Does liver damage explain the inverse association between vitamin D status and mortality? Sun, vitamin D, and cardiovascular disease. Trends and mortality effects of vitamin A deficiency in children in 138 low-income and middle-income countries between 1991 and 2013: a pooled analysis of population-based surveys. Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland Prospective association of vitamin D concentrations with mortality in postmenopausal women: results from the Women's Health Initiative (WHI). The Association of Serum Vitamin D Concentration with Serious Complications After Noncardiac Surgery Circulating 25-Hydroxyvitamin D3 and Survival after Diagnosis with Kidney Cancer Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. Effects of monthly dose and regular dosing of intravenous active vitamin D use on mortality among patients undergoing hemodialysis. Serum Antioxidant Nutrients, Vitamin A, and Mortality in U.S. Adults Circulating 25OHD, dietary vitamin D, PTH, and calcium associations with incident cardiovascular disease and mortality: the MIDSPAN Family Study. Cognitive impairment and mortality in a cohort of elderly people Should measurement of vitamin D and treatment of vitamin D insufficiency be routine in New Zealand? Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents. Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale Maternal vitamin A deficiency and infant mortality in Malawi. Parathyroid hormone and vitamin D--markers for cardiovascular and all cause mortality in heart failure. Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Antioxidant vitamin intake and mortality in three Central and Eastern European urban populations: the HAPIEE study Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection. Reduced mortality among children in southern India receiving a small weekly dose of vitamin A.
PURPOSE Several observational studies have linked vitamin D deficiency with an increased risk of all cause mortality .  Vitamin D deficiency is common among patients with liver diseases . In a r and om sample of the general population , we investigated whether the inverse association between vitamin D status and all-cause mortality could be explained by liver damage as reflected by increased levels of liver enzymes . METHODS We included a total of 2649 persons examined in 1993e1994 . Vitamin D status was assessed as serum 25-hydroxyvitamin D and liver enzyme levels were measured . Information on all-cause mortality was obtained from the Danish Central Personal Register until July 2011 . Median follow-up time was 17.0 years , and there were 736 deaths . RESULTS Multivariable Cox regression analyses with age as underlying time axis and delayed entry showed lower mortality risk with higher vitamin D levels and this was essentially unaffected by adjustment for liver enzyme levels with hazard ratio , 0.96 ( 95 % confidence interval , 0.93e0.99 ) for a 10 nmol/L higher vitamin D level . CONCLUSIONS The present study did not support our hypothesis that the well-known association between low vitamin D status and mortality is explained by liver damage as reflected by levels of liver enzymes Globally , cardiovascular disease ( CVD ) is the number one cause of death , being responsible for approximately 30 % of deaths worldwide . Urbanization and a westernized lifestyle are thought to play a major role in the development of CVD . There is accumulating evidence that vitamin D is a nonclassical risk factor for CVD . The active vitamin D metabolite , 1,25-dihydroxyvitamin D , which is synthesized from its precursor 25-hydroxyvitamin D ( 25[OH]D ) , down-regulates several negative and up-regulates various protective pathways in the heart and vasculature . First r and omized trials demonstrate that vitamin D supplementation leads to vasodilatation and suppresses cardiovascular risk markers such as triglycerides and the inflammation marker tumor necrosis factor-α . Solar UV-B radiation is the major source of vitamin D for humans . Consequently , the vitamin D status is largely influenced by season , geographic latitude , daily outdoor activities , and the percentage of body surface exposed to solar UV-B. A significant proportion of individuals in Europe and North America have  vitamin D concentrations in the deficiency range ( 25[OH]D<25 nmol/l ) . Available data indicate that low solar UV-B exposure and /or low 25(OH)D concentrations are associated with an increased risk of CVD . Large nonr and omized studies indicate that CVD mortality is more than twice as high in older individuals with deficient 25(OH)D concentrations compared with those individuals who have adequate 25(OH)D concentrations ( > 75 nmol/l ) . Together , experimental and epidemiological evidence does support a plausible role for improving vitamin D status in CVD prevention in the population at large . Nevertheless , future r and omised clinical trials are needed to evaluate whether vitamin D is effective with respect to primary , secondary , and /or tertiary prevention of CVD BACKGROUND Vitamin A deficiency is a risk factor for blindness and for mortality from measles and diarrhoea in children aged 6 - 59 months . We aim ed to estimate trends in the prevalence of vitamin A deficiency between 1991 and 2013 and its mortality burden in low-income and middle-income countries . METHODS We collated 134 population -representative data sources from 83 countries with measured serum retinol concentration data . We used a Bayesian hierarchical model to estimate the prevalence of vitamin A deficiency , defined as a serum retinol concentration lower than 0·70 μmol/L. We estimated the relative risks ( RRs ) for the effects of vitamin A deficiency on mortality from measles and diarrhoea by pooling effect sizes from r and omised trials of vitamin A supplementation . We used information about prevalences of deficiency , RRs , and number of cause-specific child deaths to estimate deaths attributable to vitamin A deficiency . All analyses included a systematic quantification of uncertainty . FINDINGS In 1991 , 39 % ( 95 % credible interval 27 - 52 ) of children aged 6 - 59 months in low-income and middle-income countries were vitamin A deficient . In 2013 , the prevalence of deficiency was 29 % ( 17 - 42 ; posterior probability [ PP ] of being a true decline=0·81 ) . Vitamin A deficiency significantly declined in east and southeast Asia and Oceania from 42 % ( 19 - 70 ) to 6 % ( 1 - 16 ; PP>0·99 ) ; a decline in Latin America and the Caribbean from 21 % ( 11 - 33 ) to 11 % ( 4 - 23 ; PP=0·89 ) also occurred . In 2013 , the prevalence of deficiency was highest in sub-Saharan Africa ( 48 % ; 25 - 75 ) and south Asia ( 44 % ; 13 - 79 ) . 94 500 ( 54 200 - 146 800 ) deaths from diarrhoea and 11 200 ( 4300 - 20 500 ) deaths from measles were attributable to vitamin A deficiency in 2013 , which accounted for 1·7 % ( 1·0 - 2·6 ) of all deaths in children younger than 5 years in low-income and middle-income countries . More than 95 % of these deaths occurred in sub-Saharan Africa and south Asia . INTERPRETATION Vitamin A deficiency remains prevalent in south Asia and sub-Saharan Africa . Deaths attributable to this deficiency have decreased over time worldwide , and have been almost eliminated in regions other than south Asia and sub-Saharan Africa . This new evidence for both prevalence and absolute burden of vitamin A deficiency should be used to reconsider , and possibly revise , the list of priority countries for high-dose vitamin A supplementation such that a country 's priority status takes into account both the prevalence of deficiency and the expected mortality benefits of supplementation . FUNDIN Bill & Melinda Gates Foundation , Gr and Challenges Canada , UK Medical Research Council 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 BACKGROUND Prospect i ve epidemiologic data on the association between vitamin D and all-cause and cause-specific mortality are limited . OBJECTIVE This study aim ed to determine whether 25-hydroxyvitamin D [ 25(OH)D ]  concentrations were prospect ively and independently associated with cardiovascular disease ( CVD ) , cancer , and all-cause mortality in postmenopausal women . DESIGN A sub study in 2429 postmenopausal women within the Women 's Health Initiative ( WHI ) with measured baseline 25(OH)D concentrations were followed for 10 y for death from CVD , cancer , and all-cause mortality . Proportional hazards models were performed to evaluate quartiles of month-adjusted 25(OH)D concentrations , with adjustment for potential confounders . Sequential model building and analysis for multiplicative interaction were performed to evaluate the effects of central adiposity on the association of low 25(OH)D with all-cause mortality . RESULTS Of the 2429 women , 224 deaths occurred , with 79 deaths from CVD and 62 deaths from cancer . Multivariate-adjusted HRs that compared quartiles 1 ( lowest ) to 4 ( highest ) of 25(OH)D for all-cause mortality ( HR : 1.25 ; 95 % CI : 0.80 , 1.95 ) , CVD mortality ( HR : 1.27 ; 95 % CI : 0.81 , 1.99 ) , and cancer mortality ( HR : 1.39 ; 95 % CI : 0.88 , 2.19 ) were not significant . There was a potential interaction ( P = 0.08 ) between abdominal obesity and low 25(OH)D concentrations that showed an increased risk of the lowest quartile of 25(OH)D concentrations ( HR : 1.85 ; 95 % CI : 1.00 , 3.44 ) with increased mortality in women with a normal waist circumference but no increased risk in women with abdominal obesity ( HR : 0.96 ; 95 % CI : 0.52 , 1.76 ) . CONCLUSION Body fat distribution may play an important role in the modulation of the effect of low vitamin D concentrations on health . This trial was registered at clinical trials.gov as NCT 00000611 BACKGROUND : Vitamin D deficiency is a global health problem . Epidemiological studies demonstrate that vitamin D is both cardioprotective and neuroprotective . Vitamin D also plays a substantial role in innate and acquired immunity . Our goal was to evaluate the association of serum vitamin D concentration on serious postoperative complications and death in noncardiac surgical patients . METHODS : We retrospectively analyzed the data of 3509 patients who had noncardiac surgery at the Clevel and Clinic Main Campus and had a serum vitamin D measurement . The relationship between serum vitamin D concentration and all-cause in-hospital mortality , in-hospital cardiovascular morbidity , and serious in-hospital infections was assessed as a common effect odds ratio ( OR ) by using a multivariate generalized estimating equation model with adjustment for demographic , medical history variables , and type and duration of surgery . RESULTS : Higher vitamin D concentrations were associated with decreased odds of in-hospital mortality/morbidity ( P = 0.003 ) . There was a linear reduction of the corresponding common effect odds ratio ( OR 0.93 , 95 % confidence interval , 0.88–0.97 ) for severe in-hospital outcomes for each 5 ng/mL increase in vitamin D concentration over the range from 4 to 44 ng/mL. In addition , we found that the odds versus patients  with vitamin D < 13 ng/mL ( i.e. , 1st quintile ) were significantly lower in patients with vitamin D 13–20 , 20–27 , 27–36 , and > 36 ng/mL ( i.e. , 2nd–5th quintiles ) ; the corresponding estimated ORs were 0.65 ( 99 % confidence interval , 0.43–0.98 ) , 0.53 ( 0.35–0.80 ) , 0.44 ( 0.28–0.70 ) , and 0.49 ( 0.31–0.78 ) , respectively . However , there was no statistically significant difference among individual quintiles > 13 ng/mL. CONCLUSIONS : Vitamin D concentrations were associated with a composite of in-hospital death , serious infections , and serious cardiovascular events in patients recovering from noncardiac surgery . While causality can not be determined from our retrospective analysis , the association suggests that a large r and omized trial of preoperative vitamin D supplementation and postoperative outcomes is warranted Prospect i ve cohort studies have provided some evidence that circulating vitamin D is associated with risk of , and survival from , renal cell carcinoma ( RCC ) , but it is unclear whether concentrations of vitamin D at the time of diagnosis of RCC are associated with prognosis . We conducted a case – cohort study of 630 RCC cases , including 203 deaths , from a multicenter case – control study in Eastern Europe .  Vitamin D was assessed as 25-hydroxyvitamin D3 [ 25(OH)D3 ] , and we used weighted Cox models to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) by categories of season-adjusted 25(OH)D3 . Higher concentrations of 25(OH)D3 were associated with lower risk of death after adjusting for stage , age , sex , and country ( HR highest vs. lowest category 0.57 ; 95 % CI , 0.34–0.97 ) . The inverse associations of 25(OH)D3 with death were most notable among those who died from non-RCC causes and those diagnosed with early-stage disease . In summary , 25(OH)D3 concentration at diagnosis of RCC was inversely associated with all-cause mortality rates , but not specifically with RCC outcome . Cancer Epidemiol Biomarkers Prev ; 24(8 ) ; 1277–81 . © 2015 AACR 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 Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers , including cancers of the esophagus and stomach . Vitamins and minerals in these foods may contribute to the reduced cancer risk . The people of Linxian County , China , have one of the world 's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients . PURPOSE We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian . METHODS Individuals of ages 40 - 69 were recruited in 1985 from four Linxian communes . Mortality and cancer incidence  during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period . The subjects were r and omly assigned to intervention groups according to a one-half replicate of a 2(4 ) factorial experimental design . This design enabled testing for the effects of four combinations of nutrients : ( A ) retinol and zinc ; ( B ) riboflavin and niacin ; ( C ) vitamin C and molybdenum ; and ( D ) beta carotene , vitamin E , and selenium . Doses ranged from one to two times U.S. Recommended Daily Allowances . RESULTS A total of 2127 deaths occurred among trial participants during the intervention period .  Cancer was the leading cause of death , with 32 % of all deaths due to esophageal or stomach cancer , followed by cerebrovascular disease ( 25 % ) . Significantly ( P = .03 ) lower total mortality ( relative risk [ RR ] = 0.91 ; 95 % confidence interval [ CI ] = 0.84 - 0.99 ) occurred among those receiving supplementation with beta carotene , vitamin E , and selenium . The reduction was mainly due to lower cancer rates ( RR = 0.87 ; 95 % CI = 0.75 - 1.00 ) , especially stomach cancer ( RR = 0.79 ; 95 % CI = 0.64 - 0.99 ) , with the reduced risk beginning to arise about 1 - 2 years after the start of supplementation with these vitamins and minerals . No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc , riboflavin and niacin , or vitamin C and molybdenum . Patterns of cancer incidence , on the basis of 1298 cases , generally resembled those for cancer mortality . CONCLUSIONS The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults , particularly with the combination of beta carotene , vitamin E , and selenium , may effect a reduction in cancer risk in this population . IMPLICATION S The results on their own are not definitive , but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements STUDY OBJECTIVES To determine if apparent protective mortality benefits of intravenous active vitamin D in patients undergoing hemodialysis extend across all groups defined by dialysis duration ; if higher monthly dose and dosing regularity are associated with reduced mortality ; and if intravenous active vitamin D use is associated with reduced cardiovascular , infectious , and cancer-related mortality . STUDY DESIGN Retrospective cohort study . DATA SOURCE Centers for Medicare and Medicaid Services End-Stage Renal Disease data base . PATIENTS A total of 193,830 patients undergoing hemodialysis during 1999 - 2000 , of whom 94,208 ( 48.6 % ) were taking intravenous active vitamin D in the baseline period . MEASUREMENTS AND MAIN RESULTS Time-varying Cox proportional hazards models were used to assess the effects of monthly vitamin D dose and dosing regularity over 3-month intervals on risk of all-cause and cause-specific death , by dialysis duration groups ( < 1 yr , 1 to <3 yrs , 3 to < 5 yrs , and > or=5 yrs from dialysis initiation ) . Models were adjusted for baseline characteristics , time-varying hospital days , monthly epoetin alfa dose , mean hemoglobin level , and urea reduction ratio in the 3-month intervals . Maximum follow-up time was 5.25 years . Adjusted all-cause mortality risk was reduced 7 - 17 % among patients receiving vitamin D each month of the 3-month interval , with the highest reduction among patients with shorter dialysis duration . However , regular vitamin D dosing did not show consistent benefit across dialysis duration groups for cardiovascular , infectious , cancer , or other ( all deaths not attributable to cardiovascular disease , infection , or cancer ) mortality . CONCLUSION Mortality benefits of intravenous vitamin D can not be easily explained by currently proposed biologic mechanisms . R and omized controlled trials are needed to show definitively whether intravenous vitamin D can reduce all-cause and cause-specific mortality in patients undergoing dialysis compared with placebo Background : Observational studies have suggested that antioxidant nutrients may reduce cancer and overall mortality risks . However , most r and omized trials have failed to show survival benefits . Examining nonlinear associations between antioxidant levels and health outcomes may help to explain these discrepant findings . Methods : We evaluated all-cause , cancer , and cardiovascular mortality risks associated with quintiles ( Q1–Q5 ) of serum antioxidant ( vitamins C and E , β-carotene , and selenium ) and vitamin A levels , in 16,008 adult participants of The Third National Health and Nutrition Examination Survey ( NHANES III ; 1988–1994 ) . Results : Over a median follow-up period of 14.2 years , there were 4,225 deaths , including 891 from cancer and 1,891 from cardiovascular disease . We observed a dose – response decrease in cancer and overall mortality risks with higher vitamin C levels . In contrast , for vitamin A , risk of cancer death decreased from Q1–Q2 , with no further decline in risk at higher levels . For vitamin E , having levels in Q4 was associated with the lowest cancer mortality risk . Both vitamin A and E had U-shaped associations with all-cause mortality . Cancer mortality risks decreased from Q1–Q2 for β-carotene and from Q1–Q4 for selenium . However , for β-carotene and selenium , overall mortality risks decreased from Q1–Q2 but then did not change significantly with higher levels . Conclusions : Antioxidant supplement use should be studied in the context of overall mortality and other competing mortality risks . Impact : These data suggest the need for novel intervention studies where doses of these agents are individualized based on their serum levels , and possibly , markers of oxidative stress and systemic inflammatory response . Cancer Epidemiol Biomarkers Prev ; 22(12 ) ; 2202–11 . © 2013 AACR 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 Abstract Objectives : To investigate the relation between cognitive function and cause specific mortality in people aged 65 and over . Design : A 20 year follow up study of a cohort of r and omly selected elderly people living in the community who in 1973 - 4 had taken part in a nutritional survey funded by the Department of Health and Social Security . Setting : Eight areas in Britain ( five in Engl and , two in Scotl and , and one in Wales ) . Subjects : 921 men and women whose cognitive function was assessed by a geriatrician in 1973 - 4 and for whom data on health , socioeconomic circumstances , and diet had been recorded . Results : Cognitive impairment was associated with increased mortality , in particular death from ischaemic stroke . Those who scored 7 or less on the Hodkinson mental test had a relative risk of dying from stroke of 2.8 ( 95 % confidence interval 1.4 to 5.5 ) , compared with those who gained the maximum score ( 10 ) , after adjustment for age , sex , blood pressure , serum cholesterol concentration , and vitamin C intake . These associations were independent of illness or social class . At the time of the nutritional survey , cognitive function was poorest in those with the lowest vitamin C status , whether measured by dietary intake or plasma ascorbic acid concentration . The relation between vitamin C status and cognitive function was independent of age , illness , social class , or other dietary variables . Conclusion : The relation between cognitive function and risk of death from stroke suggests that cerebrovascular disease is an important cause of declining cognitive function . Vitamin C status may be a determinant of cognitive function in elderly people through its effect on atherogenesis . A high vitamin C intake may protect against both cognitive impairment and cerebrovascular disease . Key messages Key messages In this prospect i ve study of 921 elderly people cognitive impairment was a strong predictor of death from ischaemic stroke Low vitamin C intake and low plasma ascorbate concentrations were also important risk factors for death from stroke Cognitive performance was poorest in people with the lowest vitamin C status A high vitamin C intake may protect against both cognitive impairment and cerebrovascular Epidemiological studies have reported associations between lower vitamin D levels and a great variety of diseases , prompting calls for widespread treatment of individuals with low vitamin D levels . Most of New Zeal and 's population have vitamin D levels for at least part of the year that are considered insufficient ( 25-hydroxyvitamin D < 50 - 80 nmol/L ) . However , evidence for benefits of vitamin D supplementation in such population s is controversial and there is some evidence of harmful effects . Until adequately powered , r and omised , controlled trials of vitamin D supplementation demonstrate safe improvements in health , clinicians should not focus on detecting/treating individuals with vitamin D insufficiency , instead treating those at high risk of vitamin D deficiency ( 25-hydroxyvitamin D < 25 nmol/L ) , such as the frail elderly , and those with specific clinical indications . Treatment for such individuals does not require vitamin D measurements . Requests for vitamin D measurements in Auckl and have nearly quadrupled in the past decade , from 8500 in the year 2000 to 32,800 in 2010 , with substantial increases in cost . Vitamin D measurement is often inaccurate and imprecise , and the vast majority of tests performed currently do not reveal vitamin D deficiency . Therefore , a move away from  routine vitamin D measurements  seems sensible , though they are still indicated when investigating suspected metabolic bone disease or hypocalcaemia 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 Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . This is a grade I recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found poor evidence to determine whether supplementation with these vitamins reduces the risk for cardiovascular disease or cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) The available evidence from r and omized trials is either inadequate or conflicting , and the influence of confounding variables on observed outcomes in observational studies can not be determined . As a result , the USPSTF could not determine the balance of benefits and harms of routine use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . The USPSTF recommends against the use of beta-carotene supplements , either alone or in combination , for the prevention of cancer or cardiovascular disease . This is a grade D recommendation . The USPSTF found good evidence that -carotene supplementation provides no benefit in the prevention of cancer or cardiovascular disease in middle-aged and older adults . In two trials restricted to heavy smokers , -carotene supplementation was associated with higher incidence of lung cancer and higher all-cause mortality . The USPSTF concludes that -carotene supplements are unlikely to provide important benefits and might cause harm in some groups . Clinical Considerations The USPSTF did not review evidence regarding vitamin supplementation for patients with known or potential nutritional deficiencies , including pregnant and lactating women , children , elderly persons , and people with chronic illnesses .  Dietary supplements may be appropriate for people whose diet does not provide the recommended dietary intake of specific vitamins . Individuals may wish to consult a health care provider to discuss whether dietary supplements are appropriate . With the exception of vitamins for which there is compelling evidence of net harm ( for example , beta-carotene supplementation in smokers ) , there is little reason to discourage people from taking vitamin supplements . Patients should be reminded that taking vitamins does not replace the need to eat a healthy diet . All patients should receive information about the benefits of a diet high in fruits and vegetables , as well as information on other foods and nutrients that should be emphasized or avoided in their diet ( see the 2002 USPSTF recommendations on counseling to promote a healthy diet [ 1 ] ) . Patients who choose to take vitamins  should be encouraged to adhere to the dosages recommended in the Dietary Reference Intakes of the Institute of Medicine . Some vitamins , such as A and D , may be harmful in higher doses ; therefore , doses greatly exceeding the Recommended Dietary Allowance or Adequate Intake should be taken with care while considering whether potential harms outweigh potential benefits . Vitamins and minerals sold in the United States are classified as dietary supplements , and there is a degree of quality control over content if they have a U.S. Pharmacopeia seal ( 2 ) . Nevertheless , imprecision in the content and concentration of ingredients could pose a theoretical risk not reflected in clinical trials using calibrated compounds . The adverse effects of beta-carotene on smokers have been observed primarily in those taking large supplemental doses . There is no evidence to suggest that beta-carotene is harmful to smokers at levels occurring naturally in foods . The USPSTF did not review evidence supporting folic acid supplementation among pregnant women to reduce neural tube defects . In 1996 , the USPSTF recommended folic acid for all women who are planning , or capable of , pregnancy ( see the 1996 USPSTF chapter on screening for neural tube defects [ 3 ] ) . Clinicians and patients should discuss the possible need for vitamin supplementation when taking certain medications ( for example , folic acid supplementation for patients taking methotrexate ) . Scientific Evidence The USPSTF review s ( 4 - 6 ) focused on the quality of the evidence regarding the effect of routine supplementation with certain vitamins on primary prevention of cancer and cardiovascular disease . These review s were undertaken because of the growing epidemiologic evidence that dietary factors may play a role in the etiology of these diseases ( 7 - 9 ) . The review s focused on prospect i ve trials of vitamin supplementation and observational studies of associations between the use of specific supplements and the risk for cancer or cardiovascular disease . The value of vitamins naturally occurring in food , the use of vitamin supplements for the prevention of other conditions ( for example , neural tube defects ) , and the use of vitamin supplements for the secondary prevention of complications in patients with existing disease were outside the scope of these review s. Vitamin A No prospect i ve trials have examined the effect of vitamin A supplements alone on the risk for cancer . Observational studies provide no evidence that such supplements prevent cancer in men . In women , observational studies have reported a statistically significant inverse association between use of vitamin A supplements and risk for colon and breast cancer ( 10 , 11 ) . Despite efforts to adjust for confounding variables , the observational , nonr and om design of these studies makes it difficult to assess the extent to which the reduced cancer risk is attributable to vitamin A or to other characteristics of women who take vitamin A supplements .  No evidence from prospect i ve trials is available regarding the benefits of vitamin A alone in preventing cardiovascular disease . One good- quality cohort study found no effect of vitamin A supplementation in reducing cardiovascular disease mortality ( 12 ) . Vitamin C No primary prevention trial of the effect of vitamin C supplementation alone on cancer or cardiovascular disease has been reported . Observational studies have generally shown no statistically significant associations between use of vitamin C supplements and risk for cancer of the breast , prostate , colon , or lung ( 12 - 14 ) . The observational cohort studies examining the effects of vitamin C on cardiovascular disease have produced inconsistent results ( 12 , 15 , 16 ) . Vitamin E Only a few trials have examined the effects of vitamin E on the primary prevention of cancer or cardiovascular disease . A r and omized , controlled trial ( RCT ) involving Finnish male smokers found that vitamin E supplementation is not protective against lung cancer but may have a beneficial impact on prostate cancer ( 14 ) . Because prostate cancer was not a primary end point of the trial and the trial had other limitations , further evidence is needed to confirm this finding . Observational studies have shown no statistically significant association between use of vitamin E supplements and risk for prostate , lung , or breast cancer ( 5 ) . One study suggested that vitamin E protects against colon cancer , but the influence of confounding variables can not be fully excluded ( 17 ) . Among primary prevention trials , two good- quality trials ( 14 , 18 ) and one fair- quality trial ( 19 ) found no statistically significant benefit of vitamin E supplementation in preventing cardiovascular disease ( 20 ) . Only one of seven trials of vitamin E supplementation for secondary prevention demonstrated a statistically significant reduction in cardiac events ( 4 ) . Some prospect i ve cohort studies have suggested a significant benefit , but the results are mixed and the influence of confounding variables can not be excluded ( 4 ) . -Carotene A consistent body of evidence from clinical trials suggests that beta-carotene supplementation does not decrease the risk for lung , prostate , colon , breast , or nonmelanoma skin cancer ( 14 , 21 - 25 ) . -Carotene supplements were associated with an increased risk for lung cancer among smokers , especially heavy smokers , in two RCTs ( 14 , 25 ) . Results from four RCTs demonstrated no reduced risk for cardiovascular events or death after beta-carotene supplementation ( 14 , 21 , 22 , 26 - 28 ) . Antioxidant Vitamin Combinations Studies of the effects of antioxidant vitamin combinations to prevent cancer have yielded mixed results . A recent RCT reported no statistically significant effect of daily supplementation with a combination of antioxidants : vitamin E , vitamin C , and beta-carotene ( 29 ) . Some studies have suggested an adverse effect of antioxidant combinations on cancer , but the results may have been confounded by the inclusion of beta-carotene ( 5 ) . Some observational studies of antioxidant vitamin combinations have suggested a benefit in preventing cardiovascular disease ( 13 , 30 , 31 ) , but other studies , including well- design ed RCTs , have shown no benefit ( 29 , 32 , 33 ) . One secondary prevention trial showed an increase in all-cause mortality among women taking antioxidant supplements  ( 34 ) . Multiple Vitamin Combinations The incremental benefit of taking supplemental doses of folic acid and B vitamins has been examined by comparing the outcomes of observational studies while controlling for the total intake of antioxidant vitamin supplements ( 35 ) . In these analyses , folic acid supplementation was associated with significantly decreased risk for colon cancer , but the protective effect requires confirmation in prospect i ve trials . There is conflicting evidence regarding the use of multivitamins and the risk for cardiovascular disease . Among cohort studies , one good- quality study reported a statistically significant reduction in coronary events ( 36 ) , two good- quality studies reported no statistically significant effect on mortality ( 16 , 37 ) , and one The relationship between maternal vitamin A deficiency during pregnancy and infant mortality is unclear . We conducted a prospect i ve cohort study of 377 HIV-negative women and their infants in Blantyre , Malawi .  Serum vitamin A levels  were measured during the second or third trimester of pregnancy and infants were followed during the first year of life . From delivery until 12 months of age , 18 infants died ( 47.7 per 1000 ) . Mothers of infants who died had lower serum vitamin A levels during pregnancy ( 0.74 + /- 0.13 mumol/l ) compared with mothers of infants who did not die ( 1.02 + /- 0.03 mumol/l ) ( p = 0.055 ) . Infants born to women whose vitamin A levels were in the lowest quartile ( < 0.32 mumol/l ) had three-fold higher likelihood of mortality than infants born to women whose vitamin A levels were in the higher quartiles ( p < 0.03 ) . These results suggest that maternal vitamin A deficiency during pregnancy may contribute to higher infant mortality rates AIMS To investigate levels of vitamin D and parathyroid hormone ( PTH ) in a population of heart failure ( HF ) patients , and to evaluate whether vitamin D and PTH are related to prognosis . METHODS AND RESULTS This was a prospect i ve study of 148 HF out patients ( mean age 68 years , 102 men ) with follow-up for mortality after 3½ years . Levels of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , PTH , 25-hydroxyvitamin D ( 25-OHD ) , and several other biomarkers were examined . Mortality and cardiovascular mortality were analysed in multivariable regression analyses adjusting for other independent prognostic variables . Vitamin D deficiency ( ≤50 nmol/L ) was prevalent in 43 % of the population ; 26 % had elevated PTH levels ; none had primary hyperparathyroidism . We found a strong and independent significant association of both PTH and vitamin D  to mortality , which was independent of other clinical ly important parameters [ NT-proBNP , estimated glomerular filtration rate ( eGFR ) , age , and left ventricular ejection fraction ( LVEF ) ] . Both PTH and vitamin D were also significantly associated with all cause mortality . In an adjusted model , we found a hazard ratio of 1.9 ( confidence interval 1.1 - 3.4 ) for vitamin D deficiency and 2.0 ( 1.0 - 3.8 ) for the upper median of PTH , respectively . CONCLUSION In this relatively small prospect i ve study , PTH and vitamin D were independently associated with all cause and cardiovascular mortality in patients with HF . This was independent of other known risk factors such as eGFR , LVEF , NT-proBNP , and age BACKGROUND AND AIMS Emerging evidence suggests that low levels of vitamin D may be an important risk factor for multiple chronic diseases and mortality , but the evidence is mixed . Vitamin D levels are associated with sun exposure , diet , and metabolic status . One potential explanation for the lack of consistent findings amongst various studies is that low vitamin levels may be associated with poor diets or other risk factors that we were not adequately controlled for in different analyses . METHODS Prospect i ve analysis of adults over the age of 35 in NHANES III data ( 1988 - 1994 ) with 20 year mortality follow-up . Sequential Cox proportional hazard models quartiles of 25OH vitamin D adjusted for age , season , geography , sociodemographic ( SD ) , CVD risk factors ( CVD ) and nutritional factors ( NF ) were performed . RESULTS Gender , race , diabetes , anti-hypertensive meds , income , taking  vitamin D supplements , physical activity , alcohol consumption , region , body mass index , blood pressure , creatinine , albumin , CRP , thyroxine , iron , RBC folate , vitamin A , E , alpha-carotene , and lycopene were all associated with different quartiles of vitamin D and as well as CHD and all-cause mortality and thus are important potential confounders of this relationship . Adjusting for the confounding factors , higher levels of vitamin D demonstrate an inverse relationship with all-cause mortality , but only the top quartile of vitamin D shows an inverse relationship with CHD mortality . CONCLUSIONS The highest quartile compared to the lowest quartile of 25OH vitamin D levels is inversely associated with CHD and all-cause mortality adjusting for multiple confounders . Whether supplementation of individuals with low vitamin D will result in similar benefits will require a r and omized clinical trial BACKGROUND A meta- analysis of 19 trials suggested a small increase in the risk of all-cause mortality with high-dose vitamin E supplementation . Little is known , however , about the relation between mortality and circulating concentrations of vitamin E result ing from dietary intake , low-dose supplementation , or both . OBJECTIVE We examined whether baseline serum alpha-tocopherol concentrations are associated with total and cause-specific mortality . DESIGN A prospect i ve cohort study of 29 092 Finnish male smokers aged 50 - 69 y who participated in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention ( ATBC ) Study was carried out . Fasting serum alpha-tocopherol was measured at baseline by using HPLC . Only 10 % of participants reported vitamin E supplement use at baseline , and thus serum concentrations of vitamin E mainly reflected dietary intake and other host factors . Risks of total and cause-specific mortality were estimated by using proportional hazards models . RESULTS During up to 19 y of follow-up , 13 380 deaths ( including 4518 and 5776 due to cancer and cardiovascular disease , respectively ) were identified . Men in the higher quintiles of serum alpha-tocopherol had significantly lower risks of total and cause-specific mortality than did those in the lowest quintile [ relative risk ( RR ) = 0.82 ( 95 % CI : 0.78 , 0.86 ) for total mortality and 0.79 ( 0.72 , 0.86 ) , 0.81 ( 0.75 , 0.88 ) , and 0.70 ( 0.63 , 0.79 ) for deaths due to cancer , cardiovascular disease , and other causes , respectively ; P for trend for all < 0.0001 ] . Cubic regression spline analysis of continuous serum alpha-tocopherol values indicated greater risk reductions with increasing concentrations up to approximately 13 - 14 mg/L , after which no further benefit was noted . CONCLUSION Higher circulating concentrations of alpha-tocopherol within the normal range are associated with significantly lower total and cause-specific mortality in older male smokers Purpose The aim of the study was to assess the relationships between individual-level dietary intakes of antioxidant vitamins C , E and beta-carotene with all-cause and cause-specific mortality in three Central and Eastern European ( CEE ) population s. Methods Data from the Health , Alcohol and Psychosocial factors in Eastern Europe cohort study were used . At the baseline survey , between 2002 and 2005 , 28,945 men and women aged 45–69 years were examined in Novosibirsk ( Russia ) , Krakow ( Pol and ) and seven Czech towns . Deaths in the cohorts were identified through mortality registers . Cox regression was used to estimate the association between vitamin consumption and all-cause , cardiovascular ( CVD ) disease and cancer mortality . Results In multivariable-adjusted analyses , there were no clear inverse associations between  antioxidant vitamin  intakes and mortality , although in some groups , several hazard ratios ( HRs ) were significant . For example , in men , compared with the lowest quintile of  vitamin C intake , all-cause mortality in the third and fourth quintiles was lower by 28 % ( HR 0.72 ; 95 % CI 0.61–0.85 ) and by 20 % ( HR 0.80 ; 95 % CI 0.68–0.95 ) , respectively . CVD mortality was lower by 35 % ( HR 0.65 ; 95 % CI 0.50–0.84 ) and by 23 % ( HR 0.77 ; 95 % CI 0.59–0.99 ) in third and fourth quintile of vitamin C intake , respectively . In women , the third and fourth quintiles of dietary intake of vitamin E were associated with reduced risk of all-cause death by 33 % ( HR 0.67 ; 95 % CI 0.53–0.84 ) and by 23 % ( HR 0.77 ; 95 % CI 0.61–0.97 ) , respectively . Consumption of vitamin C , vitamin E and beta-carotene was not related to CVD mortality in women and to cancer mortality in either gender . Conclusion This large prospect i ve cohort study in CEE population s with low prevalence of vitamin supplementation did not find a strong , dose – response evidence for protective effects of antioxidant vitamin intake OBJECTIVE To determine whether plasma vitamin A levels are associated with immunologic status and clinical outcome during human immunodeficiency virus type 1 ( HIV-1 ) infection . PATIENTS AND METHODS Analysis of  vitamin A levels , CD4 T cells , complete blood cell count , and serologic markers for liver disease in a r and om sub sample of 179 subjects from a cohort of more than 2000 intravenous drug users with longitudinal follow-up to determine survival . RESULTS Mean ( + /- SE ) follow-up time was 22.8 + /- 1.1 months , and 15 subjects died during follow-up . More than 15 % of the HIV-1-seropositive individuals had plasma vitamin A levels less than 1.05 mumol/L , a level consistent with vitamin A deficiency . The HIV-1-seropositive individuals had lower mean plasma vitamin A levels than HIV-1-seronegative individuals ( P < .001 ) . Vitamin A deficiency was associated with lower CD4 levels among both seronegative individuals ( P < .05 ) and seropositive individuals ( P < .05 ) . In the HIV-seropositive participants , vitamin A deficiency was associated with increased mortality ( relative risk = 6.3 ; 95 % confidence interval , 2.1 to 18.6 ) . CONCLUSION Vitamin A deficiency may be common during HIV-1 infection , and vitamin A deficiency is associated with decreased circulating CD4 T cells and increased mortality . Vitamin A is an essential micronutrient for normal immune function , and vitamin A deficiency seems to be an important risk factor for disease progression during HIV-1 infection BACKGROUND Clinical vitamin A deficiency affects millions of children worldwide , and sub clinical deficiency is even more common . Supplemental vitamin A has been reported to reduce mortality among these children , but the results have been question ed . METHODS We conducted a r and omized , controlled , masked clinical trial for one year in southern India involving 15,419 preschool-age children who received either 8.7 mumol ( 8333 IU ) of vitamin A and 46 mumol ( 20 mg ) of vitamin E ( the treated group ) or vitamin E alone ( the control group ) . Vitamin supplements were delivered weekly by community health volunteers who also recorded mortality and morbidity . Weekly contact was made with at least 88 percent of the children in both study groups . The base-line characteristics of the children were similar and documented a high prevalence of vitamin A deficiency and undernutrition . RESULTS One hundred twenty-five deaths occurred , of which 117 were not accidental . The risk of death in the group treated with vitamin A was less than half that in the control group ( relative risk , 0.46 ; 95 percent confidence interval , 0.30 to 0.71 ) . The risk was most reduced among children under 3 years of age ( 6 to 11 months -- relative risk , 0.28 ; 95 percent confidence interval , 0.09 to 0.85 ; 12 to 35 months -- relative risk , 0.46 ; 95 percent confidence interval , 0.26 to 0.81 ) and among those who were chronically undernourished , as manifested by stunting ( relative risk , 0.11 ; 95 percent confidence interval , 0.03 to 0.36 ) . The symptom-specific risk of mortality was significantly associated with diarrhea , convulsions , and other infection-related symptoms . CONCLUSIONS The regular provision of a supplement of vitamin A to children , at a level potentially obtainable from foods , in an area where vitamin A deficiency and under-nutrition are documented public health problems contributed substantially to children 's survival ; mortality was reduced on average by 54 percent
The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality .
This association appeared to be non-linear , with progressively lower mortality with increasing 25(OH)D up to a point , beyond which there was no further decrease .
There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases , while for cardiovascular mortality , there is weak evidence of an association in observational studies , which is not supported by the data from intervention or Mendelian r and omization studies .
Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality , but it is unclear whether this is explained by reverse causation , and if there are specific causes of death for which vitamin D might be important .