Association of low serum 25-hydroxyvitamin D levels and high arterial blood pressure in the elderly. Low serum 25-hydroxyvitamin D concentrations are associated with greater all-cause mortality in older community-dwelling women. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. The Association of 25-Hydroxyvitamin D3 and D2 with Behavioural Problems in Childhood Associations between serum 25-hydroxyvitamin D concentrations and multiple health conditions, physical performance measures, disability, and all-cause mortality: the Concord Health and Ageing in Men Project. Chronic kidney disease, hypovitaminosis D, and mortality in the United States. Associations between 25-hydroxyvitamin D and weight gain in elderly women. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Low levels of vitamin D are associated with increased mortality in patients attending a university hospital in Denmark Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults Multivariate Path Analysis of Serum 25-Hydroxyvitamin D Concentration, Inflammation, and Risk of Type 2 Diabetes Mellitus Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures Low Serum Levels of 25-Hydroxyvitamin D Predict Fatal Cancer in Patients Referred to Coronary Angiography Serum 25‐hydroxyvitamin D as a predictor of mortality and cardiovascular events: A 20‐year study of a community‐based cohort The inverse association between serum 25-hydroxyvitamin D and mortality may be modified by vitamin A status and use of vitamin A supplements Relationship between the effect of eldecalcitol and serum 25(OH)D level Plasma 25-Hydroxyvitamin D Levels and Risk of Incident Hypertension
BACKGROUND Vitamin D and calcium metabolism are involved in vascular smooth muscle cell proliferation , endothelial function and blood pressure ( BP ) regulation . Their physiopathology has been a matter of intensive clinical investigation with variable and sometimes contradictory results . Vitamin D insufficiency is highly prevalent in the general population , particularly among the elderly . We evaluated the association between serum 25(OH)-D levels and arterial BP in this population . METHODS An epidemiological cross-sectional study was design ed to analyse the prevalence of hypovitaminosis D ( ' D'AVIS ' study ) in our reference area . The study was performed on a representative r and om sample of the population over 64 years of age obtained from five primary health care areas . A medical record , arterial BP and biological analysis : serum 25(OH)-D , iPTH , creatinine , urea , calcium , albumin were obtained . RESULTS A total of 237 subjects ( 53 % women ) , aged between 64 and 93 ( mean 71.7 + /- 5.3 ) , were evaluated . The mean serum 25(OH)-D levels were 17.21 + /- 7.57 ng/ml ( interval 5 - 54 ; 86 % had < 25 ng/ml ) . The mean BP was 138.8 + /- 14/80 + /- 7.4 mmHg , and 46 % were on antihypertensive treatment . A significant negative association was observed between serum 25(OH)-D levels and systolic ( r = -0.153 , P = 0.018 ) and diastolic BP ( r = -0.152 , P = 0.019 ) . This association persisted after controlling for possible confounders in the multivariate analyses . CONCLUSIONS Low serum 25(OH)-D levels were inversely and independently associated with BP . Supplemental measures to prevent hypovitaminosis D in this population would be important , not only to protect the skeletal system but also for the possible beneficial effects on the cardiovascular system and the BP regulation Vitamin D deficiency is associated with osteoporosis , poor muscle strength , falls , and fractures . The relationship between serum vitamin D concentrations and mortality in older community-dwelling women has not been well characterized . We hypothesized that women with lower 25-hydroxyvitamin D ( 25[OH]D ) concentrations were at higher risk of mortality . We examined the association between serum 25[OH]D concentrations and all-cause mortality in a prospect i ve , population -based study of 714 community-dwelling women , aged 70 to 79 years , the Women 's Health and Aging Studies I and II in Baltimore , Md. The studies were originally design ed to evaluate the causes and course of physical disability in older women living in the community .  Vital status was determined through follow-up interviews and matching with the National Death Index . During a median of 72 months of follow-up , 100 ( 14 % ) of 714 women died . Women in the lowest quartile of 25(OH)D ( < 15.3 ng/mL or 38.2 nmol/L ) were at higher risk of death ( hazards ratio , 2.45 ; 95 % confidence interval , 1.12 - 5.36 ; P = .02 ) compared to women in the highest quartile ( > 27.0 ng/mL or 67.4 nmol/L ) of 25(OH)D in a multivariate Cox proportional hazards model adjusting for demographics , season , and conventional risk factors . Older community-dwelling women with low 25(OH)D levels are at an increased risk of death BACKGROUND Recent studies suggest a role for vitamin D in innate immunity , including the prevention of respiratory tract infections ( RTIs ) . We hypothesize that serum 25-hydroxyvitamin D ( 25[OH]D ) levels are inversely associated with self-reported recent upper RTI ( URTI ) . METHODS We performed a secondary analysis of the Third National Health and Nutrition Examination Survey , a probability survey of the US population conducted between 1988 and 1994 . We examined the association between 25(OH)D level  and  recent URTI in 18 883 participants 12 years and older . The analysis adjusted for demographics and clinical factors ( season , body mass index , smoking history , asthma , and chronic obstructive pulmonary disease ) . RESULTS The median serum 25(OH)D level was 29 ng/mL ( to convert to nanomoles per liter , multiply by 2.496 ) ( interquartile range , 21 - 37 ng/mL ) , and 19 % ( 95 % confidence interval [ CI ] , 18%-20 % ) of participants reported a recent URTI . Recent URTI was reported by 24 % of participants with 25(OH)D levels less than 10 ng/mL , by 20 % with levels of 10 to less than 30 ng/mL , and by 17 % with levels of 30 ng/mL or more ( P < .001 ) . Even after adjusting for demographic and clinical characteristics , lower 25(OH)D levels were independently associated with recent URTI ( compared with 25[OH]D levels of > or = 30 ng/mL : odds ratio [ OR ] , 1.36 ; 95 % CI , 1.01 - 1.84 for < 10 ng/mL and 1.24 ; 1.07 - 1.43 for 10 to < 30 ng/mL ) . The association between 25(OH)D level and URTI seemed to be stronger in individuals with asthma and chronic obstructive pulmonary disease ( OR , 5.67 and 2.26 , respectively ) . CONCLUSIONS Serum 25(OH)D levels are inversely associated with recent URTI . This association may be stronger in those with respiratory tract diseases . R and omized controlled trials are warranted to explore the effects of vitamin D supplementation on RTI Background Higher serum concentrations of 25-hydroxyvitamin D ( 25(OH)D ) , an indicator of vitamin D synthesis and intake , have been associated with better mental health and cognitive function . Concentrations of 1,25-dihydroxyvitamin D3 ( the active vitamin D3 metabolite ) have been associated with openness and extrovert behaviour , but 25(OH)D concentrations have not been associated with behavioural problems in humans . Methods We investigated the prospect i ve association between the different forms of 25(OH)D - 25(OH)D3 and 25(OH)D2–  and childhood behavioural problems in Avon Longitudinal Study of Parents and Children ( ALSPAC ) .  Serum 25(OH)D3 and 25(OH)D2 concentrations were assessed at mean age 9.9 years . Incident behavioural problems were assessed with Strengths and Difficulties Question naire ( SDQ ; emotional symptoms , conduct problems , hyperactivity-inattention problems , peer relationship problems and pro-social behaviour subscales and total difficulties score ) at mean age 11.7 . Sample sizes varied between 2413 - 2666 depending on the outcome . Results Higher 25(OH)D3 concentrations were weakly associated with lower risk of prosocial problems ( fully adjusted odds ratio : OR ( 95 % confidence interval : CI ) 0.85 ( 0.74 , 0.98 ) ) . Serum 25(OH)D3 or 25(OH)D2 concentrations were not associated with other subscales of SDQ or total difficulties score after adjusting for concfounders and other measured analytes related to vitamin D. Conclusions Our findings do not support the hypothesis that 25-hydroxyvitamin D status in childhood has important influences on behavioural traits in humans OBJECTIVES To explore associations between serum  25-hydroxyvitamin D ( 25(OH)D ) levels and a wide range of health conditions , physical performance measures , disability , and mortality in a large epidemiological study to identify an optimum range for 25(OH)D concentrations . DESIGN Cross-sectional study , with additional prospect i ve data on falls and mortality . SETTING Concord Health and Ageing in Men Project , Sydney , Australia . PARTICIPANTS Community-dwelling men aged 70 and older ( N = 1,659 ) . MEASUREMENTS  Serum 25(OH)D levels , general health status , self-reported diseases , physical performance measures , disability ( activities of daily living and instrumental activities of daily living ) and falls . RESULTS Fair , poor , and very poor health ; self-reported diabetes mellitus ; hyperglycemia ; depression ; muscle weakness ; poor balance ; and all-cause mortality were all associated with serum 25(OH)D levels less than 50 nmol/L , even after adjustment for confounding . The findings also suggest that , in older men , for a wide range of health conditions , physical performance measures , disability , falls , and mortality , the optimum range of 25(OH)D is between 50.0 and 74.9 nmol/L , with no additional benefit for 25(OH)D levels of 75.0 nmol/L or greater . CONCLUSION Programs aim ed at achieving an optimum range of serum 25(OH)D at levels between 50.0 and 74.9 nmol/L may have overall health benefits and such levels are adequate for older men Low serum 25-hydroxy vitamin D ( 25OHD ) predicts a higher cardiovascular risk in the general population . Because patients with chronic kidney disease are more likely to have low serum 25OHD , we determined the relationship between hypovitaminosis D and death in this group . Analysis was done using a cohort composed of 3011 patients from the Third National Health and Nutrition Examination Survey who had chronic kidney disease but were not on dialysis and who had a mean follow-up of 9 years . In analyses adjusted for demographics , cardiovascular risk factors , serum phosphorus , albumin , hemoglobin , stage of chronic kidney disease , albuminuria , and socioeconomic status , individuals with serum 25OHD levels less than 15 ng/ml had an increased risk for all-cause mortality when compared to those with levels over 30 ng/ml . This significantly higher risk for death with low serum 25OHD was evident in 15 of the 23 subgroups . The higher risk for cardiovascular and non-cardiovascular mortality became statistically nonsignificant on multivariable adjustment . The trend for higher mortality in patients with 25OHD levels 15 - 30 ng/ml was not statistically significant . Our results indicate there is a grade d relationship between serum 25OHD and the risk for death among subjects with chronic kidney disease who are not undergoing dialysis . R and omized , controlled trials are needed to conclusively determine whether vitamin D supplementation reduces mortality BACKGROUND 25-Hydroxyvitamin D [ 25(OH)D ] levels are lower in obese individuals . Determining whether low vitamin D status can predispose weight gain requires a longitudinal study . METHODS From a community-based multicenter U.S. prospect i ve cohort of 9704 ( Study of Osteoporotic Fractures [ SOF ] ) , 4659 women aged ≥65 with baseline 25(OH)D measurement were followed for 4.5 years . They were weighed at baseline and follow-up visits , and a subset ( n=1054 ) had 25(OH)D levels remeasured at follow-up . RESULTS Women with 25(OH)D levels ≥30 ng/mL had lower baseline weight ( 141.6 pounds ) compared to women with 25(OH)D levels < 30 ng/mL ( 148.6 pounds ) ( p<0.001 ) . Overall , 25(OH)D status was not associated with weight change over 4.5 years , although there was a significant interaction between 25(OH)D status and weight change category ( loss , gain , stable ) ( p<0.0001 ) . In women who gained ≥5 % weight , those with baseline 25(OH)D levels ≥30 ng/mL gained 16.4 pounds ( 12.2 % of baseline weight ) over 4.5 years compared to 18.5 pounds ( 13.9 % of baseline weight ) in women with levels < 30 ng/mL ( p=0.04 ) . In women who lost ≥5 % weight or remained stable ( < 5 % weight change ) , there was no association between 25(OH)D status at baseline and weight change . Among women who gained weight and had 25(OH)D measured at both visits , having sustained or developing 25(OH)D levels ≥30 ng/mL was associated with less weight gain between visits ( 14.81 vs. 16.34 pounds , p=0.04 ) . CONCLUSIONS Higher 25(OH)D levels are associated with lower weight gains , suggesting low vitamin D status may predispose to fat accumulation 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 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 Background / Objectives : Vitamin D deficiency is associated with cardiovascular disease , osteoporosis , poor muscle strength , falls , fractures and mortality . Although older adults are at a higher risk of vitamin D deficiency , the relationship of serum 25-hydroxyvitamin D ( 25(OH)D ) with all-cause and cardiovascular disease mortality has not been well characterized in the elderly . We hypothesized that low serum 25(OH)D levels predicted mortality in older adults . Subjects/ Methods : Serum 25(OH)D  as well as all-cause and cardiovascular disease mortality were examined in 1006 adults , aged ⩾65 years , who participated in the InCHIANTI ( Invecchiare in Chianti , Aging in the Chianti Area ) study , a population -based , prospect i ve cohort study of aging in Tuscany , Italy . Serum 25(OH)D levels were measured at the time of enrollment in 1998–1999 , and participants were followed up for mortality . Results : During 6.5 years of follow-up , 228 ( 22.7 % ) participants died , of whom 107 died due to cardiovascular diseases . Compared with participants in the highest quartile of serum 25(OH)D ( > 26.5 ng/ml ) ( to convert to nmol/l , multiply by 2.496 ) , those in the lowest quartile ( < 10.5 ng/ml ) had increased risk of all-cause mortality ( Hazard Ratio ( H.R. ) 2.11 , 95 % Confidence Interval ( 95 % C.I. ) : 1.22–3.64 , P=0.007 ) and cardiovascular disease mortality ( H.R. 2.64 , 95 % C.I. : 1.14–4.79 , P=0.02 ) , in multivariate Cox proportional hazards models that adjusted for age , sex , education , season , physical activity and other potential confounders . Conclusions : Older community-dwelling adults with low serum 25(OH)D levels are at higher risk of all-cause and cardiovascular disease mortality Background and Aims . Despite growing interest in the protective role that vitamin D may have in health outcomes , little research has examined the mechanisms underlying this role . This study aim ed to test two hypotheses : ( 1 ) serum 25-hydroxyvitamin D [ 25(OH)D ] is inversely associated with type 2 diabetes mellitus ( T2DM ) and elevated hemoglobin A1c ; ( 2 ) these associations are mediated by serum C-reactive protein ( CRP ) . Methods . Participants aged 20 and older in 2001–2006 National Health and Nutrition Examination Surveys ( n = 8,655 ) with measures of serum 25(OH)D , CRP , hemoglobin A1c , and other important covariates were included in the present study . Logistic regression and path analysis methods were applied to test the study hypotheses . Results . Decreased serum 25(OH)D concentration was significantly associated with increased odds of T2DM .  In males , an estimated 14.9 % of the association between 25(OH)D and hemoglobin A1c was mediated by serum CRP . However , this mediation effect was not observed in females . Conclusion . Using a nationally representative sample , the present study extends previous research and provides new evidence that the effect of  decreased serum vitamin D concentration on T2DM may proceed through increased systemic inflammation in males . Longitudinal studies and r and omized control trials are needed to confirm the present findings Context Vitamin D supplementation may help prevent fractures , but the relationship between blood vitamin D concentrations and fracture risk is unclear . Contribution These authors observed an increased risk for hip fracture among women with lower serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations that was independent of measures of frailty , body mass index , physical function , and falls . Caution The authors did not measure bone mineral density ( BMD ) , so they could not determine whether 25(OH ) vitamin D concentrations give different information about fracture risk than that offered by BMD . Implication Low serum 25(OH ) vitamin D concentrations seem to be associated with a higher hip fracture risk . The Editors Vitamin  D deficiency is common in older adults , especially during the winter ( 1 ) and in homebound population s ( 2 ) , general medical in patients ( 3 ) , and community-dwelling women admitted to the hospital with acute hip fracture ( 4 ) . A recently published evidence -based report on vitamin D and bone health ( 5 ) found the level of evidence for an association between serum 25-hydroxyvitamin D [ 25(OH ) vitamin D ] concentrations and fracture risk to be inconsistent ( 5 ) . Since publication of that review , 1 prospect i ve study ( 6 ) reported no relationship between serum 25(OH ) vitamin D concentrations and fractures , whereas another ( 7 ) reported a significantly lower risk for hip fracture with 25(OH ) vitamin D concentrations greater than 60 nmol/L. Vitamin D concentration could be associated with fractures in several ways . It could influence muscle strength and balance , both of which contribute to falls and disability ( 810 ) . The association between 25(OH ) vitamin D concentrations and fracture may also be influenced by renal function , because renal insufficiency has been linked to fracture ( 11 ) and to vitamin D deficiency ( 12 ) . Several interactions between vitamin D and estrogen receptors have been described ( 13 ) ; hormone therapy has been shown to reverse abnormalities in vitamin D metabolism ( 14 ) , and low vitamin D concentrations have also been linked to higher bone turnover ( 15 , 16 ) . Thus , sex-steroid hormones and bone turnover could contribute to the association between 25(OH ) vitamin D concentration and fractures . We conducted a nested casecontrol study within the WHI-OS ( Women 's Health Initiative Observational Study ) among 400 case- patients with adjudicated incident hip fracture and 400 control participants . We tested whether low serum 25(OH ) vitamin D concentrations are associated with a higher risk for hip fractures in community-dwelling women and whether this relationship may be mediated by poor physical functioning , frailty , falls , sex-steroid hormones , renal function , or bone turnover . Methods Study Population Our study population came from the WHI-OS , a prospect i ve cohort study that enrolled 93676 women between 1994 and 1998 at 40 U.S. clinical centers ( age range , 50 to 79 years ) . Study methods are described in detail elsewhere ( 17 ) . In brief , women were eligible if they were postmenopausal , were unlikely to move or die within 3 years , were not enrolled in the WHI clinical trials , and were not currently participating in any other clinical trial . The human subjects review committees from each participating institution approved the study . Follow-up and Outcome Ascertainment We sent women question naires annually to report any hospitalization and other outcomes , including fractures . As of August 2004 , median follow-up duration was 7.1 years ( range , 0.7 to 9.3 years ) . At that time , 3.7 % of participants had withdrawn or were lost to follow-up and 5.3 % had died . We review ed medical records to verify cases of hip fracture , and blinded central adjudicators confirmed the cases ( 18 ) . We excluded patients with pathologic hip fractures . Nested CaseControl Study Design The present study is a casecontrol study nested within the prospect i ve design of WHI-OS . We excluded women who had a history of hip fracture ; were receiving hormone therapy up to 1 year before enrollment ; or were currently receiving and rogens , selective estrogen receptor modulators , antiestrogens , or other osteoporosis treatments ( bisphosphonates , calcitonin , or parathyroid hormone ) . We also excluded women with insufficient serum stored or of unknown ethnicity , leaving 39793 eligible participants . Of these , 404 women had a hip fracture . We r and omly selected 400 of these women to form the incident hip fracture group . For each case-patient , we selected 1 control participant who was within 1 year of the case-patient 's age at screening , was of matching race or ethnicity , and had their blood drawn within 120 days of the case-patient 's blood draw date ; 99 % of case- patients and control participants were matched within 30 days . Baseline Clinical Variables We divided clinical centers into 3 geographic regions on the basis of latitude : northern ( > 40 N ) , middle ( 35 to 40 N ) , and southern ( < 35 N ) . We ascertained all covariates at baseline . Clinic interviewers recorded current use of prescription medications by direct inspection of medicine containers . We entered prescription names into the WHI data base and assigned drug codes by using Medispan software ( First Data Bank , San Bruno , California ) . Average amounts of elemental calcium and vitamin D preparations were entered directly from supplement containers . Dietary intakes of calcium and vitamin D were assessed by using a semiquantitative food-frequency question naire ( 19 ) . Total calcium and vitamin D intake was defined as the sum of diet and supplements . We used question naires to ascertain date of birth , race or ethnicity , age at menopause , history of any fracture after age 55 years , smoking , parental history of hip fracture , self-rated health status , and alcohol consumption . We classfied physical activity on the basis of frequency and duration of walking and mild , moderate , and strenuous activities in the previous week . We calculated kilocalories of energy expended in 1 week as the metabolic equivalent ( kcal hours/week per kg ) ( 20 ) . We measured physical function by using the R AND Short Form-36 physical function scale , which comprises 10 items measuring whether health now limits physical function in moderate or vigorous activity ( 2 items ) ; strength to lift , carry , stoop , bend , or stair climb ( 4 items ) ; ability to walk various distances without difficulty ( 3 items ) ; and self-care ( 1 item ) ( 21 ) . The scale is scored from 0 to 100 , with higher scores indicating better physical function . We compared women with a score greater than 90 versus those with a score less than or equal to 90 , a cutoff value corresponding to the median score . We computed a frailty score , which included self-reported muscle weakness and impaired walking speed ( R AND Short Form-36 physical function scale score < 75 ) , exhaustion ( R AND Short Form-36 vitality scale score < 55 ) , low physical activity ( lowest quartile of physical activity ) , and unintended weight loss between baseline and 3 years of follow-up ( 22 ) . A woman was considered frail if she reported 3 or more of these indicators . Weight was measured on a balance-beam scale with the participant dressed in indoor clothing without shoes . Height was measured by using a wall-mounted stadiometer . Body mass index was calculated as weight ( in kg ) divided by height ( in m2 ) . Laboratory Procedures Laboratory personnel blinded to casecontrol status obtained a 12-hour fasting blood sample at the baseline visit , which was processed and stored at 80C according to strict quality control procedures ( 23 ) . Serum 25(OH ) vitamin D concentrations and sex-steroid hormone levels were measured at the Reproductive Endocrine Research Laboratory at the University of Southern California .  25-Hydroxyvitamin vitamin D was measured by using a radioimmunoassay with DiaSorin reagents ( DiaSorin , Stillwater , Minnesota ) . The sensitivity of the assay was 3.75 nmol/L. The interassay coefficients of variation were 11.7 % , 10.5 % , 8.6 % , and 12.5 % at 14.0 , 56.8 , 82.5 , and 122.5 nmol/L , respectively . Estradiol and testosterone concentrations were quantified by using sensitive and specific radioimmunoassays after organic solvent extraction and celite column partition chromatography ( 2427 ) . The intra- and interassay coefficients of variation were 7.9 % and 8 % to 12 % , respectively , for estradiol and 6 % and 10 % to 12 % , respectively , for testosterone . We calculated bioavailable hormone concentrations by using mass action equations ( 2830 ) . We measured sex hormonebinding globulin by using a solid-phase , 2-site chemiluminescent immunoassay . The intra- and interassay coefficients of variation were 4.1 % to 7.7 % and 5.8 % to 13 % , respectively . Serum cystatin C , a marker of renal function that is independent of age and weight , was measured at Medical Research Laboratories International , Highl and Heights , Kentucky , by using the Dade Behring BN-II nephelometer and Dade Behring reagents ( Dade Behring , Ramsey , Minnesota ) in a particle-enhanced immunonepholometric assay . Serum C-terminal telopeptide of type I collagen and aminoterminal procollagen extensions propeptide were measured by immunoassay ( Synarc , Lyon , France ) . Statistical Analysis We used chi-square and t tests to compare baseline characteristics between case- patients with hip fracture and matched control participants . We assigned 25(OH ) vitamin D concentrations to quartile categories defined on the basis of the distribution in the control participants . To further assess confounding , we compared baseline characteristics across quartiles of 25(OH ) vitamin D concentrations in case- patients and control participants combined . We calculated the P values for trend by using logistic regression and coding the variable of interest as a continuous variable . We assessed the association between serum 25(OH ) vitamin D concentrations and incident hip fracture in conditional logistic regression models that retained the matched casecontrol design . We first examined the unadjusted associations and then adjusted for age , Accumulating evidence suggests that vitamin D may protect against cancer , but results from epidemiologic studies are inconclusive so far , and other studies looking into the prospect i ve association of total cancer mortality and serum 25-hydroxyvitamin D [ 25(OH)D ] levels , which are considered to be the best indicator of vitamin D status , are scarce . We measured 25(OH)D and 1,25-dihydroxyvitamin D in 3,299 patients from the Ludwigshafen Risk and Cardiovascular Health study . The baseline examination was done between July 1997 and January 2000 and included a fasting blood sampling in the morning before coronary angiography . During a median follow-up period of 7.75 years , 95 patients died due to cancer . After adjustment for possible confounders , the Cox proportional hazard ratio ( 95 % confidence interval ) of the fourth 25(OH)D quartile was 0.45 ( 0.22 - 0.93 ) when compared with the first quartile and the hazard ratio per increase of 25 nmol/L in serum 25(OH)D concentrations was 0.66 ( 0.49 - 0.89 ) . We found no association between serum 1,25-dihydroxyvitamin D levels and fatal cancer . In summary , our data suggest that low levels of 25(OH)D are associated with increased risk of fatal cancer in patients referred to coronary angiography and that the maintenance of a sufficient vitamin D status might therefore be a promising approach for the prevention and /or treatment of cancer . ( Cancer Epidemiol Biomarkers Prev 2008;17(5):1228–33 Prospect i ve studies , mostly from Europe and North America , suggest that serum 25‐hydroxyvitamin D ( 25(OH)D ) is inversely associated with mortality and cardiovascular disease ( CVD ) risk . Data from other regions are limited , and threshold levels for adverse cardiovascular outcomes are uncertain . We examined serum 25(OH)D  as a predictor of total mortality and cardiovascular outcomes in an Australian cohort Background Low serum 25-hydroxyvitamin D [ 25(OH)D ] levels have been associated with higher risk of many diseases that affect mortality , including cardiovascular disease ( CVD ) and cancer . The inverse association between serum 25(OH)D and mortality may be modified by excess circulating vitamin A , due to interactions of vitamin A at the level of the vitamin D nuclear receptor . In this prospect i ve cohort study , we investigated whether the association of 25(OH)D with all-cause , cancer , and CVD mortality  was modified by circulating vitamin A or preformed vitamin A intake from supplements . Methods We analyzed 15,998 adults in the Third National Health and Nutrition Examination Survey ( NHANES III ) , 1988–1994 . Mortality data for all-cause ( n = 3890 ) , cancer ( n = 844 ) , and CVD mortality ( n = 1715 ) were assessed through December 2006 .  Serum 25(OH)D was measured using a radioimmunoassay kit , vitamin A biomarkers were measured by HPLC , and information on supplement use was obtained by self-report . Multivariable hazard ratios ( HRs ) and corresponding 95 % confidence intervals ( CI ) were estimated by proportional hazards regression . Results Serum 25(OH)D was significantly inversely associated with all-cause mortality ( HR 0.93 , 95 % CI 0.89 , 0.97 , per 10 ng/mL increase ) and also with CVD mortality and mortality due to non-cancer/non-cardiovascular causes , but not with cancer mortality . The observed inverse associations remained statistically significant only among participants with serum retinyl esters < 7.0 μg/dL. High intake ( > 5000 IU/day ) of preformed vitamin A from supplements attenuated the inverse association of 25(OH)D with overall mortality . The observed interactions were not statistically significant . Conclusions 25(OH)D was inversely associated with overall mortality , CVD mortality , and mortality due to non-cancer/non-CVD causes , but not with cancer mortality . A possible interaction between vitamin A exposure and 25(OH)D concentration appears to be associated with an attenuation of the inverse association between risk of death and quartile of 25(OH)D concentration In previous studies , we demonstrated that 12-month treatment with 0.75μg/day eldecalcitol increased bone mineral density in osteoporotic patients regardless of serum 25-hydroxyvitamin D ( 25(OH)D ) level , and in a 3-year r and omized double-blind clinical trial , eldecalcitol significantly reduced the incidences of vertebral and wrist fractures compared to alfacalcidol . However , it remains unclear whether the fracture risk reduction by eldecalcitol is affected by serum 25(OH)D. In the fracture prevention trial , patients with low 25(OH)D level at baseline were supplemented with 400IU/day native vitamin D3 . In the current study , patients from that trial were divided according to the tertiles of serum 25(OH)D level at 6 months after treatment initiation . The increases in lumbar and hip BMD by eldecalcitol were significantly higher in all tertiles than those by alfacalcidol .  The incidences of vertebral and osteoporotic fractures tended to be lower in each tertile of the eldecalcitol-treated group than in the corresponding tertile of the alfacalcidol-treated group , with the exception of vertebral fractures in the low tertile . We also investigated whether eldecalcitol treatment affected levels of serum 25(OH)D , serum 1,25(OH)2D , and parathyroid hormone in patients without vitamin D supplementation .  With eldecalcitol treatment , serum 1,25(OH)2D concentration was reduced by approximately 50 % , whereas serum levels of parathyroid hormone and 25(OH)D were not affected . The major findings of the present study were that eldecalcitol did not affect serum 25(OH)D levels , and that it reduced the incidence of osteoporotic fractures and increased BMD in comparison with alfacalcidol regardless of serum 25(OH)D level within the range of serum 25(OH)D concentrations at or higher than 20ng/mL. Whether eldecalcitol is similarly effective at vitamin D deficient serum 25(OH)D levels remains to be clarified . This article is part of a Special Issue entitled ' Vitamin D Workshop ' Hydroxylation of 25(OH)D to 1,25-dihydroxyvitamin D and signaling through the vitamin D receptor occur in various tissues not traditionally involved in calcium homeostasis . Laboratory studies indicate that 1,25-dihydroxyvitamin D suppresses renin expression and vascular smooth muscle cell proliferation ; clinical studies demonstrate an inverse association between ultraviolet radiation , a surrogate marker for vitamin D synthesis , and blood pressure . We prospect ively studied the independent association between measured plasma 25-hydroxyvitamin D [ 25(OH)D ] levels and  risk of incident hypertension  and also the association between predicted plasma 25(OH)D levels and risk of incident hypertension .  Two prospect i ve cohort studies including 613 men from the Health Professionals ’ Follow-Up Study and 1198 women from the Nurses ’ Health Study with measured 25(OH)D levels were followed for 4 to 8 years . In addition , 2 prospect i ve cohort studies including 38 388 men and 77 531 women with predicted 25(OH)D levels were followed for 16 to 18 years . During 4 years of follow-up , the multivariable relative risk of incident hypertension among men whose measured plasma 25(OH)D levels were < 15 ng/mL ( ie , vitamin D deficiency ) compared with those whose levels were ≥30 ng/mL was 6.13 ( 95 % confidence interval [ CI ] : 1.00 to 37.8 ) . Among women , the same comparison yielded a relative risk of 2.67 ( 95 % CI : 1.05 to 6.79 ) . The pooled relative risk combining men and women with measured 25(OH)D levels using the r and om-effects model was 3.18 ( 95 % CI : 1.39 to 7.29 ) . Using predicted 25(OH)D levels in the larger cohorts , the multivariable relative risks comparing the lowest to highest deciles were 2.31 ( 95 % CI : 2.03 to 2.63 ) in men and 1.57 ( 95 % CI : 1.44 to 1.72 ) in women . Plasma 25(OH)D levels are inversely associated with risk of incident hypertension
The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health .
Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D , which would explain why low vitamin D status is reported in a wide range of disorders .
In elderly people , restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival
Low serum concentrations of 25-hydroxyvitamin D ( 25[OH]D ) have been associated with many non-skeletal disorders .
However , whether low 25(OH)D is the cause or result of ill health is not known .