Low serum 25-hydroxyvitamin D levels are associated with increased all-cause mortality risk in a general population: the Tromsø study. Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes. The inverse association between serum 25-hydroxyvitamin D and mortality may be modified by vitamin A status and use of vitamin A supplements Low serum 25-hydroxyvitamin D concentrations are associated with greater all-cause mortality in older community-dwelling women. Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) The effect of vitamin D and frailty on mortality among non-institutionalized US older adults Genetically low vitamin D concentrations and increased mortality: mendelian randomisation analysis in three large cohorts Vitamin D and Calcitonin Treatment in Patients with Femoral Neck Fracture: A Prospective Controlled Clinical Study Season and ethnicity are determinants of serum 25-hydroxyvitamin D concentrations in New Zealand children aged 5-14 y. The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know Prospective study of serum 25-hydroxyvitamin D concentration and mortality in a Chinese population. Bread fortified with cholecalciferol increases the serum 25-hydroxyvitamin D concentration in women as effectively as a cholecalciferol supplement. Effect of Bimonthly Supplementation With Oral Cholecalciferol on Serum 25-Hydroxyvitamin D Concentrations in HIV-Infected Children and Adolescents Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents. Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland Calcium malabsorption in the elderly: the effect of treatment with oral 25‐hydroxyvitamin D3 Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. A randomized controlled trial of vitamin D supplementation on perinatal depression: in Iranian pregnant mothers 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. The association between serum 25-hydroxyvitamin D3 concentration and risk of disease death in men: modification by magnesium intake Serum 25-Hydroxyvitamin D Concentrations and Depressive Symptoms among Young Adult Men and Women Calcium Absorption Varies within the Reference Range for Serum 25-Hydroxyvitamin D
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 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 Background Low serum 25-hydroxyvitamin D [ 25(OH)D ] levels have been associated with higher risk of many diseases that affect mortality , including cardiovascular disease ( CVD ) and cancer . The inverse association between serum 25(OH)D and mortality may be modified by excess circulating vitamin A , due to interactions of vitamin A at the level of the vitamin D nuclear receptor . In this prospect i ve cohort study , we investigated whether the association of 25(OH)D with all-cause , cancer , and CVD mortality  was modified by circulating vitamin A or preformed vitamin A intake from supplements . Methods We analyzed 15,998 adults in the Third National Health and Nutrition Examination Survey ( NHANES III ) , 1988–1994 . Mortality data for all-cause ( n = 3890 ) , cancer ( n = 844 ) , and CVD mortality ( n = 1715 ) were assessed through December 2006 .  Serum 25(OH)D was measured using a radioimmunoassay kit , vitamin A biomarkers were measured by HPLC , and information on supplement use was obtained by self-report . Multivariable hazard ratios ( HRs ) and corresponding 95 % confidence intervals ( CI ) were estimated by proportional hazards regression . Results Serum 25(OH)D was significantly inversely associated with all-cause mortality ( HR 0.93 , 95 % CI 0.89 , 0.97 , per 10 ng/mL increase ) and also with CVD mortality and mortality due to non-cancer/non-cardiovascular causes , but not with cancer mortality . The observed inverse associations remained statistically significant only among participants with serum retinyl esters < 7.0 μg/dL. High intake ( > 5000 IU/day ) of preformed vitamin A from supplements attenuated the inverse association of 25(OH)D with overall mortality . The observed interactions were not statistically significant . Conclusions 25(OH)D was inversely associated with overall mortality , CVD mortality , and mortality due to non-cancer/non-CVD causes , but not with cancer mortality . A possible interaction between vitamin A exposure and 25(OH)D concentration appears to be associated with an attenuation of the inverse association between risk of death and quartile of 25(OH)D concentration Vitamin D deficiency is associated with osteoporosis , poor muscle strength , falls , and fractures . The relationship between serum vitamin D concentrations and mortality in older community-dwelling women has not been well characterized . We hypothesized that women with lower 25-hydroxyvitamin D ( 25[OH]D ) concentrations were at higher risk of mortality . We examined the association between serum 25[OH]D concentrations and all-cause mortality in a prospect i ve , population -based study of 714 community-dwelling women , aged 70 to 79 years , the Women 's Health and Aging Studies I and II in Baltimore , Md. The studies were originally design ed to evaluate the causes and course of physical disability in older women living in the community .  Vital status was determined through follow-up interviews and matching with the National Death Index . During a median of 72 months of follow-up , 100 ( 14 % ) of 714 women died . Women in the lowest quartile of 25(OH)D ( < 15.3 ng/mL or 38.2 nmol/L ) were at higher risk of death ( hazards ratio , 2.45 ; 95 % confidence interval , 1.12 - 5.36 ; P = .02 ) compared to women in the highest quartile ( > 27.0 ng/mL or 67.4 nmol/L ) of 25(OH)D in a multivariate Cox proportional hazards model adjusting for demographics , season , and conventional risk factors . Older community-dwelling women with low 25(OH)D levels are at an increased risk of death Background 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 Introduction Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures . A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects . Purpose and Methods Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have review ed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases , providing recommendations and guidelines for future studies in this field . Results and conclusions Robust mechanistic evidence is available from in vitro studies and in vivo animal studies , usually employing cholecalciferol , calcidiol or calcitriol in pharmacologic rather than physiologic doses . Although many cross-sectional and prospect i ve association studies in humans have shown that low 25-hydroxyvitamin D levels ( i.e. , < 50 nmol/L ) are consistently associated with chronic diseases , further strengthened by a dose-response relationship , several meta-analyses of clinical trials have shown contradictory results . Overall , large r and omized controlled trials with sufficient doses of vitamin D are missing , and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels  > 50 nmol/L , did not simultaneously assess multiple outcomes , and did not report overall safety ( e.g. , falls ) . Thus , no recommendations can be made to date for the use of vitamin D supplementation in general , parental compounds , or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases . Moreover , attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health can not be recommended based on current evidence , since safety has yet to be confirmed . Finally , the promising findings from mechanistic studies , large cohort studies , and small clinical trials obtained for autoimmune diseases ( including type 1 diabetes , multiple sclerosis , and systemic lupus erythematosus ) , cardiovascular disorders , and overall reduction in mortality require further confirmation BACKGROUND / OBJECTIVES : Although both frailty and low vitamin D have been separately associated with an increased risk for adverse health , their joined effects on mortality have not been reported . The current study examined prospect ively the effects of frailty and vitamin D status on mortality in US older adults . SUBJECTS/ METHODS : Participants aged ⩾60 years in The Third National Health and Nutrition Examination Survey with 12 years of mortality follow-up were included in the analysis ( n=4731 ) . Frailty was defined as meeting three or more criteria and pre-frailty as meeting one or two of the five frailty criteria ( low body mass index ( BMI ) , slow walking , weakness , exhaustion and low physical activity )  . Vitamin D status  was assessed by serum 25-hydroxyvitamin D ( 25(OH)D )  and categorized into quartiles . Analyses were adjusted for gender , race , age , smoking , education , latitude and other comorbid conditions . RESULTS : Serum 25(OH)D concentrations were lowest in participants with frailty , intermediate in participants with pre-frailty and highest in participants without frailty . The odds of frailty in the lowest quartile of serum 25(OH)D was 1.94 times the odds in the highest quartile ( 95 % confidence interval ( CI ) : 1.09–3.44 ) . Mortality was positively associated with frailty , with the risk among participants who were frail and had low serum 25(OH)D being significantly higher than those who were not frail and who had high concentrations of serum 25(OH)D ( hazards ratio 2.98 ; 95 % CI : 2.01–4.42 ) . CONCLUSION : Our results suggest that low serum 25(OH)D is associated with frailty , and there is additive joint effects of serum 25(OH)D and frailty on all-cause mortality in older adults Objective To test the hypothesis that genetically low 25-hydroxyvitamin D concentrations are associated with increased mortality . Design Mendelian r and omisation analysis . Setting Copenhagen City Heart Study , Copenhagen General Population Study , and Copenhagen Ischemic Heart Disease Study . Participants 95 766 white participants of Danish descent from three cohorts , with median follow-up times of 19.1 , 5.8 , and 7.9 years , genotyped for genetic variants in DHCR7 and CYP2R1 affecting plasma 25-hydroxyvitamin D concentrations ; 35 334 also had plasma 25-hydroxyvitamin D measurements . Participants were followed from study entry through 2013 , during which time 10 349 died . Main outcome measures All cause mortality and cause specific mortality , adjusted for common risk factors for all cause mortality based on the World Health Organization ’s global health status . Results The multivariable adjusted hazard ratios for a 20 nmol/L lower plasma 25-hydroxyvitamin D concentration were 1.19 ( 95 % confidence interval 1.14 to 1.25 ) for all cause mortality , 1.18 ( 1.09 to 1.28 ) for cardiovascular mortality , 1.12 ( 1.03 to 1.22 ) for cancer mortality , and 1.27 ( 1.15 to 1.40 ) for other mortality . Each increase in DHCR7/CYP2R1 allele score was associated with a 1.9 nmol/L lower plasma 25-hydroxyvitamin D concentration and with increased all cause , cancer , and other mortality but not with cardiovascular mortality . The odds ratio for a genetically determined 20 nmol/L lower plasma 25-hydroxyvitamin D concentration was 1.30 ( 1.05 to 1.61 ) for all cause mortality , with a corresponding observational multivariable adjusted odds ratio of 1.21 ( 1.11 to 1.31 ) . Corresponding genetic and observational odds ratios were 0.77 ( 0.55 to 1.08 ) and 1.13 ( 1.03 to 1.24 ) for cardiovascular mortality , 1.43 ( 1.02 to 1.99 ) and 1.10 ( 1.02 to 1.19 ) for cancer mortality , and 1.44 ( 1.01 to 2.04 ) and 1.17 ( 1.06 to 1.29 ) for other mortality . The results were robust in sensitivity analyses . Conclusions Genetically low 25-hydroxyvitamin D concentrations were associated with increased all cause mortality , cancer mortality , and other mortality but not with increased cardiovascular mortality . These findings are compatible with the notion that genetically low 25-hydroxyvitamin D concentrations may be causally associated with cancer and other mortality but also suggest that the observational association with cardiovascular mortality could be the result of confounding The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9 ) and 25 μg calcitonin given subcutaneously 30 times ( n=10 ) in 10 weeks were studied against a  control ( n = ll ) . Bone histology and histomorphometry showed non-age related osteoporosis in 30 % and osteomalacia in 22 % of the patients studied . Impaired serum vitamin D status was found in 47 – 88 % of patients , secondary hyperparathyroidism and increased serum parathyroid hormone in 59 % and decreased serum calcitonin levels in 69 % . On histology , normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3 . Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia . Calcitonin improved calcium balance , reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia .  Vitamin  D reduced osteomalacia , slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone . Both treatments gave a similar slight decrease in serum calcitonin concentrations . A mechanism of action for the treatments is suggested New Zeal and children , particularly those of Māori and Pacific ethnicity , may be at risk for low vitamin D status because of low vitamin D intakes , the country 's latitude ( 35 - 46 degrees S ) , and skin color . The aim of this study was to determine 25-hydroxyvitamin D concentrations and their determinants in a national sample of New Zeal and children aged 5 - 14 y. The 2002 National Children 's Nutrition Survey was design ed to survey New Zeal and children , including oversampling of Māori and Pacific children to allow ethnic-specific analyses . A 2-stage recruitment process occurred using a r and om selection of schools , and children within each school .  Serum 25-hydroxyvitamin D concentration [ mean ( 99 % CI ) nmol/L ] in Māori children ( n = 456 ) was 43 ( 38,49 ) , in Pacific ( n = 646 ) 36 ( 31,42 ) , and in New Zeal and European and Others ( NZEO ) ( n = 483 ) 53 ( 47,59 ) . Among Māori , Pacific , and NZEO , the prevalence ( % , 99 % CI ) of serum 25-hydroxyvitamin D deficiency ( < 17.5 nmol/L ) was 5 ( 2,12 ) , 8 ( 5,14 ) , and 3 ( 1,7 ) , respectively . The prevalence of insufficiency ( < 37.5 nmol/L ) was 41 ( 29,53 ) , 59 ( 42,75 ) , and 25 ( 15,35 ) , respectively . Multiple regression analysis found that 25-hydroxyvitamin D concentrations were lower in winter than summer [ adjusted mean difference ( 99 % CI ) nmol/L ; 15 ( 8,22 ) ] , lower in girls than boys [ 5 ( 1,10 ) ] , and lower in obese children than in those of " normal " weight [ 6 ( 1,11 ) ] . Relative to NZEO , 25-hydroxyvitamin D concentrations were lower in Māori [ 9 ( 3,15 ) ] and Pacific children [ 16 ( 10,22 ) ] . Ethnicity and season are major determinants of serum 25-hydroxyvitamin D. There is a high prevalence of vitamin D insufficiency in New Zeal and children , which may or may not contribute to increased risk of osteoporosis and other chronic disease . There is a pressing need for more convincing evidence concerning the health risks associated with the low  vitamin D status in New Zeal and children 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 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 Fortification of foods is a feasible way of preventing low vitamin D status .  Bread could be a suitable vehicle for fortification because it is a common part of diets worldwide . The bioavailability of cholecalciferol from bread is not known . We studied cholecalciferol stability , the concentration of the added cholecalciferol , the dispersion of cholecalciferol in bread , and the bioavailability of cholecalciferol from fortified bread . Three batches of fortified low-fiber wheat and high-fiber rye breads were baked ; from each batch , 3 sample s of dough and bread were analyzed for their cholecalciferol content . In a single-blind bioavailability study , 41 healthy women , 25 - 45 y old , with mean serum 25-hydroxyvitamin D concentration 29 nmol/L ( range 12 - 45 nmol/L ) , were r and omly assigned to 4 study groups . Each group consumed fortified wheat bread , fortified rye bread , regular wheat bread ( control ) , or regular wheat bread and a cholecalciferol supplement ( vitamin D control ) daily for 3 wk . The daily dose of vitamin D was 10 mug in all groups except the control group . The vitamin dispersed evenly in the breads and was stable . Both fortified breads increased serum 25-hydroxyvitamin D concentration as effectively as the cholecalciferol supplement . Supplementation or fortification did not affect serum intact parathyroid hormone concentration or urinary calcium excretion . In conclusion , fortified bread is a safe and feasible way to improve vitamin D nutrition OBJECTIVE . Vitamin D insufficiency occurs commonly in HIV-infected youth in the United States . In light of the importance of vitamin D for skeletal and nonskeletal health , including innate immunity , developing methods for improving vitamin D status in HIV-infected children and adolescents is an important area of clinical research . The objective of this study was to evaluate the effect of administration of oral cholecalciferol , 100000 IU every 2 months , and 1 g/day calcium on serum 25-hydroxyvitamin D concentrations , serum and urine calcium , and HIV disease progression during a 12-month period . METHODS . HIV-infected children and adolescents who were aged 6 to 16 years were r and omly assigned to receive vitamin D ( 100000 IU bimonthly ) and calcium ( 1 g/day ; n = 29 ) or double placebo ( n = 27 ) . Serum 25-hydroxyvitamin D concentrations as measured by radioimmunoassay , albumin-corrected calcium concentrations , and spot urinary calcium-creatinine ratios were determined monthly . RESULTS . No abnormalities in serum calcium concentration were observed . One participant who received placebo  developed hypercalciuria . No group differences were seen in the change in CD4 count or CD4 % or viral load during 12 months . The overall mean monthly serum 25-hydroxyvitamin D concentrations were higher in the group that received vitamin D and calcium than in the placebo group , as was the monthly serum 25-hydroxyvitamin D area under the curve . After completing 12 months of study , 2 ( 6.7 % ) participants in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration < 20 ng/mL compared with 14 ( 50 % ) in the placebo group . Twelve ( 44.4 % ) in the group that received vitamin D and calcium  had a trough serum 25-hydroxyvitamin D concentration of ≥30 ng/mL compared with 3 ( 11.1 % ) in the placebo group . CONCLUSIONS . Administration of oral cholecalciferol to HIV-infected children and adolescents at a dosage of 100000 IU every 2 months , together with 1 g/day calcium , is safe and results in significant increases in serum 25-hydroxyvitamin D concentrations CONTEXT Vitamin D deficiency contributes to skeletal diseases and is highly prevalent among institutionalized elderly patients . Whether low 25-hydroxyvitamin D ( 25[OH]D ) concentrations are an independent risk factor for mortality in these patients is , however , unclear . OBJECTIVE We aim ed to evaluate whether 25(OH)D concentrations are associated with mortality . DESIGN , SETTING , AND PARTICIPANTS This is a prospect i ve cohort study among elderly female patients ( age > 70 yr ) recruited from 95 nursing homes in Austria . MAIN OUTCOME MEASURES We calculated Cox proportional hazard ratios ( HR ) for all-cause mortality according to 25(OH)D quartiles . RESULTS We examined 961 study participants ( age 83.7 ± 6.1 yr ) . Median 25(OH)D concentration was 17.5 ( interquartile range 13.7 - 25.5 ) nmol/liter , and 93 % of our cohort had 25(OH)D levels below 50 nmol/liter . During a mean follow-up time of 27 ± 8 months , 284 patients died . Compared with the fourth quartile ( 25[OH]D > 25.5 nmol/liter ) , the age-adjusted HR ( with 95 % confidence interval ) was 1.49 ( 1.07 - 2.10 ) in the first 25(OH)D quartile ( 25[OH]D < 14.0 nmol/liter ) , and this association remained significant after multivariate adjustments ( HR = 1.56 ; 95 % confidence interval = 1.01 - 2.40 ) . CONCLUSIONS This Austrian study suggests that the majority of institutionalized female patients are vitamin D deficient during winter and that there was an inverse association of 25(OH)D and mortality . These data underscore the urgent need for effective strategies for the prevention and treatment of vitamin D deficiency , in particular in the setting of nursing homes 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 Abstract . Calcium malabsorption is common in the elderly and may contribute to the development of age‐related bone loss . To investigate its cause , we have measured  radio‐calcium absorption , plasma 25‐hydroxyvitamin D , 1,25‐dihydroxyvitamin D and parathyroid hormone  in forty‐eight elderly women with a normal plasma creatinine . Calcium malabsorption was associated with low 25‐hydroxyvitamin D concentrations and was corrected by increasing these into the normal range by treatment with oral 25‐hydroxyvitamin D3 . Treatment also increased 1,25‐dihydroxyvitamin D , and decreased parathyroid hormone concentrations 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 Background Mood disorders in pregnancy and post-partum period are common and considered as a public health issue . Research ers have studied the relationship between low serum vitamin D concentration and perinatal depression , although no clinical trial has been conducted on vitamin D ’s effects on depression related to childbirth . This study evaluated the effect of vitamin D3 supplementation on perinatal depression scores . Methods This r and omized clinical trial was done in pregnant women who were under prenatal care in a teaching hospital in Shiraz , Iran . The inclusion criteria were : being 18 years or older , no history of mental illness and internal diseases , a singleton live fetus , without any pregnancy complications , gestational age of 26–28 weeks upon enrollment , and depression score of 0 to 13 . The Edinburgh Postnatal Depression scale was used to evaluate depression scores . A total of 169 participants were assigned to the two groups of placebo and vitamin D through block r and omization design . Vitamin D group received 2000 IU vitamin D3 daily from 26 to 28 weeks of gestation until childbirth . Maternal serum 25-hydroxyvitamin D concentrations were measured at baseline and childbirth . Besides , depression scores were evaluated four times : at 26–28 and 38–40 weeks of gestation , and finally at 4 and 8 weeks after birth . Results The two groups were similar in relation to baseline 25-hydroxyvitamin D concentrations . However , at childbirth , the vitamin D group had significantly higher 25-hydroxyvitamin D concentration in comparison to the control group ( p < 0.001 ) . At baseline , no correlation was observed between 25-hydroxyvitamin D concentration and depression score ( r = 0.13 , p = 0.09 ) . There was no significant difference between the two study groups in relation to the baseline depression score . While , the vitamin D group had greater reduction in depression scores than the control group at 38–40 weeks of gestation ( p = 0.01 ) also , at 4 and 8 weeks after birth ( p < 0.001 ) . Conclusions The present trial showed that consuming 2000 IU vitamin D3 daily during late pregnancy was effective in decreasing perinatal depression levels . We suggest further clinical trial in pregnant mothers who are at risk for postnatal depression . Trial registration Iranian Registry of Clinical Trials I RCT 2015020310327N11 . Date of registration : March 9th 2015 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 vitamin D status increases the risk of death . Magnesium plays an essential role in vitamin D metabolism and low magnesium intake may predispose to vitamin D deficiency and potentiate the health problems . We investigated whether magnesium intake modifies the serum 25(OH)D3 concentration and its associations with mortality in middle-aged and older men . We included 1892 men aged 42–60 years without cardiovascular disease or cancer at baseline in 1984–1989 from the prospect i ve , population -based Kuopio Ischaemic Heart Disease Risk Factor Study .  Serum 25(OH)D3 was measured with the high-performance liquid chromatography using coulometric electrode array detection . Magnesium intake was assessed with 4-day food recording .  Deaths were ascertained by a computer linkage to the national cause of death register . Deaths due accidents and suicides were excluded . Cox proportional hazards regression models were used to analyze the associations . The multivariate-adjusted hazard ratio ( HR ) for death in the lowest ( < 32.1 nmol/L ) versus the highest ( > 49.4 nmol/L ) serum 25(OH)D3 tertile was 1.31 ( 95 % CI 1.07–1.60 , Ptrend = 0.01 ) . Stratified by the magnesium intake , the higher risk was observed only in the lower magnesium intake median ( < 414 mg/day ) ; HR = 1.60 ( 95 % CI 1.19–2.13 , Ptrend = 0.002 ) in the lowest versus the highest 25(OH)D3 tertile , whereas the corresponding HR = 1.07 , 95 % CI 0.75–1.36 , Ptrend = 0.63 ) in the higher magnesium intake median , P for interaction = 0.08 . In this cohort of middle-aged and older men  low serum 25(OH)D3 concentration was associated with increased risk of death mainly in those with lower magnesium intake There has been an increased interest in the role of vitamin D in depression ; however , there have been few studies conducted in younger population groups . Our aim was to investigate the association between vitamin D status and depressive symptoms in a non- clinical young adult sample living in Dunedin , New Zeal and . A cross-sectional sample of 615 young adults completed a question naire including demographics and the  Centre  for Epidemiological Studies Depression Scale ( CES-D ) . Height , weight and a blood sample for 25-hydroxyvitamin D [ 25(OH)D ] was obtained . Serum 25(OH)D was used to predict depression scores , adjusting for potential confounders including time spent outdoors for 13 consecutive days , BMI , age , sex and ethnicity . Prevalence of low vitamin D was high even in this age group , and serum 25(OH)D was negatively associated with depression symptoms before and after adjustment . When investigating the relationship between the presence versus absence of depressive symptoms and quartiles of 25(OH)D , participants in the lowest quartile were more likely to report depressive symptoms compared with those in the highest quartile . Although our findings suggest that vitamin D is a predictor of depression symptomatology , even when controlling for time spent outdoors , a r and omised controlled trial in this young adult target group is needed to confirm the association Background : Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency , but the vitamin D status that fully normalizes absorption is not known for humans . Objective : To quantify calcium absorption at two levels of vitamin D repletion , using pharmacokinetic methods and commercially marketed calcium supplements . Design : Two experiments performed in the spring of the year , one year apart . In the first , in which participants were pretreated with 25-hydroxyvitamin D ( 25OHD )  , mean serum 25OHD concentration was 86.5 nmol/L ; and in the other , with no pretreatment , mean serum concentration was 50.2 nmol/L. Participants received 500 mg oral calcium loads as a part of a st and ard low calcium breakfast . A low calcium lunch was provided at mid-day . Blood was obtained fasting and at frequent intervals for 10 to 12 hours thereafter . Methods : Relative calcium absorption at the two 25OHD concentrations was estimated from the area under the curve ( AUC ) for the load-induced increment in serum total calcium . Results : AUC9 ( ± SEM ) , was 3.63 mg hr/dL ± 0.234 in participants pretreated with 25OHD  and 2.20 ± 0.240 in those not pretreated ( P < 0.001 ) . In brief , absorption was 65 % higher at serum 25OHD levels averaging 86.5 nmol/L than at levels averaging 50 nmol/L ( both values within the nominal reference range for this analyte ) . Conclusions : Despite the fact that the mean serum 25OHD level in the experiment without supplementation was within the current reference ranges , calcium absorptive performance at 50 nmol/L was significantly reduced relative to that at a mean 25OHD level of 86 nmol/L. Thus , individuals with serum 25-hydroxyvitamin D levels at the low end of the current reference ranges may not be getting the full benefit from their calcium intake . We conclude that the lower end of the current reference range is set too low
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 .