Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. A secondary prevention trial of antioxidant vitamins and cardiovascular disease in women. Rationale, design, and methods. The WACS Research Group. Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up. Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial Dietary supplement use and mortality in a cohort of Swedish men. Vitamin D and HIV Progression among Tanzanian Adults Initiating Antiretroviral Therapy Circulating 25OHD, dietary vitamin D, PTH, and calcium associations with incident cardiovascular disease and mortality: the MIDSPAN Family Study. Vitamin A supplementation during war-emergency in Guinea-Bissau 1998-1999. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL). Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial.
Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . This is a grade I recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found poor evidence to determine whether supplementation with these vitamins reduces the risk for cardiovascular disease or cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) The available evidence from r and omized trials is either inadequate or conflicting , and the influence of confounding variables on observed outcomes in observational studies can not be determined . As a result , the USPSTF could not determine the balance of benefits and harms of routine use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . The USPSTF recommends against the use of beta-carotene supplements , either alone or in combination , for the prevention of cancer or cardiovascular disease . This is a grade D recommendation . The USPSTF found good evidence that -carotene supplementation provides no benefit in the prevention of cancer or cardiovascular disease in middle-aged and older adults . In two trials restricted to heavy smokers , -carotene supplementation was associated with higher incidence of lung cancer and higher all-cause mortality . The USPSTF concludes that -carotene supplements are unlikely to provide important benefits and might cause harm in some groups . Clinical Considerations The USPSTF did not review evidence regarding vitamin supplementation for patients with known or potential nutritional deficiencies , including pregnant and lactating women , children , elderly persons , and people with chronic illnesses .  Dietary supplements may be appropriate for people whose diet does not provide the recommended dietary intake of specific vitamins . Individuals may wish to consult a health care provider to discuss whether dietary supplements are appropriate . With the exception of vitamins for which there is compelling evidence of net harm ( for example , beta-carotene supplementation in smokers ) , there is little reason to discourage people from taking vitamin supplements . Patients should be reminded that taking vitamins does not replace the need to eat a healthy diet . All patients should receive information about the benefits of a diet high in fruits and vegetables , as well as information on other foods and nutrients that should be emphasized or avoided in their diet ( see the 2002 USPSTF recommendations on counseling to promote a healthy diet [ 1 ] ) . Patients who choose to take vitamins  should be encouraged to adhere to the dosages recommended in the Dietary Reference Intakes of the Institute of Medicine . Some vitamins , such as A and D , may be harmful in higher doses ; therefore , doses greatly exceeding the Recommended Dietary Allowance or Adequate Intake should be taken with care while considering whether potential harms outweigh potential benefits . Vitamins and minerals sold in the United States are classified as dietary supplements , and there is a degree of quality control over content if they have a U.S. Pharmacopeia seal ( 2 ) . Nevertheless , imprecision in the content and concentration of ingredients could pose a theoretical risk not reflected in clinical trials using calibrated compounds . The adverse effects of beta-carotene on smokers have been observed primarily in those taking large supplemental doses . There is no evidence to suggest that beta-carotene is harmful to smokers at levels occurring naturally in foods . The USPSTF did not review evidence supporting folic acid supplementation among pregnant women to reduce neural tube defects . In 1996 , the USPSTF recommended folic acid for all women who are planning , or capable of , pregnancy ( see the 1996 USPSTF chapter on screening for neural tube defects [ 3 ] ) . Clinicians and patients should discuss the possible need for vitamin supplementation when taking certain medications ( for example , folic acid supplementation for patients taking methotrexate ) . Scientific Evidence The USPSTF review s ( 4 - 6 ) focused on the quality of the evidence regarding the effect of routine supplementation with certain vitamins on primary prevention of cancer and cardiovascular disease . These review s were undertaken because of the growing epidemiologic evidence that dietary factors may play a role in the etiology of these diseases ( 7 - 9 ) . The review s focused on prospect i ve trials of vitamin supplementation and observational studies of associations between the use of specific supplements and the risk for cancer or cardiovascular disease . The value of vitamins naturally occurring in food , the use of vitamin supplements for the prevention of other conditions ( for example , neural tube defects ) , and the use of vitamin supplements for the secondary prevention of complications in patients with existing disease were outside the scope of these review s. Vitamin A No prospect i ve trials have examined the effect of vitamin A supplements alone on the risk for cancer . Observational studies provide no evidence that such supplements prevent cancer in men . In women , observational studies have reported a statistically significant inverse association between use of vitamin A supplements and risk for colon and breast cancer ( 10 , 11 ) . Despite efforts to adjust for confounding variables , the observational , nonr and om design of these studies makes it difficult to assess the extent to which the reduced cancer risk is attributable to vitamin A or to other characteristics of women who take vitamin A supplements .  No evidence from prospect i ve trials is available regarding the benefits of vitamin A alone in preventing cardiovascular disease . One good- quality cohort study found no effect of vitamin A supplementation in reducing cardiovascular disease mortality ( 12 ) . Vitamin C No primary prevention trial of the effect of vitamin C supplementation alone on cancer or cardiovascular disease has been reported . Observational studies have generally shown no statistically significant associations between use of vitamin C supplements and risk for cancer of the breast , prostate , colon , or lung ( 12 - 14 ) . The observational cohort studies examining the effects of vitamin C on cardiovascular disease have produced inconsistent results ( 12 , 15 , 16 ) . Vitamin E Only a few trials have examined the effects of vitamin E on the primary prevention of cancer or cardiovascular disease . A r and omized , controlled trial ( RCT ) involving Finnish male smokers found that vitamin E supplementation is not protective against lung cancer but may have a beneficial impact on prostate cancer ( 14 ) . Because prostate cancer was not a primary end point of the trial and the trial had other limitations , further evidence is needed to confirm this finding . Observational studies have shown no statistically significant association between use of vitamin E supplements and risk for prostate , lung , or breast cancer ( 5 ) . One study suggested that vitamin E protects against colon cancer , but the influence of confounding variables can not be fully excluded ( 17 ) . Among primary prevention trials , two good- quality trials ( 14 , 18 ) and one fair- quality trial ( 19 ) found no statistically significant benefit of vitamin E supplementation in preventing cardiovascular disease ( 20 ) . Only one of seven trials of vitamin E supplementation for secondary prevention demonstrated a statistically significant reduction in cardiac events ( 4 ) . Some prospect i ve cohort studies have suggested a significant benefit , but the results are mixed and the influence of confounding variables can not be excluded ( 4 ) . -Carotene A consistent body of evidence from clinical trials suggests that beta-carotene supplementation does not decrease the risk for lung , prostate , colon , breast , or nonmelanoma skin cancer ( 14 , 21 - 25 ) . -Carotene supplements were associated with an increased risk for lung cancer among smokers , especially heavy smokers , in two RCTs ( 14 , 25 ) . Results from four RCTs demonstrated no reduced risk for cardiovascular events or death after beta-carotene supplementation ( 14 , 21 , 22 , 26 - 28 ) . Antioxidant Vitamin Combinations Studies of the effects of antioxidant vitamin combinations to prevent cancer have yielded mixed results . A recent RCT reported no statistically significant effect of daily supplementation with a combination of antioxidants : vitamin E , vitamin C , and beta-carotene ( 29 ) . Some studies have suggested an adverse effect of antioxidant combinations on cancer , but the results may have been confounded by the inclusion of beta-carotene ( 5 ) . Some observational studies of antioxidant vitamin combinations have suggested a benefit in preventing cardiovascular disease ( 13 , 30 , 31 ) , but other studies , including well- design ed RCTs , have shown no benefit ( 29 , 32 , 33 ) . One secondary prevention trial showed an increase in all-cause mortality among women taking antioxidant supplements  ( 34 ) . Multiple Vitamin Combinations The incremental benefit of taking supplemental doses of folic acid and B vitamins has been examined by comparing the outcomes of observational studies while controlling for the total intake of antioxidant vitamin supplements ( 35 ) . In these analyses , folic acid supplementation was associated with significantly decreased risk for colon cancer , but the protective effect requires confirmation in prospect i ve trials . There is conflicting evidence regarding the use of multivitamins and the risk for cardiovascular disease . Among cohort studies , one good- quality study reported a statistically significant reduction in coronary events ( 36 ) , two good- quality studies reported no statistically significant effect on mortality ( 16 , 37 ) , and one 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 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 The evidence for a potential benefit of antioxidant vitamins in the prevention and therapy of atherosclerotic disease is derived from laboratory , clinical , and observational epidemiologic studies but remains inconclusive . Data from r and omized clinical trials are sparse , particularly for women . Therefore , it is both timely and important to conduct large-scale primary and secondary prevention trials of antioxidants and cardiovascular disease ( CVD ) . The Women 's Antioxidant and Cardiovascular Study ( WACS ) is a r and omized , double-blind , placebo-controlled secondary prevention trial of the balance of benefits and risks of antioxidant vitamins ( vitamins E and C , and beta-carotene ) among 8000 women with preexisting CVD . This secondary prevention trial will be conducted as a companion to the recently started Women 's Health Study , a primary prevention trial of vitamin E and beta-carotene , as well as aspirin . In the WACS , US female health professionals aged 40 years and older with a history of myocardial infa rct ion , angina pectoris , coronary revascularization , stroke , transient cerebral ischemia , carotid endarterectomy , or peripheral artery surgery will be r and omly assigned , utilizing a 2 x 2 x 2 factorial design , to receive vitamin E , vitamin C , beta-carotene , and /or placebo . Cardiovascular end points include nonfatal myocardial infa rct ion , nonfatal stroke , coronary revascularization procedures , and total CVD mortality . The present article describes the rationale , design , and methods of the trial BACKGROUND AND AIMS Emerging evidence suggests that low levels of vitamin D may be an important risk factor for multiple chronic diseases and mortality , but the evidence is mixed . Vitamin D levels are associated with sun exposure , diet , and metabolic status . One potential explanation for the lack of consistent findings amongst various studies is that low vitamin levels may be associated with poor diets or other risk factors that we were not adequately controlled for in different analyses . METHODS Prospect i ve analysis of adults over the age of 35 in NHANES III data ( 1988 - 1994 ) with 20 year mortality follow-up . Sequential Cox proportional hazard models quartiles of 25OH vitamin D adjusted for age , season , geography , sociodemographic ( SD ) , CVD risk factors ( CVD ) and nutritional factors ( NF ) were performed . RESULTS Gender , race , diabetes , anti-hypertensive meds , income , taking  vitamin D supplements , physical activity , alcohol consumption , region , body mass index , blood pressure , creatinine , albumin , CRP , thyroxine , iron , RBC folate , vitamin A , E , alpha-carotene , and lycopene were all associated with different quartiles of vitamin D and as well as CHD and all-cause mortality and thus are important potential confounders of this relationship . Adjusting for the confounding factors , higher levels of vitamin D demonstrate an inverse relationship with all-cause mortality , but only the top quartile of vitamin D shows an inverse relationship with CHD mortality . CONCLUSIONS The highest quartile compared to the lowest quartile of 25OH vitamin D levels is inversely associated with CHD and all-cause mortality adjusting for multiple confounders . Whether supplementation of individuals with low vitamin D will result in similar benefits will require a r and omized clinical trial BACKGROUND Supplementation of vitamin A in children aged 6 - 59 months improves child survival and is implemented as global policy . Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results . We aim ed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days ( 6 months ) . METHODS We did an individually r and omised , double-blind , placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania . Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam . In Kilombero , Ulanga , and Kilosa districts , women were seen at home as part of the health and demographic surveillance system . Newborn infants were eligible for r and omisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months . We r and omly assigned infants to receive one dose of 50,000 IU of vitamin A or placebo in the first 3 days after birth . Infants were r and omly assigned in blocks of 20 , and investigators , participants ' families , and data analysis teams were masked to treatment assignment . We assessed infants on day 1 and day 3 after dosing , as well as at 1 , 3 , 6 , and 12 months after birth . The primary endpoint was mortality at 6 months , assessed by field interviews . The primary analysis included only children who were not lost to follow-up . This trial is registered with the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , number ACTRN12610000636055 . FINDINGS Between Aug 26 , 2010 , and March 3 , 2013 , 31,999 newborn babies were r and omly assigned to receive vitamin A ( n=15,995 ) or placebo ( n=16,004 ; 15,428 and 15,464 included in analysis of mortality at 6 months , respectively ) . We did not find any evidence for a beneficial effect of vitamin A  supplementation on mortality in infants at 6 months ( 26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group ; risk ratio 1·10 , 95 % CI 0·95 - 1·26 ; p=0·193 ) . There was no evidence of a differential effect for vitamin A supplementation on mortality by sex ; risk ratio for mortality at 6 months for boys was 1·08 ( 0·90 - 1·29 ) and for girls was 1·12 ( 0·91 - 1·39 ) . There was also no evidence of adverse effects of supplementation within 3 days of dosing . INTERPRETATION Neonatal vitamin A supplementation did not result in any immediate adverse events , but had no beneficial effect on survival in infants in Tanzania . These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation . FUNDING Bill & Melinda Gates Foundation to WHO 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 The use of dietary supplements has increased substantially in most industrialized countries . The aim of this study was to prospect ively examine the association between use of dietary supplements and  all-cause mortality , cancer mortality and CVD mortality in men . We used the population -based prospect i ve cohort of 38 994 men from central Sweden , 45 - 79 years of age , with no cancer or CVD at baseline and who completed a self-administered FFQ including questions on dietary supplement use and life-style factors in 1997 . During average 7.7 years of follow-up , 3403 deaths were ascertained ; among them , 771 due to cancer and 930 due to CVD ( during 5.9 years of follow-up ) . In multivariate adjusted models including all men there was no association observed between use of any dietary supplement or of multivitamins , vitamin C , vitamin E or fish oil specifically and all-cause mortality , cancer or CVD mortality . Among current smokers , regular use of any supplement was associated with statistically significant increased risk of cancer mortality : relative risk ( RR ) 1.46 ( 95 % CI 1.06 , 1.99 ) . Among men reporting an inadequate diet at baseline ( assessed by Recommended Food Score ) , there was a statistically significant inverse association between use of any dietary supplement and CVD mortality ( RR 0.72 ; 95 % CI 0.57 , 0.91 ) , no associations were observed among men with adequate diets . In conclusion , we can not exclude that the use of dietary supplements is harmful for smokers . On the other h and , among men with an insufficient diet , the use of supplements might be beneficial in reducing CVD mortality 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 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 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 Evidence for a role of supplemental vitamin D and marine omega-3 fatty acids in preventing cancer and cardiovascular disease ( CVD ) remains inconclusive and insufficient to inform nutritional recommendations for primary prevention . The VITamin D and Omega-A 3 TriaL ( VITAL ) is an ongoing nationwide , r and omized , double-blind , placebo-controlled clinical trial design ed to fill this knowledge gap . The study population consists of 25,874 U.S. adults without cancer or CVD at baseline , who were selected only on age ( men aged ≥50 and women aged ≥55 ) , with an oversampling of African Americans ( n=5,107 ) . In a 2 × 2 factorial design , participants were r and omized to one of four supplement groups : [ 1 ] active vitamin D3 ( cholecalciferol ; 2000 IU/d ) and active marine omega-3 fatty acids ( Omacor ® fish oil , eicosapentaenoic acid [ EPA ] and docosahexaenoic acid [ DHA ] , 1g/d ) ; [ 2 ] active vitamin D and omega-3 placebo ; [ 3 ] vitamin D placebo and active marine omega-3 fatty acids ; or [ 4 ] vitamin D placebo and omega-3 placebo . The mean length of the r and omized treatment period will be 5 years . The r and omization was successful , as evidence d by similar distributions of baseline demographic , health , and behavioral characteristics across treatment groups . The similar distribution of known potential confounders across treatment groups strongly suggests that unmeasured or unknown potential confounders are also equally distributed . VITAL is expected to provide important information on the benefit-risk balance of vitamin D and omega-3 fatty acid supplementation when taken for the primary prevention of cancer and CVD 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 B-12 deficiency is associated with cognitive impairment in older people . However , evidence from r and omized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive . OBJECTIVE The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged > /=70 y with mild vitamin B-12 deficiency . DESIGN In a double-blind , placebo-controlled trial , 195 subjects were r and omly assigned to receive 1000 microg vitamin B-12 , 1000 microg vitamin B-12 + 400 microg folic acid , or placebo for 24 wk . Vitamin B-12 status was assessed on the basis of methylmalonic acid , total homocysteine ( tHcy ) , and holotranscobalamin ( holoTC ) concentrations before and after 12 and 24 wk of treatment . Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention , construction , sensomotor speed , memory , and executive function . RESULTS Vitamin B-12 status did not change significantly after treatment in the placebo group ; however , oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency .  Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36 % . Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone ( P = 0.0036 ) . Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains . CONCLUSION Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function
Vitamin D in the form of vitamin D(3 ) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care .
Vitamin D(2 ) , alfacalcidol , and calcitriol had no statistically significant effect on mortality .
Vitamin D(3 ) combined with calcium significantly increased nephrolithiasis .
Both alfacalcidol and calcitriol significantly increased hypercalcaemia
BACKGROUND The available evidence on vitamin D and mortality is inconclusive .
OBJECTIVES To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults .