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. Vitamin D and HIV Progression among Tanzanian Adults Initiating Antiretroviral Therapy Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Double blind, cluster randomised trial of low dose supplementation with vitamin A or β carotene on mortality related to pregnancy in Nepal Vitamin E may reduce prostate-cancer incidence Vitamin A supplementation during war-emergency in Guinea-Bissau 1998-1999. Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet. Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study Multiple micronutrient supplementation in Tanzanian infants born to HIV-infected mothers: a randomized, double-blind, placebo-controlled clinical trial. Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Vitamin A supplementation in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality Effect of vitamin A supplementation on morbidity of low-birth-weight neonates. The effect of at-birth vitamin A supplementation on differential leucocyte counts and in vitro cytokine production: an immunological study nested within a randomised trial in Guinea-Bissau. Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality. Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial Childhood mortality after a high dose of vitamin A in a high risk population. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women's Health Initiative (WHI) limited-access data set. Vitamin D Status of HIV-Infected Women and Its Association with HIV Disease Progression, Anemia, and Mortality Vitamin and Mineral Supplements: What Clinicians Need to Know. Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults. Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. Vitamin D for health: a global perspective. Vitamin A Supplementation at Birth Might Prime the Response to Subsequent Vitamin A Supplements in Girls. Three Year Follow-Up of a Randomized Trial The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Impact of massive dose of vitamin A given to preschool children with acute diarrhoea on subsequent respiratory and diarrhoeal morbidity Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Impact of vitamin D supplementation during a resistance training intervention on body composition, muscle function, and glucose tolerance in overweight and obese adults. Vitamin E and depressive symptoms are not related. The Rotterdam Study. A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania. Vitamin C and risk of coronary heart disease in women. Effect of winter oral vitamin D3 supplementation on cardiovascular risk factors in elderly adults. Effects of long-term vitamin E supplementation in alcoholic cirrhotics. Antioxidant vitamin intake and mortality in three Central and Eastern European urban populations: the HAPIEE study
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 Background There is growing evidence of an association between low vitamin D and HIV disease progression ; however , no prospect i ve studies have been conducted among adults receiving antiretroviral therapy ( ART ) in sub-Saharan Africa . Methods Serum 25-hydroxyvitamin D ( 25(OH)D ) levels were assessed at ART initiation for a r and omly selected cohort of HIV-infected adults enrolled in a trial of multivitamins ( not including vitamin D ) in Tanzania during 2006–2010 . Participants were prospect ively followed at monthly clinic visits for a median of 20.6 months . CD4 T-cell measurements were obtained every 4 months . Proportional hazard models were utilized for mortality analyses while generalized estimating equations were used for CD4 T-cell counts . Results Serum 25(OH)D was measured in 1103 adults 9.2 % were classified as vitamin D deficient ( < 20 ng/ml ) , 43.6 % insufficient ( 20–30 ng/mL ) , and 47.2 % as sufficient ( > 30 ng/mL ) . After multivariate adjustment , vitamin D deficiency was significantly associated with increased mortality as compared to vitamin D sufficiency ( HR : 2.00 ; 95 % CI : 1.19–3.37 ; p = 0.009 ) , whereas no significant association was found for vitamin D insufficiency ( HR : 1.24 ; 95 % CI : 0.87–1.78 ; p = 0.24 ) . No effect modification by ART regimen or change in the associations over time was detected . Vitamin D status was not associated with change in CD4 T-cell count after ART initiation . Conclusions Deficient vitamin D levels may lead to increased mortality in individuals receiving ART and this relationship does not appear to be due to impaired CD4 T-cell reconstitution . R and omized controlled trials are needed to determine the safety and efficacy of vitamin D supplementation for individuals receiving ART BACKGROUND Cases of enhanced anticoagulant effect in response to high-dose vitamin E supplementation have been reported among patients taking oral anticoagulants .  Although a vitamin E-vitamin K interaction was proposed to underlie this effect , it has not been systematic ally investigated in adults with normal baseline coagulation status . OBJECTIVE The objective was to study the effect of 12 wk of supplementation with 1000 IU RRR-alpha-tocopherol/d on biochemical measures of vitamin K status in men and women not taking oral anticoagulants . DESIGN  Vitamin K status , which was assessed with the use of plasma phylloquinone concentrations , the degree of under-gamma-carboxylation of prothrombin ( proteins induced by vitamin K absence-factor II , PIVKA-II ) , and the percentage of undercarboxylated osteocalcin ( ucOC ) , was determined in 38 men and women with rheumatoid arthritis ( study A ) and in 32 healthy men ( study B ) participating in 2 independent , 12-wk r and omized clinical trials of vitamin E supplementation ( 1000 IU/d ) . RESULTS Mean ( + /- SD ) PIVKA-II increased from 1.7 + /- 1.7 to 11.9 + /- 16.1 ng/mL ( P < 0.001 ) in study A and from 1.8 + /- 0.6 to 5.3 + /- 3.9 ng/mL ( P < 0.001 ) in study B in response to 12 wk of vitamin E supplementation . An increase in PIVKA-II is indicative of poor vitamin K status . In contrast , the other measures of vitamin K status ( ie , plasma phylloquinone concentration and percentage of ucOC ) did not change significantly in response to the supplementation . CONCLUSIONS High-dose vitamin E supplementation increased PIVKA-II in adults not receiving oral anticoagulant therapy . The clinical significance of these changes warrants further investigation , but high doses of vitamin E may antagonize vitamin K. Whether such an interaction is potentially beneficial or harmful remains to be determined BACKGROUND Vitamin C acts as a potent antioxidant ; however , it can also be a prooxidant and glycate protein under certain circumstances in vitro . These observations led us to hypothesize that a high intake of vitamin C in diabetic persons might promote atherosclerosis . OBJECTIVE The objective was to examine the relation between vitamin C intake and mortality from cardiovascular disease . DESIGN We studied the relation between vitamin C intake and mortality from total cardiovascular disease ( n = 281 ) , coronary artery disease ( n = 175 ) , and stroke ( n = 57 ) in 1923 postmenopausal women who reported being diabetic at baseline .  Diet was assessed with a food-frequency question naire at baseline , and subjects initially free of coronary artery disease were prospect ively followed for 15 y. RESULTS After adjustment for cardiovascular disease risk factors , type of diabetes medication used , duration of diabetes , and intakes of folate , vitamin E , and beta-carotene , the adjusted relative risks of total cardiovascular disease mortality were 1.0 , 0.97 , 1.11 , 1.47 , and 1.84 ( P for trend < 0.01 ) across quintiles of total vitamin C intake from food and supplements . Adjusted relative risks of coronary artery disease were 1.0 , 0.81 , 0.99 , 1.26 , and 1.91 ( P for trend = 0.01 ) and of stroke were 1.0 , 0.52 , 1.23 , 2.22 , and 2.57 ( P for trend < 0.01 ) . When dietary and supplemental vitamin C were analyzed separately , only supplemental vitamin C showed a positive association with mortality endpoints .  Vitamin C intake was unrelated to mortality from cardiovascular disease in the nondiabetic subjects at baseline . CONCLUSION A high vitamin C intake from supplements is associated with an increased risk of cardiovascular disease mortality in postmenopausal women with diabetes OBJECTIVE To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A , either preformed or as beta carotene . DESIGN Double blind , cluster r and omised , placebo controlled field trial . SETTING Rural southeast central plains of Nepal ( Sarlahi district ) . SUBJECTS 44 646 married women , of whom 20 119 became pregnant 22 189 times . INTERVENTION 270 wards r and omised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo , vitamin A ( 7000 micrograms retinol equivalents ) or beta carotene ( 42 mg , or 7000 micrograms retinol equivalents ) for over 31/2 years . MAIN OUTCOME MEASURES All cause mortality in women during pregnancy up to 12 weeks post partum ( pregnancy related mortality ) and mortality during pregnancy to 6 weeks postpartum , excluding deaths apparently related to injury ( maternal mortality ) . RESULTS Mortality related to pregnancy in the placebo , vitamin A , and beta carotene groups was 704 , 426 , and 361 deaths per 100 000 pregnancies , yielding relative risks ( 95 % confidence intervals ) of 0 . 60 ( 0.37 to 0.97 ) and 0.51 ( 0.30 to 0.86 ) . This represented reductions of 40 % ( P<0.04 ) and 49 % ( P<0.01 ) among those who received vitamin A and beta carotene . Combined , vitamin A or beta carotene  lowered mortality by 44 % ( 0.56 ( 0.37 to 0.84 ) , P<0.005 ) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births , or by 40 % ( P<0.02 ) . Differences in cause of death could not be reliably distinguished between supplemented and placebo groups . CONCLUSION Supplementation of women with either vitamin A or beta carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural , undernourished population s of south Asia itamin E supplements could V reduce prostate-cancer incidence and mortality by one-third in men who smoke , according to the results of a large primary -prevention trial in Finnish men . Prostate cancer is the fourth most common male cancer . As part of the Alpha-Tocopherol , Beta-Carotene ( ATBC ) study ( US National Cancer Institute and University of Helsinki , Finl and ) , more than 29 000 male smokers aged 50 - 69 years were r and omly assigned to receive 50 mg atocopherol , 20 mg P-carotene , both , or placebo daily for up to 8 years . At the end of the study , 246 new cases of prostate cancer and 62 deaths from the disease had occurred . Incidence was 32 % lower , and mortality 41 % lower , in men taking a-tocopherol , with or without P-carotene , than in those not taking the vitamin Nad Cancer Znst 1998 ; 90 : 440 - 46 ) . Men taking P-carotene had a 23 % . amin supplementation can be diffihigher incidence of , and 15 % higher cult to interpret , especially when mortality from , prostate cancer than there are multiple endpoints and no those not taking it . But these differences were not statistically significant . In addition , the investigators found that p-carotene nonsignificantly reduced the risk of prostate cancer in nondrinkers and increased the risk in drinkers , the risk rising with increasing strong a priori hypothesis . “ If the effect of a vitamin supplement is examined at , say , 20 cancer sites ” , says Franceschi , “ it is likely to appear protective at one site purely by chance . ” “ Studies with vitamin supplements are not a good basis for dietary advice ” , consumpDeserves further BACKGROUND Vitamin A supplementation is recommended by WHO in emergency situations . OBJECTIVE To evaluate the impact of Vitamin A supplementation on  childhood mortality  in an emergency situation . DESIGN Since this was not a r and omised study , we evaluated the impact in different ways ; we used the variation in the delay of provision of Vitamin A in a step-wedged design , compared wartime with pre-wartime mortality and examined whether Vitamin A as a free commodity reduced cultural and social-economic inequalities in childhood mortality . SUBJECTS 5926 children 6 months to 5 years of age , resident in four suburbs in the capital of Guinea-Bissau between October 1 , 1998 and March 31 , 1999 . INTERVENTIONS From October 1 , 1998 until the end of the war in 1999 all children present in the study area were offered Vitamin A at regular three-monthly visits to their homes . RESULTS Using the variation in the provision of Vitamin A , we found a slight non-significant reduction in mortality for children between 6 months and 5 years of age ( mortality ratio ( MR ) 0.49 ; 95 % CI 0.09 - 2.70 ) . Comparing with a three-year period before the war , children offered Vitamin A at home during the war had a 12 % reduction in mortality ( MR 0.88 ; 0.41 - 1.87 ) , whereas the overall impact of the war was an 89 % increase in mortality ( MR 1.89 ; 1.32 - 2.71 ) . Vitamin A supplementation was associated with a reduction in cultural and socio-economic inequalities . CONCLUSIONS Vitamin A supplementation may have a beneficial impact on  childhood mortality  in an emergency situation Elevated homocysteine has been identified as an independent risk factor for cardiovascular and cerebrovascular disease . Although multivitamin use has been associated with low plasma homocysteine concentrations in several observational studies , no clinical trials have been conducted using multivitamin/mineral supplements to lower homocysteine . We determined whether a multivitamin/mineral supplement formulated at about 100 % Daily Value will further lower homocysteine concentration and improve B-vitamin status in healthy older adults already consuming a diet fortified with folic acid . In this r and omized , double-blind , placebo-controlled trial , 80 free-living men and women aged 50 - 87 y with total plasma homocysteine concentrations of > or = 8 micromol/L received either a multivitamin/mineral supplement or placebo for 56 d while consuming their usual diet . After the 8-wk treatment , subjects taking the supplement had significantly higher B-vitamin status and lower homocysteine concentration than controls ( P : < 0.01 ) . Plasma folate , pyridoxal phosphate ( PLP ) and vitamin B-12 concentrations were increased 41.6 , 36.5 and 13.8 % , respectively , in the supplemented group , whereas no changes were observed in the placebo group . The mean homocysteine concentration decreased 9.6 % in the supplemented group ( P : < 0.001 ) and was unaffected in the placebo group . There were no significant changes in dietary intake during the intervention . Multivitamin/mineral supplementation can improve B-vitamin status and reduce plasma homocysteine concentration in older adults already consuming a folate-fortified diet Objectives Vitamin D is an immunomodulator and can alter response to tuberculosis ( TB ) treatment , though r and omised trials have been inconclusive to date . We present one of the first comprehensive analysis of the associations between vitamin D status and TB treatment , T-cell counts and nutritional outcomes by HIV status . Design Cohort study . Setting Outpatient clinics in Tanzania . Participants 25-hydroxyvitamin D levels were assessed in a cohort of 677 patients with TB ( 344 HIV infected ) initiating anti-TB treatment at enrolment in a multivitamin supplementation ( excluding vitamin D ) trial ( Clinical trials.gov identifier : NCT00197704 ) . Primary and secondary outcome measures Information on treatment outcomes such as failure and relapse , HIV disease progression , T-cell counts and anthropometry was collected routinely , with a median follow-up of 52 and 30 months for HIV-uninfected and HIV-infected patients , respectively . Cox and binomial regression , and generalised estimating equations were used to assess the association of vitamin D status with these outcomes . Results Mean 25-hydroxyvitamin D concentrations at enrolment were 69.8 ( ±21.5 ) nmol/L ( 27.9 ( ±8.6 ) ng/mL ) . Vitamin D insufficiency ( < 75 nmol/L ) was associated with a 66 % higher risk of relapse ( 95 % CI 4 % to 164 % ; 133 % higher risk in HIV-uninfected patients ) . Each unit higher 25-hydroxyvitamin D levels at baseline were associated with a decrease of 3 ( p=0.004 ) CD8 and 3 ( p=0.01 ) CD3 T-cells/µL during follow-up in patients with HIV infection . Vitamin D insufficiency was also associated with a greater decrease of body mass index ( BMI ; –0.21 kg/m2 ; 95 % CI −0.39 to −0.02 ) , during the first 8 months of follow-up . No association was observed  for vitamin D status with mortality or HIV disease progression . Conclusions Adequate vitamin D status is associated with a lower risk of relapse and with improved nutritional indicators such as BMI in patients with TB , with or without HIV infection . Further research is needed to determine the optimal dose of vitamin D and effectiveness of daily vitamin D supplementation among patients with TB BACKGROUND Multiple micronutrients ( vitamin B complex and vitamins C and E ) were effective at reducing infectious disease morbidity , HIV disease progression , and poor pregnancy outcomes in HIV-infected women . OBJECTIVE The objective was to evaluate whether direct supplementation of these micronutrients to HIV-exposed infants reduces mortality and morbidity . DESIGN Infants born to HIV-infected women from Dar es Salaam , Tanzania , were r and omly assigned to receive daily oral supplementation of multiple multivitamins ( vitamin B complex and vitamins C and E ) or placebo from age 6 wk for 24 mo . All-cause mortality , hospitalizations , and unscheduled clinic visits were recorded . Morbidities were recorded during monthly follow-up visits . All mothers received multiple micronutrients throughout the study . RESULTS A total of 1193 infants were r and omly assigned to receive  micronutrients  and 1194 to receive placebo .  There were 138 child deaths in the multivitamin group and 124 deaths in the placebo group ( HR : 1.13 ; 95 % CI : 0.88 , 1.44 ; P = 0.33 ) . Hospitalizations ( RR : 0.83 ; 95 % CI : 0.62 , 1.13 ; P = 0.23 ) , unscheduled clinic visits ( RR : 0.97 ; 95 % CI : 0.85 , 1.10 ; P = 0.59 ) , and maternal reports of diarrhea ( RR : 0.97 ; 0.87 , 1.10 ; P = 0.64 ) were not significantly different between the 2 groups . Fever ( P = 0.02 ) and vomiting ( P = 0.007 ) were significantly lower in the multivitamin group . Among 429 children whose mothers received antiretroviral ( ARV ) therapy , multivitamin use had no effect on mortality but was associated with a significant reduction in hospitalizations ( P = 0.035 ) , episodes of fever ( P = 0.005 ) , and episodes of fever and cough ( P = 0.019 ) . CONCLUSIONS In the setting of maternal micronutrient supplementation , supplementation of HIV-exposed infants with vitamin B and vitamins C and E does not reduce mortality . Studies of nutrition supplementation in ARV-exposed infants may be warranted A clinical trial of vitamin E and beta-carotene supplementation for lung cancer prevention among male smokers in Finl and recently reported an unexpected , strong protective effect of vitamin E against prostate cancer incidence and mortality . Our objective was to prospect ively examine supplemental vitamin E intake and prostate cancer risk in a distinct U.S. population . In 1986 , we identified 47,780 U.S. male health professionals , free from diagnosed cancer , who completed a dietary and lifestyle question naire ; supplemental vitamin E and prostate cancer incidence were up date d biennially through 1996 . We estimated relative risks ( RRs ) from multivariate pooled logistic regression models . There were 1896 total ( non-stage A1 ) , 522 extraprostatic , and 232 metastatic or fatal incident prostate cancer cases diagnosed between 1986 - 1996 . Men consuming at least 100 IU of supplemental vitamin E daily had multivariate RRs of 1.07 ( 95 % confidence interval [ CI ] , 0.95 - 1.20 ) for total and 1.14 ( 95 % CI , 0.82 - 1.59 ) for metastatic or fatal prostate cancer compared with those consuming none . Current use , dosage , and total duration of use of specific vitamin E supplements or multivitamins were not associated with risk . However , among current smokers and recent quitters , those who consumed at least 100 IU of supplemental vitamin E per day had a RR of 0.44 ( 95 % CI , 0.18 - 1.07 ) for metastatic or fatal prostate cancer compared with nonusers . Thus , supplemental vitamin E was not associated with prostate cancer risk generally , but a suggestive inverse association between supplemental vitamin E and risk of metastatic or fatal prostate cancer among current smokers and recent quitters was consistent with the Finnish trial among smokers and warrants further investigation Although most studies on the effect of vitamin A supplementation have reported reductions in childhood mortality , the effects on morbidity are less clear . We have carried out two double-blind , r and omised , placebo-controlled trials of vitamin A supplementation in adjacent population s in northern Ghana to assess the impact on  childhood morbidity and mortality . The Survival Study included 21,906 children aged 6 - 90 months in 185 geographical clusters , who were followed for up to 26 months . The Health Study included 1455 children aged 6 - 59 months , who were monitored weekly for a year . Children were r and omly assigned either 200,000 IU retinol equivalent ( 100,000 IU under 12 months ) or placebo every 4 months ; r and omisation was by individual in the Health Study and by cluster in the Survival Study . There were no significant differences in the Health Study between the vitamin A and placebo groups in the prevalence of diarrhoea or acute respiratory infections ; of the symptoms and conditions specifically asked about , only vomiting and anorexia were significantly less frequent in the supplemented children . Vitamin-A-supplemented children had significantly fewer attendances at clinics ( rate ratio 0.88 [ 95 % CI 0.81 - 0.95 ] , p = 0.001 ) , hospital admissions ( 0.62 [ 0.42 - 0.93 ] , p = 0.02 ) , and deaths ( 0.81 [ 0.68 - 0.98 ] , p = 0.03 ) than children who received placebo . The extent of the effect on morbidity and mortality did not vary significantly with age or sex . However , the mortality rate due to acute gastroenteritis was lower in vitamin-A-supplemented than in placebo clusters ( 0.66 [ 0.47 - 0.92 ] , p = 0.02 ) ; mortality rates for all other causes except acute lower respiratory infections and malaria were also lower in vitamin A clusters , but not significantly so . Improving the vitamin A intake of young children in population s where xerophthalmia exists , even at relatively low prevalence , should be a high priority for health and agricultural services in Africa and elsewhere BACKGROUND Low-birth-weight ( LBW ) infants ( < 2,500 g ) are at increased risk of respiratory infection in the first few months of life and have low liver stores of vitamin A. As retinol is essential for respiratory epithelial cell differentiation , deficiency could result in pathological changes in the respiratory epithelium , with respiratory problems . OBJECTIVE A r and omised , double-blind , placebo-controlled trial to investigate the effect of vitamin A supplementation on the incidence and severity of respiratory infections in LBW infants during their first year of life . METHOD One hundred and thirty LBW infants ( gestational age < 36 weeks and birth weight 950 - 1,700 g ) were enrolled in the study . The infants were r and omly allocated to a vitamin A or placebo group . Infants in the vitamin A group received 25,000 IU of vitamin A ( retinyl palmitate , Arovit drops , Roche , Basle , Switzerl and ) on study days 1 , 4 and 8 . Study day 1 was between 36 and 60 hours after delivery . Infants in the placebo group received a placebo ( formulated by Roche ) with a similar appearance and packed in the same dropper bottles as the vitamin A drops . RESULTS Vitamin A supplementation markedly improved serum retinol levels . After the last vitamin A dose , the vitamin A group had higher mean serum retinol concentrations than the placebo group ( 45.77 + /- 17.07 micrograms/dl v. 12.88 + /- 6.48 micrograms/dl , P = 0.0001 ) . There was no evidence of improvement in neonatal or post-neonatal respiratory problems associated with vitamin A supplementation . Vitamin A and placebo groups did not differ in the occurrence or duration of respiratory distress or the need for head-box oxygen . There were also no significant differences in the cumulative probability of developing lower or upper respiratory tract infection through the first year of life . There was a slight suggestion of an increase in the risk of hospitalisation with pneumonia associated with vitamin A supplementation . The cumulative probability of being hospitalised with pneumonia by 6 months of age was 24.6 % ( 7 hospitalisations ) in the vitamin A group compared with 7.4 % ( 2 hospitalisations ) in the placebo group ( log rank test P = 0.04 ) . After adjusting for risk factors this difference was no longer significant . CONCLUSION Vitamin A supplementation in LBW neonates may not reduce incidence or severity of respiratory infections . These results do not negate the importance of improving vitamin A status in children as an important public health measure to reduce morbidity and mortality from other childhood infections Vitamin A supplementation ( VAS ) at birth was not associated with improved survival in a r and omised , placebo-controlled trial in Guinea-Bissau . However , a negative sex-differential effect , which became evident after diphtheria-tetanus-pertussis ( DTP ) vaccination , was noted ; among girls who had received DTP , VAS at birth was associated with two-fold higher mortality than placebo . The objective of the present study was to investigate the immunological effects of VAS at birth within a subgroup of participants in the r and omised trial . Guided by the mortality results , we further explored whether VAS had a differential effect according to sex and DTP status . At 6 weeks after r and omisation and supplementation , we measured differential leucocyte counts and TNF-α , interferon-γ , IL-10 , IL-13 and IL-5 production in a whole-blood culture assay . A total of 471 children were included .  VAS compared with placebo at birth was associated with a higher proportion of monocytes ( relative risk ratio 1·26 , 95 % CI 1·07 , 1·49 , P=0·04 ) , while spontaneous TNF-α production was lower in the VAS group ( geometric mean ratio 0·54 , 95 % CI , 0·37 , 0·78 , P=0·001 ) . Stratified analysis showed that VAS was associated with lower TNF-α and IL-10 production for girls without DTP and boys with DTP , result ing in significant three-way interactions between VAS , sex and DTP vaccination status ( P=0·03 and P=0·04 , respectively ) for spontaneous TNF-α and IL-10 production . The results substantiate the potential role of VAS as an immunomodulatory intervention , which has different effects depending on concomitant health interventions and the sex of the recipient BACKGROUND Although basic research suggests that vitamins may have an important role in the prevention of cardiovascular diseases ( CVD ) , the data from cohort studies and clinical trials are inconclusive . METHODS This prospect i ve cohort study was conducted among 83 639 male physicians residing in the United States who had no history of CVD or cancer . At baseline , data on use of vitamin E , ascorbic acid ( vitamin C ) , and multivitamin supplements were provided by a self-administered question naire . Mortality from CVD and coronary heart disease ( CHD ) was assessed by death certificate review . RESULTS Use of supplements was reported by 29 % of the participants . During a mean follow-up of 5.5 years , 1037 CVD deaths occurred , including 608 CHD deaths . After adjustment for several cardiovascular risk factors , supplement use was not significantly associated with total CVD or CHD mortality . For vitamin E use , the relative risks ( RRs ) were 0.92 ( 95 % confidence interval [ CI ] , 0.70 - 1.21 ) for total CVD mortality and 0.88 ( 95 % CI , 0.61 - 1.27 ) for CHD mortality ; for use of vitamin C , the RRs were 0.88 ( 95 % CI , 0.70 - 1.12 ) for total CVD mortality and 0.86 ( 95 % CI , 0.63 - 1.18 ) for CHD mortality ; and for use of multivitamin supplements , the RRs were 1.07 ( 95 % CI , 0.91 - 1.25 ) for total CVD mortality and 1.02 ( 95 % CI , 0.83 - 1.25 ) for CHD mortality . CONCLUSIONS In this large cohort of apparently healthy US male physicians , self-selected supplementation with vitamin E , vitamin C , or multivitamins was not associated with a significant decrease in total CVD or CHD mortality . Data from ongoing large r and omized trials will be necessary to definitely establish small potential benefits of vitamin supplements on subsequent cardiovascular risk Background : Increased dietary vitamin E intake is associated with a reduced incidence of asthma , and combinations of antioxidant supplements including vitamin E are effective in reducing ozone induced bronchoconstriction . A study was undertaken to investigate the effect of supplementation with vitamin E for 6 weeks on bronchial hyperresponsiveness in atopic adults with asthma . Methods : 72 participants from a clinical trial register of adults with asthma were r and omised to receive 500 mg natural vitamin E or matched placebo for 6 weeks in a placebo controlled , double blind parallel group clinical trial . Inclusion criteria included age 18–60 years , maintenance treatment of at least one dose of inhaled corticosteroid per day , a positive skin prick test to one of three common allergens , and bronchial hyperresponsiveness to methacholine ( defined as a dose provoking a 20 % fall in forced expiratory volume in 1 second ( FEV1 ) ( PD20 ) of 12.25 μmol ) . Secondary outcomes were FEV1 , forced vital capacity , mean morning and evening peak flow , symptom scores , bronchodilator use , and serum immunoglobulin E levels . Results : In the primary intention to treat analysis the change in PD20 was similar in the vitamin E and placebo groups with a mean difference of + 0.25 doubling doses of methacholine ( 95 % confidence interval −0.67 to + 1.16 greater with vitamin E ) . There was no effect of vitamin E supplementation on any other measure of asthma control , either in the intention to treat or per protocol analysis . There was also no effect of vitamin E supplementation on serum immunoglobulin levels . Conclusion : Dietary supplementation with vitamin E adds no benefit to current st and ard treatment in adults with mild to moderate asthma OBJECTIVES --To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme . DESIGN --Opportunistic controlled trial . SETTING --Jumla district , Nepal . SUBJECTS -- All children aged under 5 years ; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation .  MAIN OUTCOME MEASURES --Mortality and cause of death in the five months after supplementation . RESULTS --Risk of death for children aged 1 - 59 months in supplemented communities was 26 % lower ( relative risk 0.74 , 95 % confidence interval 0.55 to 0.99 ) than in unsupplemented communities . The reduction in mortality was greatest among children aged 6 - 11 months : death rate ( deaths/1000 child years at risk ) was 133.8 in supplemented children and 260.8 in unsupplemented children ( relative risk 0.51 , 0.30 to 0.89 ) . The death rate from diarrhoea was also reduced ( 63.5 supplemented v 97.5 unsupplemented ; relative risk 0.65 , 0.44 to 0.95 ) . The extra cost per death averted was about $ 11 . CONCLUSION --The results support a role for Vitamin A in increasing child survival . The supplementation programme was readily integrated with the ongoing community health programme at little extra cost BACKGROUND Frequent use of personal , non protocol calcium supplements obscured an adverse effect of coadministered calcium and vitamin D ( CaD ) on cardiovascular risk in the Women 's Health Initiative ( WHI ) . OBJECTIVE We investigated the effects of the use of personal calcium or vitamin D supplements on other outcomes in the WHI CaD Study ( WHI CaD ) by using the WHI limited-access clinical trials data set . DESIGN The WHI CaD was a 7-y , r and omized , placebo-controlled trial of CaD ( 1 g Ca/400 IU vitamin D daily ) in 36,282 community-dwelling , postmenopausal women . The incidence of total cancer ( excluding nonmelanoma skin cancers ) , breast and colorectal cancers , hip and total fracture , and mortality was assessed by using Cox proportional hazards models . RESULTS In the WHI CaD , interactions between the use of either personal calcium or vitamin D supplements and CaD were found for total , breast , and colorectal cancers but not for fracture or mortality .  In 15,646 women ( 43 % ) who were not taking personal calcium or vitamin D supplements at r and omization , CaD significantly decreased the risk of total , breast , and invasive breast cancers by 14 - 20 % and nonsignificantly reduced the risk of colorectal cancer by 17 % . In women taking personal calcium or vitamin D supplements , CaD did not alter cancer risk ( HR : 1.06 - 1.26 ) . CONCLUSIONS For women in the WHI CaD who were not taking personal calcium or vitamin D supplements at r and omization , CaD decreased the risk of total , breast , and colorectal cancers and did not change the risk of fractures or total mortality . The nonskeletal effects of CaD may be more important than the skeletal effects and should be considered when evaluating these supplements . The WHI CaD trial is registered at clinical trials.gov as NCT00000611 Background Vitamin D has a potential role in slowing HIV disease progression and preventing mortality based on its extensive involvement in the immune system ; however , this relationship has not been examined in large studies or in re source -limited setting s. Methodology /Principal Findings Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation ( not including vitamin D ) in Tanzania . Women were followed up for a median of 69.5 months , and information on hemoglobin levels , HIV disease progression , and mortality was recorded . Proportional hazard models and generalized estimating equations were used to assess the relationship of these outcomes with vitamin D status . Conclusions / Significance Low vitamin D status ( serum 25-hydroxyvitamin D<32ng/mL ) was significantly associated with progression to WHO HIV disease stage III or greater in multivariate models ( incidence rate ratio [ RR ] : 1.25 ; 95 % confidence intervals [ CI ] : 1.05 , 1.50 ) . No significant relationship was observed between vitamin D status and T-cell counts during follow-up . Women with low vitamin D status had 46 % higher risk of developing severe anemia during follow-up , compared to women with adequate vitamin D levels ( RR : 1.46 ; 95 % CI : 1.09 , 1.96 ) . Women in the highest vitamin D quintile had a 42 % lower risk of all-cause mortality , compared to the lowest quintile ( RR : 0.58 ; 95 % CI : 0.40 , 0.84 ) . Vitamin D status had a protective association with HIV disease progression , all-cause mortality , and development of anemia during follow-up in HIV-infected women . If confirmed in r and omized trials , vitamin D supplementation could represent a simple and inexpensive method to prolonging the time to initiation of antiretroviral therapy in HIV-infected patients , particularly in re source -limited setting Dietary supplementation is approximately a $ 30 billion industry in the United States , with more than 90 000 products on the market . In recent national surveys , 52 % of US adults reported use of at least 1 supplement product , and 10%reporteduseofatleast4suchproducts.1 Vitamins and minerals are among the most popular supplements and are taken by 48 % and 39 % of adults , respectively , typically to maintain health and prevent disease . Despite this enthusiasm , most r and omized clinical trials of vitamin and mineral supplements have not demonstrated clear benefits for primary or secondary prevention of chronic diseases not related to nutritional deficiency . Indeed , some trials suggest that micronutrient supplementation in amounts that exceed the recommended dietary allowance (RDA)—eg , high doses of beta carotene , folic acid , vitamin E , or selenium — may have harmful effects , including increased mortality , cancer , and hemorrhagic stroke.2 In this Viewpoint , we provide information to help clinicians address frequently asked questions about micronutrient supplements from patients , as well as promote appropriate use and curb inappropriate use of such supplements among generally healthy individuals . Importantly , clinicians should counsel their patients that such supplementation is not a substitute for a healthful and balanced diet and , in most cases , provides little if any benefit beyond that conferred by such a diet . Clinicians should also highlight the many advantages of obtaining vitamins and minerals from food instead of from supplements . Micronutrients in food are typically better absorbed by the body and are associated with fewer potential adverse effects.2,3 A healthful diet provides an array of nutritionally important substances in biologically optimal ratios as opposed to isolated compounds in highly concentrated form . Indeed , research shows that positive health outcomes are more strongly related to dietary patterns and specific food types than to individual micronutrient or nutrient intakes.3 Although routine micronutrient supplementation is not recommended for the general population , targeted supplementation may be warranted in high-risk groups for whom nutritional requirements may not be met through diet alone , including people at certain life stages and those with specific risk factors ( discussed in the next 3 sections and in the Box ) There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity . Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation , results have been equivocal . The aim of this r and omised , placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol ( 25(OH)D ) response to 15 μg cholecalciferol per d in healthy young and older Irish adults . A total of 110 young adults ( 20 - 40 years ) and 102 older adults ( ≥ 64 years ) completed the 22-week intervention with > 85 % compliance . The change in 25(OH)D from baseline was calculated . Anthropometric measures of adiposity taken at baseline included height , weight and waist circumference ( WC ) , along with skinfold thickness measurements to estimate fat mass ( FM ) . FM was subsequently expressed as FM ( kg ) , FM ( % ) , FM index ( FMI ( FM kg/height m2 ) ) and as a percentage ratio to fat-free mass ( FFM ) . In older adults , vitamin D status was inversely associated with BMI ( kg/m2 ) , WC ( cm ) , FM ( kg and % ) , FMI ( kg/m2 ) and FM : FFM ( % ) at baseline ( r - 0·33 , - 0·36 , - 0·33 , - 0·30 , - 0·33 and - 0·27 , respectively , all P values < 0·01 ) . BMI in older adults was also negatively associated with the change in 25(OH)D  following supplementation ( β - 1·27 , CI - 2·37 , - 0·16 , P = 0·026 ) ; however , no such associations were apparent in younger adults . Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes BACKGROUND We previously reported that maternal micronutrient supplementation in rural Nepal decreased low birth weight by approximately 15 % . OBJECTIVE We examined the effect of daily maternal micronutrient supplementation on  fetal loss and infant mortality .  DESIGN The study was a double-blind , cluster-r and omized , controlled trial among 4926 pregnant women and their 4130 infants in rural Nepal . In addition to vitamin A ( 1000 microg retinol equivalents ) , the intervention groups received either folic acid ( FA ; 400 microg ) , FA + iron ( 60 mg ) , FA + iron + zinc ( 30 mg ) , or multiple micronutrients ( MNs ; the foregoing plus 10 microg vitamin D , 10 mg vitamin E , 1.6 mg thiamine , 1.8 mg riboflavin , 2.2 mg vitamin B-6 , 2.6 microg vitamin B-12 , 100 mg vitamin C , 64 microg vitamin K , 20 mg niacin , 2 mg Cu , and 100 mg Mg ) . The control group received vitamin A only . RESULTS None of the supplements reduced fetal loss . Compared with control infants , infants whose mothers received FA alone or with iron or iron + zinc had a consistent pattern of 15 - 20 % lower 3-mo mortality ; this pattern was not observed with MNs . The effect on mortality was restricted to preterm infants , among whom the relative risks ( RRs ) were 0.36 ( 95 % CI : 0.18 , 0.75 ) for FA , 0.53 ( 0.30 , 0.92 ) for FA + iron , 0.77 ( 0.45 , 1.32 ) for FA + iron + zinc , and 0.70 ( 0.41 , 1.17 ) for MNs . Among term infants , the RR for mortality was close to 1 for all supplements except MNs ( RR : 1.74 ; 95 % CI : 1.00 , 3.04 ) . CONCLUSIONS Maternal micronutrient supplementation failed to reduce overall fetal loss or early infant mortality .  Among preterm infants , FA alone or with iron reduced mortality in the first 3 mo of life . MNs may increase mortality risk among term infants , but this effect needs further evaluation It is now generally accepted that vitamin D deficiency is a worldwide health problem that affects not only musculoskeletal health but also a wide range of acute and chronic diseases . However , there remains cynicism about the lack of r and omized controlled trials to support the association studies regarding the nonskeletal health benefits of vitamin D. This review was obtained by search ing English- language studies published up to April 1 , 2013 , in PubMed , MEDLINE , and the Cochrane Central Register of Controlled Trials ( search terms : vitamin D and supplementation ) and focuses on recent challenges regarding the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D concentrations from dietary sources , supplements , and sun exposure . The effect of vitamin D on fetal programming epigenetics and gene regulation could potentially explain why vitamin D has been reported to have such wide-ranging health benefits throughout life . There is potentially a great upside to increasing the vitamin D status of children and adults worldwide for improving musculoskeletal health and reducing the risk of chronic illnesses , including some cancers , autoimmune diseases , infectious diseases , type 2 diabetes mellitus , neurocognitive disorders , and mortality Objectives Within a r and omised trial of neonatal vitamin A supplementation ( VAS ) in Guinea-Bissau , neonatal VAS did not affect overall  infant mortality . We conducted a post-hoc analysis to test the hypothesis that neonatal VAS primes the response to subsequent vitamin A. Methods All trial children were offered VAS after follow-up ended at 1 year of age ( FU-VAS ) . We compared mortality between 1 and 3 years of age according to initial r and omization to neonatal VAS or placebo in Cox-regression models ; we expected that children r and omized to neonatal VAS compared with those r and omized to placebo would have lower mortality after reception of FU-VAS . Results Of 4345 infants enrolled in the original trial , 3646 lived in the study area at 1 year of age and 2958 received FU-VAS .  Between 1 and 3 years of age , 112 children died . After FU-VAS , neonatal VAS was associated with lower mortality than placebo : Mortality Rate Ratio ( MRR ) = 0.54 ( 95%CI : 0.31–0.94 ) . The effect was more pronounced in girls ( MRR = 0.37 ( 0.16–0.89 ) ) than boys ( MRR = 0.73 ( 0.35–1.51 ) ) . The beneficial effect of neonatal VAS may have been particularly strong for girls who received both VAS in a campaign and FU-VAS ( MRR = 0.15 ( 0.03–0.67 ) ) . Among children who had not received FU-VAS , mortality in the second and third year of life did not differ according to reception of neonatal VAS or placebo . Hence , in the second and third year of life the effect of neonatal VAS versus placebo was different in girls who had or had not received FU-VAS ( p for homogeneity = 0.01 ) . Conclusions The present results suggest that neonatal VAS primes the response in girls such that they get a beneficial effect after a subsequent dose of VAS . Trial Registration Clinical trials.gov BACKGROUND It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer . To date , however , the published results of r and omized , placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect . We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population . METHODS The Supplementation en Vitamines et Mineraux Antioxydants ( SU.VI.MAX ) study is a r and omized , double-blind , placebo-controlled primary prevention trial . A total of 13 017 French adults ( 7876 women aged 35 - 60 years and 5141 men aged 45 - 60 years ) were included . All participants took a single daily capsule of a combination of 120 mg of ascorbic acid , 30 mg of vitamin E , 6 mg of beta carotene , 100 mug of selenium , and 20 mg of zinc , or a placebo . Median follow-up time was 7.5 years . RESULTS No major differences were detected between the groups in total cancer incidence ( 267 [ 4.1 % ] for the study group vs 295 [ 4.5 % ] for the placebo group ) , ischemic cardiovascular disease incidence ( 134 [ 2.1 % ] vs 137[2.1 % ] ) , or all-cause mortality ( 76 [ 1.2 % ] vs 98 [ 1.5 % ] ) . However , a significant interaction between sex and group effects on cancer incidence was found ( P = .004 ) . Sex-stratified analysis showed a protective effect of antioxidants in men ( relative risk , 0.69 [ 95 % confidence interval [ CI ] , 0.53 - 0.91 ] ) but not in women ( relative risk , 1.04 [ 95 % CI , 0.85 - 1.29 ] ) . A similar trend was observed for all-cause mortality ( relative risk , 0.63 [ 95 % CI , 0.42 - 0.93 ] in men vs 1.03 [ 95 % CI , 0.64 - 1.63 ] in women ; P = .11 for interaction ) . CONCLUSIONS After 7.5 years , low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women . Supplementation may be effective in men only because of their lower baseline status of certain antioxidants , especially of beta carotene Abstract Objective : To assess the impact of vitamin A supplementation on  morbidity from acute respiratory tract infections and diarrhoea .  Design : Double blind r and omised placebo controlled field trial . Setting : An urban slum area in New Delhi , India . Subjects—900 children aged 12 - 60 months attending a local health facility for acute diarrhoea of less than seven days ' duration r and omly allocated to receive vitamin A 200000 IU or placebo . Main outcome measures : Incidence and prevalence of acute lower respiratory tract infections and diarrhoea during the 90 days after termination of the enrolment diarrhoeal episode measured by twice weekly household surveillance . Results : The incidence ( relative risk 1.07 ; 95 % confidence interval 0.92 to 1.26 ) and average number of days spent with acute lower respiratory tract infections were similar in the vitamin A supplementation and placebo groups . Among children aged 23 months or less there was a significant reduction in the incidence of measles ( relative risk 0.06 ; 95 % confidence interval 0.01 to 0.48 ) . The incidence of diarrhoea was also similar ( relative risk 0.95 ; 0.86 to 1.05 ) in the two groups . There was a 36 % reduction in the mean daily prevalence of diarrhoea associated with fever in the vitamin A supplemented children older than 23 months . Conclusions : Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation noted in other trials and a possible reduction in the severity of diarrhoea CONTEXT Vitamin D or calcium supplementation may have effects on  vascular disease and cancer .  OBJECTIVE Our objective was to investigate whether vitamin D or calcium supplementation affects mortality , vascular disease , and cancer in older people . DESIGN AND SETTING The study included long-term follow-up of participants in a two by two factorial , r and omized controlled trial from 21 orthopedic centers in the United Kingdom . PARTICIPANTS Participants were 5292 people ( 85 % women ) aged at least 70 yr with previous low-trauma fracture . INTERVENTIONS Participants were r and omly allocated to daily vitamin D(3 ) ( 800 IU ) , calcium ( 1000 mg ) , both , or placebo for 24 - 62 months , with a follow-up of 3 yr after intervention . MAIN OUTCOME MEASURES All-cause mortality , vascular disease mortality , cancer mortality , and cancer incidence were evaluated . RESULTS In intention-to-treat analyses , mortality [ hazard ratio ( HR ) = 0.93 ; 95 % confidence interval ( CI ) = 0.85 - 1.02 ] , vascular disease mortality ( HR = 0.91 ; 95 % CI = 0.79 - 1.05 ) , cancer mortality ( HR = 0.85 ; 95 % CI = 0.68 - 1.06 ) , and cancer incidence ( HR = 1.07 ; 95 % CI = 0.92 - 1.25 ) did not differ significantly between participants allocated vitamin D and those not . All-cause mortality ( HR = 1.03 ; 95 % CI = 0.94 - 1.13 ) , vascular disease mortality ( HR = 1.07 ; 95 % CI = 0.92 - 1.24 ) , cancer mortality ( HR = 1.13 ; 95 % CI = 0.91 - 1.40 ) , and cancer incidence ( HR = 1.06 ; 95 % CI = 0.91 - 1.23 ) also did not differ significantly between participants allocated calcium and those not . In a post hoc statistical analysis adjusting for compliance , thus with fewer participants , trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated , although all results remain nonsignificant . CONCLUSIONS Daily vitamin D or calcium supplementation did not affect mortality , vascular disease , cancer mortality , or cancer incidence BACKGROUND B-vitamin deficiencies have been associated with depression ; however , there is very little prospect i ve evidence from population -based studies of older adults . OBJECTIVE We examined whether dietary intakes of vitamins B-6 , folate , or vitamin B-12 were predictive of depressive symptoms over an average of 7.2 y in a community-based population of older adults . DESIGN The study sample consisted of 3503 adults from the Chicago Health and Aging project , an ongoing , population -based , biracial ( 59 % African American ) study in adults aged > or = 65 y.  Dietary assessment was made by food-frequency question naire . Incident depression was measured by the presence of > or = 4 depressive symptoms from the 10-item version of the Center for Epidemiologic Studies Depression scale . RESULTS The logistic regression models , which used generalized estimating equations , showed that higher total intakes , which included supplementation , of vitamins B-6 and B-12 were associated with a decreased likelihood of incident depression for up to 12 y of follow-up , after adjustment for age , sex , race , education , income , and antidepressant medication use . For example , each 10 additional milligrams of vitamin B-6 and 10 additional micrograms of vitamin B-12 were associated with 2 % lower odds of depressive symptoms per year . There was no association between depressive symptoms and food intakes of these vitamins or folate . These associations remained after adjustment for smoking , alcohol use , widowhood , caregiving status , cognitive function , physical disability , and medical conditions . CONCLUSION Our results support the hypotheses that high total intakes of vitamins B-6 and B-12 are protective of depressive symptoms over time in community-residing older adults BACKGROUND & AIMS The impact of vitamin D supplementation in overweight and obese adults during resistance training on body composition , muscle function , and glucose tolerance was investigated . METHODS Twenty-three overweight and obese ( age : 26.1±4.7 y ; BMI : 31.3±3.2 kg/m(2 ) ; 25-hydroxyvitamin D : 19.3±7.2 ng/mL ) adults were recruited for participation in a double-blind , placebo-controlled trial . Participants were r and omly divided into vitamin D ( VitD , 4000 IU/d ; 5 females , 5 males ) and placebo ( PL ; 7 females , 6 males ) groups . Both groups completed 12 weeks of resistance training . 25-hydroxyvitamin D , parathyroid hormone , body composition , and glucose tolerance were assessed at baseline and 12 weeks . Muscle function ( strength and power ) was assessed at baseline , 4 , 8 , and 12 weeks . RESULTS During the intervention , 25-hydroxyvitamin D increased and parathyroid hormone decreased in the VitD group ( P<0.05 ) . Peak power was significantly increased at 4 weeks in the VitD group only ( P<0.05 ) . Regression analysis revealed an inverse association between the change in 25-hydroxyvitamin D with the change in waist-to-hip ratio ( R(2)=0.205 , P=0.02 ) . No other improvements were observed with supplementation . CONCLUSIONS Vitamin D supplementation in overweight and obese adults during resistance training induced an early improvement in peak power , and elevated vitamin D status was associated with reduced waist-to-hip ratio . CLINICAL TRIAL REGISTRATION NUMBER NCT01199926 OBJECTIVE To investigate the reported association between low vitamin E levels and depressive symptoms in a population -based study . METHODS The study is based on a cohort of 3884 adults aged 60 years and over who participated in the third survey of the Rotterdam Study , were screened for depressive symptoms with the Center of Epidemiological Studies Depression Scale and from whom blood was drawn . All screen-positive subjects had a psychiatric work-up .  Blood levels of vitamin E  were compared between 262 cases with depressive symptoms and 459 r and omly selected reference subjects . All analyses were stratified by sex , and adjusted for age , cholesterol , cognitive score , smoking , dietary supplement use , marital status , living alone , and functional disability score . RESULTS  Vitamin E levels in men with depressive symptoms were lower than in non-depressed men after adjusting for age , whereas no such difference was found in women . This association in men was substantially weakened after controlling for biological factors , and disappeared with additional adjustment for nutritional behaviour and social factors . No differences were observed when the analyses were restricted to cases with depression as defined in the Diagnostic and Statistical Manual of Mental Disorders IV . CONCLUSIONS After control for several biological and behavioural factors relating to health we found no association between low vitamin E levels and depressive symptoms or depression in the elderly OBJECTIVES To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children . DESIGN R and omized , double blind , placebo-controlled trial . METHODS Starting in April , 1993 , we r and omized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia . Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded . At baseline children received placebo or 400 000 IU ( or half that for infants ) of vitamin A , in addition to st and ard treatment for pneumonia . They received further doses of the same regimen 4 and 8 months after hospital discharge . Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests . For positive children < 15 months of age , HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays . HIV status was ascertained for 648 of 687 enrolled children . The mean duration of follow-up was 24.4 months ( SD = 12.1 ) . RESULTS Of 648 children 58 ( 9 % ) were HIV-infected . Compared with uninfected children , all-cause mortality was higher among HIV-infected children , as was mortality caused by pneumonia or diarrhea ( P < 0.001 for each ) . Overall vitamin A supplements result ed in a 49 % reduction in mortality [ relative risk ( RR ) , 0.51 ; 95 % confidence interval ( CI ) , 0.29 to 0.90 , P = 0.02 ] . Vitamin A supplements reduced all-cause mortality by 63 % among HIV-infected children ( RR 0.37 ; CI 0.14 to 0.95 , P = 0.04 ) and by 42 % among uninfected children ( RR 0.58 , CI 0.28 to 1.19 , P = 0.14 ) . Vitamin A supplements were also associated with a 68 % reduction in AIDS-related deaths ( P = 0.05 ) and a 92 % reduction in diarrhea-related deaths ( P = 0.01 ) . CONCLUSION Vitamin A deficiency , which is common among children in many developing countries , is particularly severe among HIV-infected children . Our findings indicate that vitamin A supplements , a low cost intervention , reduce mortality of HIV-infected children OBJECTIVES Our objective was to prospect ively examine the relation between vitamin C intake and risk of coronary heart disease ( CHD ) in women . BACKGROUND Results from prospect i ve investigations of the relation between vitamin C intake and risk of CHD have been inconsistent . The lack of clear evidence for a protective association despite a plausible mechanism indicates the need to evaluate further the association between vitamin C intake and risk of CHD . METHODS In 1980 , 85,118 female nurses completed a detailed semiquantitative food-frequency question naire that assessed their consumption of vitamin C and other nutrients . Nurses were followed up for 16 years for the development of incident CHD ( nonfatal myocardial infa rct ion and fatal CHD ) . RESULTS During 16 years of follow-up ( 1,240,566 person-years ) , we identified 1,356 incident cases of CHD . After adjustment for age , smoking , and a variety of other coronary risk factors , we observed a modest significant inverse association between total intake of vitamin C and risk of CHD ( relative risk [ RR ] = 0.73 ; 95 % confidence interval [ CI ] 0.57 to 0.94 ) . Among women who did not use vitamin C supplements or multivitamins  , the association between intake of vitamin C  from diet alone and incidence of CHD was weak and not significant ( RR = 0.86 ; 95 % CI 0.59 to 1.26 ) . In multivariate models adjusting for age , smoking , and a variety of other coronary risk factors , vitamin C supplement use was associated with a significantly lower risk of CHD ( RR = 0.72 ; 95 % CI 0.61 to 0.86 ) . CONCLUSIONS Users of vitamin C supplements appear to be at lower risk for CHD OBJECTIVE A possible role for vitamin D deficiency in contributing to the winter increase in  cardiovascular disease  mortality was investigated by testing the effect of vitamin D supplementation on blood pressure and other cardiovascular risk factors during winter . DESIGN R and omised double-blind trial of vitamin D supplementation in winter . SUBJECTS Men and women , mean age 70 years ( range 63 - 76 ) recruited from general practitioner age-sex registers in Cambridge ( UK ) . INTERVENTION 95 people received a single oral dose of 2.5 mg cholecalciferol and 94 received the placebo at baseline interviews during December 1991 . Follow-up assessment was 5 weeks later during January 1992 . RESULTS Comparing follow-up with baseline assessment , serum 25-hydroxyvitamin D increased in the treated group and decreased slightly in the placebo group [ mean ( s.d . ) change : 7.2 ( + /- 3.8 ) vs -1.4 ( + /- 1.1 ) ng/ml , P = 0.0001 ] ; while parathyroid hormone decreased in the treated , and increased in the placebo , group [ -0.27 ( + /- 0.78 ) vs 0.13 ( + /- 0.75 ) pmol/l , P = 0.0004 ] . However , the mean change in blood pressure was similar in both groups : systolic -5 ( + /- 13 ) vs -5 ( + /- 16 ) mmHg , P = 0.81 ; diastolic -1 ( + /- 9 ) vs -1 ( + /- 9 ) , P = 0.92 ; as was the mean change in serum cholesterol [ -0.07 ( + /- 0.52 ) vs -0.05 ( + /- 0.60 ) mmol/l , P = 0.81 ] . In contrast , the mean change in radial pulse was significantly decreased in the treated group compared with placebo [ -2 ( + /- 9 ) vs 1 ( + /- 7 ) beats per min , P = 0.030 ] . CONCLUSIONS The failure of vitamin D supplementation to change blood pressure or serum cholesterol suggests that the winter increase in these factors is not caused by decreased vitamin D levels OBJECTIVE Alcohol ingestion promotes lipoperoxidation and alters cellular antioxidant mechanisms . Alpha-tocopherol levels decrease in alcoholics as severity of liver damage increases . The aim of this protocol was to study the effects of a long-term oral 500 mg vitamin E daily supplementation in decompensated ambulatory alcoholic cirrhotics . PATIENTS AND METHODS 67 subjects were included in this double blind trial ; 33 patients received vitamin E and 34 patients received placebo tablets of identical appearance during 1 year . Each month , the patients were seen by a nurse practitioner who was in charge of detecting alcohol ingestion and checking adherence to treatment . Every 3 months , the patients underwent a medical examination , and blood sample s were taken for clinical laboratory analysis and serum vitamin E measurement . RESULTS Alpha-tocopherol levels were significantly lower in patients with more severe liver disease . This difference was not significant when vitamin E levels were corrected by cholesterol . Oral supplementation significantly increased serum vitamin E levels in the experimental group . Alcohol ingestion and hospitalization rates were similar in both groups . Life table analysis did not show significant differences in mortality between the two groups . DISCUSSION Vitamin E supplementation with adequate doses of an alpha-tocopheryl acetate formulation during 1 year did not influence hepatic laboratory parameters , mortality or hospitalization rates of decompensated alcoholic cirrhotics , although serum levels of the vitamin significantly increased 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
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 .