older Patients With Heart Failure: A Randomized Controlled Trial Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study Vitamin D and breast cancer recurrence in the Women's Healthy Eating and Living (WHEL) Study. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. Serum 25(OH)D Is a 2-Year Predictor of All-Cause Mortality, Cardiac Death and Sudden Cardiac Death in Chest Pain Patients from Northern Argentina Serum 25-hydroxyvitamin D status and cardiovascular outcomes in chronic peritoneal dialysis patients: a 3-y prospective cohort study. Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation Circulating 25OHD, dietary vitamin D, PTH, and calcium associations with incident cardiovascular disease and mortality: the MIDSPAN Family Study. Vitamin D Levels, Microvascular Complications, and Mortality in Type 1 Diabetes Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland A higher dose of vitamin d reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Prospective study of serum 25-hydroxyvitamin D concentration and mortality in a Chinese population. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Vitamin D affects survival independently of vascular calcification in chronic kidney disease. A prospective study of serum 25-hydroxyvitamin d levels and mortality among African Americans and non-African Americans. Dietary vitamin D intake and serum 25‐hydroxyvitamin D level in relation to disease outcomes in head and neck cancer patients Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Circulating calcitriol concentrations and total mortality. Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes. Vitamin D status and the risk of cardiovascular disease death. Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia. Vitamin D status and clinical outcomes in incident dialysis patients: results from the NECOSAD study. Vitamin D status in patients with stage IV colorectal cancer: findings from Intergroup trial N9741. Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial Do vitamin D supplements improve the physical capabilities of elderly hospital patients? Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. Vitamin D insufficiency and prognosis in non-Hodgkin's lymphoma. 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. Serum 25-hydroxyvitamin D3 levels are associated with breslow thickness at presentation and survival from melanoma. Prediagnostic 25-Hydroxyvitamin D, VDR and CASR Polymorphisms, and Survival in Patients with Colorectal Cancer in Western European Populations Circulating 25-hydroxyvitamin D levels and frailty status in older women. Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Cytokine profile in patients with multiple sclerosis following vitamin D supplementation Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Prognostic effects of 25-hydroxyvitamin D levels in early breast cancer. Relationship between vitamin D status and incidence of vascular events in the Veterans Affairs Diabetes Trial. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Randomised controlled trial of prevention of falls in people aged ≥75 with severe visual impairment: the VIP trial Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men. The effects of calcitriol on falls and fractures and physical performance tests Impact of Hypovitaminosis D and Alfacalcidol Therapy on Survival of Hemodialysis Patients: Results from the French ARNOS Study Low levels of vitamin D are associated with increased mortality in patients attending a university hospital in Denmark Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). Low serum 25-hydroxyvitamin D concentrations are associated with greater all-cause mortality in older community-dwelling women. Vitamin D deficiency in dialysis patients: effect of dialysis modality and implications on outcome. Vitamin D levels do not predict cardiovascular events in statin-treated patients with stable coronary disease. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). 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. A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know Contributions of 25-hydroxyvitamin D, co-morbidities and bone mass to mortality in Japanese postmenopausal women. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Dose Response to Vitamin D Supplementation in Postmenopausal Women 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: BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) Background Recently , serum 25-hydroxyvitamin D ( 25OHD ) levels were shown to be associated with the survival of patients with colorectal cancer . However , 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels . In this study , we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer . Methods We started a prospect i ve cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum sample s and clinical data . As part of a post-hoc analysis ,  serum 25OHD levels  were measured by radioimmunoassay . Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis , gender , cancer stage , residual tumor after surgery , time period of surgery , location of tumor , adjuvant chemotherapy and number of lymph nodes with metastasis at surgery . Unadjusted and adjusted hazard ratios ( HR ) and 95 % confidence intervals ( 95 % CI ) were determined . Results Serum 25OHD levels were measured in 257 patients . Only 3 % had sufficient levels ( 30 ng/ml and greater ) . Based on month of blood sampling , an annual oscillation of 25OHD levels was seen , with levels being lower in spring and higher in late summer . Higher 25OHD levels were associated with better overall survival under multi-variate analysis ( HR , 0.91 : 95 % CI , 0.84 to 0.99 , P = 0.027 ) . Conclusions These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months .  Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels < 50 nmol/L ( 20 ng/mL ) received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P<0.001 ) and maintained this increase at 20 weeks . The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896 Introduction Vitamin D has been postulated to be involved in cancer prognosis . Thus far , only two studies reported on its association with recurrence and survival after breast cancer diagnosis yielding inconsistent results . Therefore , the aim of our study was to assess the effect of post-diagnostic serum 25-hydroxyvitamin D [ 25(OH)D ] concentrations on overall survival and distant disease-free survival . Methods We conducted a prospect i ve cohort study in Germany including 1,295 incident postmenopausal breast cancer patients aged 50 - 74 years . Patients were diagnosed between 2002 and 2005 and median follow-up was 5.8 years . Cox proportional hazards models were stratified by age at diagnosis and season of blood collection and adjusted for other prognostic factors . Fractional polynomials were used to assess the true dose-response relation for 25(OH)D. Results Lower concentrations of 25(OH)D were linearly associated with higher risk of death ( hazard ratio ( HR ) = 1.08 per 10 nmol/L decrement ; 95 % confidence interval ( CI ) , 1.00 to 1.17 ) and significantly higher risk of distant recurrence ( HR = 1.14 per 10 nmol/L decrement ; 95%CI , 1.05 to 1.24 ) . Compared with the highest tertile ( ≥ 55 nmol/L ) , patients within the lowest tertile ( < 35 nmol/L ) of 25(OH)D had a HR for overall survival of 1.55 ( 95%CI , 1.00 to 2.39 ) and a HR for distant disease-free survival of 2.09 ( 95%CI , 1.29 to 3.41 ) . In addition , the association with overall survival was found to be statistically significant only for 25(OH)D levels of blood sample s collected before start of chemotherapy but not for those of sample s taken after start of chemotherapy ( P for interaction = 0.06 ) . Conclusions In conclusion , lower serum 25(OH)D concentrations may be associated with poorer overall survival and distant disease-free survival in postmenopausal breast cancer patients BACKGROUND There is a paucity of research evaluating the relation between  vitamin D  and recurrence of breast cancer after treatment . OBJECTIVE This study was design ed to evaluate the associations between circulating concentrations of  25-hydroxyvitamin D [ 25(OH)D ]  and dietary , supplemental , and total intake of vitamin D  and recurrent or new breast cancer events within the Women 's Healthy Eating and Living ( WHEL ) Study . DESIGN A prospect i ve cohort study design ( n = 3085 ) was used to evaluate the relation between dietary , supplemental , and total vitamin D intake and recurrent breast cancer , and a nested case-control study with 512 matched pairs was used for analysis of the association between 25(OH)D and breast cancer recurrence . RESULTS No relation between 25(OH)D and breast cancer recurrence was observed . Compared with women with serum concentrations of 25(OH)D ≥ 30 ng/mL , adjusted odds ratios ( 95 % CI ) for breast cancer recurrence were 1.14 ( 0.57 , 2.31 ) for those with concentrations < 10 ng/mL , 1.00 ( 0.68 - 1.48 ) for concentrations ≥ 10 and < 20 ng/mL , and 1.05 ( 0.76 , 1.47 ) for concentrations ≥ 20 and < 30 ng/mL. No significant associations were observed when analyses were stratified by pre- and postmenopausal status or for local , regional , or distant recurrence or death . Vitamin D intake was not related to breast cancer recurrence overall , although for premenopausal women there was a significant inverse association between dietary vitamin D intake and recurrence ( P for trend = 0.02 ) . CONCLUSION These results do not provide support for a relation between concentrations of 25(OH)D after treatment and the recurrence of breast cancer . This trial is registered at clinical trials.gov for the WHEL Study as NCT00003787 PURPOSE To compare the safety and activity of DN-101 , a new high-dose oral formulation of calcitriol design ed for cancer therapy , and docetaxel with placebo and docetaxel . PATIENTS AND METHODS Patients with progressive metastatic and rogen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 microg DN-101 or placebo taken orally 1 day before docetaxel . The primary end point was prostate-specific antigen ( PSA ) response within 6 months of enrollment , defined as a 50 % reduction confirmed at least 4 weeks later . RESULTS Two hundred fifty patients were r and omly assigned . Baseline characteristics were similar in both arms . Within 6 months , PSA responses were seen in 58 % in DN-101 patients and 49 % in placebo patients ( P = .16 ) . Overall , PSA response rates were 63 % ( DN-101 ) and 52 % ( placebo ) , P = .07 . Patients in the DN-101 group had a hazard ratio for death of 0.67 ( P = .04 ) in a multivariate analysis that included baseline hemoglobin and performance status . Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio , compared with 16.4 months for placebo . Grade 3/4 adverse events occurred in 58 % of DN-101 patients and in 70 % of placebo-treated patients ( P = .07 ) . Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia ( 10 % v 8 % ) , fatigue ( 8 % v 16 % ) , infection ( 8 % v 13 % ) , and hyperglycemia ( 6 % v 12 % ) . CONCLUSION This study suggests that DN-101 treatment was associated with improved survival , but this will require confirmation because survival was not a primary end point . The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel Background Several studies have shown an association between vitamin D deficiency and cardiovascular risk . Vitamin D status is assessed by determination of 25-hydroxyvitamin D [ 25(OH)D ] in serum . Methods We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome ( ACS ) from Salta , Northern Argentina . 2-year follow-up data including all-cause mortality , cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D , applying univariate and multivariate analysis . Results There were statistically significant changes in seasonal 25(OH)D levels . At follow-up , 119 patients had died . The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors , both in the total population and in patients with a troponin T ( TnT ) release ( n = 388 ) . When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality , the hazard ratio ( HR ) for cardiac death and sudden cardiac death in the total population was 0.37 ( 95 % CI , 0.19–0.73 ) , p = 0.004 , 0.23 ( 95 % CI , 0.08–0.67 ) , p = 0.007 , and 0.32 ( 95 % CI , 0.11–0.94 ) , p = 0.038 , respectively . In patients with TnT release , the respective HR was 0.24 ( 95 % CI , 0.10–0.54 ) , p = 0.001 , 0.18 ( 95 % CI , 0.05–0.60 ) , p = 0.006 and 0.25 ( 95 % CI , 0.07–0.89 ) , p = 0.033 . 25(OH)D had no prognostic value in patients with no TnT release . Conclusion Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS . Trial registration Clinical Trials.gov BACKGROUND Patients with kidney disease are at high risk of developing 25-hydroxyvitamin D [ 25(OH)D ] deficiency . OBJECTIVE We studied the association between serum 25(OH)D status and clinical outcomes of chronic peritoneal dialysis patients . DESIGN We measured serum 25(OH)D concentrations in 230 prevalent peritoneal dialysis patients and then followed these patients prospect ively for 3 y or until death . RESULTS Serum 25(OH)D was deficient or insufficient ( ie , < 75 nmol/L ) in 87 % of the patients . Adjusting for clinical and demographic factors , every 1-unit increase in log-transformed serum 25(OH)D was associated with a 44 % reduction in the hazard of fatal or nonfatal cardiovascular events ( 95 % CI : 0.35 , 0.91 ; P = 0.018 ) . However , the association was gradually lost when additional adjustment was made in a stepwise fashion for residual glomerular filtration rate ( P = 0.078 ) and echocardiographic measures ( P = 0.39 ) . Kaplan-Meier estimates showed a significantly greater fatal or nonfatal cardiovascular event-free survival probability among patients with serum 25(OH)D > 45.7 nmol/L ( median ) than among patients with concentrations < or= 45.7 nmol/L ( P = 0.004 ) . In addition , patients with 25(OH)D > 45.7 nmol/L had a significantly higher cardiovascular event-free survival probability than did patients with 25(OH)D < or= 45.7 nmol/L in the stratified analysis for patients with left ventricular mass index less than the median ( P = 0.013 ) or normal systolic function ( P = 0.005 ) . CONCLUSIONS A lower serum 25(OH)D concentration was associated with an increased risk of cardiovascular events in chronic peritoneal dialysis patients . Furthermore , serum 25(OH)D status appeared to show a differential influence on the cardiovascular outcomes of peritoneal dialysis patients depending on the degree of left ventricular hypertrophy and systolic dysfunction Introduction Osteoporotic fractures in older people are a major and increasing public health problem . We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation . Methods In a pragmatic double blind r and omised controlled trial of 3 years duration , we examined 3,440 people ( 2,624 women and 816 men ) living in residential or care home . We used four-monthly oral supplementation using 100,000 IU vitamin D2 ( ergocalciferol ) . As a main outcome measure , we used the incidence of first fracture using an intention to treat analysis . This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales , UK . Results The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up ( 7 fractures per 100 people per year of follow-up ) , with 218 first fractures in the control group over 2,860 person years of follow-up . The hazard ratio of 0.95 ( 95 % confidence interval 0.79–1.15 ) for intervention compared to control was not statistically significant . ConclusionS upplementation with four-monthly 100,000 IU of oral vitamin D2 is not sufficient to affect fracture incidence among older people living in institutional care 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 OBJECTIVE To evaluate vitamin D as a predictor of all-cause mortality , progression from normoalbuminuria to micro- or macroalbuminuria , and the development of background or proliferative retinopathy in patients with type 1 diabetes . RESEARCH DESIGN AND METHODS A prospect i ve observational follow-up study in which an inception cohort of type 1 diabetic patients was followed from onset of diabetes diagnosed between 1979 and 1984 .  Plasma vitamin D [ 25(OH)D3 ] levels  were determined by high performance liquid chromatography/t and em mass spectrometry in 227 patients before the patients developed microalbuminuria . Values equal to or below the 10 % percentile ( 15.5 nmol/L ) were considered severe vitamin D deficiency . RESULTS Median ( range ) vitamin D  was 44.6 ( 1.7–161.7 ) nmol/L.  Vitamin D level was not associated with age , sex , urinary albumin excretion rate ( UAER ) , or blood pressure . During follow-up , 44 ( 18 % ) patients died . In a Cox proportional hazards model , the hazard ratio for mortality in subjects with severe vitamin D deficiency was 2.7 ( 1.1–6.7 ) , P = 0.03 , after adjustment for UAER , HbA1c , and conventional cardiovascular risk factors ( age , sex , blood pressure , cholesterol , smoking ) . Of the 220 patients , 81 ( 37 % ) developed microalbuminuria and 27 ( 12 % ) of these progressed to macroalbuminuria . Furthermore , 192 ( 87 % ) patients developed background retinopathy , whereas 34 ( 15 % ) progressed to proliferative retinopathy . Severe vitamin D deficiency at baseline did not predict the development of these microvascular complications . CONCLUSIONS In patients with type 1 diabetes , severe vitamin D deficiency independently predicts all-cause mortality but not development of microvascular complications in the eye and kidney . Whether vitamin D substitution in type 1 diabetic patients can improve the prognosis remains to be investigated Conflicting data regarding cardiovascular effects of thiazolidinediones ( TZDs ) and extra-skeletal effects of vitamin D supported the need for a definitive trial . The Thiazolidinedione Intervention with vitamin D Evaluation ( TIDE ) trial aim ed to assess the effects of TZDs ( rosiglitazone and pioglitazone ) on cardiovascular outcomes and the effects of vitamin D ( cholecalciferol ) on  cancers and mortality . A large multicentre 3 × 2 factorial double-blind placebo-controlled r and omised trial recruited from outpatient primary care and specialty clinics in 33 countries . From June 2009 to July 2010 , 1,332 people with type 2 diabetes and other cardiovascular risk factors aged ≥50 years whose HbA1c was 6.5–9.5 % ( 48–80 mmol/mol ) when using two or fewer glucose-lowering drugs were r and omised by a central computer system to placebo ( n = 541 ) , rosiglitazone 4–8 mg/day ( n = 399 ) or pioglitazone 30–45 mg/day ( n = 392 ) ; 1,221 participants were r and omised to placebo ( n = 614 ) or vitamin D 1,000 IU/day ( n = 607 ) . Participants and all study personnel were blind to treatment allocation . The primary outcome for the TZD arm was the composite of myocardial infa rct ion , stroke or cardiovascular death , and for the vitamin D arm it was cancer or all-cause death . All r and omised participants were included in the primary analysis . From the study design , 16,000 people were to be followed for approximately 5.5 years . However , the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data . In the TZD arm , the cardiovascular outcome occurred in five participants ( 0.9 % ) in the placebo groups and three participants ( 0.4 % ) in the TZD groups ( two allocated to pioglitazone , one to rosiglitazone ) . In the vitamin D arm , the primary outcome occurred in three participants ( 0.5 % ) in the placebo group and in two participants ( 0.3 % ) receiving vitamin D. Adverse events were comparable in all groups . Uncertainty persists regarding the clinical ly relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial . Clinical Trials.gov NCT00879970 The study was funded by GlaxoSmithKline 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 CONTEXT Epidemiological and experimental evidence suggests that high levels of vitamin D , a potent immunomodulator , may decrease the risk of  multiple sclerosis .  There are no prospect i ve studies addressing this hypothesis . OBJECTIVE To examine whether levels of 25-hydroxyvitamin D  are associated with risk of multiple sclerosis . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nested case-control study among more than 7 million US military personnel who have serum sample s stored in the Department of Defense Serum Repository . Multiple sclerosis cases were identified through Army and Navy physical disability data bases for 1992 through 2004 , and diagnoses were confirmed by medical record review . Each case ( n = 257 ) was matched to 2 controls by age , sex , race/ethnicity , and date s of blood collection . Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum sample s collected before the date of initial multiple sclerosis symptoms . MAIN OUTCOME MEASURES Odds ratios of multiple sclerosis associated with continuous or categorical levels ( quantiles or a priori-defined categories ) of serum 25-hydroxyvitamin D within each racial/ethnic group . RESULTS Among whites ( 148 cases , 296 controls ) , the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D ( odds ratio [ OR ] for a 50-nmol/L increase in 25-hydroxyvitamin D , 0.59 ; 95 % confidence interval , 0.36 - 0.97 ) . In categorical analyses using the lowest quintile ( < 63.3 nmol/L ) as the reference , the ORs for each subsequent quintile were 0.57 , 0.57 , 0.74 , and 0.38 ( P = .02 for trend across quintiles ) . Only the OR for the highest quintile , corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L , was significantly different from 1.00 ( OR , 0.38 ; 95 % confidence interval , 0.19 - 0.75 ; P = .006 ) . The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years . Among blacks and Hispanics ( 109 cases , 218 controls ) , who had lower 25-hydroxyvitamin D levels than whites , no significant associations between vitamin D and multiple sclerosis risk were found . CONCLUSION The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis 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 OBJECTIVES To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents . DESIGN Secondary data analysis of a previously conducted r and omized clinical trial . SETTING Seven hundred twenty-five-bed long-term care facility . PARTICIPANTS One hundred twenty-four nursing home residents ( average age 89 ) . INTERVENTION Participants were r and omly assigned to receive one of four vitamin D supplement doses ( 200 IU , 400 IU , 600 IU , or 800 IU ) or placebo daily for 5 months . MEASUREMENTS Number of fallers and number of falls assessed using facility incident tracking data base . RESULTS Over the 5-month study period , the proportion of participants with falls was 44 % in the placebo group ( 11/25 ) , 58 % ( 15/26 ) in the 200 IU group , 60 % ( 15/25 ) in the 400 IU group , 60 % ( 15/25 ) in the 600 IU group , and 20 % ( 5/23 ) in the 800 IU group . Participants in the 800 IU group had a 72 % lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months ( rate ratio=0.28 ; 95 % confidence interval=0.11 - 0.75 ) . No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups . CONCLUSION Nursing home residents in the highest vitamin D group ( 800 IU ) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses . Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867 BACKGROUND AND OBJECTIVES Cardiovascular disease is the main cause of mortality in chronic kidney disease ( CKD ) patients .  Vitamin D might have beneficial effects on vascular health . The aim of this study was to determine the prevalence of vitamin D deficiency ( 25-hydroxyvitamin D [ 25D ] < or= 15 ng/ml ) and insufficiency ( 25D levels between 16 and 30 ng/ml ) in a cohort of patients at different CKD stages and the relationships between vitamin D serum levels , vascular calcification and stiffness , and the mortality risk . DESIGN , SETTING , PARTICIPANTS & MEASUREMENTS One hundred forty CKD patients ( 85 men , mean age 67 + /- 12 yr ; CKD stages 2 [ 8 % ] , 3 [ 26 % ] , 4 [ 26 % ] , 5 [ 7 % ] , and 5D [ ( 33 % ] ) were allocated for a prospect i ve study . Serum levels of 25D and 1,25-dihydroxyvitamin D , aortic calcification score , and pulse wave velocity ( PWV ) were evaluated . RESULTS There was a high prevalence of vitamin D deficiency ( 42 % ) and insufficiency ( 34 % ) . Patients with 25D < or= 16.7 ng/ml ( median ) had a significantly lower survival rate than patients with 25D > 16.7 ng/ml ( mean follow-up , 605 + /- 217 d ; range , 10 to 889 ; P = 0.05 ) . Multivariate adjustments ( included age , gender , diabetes , arterial pressure , CKD stage , phosphate , albumin , hemoglobin , aortic calcification score and PWV ) confirmed 25D level as an independent predictor of all-cause mortality . CONCLUSIONS Vitamin D deficiency and insufficiency were highly prevalent in this CKD cohort . Low 25D levels affected mortality independently of vascular calcification and stiffness , suggesting that 25D may influence survival in CKD patients via additional pathways that need to be further explored 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 Low pretreatment vitamin D status has been associated with worsened disease outcomes in patients with cancer at various sites . Its prognostic significance in head and neck cancer ( HNC ) patients has not been studied . Patients with HNC who participated in a r and omized trial were evaluated for : ( i )  total intake of vitamin D from diet and supplements using a vali date d food frequency question naire ( all trial participants , n = 540 ) and ( ii )  pretreatment serum 25‐hydroxyvitamin D through a radioimmunoassay ( n = 522 ) . The association of dietary/serum measures of vitamin D status with HNC recurrence , second primary cancer ( SPC ) incidence , and overall mortality was evaluated using multivariate Cox proportional hazard models . There was no significant association between dietary or serum vitamin D measures and the three HNC outcomes . The hazard ratios ( HRs ) comparing the highest with the lowest quartile of dietary/supplemental vitamin D intake were 1.10 ( 95 % confidence interval ( CI ) : 0.66–1.84 ) for recurrence , 1.05 ( 95 % CI : 0.63–1.74 ) for SPC , and 1.27 ( 95 % CI : 0.87–1.84 ) for overall mortality . HRs comparing the uppermost to the lowest quartile of serum 25‐hydroxyvitamin D levels were 1.12 ( 95 % CI : 0.65–1.93 ) for recurrence , 0.72 ( 95 % CI : 0.40–1.30 ) for SPC , and 0.85 ( 95 % CI : 0.57–1.28 ) for overall mortality . There was no effect modification by cancer stage , season of initial treatment , or trial arm . Among patients with HNC , vitamin D status before treatment does not influence disease outcomes . Our results contrast with those from most published studies , which suggest prognostic significance of vitamin D status in cancer patients at least in subgroups In prospect i ve studies , disease rates during follow-up are typically analyzed with respect to the values of factors measured during an initial baseline survey . However , because of " regression dilution , " this generally tends to underestimate the real associations of disease rates with the " usual " levels of such risk factors during some particular exposure period . The " regression dilution ratio " describes the ratio of the steepness of the uncorrected association to that of the real association . To assess the relevance of the usual value of a risk factor during particular exposure periods ( e.g. , first , second , and third decades ) to disease risks , regression dilution ratios can be derived by relating baseline measurements of the risk factor to replicate measurements from a reasonably representative sample of study participants after an interval equivalent to about the midpoint of each exposure period ( e.g. , at 5 , 15 , and 25 years , respectively ) . This report illustrates the impact of this time interval on the magnitude of the regression dilution ratios for blood pressure and blood cholesterol . The analyses were based on biennial re measurements over 30 years for participants in the Framingham Study ( Framingham , Massachusetts ) and a 26-year resurvey for a sample of men in the Whitehall Study ( London , Engl and ) . They show that uncorrected associations of disease risk with baseline measurements underestimate the strength of the real associations with usual levels of these risk factors during the first decade of exposure by about one-third , the second decade by about one-half , and the third decade by about two-thirds . Hence , to correct appropriately for regression dilution , replicate measurements of such risk factors may be required at varying intervals after baseline for at least a sample of participants 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 Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections . This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections . Methodology / Findings In this prospect i ve cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009–2010 in 198 healthy adults , blinded to the nature of the substance being measured . The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations . The incidence of infection in participants with different concentrations of vitamin D was determined . One hundred ninety-five ( 98.5 % ) of the enrolled participants completed the study . Light skin pigmentation , lean body mass , and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant ( p<0.0001 ) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill . Conclusions / Significance Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby , at least during the fall and winter in temperate zones . The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections , including influenza , in the general population and in sub population s with lower 25-hydroxyvitamin D concentrations , such as pregnant women , dark skinned individuals , and the obese Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community  Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33 CONTEXT Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large , prospect i ve community-based studies . Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity , and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D. OBJECTIVE To investigate whether common variation within genes encoding the vitamin D-binding protein , megalin , cubilin , CYP27B1 , CYP24A1 , and the vitamin D receptor ( VDR ) modify associations of low 25-hydroxyvitamin D with major clinical outcomes . DESIGN , SETTING , AND PARTICIPANTS Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants ( who were recruited from 4 US regions ) from the community-based Cardiovascular Health Study . Participants had serum 25-hydroxyvitamin D measurements in 1992 - 1993 and were followed up for a median of 11 years ( through 2006 ) . Replication meta-analyses were conducted across the independent , community-based US Health , Aging , and Body Composition ( n = 922 ; follow-up : 1998 - 1999 through 2005 ) , Italian Invecchiare in Chianti ( n = 835 ; follow-up : 1998 - 2000 through 2006 ) , and Swedish Uppsala Longitudinal Study of Adult Men ( n = 970 ; follow-up : 1991 - 1995 through 2008 ) cohort studies . MAIN OUTCOME MEASURE Composite outcome of incident hip facture , myocardial infa rct ion , cancer , and mortality over long-term follow-up . RESULTS Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta- analysis . Among Cardiovascular Health Study participants , low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 ( 95 % CI , 1.12 - 1.74 ) for those who had 1 minor allele at rs7968585 and 1.82 ( 95 % CI , 1.31 - 2.54 ) for those with 2 minor alleles at rs7968585 . In contrast , there was no evidence of an association ( estimated hazard ratio , 0.93 [ 95 % CI , 0.70 - 1.24 ] ) among participants who had 0 minor alleles at this single-nucleotide polymorphism . CONCLUSION Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor 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 Vitamin D insufficiency is common globally and low levels are linked to higher cancer incidence . Although vitamin D insufficiency is related to inferior prognosis in some cancers , no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma ( CLL/SLL ) . We evaluated the relationship of 25(OH)D serum levels with time-to-treatment ( TTT ) and overall survival ( OS ) in newly diagnosed CLL patients participating in a prospect i ve cohort study ( discovery cohort ) and a separate cohort of previously untreated patients participating in an observational study ( confirmation cohort ) . Of 390 CLL patients in the discovery cohort , 119 ( 30.5 % ) were 25(OH)D insufficient . After a median follow-up of 3 years , TTT ( hazard ratio[HR ] = 1.66 ; P = .005 ) and OS ( HR = 2.39 ; P = .01 ) were shorter for 25(OH)D-insufficient patients . In the validation cohort , 61 of 153 patients ( 39.9 % ) were 25(OH)D insufficient . After a median follow-up of 9.9 years , TTT ( HR = 1.59 ; P = .05 ) and OS ( HR 1.63 ; P = .06 ) were again shorter for 25(OH)D-insufficient patients . On pooled multivariable analysis of patients in both cohorts adjusting for age , sex , Rai stage , CD38 status , ZAP-70 status , immunoglobulin heavy chain variable ( IGHV ) gene mutation status , CD49d status , and cytogenetic abnormalities assessed by interphase fluorescent in situ hybridization testing , 25(OH)D insufficiency remained an independent predictor of TTT ( HR = 1.47 ; P = .008 ) , although the association with OS was not significant ( HR = 1.47 ; P = .07 ) . Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients . Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing BACKGROUND The majority of dialysis patients suffer from vitamin D deficiency , which might contribute to an adverse health outcome . We aim ed to eluci date whether European dialysis patients with low 25-hydroxyvitamin D ( 25(OH)D ) levels are at increased risk of mortality and specific fatal events . METHODS This was a prospect i ve cohort study of incident dialysis patients in the Netherl and s ( the NECOSAD ) . We selected all patients with measured 25(OH)D at 12 months after the start of dialysis , the baseline for our study . By Cox regression analyses , we assessed the impact of 25(OH)D levels on short-term ( 6 months of follow-up ) as well as longer-term mortality ( 3 years of follow-up ) . Associations of 25(OH)D levels with cardiovascular and non-cardiovascular mortality were also determined . RESULTS The data from 762 patients ( 39 % females , age 59 ± 15 years , 25(OH)D = 18 ± 11 ng/mL ) were available . Fifty-one and 213 patients  died during a follow-up of 6 months and 3 years , respectively . After adjustments for possible confounders , the hazard ratio ( HR ) ( with 95 % CI ) for mortality was 2.0 ( 1.0 - 3.8 ) for short-term and 1.5 ( 1.0 - 2.1 ) for longer-term mortality when comparing patients with 25(OH)D levels ≤ 10 ng/mL with those presenting with 25(OH)D levels > 10 ng/mL. Adjusted HRs for cardiovascular mortality were 2.7 ( 1.1 - 6.5 ) and 1.7 ( 1.1 - 2.7 ) for short- and longer-term mortality , respectively . For non-cardiovascular mortality , we observed no relevant association overall . The impact of 25(OH)D levels on clinical events was modified by parathyroid hormone ( PTH ) status , with low 25(OH)D levels meaningfully affecting outcomes only in patients with PTH levels above the median of 123 pmol/L. CONCLUSIONS Vitamin D deficiency in dialysis patients is associated with an adverse health outcome , in particular with short-term cardiovascular mortality . Intervention studies are urgently needed to evaluate whether vitamin D supplementation improves health outcomes of dialysis patients PURPOSE Previous studies have suggested that higher plasma 25-hydroxyvitamin D(3 ) [ 25(OH)D ] levels are associated with decreased colorectal cancer risk and improved survival , but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown . PATIENTS AND METHODS We prospect ively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a r and omized trial of chemotherapy . Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL , insufficiency as 20 to 29 ng/mL , and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics . Cox proportional hazards models were used to calculate hazard ratios ( HR ) for death , disease progression , and tumor response , adjusted for prognostic factors . RESULTS Among 515 eligible patients , 50 % of the study population was vitamin D deficient , and 82 % were vitamin D insufficient . Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race ( median , 10.7 v 21.1 v 19.3 ng/mL , respectively ; P < .001 ) , and females compared to males ( median , 18.3 v 21.7 ng/mL , respectively ; P = .0005 ) . Baseline plasma 25(OH)D levels were not associated with patient outcome , although given the distribution of plasma levels in this cohort , statistical power for survival analyses were limited . CONCLUSION Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy , particularly in black and female patients OBJECTIVE Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects . The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-st and ing stroke by vitamin D supplementation . METHODS Ninety-six elderly women with poststroke hemiplegia were followed for two years . Patients were r and omly assigned to one of the two groups , and 48 patients received 1,000 IU ergocalciferol daily , and the remaining 48 received placebo . The number of falls per person and incidence of hip fractures were compared between the two groups . Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study . RESULTS At baseline , serum 25-hydroxyvitamin D levels were in the deficient range ( < 10 ng/ml ) in all patients ; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels .  Vitamin D treatment accounted for a 59 % reduction in falls ( 95 % CI , 28 - 81 % ; p = 0.003 ) . There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group . Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period ( log-rank , p = 0.049 ) . CONCLUSION Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers , which may lead to decreased falls and hip fractures A r and omized double-blind controlled trial of the effect of vitamin D supplementation on the abilities of elderly hospital patients to carry out basic activities of daily life is described . Those patients included in the trial had plasma 25-hydroxyvitamin D concentrations which were low or low normal as judged by the normal range in young adults . After 2 to 9 months on the trial there was no significant difference in the performance of the control and treatment groups The purpose of the study was to determine the effect of vitamin D supplementation on bone turnover and bone loss in elderly women . Three hundred forty-eight women , ages 70 yr and older , were r and omized to receive 400 IU vitamin D3 per day ( n = 177 ) or placebo ( n = 171 ) , double-blind , for a period of 2 yr . Main outcome measures were bone mineral density of both hips ( femoral neck and trochanter ) and the distal radius , as well as biochemical markers of bone turnover . The effect of vitamin D supplementation was expressed as the difference in mean ( percentage ) change between the placebo group and the vitamin D group . The measurements were repeated in 283 women after 1 yr and in 248 women after 2 yr . Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D ( 250HD ) ( + 35 nmol/L ) and 1,25-dehydroxyvitamin D [ 1,25-(OH)2D ] ( + 7.0 pmol/L ) levels and urinary calcium/creatinine ratios ( + 0.5 % ) and significantly decreased PTH(1 - 84 ) secretion ( -0.74 pmol/L ) after 1 yr . No effect was found for the parameters of bone turnover . The effect on the bone mineral density of the left femoral neck was + 1.8 % in the first yr , + 0.2 % in the second yr , and + 1.9 % during the whole period ( 95 % confidence interval 0.4 , 3.4 % ) . At the right femoral neck the effects were + 1.5 % , + 1.1 % , and + 2.6 % ( confidence interval 1.1 , 4.0 % ) , respectively . No effect was found at the femoral trochanter and the distal radius . Supplementation with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion and increases bone mineral density at the femoral neck PURPOSE Vitamin D insufficiency is common in the United States , with low levels linked in some studies to higher cancer incidence , including non-Hodgkin 's lymphoma ( NHL ) . Recent data also suggest that vitamin D insufficiency is related to inferior prognosis in some cancers , although there are no data for NHL . PATIENTS AND METHODS We tested the hypothesis that circulating 25-hydroxyvitamin D [ 25(OH)D ] levels are predictive of event-free survival ( EFS ) and overall survival ( OS ) in a prospect i ve cohort of 983 newly diagnosed patients with NHL .  25(OH)D and 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] levels were measured by liquid chromatography-t and em mass spectrometry . RESULTS Mean age at diagnosis was 62 years ( range , 19 to 94 years ) ; 44 % of patients had insufficient 25(OH)D levels ( < 25 ng/mL ) within 120 days of diagnosis . Median follow-up was 34.8 months ; 404 events and 193 deaths ( 168 from lymphoma ) occurred . After adjusting for known prognostic factors and treatment , 25(OH)D insufficient patients with diffuse large B-cell lymphoma ( DLBCL ) had inferior EFS ( hazard ratio [ HR ] , 1.41 ; 95 % CI , 0.98 to 2.04 ) and OS ( HR , 1.99 ; 95 % CI , 1.27 to 3.13 ) ; 25(OH)D insufficient patients with T-cell lymphoma also had inferior EFS ( HR , 1.94 ; 95 % CI , 1.04 to 3.61 ) and OS ( HR , 2.38 ; 95 % CI , 1.04 to 5.41 ) . There were no associations with EFS for the other NHL subtypes . Among patients with DLBCL and T-cell lymphoma , higher 1,25(OH)(2)D levels were associated with better EFS and OS , suggesting that any putative tumor 1-α-hydroxylase activity did not explain the 25(OH)D associations . CONCLUSION 25(OH)D insufficiency was associated with inferior EFS and OS in DLBCL and T-cell lymphoma . Whether normalizing vitamin D levels in these patients improves outcomes will require testing in future trials 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 PURPOSE A cohort study was carried out to test the hypothesis that higher vitamin D levels reduce the risk of relapse from melanoma . METHODS A pilot retrospective study of 271 patients with melanoma suggested that vitamin D may protect against recurrence of melanoma . We tested these findings in a survival analysis in a cohort of 872 patients recruited to the Leeds Melanoma Cohort ( median follow-up , 4.7 years ) . RESULTS In the retrospective study , self-reports of taking vitamin D supplements were nonsignificantly correlated with a reduced risk of melanoma relapse ( odds ratio = 0.6 ; 95 % CI , 0.4 to 1.1 ; P = .09 ) . Nonrelapsers had higher mean 25-hydroxyvitamin D(3 ) levels than relapsers ( 49 v 46 nmol/L ; P = .3 ; not statistically significant ) . In the cohort ( prospect i ve ) study , higher 25-hydroxyvitamin D(3 ) levels were associated with lower Breslow thickness at diagnosis ( P = .002 ) and were independently protective of relapse and death : the hazard ratio for relapse-free survival ( RFS ) was 0.79 ( 95 % CI , 0.64 to 0.96 ; P = .01 ) for a 20 nmol/L increase in serum level . There was evidence of interaction between the vitamin D receptor ( VDR ) BsmI genotype and serum 25-hydroxyvitamin D(3 ) levels on RFS . CONCLUSION Results from the retrospective study were consistent with a role for vitamin D in melanoma outcome . The cohort study tests this hypothesis , providing evidence that higher 25-hydroxyvitamin D(3 ) levels , at diagnosis , are associated with both thinner tumors and better survival from melanoma , independent of Breslow thickness . Patients with melanoma , and those at high risk of melanoma , should seek to ensure vitamin D sufficiency . Additional studies are needed to establish optimal serum levels for patients with melanoma Background : Individuals with higher blood 25-hydroxyvitamin D [ 25(OH)D ] levels have a lower risk of developing colorectal cancer ( CRC ) , but the influence of 25(OH)D on mortality after CRC diagnosis is unknown . Methods : The association between prediagnostic 25(OH)D levels and CRC-specific ( N = 444 ) and overall mortality ( N = 541 ) was prospect ively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort . Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95 % CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes . Potential dietary , lifestyle , and metabolic effect modifiers were also investigated . Results : There were 541 deaths , 444 ( 82 % ) due to CRC . Mean follow-up was 73 months . In multivariable analysis , higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific ( Ptrend = 0.04 ) and overall mortality ( Ptrend = 0.01 ) . Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 ( 95 % CI : 0.50–0.93 ) for CRC-specific mortality and 0.67 ( 95 % CI : 0.50–0.88 ) for overall mortality , compared with the lowest quintile . Except for a possible interaction by prediagnostic dietary calcium intake ( Pinteraction = 0.01 ) , no other potential modifying factors related to CRC survival were noted . The VDR ( FokI and BsmI ) and CASR ( rs1801725 ) genotypes were not associated with survival . Conclusions : High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC . Impact : Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before , at , and after CRC diagnosis on outcomes in CRC patients . Cancer Epidemiol Biomarkers Prev ; 21(4 ) ; 582–93 . © 2012 AACR CONTEXT Vitamin D deficiency and frailty are common with aging , but the association between these conditions is uncertain . OBJECTIVE To determine the association between  25-hydroxyvitamin D ( 25(OH)D ) levels and prevalent and incident frailty status among older women . DESIGN Cross-sectional and longitudinal analyses of a prospect i ve cohort study . SETTING Four U.S. centers . PARTICIPANTS 6307 women aged≥69 years . MAIN OUTCOME MEASURES Frailty status classified as robust , intermediate stage , or frail at baseline ; and robust , intermediate stage , frail , or dead ( all-cause mortality ) at follow-up an average of 4.5 years later . RESULTS At baseline , there was a U-shaped association between 25(OH)D level and odds of frailty with the lowest risk among women with levels 20.0 - 29.9 ng/ml ( referent group ) . Compared with this group , the odds of frailty were higher among those with levels<15.0 ng/ml [ multivariable odds ratio ( MOR ) 1.47 , 95 % confidence interval ( CI ) , 1.19 - 1.82 ] , those with levels 15.0 - 19.9 ng/ml ( MOR 1.24 , 95 % CI 0.99 - 1.54 ) , and those with levels≥30 ng/ml ( MOR 1.32 , 95 % CI 1.06 - 1.63 ) . Among 4551 nonfrail women at baseline , the odds of frailty/death ( vs. robust/intermediate ) at follow-up appeared higher among those with levels 15.0 - 19.9 ng/ml ( MOR 1.21 , 95 % CI 0.99 - 1.49 ) , but the CI overlapped 1.0 . The odds of death ( vs. robust/intermediate/frail at follow-up ) was higher among those with levels<15.0 ng/ml ( MOR 1.40 , 95 % CI 1.04 - 1.88 ) and those with levels 15.0 - 19.9 ng/ml ( MOR 1.30 , 95 % CI 0.97 - 1.75 ) , although the latter association did not quite reach significance . CONCLUSION Lower ( < 20 ng/ml ) and higher ( ≥30 ng/ml ) levels of 25(OH)D among older women were moderately associated with a higher odds of frailty at baseline . Among nonfrail women at baseline , lower levels ( < 20 ng/ml ) were modestly associated with an increased risk of incident frailty or death at follow-up OBJECTIVES To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation . DESIGN A r and omised controlled trial of cluster design . SETTING AND SUBJECTS 223 Residential units ( mainly identical 30-bedded units ) , within 118 homes for elderly people throughout Britain , with 3,717 participating residents ( 76 % women , average age 85 years ) . The units provided mainly or entirely residential care ( 35 % of residents ) , nursing care ( 42 % ) or care for elderly mentally infirm ( EMI ) residents ( 23 % ) . METHODS Participants were r and omly allocated by residential unit ( cluster design ) to a treated group offered ergocalciferol 2.5 mg every 3 months ( equivalent to a daily dose of 1,100 IU ) , or to a control group .  Fractures were reported by staff and confirmed in hospital , and routinely collected data on reported falls were obtained . RESULTS After median follow-up of 10 months ( interquartile range 7 - 14 months ) , 64 ( 3.6 % ) of 1,762 vitamin D-treated residents and 51 ( 2.6 % ) of 1,955 controls had one or more non-vertebral fractures , and 24 ( 1.3 % ) and 20 ( 1.0 % ) , respectively , had a hip fracture . The proportion reporting at least one fall was 44 % in vitamin D-treated and 43 % in control residents . The differences between the vitamin D and control groups were not statistically significant . The incidence of all non-vertebral fractures in the care homes ( 3.2 % per year ) and of hip fractures ( 1.1 % per year ) was low , similar to rates in elderly people in sheltered accommodation , and the pre-treatment serum 25-hydroxy vitamin D concentration was high [ median 47 nmol/l , measured in a 1 % ( n = 18 ) sample ] . CONCLUSIONS We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation Multiple sclerosis ( MS ) patients were r and omized , in a double blind design , and placed into either a vitamin D supplemented group or a placebo control group . As expected , serum 25-hydroxyvitamin D levels increased significantly following 6 month vitamin D supplementation ( 17+/-6 ng/ml at baseline to 28+/-8 ng/ml at 6 months ) . Vitamin D supplementation also significantly increased serum transforming growth factor (TGF)-beta 1 levels from 230+/-21 pg/ml at baseline to 295+/-40 pg/ml 6 months later . Placebo treatment had no effect on serum TGF-beta 1 levels . Tumor necrosis factor (TNF)-alpha , interferon (IFN)-gamma , and interleukin (IL)-13 were not different following vitamin D supplementation . IL-2 mRNA levels decreased following vitamin D supplementation but the differences did not reach significance . Vitamin D supplementation of MS patients for 6 months was associated with increased vitamin D status and serum TGF-beta 1 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 PURPOSE Vitamin D has been linked to breast cancer risk , but prognostic effects are unknown . Such effects are biologically plausible given the presence of vitamin D receptors in breast cancer cells , which act as nuclear transcription factors to regulate gene activity . PATIENTS AND METHODS The study was conducted in a prospect i ve inception cohort of 512 women with early breast cancer diagnosed 1989 to 1996 .  Vitamin D levels were measured in stored blood . Clinical , pathologic , and dietary data were accessed to examine prognostic effects of vitamin D. RESULTS Mean age was 50.4 years , mean vitamin D was 58.1 + /- 23.4 nmol/L.  Vitamin D levels were deficient ( < 50 nmol/L ) in 37.5 % of patients , insufficient ( 50 to 72 nmol/L ) in 38.5 % of patients , and sufficient ( > 72 nmol/L ) in 24.0 % of patients . There was little variation in mean vitamin D levels between summer and winter months . Mean follow-up was 11.6 years ; 116 women had distant recurrences , and 106 women died . Women with deficient vitamin D levels had an increased risk of distant recurrence ( hazard ratio [ HR ] = 1.94 ; 95 % CI , 1.16 to 3.25 ) and death ( HR = 1.73 ; 95 % CI , 1.05 to 2.86 ) compared with those with sufficient levels . The association remained after individual adjustment for key tumor and treatment related factors but was attenuated in multivariate analyses ( HR = 1.71 ; 95 % CI , 1.02 to 2.86 for distant recurrence ; HR = 1.60 ; 95 % CI , 0.96 to 2.64 for death ) . CONCLUSION Vitamin D deficiency may be associated with poor outcomes in breast cancer OBJECTIVE Few studies have examined the relationship between vitamin D levels and incident cardiovascular events in large well-characterized patient cohorts . Therefore , our objective was to determine if low vitamin D levels predicted vascular complications of diabetes . METHODS Prospect i ve analysis of 936 veterans with type 2 diabetes ( 59.7 ± 8.4 years , 96.9 % male ) who participated in the Veteran Affairs Diabetes Trial ( VADT ) was conducted .  25(OH)-vitamin D  was measured a median of two years after entry and participants were subsequently followed 3.7 years . Hazard ratios ( HRs ) were calculated for cardiovascular endpoints in relation to 25(OH)-vitamin  D quartile . For microvascular endpoints , logistic regression was used to calculate odds ratios . RESULTS After adjusting for age , minority status , treatment arm and history of prior event , individuals in the lowest vitamin D quartile ( i.e. , 1 - 15.9 ng/ml ) were at similar risk of MI [ HR = 1.13 ( 95 % CI : 0.53 , 2.42 ) ] , CHD [ HR = 0.87 ( 95 % CI : 0.49 , 1.55 ) ] , congestive heart failure [ HR = 1.44 ( 95 % CI : 0.67 , 3.06 ) ] , and death from any cause [ HR = 1.04 ( 95 % CI : 0.53 , 2.04 ) ] as individuals in the highest vitamin D quartile ( i.e. , 29.9 - 77.2 ng/ml ) . Similarly , there were no differences in the odds associated with retinopathy or renal disease onset or progression in the lowest versus highest vitamin D quartile . CONCLUSIONS These data indicate that vitamin D status had no significant impact on the incidence of vascular events in a cohort of high-risk veterans with diabetes in which traditional risk factors were managed according to current treatment guidelines OBJECTIVES Low trauma fractures in older people incur enormous physical , social and economic costs . Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group . This strategy requires validation in a population setting . METHODS R and omized , double-blind , placebo-controlled trial of 300,000 IU intramuscular ( i.m . ) vitamin D2 ( ergocalciferol ) injection or matching placebo every autumn over 3 years . 9440 people ( 4354 men and 5086 women ) aged 75 yrs and over were recruited from general practice registers in Wessex , Engl and . Primary outcome measure was all non-vertebral fracture . Secondary outcomes were hip and wrist fractures , and all falls . RESULTS 585 subjects had incident non-spine fractures  ( hip 110 , wrist 116 , ankle 37 ) . Hazard ratios ( HRs ) for fracture in the vitamin D group were : 1.09 [ 95 % confidence interval ( CI ) 0.93 - 1.28 , P = 0.29 ] for any first fracture , 1.49 ( 95 % CI 1.02 - 2.18 , P = 0.04 ) for hip and 1.22 ( 95 % CI 0.85 - 1.76 , P = 0.28 ) for wrist . There was no effect on falls : HR 0.98 ( 0.93 - 1.04 ) . No protective effect was observed in any subgroup when the cohort was stratified by sex , age , previous fracture or mobility . CONCLUSIONS An annual i.m . injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population Abstract Objectives To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision . Design R and omised controlled trial . Setting Dunedin and Auckl and , New Zeal and . Participants 391 women and men aged ≥(1 ) 75 with visual acuity of 6/24 or worse who were living in the community ; 92 % ( 361 of 391 ) completed one year of follow-up . Interventions Participants received a home safety assessment and modification programme delivered by an occupational therapist ( n = 100 ) , an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation ( n = 97 ) , both interventions ( n = 98 ) , or social visits ( n = 96 ) . Main outcome measures Numbers of falls and injuries result ing from falls , costs of implementing the home safety programme . Results Fewer falls occurred in the group r and omised to the home safety programme but not in the exercise programme ( incidence rate ratios 0.59 ( 95 % confidence interval 0.42 to 0.83 ) and 1.15 ( 0.82 to 1.61 ) , respectively ) . However , within the exercise programme , stricter adherence was associated with fewer falls ( P = 0.001 ) . A conservative analysis showed neither intervention was effective in reducing injuries from falls . Delivering the home safety programme cost $ NZ650 ( £ 234 , 344 euros , $ US432 ) ( at 2004 prices ) per fall prevented . Conclusion The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision .  The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group , possibly due to low levels of adherence . Trial registration number IS RCT N15342873 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 There is an increase in the incidence of falls with aging and about 10 % of falls lead to fractures . Nearly all hip fractures are due to falls and hip fractures are the most severe of the osteoporotic fractures because they lead to a 20 % mortality rate and a loss of independent living in 50 % of cases . Although there are multiple factors associated with falls , our interest is the role that vitamin D metabolism plays in the pathogenesis of falls . Recent clinical trials show that both vitamin D and the metabolite calcitriol reduce the number of falls by 30 - 40 % in elderly subjects . This should also reduce the number of fractures . In European studies , the decrease in falls could be attributed to an improvement in the muscle weakness that often accompanies vitamin D deficiency . However , in the studies using calcitriol there was no vitamin D deficiency , so the mechanism of its efficacy is less clear . It could be due to increased muscle strength , an improvement in the neurological control of balance or both . Underst and ing these mechanisms would allow us to search for analogs of vitamin D that act more selectively on muscle and on the central nervous system Background : In chronic kidney disease and dialysis patients , vitamin D deficiency is associated with mortality . In some observational studies , calcitriol analogue therapy was associated with a better survival rate in hemodialysis ( HD ) patients . The aim of this study was to determine the relationship between serum 25-hydroxyvitamin D ( 25-OHD ) levels and alfacalcidol therapy with HD patients ’ outcomes . Methods : We measured baseline 25-OHD levels using a cross-sectional analysis in 648 HD prevalent patients from the regional ARNOS French cohort . A 42-month survival analysis was applied according to serum 25-OHD level and calcitriol analogue therapy . Results : The prevalence of 25-OHD insufficiency < 30 ng/ml was high ( 73 % ) , with only 22 % taking native vitamin D supplementation . A baseline 25-OHD level above the median value ( 18 ng/ml ) was associated with lower all-cause mortality [ hazard ratio ( HR ) , 0.73 ( 0.5–0.96 ) ; p = 0.02 ] after adjustment for age , gender , dialysis vintage , calcemia , phosphatemia , cardiovascular disease , and diabetes . Only in monovariate analysis was low-dose oral alfacalcidol therapy associated with a better survival rate in patients with and without 25-OHD deficiency [ HR , 0.7 ( 0.5–0.92 ) ; p = 0.05 ] . Conclusions : Our study shows that , among prevalent HD patients , low 25-OHD levels affect  mortality .  Alfacalcidol therapy , especially in small doses , may provide compensation , but this needs to be further confirmed using prospect i ve controlled studies comparing native and active vitamin D compounds 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 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 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 OBJECTIVE Vitamin D deficiency has been linked to cardiovascular disease and mortality in hemodialysis ( HD ) patients . The purpose of the present cross-sectional study was to analyze the Vitamin D status of dialysis patients from a single center , study determinants of Vitamin D deficiency , and assess its implication s on outcome . METHODS A prospect i ve observational study of 115 prevalent dialysis patients was carried out , in which clinical and dialysis-related characteristics including routine biochemistry were studied in relation to levels of  25-hydroxyvitamin-D ( 25[OH]D , chemiluminescence )  . Survival was assessed after a median follow-up period of 413 days . RESULTS 25(OH)D deficiency and insufficiency was present in 51 % and 42 % of the patients , respectively . Only 7 % of the patients showed normal 25(OH)D levels .  Peritoneal dialysis  patients presented the lowest 25(OH)D levels . Also , a significant difference was found between on-line hemodiafiltration ( OL-HDF ) and conventional HD ( 11 [ 6 to 16 ] versus 19 [ 13 to 27 ] ng/mL ; P < 0.001 ; 25th to 75th percentiles , conventional HD versus OL-HDF respectively ) . In multinomial logistic regression analysis , patients on conventional HD had 8.35 greater odds ( 95 % CI [ 2.04 to 34.20 ] ) of 25(OH)D deficiency than OL-HDF even after adjustment for sex , parathyroid hormone , pH , and Charlson comorbidity index . During the follow-up period , 18 patients died . Both crude and adjusted ( hazard ratio , 6.96 ; 95 % CI [ 1.44 to 33.64 ] ) Cox analysis identified 25(OH)D deficiency as a mortality risk factor . CONCLUSION This observational study underlines the high prevalence of hypovitaminosis D in dialysis patients and its strong implication s on outcome . Furthermore , our results suggest that OL-HDF was associated with a better preservation of the vitamin D status as compared with conventional HD BACKGROUND This post hoc nested case-control analysis of the TNT study was design ed to investigate whether baseline vitamin D level is a significant predictor of cardiovascular risk among statin-treated patients and whether changes in vitamin D after treatment with atorvastatin are associated with improved cardiovascular outcomes . METHODS A total of 10,001 patients with stable coronary heart disease were r and omized to atorvastatin  80 or 10 mg for a median of 4.9 years . This analysis included 1,509 patients ( 497 with a subsequent cardiovascular event and 1,012 without an event ) with vitamin D levels determined at baseline and 1 year . Event rates were analyzed by Cox proportional hazard model by baseline vitamin D levels , with vitamin D as a continuous variable , and with change in vitamin D level as the predictor . RESULTS Vitamin D deficiency ( < 15 ng/mL ) or insufficiency ( 15- < 30 ng/mL ) was present in 108 ( 7.2 % ) of 1,509 and 625 ( 41.4 % ) of 1,509 of patients , whereas 46 ( 3.0 % ) of 1,509 had elevated vitamin D. There was no relationship between baseline vitamin D levels or change in vitamin D levels and cardiovascular events or mortality . Modeling of events with vitamin D as a continuous variable similarly showed no relationship of vitamin D to events . These findings held true after adjustment for seasonal variations in vitamin D and other confounders . CONCLUSION In statin-treated patients with stable coronary heart disease , vitamin D levels did not predict cardiovascular risk . Changes in plasma concentrations of vitamin D after 1 year of treatment made no contribution to the efficacy of atorvastatin therapy OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( < 12 ng/mL ) at baseline . CONCLUSION Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people 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 BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine ( IOM ) . An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes . The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health , consistent with a cause- and -effect relationship and providing a sound basis for determination of intake requirements . For extraskeletal outcomes , including cancer , cardiovascular disease , diabetes , and autoimmune disorders , the evidence was inconsistent , inconclusive as to causality , and insufficient to inform nutritional requirements . R and omized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative . Based on bone health , Recommended Dietary Allowances ( RDAs ; covering requirements of ≥97.5 % of the population ) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age . For vitamin D , RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older , corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml ( 50 nmol/liter ) , meet the requirements of at least 97.5 % of the population . RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer . Higher values were not consistently associated with greater benefit , and for some outcomes U-shaped associations were observed , with risks at both low and high levels . The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated . Urgent research and clinical priorities were identified , including re assessment of laboratory ranges for 25-hydroxyvitamin D , to avoid problems of both undertreatment and overtreatment 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 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 BACKGROUND Serum 25-hydroxyvitamin D ( 25-[OH]D ) is considered the best biomarker of clinical vitamin D status . OBJECTIVE To determine the effect of increasing oral doses of vitamin D(3 ) on serum 25-(OH)D and serum parathyroid hormone ( PTH ) levels in postmenopausal white women with vitamin D insufficiency ( defined as a 25-[OH]D level ≤50 nmol/L ) in the presence of adequate calcium intake . These results can be used as a guide to estimate the Recommended Dietary Allowance ( RDA ) ( defined as meeting the needs of 97.5 % of the population ) for vitamin D(3 ) . DESIGN R and omized , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00472823 ) SETTING Creighton University Medical Center , Omaha , Nebraska . PARTICIPANTS 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year . INTERVENTION Participants were r and omly assigned to receive placebo or vitamin D(3 ) , 400 , 800 , 1600 , 2400 , 3200 , 4000 , or 4800 IU once daily . Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg . MEASUREMENTS The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months . RESULTS The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3 ) . The RDA of vitamin D(3 ) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d . A mixed-effects model predicted that 600 IU of vitamin D(3 ) daily could also meet this goal . Compared with participants with a normal body mass index ( < 25 kg/m(2 ) ) , obese women ( ≥30 kg/m(2 ) ) had a 25-(OH)D level that was 17.8 nmol/L lower . Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3 ) ( P = 0.012 ) . Depending on the criteria used , hypercalcemia occurred in 2.8 % to 9.0 % and hypercalciuria in 12.0 % to 33.0 % of participants ; events were unrelated to dose . LIMITATION Findings may not be generalizable to other age groups or persons with substantial comorbid conditions . CONCLUSION A vitamin D(3 ) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5 % of women ; however , a model predicted the same response with a vitamin D(3 ) dosage of 600 IU/d . These results can be used as a guide for the RDA of vitamin D(3 ) , but prospect i ve trials are needed to confirm the clinical significance of these results . PRIMARY FUNDING SOURCE National Institute on Aging 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: 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 .
background: 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 .