The inverse association between serum 25-hydroxyvitamin D and mortality may be modified by vitamin A status and use of vitamin A supplements Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. Circulating 25OHD, dietary vitamin D, PTH, and calcium associations with incident cardiovascular disease and mortality: the MIDSPAN Family Study. Antioxidant vitamin intake and mortality: the Leisure World Cohort Study. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial Micronutrient intake in relation to all-cause mortality in a prospective Danish cohort Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections in young children in Brazil Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial Predictors of inhospital mortality and re-hospitalization in older adults with community-acquired pneumonia: a prospective cohort study Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up. Vitamin/mineral supplementation and cancer, cardiovascular, and all-cause mortality in a German prospective cohort (EPIC-Heidelberg) Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality. Vitamin D supplementation reduces insulin resistance in Japanese adults: a secondary analysis of a double-blind, randomized, placebo-controlled trial. Multivitamin use and mortality in a large prospective study. Association Between Vitamin D Supplementation During Pregnancy and Offspring Growth, Morbidity, and Mortality Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group. 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. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. Effect of periodic vitamin A supplementation on mortality and morbidity of human immunodeficiency virus-infected children in Uganda: A controlled clinical trial. Serum Antioxidant Nutrients, Vitamin A, and Mortality in U.S. Adults Lifestyle influences on the association between pre-diagnostic hormone replacement therapy and breast cancer prognosis - results from The Danish 'Diet, Cancer and Health' prospective cohort. Cholecalciferol supplementation throughout winter does not affect markers of bone turnover in healthy young and elderly adults.
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 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 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 To assess the relationship between antioxidant vitamin intake and all-cause  mortality in older adults , we examined these associations using data from the Leisure World Cohort Study , a prospect i ve study of residents of the Leisure World retirement community in Laguna Hills , California . In the early 1980s , participants ( who were aged 44 - 101 years ) completed a postal survey , which included details on use of vitamin supplements and dietary intake of foods containing vitamins A and C. Age-adjusted and multivariate-adjusted ( for factors related to mortality in this cohort — smoking , alcohol intake , caffeine consumption , exercise , body mass index , and histories of hypertension , angina , heart attack , stroke , diabetes , rheumatoid arthritis , and cancer ) hazard ratios for death were calculated using Cox regression for 8,640 women and 4,983 men ( median age at entry , 74 years ) . During follow-up ( 1981 - 2013 ) , 13,104 participants died ( median age at death , 88 years ) . Neither dietary nor supplemental intake of vitamin A or vitamin C nor supplemental intake of vitamin E  was significantly associated with mortality after multivariate adjustment . A compendium that summarizes previous findings of cohort studies evaluating vitamin intake and mortality is provided . Attenuation in the observed associations between mortality and antioxidant vitamin  use after adjustment for confounders in our study and in previous studies suggests that such consumption identifies persons with other mortality-associated lifestyle and health risk factors BACKGROUND The General Population Nutrition Intervention Trial was a r and omized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991 , in which 29,584 adult participants in Linxian , China , were given daily vitamin and mineral supplements . Treatment with " factor D , " a combination of 50 microg selenium , 30 mg vitamin E , and 15 mg beta-carotene , led to decreased mortality from all causes , cancer overall , and gastric cancer . Here , we present 10-year follow-up after the end of active intervention . METHODS Participants were assessed by periodic data collection , monthly visits by village health workers , and quarterly review of the Linxian Cancer Registry . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models . RESULTS Through May 31 , 2001 , 276 participants were lost to follow-up ; 9727 died , including 3242 from cancer ( 1515 from esophageal cancer and 1199 from gastric cancer ) . Participants who received factor D had lower overall mortality ( HR = 0.95 , 95 % CI = 0.91 to 0.99 ; P = .009 ; reduction in cumulative mortality from 33.62 % to 32.19 % ) and gastric cancer mortality ( HR = 0.89 , 95 % CI = 0.79 to 1.00 ; P = .043 ; reduction in cumulative gastric cancer mortality from 4.28 % to 3.84 % ) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years . Esophageal cancer deaths between those who did and did not receive factor D were not different overall ; however , decreased 17 % among participants younger than 55 ( HR = 0.83 , 95 % CI = 0.71 to 0.98 ; P = .025 ) but increased 14 % among those aged 55 years or older ( HR = 1.14 , 95 % CI = 1.00 to 1.30 ; P = .047 ) [ corrected ] . Vitamin A and zinc supplementation was associated with increased total and stroke mortality ; vitamin C and molybdenum supplementation , with decreased stroke mortality . CONCLUSION The beneficial effects of selenium , vitamin E , and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants . Late effects of other supplementation regimens were also observed Objective To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates . Design R and omised , placebo controlled , two by two factorial trial . Setting Bissau , Guinea-Bissau . Participants 1717 low birthweight neonates born at the national hospital . Intervention Neonates who weighed less than 2.5 kg were r and omly assigned to 25 000 IU vitamin A or placebo , as well as to early BCG vaccine or the usual late BCG vaccine , and were followed until age 12 months . Main outcome measure Mortality , calculated as mortality rate ratios ( MRRs ) , after follow-up to 12 months of age for infants who received vitamin A supplementation compared with those who received placebo . Results No interaction was observed between vitamin A supplementation and BCG vaccine allocation ( P=0.73 ) . Vitamin A supplementation at birth was not significantly associated with mortality : the MRR of vitamin A supplementation compared with placebo , controlled for r and omisation to “ early BCG ” versus “ no early BCG ” was 1.08 ( 95 % CI 0.79 to 1.47 ) . Stratification by sex revealed a significant interaction between vitamin A supplementation and sex ( P=0.046 ) , the MRR of vitamin A supplementation being 0.74 ( 95 % CI 0.45 to 1.22 ) in boys and 1.42 ( 95 % CI 0.94 to 2.15 ) in girls . When these data were combined with data from a complementary trial among normal birthweight neonates in Guinea-Bissau , the combined estimate of the effect of neonatal vitamin A supplementation on mortality was 1.08 ( 95 % CI 0.87 to 1.33 ) ; 0.80 ( 95 % CI 0.58 to 1.10 ) in boys and 1.41 ( 95 % CI 1.04 to 1.90 ) in girls ( P=0.01 for interaction between neonatal vitamin A and sex ) . Conclusions The combined results of this trial and the complementary trial among normal birthweight neonates have now shown that , overall , it would not be beneficial to implement a neonatal vitamin A supplementation policy in Guinea-Bissau . Worryingly , the trials show that vitamin A supplementation at birth can be harmful in girls . Previous studies and future trials should investigate the possibility that vitamin A supplementation has sex differential effects . Trial registration Clinical Trials.gov NCT00168610 Background Few studies have considered source -specific micronutrient intake in relation to mortality under the consideration that dietary and supplemental intake could exhibit different effects . Objective To evaluate the association between intake of vitamin C , E , folate , beta-carotene from diet and supplements , and overall mortality . Furthermore , to examine effect modification by smoking , alcohol intake , and BMI and to investigate if the effect of supplement use differs with dietary micronutrient intake . Methods and Material In a prospect i ve cohort study of 55,453 middle-aged Danes , information regarding diet , supplement use , and lifestyle was collected through question naires . During follow-up , 6,767 deaths were identified and incidence rate ratios ( IRRs ) of mortality related to micronutrient intake were calculated using Cox proportional hazards models . Results The present study found no effect of dietary vitamin C , E , folate , or beta-carotene in relation to mortality . In contrast , supplemental folic acid was associated with a significantly increased mortality , whereas no other micronutrient supplement was associated with mortality . Effect modification by smoking and alcohol intake , but not BMI , was suggested in relation to some dietary micronutrients . The effect of supplements did not differ in groups defined by dietary micronutrient intake . Conclusion This study suggests no effect of dietary micronutrients in relation to overall mortality . Supplemental folic acid was found to be associated with increased mortality , but further studies are required . No other supplemental micronutrient was associated with mortality A beneficial effect of periodic vitamin A supplementation on  childhood mortality  has been demonstrated , but the effect on morbidity is less clear . We investigated the effect of vitamin A supplementation on  diarrhoea and acute lower-respiratory-tract infections ( ALRI ) in children from northeastern Brazil in a r and omised , double-blind , placebo-controlled community trial . 1240 children aged 6 - 48 months were assigned vitamin A or placebo every 4 months for 1 year . They were followed up at home three times a week , and data about the occurrence and severity of diarrhoea and ALRI were collected . Any child with cough and respiratory rate above 40 breaths per min was visited by a paediatrician . The overall incidence of diarrhoea episodes was significantly lower in the vitamin-A-supplemented group than in the placebo group ( 18.42 vs 19.58 x 10(-3 ) child-days ; rate ratio 0.94 [ 95 % Cl 0.90 - 0.98 ] ) . The benefit of supplementation was greater as regards severe episodes of diarrhoea ; the incidence was 20 % lower in the vitamin A group than in the placebo group ( rate ratio 0.80 [ 0.65 - 0.98 ] ) . With the st and ard definition of diarrhoea ( > or = 3 liquid or semi-liquid stools in 24 h ) the effect of vitamin A on mean daily prevalence did not reach significance , but as the definition of diarrhoea was made more stringent ( increasing number of stools per day ) , a significant benefit became apparent , reaching for diarrhoea with 6 or more liquid or semi-liquid stools in 24 h a 23 % lower prevalence . We found no effect of vitamin A supplementation on the incidence of ALRI . The reduction in severity of diarrhoea may be the most important factor in the lowering of mortality by vitamin A supplementation Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality . Design R and omised placebo controlled trial . Setting B and i m Health Project ’s demographic surveillance system in Guinea-Bissau , covering approximately 90 000 inhabitants . Participants 4345 infants due to receive BCG . Intervention Infants were r and omised to 50 000 IU vitamin A or placebo and followed until age 12 months . Main outcome measure Mortality rate ratios . Results 174 children  died during follow-up ( mortality=47/1000 person-years ) . Vitamin A supplementation was not significantly associated with mortality ; the mortality rate ratio was 1.07 ( 95 % confidence interval 0.79 to 1.44 ) . The effect was 1.00 ( 0.65 to 1.56 ) during the first four months and 1.13 ( 0.75 to 1.68 ) from 4 to 12 months of age . The mortality rate ratio in boys was 0.84 ( 0.55 to 1.27 ) compared with 1.39 ( 0.90 to 2.14 ) in girls ( P for interaction=0.10 ) . An explorative analysis revealed a strong interaction between vitamin A and season of administration . Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting . Although little doubt exists that vitamin A supplementation reduces mortality in older children , a global recommendation of supplementation for all newborn infants may not contribute to better survival . Trial registration Clinical trials NCT00168597 Background A better underst and ing of potentially modifiable predictors of in-hospital mortality and re-admission to the hospital following discharge may help to improve management of community-acquired pneumonia in older adults . We aim ed to assess the associations of potentially modifiable factors with mortality and re-hospitalization in older adults hospitalized with community-acquired pneumonia . Methods A prospect i ve cohort study was conducted from July 2003 to April 2005 in two Canadian cities . Patients aged 65 years or older hospitalized for community-acquired pneumonia were followed up for up to 30 days from initial hospitalization for mortality and these patients who were discharged alive within 30 days of initial hospitalization were followed up to 90 days of initial hospitalization for re-hospitalization . Separate logistic regression analyses were performed identify the predictors of mortality and re-hospitalization . Results Of 717 enrolled patients hospitalized for community-acquired pneumonia , 49 ( 6.8 % ) died within 30 days of hospital admission . Among these patients , 526 were discharged alive within 30 days of hospitalization of whom 58 ( 11.2 % ) were re-hospitalized within 90 days of initial hospitalization . History of hip fracture ( odds ratio ( OR ) = 4.00 , 95 % confidence interval ( CI ) = ( 1.46 , 10.96 ) , P = .007 ) , chronic obstructive pulmonary disease ( OR = 2.31 , 95 % CI = ( 1.18 , 4.50 ) , P = .014 ) , cerebrovascular disease ( OR = 2.11 , 95 % CI = ( 1.03 , 4.31 ) , P = .040 ) were associated with mortality . Male sex ( OR = 2.35 , 95 % CI = ( 1.13 , 4.85 ) , P = .022 ) was associated with re-hospitalization while vitamin E supplementation was protective ( OR = 0.37 ( 0.16 , 0.90 ) , P = .028 ) . Lower socioeconomic status , prior influenza and pneumococcal vaccinations , appropriate antibiotic prescription upon admission , and lower nutrition risk were not significantly associated with mortality or re-hospitalization . Conclusion Chronic comorbidities appear to be the most important predictors of death and re-hospitalization in older adults hospitalized with community-acquired pneumonia while vitamin E supplementation was protective 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 Purpose To prospect ively evaluate the association of vitamin/mineral supplementation with  cancer , cardiovascular , and all-cause mortality .  Methods In the Heidelberg cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Heidelberg ) , which was recruited in 1994–1998 , 23,943 participants without pre-existing cancer and myocardial infa rct ion/stroke at baseline were included in the analyses . Vitamin/mineral supplementation was assessed at baseline and during follow-up . Cox regression models were used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . Results After an average follow-up time of 11 years , 1,101 deaths were documented ( cancer deaths = 513 and cardiovascular deaths = 264 ) . After adjustment for potential confounders , neither any vitamin/mineral supplementation nor multivitamin supplementation at baseline was statistically significantly associated with cancer , cardiovascular , or all-cause mortality . However , baseline users of antioxidant vitamin supplements had a significantly reduced risk of cancer mortality ( HR : 0.52 ; 95 % CI : 0.28 , 0.97 ) and all-cause mortality ( HR : 0.58 ; 95 % CI : 0.38 , 0.88 ) . In comparison with never users , baseline non-users who started taking vitamin/mineral supplements during follow-up had significantly increased risks of cancer mortality ( HR : 1.74 ; 95 % CI : 1.09 , 2.77 ) and all-cause mortality ( HR : 1.58 ; 95 % CI : 1.17 , 2.14 ) . Conclusions Based on limited numbers of users and cases , this cohort study suggests that supplementation of antioxidant vitamins might possibly reduce cancer and all-cause mortality . The significantly increased risks of cancer and all-cause mortality among baseline non-users who started taking supplements during follow-up may suggest a “ sick-user effect , ” which research ers should be cautious of in future observational studies BACKGROUND Low maternal serum retinol level is a risk factor for mother-to-child transmission ( MTCT ) of human immunodeficiency virus ( HIV ) . Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality . The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency ; neonatal dosing is under consideration . We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT , HIV-free survival , and mortality in HIV-exposed infants . METHODS A total of 14,110 mother-infant pairs were enrolled < or = 96 h after delivery , and both mother and infant , mother only , infant only , or neither received vitamin A supplementation in a r and omized , placebo-controlled trial with a 2 x 2 factorial design . All but 4 mothers initiated breast-feeding . A total of 4495 infants born to HIV-positive women were included in the present analysis . RESULTS Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months . However , the timing of infant HIV infection modified the effect that supplementation had on mortality .  Vitamin A supplementation had no effect in infants who were polymerase chain reaction ( PCR ) positive [ corrected ] for HIV at baseline . In infants who were PCR negative at baseline and PCR positive at 6 weeks , neonatal supplementation reduced mortality by 28 % ( P=.01 ) , but maternal supplementation had no effect . In infants who were PCR negative at 6 weeks , all 3 vitamin A regimens were associated with ~2-fold higher mortality ( P < or = .05 ) . CONCLUSIONS Targeted vitamin A supplementation of HIV-positive children prolongs their survival . However , postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks . These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas Higher circulating 25-hydroxyvitamin D ( 25[OH]D ) concentration has been linked to a lower prevalence of insulin resistance and type 2 diabetes mellitus . However , r and omized controlled trials have not clarified the effect of vitamin D supplementation on insulin resistance in healthy adults . The objective of this study was to assess the effect of vitamin D supplementation for 1 year on insulin resistance ; the study was a secondary analysis of a clinical trial . We hypothesized that increased 25(OH)D concentration after vitamin D supplementation for 1 year would significantly improve insulin resistance .  Ninety-six healthy adults participated in this study , of whom 81 completed the study . The participants r and omly received daily either 420 IU vitamin D3 or placebo in a double-blind manner for 1 year . The levels of fasting insulin , glucose , and other parameters were assessed at baseline and after 1 year of intervention . Homeostasis model assessment of insulin resistance index was calculated from insulin and glucose levels . Visceral fat area and physical activity were also investigated . Serum 25(OH)D and 1,25-dihydroxyvitamin D concentrations were significantly increased by approximately 29.5 nmol/L and 7.0 pg/mL , respectively , after 1-year vitamin D supplementation . After vitamin D supplementation , fasting glucose levels and values of homeostasis model assessment of insulin resistance index significantly decreased from 88.3 to 85.3 mg/dL ( P < .01 ) and 1.17 to 0.84 ( P < .01 ) , respectively , and the results were independent of physical activity and visceral fat accumulation . In conclusion , the present study showed that vitamin D supplementation for 1 year effectively improves fasting glucose level and insulin resistance in healthy Japanese adults To determine the relation between multivitamin use and death from heart disease , cerebrovascular disease , and cancer  , the authors examined a prospect i ve cohort of 1,063,023 adult Americans in 1982 - 1989 and compared the mortality of users of multivitamins alone ; vitamin A , C , or E alone ; and multivitamin and vitamin A , C , or E in combination with that of vitamin nonusers  by using multivariate Cox proportional hazard models .  Multivitamin users had heart disease and cerebrovascular disease mortality risks similar to those of nonusers , whereas combination users had mortality risks that were 15 % lower than those of nonusers . Multivitamin and combination use had minimal effect on cancer mortality overall , although mortality from all cancers combined was increased among male current smokers who used multivitamins alone ( relative risk ( RR ) = 1.13 , 95 % confidence interval ( CI ) : 1.05 , 1.23 ) or in combination with vitamin A , C , or E ( RR = 1.16 , 95 % CI : 1.06 , 1.26 ) , but decreased in male combination users who had never ( RR = 0.86 , 95 % CI : 0.74 , 0.99 ) or had formerly ( RR = 0.90 , 95 % CI : 0.82 , 0.98 ) smoked . No such associations were seen in women . These observational data provide limited support for the hypothesis that multivitamin use in combination with vitamin A , C , or E may reduce heart disease and cardiovascular disease mortality , but add to concerns raised by r and omized studies that some vitamin supplements may adversely affect male smokers Importance Whether vitamin D supplementation during pregnancy is beneficial and safe for offspring is unclear . Objective To systematic ally review studies of the effects of vitamin D supplementation during pregnancy on offspring growth , morbidity  , and mortality . Data Sources Search es of Medline , Embase , and the Cochrane Data base of Systematic Review s were conducted up to October 31 , 2017 . Key search terms were vitamin D , pregnancy , r and omized controlled trials , and offspring outcomes . Study Selection R and omized clinical trials of vitamin D supplementation during pregnancy and offspring outcomes . Data Extraction and Synthesis Two authors independently extracted data , and the quality of the studies was assessed . Summary risk ratio ( RR ) , risk difference ( RD ) or mean difference ( MD ) , and 95 % CI were calculated using fixed-effects or r and om-effects meta- analysis . Main Outcomes and Measures Main outcomes were fetal or neonatal mortality , small for gestational age ( SGA ) , congenital malformation , admission to a neonatal intensive care unit , birth weight , Apgar scores , neonatal 25-hydroxyvitamin D ( 25[OH]D ) and calcium concentrations , gestational age , preterm birth , infant anthropometry , and respiratory morbidity during childhood . Results Twenty-four clinical trials involving 5405 participants met inclusion criteria . Vitamin D supplementation during pregnancy was associated with a lower risk of SGA ( RR , 0.72 ; 95 % CI , 0.52 to 0.99 ; RD , −5.60 % ; 95 % CI , −0.86 % to −10.34 % ) without risk of fetal or neonatal mortality ( RR , 0.72 ; 95 % CI , 0.47 to 1.11 ) or congenital abnormality ( RR , 0.94 ; 95 % CI , 0.61 to 1.43 ) . Neonates with prenatal vitamin D supplementation had higher 25(OH)D levels ( MD , 13.50 ng/mL ; 95 % CI , 10.12 to 16.87 ng/mL ) , calcium levels ( MD , 0.19 mg/dL ; 95 % CI , 0.003 to 0.38 mg/dL ) , and weight at birth ( MD , 75.38 g ; 95 % CI , 22.88 to 127.88 g ) , 3 months ( MD , 0.21 kg ; 95 % CI , 0.13 to 0.28 kg ) , 6 months ( MD , 0.46 kg ; 95 % CI , 0.33 to 0.58 kg ) , 9 months ( MD , 0.50 kg ; 95 % CI , 0.01 to 0.99 kg ) , and 12 months ( MD , 0.32 kg ; 95 % CI , 0.12 to 0.52 kg ) . Subgroup analysis by doses showed that low-dose vitamin D supplementation ( ⩽2000 IU/d ) was associated with a reduced risk of fetal or neonatal mortality ( RR , 0.35 ; 95 % CI , 0.15 to 0.80 ) , but higher doses ( > 2000 IU/d ) did not reduce this risk ( RR , 0.95 ; 95 % CI , 0.59 to 1.54 ) . Conclusions and Relevance Vitamin D supplementation during pregnancy is associated with a reduced risk of SGA and improved infant growth without risk of fetal or neonatal mortality or congenital abnormality . Vitamin D supplementation with doses of 2000 IU/d or lower during pregnancy may reduce the risk of fetal or neonatal mortality In Linxian China , the esophageal/gastric cardia cancer mortality rates are among the highest in the world . There is suspicion that the population 's chronic deficiencies of multiple micronutrients are etiologically involved . We conducted two r and omized , placebo-controlled nutrition intervention trials to test the effects of vitamin and mineral supplements in lowering the rates of esophageal/gastric cancer . In the first trial , the dysplasia trial , 3318 adults with a cytological diagnosis of esophageal dysplasia received daily supplementation with 26 vitamins and minerals in doses typically 2 - 3 times the United States Recommended Daily Allowances , or placebos , for 6 years . The second trial , the general population trial , involved 29,584 adults and used a one-half replicate of a 2(4 ) factorial experimental design which tested 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 for these daily supplements ranged from 1 to 2 times the United States Recommended Daily Allowances , and the different vitamin/mineral combinations or placebos were taken for a period of 5.25 years . As part of the general population trial , and end-of-intervention endoscopy survey was carried out in a small ( 1.3 % ) sample of subjects to see if supplementation affected the prevalence of dysplasia and early cancer . Herein we review the methods of these trials and the results of the endoscopic survey . Fifteen esophageal and 16 gastric cancers were identified in endoscopic biopsies from the 391 subjects evaluated from two villages , and nearly all were asymptomatic . No significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen with any of the four supplement groups . However , the prevalence of gastric cancer among participants receiving retinol and zinc was 62 % lower than those not receiving those supplements ( P = 0.09 ) , while participants receiving beta-carotene , vitamin E , and selenium had a 42 % reduction in esophageal cancer prevalence ( 0.34 ) . We have reported separately that cancer mortality over the entire 5.25-year period was significantly reduced among those receiving beta-carotene , vitamin E , and selenium . The findings from the overall trial and the endoscopic sample offer a hopeful sign and should encourage additional studies with these agents in larger numbers of subjects 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 BACKGROUND A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals . In humans , epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers . Vitamins and minerals in these foods may contribute to the reduced cancer risk . The people of Linxian , China , have persistently low intake of multiple nutrients and exhibit one of the world 's highest rates of esophageal/gastric cardia cancer , with an exceptionally high risk of esophageal dysplasia . PURPOSE To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia , we conducted a 6-year prospect i ve intervention trial in Linxian . METHODS Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were r and omly assigned to receive , throughout that period , daily supplementation with 14 vitamins and 12 minerals or placebo . Doses were typically two to three times U.S. Recommended Daily Allowances . Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from sample s of individuals r and omly selected without replacement every 3 months throughout the trial . Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years . RESULTS A total of 324 deaths occurred during the 6-year intervention period ; 167 occurred in the control ( placebo ) group and 157 occurred in the  supplement  group . Cancer was the leading cause of death ( 54 % of all deaths ) ; 18 % were due to cerebrovascular diseases and 29 % to other causes . Cumulative esophageal/gastric cardia death rates were 8 % lower ( relative risk [ RR ] = 0.92 ; 95 % confidence interval [ CI ] = 0.67 - 1.28 ) among individuals receiving supplements rather than placebo , a nonsignificant ( P > .10 ) difference . Risk of total mortality was 7 % lower ( RR = 0.93 ; 95 % CI = 0.75 - 1.16 ; P > .10 ) , total cancer 4 % lower ( RR = 0.96 ; 95 % CI = 0.71 - 1.29 ; P > .10 ) , cerebrovascular disease 38 % lower ( RR = 0.62 ; 95 % CI = 0.37 - 1.06 ; P = .08 ) , and other diseases 12 % higher ( RR = 1.12 ; 95 % CI = 0.74 - 1.69 ; P > .10 ) among the treated group . Cumulative cancer incidence rates were nearly the same in the two groups . CONCLUSIONS No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus . IMPLICATION S Although no statistically significant short-term benefits were observed , longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia OBJECTIVE We investigated whether vitamin A supplementation would decrease mortality and morbidity rates in children infected with the human immunodeficiency virus ( HIV ) . METHODS We conducted a r and omized , double-blind , placebo-controlled clinical trial at Mulago Hospital , a large hospital that serves the urban and semiurban population s of Kampala , Ug and a. One hundred eighty-one HIV-infected children were enrolled at 6 mo and r and omized to receive vitamin A supplementation , 60 mg retinol equivalent , or placebo every 3 mo from ages 15 to 36 mo . Morbidity was assessed through a 7-d morbidity history every 3 mo , and vital events were measured . Children received daily trimethoprim-sulfamethoxazole prophylactic therapy . RESULTS After age 15 mo , children were followed for a median of 17.8 mo ( interquartile range = 11.1 to 21.0 mo ) . The trial was stopped when there was a new policy to implement a program of mass supplementation of vitamin A in the country . Mortality rates among 87 children in the  vitamin A group and 94 children in the control group were 20.6 % and 32.9 % , respectively , yielding a relative risk of 0.54 ( 95 % confidence interval , 0.30 to 0.98 ; P = 0.044 ) after adjusting for baseline weight-for-height Z score . Children who received vitamin A had lower modified point prevalences of persistent cough ( odds ratio , 0.47 ; 95 % confidence interval , 0.23 to 0.96 ; P = 0.038 ) and chronic diarrhea ( odds ratio , 0.48 ; 95 % confidence interval , 0.19 to 1.18 ; P = 0.11 ) and a shorter duration of ear discharge ( P = 0.03 ) . Vitamin A supplementation had no significant effect on modified point prevalences of fever , ear discharge , bloody stools , or hospitalizations . CONCLUSIONS Vitamin A supplementation decreases mortality rate in HIV-infected children and should be considered in the care for these children in developing countries 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 OBJECTIVES The association between pre-diagnostic  hormone replacement therapy ( HRT ) and breast cancer specific mortality as well as potential influences from other lifestyle factors on the association was investigated . STUDY DESIGN Female participants from the prospect i ve cohort " Diet , Cancer , and Health " diagnosed with breast cancer ( BC ) were identified and their pre-diagnostic HRT use evaluated for association with tumour biology and breast cancer outcome in multivariate analysis . MAIN OUTCOME MEASURE Breast cancer specific mortality . RESULTS Of the 1212 patients originally considered 1064 were included . Of these , 105 women died from breast cancer during a median follow-up of 6.3 years ( range 0.2 - 14.3 years ) . In multivariate analyses women who used HRT at enrolment into the cohort study had 47 % lower risk of dying from breast cancer as compared to women who had previously or never used HRT ( adjusted HR : 0.53 ; 95 % CI , 0.37 - 0.85 ) . Pre-diagnostic HRT use was associated with smaller tumour size at the time of diagnosis and a higher frequency of receptor positive breast cancer . Paradoxically , a high pre-diagnostic intake of vitamin D supplements was associated with HRT use but also with a higher BC specific mortality ( HR : 1.47 ; 95 % CI , 1.07 - 2.00 ) CONCLUSIONS : HRT use at enrolment was associated with breast tumours of smaller size at the time of diagnosis and positive receptor status , and with a lower BC mortality . The found association between vitamin D from supplements and higher BC mortality warrants further exploration Although there have been several studies of the effect of vitamin D status on bone turnover in the elderly , the findings are unclear , and , furthermore , to date very few have investigated this in young adults . The objective of these r and omized , placebo-controlled , double-blind , 2-center intervention studies was to investigate the effect of cholecalciferol supplementation ( 0 , 5 , 10 , and 15 microg cholecalciferol/d ) throughout winter time on indices of vitamin D status and bone turnover in young ( aged 20 - 40 y ; n = 215 ) and elderly ( aged > or = 64 y ; n = 204 ) adults , with relatively high mean calcium intakes of 976 and 874 mg/d , respectively .  Fasting serum concentrations of 25-hydroxyvitamin D [ 25(OH)D ] , parathyroid hormone ( PTH ) , osteocalcin , bone-specific alkaline phosphatase , and carboxyterminal collagen crosslinks were measured by enzyme immunoassays at baseline and endpoint . Fok I and Taq I vitamin D receptor ( VDR ) genotypes were determined by real-time PCR . Endpoint serum 25(OH)D increased ( P < 0.0001 ) in a dose-related manner with increasing supplemental cholecalciferol ( up to 15 microg/d ) in 20 - 40-y olds and up to 10 microg/d in > or = 64-y olds . Endpoint serum PTH was lower ( P < 0.05 ) in the 3 cholecalciferol-supplemented groups compared with that in the placebo group in > or = 64-y olds , but cholecalciferol supplementation did not affect other markers in either cohort and there was no significant interaction with VDR genotype . In conclusion , cholecalciferol supplementation alone throughout winter did not affect bone turnover markers in apparently healthy young and elderly adults , even when stratified by VDR genotype
In subgroup analyses , all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation ( P for interaction=0.04 ) ; neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality .
CONCLUSIONS Vitamin D supplementation alone was not associated with  all cause mortality in adults compared with placebo or no treatment .
Vitamin D supplementation reduced the risk of cancer death by 16 % .
Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality .
OBJECTIVE To investigate whether vitamin D supplementation is associated with lower mortality in adults .